Minimal change disease

Minimal-change disease is more common in children than in adults. It is rare in black children and adults of sub-Saharan Africa. Minimal-change responds well to steroids. However, it may recur after prednisone is decreased or discontinued. In such cases, the addition of cyclophosphamide or chlorambucil may produce a response. The GFR is normal. Progression to renal failure does not occur unless focal glomerulosclerosis is present. 

The cytoplasmic part of nephrin interacts also with ZO-1 protein and actin (K10). Interaction of the antibody or toxin with the extracellular part of nephrin could thus also result in intracellular signaling (phophorylation of tyrosine residues in the cytoplasmic part of nephrin), change of the actin cytoskeleton, and foot process fusion. Indeed, increased levels of phosphotyrosine were demonstrated in renal biopsies of patients with minimal change disease and membranous nephropathy (B2). 

In the following we concentrate mainly on the pathogenesis of minimal change disease, focal and segmental glomerulosclerosis, and idiopathic membranous nephropathy. These three diseases are responsible for about 60-95% of nephrotic syndromes and their prevalence depends on age. 

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. 

Charge selectivity is probably mediated mainly by the polyanionic glycosamino-glycans present in the glomerular basement membrane (C5, G6). This barrier restricts mostly the movement of relatively small polyanionic proteins (molecular weight 70-150 kDa), mainly albumin. Loss of charge selectivity is believed to be the main cause of albuminuria (selective proteinuria) in minimal change disease (B10). 

Pathogenesis of foot process fusion in various human glomerulopathies may be different. On one hand, in membranous nephropathy, foot process fusion may be the consequence of complement-induced podocyte damage (Cl 1) on the other hand, in minimal change disease, proteinuria may be caused by direct damage to the slit diaphragm with consequent foot process fusion. In any case, foot process fusion results in the formation of large pores and proteinuria. 

Patients with decreased intravascular blood volume should have hypotension, but many nephrotic patients (apart from nephrotics with minimal change disease) are hypertensive (K28). Adults with nephrotic syndrome were repeatedly demonstrated to have normal or increased (not decreased) plasma volume (G4). 

Nephrotic patients (especially children) are prone to bacterial infections. Before antibiotics and corticosteroids were introduced into the therapy, pneumonia, peritonitis, and sepsis (usually caused by pneumococci) were the most frequent cause of death of nephrotic children with minimal change disease. Infections are more frequent in nephrotic children and after the age of 20 their prevalence markedly decreases because the majority of adults have antibodies against the capsular antigens of pneumococci. Infections remain an important complication of nephrotic syndrome in developing countries. In developed countries, nephrotic patients treated by immunosuppressive agents may frequently suffer from viral infections (mainly herpesvirus infections, e.g., cytomegalovirus and Epstein-Barr virus infections). 

Apart from nephrotic syndrome in minimal change disease, persistent nephrotic syndrome confers a substantial risk of progression to chronic renal failure. The risk of progression is usually related to the degree of proteinuria. Progression is moderate in patients with proteinuria lower than 2 g/24 hr, but is high in the patients with proteinuria higher than 5 g/24 hr. 

Nephrotic syndrome. Patients with minimal change disease respond well to daily or alternate day therapy. With a total of prednisolone 60 mg/d, 90% of those who will lose their proteinuria will have done so within 4-6 weeks, and the dose is tapered off over 3-4 months. Longer courses only induce adverse effects. Relapses are common (50%) and it is then necessary to find a minimum dose of steroid that will keep the patient well. If a steroid is for any reason undesirable, cyclophosphamide or chlorambucil may be substituted. Membranous nephropathy may respond to high dose corticosteroid with or without chlorambucil. 

Low-dose methotrexate is usually not regarded as nephrotoxic, and one report of nephrotic syndrome with minimal change disease on renal biopsy should be regarded with caution, since there was recovery after glucocorticoid treatment and withdrawal of concomitant NSAIDs (SEDA-22, 416). 

A 12-year-old boy with a history of a generalized pruritic rash after penicillin took penicillamine up to 500 mg/day for Wilson s disease. He had a rash after using penicillamine for 1 week. The penicillamine was stopped for 3 days. He developed nephrotic syndrome 2 weeks after restarting penicillamine. On electron microscopy, there was the typical picture of minimal change disease with extensive foot process effacement. 

Non-steroidal anti-inflammatory drugs are known to induce a nephrotic syndrome in addition to acute tubulointerstitial nephritis (discussed in [77]). Glomerulopathies include minimal change disease, focal glomerulosclerosis that could represent a continuum with the former entity and membranous glomerulopathy. A review of 97 patients with non-steroidal anti-in-... 

An association between tubulointerstitial nephritis and minimal change disease has been reported in 18/27 patients treated with non-steroidal drugs [84]. 

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