Membranous nephropathy associated with hepatitis B in Spanish children

AIM: To examine retrospectively long-term evolution and treatment of pediatric membranous nephropathy (MN) cases associated with hepatitis B (HB) in the hospital "La Paz". MATERIAL AND METHODS: The clinical records of 12 children diagnosed with HB-associated MN in our hospital between 1970 and 1996. RESULTS: All patients were positive for hepatitis B surface antigen (HBsAg); 6 were tested for hepatitis Be antigen (HBeAg) and were also positive. At onset, all of them had proteinuria (8 in nephrotic range), 6 had microscopic hematuria and 4 macroscopic hematuria. Seven of 8 children who started with a nephrotic syndrome received steroids and all of them were steroid-resistant. After 9.95 +/- 5.88 years of follow-up, renal function remained normal and proteinuria and hematuria have disappeared in all of them. A family study for hepatitis B was carried out in 8 cases and 7 of them were positive. Only in one case vertical transmission was demonstrated; this patient remained HBeAg positive. In 7 patients, hepatic biopsy was performed: 3 had a chronic active hepatitis, 3 a persistent chronic hepatitis and one a residual acute hepatitis. CONCLUSIONS: Membranous nephropathy is a rare pediatric disease in our area and most of the cases are related to hepatitis B (HB). The outcome was excellent with and without treatment but all of them remained HBsAg positive.     

Survival in idiopathic membranous glomerulonephritis

Sixty-seven patients with idiopathic membranous glomerulonephritis (iMGN) were analyzed clinically. Their mean age was 39.3 years, and 47 (70%) of them were male. Fifty (74.6%) showed nephrotic syndrome (NS) initially and five (7.5%) had additionally chronic renal failure. Hypertension was present in 27%. During the follow-up (mean 6.7 years) renal death occurred in four patients 12-151 (mean 84.2) months after the diagnosis of iMGN. Four patients died of non-renal causes. The actuarial life-table survival at 5, 10 and 15 years was 94%, 83% and 69%, respectively. To some extent renal function deteriorated in 13 patients (19%). These patients were older (49.9 vs. 36.8 years, p less than 0.01) than those with preserved renal function, and many of them had serum creatinine levels of 125 mumol/l or more initially. Sex did not correlate with the development of renal insufficiency. Patients with slight proteinuria never showed loss of renal function. The retrospective comparison of survival in patients who did (N = 31) or did not (N = 19) receive corticosteroids and/or immunosuppressive drugs for the treatment of NS revealed no evident difference at 5 or 10 years. This clinical analysis emphasizes the fairly favorable outcome of patients with iMGN. Hence a reserved view must be taken when treatment with potentially dangerous agents is considered in a disease with unknown etiology and pathogenesis.     

Membranous glomerulonephritis associated with renal cell carcinoma: failure to detect a nephritogenic tumor antigen

A 57-year-old man with renal cell carcinoma associated with membranous glomerulonephropathy (MGN) developed a transient amelioration of the nephrotic syndrome after excision of the tumor. We tried to identify a nephritogenic tumor antigen using the immunoblotting technique in this patient with MGN, since previous studies examined the interaction between tumor antigens and IgG eluted from the kidney tissue using immunofluorescence or immunodiffusion techniques, and no studies have identified the specific tumor antigen with the immunoblotting method. In the present study, no significant immunoreactivity was noted between the IgG eluted from renal cortical tissues of the patient and renal cell carcinoma proteins. Further studies are necessary to establish the pathogenic mechanism of MGN associated with malignancy.     

Membranous glomerulonephritis associated with enterococcal endocarditis

An autopsy case of membranous glomerulonephritis associated with enterococcal endocarditis was reported. Although enterococcal antigen was not identified in glomerular deposits, the eluate from the patient's renal tissue was shown to specifically recombine with cells of the enterococcus isolated from his own ante mortem blood. Hypocomplementemia, circulating immune complexes and antienterococcal antibodies were also observed. These findings suggest that enterococcus-related immune complexes played a role in the pathogenesis of glomerulonephritis associated with enterococcal endocarditis in this patient.     

Association of hepatitis B (HBs) antigenaemia and membranous glomerulonephritis in Zimbabwean children

8 Zimbabwean children are discussed in whom the nephrotic syndrome (NS) was a manifestation of membranous glomerulonephritis (GN) which was associated in every case with hepatitis B antigenaemia. This marks the first occasion that such an association has been reported in African children, although it has been thoroughly documented in children in Europe, the Far East and America. Microhaematuria, hypertension and mild to moderate renal insufficiency were frequent early associated findings, and every child exhibited hypocomplementaemia and a markedly diminished immunoglobulin G (IgG) level. The disease followed a benign course in the majority, and only 1 child died in renal failure.     

