Kidney disease nephrotic syndrome

Inherited defects in lipoprotein metabofism lead to the primary condition of either hypo- or hyperlipoproteinemia (Table 26-1). In addition, diseases such as diabetes mellitus, hypothyroidism, kidney disease (nephrotic syndrome), and atherosclerosis are associated with secondary abnormal hpoprotein patterns that are very similar to one or another of the primary inherited conditions. Virtually all of the primary conditions are due to a defect at a stage in hpoprotein formation, transport, or destruction (see Figures 25—, 26-5, and 26-6). Not all of the abnormafities are harmful. 

These studies led to the realization that proteinuria— the abnormal appearance of protein in the urine— could result not only from the enlargement of submicroscopic holes in the glomerular capillary wall, but also from the loss or neutralization of its negatively charged components. This finding has provided a new direction for research on the molecular basis for the nephrotic syndrome, a group of kidney diseases all characterized by massive proteinuria. 

Bumetanide is used for relieving edema associated with cardiac insufficiency, for liver and kidney diseases including nephrotic syndrome, for ascites, and hypertension. Synonyms of this drug are bumex and others. 

Patients with renal diseases leading to the nephrotic syndrome often present complex problems in volume management. These patients may exhibit fluid retention in the form of ascites or edema but have reduced plasma volume due to reduced plasma oncotic pressures. This is very often the case in patients with "minimal change" nephropathy. In these patients, diuretic use may cause further reductions in plasma volume that can impair GFR and may lead to orthostatic hypotension. Most other causes of nephrotic syndrome are associated with primary retention of salt and water by the kidney, leading to expanded plasma volume and hypertension despite the low plasma oncotic pressure. In these cases, diuretic therapy may be beneficial in controlling the volume-dependent component of hypertension. 

Aspirin and similar NSAIDs can cause other toxic side effects if used improperly or if taken by patients who have preexisting diseases. For instance, serious hepato-toxicity is rare with normal therapeutic use, but high doses of aspirinlike drugs can produce adverse changes in hepatic function in patients with liver disease.85,99 Likewise, aspirin does not seem to cause renal disease in an individual with normal kidneys,84 but problems such as nephrotic syndrome, acute interstitial nephritis, and even acute renal failure have been observed when aspirin is given to patients with impaired renal function, or people with decreased body water (volume depletion).35,102... 

Minimal change disease is the most common cause of nephrotic syndrome in children, presenting typically with rapid onset of mostly steroid-sensitive nephrotic syndrome, usually with selective proteinuria (albuminuria). Light-microscopic morphology of the kidney is normal and immunofluorescence is negative. Foot process effacement on electron microscopy is the only observed pathology. 

Ordonez, J. D., Hiatt, R. A., Killebrew, E. J., and Fireman, B. H., The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int. 44, 638-642 (1993). 

In 54 patients, a kidney biopsy was performed 13.2 8.9 days after onset (n = 32). In all patients, the findings suggested either acute tubular necrosis or its recovery phase. The underlying diseases included kidney diseases such as IgA nephropathy [138], minimal change nephrotic syndrome [139], autosomal dominant polycystic kidney disease (ADPKD) [140], and cystinuria [67]. 

Fig. 11. Cluster analysis used to assist in diagnosis of kidney diseases (adapted from Batchelor 418>). (A) acute nephritis, (B) nephrotic syndrome, (C) normal, (D) acute renal infection, (E) essential hypertension, and (F) chronic renal failure...

Cyclosporine is an important drug in preventing rejection after kidney, hver, heart and other organ transplantation (Haberal et al., 2004). Cyclosporine usually is combined with other immunosuppressives especially glucocorticoids and either azathioprine or mycophenolate mofedl and sirolimus (Krensky et al., 2005). In renal alio transplants it has improved graft acceptance in most clinics to 95 percent. In addition to its use in transplantation cyclosporine is used for the treatment of a number of autoimmune diseases. In autoimmune diseases, as might be anticipated, cyclosporine is most effective in those which are T cell mediated. These include several forms of psoriasis, rheumatoid arthritis refractive to all other therapy, uveitis, nephrotic syndrome and type I diabetes mellitus. 

All types of kidney damage were reported, ranging from a transitory fall in glomerular filtration rate and reversible renal insufficiency (part of multisystem disease with circulating LE cells) to the nephrotic syndrome. 

Antoniskis et al reported four cases of reversible acute kidney injury in patient with AIDS who received both intravenous pentamidine (for PCP) and amphotericin B (for systemic mycoses). Of note, nephrotoxicity did not develop in three AIDS patients treated with both TMP-SMZ and amphotericin B or in two patients who concomitantly received inhaled pentamidine and amphotericin B [160]. Reports of renal damage in patients receiving parenteral pentamidine for the treatment of non-HIV diseases continue. Reversible acute kidney injury and nephrotic syndrome were documented in a young child given pentamidine mesylate and an antimonial salt for the treatment of visceral leishmaniasis [161]. In Africa (Kenya) patients with visceral leishmaniasis have developed renal toxicity during prolonged treatment (1 to 10 months) with pentamidine [162]. 

Alper AB, Jr., Meleg-Smith S, Krane NK, Alper ABJ, Meleg-Smith S, Krane NK. Nephrotic syndrome and interstitial nephritis associated with celecoxib. American Journal of Kidney Diseases 2002 40 1086-1090. 

Cyclosporine was approved for transplant immunosuppression in 1983. It is administered to prevent organ rejection after transplant of kidney, liver, lung, heart, or bone marrow. In addition, it has been given to patients with nephrotic syndrome, rheumatoid arthritis, psoriasis, severe Crohn s disease, and for other medical conditions. 

AA protein is often deposited in chronic inflammatory diseases such as rheumatoid arthritis (incidence up to 20%) and other inflammatory joint diseases, and in chronic suppurative and granulomatous infections such as tuberculosis and osteomyelitis. Deposits of AA protein are also observed in nonlymphoid tumors such as renal and gastric carcinomas and in Hodgkin s disease. Deposits of AA protein are most often found in the kidneys, liver, and spleen, usually resulting in nephrotic syndrome and hepatosplenomegaly. 

Although the data are not conclusive, hyperlipidemia has been associated as a susceptibility factor for CKD in both animal and human studies. The use of lipid-lowering agents in some animal models has been found to decrease the extent of glomerular injury when both underlying renal disease and hyperlipidemia are present. Therefore the correction of lipid abnormalities in patients with CKD was proposed to have a beneficial effect on the rate of progression of the disease. CKD with or without nephrotic syndrome is frequently accompanied by abnormalities in fipoprotem metabolism. The prevalence of hyperlipidemia appears to increase as kidney function declines and with the presence of the nephrotic syndrome. ... 

In patients with nephrotic syndrome, dietary measures involve restriction of sodium intake to 50 to 100 mEq/day, protein intake of 0.8 to 1 g/day, and a low-lipid diet of less than 200 mg cholesterol. Total fat should account for less than 30% of daily total calories. Sodium restriction is important not only in the control of edema, but also in the control of hypertension and proteinuria. Similarly, protein restriction not only helps to reduce proteinuria, but also has a potential role in retarding the progression of renal disease. Patients should also stop smoking because a dose-dependent increase in risk for developing ESKD was observed in men with primary inflammatory (IgA glomerulonephritis) or noninflammatory (polycystic kidney disease) renal diseases. ... 

A report of the International Study of Kidney Disease in Children The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome for initial response to prednisone. JPediatr 1981 98 561-564. 

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