Minimal change disease and idiopathic FSGS: manifestations of the same disease.

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the key histological findings in patients with idiopathic nephrotic syndrome (INS). Although MCD and idiopathic FSGS are often considered to represent separate entities based on differences in their presenting characteristics, histology and outcomes, little evidence exists for this separation. We propose that MCD and idiopathic FSGS are different manifestations of the same progressive disease. The gradual development of FSGS in patients with non-remitting or relapsing INS has been well documented. Moreover, FSGS is the uniform result of substantial podocyte loss in animal models, and a common feature of virtually all progressive human glomerulopathies. As evidence suggests a common aetiology, the pathogenesis of MCD and idiopathic FSGS should be studied together. In clinical trials, idiopathic FSGS should be considered to represent an advanced stage of disease progression that is less likely to respond to treatment than the earlier stage of disease, which is usually defined as MCD.

Management of childhood onset nephrotic syndrome.

The therapeutic approach to childhood nephrotic syndrome is based on a series of studies that began with an international collaborative effort sponsored by the International Study of Kidney Disease in Children in 1967. The characteristics of children presenting with nephrotic syndrome have changed over recent decades with greater frequency of the challenging condition focal segmental glomerulosclerosis and a greater prevalence of obesity and diabetes mellitus, which may be resistant to glucocorticoids in the former and exacerbated by long-term glucocorticoid therapy in the latter 2 conditions. The Children's Nephrotic Syndrome Consensus Conference was formed to systematically review the published literature and generate a children's primary nephrotic syndrome guideline for use in educational, therapeutic, and research venues.

Nephrotic syndrome associated with diffuse mesangial hypercellularity: is it a heterogeneous disease entity?

Diffuse mesangial hypercellularity (DMH) is a rare primary mesangial proliferative glomerulonephritis associated with idiopathic nephrotic syndrome (INS). We conducted this study on 15 patients, including 5 patients with repeated specimens, with a follow-up of 0.9-17.5 years and evaluated the clinical course and pathological findings. Seven patients were male. Ten patients were under 14 years of age. All specimens had INS and were diagnosed morphologically with primary diffuse mesangial proliferative glomerulonephritis at initial biopsy; 4 were diagnosed with focal segmental glomerulosclerosis (FSGS) within 3 years by the second biopsy. The remaining 11 patients included 8 initial responders and 3 initial nonresponders to 8 weeks' steroid therapy and had the histologic variant of the minimal-change nephrotic syndrome (MCNS). Ten of the 11 patients had normal renal function during the investigation period. One patient with the MCNS variant who was refractory to steroid therapy developed end-stage renal disease (ESRD) within 6 years. Four patient with the histologic variant of FSGS included 1 initial responder, 2 late responders, and 1 steroid-refractory case. One patient with the FSGS variant developed ESRD within 4 years. The follow-up biopsies documented that the severity of mesangial hypercellularity was associated with the severity of proteinuria or hematuria. We conclude that DMH may be divided into heterogeneous disease entities, whereas morphologic changes in initial biopsies were similar. Each variant as well as the degree of DMH should be recognized routinely by follow-up biopsy, because they are prognostic indicators.

The nonspecificity of focal segmental glomerulosclerosis. The defining characteristics of primary focal glomerulosclerosis, mesangial proliferation, and minimal change.

We performed a detailed clinical review and pathologic analysis of the kidney biopsies of 134 children with nephrotic syndrome or asymptomatic proteinuria. This analysis challenges some of our concepts about the classification of conditions associated with these disorders. The presence of focal segmental sclerotic lesions does not define a unique disorder in childhood. Some children with such lesions will have unaffected glomeruli that are ultrastructurally completely normal. These patients, predominately black adolescents, present either with nephrotic syndrome or asymptomatic proteinuria. We classify this disorder as primary focal segmental glomerulosclerosis (FSGS) and have never found it to recur after transplantation. Most other children with FSGS have 1 of 2 specific glomerulopathies. Those with minimal change have generalized fusion of podocyte foot processes. Those with mesangial proliferation have similar foot process changes combined with mesangial expansion and proliferation and, frequently, thinning of the lamina densa and tubuloreticular inclusions. The presence of segmental lesions in these glomerulopathies appears to be nothing more than a marker of severity. Children with these glomerulopathies are generally younger white children, virtually all of whom have nephrotic syndrome. These disorders have a strong propensity to recur after transplantation. The presence of mesangial labeling of IgM or C1q has no significance in any of these 3 disorders. The classification of disorders associated with nephrotic syndrome or asymptomatic proteinuria must concentrate less on the presence or absence of focal sclerosis and more on the histologic appearance of the rest of the glomeruli.

Epidemiology and natural course of idiopathic nephrotic syndrome.

The term "idiopathic nephrotic syndrome" is poorly defined and is used to refer to a variety of glomerular lesions. This article seeks to clarify the situation by considering the case for treating minimal-change nephropathy, focal and segmental glomerulosclerotic lesions, and mesangioproliferative lesions with predominantly IgM deposition as separate disease entities. In children, nephrotic syndrome has a pattern different from that in adults, in whom a wider pathogenetic spectrum is seen. There is support for the use of prospective clinicopathological data as the basis of identifying those patients with nephrotic syndrome who will progress to end-stage renal failure. Very heavy, persisting proteinuria is one marker of such progression and is also an indicator of metabolic complications, such as cardiovascular disease, which further increase the risks of mortality and morbidity in this group of patients.

Nephrotic syndrome in the first three months of life.

When the nephrotic syndrome develops within the first 3 months of life it is considered as congenital. In a review, different types of renal diseases are found behind the syndrome in early infancy. A classification of these is proposed, based on clinicopathology. Five classes with subgroups are described, and the necessity of recognizing these for prognosis, therapy and genetic counselling is emphasized.