How I Healed my Kidney Problems

Kidney Function Restoration Program

The All Natural Kidney Health & Kidney Function Restoration Program is a compilation of the best and most effective natural treatments for kidney disease from around the world. The system is meant to complement your usual medication and not to replace it. This easy to understand kidney disease program can help you make better-informed decisions about what is the right thing to do to support your kidney and return it to its former healthy state. The techniques shared in this program will help cure and retain your kidney back to its natural wellness. You may even be able to postpone or entirely avoid dialysis or a kidney transplant forever. The All Natural Kidney Health and Kidney Function Restoration Program contain zero filler and is fully backed by modern-day scientific research. Everything contained in this program is safe, natural, and with good safety profiles, proven case studies and doctor recommended. Many of the products including the diet, herbs, and supplements have been used safely in other countries for many years and in several hospitals in the United States. Read more here...

Kidney Function Restoration Program Summary


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Kidney Function Restoration Program Review

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All of the information that the author discovered has been compiled into a downloadable pdf so that purchasers of Kidney Function Restoration Program can begin putting the methods it teaches to use as soon as possible.

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Effects of Impaired Renal Function on Nonrenal Metabolism

Most drugs are not excreted unchanged by the kidneys but first are biotransformed to metabolites that then are excreted. Renal failure not only may retard the excretion of these metabolites, which in some cases have important pharmacologic activity, but, in some cases, alters the nonrenal as well as the renal metabolic clearance of drugs (15, 24). The impact of impaired renal function on drug metabolism is dependent on the metabolic pathway, as indicated in Table 5.2. In most

Calculation of Dialysis Clearance

2018 Dialysis Drugs

Currently, the efficiency of hemodialysis is expressed in terms of dialysis clearance. Dialysis clearance (CLd) is usually estimated from the Fick equation as follows Dialysis bath solute concentration (Bath) had to be considered in describing the performance of recirculating dialyzers and was included in the equation for calculating dialysance (D), as shown in the following equation (7) Considerable confusion surrounds the proper use of Equation 6.2 to calculate dialysis clearance. There is general agreement that blood clearance is calculated when Q is set equal to blood flow and A and V are expressed as blood concentrations. In conventional practice, plasma clearance is obtained by setting Q equal to plasma flow and expressing A and V as plasma concentrations. In fact, this estimate of plasma clearance is only the same as plasma clearance calculated by standard pharmacokinetic techniques when the solute is totally excluded from red blood cells. This dilemma is best avoided by...

Evaluation Of The Kidney Transplant Recipient 411 General Indications

The most common conditions that lead to chronic renal failure and end-stage renal disease (ESRD) requiring dialysis and evaluation for kidney transplantation (KT) are outlined in Table 4.1. Diabetes mellitus (DM) is the most common indication for renal transplantation. This is complicated by the fact that patients with DM on dialysis have a very high mortality. Some of these patients may be candidates for a combined kidney-pancreas transplant in its different modalities, as outlined later in this chapter. Chronic glomerulonephritis from various etiologies can lead to renal failure and ultimately necessitate KT. Polycystic kidney disease (PKD), an autosomal-dominant inherited disease, is most prevalent in Caucasians. Hypertensive nephropathy with nephrosclerosis, though widely prevalent, is more commonly seen in the African American population, due to the prevalence of hypertension in this group. Other causes of renal failure are less common and need individualized evaluation for KT....

Patient Factors Affecting Hemodialysis of Drugs

Because elimination clearances are additive, total solute clearance during hemodialysis (CLt) can be expressed as the sum of dialysis clearance (CLd), and the patient's renal clearance (CLr) and nonrenal clearance (CLnr) When CLd is small relative to the sum of CLr and CLnr, hemodialysis can be expected to have little impact on the overall rate of drug removal. The extent of drug binding to plasma proteins is the most important patient factor affecting dialysis clearance, and in that sense dialysis clearance is restrictive. However, partitioning into erythrocytes has been shown to enhance rather than retard the clearance of at least some drugs. A large distribution volume also reduces the fraction of total body stores of a drug that can be removed by hemodialysis, and limits the effect of hemodialysis on shortening drug elimination half-life, Hemodynamic Changes during Dialysis Few studies of pharmacokinetics during hemodial-ysis have utilized the recovery method of calculating...

Renal Failure

P. falciparum is the only species which causes acute renal failure (although P. malariae can cause a chronic nephropathy leading to nephrotic syndrome and chronic renal failure). Sequestration of parasitised erythrocytes is evident in glomerular and interstitial vessels. There is also evidence of reduced renal blood flow and oxygen delivery in P. falciparum malaria (Day et al., 1997). It is unclear whether this is a result of sequestration of parasitised erythrocytes in the kidney or a local or systemic effect of circulating vasoactive compounds. Malaria-associated ARF has features of acute tubular necrosis (ATN), seen in bacterial sepsis. Histologically there are changes in the tubules consistent with ATN, and haemoglobin tubular casts and tubular atrophy have been demonstrated in cases of blackwater fever (Sitprija et al., 1967 Day et al., 1997). Glomerulonephritis is rare. The descriptive term 'blackwater fever' refers to a clinical setting in which the patient passes very dark...

Longterm dialysis

As folate is only loosely bound to plasma proteins, it is easily removed from plasma by haemodialysis or peritoneal dialysis (in contrast, cobalamin is not removed from plasma by dialysis as it is firmly protein bound). The amount of body folate that can be removed in this way is relatively small. Nevertheless, in patients with anorexia, vomiting, infections and haemolysis, folate stores may become depleted and megaloblastic anaemia can supervene. Routine folate prophylaxis is now given.

Acute renal failure

Acute renal failure and pre-eclampsia are uncommon (Krane, 1988). In a series of 245 cases of eclampsia, none required dialysis for renal failure (Cunningham et al., 1984). However, 7 of 435 women with HELLP syndrome developed acute renal failure long-term prognosis was generally favorable in the absence of pre-existing chronic hypertension (Sibai and Ramadan, 1993). Acute renal failure secondary to pre-eclampsia is usually the result of acute tubular necrosis but may be secondary to bilateral cortical necrosis. Precipitating factors include abruption, coagulopathy, hemorrhage, and severe hypotension (Grunfeld and Pertuiset, 1987). Severe renal dysfunction in

Cost of Screening Strategies

Screening strategies for CRC seem to be cost-effective compared with no screening 227, 228 . CRC screening compares favourably to other cancer screening strategies (cervical cancer screening and mammographic screening) 229 or other life-saving treatments such as kidney dialysis or coronary artery bypass surgery 230 . Colorectal screening may have an average cost-effectiveness ratio between US 10 000 and 30 000 per year of life saved, thus below the US 40 000 threshold 231 . From an economic point of view, results indicate that CRC screening should be warranted for the average-risk adult over the age of 50 years until the age of 80 years 221 .

Sammy SaabSteven Huy Han and Paul Martin

Rine, octapressin), and antagonists of renal vasoconstriction (angiotensin II receptor antagonists, intrarenal phentolamine) have all been generally unsuccessful. Preliminary data suggest that the combination of volume expansion and systemic vasoconstrictors may help reverse HRS. In addition, a modified extracorporeal dialysis system may also improve HRS. TIPS may be useful, but its precise role remains to be defined for this indication.

Patterns of Clinical Disease

Symptomatic infections are more common and may occur at any age in areas where transmission of malaria is low or erratic ('unstable' malaria). Severe malaria, which may manifest as cerebral malaria, pulmonary oedema, jaundice and or acute renal failure (ARF), is also more common in adults in areas of unstable malaria (Hien et al., 1996). If malaria transmission rates in a hyper- or holoendemic area fall, either as a result of malaria control measures or reduced rainfall, severe malaria is occasionally observed in adults with waning immunity and epidemics may occur.

Flows through the vessels surrounding the tubule because there will be a concentration gradient in the direction

One of the factors which affects excretion is the urinary pH. If the compound which is filtered or diffuses into the tubular fluid is ionized at the pH of that fluid, it will not be reabsorbed into the bloodstream by passive diffusion. For example, an acidic drug such as phenobarbital is ionized at alkaline urinary pH and a basic drug such as amphetamine is ionized at an acidic urinary pH. This factor is utilized in the treatment of poisoning with barbiturates and salicylic acid for example (see Chapter 7). Thus by giving sodium bicarbonate to the patient, the urine becomes more alkaline and excretion of acidic metabolites is increased. The pH of urine may be affected by diet high protein diet for instance causes urine to become more acid. The rate of urine flow from the kidney into the bladder is also a factor in the excretion of foreign compounds high fluid intake, and therefore production of copious urine, will tend to facilitate excretion. Factors which affect kidney function such...

Benign prostatic hyperplasia

Acute retention Suprapubic pain and a distented palpable bladder. Chronic retention A large distended painless bladder (residual volumes 1L) and there may be signs of renal failure. Bloods U&Es for impaired renal function, PSA. Midstream urine For microscopy, culture and sensitivity. Imaging Ultrasound imaging of the renal tract to check for dilatation of the upper urinary tract. Bladder scanning to measure pre- and postvoiding volumes. TRUS to measure prostate size and guide biopsies. Flexible cystoscopy to visualise the bladder outlet and bladder changes (e.g. trabeculation). Other Urinary flow studies (flowmetry). Recurrent urinary infections, acute or chronic urinary retention, urinary stasis and bladder diverticulae or stone development, obstructive renal failure, post-obstructive diuresis.

