Nephrotic syndrome in children : Functional, morphological and therapeutical aspects

University dissertation from Stockholm : Karolinska Institutet, Department of Surgical Science

Abstract: Although cure rates of the idiopathic nephrotic syndrome in children have improved because of advances in immunosuppressive therapy, the pathogenesis and course of the disease remain controversial. We have followed children with nephrotic syndrome to study renal function and morphological changes in kidney biopsies and in an experimental study. Immunosuppressive treatment with cyclosporine in severe nephrotic syndrome has been shown to be effective, but nephrotoxicity is a major concern. Some studies have suggested that glomerular hypertrophy precedes the development into FSGS, which comprises focal and segmental scarring of the glomerulus, a frequent cause of renal failure.ln this syndrome the podocyte and its foot processes show foot process effacement, usually reversible.However, if the disease becomes worse, it leads to detachment of the foot processes from the glomerular basement membrane and initiates renal scarring of the glomerulus. DMP and FSGS are regarded as more severe types of the nephrotic syndrome, clinically and histopathologically, than MCNS. In 58 children with MCNS (40), DMP (4) and FSGS (14) we investigated retrospectively the glomerular volume. GFR and ERPF were used to determine renalfunction. The patients were BSA or age matched. The glomerular volumes in DMP and FSGS were significantly larger than in those with MCNS(P<0.005, P <0.002). We also found direct correlation between glomerlar volume and GFR and ERPF in all patients. In conclusion these results show that renal hemodynamics may contribute to glomerular hypertrophy. Moreover, in an experimental study in rats with PAN-induced nephrotic syndrome, mimics the nephrotic syndrome in children, we found that the severity of the foot process effacement and the increasing length of the slit pores and fractional albumin excretion were related to a reduction in glomerular filtration. In an early stage of the disease the glomerular volume was enhanced. To investigate GFR and ERPF in relation to oncotic pressure (s-albumin concentration) we evaluated 119 children who had various types of the nephrotic syndrome. The renal function was determined at additional times according to the clinical course of the nephrotic stage, the recovery stage and in remission. In the nephrotic stage the GFR was significantly lower than in remission ( and compared to controls), while ERPF was higher in the nephrotic stage, especially in the types with histological lesions. Thus, the filtration fraction was much lower in the nephrotic stage. The low GFR was therefore caused not by hypoperfusion, but by on a very low ultrafiltration coefficient. In therapy-resistant MCNS and FSGS, cyclosporine is used as immunosuppressive therapy. In a prospective study which started in 1987, 22 children were investigated as regards to GFR and ERPF every sixth month and repeated kidney biopsies were taken to evaluate cyclosporine nephrotoxicity. We found very mild morphological changes in the MCNS patients. Most of the FSGS children showed a decline in proteinuria, which may delay or induce a sustained remission. In both groups, renal function declined from the first to the last investigation, as assessed by GFR (from1 10 to 93 and from 96 to 77 ml/min per 1.73M2 in the MCNS and FSGS; respectively) and ERPF (from 521 to 468 and 581 to 398 ml/min per 1.73m2, respectively). In the MCNS patients, the GFR normalized after cessation of treatment in 4 patients, who have had renal function tests after CsA treatment. Both groups responded well to CsA. Therefore, CsA can be used as long-term treatment in selected cases.

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