Idiopathic membranous nephropathy in children

Idiopathic membranous nephropathy (MN) is a rare cause of asymptomatic proteinuria (AP) or nephrotic syndrome (NS) in childhood. To improve our understanding of its clinical course, we retrospectively reviewed 19 cases of idiopathic MN seen in our hospital over a period of 28.5 years, i.e., from January 1977 to July 2005. Eight patients (39%) had AP and 11 (61%) presented with NS. All eight AP patients achieved remission, regardless of treatment modality. Oral corticosteroid was given to all 11 NS patients, but only three of them responded to corticosteroid. Of the eight steroid non-responders, three achieved remissions with the addition of cyclosporine, and the five who were not administered additional immunosuppressive drugs had persistent NS. At the latest evaluation, all six NS patients that achieved remission remained free of proteinuria and had a normal renal function. Moreover, two of the 5 steroid non-responders showed persistent nephrotic-range proteinuria but a stable renal function. The remaining three steroid non-responders progressed into chronic renal insufficiency, and this progression was preceded by renal vein thrombosis (RVT) in two of the three patients. Presentation with NS (P=0.045) and the development of RVT (P=0.010) were identified as poor prognostic factors.     

Idiopathic membranous nephropathy in the elderly

In this retrospective non-randomized study we reviewed the outcomefor 41 patients with membranous nephropathy older than 65 yearsat onset and followed for at least 1 year. Twelve of the patientsnever received any specific treatment (group A), 15 were treatedwith a 6-month course of methylpredniso-lone alternated to chlorambucilevery other month (group B), and 14 received corticosteroidsalone for 3–12 months (group C). At the end of a meanfollow-up of 92±61 months in group A, 53±35 ingroup B, and 38±25 in group C there were significantlymore remissions of nephrotic syndrome in group B than in groupA (P=0.035) or in group C (P = 0.010). Moreover patients ingroup B spent a significantly longer period without nephroticsyndrome than patients in group A (P=0.000) and C (P=0.000).Three patients in group A and one in group B died. During thefollow-up six patients of group A, two of group B, and fiveof group C developed renal function deterioration. In patientsfollowed for at least 5 years the mean plasma creatinine increasedfrom a basal of 112±29 to 239±287 µmol/lat the 5th year in group A and from 113±14 to 124±30µmol/l in group B. The mean urine protein excretion remainedunchanged in group A (basal 4.6±2.3 versus 4.8±5.7g/day at 5 years) while it decreased in group B (from a basalof 6.8±3.5 to 1.1±0.4 g/day at 5 years). The natural course of membranous nephropathy in older patientsis similar to that of patients of the second age. Corticosteroidsalone do not modify the outcome. Corticosteroids alternatedwith chlorambucil seem to improve the chances of remission andto protect from renal dysfunction, but elderly patients aremore exposed to the side-effects of this regimen. Thus thistreatment should be limited to patients with severe nephroticsyndrome and/or incipient renal insufficiency, using some particularcautions.     

Idiopathic membranous nephropathy: an autoimmune disease

For more than 50 years researchers have debated the evidence for an autoimmune basis of human idiopathic membranous nephritis (MN). Work published in the past 2 years has substantially strengthened the belief that MN is indeed an autoimmune disease of the kidney. Autoantibodies of the IgG4 subclass to at least three podocyte membrane proteins including phospholipase A₂-receptor, aldose reductase, and manganese superoxide dismutase have been detected by immunoblotting in sera as well as in acid eluates prepared from renal biopsy tissue of patients with this disease, using either whole tissue or microdissected glomeruli from frozen sections. In each case the podocyte antigen has been shown to co-localize with the subepithelial glomerular immune deposits in renal tissue of the same patients. It is not certain if any of these podocyte proteins is an inciting/primary autoantigen or whether they are secondary antigens recruited by intermolecular epitope-spreading, initiating from a yet-to-be-discovered autoantigen. Although it is clear that autoantibodies to podocyte membrane proteins are elicited in idiopathic MN and contribute to the formation of the subepithelial deposits, many questions remain concerning the triggers for their development and their contribution toward proteinuria and progression of the disease.     

Two brothers with idiopathic membranous nephropathy and familial sensorineural deafness

Genetic factors could play an important role in the pathogenesis of idiopathic membranous nephropathy, and a few cases of familial membranous nephropathy have been described: an increased incidence of some HLA antigens as DR3 and others has been reported. We present two brothers with idiopathic membranous nephropathy and sensorineural deafness. HLA typing was performed in the two patients and in the members of the family, and it showed the absence of linkage of an HLA antigen with the renal disease in the family.     

Idiopathic membranous nephropathy associated with polycystic kidney disease

Membranous nephropathy (MN) and polycystic kidney disease are both relatively rare diseases in children. On rare exceptions, these two conditions have been associated in adults. We report here the first case of a pediatric patient with this association. This 6-year-old child presented with gross hematuria, nephrotic syndrome, and mild renal failure. A renal ultrasound subsequently revealed that the patient also had polycystic kidney disease.     