Loosely Bound Iron Participates In The Formation Of Dnic

After the discovery of endogenous DNICs in yeast cells and animal tissues, it was initially thought that the iron-sulfur clusters be the main source of the iron and that the DNIC be formed after the disruption of the clusters by free NO radicals 3 . In vitro studies certainly confirm that exposure of iron-sulfur clusters to free NO leads to the formation of DNIC (cf Chapters 5 and 6). Whether this disruption is the dominant pathway for DNIC formation in vivo is a different matter. Subsequent studies found that loosely bound iron is the main source of endogenous DNIC in animal tissues and yeast. This loosely bound iron is often referred to as free iron or the labile iron pool. In vitro studies of the effect of gaseous NO on tissue homogenates and supernatant fractions have given further support that DNIC is formed from such loosely bound iron 132 . Independently, the same conclusion was reached by Nagata et al. 133 who observed the formation DNIC in rat liver supernatant after adding...

Fluid and Electrolyte Balance

It is important to assess the state of hydration of patients on admission carefully, as dehydration may contribute to hypovolaemia and shock (particularly in children) and result in acute renal failure. In contrast, fluid overload may exacerbate non-cardiogenic pulmonary oedema, particularly in adults. The average adult may require 10-15 ml kg of crystalloid solution in the first 24 hours to achieve normovolaemia. Recently it has been recognised that there is a strong correlation between acidosis, disease severity and outcome. Underlying acidosis in a dehydrated patient may cause respiratory symptoms that were previously attributed to pulmonary oedema and managed by fluid restriction (English et al., 1997 Crawley et al., 1998). The central venous pressure should therefore be maintained between 0 and 5 cm of water, with a pulmonary capillary pressure that is compatible with adequate cardiac and renal output. If pulmonary oedema does develop, the patient should be treated with...

Clinical Considerations

From the clinical standpoint, the two main phar-macokinetic considerations regarding renal replacement therapy deal with the use of these therapeutic modalities to treat drug toxicity and, more frequently, the need to administer supplemental drug doses to patients whose impaired renal function necessitates intervention. The factors that determine the extent of drug removal by renal replacement therapy are summarized in Table 6.4. As yet, there has been no attempt to analyze the interaction of all these factors with sufficient rigor to provide precise guidelines for clinical practice. However, extensive protein binding and large distribution volume are the most important factors limiting the extent to which most drugs are removed by hemodialysis or hemofiltration. Accordingly, neither conventional intermittent hemodialysis nor continuous renal replacement therapy will significantly enhance the removal of drugs such as pheny-toin, which is extensively bound to plasma proteins, or...

Waiting Lists and Waiting Period

During the waiting period, both the nephrology team and the transplant team follows the ESRD patient. Scheduled serum samples are taken at regular intervals during dialysis visits to ascertain fluctuations of the PRA and crossmatch status. In general, waiting periods can be measured in years for these patients. During this time, dialysis allows for patient optimization, though progressive loss of vascular access can be a life-threatening factor, especially for diabetic patients. Also during this period, the patient may undergo surgical intervention aimed at optimizing the outcome of the future KT. These commonly include bilateral nephrectomy (e.g., for polycystic disease or chronically infected kidneys), cholecystectomy (for gallstones) and coronary artery bypass grafting (for CAD).

Indications and Testing

Simultaneous Pancreas-Kidney Transplantation (SPK) SPK has become an accepted therapy for the treatment of patients with insulin-dependent DM and renal failure or insufficiency (creatinine clearance 70). The predialytic patient will benefit from the reduced costs, facilitated rehabilitation, and avoidance of complications associated with dialysis and uremia. Roughly 85 of pancreata are transplanted in this manner. Patient 1-year survival is over 90 , and graft 1-year survival is over 80 . The use of dual organs from scarce cadaver sources has caused some surgeons to perform live donor nephrec- 4.2.3. Pancreas after Kidney Transplantation (PAK) This technique has been traditionally reserved for the patient with life-threatening glucose unawareness, without secondary renal failure (i.e., with a creatinine clearance 70). Roughly 5 of all pancreata are transplanted in this manner. Nowadays, more centers are performing pancreas transplants alone in order to correct glucose imbalance...

Use Of Therapeutic Drugs In Patients With Liver Disease

A number of clinical classification schemes and laboratory measures have been proposed as a means of guiding dose adjustments in patients with liver disease, much as creatinine clearance has been used to guide dose adjustments in patients with impaired renal function. The Pugh modification of Child's classification of liver disease severity (Table 7.4) is the classification scheme that is used most commonly in studies designed to formulate drug dosing recommendations for patients with liver disease (31, 32). Because patients with only mild or moderately severe liver disease usually are enrolled in these studies, there are relatively few data from patients with severe liver disease, in whom both pharmacokinetic changes and altered pharmacologic response are expected to be most pronounced. The administration of narcotic, sedative, and psychoactive drugs to patients with severe liver disease is particularly hazardous because these drugs have the potential to precipitate life-threatening...

Effects of Liver Disease on Patient Response

When diuretic therapy does result in effective fluid removal in cirrhotic patients, it is associated with a very high incidence of adverse reactions. In one study of diuretic therapy in cirrhosis, furosemide therapy precipitated the hepatorenal syndrome in 12.8 , and hepatic coma in 11.6 , of the patients (56). Although daily doses of this drug did not differ, patients who had adverse drug reactions received total furosemide doses that averaged 1384 mg, whereas patients without adverse reactions received lower total doses that averaged 743 mg. Accordingly, when spironolactone therapy does not provide an adequate diuresis, only small frequent doses of loop diuretics should be added to the spironolactone regimen (55). Cirrhotic patients also appear to be at an increased risk of developing acute renal failure after being treated with angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs (57).

Diagnostic Frameworks for General Practice

'The masqueraders can be grouped into primary and secondary groups. The primary (most common) masqueraders are depression, diabetes mellitus, drugs, anemia, thyroid disease, spinal dysfunction, and urinary tract infection. A secondary (less common) list includes chronic renal failure, HIV AIDS, rare bacterial infections (e.g. subacute bacterial endocarditis, tuberculosis), systemic viral infections (e.g. infectious mononucleosis, hepatitis A, B, C, D, E), neurological dilemmas (e.g. Parkinson's disease, multiple sclerosis), connective tissue disorders (e.g. systemic lupus erythe-matosus, polymyalgia rheumatica).

Denaturing the Fusion Protein

During refolding, one has to balance between two objectives. For factor Xa to cleave it must be present before the protein has completely refolded, so removing the denaturant quickly is desirable. However, when the denaturant is removed quickly, some proteins will fail to refold properly and precipitate. Stepwise dialysis against buffer containing decreasing amounts of guanidine hydrochloride can prevent precipitation of the fusion protein halving the guanidine concentration at each step is convenient, but cases where 0 1M steps are necessary have been reported. However, if the fusion protein is able to refold into a factor Xa-resistant conformation, it may be better to dialyze away the denaturant in one step and take the loss from precipitation in order to maximize the amount of cleavable fusion protem recovered.

Obesity and Spontaneous Preterm Birth

Even though obesity is detrimental for numerous aspects of human health and disease, high BMIs are associated with better outcomes of both congestive heart failure and atherosclerotic heart disease among people with chronic renal disease (Beddhu, 2004 Kalantar-Zadeh et al., 2004). It has been hypothesized that these epidemiological paradoxes may be the result of obesity-related changes in systemic inflammation (Beddhu, 2004 Kalantar-Zadeh et al., 2004).

Associated Medical Problems

Low levels of potassium and sodium and other imbalances in the body's electrolytes can lead to cardiac arrest, kidney failure, weakness, confusion, poor memory, disordered thinking, and mood swings. The death rate for anorexics is high About 5 percent will die within eight years of being diagnosed and 20 percent within twenty years.

Detection of lung damage

Unlike liver and kidney damage there are currently no general biochemical tests for lung damage. Lung damage may be detected pathologically by light and electron microscopy of lung tissue and simple measurements such as the lung wet weight dry weight ratio will detect oedema. Bronchoscopy can be employed for the detection of gross changes and samples may be taken at the same time for histopathology. Lung dysfunction is detected by physiological tests such as forced expiratory volume (FEV) over a particular time, and forced vital capacity. Measurement of pulmonary mechanics such as flow resistance may also be useful for detection of lung irritants or pharmacologically active agents. These measurements are more difficult to perform in conscious animals than in humans, but determination of lung function is possible in experimental animals.

Oncolytic Viral Therapy

It will become critical to temporarily suppress the host's immune system or enhance the killing activity of the virus so that it can eliminate tumors within a shorter period of time, allowing it to escape attack from the host immune system. Early clinical trials administered immunosuppressants such as corticosteroids at the time of injection however, shutdown of the entire immune system could be problematic during infection with replication-competent Ads. For this reason, genes encoding immunosuppressive molecules could be delivered via a PSRCA directly to the local tumor environment. Among the immune regulators, transforming growth factor (TGF)-P and Fas-ligand (Fas-L) are likely the best candidates for incorporation into a PSRCA. There are five members reported in the TGF-P family three of them (TGF-P 1, TGF-P 2, and TGF-P 3) are expressed in mammals. These three isoforms share a high degree of sequence homology in the mature domain, and have similar actions on cells in tissue...