Presence of HBe antibody in glomerular deposits in membranous glomerulonephritis is associated with hepatitis B virus infection

The specificity of IgG on the glomerular capillary wall was investigated in 3 patients with hepatitis B virus associated membranous glomerulonephritis. The immune deposits on the capillary walls were stained by immunofluorescent antibody against HBe antigen and IgG. The eluted fluid (0.02 M citrate buffer, pH 3.2) from renal biopsy slices contained significant activity of HBe antibody, but not of HBs and HBc antibodies. After elution, the disappearance of IgG on the capillary walls was confirmed by immunofluorescence. Heterologous complement activation with fresh guinea pig complement was positive in the glomerular capillary walls from all 3 patients. Our observations support the notion that this disease is caused by HBe antigen-anti-HBe immune complexes.     

Membranous glomerulonephritis associated with hepatitis C virus infection: case report and literature review

We describe the case of a 51-year-old man with hepatitis C virus (HCV) infection and a 3-month history of facial edema. Laboratory tests upon admission for renal biopsy showed normal renal function and normocomplementemia. Serum HCV antibody (Ab) and cryoglobulin were positive. Renal biopsy specimens showed features of membranous glomerulonephritis. The likely cause was immune complex-mediated glomerulonephritis associated with HCV infection. Reports of similar cases in the literature show the normocomplementemia and negative or slightly positive cryoglobulins observed in our case as well as seropositivity for circulating immune complexes containing HCV RNA. In our case, electron microscopic examination of the subepithelial glomerular lesions revealed massive virus-like particles within unusual multilayers of electron-dense deposits (EDDs), suggesting the existence of HCV in the glomeruli. In the addition to the unique histopathological feature the presence of La/SS-B antibody in his serum indicated an abnormal immune response associated with HCV. We advise him to undergo the therapy with new type of IFN such as pegIFN-alpha2a and/or anti-viral agent like ribavirin to achieve clinical and histopathological improvement.     

Reversible membranous glomerulonephritis associated with ketoprofen

An 87-year-old woman presented with the nephrotic syndrome 12 months after administration of ketoprofen, 100 mg daily for osteoarthritis. Clinical course and laboratory data were consistent with drug-induced nephropathy. Kidney biopsy showed membranous glomerulonephritis. Evolution was favorable with resolution of proteinuria after drug withdrawal and steroid administration. A review of the literature on nephrotic syndrome associated with NSAID reveals membranous glomerulonephritis to be an unusual complication.     

Focal glomerulosclerosis in idiopathic membranous glomerulonephritis.

The significance of the finding of focal glomerulosclerosis (FGS) in idiopathic membranous glomerulonephritis (MGN) is uncertain. Twenty-seven patients with mixed FGS and MGN (MGN-FGS) were compared to 25 patients with MGN alone (generally matched for age, sex and stage of glomerular lesion) with respect to pathology, presenting clinical and laboratory features, and course of disease. Biopsies from the MGN-FGS patients showed significantly more extensive tubulointerstitial disease (P less than 0.001) than did those with MGN alone. At the time of biopsy, the MGN-FGS group had a significantly higher proportion of patients with hypertension (P = 0.006) and microhematuria (P = 0.006), a marginally higher percentage of patients with the nephrotic syndrome (P = 0.051), and a greater mean 24-hour urinary protein excretion (P = 0.004). A similar proportion of patients in each group were treated with either prednisone alone or prednisone with an immunosuppressive. Forty-eight percent of MGN-FGS patients and 13% of the MGN patients developed established renal failure in the follow-up period (P = 0.008). The renal survival rate for the MGN-FGS group was significantly lower at 24 months (0.61 vs. 0.93, P less than 0.05), 60 months (0.48 vs. 0.88, P less than 0.025), and over the entire follow-up period (P less than 0.05). The results indicate that FGS in MGN is associated with a significantly poorer prognosis than MGN without this lesion.     

Transformation of hepatitis B virus-related membranous glomerulonephritis to crescentic form

We report a case of hepatitis B virus-(HBV) related membranous glomerulonephritis which progressed to crescentic transformation after withdrawal of immunosuppressive treatment. Immunosuppressive therapy probably enhanced HBV replication, and its withdrawal led to a return of immune competence resulting in progression of the glomerulonephritis. Prior screening of all patients for hepatitis B surface antigen, before using immunosuppressive therapy may prevent this complication. The usage of immunosuppressive therapy as a first-line choice in HBV-related glomerulonephritis may result in harmful complications.     