Idiopathic nephrotic syndrome and hexadactyly in two brothers

Familial idiopathic nephrotic syndrome is rare. Only about 3% of patients have affected siblings. The association of familial nephrotic syndrome with congenital abnormalities is even more uncommon. To our knowledge this is the first report of the association of steroid-sensitive nephrotic syndrome and postaxial hexadactyly in two brothers born to consanguineous parents. Received July 3, 1997; received in revised form and accepted December 1, 1997     

Idiopathic membranous nephropathy: the natural history of untreated patients

We reviewed the diagnostic features and clinical course of 140 patients with idiopathic membranous nephropathy who had their index renal biopsies performed at the Mayo Clinic between 1972 and 1984. There were 93 males and 47 females (average age, 50.8 +/- 17 years); 116 patients (83%) had the nephrotic syndrome and 42 (30%) were hypertensive at diagnosis. Eighty-nine patients were not treated with corticosteroid or immunosuppressive drugs and 51 patients were treated mainly with short-term courses of prednisone alone; a minority of patients also received meclofenamate, cyclophosphamide, azathioprine, or chlorambucil. Five-year survival, including patients who received dialysis or a renal transplant, was 85%, 75% at 10 years, and no different from expected survival; there was no difference between untreated and treated groups. Also, there were no differences in the outcomes of renal function and protein excretion between untreated and treated patients. Among 28 patients (20%) who developed end-stage renal disease, 17 showed rapid progression within 2.5 years after diagnosis. Fifteen of the 17 patients were males; all were severely nephrotic and had impaired renal function at diagnosis. Only 1 of 24 patients with nonnephrotic proteinuria at index renal biopsy progressed to end-stage renal disease. Overall, a level of baseline proteinuria of 10 g or more per 24 hours and variable blood pressure control in hypertensive patients were associated with renal progression.     

Idiopathic membranous nephropathy: definition and relevance of a partial remission

BACKGROUND: Membranous nephropathy (MGN) remains the most common cause of adult onset nephrotic syndrome, and within the primary glomerulonephritis group is a leading cause of renal failure. A complete remission (CR) confers an excellent long-term prognosis, but the quantitative benefits of partial remissions (PR) have not been defined. METHODS: This study evaluated the rate of renal function decline (slope), relapse, and renal survival in nephrotic MGN patients with CR, PR, or no remission (NR). Multivariate analysis included clinical and laboratory data at presentation and over follow-up, blood pressure control and agents employed, and immunosuppressive therapy. RESULTS: The study cohort consisted of 348 nephrotic MGN patients with a minimum of 12 months follow-up identified from the Toronto Glomerulonephritis Registry. Over a median follow-up of 60 months, 102 experienced a CR, 136 had a PR, and 110 had no remission. A PR was independently predictive of slope and survival from renal failure by multivariate analysis (hazard ratio 0.08, 95% CI 0.03-0.19, P < 0.001). Benefit from immunosuppression could only be shown in a subset of high-risk patients. Treatment-related PR had the same long-term implication as spontaneous ones. Relapses from PR were high (47%) but often reversible. CONCLUSION: A partial remission is an important therapeutic target with implications for both progression rate and renal survival.     

Idiopathic membranous glomerulonephritis in Brazil

Summary: A survey of the medical records and renal biopsy reports of 41 patients with a diagnosis of membranous glomerulonephritis seen at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo was undertaken between 1961 and April 1992. Twenty-three of these patients were found to have idiopathic membranous glomerulonephritis (IMG) and 22 of them were treated with corticosteroids and/or immunosuppressants. Data for these 22 patients showed that the age at clinical presentation was 36.3± 17.5 years, white skin colour predominated (14 patients), and 15 were males; nephrotic syndrome was the clinical presentation in 20 patients and proteinuria was accidentally discovered in two patients. On the first hospital visit 11 patients presented proteinuria of up to 3 g/24 h and 16 presented serum creatinine below 1.5 mg/dL, and 14 developed renal hypertension during follow up. Clinicalmorphological correlation permitted us to conclude (in agreement with the literature) that advanced patient age, intensity of proteinuria, serum creatinine levels above 1.5 mg/dL on the occasion of the first hospital visit, and arterial hypertension are clinical-laboratory factors indicating a poor prognosis for IMG. More advanced staging of glomerular damage, presence of segmental mesangial sclerosis and tubulointerstitial involvement are microscopic factors indicating a poor prognosis for IMG.     

Segmental membranous nephropathy

Clinical and Experimental Nephrology - Most cases of membranous nephropathy (MGN) present with global and diffuse distribution of subepithelial deposits. However, segmental MGN, in which there is...