Identification And Evaluation Of Biomarkers

Statistical criteria have played an important role in assessing the predictive utility of biomarkers (criterion validity), but it is always hazardous to equate causation with statistical association. For that reason, increasing emphasis has been placed on establishing the biological plausibility, or construct validity, of biomarkers. Thus, clinical and epidemiological observations led to the conclusion that elevated blood pressure was associated with an increased risk of atherosclerotic cardiovascular disease, heart failure, stroke, and kidney failure (16). Subsequent pathophysiologic studies in humans and in animal models then were particularly helpful in establishing a firm linkage between hypertension and cerebral hemorrhage and infarction (17). A later epidemiologic study demonstrated that the risk of stroke and coronary heart disease is correlated with the extent of diastolic blood pressure elevation (18). In the aggregate, this considerable evidence supports the biological...

Complications Of Transfusion

Acute haemolytic reactions from mismatched blood require immediate cessation of blood administration and a full investigation, which should include a haematocrit to check for the presence of haemolysis, culture of the patient's and donor's blood to exclude bacterial contamination, repeat cross-matching, a full blood count and examination of red cell morphology, and a Coombs' test. The donor blood should be returned to the blood bank and advice sought from the haematologist regarding any further investigation thought desirable. All aspects should be rigorously documented. The urinary output must be carefully monitored while an attempt is made to obtain a brisk diuresis. Severe reactions can occur from 30 mL of mismatched blood, are life threatening, and may require dialysis. Non-haemolytic reactions, often with severe associated urticaria, usually occur after administration of larger quantities of whole blood or packed cells, and may often be controlled with intravenous...

M C Smith and J M Davison

The healthy kidney undergoes considerable vascular adaptation in pregnancy and it is therefore not surprising that pre-eclampsia, with widespread endothelial dysfunction, is associated with substantial renal consequences, an understanding of which provides insight into the overall vascular pathology. It is important to interpret impaired renal function secondary to pre-eclampsia in the context of the substantially enhanced renal performance of normal pregnancy, otherwise significant end organ damage in pre-eclamptic patients will go unrecognized.

Early pregnancy assessment

Patients with pre-existing renal problems, during or independent of pregnancy, are more likely to develop pre-eclampsia and their antenatal surveillance should reflect this. In the past, patients with chronic renal disease were discouraged from pursuing pregnancy because of the high frequency of fetal and maternal complications including pre-eclampsia. Today the advice given depends largely upon the severity of existing renal disease and pregnancies in patients with mild disease (serum creatinine

Renal imaging findings

Ultrasound examination of the maternal kidneys is not helpful for the diagnosis of pre-eclampsia per se. However, abnormalities encountered on renal ultrasound may well suggest underlying renal disease. These findings can include renal parenchymal disease (dysplasia, polycystic kidney disease, hydronephrosis, etc.), nephrolithiasis and or adrenal disease (adenomas, hyperplasia, pheochromocytoma, etc.).

Endocrine imaging findings

Of primary hyperaldosteronism in pregnancy. Obstet. Gynecol., 86, 644. Basdogan, F., Visser, W., Struijk, P.C., et al. (2000). Automated cardiac output measurements by ultrasound are inaccurate at high cardiac outputs. Ultrasound Obstet. Gynecol., 15, 508-12. Belfort, M.A., Saade, G.R., Grunewald, C., et al. (1999). Association of cerebral perfusion pressure with headache in women with pre-eclampsia. Br. J. Obstet. Gynaecol., 106, 814-21. Burrows, R. F. and Kelton, J. G. (1990). Thrombocytopenia at delivery a prospective survey of 6715 deliveries. Am. J. Obstet. Gynecol., 162, 731-4. Connolly, G., Razak, A. R., Hayanga, A., Russell, A., McKenna, P., McNicholas, W.T. (2001). Inspiratory flow limitation during sleep in pre-eclampsia comparison with normal pregnant and nonpregnant women. Eur. Respir. J., 18, 672-6. Contreras, G., Gutierrez, M., Beroiza, T., et al. (1991). Ventilatory drive and respiratory muscle function in pregnancy. Am. Rev. Respir. Dis., 144, 837-41. Cunningham, F....

Renal artery stenosis 169

D Stenosis of the renal artery that can result in hypertension and renal failure. E Signs of hypertension (e.g. vascular changes on fundoscopy). Renal failure. P Atherosclerotic RAS is usually due to widespread aortic disease involving the renal artery ostia, can be classified as osteal or non-osteal. Fibromuscular dysplasia (aetiology unknown) results in focal stenosis (see Fig. 26a) that may be associated with micro-aneurysms in the mid and distal renal arteries (resembling string of beads on angiography). Renal hypoperfusion stimulates the renin-angiotensin system leading to circulating angiotensin II and aldosterone, increasing BP, which in turn, with time, causes fibrosis, glomerosclerosis and renal failure. Intervention In cases of uncontrolled hypertension, progressive renal failure, flash pulmonary oedema, stenoses 60 . C Drug-refractory hypertension, renal failure. P Untreated hypertension will progress to renal failure. With intervention 50-70 will have improvement in BP and...

Malaria and Pregnancy

These data suggest that the highest risk of malaria in pregnant travelers is in those women returning to an endemic area to see their family(18 25 US residents). Travel medicine practitioners should promote chemophylaxis in this high-risk group. Most cases of malaria were acquired in Africa and most cases were falciparum plasmodium. According to the data collected most of the pregnant travelers did not take, or took inappropriate, prophylaxis for the area of destination (20 25 US residents) 47 of the women were hospitalized. Complications during treatment included adult respiratory distress syndrome, renal failure and anemia. None of the cases was fatal.

Quantification of viral load

Quantitative PCR analysis of viral nucleic acid is now used by diagnostic laboratories worldwide and is particularly useful for monitoring viral loads in patients to assess the effect of anti-viral therapy and potentially to detect drug-resistant viral strains. In clinical virology, qPCR is commonly used for the detection and quantification of blood-borne viruses, including hepatitis B and C and human immunodeficiency viruses. However, it is also increasingly used to monitor viral pathogens of transplant patients, including Epstein-Barr virus, cytomegalovirus and BK virus. In recent years, our laboratory has used quantitative real-time PCR to investigate BK viral loads in a transplant patient population (see Protocol 14.3). BKV can cause several clinical manifestations in immunocompromised patients including hemorrhagic cystitis and allograft nephropathy. Since adopting qPCR, several limitations of this technology have been identified, including the impact of PCR inhibitors, poor...

Capillary Electrophoresis Mass Spectrometry

Nostic purposes using CE coupled with ESI-TOF-MS. In their earliest study (Wittke et al., 2003), urine samples of five patients with renal diseases and impaired renal function and eighteen healthy volunteers were obtained and stored at -20 C until analysis time. Thawed urine was applied onto a C-2 column to remove urea, electrolytes, salts, and other interfering components, to decrease matrix effects that would interfere with the CE resolution and MS detection and to enrich for the polypeptides present. Polypeptides were eluted with 50 (v v) acetonitrile in HPLC-grade water containing 0.5 (v v) formic acid. The pretreated samples were lyophilized and resuspended in 20 L of HPLC-grade water and analyzed by CE-ESI-TOF-MS. Analysis of the individual CE-MS spectra of the eighteen healthy volunteers, which were similar and comparable, allowed the establishment of a normal urine polypeptide pattern, consisting of 247 polypeptides, each of which was found in more than 50 of the healthy...

Choice of Concentration Scale

Consider initially an experiment in which a solution of protein (A) is brought into dialysis equilibrium with solvent (s). Since aqueous solutions are being considered, it will be assumed that both solvent and solution are incompressible, a simplification that allows the partial molar volumes of all constituents to be regarded as constants. In thermodynamic studies, the chemical potential (fji,) of a solute component is considered to be the sum of a standard state value ( jl ) and a part that, under ideal conditions, depends logarithmically upon solute concentration. Although the solute concentration may be measured on the mole-fraction, molal, molar, or weight-based scale, the choice of concentration scale serves only to dictate the value of the standard state chemical potential 28,29 , For very dilute solutions, all concentration scales are related to each other in approximately linear The addition of protein to solvent at constant temperature gives rise to one of two situations,...

Tissue Lesions Lung Damage

This bipyridylium herbicide causes lung fibrosis and sometimes kidney failure. It is an irritant chemical, exposure to which has a high fatality rate. It is actively accumulated by the lung tissue via the polyamine uptake system. By accepting an electron from NADPH it readily forms a stable free radical, which in the presence of oxygen produces superoxide anion radical. This may overwhelm the superoxide dismutase available and then hydroxyl radicals and hydrogen peroxide may be formed, leading to lipid peroxidation and tissue damage.

The oliguric preeclamptic

Patients who fail to respond to either of these measures may require more intensive monitoring. As outlined above, both echocardiography and pulmonary artery catheters are useful adjuncts in securing optimal left ventricular preload and after-load. The volume-replete vasodilated patient who fails to pass urine should be considered to have intrinsic renal pathology, namely acute tubular necrosis. A single large dose of furosemide (0.5-1 g intravenously) may convert these patients to high output renal failure. Should this measure also fail, care must be taken to avoid fluid overload and the patient should be prepared for dialysis.