Biochemical and serological characteristics of children with membranous nephropathy due to hepatitis B virus infection: correlation with hepatitis B e antigen, hepatitis B DNA and hepatitis D

Fourteen children with biopsy-proven membranous nephropathy associated with hepatitis B virus (HBV-MN) were evaluated biochemically and serologically and compared to 45 children with idiopathic nephrotic syndrome (INS). The mean ages of the two groups were similar (4.9 +/- 1.6 vs. 4.6 +/- 2.6 years). Serum albumin levels were similar in both groups, but serum cholesterol was significantly reduced in children with HBV-MN compared to INS. Serum C3 was also significantly depressed in children with HBV-MN compared to INS, but no differences in C4 levels were noted. Serum alanine transaminase as well as aspartate transaminase concentrations were significantly elevated in children with HBV-MN compared to those with INS, suggesting the presence of chronic hepatitis in children with HBV-MN. Hepatitis B surface and e antigens were present in serum of all children with HBV-MN, but only 54% had circulating HBV-DNA particles demonstrable in their serum. Serum C3 levels were higher in children with HBV-MN and circulating HBV-DNA, compared to those without circulating HBV-DNA. No other serological or biochemical differences occurred between these two groups. Glomerular deposition of IgG and C3 occurred in 91% of children with HBV-MN; but IgM deposition appeared to occur more frequently and with greater intensity in those children positive for circulating HBV-DNA. Antibody to delta antigen was negative in all children with HBV-MN. We conclude that biochemical and serological differences can be identified between HBV-MN and INS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children

Two Chinese boys, aged 3.5 and 5 years, developed nephrotic syndrome and were chronic carriers of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg). Renal biopsy showed membranous glomerulonephritis and liver biopsy showed chronic persistent hepatitis. They were given interferon--2a at a dose of 5 MU/m² on alternate days for 12 and 16 weeks after 2 years of persistent nephrotic syndrome. Patient 1 showed complete remission and resolution of hepatosplenomegaly, but his serum remained positive for HBsAg, HBeAg and hepatitis B virus DNA. Patient 2 showed only a transient clinical response and seroconversion from HBeAg to anti-HBe status. Although not always successful, interferon treatment should be considered in severe persistent nephrotic states, since there is at present no satisfactory treatment for this form of glomerulonephropathy.     

Membranous nephropathy in 52 hepatitis B surface antigen (HBsAg) carrier children in Taiwan

To elucidate the prognosis and the causative viral antigens of hepatitis B virus (HBV)-associated childhood membranous nephropathy (MN), the clinical course and glomerular HBV antigens were studied in 52 HBsAg carrier children with MN (40 boys, 12 girls). With Fab fragments of monoclonal antibodies, hepatitis Be antigen (HBeAg) was detected in the glomerular deposits in 41 (95%) of 43 cases but HBsAg and hepatitis B core antigen (HBcAg) in none. HBeAg was detected in sera from 43 (93%) of 46 children examined. These results suggest that HBeAg plays an important role in the development of MN in HBsAg carrier children. During the follow-up period (mean, 4 years), complete remission was found in 64% and 92% of the patients followed for one and seven years, respectively; only one child had mild renal function impairment. These findings suggest a favorable outcome of HBsAg-associated childhood MN. The patient's age, disease duration, amount of glomerular deposit, focal sclerosis and disease stage appeared to affect the clinical course. HBsAg seroconversion to HBsAg-negative occurred in seven cases, and all (100%) had quick remission in two years. In patients with persistent HBsAg carriage, serum HBeAg status alone did not correlate with remission rate and remission occurred usually before the HBeAg seroconversion to anti-HBe. These findings, together with the predominant horizontal infection in these children in contrast to the frequent vertical (perinatal) transmission from HBsAg carrier mothers in HBsAg carriers in Taiwan, suggest that factors other than HBeAg per se may also play important roles.     

Childhood idiopathic membranous glomerulonephritis with isolated antinuclear antibody positivity

Background. The occurrence of idiopathic (primary) membranous glomerulonephritis (MGN) is relatively uncommon in childhood. Although a proportion of children with idiopathic MGN may show isolated antinuclear antibody (ANA) positivity, its clinical impact remains unclear. Methods. During the past 12 years, we have treated six children with idiopathic MGN at our institution. Of these, three children with isolated ANA positivity were retrospectively evaluated. Results. The patients consisted of two boys and a girl, aged 5, 12, and 13 years at presentation, respectively. They showed proteinuria of around 1 g/day with hematuria, and isolated ANA positivity without anti-DNA antibody or hypocomplementemia. A percutaneous renal biopsy revealed MGN stage II in two of the children and stage III in one, without endothelial tubuloreticular inclusion. Two children received a 6-month course of prednisolone therapy. At the latest observation (mean interval of 42 months), all showed negative for proteinuria, and no patients had progressed to systemic lupus erythematosus (SLE). A decrease in the ANA titer with subsidence of urine abnormalities was observed in two patients. Conclusion. Although the long-term prognosis of ANA-positive idiopathic MGN in childhood remains unclear, isolated ANA postivity itself may be nonspecific, and may not indicate a subsequent progression to SLE. Received: May 8, 2002 / Accepted: July 23, 2002 Correspondence to:H. Tanaka