Acute fatty liver of pregnancy

Management principles include delivery of the fetus and treatment of the acute liver failure. Coagulopathy may complicate the delivery and must be corrected beforehand. Management of liver failure also includes maintenance of the blood glucose level, the use oflactulose to limit the effects of intestinal bacteria and administration of vitamin K to mother and baby. Intubation and ventilation may be necessary in the comatose mother who cannot protect her airway. Associated complications of renal failure and pancreatitis need to be managed individually.

Insulin Products for Travel

Populations that have a relatively high prevalence of this disease. One in five Indo-Asians over the age of 65 is diabetic (Roshan et al., 1996), with a high prevalence of obesity, insulin resistance and complications, including diabetic nephropathy and myocardial infarction. During travel they may also be fasting for religious reasons.

Metabolic Advantage of Reduced Protein Formula

Dehydration and Kidney Functions Potential renal solute load refers to solutes of dietary origin that would need to be excreted in the urine if not utilized by the body. It represents the sum of dietary nitrogen, sodium, potassium, chloride and phosphorus 18 and is a suitable parameter to measure the risk of dehydration illness. When ingested in excess, proteins constitute a considerable part of the solutes that must be excreted by the kidneys. Taking this into consideration, Ziegler and Fomon 18 recommended reducing the maximum protein content of infant formula from the level of 4.5g 100kcal, specified by the Food and Drug Administration, to 3.2g 100kcal. As an adaptive response to a high solute load, glomerular filtration rate and kidney size increase. While the adverse effects of a high protein intake in patients with kidney disease have been documented, there is to date no clear evidence of such detrimental effects in healthy individuals. The effect of formula- vs. breastfeeding...

Hospital Infection Control and Antibiotic Prophylaxis

Hospital infection control measures may prevent a proportion of nosocomial infections. Handwashing plays a central role, reducing transmission of pathogens between individuals and from the hands of a given individual to vulnerable sites such as wounds and dialysis catheters. Perioperative antibiotic prophylaxis is also important in preventing surgical sepsis, together with good skin preparation before surgery and aseptic and surgical techniques. There is a wide range of other possible measures, implementation of which will be dictated by the global setting and healthcare infrastructure. Affluent nations can implement hospital infection control through an infection control team who devise policies, monitor hospital infections from a diagnostic microbiology laboratory or by active ward-based surveillance and implement outbreak procedures where necessary. An infection control manual containing policies detailing the approach to a wide range of issues from antibiotic use, to dealing with...

Serum methylmalonate and homocysteine levels

Deoxyadenosyl cobalamin is required as a coenzyme in the isom-erization of methylmalonyl CoA to succinyl CoA. In patients with cobalamin deficiency sufficient to cause anaemia or neuropathy, the serum methylmalonate (MMA) level is raised. Sensitive methods for measuring MMA and homocysteine in serum have been introduced and recommended for the early diagnosis of cobalamin deficiency, even in the absence of haematological abnormalities or subnormal levels of serum cobalamin or folate. Serum MMA fluctuates, however, in patients with renal failure. Mildly elevated serum MMA and or homocysteine levels occur in up to 30 of apparently healthy volunteers, with serum cobalamin levels up to 350 ng L and normal serum folate levels 15 of elderly subjects, even with cobalamin levels 350 ng L, have this pattern of raised metabolite levels. These findings bring into question the exact cut-off points for normal MMA and homocysteine levels. It is also unclear at present whether these mildly raised...

Effects of Renal Disease on Pharmacokinetics

A 67-year-old man had been functionally anephric, requiring outpatient hemodialysis for several years. He was hospitalized for revision of his arteriovenous shunt and postoperatively complained of symptoms of gastroesophageal reflux. This complaint prompted institution of cimetidine therapy. In view of the patient's impaired renal function, the usually prescribed dose was reduced by half. Three days later, the patient was noted to be confused. An initial diagnosis of dialysis dementia was made and the family was informed that dialysis would be discontinued. On teaching rounds, the suggestion was made that cime-tidine be discontinued. Two days later the patient was alert and was discharged from the hospital to resume outpatient hemodialysis therapy. Illness, aging, sex, and other patient factors may have important effects on pharmacodynamic aspects of patient response to drugs. For example, patients with advanced pulmonary insufficiency are particularly sensitive to the respiratory...

Pharmacokinetics in Patients Requiring Renal Replacement Therapy

Hemodialysis is an area of long-standing interest to pharmacologists. The pioneer American pharmacologist, John Jacob Abel, can be credited with designing the first artificial kidney (1). He conducted extensive studies in dogs to demonstrate the efficacy of hemodialysis in removing poisons and drugs. European scientists were the first to apply this technique to humans, and Kolff sent a rotating-drum artificial kidney to the United States when the Second World War ended (2, 3). Repetitive use of hemodial-ysis for treating patients with chronic renal failure finally was made possible by the development of techniques for establishing long-lasting vascular access in the 1960s. By the late 1970s, continuous peritoneal dialysis had become a therapeutic alternative for these patients and offered the advantages of simpler, non-machine-dependent home therapy and less hemodynamic stress (4). In 1977, continuous arteriovenous hemofiltration (CAVH) was introduced as a method for removing fluid...

Preimplantation Genetic Diagnosis For Single Gene Disorders

The majority (85 ) of ADPKD is caused by PKD1, assigned to chromosome 16p13.3, the rest being attributed to PKD2, located on chromosome 4q21-q23 12 . Because both PKD1 and PKD2 are characterised by enlargement of the kidneys due to the formation of bilateral or multiple unilateral fluid-filled cysts, presymptomatic diagnosis is available by abdominal ultrasound examination of young adults at risk, which also allows improving hypertension management in these patients, appearing long before the actual manifestation of renal disease. Although mutation rate is believed to be high, especially in PKD1, approximately half of the cases are still ancestry-related, allowing the diagnosis by linkage analysis. PKD1 gene contains 46 exons encoding the membrane protein poly-cystin 1 involved in cell-to-cell interaction, while PKD2 has at least 15 exons and encodes polycystin 2, which is a channel protein. Both of these proteins interact to produce new calcium-permeable nonselective cation currents,...

Effects of Liver Disease on the Renal Elimination of Drugs


Drug therapy in patients with advanced cirrhosis is further complicated by the fact that renal blood flow and glomerular filtration rate are frequently depressed in these patients in the absence of other known causes of renal failure. This condition, termed the hepatorenal syndrome, occurs in a setting of vasodilation of the splanchnic circulation that results in underfilling of the systemic circulation. This activates pressor responses, causing marked vasoconstriction of the renal circulation (44). The functional nature of this syndrome is indicated by the observations that it reverses following successful liver transplantation and is not accompanied by significant histological evidence of kidney damage.

Parenteral iron therapy

Disease, such as inflammatory bowel disease, is present. It is also occasionally necessary in gluten-induced enteropathy and when it is essential to replete body stores rapidly (e.g. where severe iron deficiency anaemia is first diagnosed in late pregnancy), or when oral iron cannot keep pace with continuing haemorrhage (e.g. in patients with hereditary haemorrhagic telangiectasia). Patients with chronic renal failure who are being treated with recombinant erythropoietin are also likely to require parenteral iron therapy. In this situation, the demand for iron by the expanded erythron may outstrip the ability to mobilize iron from stores, leading to a 'functional' iron deficiency. Increased red cell loss at dialysis contributes to iron needs and oral iron therapy is usually inadequate to prevent an impaired response to erythropoietin. The use of ' hypochromic cells' for detection of functional iron deficiency is discussed on p. 36. From all parenteral preparations, the iron complex is...

Environmental and Safety Issues on PVC

B) Stabilizer Depending on the region of the world, commonly used photothermal stabilizers in PVC include compounds of lead, tin, barium, zinc and cadmium. Toxicity of all lead compounds causing neurological effects in children, kidney damage, sterility, and even cancer is well known. Cadmium compounds and organotin compounds are also toxic, affecting the nervous system and the kidney.

Iron supply to the tissues

Iron Deficiency Bone Marrow

As iron supply to the erythron diminishes, the new red cells produced are increasingly hypochromic. Assessment of the haemoglobin content of individual red cells, which is possible using some automated cell counters, allows measurement of the percentage of hypochromic cells. Values rising to above 6 may help in the early identification of impaired iron supply in patients with chronic renal failure who are receiving treatment with recombinant erythropoietin, when associated inflammatory disease means that other measures of iron status can be misleading.

Immediate haemolytic transfusion reactions

Cell Destruction Adcc

Intravascular destruction of red cells liberates Hb into the circulation. Once haptoglobins are saturated, Hb will also appear in the urine. If haemoglobinuria is very severe, haemosiderinuria may be seen. Renal complications consist of acute renal failure with oliguria and anuria, possibly the result of hypotension and or the action of activated complement. Immediate extravascular destruction of red cells may be accompanied by hyperbilirubinaemia, occasionally haemoglo-binaemia due to antibody-dependent cytotoxicity (in severe cases), fever and failure to achieve the expected rise in Hb level. The signs and symptoms are less severe and dramatic than in intravascular haemolysis and usually appear more than 1 h after the start of transfusion (Table 16.8). There may be no signs or symptoms at all. Renal failure is very rare, even when the antibody binds the earlier components of the complement cascade. The symptoms are attributed in a large degree to liberation of cytokines from...

[ 3mt m1 dmA mi i dy 187127pn mj dm2Jr m3

The result that, at dialysis equilibrium, the interaction of the protein with the mixed solvent, expressed as interaction with component 3, can be favorable or unfavorable follows because the amount of water and ligand found in the immediate domain of the protein is defined by the relative affinities of water and ligand for the protein. By definition, in an aqueous medium, the binding of one molecule of ligand to a site on a protein molecule must displace molecules of water from that site, if for no other reason than the physical law that two bodies cannot occupy the same space at the same time. This is illustrated in Fig. 1. A contact between water mol- where P is protein with the binding site empty, PL is the protein with the site occupied by ligand, and P H2O,,, is protein with the site occupied by m molecules of water. It is clear that, at the site, there is competition between water and ligand molecules 13 , Therefore, the free energy of binding at a site, measured by dialysis...

Effects Of Pathological Conditions

Increased toxicity of drugs undergoing significant metabolism, such as chloramphenicol, has been found in uraemic patients. The half-lives of a number of drugs are prolonged in renal failure, although this effect is variable and by no means the general rule, different drugs being differently affected. Chronic renal disease may also affect metabolism, not necessarily because of impaired metabolism in the kidney, but because of an indirect effect of renal failure on liver metabolism. For example, in animals with renal failure it was observed that there was a decrease in hepatic cytochromes P-450 content, and consequently zoxazolamine paralysis time and ketamine narcosis time were prolonged. Cardiac failure may also affect metabolism by altering hepatic blood flow. However even after heart attack without hypotension or cardiac failure, metabolism may be affected. For example, the plasma clearance of lidocaine is reduced in this situation. Other diseases such as...

Complete Heparin Lyase Catalyzed Depolymerization of Radiolabeled HS

Dissolve GAG sample containing radiolabeled HS in 50 L of sodium phosphate buffer. Dialyze sample against sodium phosphate buffer using 1000 MWCO dialysis membrane or a Centricon (YM3, MWCO 3000) centrifugal filter unit (see Note 9). 9. The presence of metals, detergents, and denaturants can interfere with the activity of the lyases. Before digesting the samples, detergents should be removed by precipitation with potassium chloride or by using a detergent-removal column such as Biobeads (Bio-Rad). Urea and guanidine should be removed by exhaustive dialysis using controlled-pore dialysis membrane (MWCO 1000).

External Loop Airlift Reactor

Basic Diagram Fluidized Bed Reactor

Figure 6 Membrane reactors (a) membrane reactor with bypass membrane for perfusion mode, (b) typical membrane reactor for immobilized cells (hollow fiber reactor), and (c) membrane reactor with internal dialysis membrane (Bioengineering Ltd., Switzerland). A, air inlet G, gas exhaust M, motor P, permeate. Figure 6 Membrane reactors (a) membrane reactor with bypass membrane for perfusion mode, (b) typical membrane reactor for immobilized cells (hollow fiber reactor), and (c) membrane reactor with internal dialysis membrane (Bioengineering Ltd., Switzerland). A, air inlet G, gas exhaust M, motor P, permeate. product is leaving the reaction system on the permeate side, the culture medium passes the membrane using a bypass on the retentate side. The whole culture medium inside the bioreactor represents permeate. As shown in Fig. 6b, simultaneous nutrient and extracellular product exchange can take place in special membrane modules applied instead of cross-flow assemblies. Here the cells...

Druginduced Immune Suppression

A 57-year-old man is planning to make a trip through Southeast Asia. At the age of 50 he developed a nephropathy with proteinuria due to Henoch-Schonlein disease. He gradually developed end-stage renal insufficiency for which, after 2 years of dialysis, he received a kidney transplant. Since the transplant 1 year ago, he has been treated with mycophenolate mofetil (500mgt.d.s.) and prednisolone (10mgo.d.). He is in good general condition with only an unchanging mild renal insufficiency. He is advised to have malaria prophylaxis with mefloquine, in adjusted dosage according to the level of renal insufficiency. Mefloquine does not interact with mycophenolate mofetil or prednisolone. He had a diphtheria-tetanus and polio booster 8 years ago just before the onset of the kidney problem. He is advised to have vaccination against typhoid fever, and antibodies against hepatitis A are also measured. In the case of a negative serology result, immunoglobulin will be administered just before...

Evaluation from Protein Small Solute Covolume

Determination by Equilibrium Dialysis or Gel Chromatography Provided that the dialysis membrane or gel chromatographic matrix is chosen to confine the protein to one phase, the ratio of small-solute concentrations in the protein-containing and protein-free phases (Q, and C , respectively) may be substituted into the expression 66

Complete Chondroitin Lyase Catalyzed Depolymerization of Radiolabeled GAGs

Dissolve GAGs sample containing radiolabeled (35S, 14C, or 3H) CS or DS in 1 mL of distilled water. Exhaustively dialyze sample against water using 1000-MWC0 dialysis membrane. Freeze-dry nondialyzable retentate. Add 50 L of Tris-HCl sodium acetate buffer. Alternatively, the radiolabeled sample can be buffer exchanged using a Centricon (YM3, 3000 MWCO) centrifugal filter unit. 6. Due to batch variations in enzymes, or the age of laboratory stocks, it is always advisable to test enzyme activities on a standard substrate before using them on valuable samples. This can easily be performed by incubating chondroitin lyase with 1.5 mg mL of CS and monitoring the time course of the digest by the increase in absorbance at 232 nm. Once the digest appears to have ceased, a second addition of enzyme is useful to confirm that a true end point has been reached, rather than the enzyme having become prematurely inactivated. The quantity of enzyme and or the incubation time can then be adjusted...

The antibodies of the MNS system

A cold-reacting N-like antibody (anti-Nf) has been described in certain patients undergoing renal dialysis, regardless of their MN group. Although it may cause confusion in cross-matching tests, anti-Nf is usually of little clinical importance, but has been reported to cause hyperacute renal graft rejection. Nf arises from the effects of minute amounts of formaldehyde (used to sterilize the dialyser coil) on the patient's red cells these changed cells stimulate anti-Nf.

Relation Between Preferential Interactions And Transfer Free Energy

The redistribution of solvent components in the vicinity of a protein measured by dialysis equilibrium, (dmildmdT.v.,, , is a necessary consequence of the mutual perturbations of the chemical potentials of the protein and ligand by each other 2,6,10-12 Equation (7) has the practical meaning that depending on whether, at a given solvent composition m3, the interaction of the protein with the cosolvent-contain-ing solution is thermodynamically favorable, unfavorable, or indifferent (respectively, negative, positive, or zero value of the preferential interaction parameter), the parameter (dm ldrnj)7 l3 will be positive, negative, or zero, resulting in turn in experimentally measured preferential binding, preferential exclusion, or no interaction. Preferential exclusion of the cosolvent manifests itself in dialysis equilibrium experiments by giving negative stoichiometrics of binding. Quite evidently, this means that the solvent vicinal to the protein contains an excess of water over its...

Infections causing haemolytic anaemia

Appearance of black urine is usually accompanied by further fever and often back pain in the renal angle. Oliguric renal failure may ensue, particularly if the patient becomes hypotensive and hypovolaemic from dehydration. Pulmonary and cerebral symptoms may develop. The condition was first described in white people, most of whom had been treated with quinine, and the importance of this association was stressed. However, the condition is seen in all populations in endemic areas and certainly does not seem to be confined to non-immune individuals. In these indigenous populations, glucose-6-phosphate dehydro-genase (G6PD) deficiency may play a part in the pathogenesis as well as quinine exposure. The spread of chloroquine-resistant malaria in the Far East has led to an increased use of quinine and an increase in the incidence of blackwater fever. The degree of parasitaemia is very variable. In about one-half of the cases the parasite count may be high, whereas in others the count may be...

General Adaptation Syndrome

Selye's general adaptation syndrome involves three stages of physiological response alarm, resistance, and exhaustion. During the alarm stage, the organism detects a stressor and responds with SNS and hormonal activation. The second stage, resistance, is characterized by the body's efforts to neutralize the effects of the stressor. Such attempts are meant to return the body to a state of homeostasis, or balance. (The concept of homeostasis, or the tendency of the body to seek to achieve an optimal, adaptive level of activity, was developed earlier by Walter Cannon.) Finally, if the resistance stage is prolonged, exhaustion occurs, which can result in illness. Selye referred to such illnesses as diseases of adaptation. In this category of diseases, he included hypertension, cardiovascular disease, kidney disease, peptic ulcer, hyperthyroidism, and asthma.

How Transfer Free Energy Modulates Protein Reactions

Shed Roof Cabin Design

As shown by Eq. (1), the effect of cosolvent on a reaction in a solvent of a given composition is defined by the change in preferential binding of the cosolvent to the protein during the course of the reaction. Its effect relative to water is given by the difference between the transfer free energies in the two end states of the reaction. Examination of a large number of cosolvents by dialysis equilibrium has shown that all of the stabilizing and salting out agents are preferentially excluded from native globular proteins, that is, their contact with protein is thermodynamically unfavorable (d iiJdmi)T,p,m2 is positive. Conversely, d naturants (6 M GuaHCl, 8 M urea) mostly interact favorably with the unfolded state of the protein (3p.2 9m3)r, .m2 is negative. A selected list of typical results is given in Table 1.

David J Reich Cosme Manzarbeitia Radi Zaki Jorge A Ortiz and Sergio Alvarez

KIDNEY TRANSPLANTATION Most technical complications in the kidney transplant recipient occur during the early postoperative period (i.e., within the first month after transplant). A few of these, however, may be seen later on in the course of treatment and are briefly described here. By and large, the major cause of morbidity and kidney graft loss in the late postoperative period is the development of chronic, irreversible rejection. Finally, many of the long-term complications of immunosuppression have already been described in Chapter 18 and are not repeated here. The ureteric anastomosis is the Achilles' heel of kidney transplantation. There is a high risk of ischemic injury, a result of the segmental blood supply to the ureters. Vascular disruption of the ureters is dependent on the technique of the harvesting surgeon to maintain a significant amount of tissue around the ureters during extraction. Ureters are more vulnerable to ischemic injury during living related or living...

Removing Protein Heterogeneity by Point Mutation

They are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. ACE is a highly glycosylated protein and has proved hard to crystallize for more than two decades. Unglycosylated ACE was shown to be inactive. There are two ACE isoforms, one in somatic tissues and one in sperm cells. The testis ACE (tACE) is identical to the portion of somatic ACE that is sufficient for its cardiovascular function, except for the N-terminal 36 residues. A 2.0 A resolution structure of a truncated and chemically modified form of tACE recently became available 16, 17 . The mutant tACE (tACE3A6NJ) lacks the N-terminal 36 residues and the C-terminal hydrophobic transmembrane domain, was expressed in the presence of the a-glucosidase I inhibitor N-butyl-deoxynojirimycin and was treated with endoglycosidase H to remove all but the terminal N-acetylglucosamine residues. It was homogeneous on SDS-PAGE and retained full enzymatic activity, but the expression...

The pathological renal characteristics of preeclampsia

Proximal Tubule Cell Patch Clamp

The ultrastructural renal consequences of pre-eclampsia are primarily seen in the glomerulus. The glomerulus is large and bloodless, an appearance compatible with gestational hypertension of any cause, but it is particularly marked in pre-eclamptic specimens. In pre-eclampsia the glomer-ular enlargement is seen in isolation, without any accompanying increases in the stroma or cells, distinguishing nephropathy of a pre-eclamptic origin from that associated with glomerulonephri-tis or diabetes.

Alloimmune haemolytic anaemia

Classically, haemolysis occurs on the second or subsequent exposure to the drug and may develop within minutes or hours of drug ingestion. Severe intravascular haemolysis may occur with fever, rigors or nausea and, in extreme cases, acute renal failure. Several groups have reported fatal immune haemolysis with the third-generation cephalosporin ceftriaxone, and cefotaxime and ceftazidime have also been reported to cause immune haemolytic anaemia. Second-generation cephalosporins have also been implicated, although there are fewer reports with them than with third-generation antibiotics. Diclofenac can also cause an immune haemolytic anaemia with intravascular haemolysis, and this is thought to be mediated by both immune complex and drug adsorption mechanisms.

Nayere Zaeri and lerachmiel Daskal

Banff Schema Liver Rejection

The transplant professional counts heavily on the contributions of the pathologist for diagnosis before and after transplantation. While it is not the purpose of this manual to offer a description of all the conditions that lead to end-stage organ disease, it is important to offer an overview of posttransplant pathology as it pertains to diagnosis and management of acute rejection and other conditions that cause allograft dysfunction in the postoperative period. Finally, due to the sparse and often controversial information regarding pancreatic allograft biopsies, only liver and kidney transplantation are addressed here. 21.2. KIDNEY TRANSPLANT One of the most important roles of the transplant pathologist is to evaluate an organ for its suitability for transplantation and its postperfusion status. This assessment must take place prior to and immediately after transplantation. A small-needle biopsy is submitted for frozen-section evaluation. Commonly encountered problems consist of...

Gastrointestinal laboratory findings

AFMP is a multisystem syndrome characterized by abdominal pain, malaise, confusion or encephalopathy, hypertension and proteinuria that characteristically has its onset in the third trimester. In contrast to pre-eclampsia, these women are clinically jaundiced and have severe hepatocel-lular dysfunction. This hepatocellular dysfunction frequently manifests itself not only by elevated transaminases but also by obvious coagulopathy and hypoglycemia. This latter finding is ominous and associated with an increased mortality risk. Up to 50 of these women will also develop renal failure and pancreatitis. As with pre-eclampsia, the only known cure for AFMP is delivery. LCHAD deficiency can produce a clinical syndrome resembling AFMP or HELLP syndrome, particularly if the fetus is affected. It can sometimes also resemble persistent hyperemesis gravidarum (Wilcken et al., 1993).

Miniaturization and Microfluidics

In addition, great efforts have been made recently regarding the adaptation ofvarious sample pretreatment methods on microfluidic devices, such as sample filtration, dialysis, pre-concentration, and derivatization 56 . The aspiration is to integrate the sample pretreatment processes along with the sample analysis methods on a single microfluidic chip. Ideally, these lab-on-a-chip devices will be sophisticated enough to perform all the steps required for the complete analysis of a complex real sample autonomously.

Preventing proteolysis by denaturation

Lengthy procedures such as overnight dialysis should not be undertaken without the inclusion of proteinase inhibitors in the dialysis buffer. In some systems, for example yeasts and some filamentous fungi, prolonged incubation of extracts results in proteinase activation because endogenous inhibitors are degraded

Mechanisms of Renal Handling of Drugs

The kidney plays a major role in the clearance of insulin from the systemic circulation, removing approximately 50 of endogenous insulin and a greater proportion of insulin administered to diabetic patients (19). Insulin is filtered at the glomerulus and reabsorbed by proximal tubule cells, where it is degraded by proteolytic enzymes. Insulin requirements are markedly reduced in diabetic patients with impaired renal function. Imipenem and perhaps other Renal tubular mechanisms of excretion and reabsorption can be analyzed by stop-flow and other standard methods used in renal physiology, but detailed studies are seldom performed. For most drugs, all that has been done has been to correlate renal drug clearance with the reciprocal of serum creatinine or with creatinine clearance. Even though creatinine clearance primarily reflects glomerular filtration rate, it serves as a rough guide to the renal clearance of drugs that have extensive renal tubular secretion or reabsorption. This is a...

Diagnosis of superimposed preeclampsia in chronic hypertension renal disease and diabetes

Chronic hypertension is subdivided into essential and secondary due to underlying causes such as renal disease (e.g. glomerulonephritis, reflux nephropathy, adult polycystic kidney disease), systemic disease with renal complications (e.g. systemic lupus erythema-tosus, diabetes), renal artery stenosis or endocrine disorders (e.g. cushings, phaeochromocytoma) (Brown et al., 2000).

Restrictively Metabolized Drugs ER

It usually is assumed that the free drug concentration in blood is equal to the drug concentration to which hepatic drug-metabolizing enzymes are exposed. Although protein binding would not be anticipated to change hepatic clearance significantly for restrictively metabolized drugs that have fu 80 , displacement of highly bound (fu 20 ) drugs from their plasma protein binding sites will result in a significant increase in their hepatic clearance. However, steady-state concentrations of unbound drug will be unchanged as long as there is no change in CLint . This occurs in some drug interactions, as diagrammed in Figure 7.2. This situation also is encountered in pathological conditions in which plasma proteins or plasma protein binding is decreased, as described in Chapter 5 for phenytoin kinetics in patients with impaired renal function. Since pharmacological effects

Conditions with No Available Direct Mutation Testing

Although the availability of the sequence information is one of the major conditions in undertaking PGD for Mendelian diseases, it is also possible to perform PGD when no exact mutation is known. One of the examples demonstrating feasibility of the approach may be the most recent report of PGD for autosomal dominant polycystic kidney disease (ADPKD), caused by either PKD1 orPKD2 ADPKD is a common genetic disorder present in 1 1000 individuals worldwide, which causes progressive cyst formation and may eventually lead to renal failure by late middle age, requiring renal transplantation or dialysis 12 . The overall health implications of ADPKD are obvious from the fact that approximately 10 of all patients at need for renal transplantation or dialysis have this disease. ADPKD is caused by either PKD1 or PKD2 genes 31-33 . Because of an extremely variable expression and the age of onset, much higher in PKD2, only half of the patients carrying these genes may present with severe clinical...

Imaging of Protein Distribution

The protein adsorption that takes place on hollow-fiber dialysis membranes with nanosized pores, which are used for the treatment of patients with renal failure, has been evaluated by TOF-SIMS imaging in an effort to develop higher-performance dialysis techniques. The adsorption of a model protein, BSA, onto three commercially available, hollow-fiber dialysis membranes of different components and different structures, was measured with TOF-SIMS, and then the SIMS spectra were analyzed in the light of mutual information to select specific peaks for chemical imaging (Aoyagi et al. 2003, 2004a).

Drug Dosing Guidelines for Patients Requiring Renal Replacement Therapy

Perhaps the simplest approach is to guide dosage using standard reference tables, such as those published by Aronoff and colleagues (35). These tables are based on published literature and suggest drug dose reductions for patients with various levels of renal impairment, as well as for patients requiring conventional hemodialysis, chronic ambulatory peritoneal dialysis, and continuous renal replacement therapy. Although fewer data are available for patients treated with continuous renal replacement therapy than for those treated with conventional intermittent hemodialysis, UFR generally ranges from 10 to 16 mL min during hemofiltration without extracorporeal blood pumping and from 20 to 30 mL min when blood pumps are used (21). Accordingly, for many drugs, the dose recommendation for patients treated with continuous renal replacement therapy is considered simply to be that which is appropriate for patients with a glomerular filtration rate of 10-50 mL min. estimating this loss from...

Some Interesting Modification Stories

Erythropoietin has become the most produced recombinant protein drug in the world. It increases patient red blood cell counts hence, there is a very large market for counteracting anaemia associated with cancer treatment and kidney disease. It is also used illegally as a performance-enhancing drug in sports.

Effects Of Renal Disease On Drug Distribution

Impaired renal function is associated with important changes in the binding of some drugs to plasma proteins. In some cases the tissue binding of drugs is also affected. Phenytoin is an acidic, restrictively eliminated drug that can be used to illustrate some of the changes in drug distribution and elimination that occur in patients with impaired renal function. In patients with normal renal function, 92 of the phenytoin in plasma is protein bound. However, the percentage that is unbound or free rises from 8 in these individuals to 16 , or more, in hemodialysis-dependent patients. In a study comparing phenytoin pharmacokinetics in normal subjects and uremic patients, Odar-Cederlof and Borga (26) administered a single low dose of this drug so that first-order kinetics were approximated. The results shown in Table 5.3 can be inferred from their study. The uremic patients had an increase in distribution volume that was consistent with the observed decrease in phenytoin binding to plasma...

Modification of Drug Therapy in Patients with Liver Disease

It is advisable to avoid using certain drugs in patients with advanced liver disease. For example, angiotensin-converting enzyme inhibitors and non-steroidal anti-inflammatory drugs should be avoided because of their potential to cause acute renal failure. Paradoxically, administration of captopril

Systemic lupus erythematosus and antiphospholipid syndrome

Pregnancy in systemic lupus erythematosus (SLE) is associated with an increased risk of preeclampsia (Khamashta and Hughes, 1997). However, this risk is largely attributable to the presence of certain risk factors, particularly the presence of antiphospholipid antibodies (APAs), renal involvement of the lupus with or without hypertension, and active disease at the time of conception (Nelson-Piercy and Khamashta, 2003). Thus for women with SLE without antiphospholipid antibodies, lupus nephritis, or hypertension whose disease is quiescent at the time of conception, the risk of pre-eclampsia is probably not increased compared to the background rate. One exception to this may be women Antiphospholipid syndrome (APS) is discussed below. Women with proteinuria (as above for diabetes) or renal impairment (see below) from any cause have an increased risk of super-imposed pre-eclampsia. Even quiescent renal lupus is associated with an increased risk of fetal loss, pre-eclampsia and IUGR,...

Biochemical aspects of toxicology

The interaction of a foreign compound with a biological system is two-fold there is the effect of the organism on the compound and the effect of the compound on the organism. It is necessary to appreciate both for a mechanistic view of toxicology. The first of these includes the absorption, distribution, metabolism and excretion of xenobiotics, which are all factors of importance in the toxic process and which have a biochemical basis in many instances. The mode of action of toxic compounds in the interaction with cellular components, and at the molecular level with structural proteins and other macromolecules, enzymes and receptors, and the types of toxic response produced, are included in the second category of interaction. However, a biological system is a dynamic one and therefore a series of events may follow the initial response. For instance, a toxic compound may cause liver or kidney damage and thereby limits its own metabolism or excretion.

Pathogenesis And Clinical Significance

Almost all of the organs of the human body can be infected by one or more of the spectrum of 14 microsporidian species described in the previous section. Many tissues and cell types are involved (Table 8.1). According to site of infection, clinical manifestations may be diarrhoea, weight loss, cholecystitis, cholangitis, bronchitis, bronchiolitis, pneumonitis, sinusitis, rhinitis, hepatitis, peritonitis, nephritis, ureteritis, cystitis, urethritis, prostatitis, keratoconjunctivitis, corneal ulcer, myositis or encephalitis. The pathology has been reviewed by Weber et al. (1994) and Schwartz et al. (1996). Cardiac disease and probable pancreatic, parathyroid and thyroid dysfunction have been reported for T. anthropophthera (Yachnis et al., 1996). Without treatment, the outcome is likely to be fatal for severely immunocompromised hosts infected with the disseminating species. The kidney is a site of predilection for all three Encephalitozoon spp. (Figure 8.5F on Plate IV) and was...

Approach to Travelers Diarrhea

Preventive measures and supportive therapy should be reviewed, as well as the indications for empiric antimicrobial therapy. Antimotility agents such as loperamide and diphenoxylate can improve diarrhea, but should not be used if dysentery or fever is present. Anticholinergic effects may lead paradoxically to abdominal distension, constipation, or paralytic ileus. The older traveler may be wise to begin antimicrobial therapy early in an illness in order to minimize the risk of complications. A fluoroquinolone is the treatment of choice the dose must be reduced if renal failure is present, and caution is Prophylactic antimicrobial agents for travelers' diarrhea are generally not recommended for the healthy traveler exceptions include those who cannot afford to be ill during travel and those with a bad 'track record' for travelers' diarrhea. Many travelers, often older persons, are at increased risk of acquiring travelers' diarrhea due to reduced gastric acidity from achlorhydria,...

Vascular Complications

Renal artery stenosis is a late complication most commonly associated with living related or living unrelated kidney transplants. The lower incidence in cadaveric transplants is related to the use of a Carrel patch. The Carrel patch is a cuff of aortic tissue surrounding the orifice of the renal artery in which one can sew the anastomosis to the patch, thus avoiding stenosis of the renal artery orifice. In general, the overall incidence is falling due to decreased use of the internal iliac artery as the inflow vessel for anastomosis to the allograft renal artery. Other surgical techniques that avoid this complication include the use of the external iliac artery as the site of anastomosis, or, as in living donors, arterial punch devices to create an end-to-side anastomosis. Symptoms of renal artery stenosis include hypertension or decreased allograft function. Ultrasound findings are consistent with increased peak systolic velocities. Patients given angiotensin-converting enzyme...

Tissue Lesions Liver Necrosis

Widely used analgesic which causes liver necrosis and sometimes renal failure after overdoses in many species. The half-life is increased after overdoses due to impaired conjugation of the drug. Toxicity is due to metabolic activation and is increased in patients or animals exposed to microsomal enzyme inducers. The reactive metabolite (NAPQI) reacts with glutathione, but depletes it after an excessive dose and then binds to liver protein. Metabolic activation is catalysed by cytochrome P-450, and the particular isoform (2E1, 1A2 or 3A4) depends on the dose. Antidote is N-acetylcysteine which promotes the synthesis of new glutathione and may also be involved in the detoxication. Bromobenzene. A hepatotoxic industrial solvent which causes centrilobular liver necrosis. It is metabolized in the liver to a reactive epoxide (3,4) which is detoxified by conjugation with glutathione, leading to excretion of a mercapturic acid. Depletion of glutathione with an excess dose leads...

Tissue Binding of Drugs

The distribution volume of some drugs also can be altered when renal function is impaired. As described in Chapter 3, Sheiner et al. (27) have shown that impaired renal function is associated with a decrease in digoxin distribution volume that is described by the following equation This presumably reflects a reduction in tissue levels of Na K-ATPase, an enzyme that represents a major tissue-binding site for digoxin (28). In other cases in which distribution volume is decreased in patients with impaired renal function, the relationship between the degree of renal insufficiency and reduction in distribution volume has not been characterized nor have plausible mechanisms been proposed.

Diagnosis of folate deficiency Serum folate

The serum folate level rises in severe cobalamin deficiency because of blockage in conversion of methyl THF, the major circulating form, to THF raised levels have also been reported in the intestinal stagnant loop syndrome, acute renal failure and active liver damage. (High levels are also obtained when the patient is receiving folic acid therapy, when the serum is contaminated with folate or folate-producing bacteria or, if a sample is haemolysed, because of the high concentration of folate in red cells.)

Bioencapsuiation of Genetically Engineered E coli Cells for Urea and Ammonia Removal

Urea and ammonia removal are needed m kidney failure, liver failure, environmental decontamination and regeneration of water supply in space travel. Standard dialysis machines are usually complex and expensive. Several alternatives have not been sufficiently effective. Prakash and Chang therefore studied the use of bioencapsulated genetically engineered E coli DH5 cells containing K. aerogens urease gene (26,27). The bioencapsuiation of the genetically engineered bacteria was prepared by the general procedure using the apparatus assembly shown m Fig. 1. The details of the bioencapsuiation process parameters are described m Section 5.

Surface Modifications for Reducing Nonspecific Protein Adsorption

There have been many interests in membrane processes for last decade because of they are extremely efficient, have a low energy consumption, and are easy to carry out. Nowadays, membranes are used widely, especially in biomedical applications such as dialysis, plasmapheresis, and oxygenation of blood during cardiac surgery. However, it is well known that the major obstacle to the extensive use of membrane processes in therapeutic treatment is protein fouling of polymeric membrane materials. Protein deposition on the membrane surface can cause unstable transport characteristics, and cellular interactions with artificial surface are also assumed to be mediated through adsorbed proteins (Deppisch et al. 1998). Designing a polymer surface that rejects proteins (i. e., a nonfouling surface) has been a central issue in the field ofbiomedical materials research (Ikada 1994 Klee and Hocker 1999 Ratner et al. 1979). The adsorption of proteins is highly complex. We do understand that these...

Mechanisms Of Drug Interactions

As described in Chapter 4, medications that alter GI motility can affect drug absorption by changing the rate at which drugs are transported into and through the small intestine, the primary site of absorption for most drugs. The prokinetic agent metoclopramide, for instance, increases the rate of drug transport through the gut, thereby increasing the rate of absorption for certain drugs and also altering the extent of absorption in some cases. For instance, despite no change in cyclosporine elimination clearance, the mean area under the plasma concentration-vs-time curve (AUC) and maximum serum concentration (Cmax) of cyclosporine increased by 22 and 46 , respectively, when it was given with metoclopramide to 14 kidney transplant patients. Further, the time to reach Cmax (Tmax) was significantly shorter following administration of this combination (17).

Clinical Features

Course (Anzil et al., 1991 Martinez and Visves-vara, 1997). GAE has a clinical picture that mimics a single or multiple space-occupying lesion. Localizing neurologic signs and symptoms, such as hemiparesis and seizures, appear early in the clinical course. Mental status abnormalities, headache and stiff neck may be present. Palsies involving the third and the sixth cranial nerves may be seen. Nausea, vomiting, low-grade fever, lethargy, cerebellar ataxia and diplopia are also part of the clinical features. Chest X-rays of the lungs may demonstrate focal consolidated areas and pneumonitis. The direct cause of death in GAE is usually acute broncho-pneumonia, liver or renal failure septicemia (Carter et al., 1981 Martinez and Visvesvara, 1997 Visvesvara and Stehr-Green, 1990).

Operative and Postoperative Care and Complications

Dominguez J, Clase CM, Mahalti K, et al. Is routine ureteric stenting needed in kidney transplantation A randomized trial. Transplantation 2000 70(4) 597-601. Galazka Z, Szmidt J, Nazarewski S, et al. Kidney transplantation in recipients with atherosclerotic iliac vessels. Ann Transpl 1999 4(2) 43-44. Kahl A, Bechstein WO, Frei U. Trends and perspectives in pancreas and simultaneous pancreas and kidney transplantation. Curr Opin Urol 2001 11(2) 165-174. Paul LC, Hayry P, Foegh M, et al. Diagnostic criteria for chronic rejection accelerated graft atherosclerosis in heart and kidney transplants. Transpl Proc 1993 25 2022-2023. Schult M, Kuster J, Kliem V, et al. Native pyeloureterostomy after kidney transplantation Experience in 48 cases. Transpl Int 2000 13(5) 340-343. Burke GW, Ricordi C, Karatzas T, et al. Donor bone marrow infusion in simultaneous pancreas kidney transplant recipients A preliminary study. Transpl Proc 1995 27(6) 3121-3122. Friese CE, Narumi S, Stock P, Melzer JS....

Eradication of S aureus Carriage

Rates of S. aureus infection are higher in carriers than in non-carriers in a range of clinical settings (Weinstein 1959 Yu etal. 1986 Luzar etal. 1990 Weinke etal. 1992). This is consistent with the finding that individuals are usually infected with their own carriage isolate (Yu etal. 1986 Luzar etal. 1990 Nguyen etal. 1999 von Eiff etal. 2001b). Temporary eradication of carriage has been reported to result in a reduction in nosocomial infection in several patient groups and has been the focus of much recent interest and research. Eradication of S. aureus carriage is usually achieved by the topical application of antibiotic to the anterior nose. The most common agent in use is mupirocin, which has also been applied to exit sites of prosthetic devices such as intravenous and peritoneal dialysis catheters. A potentially promising agent currently under trial is lysostaphin, a peptidoglycan hydrolase secreted by Staphylococcus simulans that cleaves the polyglycine interpeptide bridges...

Cardiorespiratory pathology and pathophysiology

Adult respiratory distress syndrome (ARDS) is often cited as a complication of pre-eclampsia but is an unlikely primary complication of the disease although it may follow aspiration pneumonia or prolonged ventilation. Reporting the occurrence of ARDS in an obstetric intensive care unit, Mabie et al. found only 16 cases of respiratory distress attributable to ARDS over a 6-year period (Mabie et al., 1992). Only 4 of these 16 cases were linked to pre-eclampsia eclampsia. Three of these four cases had additional complications that may have contributed to the development of ARDS (including aspiration pneumonia, lupus nephritis, sepsis and a ruptured liver hematoma with massive blood transfusion). The fourth case had pulmonary edema that developed into ARDS after the patient had a respiratory arrest. These observations are important because most cases of respiratory distress will have a cardiogenic component amenable to intervention. ARDS should never be accepted as a primary diagnosis in...

Multiorgan Toxicity Metals

Widely used metal responsible for multi-organ toxicity, some of which may occur over extended periods of time and may depend on the route of exposure. Thus it causes acute testicular damage in rodents and kidney damage after chronic exposure or delayed after acute exposure. May also be hepatotoxic, causes effects on vascular tissue and bone and Leydig cell tumours. Detoxified by being bound to metallothionein and binds to other proteins containing available SH groups. Enzyme inhibition may underlie some toxicity. Testicular toxicity partly due to ischaemic necrosis following vascular constriction. Kidney damage results from release of metal from metallothionein complex in kidney. Mercury. Exists in three forms, elemental, inorganic and organic with different toxic effects. Elemental mercury is absorbed as a vapour and may enter the CNS and cause toxicity there. Inorganic mercury is

Catrin Pritchard and Margit Burmeister

Pulsed-field gel electrophoresis (PFGE) has the capacity to fractionate large fragments of DNA up to thousands of kilobases in size. This aspect of the technique has been exploited for constructing longrange restricdon maps of chromosomes from many different species including humans (see Chapters 14, 15, and 18). Besides its use for analytical purposes, PFGE has also been used as a preparative tool. Intact DNA obtained from preparative PFGE gels has been used for cloning into yeast artificial chromosome (YAC) vectors (see Chapter 16) and for constructing jumping libraries (1). In addition, DNAeluted from PFGE gels has been used for generating libraries with a smaller insert size (2-7). In this latter procedure, DNA from a somatic cell hybrid is digested with a rare-cutting restriction enzyme, separated by PFGE, and the DNA from a particular PFGE fragment is eluted, digested, and cloned into a plasmid or phage vector. The resulting library is then screened with a species-specific probe...

Timing Of Kidney And Pancreas Transplantation

Due to the current availability of dialysis technology, an increasing number of patients with ESRD are surviving much longer now than they did in the past. Subsequently, a large portion of Medicare's budget is spent in providing dialysis and access for dialysis. Furthermore, dialysis has become an imperfect modality, fraught with problems of poor quality of life, demands of long periods of repeated exhausting therapy, loss of vascular access, complications of access surgery, and decreased sexual function. Transplantation, on the other hand, offers ESRD patients the opportunity to resume a normal lifestyle without the burden of dialysis and its associated complications. Economically, the cost of transplantation, medications, and follow-up is still less than the cost of the procedure for access and a dialysis regimen. Transplantation, though the best therapeutic option for ESRD patients, is not always a viable one for several reasons. First, the number of cadaveric kidney...

Intraoperative Management

MANAGEMENT OF THE KIDNEY TRANSPLANT RECIPIENT In addition to providing anesthesia for a patient with end-stage renal disease (ESRD), the goal of management includes providing the best environment for the newly implanted kidney. One must consider the implications of the underlying disease that caused the ESRD (e.g., diabetes and hypertension), as well as the effect of ESRD on other organ systems (Table 13.3). General anesthesia is usually employed. Although region anesthesia has been used for kidney transplant, many patients have some degree of coagulopathy, and hemodynamic management may be difficult given the unknown status of intra-vascular volume and autonomic neuropathy. Systemic heparin ization (after dialysis) Altered hydration Unpredictable intravascular Iluid (before or in need of dialysis) Electrolyte imbalance Hyperkalemia Hypermagnesemia Hypocalcemia Hyperphosphatemia Metabolic acidosis Cardiovascular A CVP line is used in all patients. Posttransplant renal failure...

Three Dimensional Clinical Tissue Engineering

As one considers these historical events and the advances in tissue engineering over the past 80 years, we are seeing that tissue engineering is moving toward the regeneration and repair of increasingly complex tissues and even whole-organ replacement. This field holds the realistic promise of regenerating damaged tissues and organs in vivo (in the living body) through reparative techniques that stimulate previously irreparable organs into healing themselves. Regenerative medicine also empowers scientists to grow tissues and organs in vitro (in the laboratory) and safely implant them when the body is unable to be prompted into healing itself. We have the technological potential to develop therapies for previously untreatable diseases and conditions. Examples of diseases regenerative medicine could cure include diabetes, heart disease, renal failure, and spinal cord injuries. Virtually any disease that results from malfunctioning, damaged, or failing tissues may be potentially cured...

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