Successful steroid treatment in a patient with membranoproliferative glomerulonephritis associated with hepatitis C virus

Thirteen years ago, a 65-year-old woman was diagnosed to have chronic active hepatitis with hepatitis C virus. After starting interferonα administration, she noticed edema and hypoalbuminemia. Renal biopsy revealed mesangial proliferation with focal endocapillary proliferation, and double contour of the glomerular basement membrane due to mesangial interposition. Interferonα was discontinued, and proteinuria and edema gradually decreased. She was re-admitted due to a relapse of proteinuria 8 years later. Biopsy revealed moderate mesangial and endcapillary proliferation presenting a lobular pattern, in addition to the presence of hyaline thrombi. Granular staining of immunoglobulin M and of C3 in capillary walls were detected. Since cryoglobulinemia was positive, a final diagnosis of cryoglobulinemic membranoproliferative glomerulonephritis was made. Prednisolone was started with an initial dose of 20 mg/day. Proteinuria and hypoalbuminemia improved, and prednisolone was tapered to 5 mg/day 9 months after the 2nd renal biopsy. The hepatitis C virus-RNA titer fluctuated.     

Thrombotic microangiopathy associated with cryoglobulinemic membranoproliferative glomerulonephritis and hepatitis C

Cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) and increased incidence of vascular thromboses are complications of hepatitis C virus (HCV) infection. This report describes the clinical, laboratory, and renal biopsy findings in two HCV-positive patients with cryoglobulinemic MPGN and thrombotic microangiopathy (TMA). Testing for circulating antiphospholipid antibodies, which are detected in a significant proportion of patients with HCV, was negative in the one case in which it was done. This article discusses the possible cause of the TMA in these two cases.     

The pathogenesis of membranoproliferative glomerulonephritis in KwaZulu-Natal,South Africa is unrelated to hepatitis C virus infection

Idiopathic membranoproliferative glomerulonephritis (MPGN) is a well-defined clinicopathological entity with a poor prognosis, with 50% of patients progressing to end stage renal disease (ESRD) within 10 years. It was reported in about 36% of adult Black patients with nephrotic syndrome in our center previously [Seedat et al. 1988]. Hepatitis C virus (HCV) infection has been shown to be associated with cryoglobulinemic as well as non-cryoglobulinemic (or idiopathic glomerulonephritis). The aim of this study was to determine whether an association exists between HCV infection and idiopathic MPGN in a population with a relatively high prevalence of MPGN. We studied adult patients referred with glomerular disease over a two-year period, 104 patients had primary glomerulonephritis. All 23 (22%) patients with idiopathic MPGN were enrolled, as well as 32 age-matched patients presenting with other primary glomerular diseases. We examined serum from all 55 patients for evidence of HCV antibodies and HCV RNA. None of the 55 patients showed evidence of HCV infection. Chronic renal failure was present in 82.6% of the patients with idiopathic MPGN and it was advanced in 52,2%, who either were dialysis-requiring at presentation or progressed to ESRD soon thereafter; 30.4% had moderate chronic renal failure, while only 17.4% had normal renal function. HCV infection is not associated with idiopathic MPGN in our patients. Idiopathic MPGN remains an idiopathic disease, possibly with a poor prognosis in our population.     

Crescentic fibrillary glomerulonephritis associated with hepatitis C viral infection

Fibrillary glomerulonephritis (FGN) is a pathological diagnosis that is rarely associated with systemic disorders. In this case report, we describe a woman who presented with FGN of the crescentic type in association with hepatitis C viral infection. The existing literature on the association between these 2 disorders is reviewed, and postulated therapy is presented.     

Interferon treatment on glomerulonephritis associated with hepatitis C virus

We report on a 10-year-old girl with glomerulonephritis associated with hepatitis C virus infection, who was treated with interferon-α. On the first renal biopsy at 8 years of age, mild mesangial hypercellularity in a segmental to semiglobal pattern was present in all glomeruli. After 6 months interferon-α therapy, proteinuria diminished completely. However, mesangial proliferation was advanced on the second biopsy at 10 years of age. We concluded that the interferon-α was effective in the treatment of proteinuria despite the lack of pathological improvement. Received: 15 March 2000 / Revised: 11 July 2000 / Accepted: 14 July 2000     

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.     

Macroglobulinemia and membranoproliferative glomerulonephritis in a hepatitis C virus-positive patient

A 72-year-old female was admitted to our hospital for massive proteinuria. She had previously been diagnosed with hepatitis C virus (HCV) infection and macroglobulinemia. Renal histological examination demonstrated membranoproliferative glomerulonephritis (MPGN), and type 2 cryoglobulinemia was positive in her serum. It is generally recognized that MPGN is the most common nephritis associated with HCV infection and cryoglobulinemia, but this is the first report of an HCV-infected patient with macroglobulinemia associated with MPGN. After treatment with prednisolone and melphalan, proteinuria disappeared, but macroglobulinemia and cryoglobulinemia were not improved.     

De novo glomerulonephritis in renal allografts with hepatitis C virus infection

The purpose of this study was to examine the influence of hepatitis C virus (HCV) infection on the occurrence of posttransplant de novo glomerulonephritis (GN). Of 165 patients selected for the study, 44 were HCV positive and 121 HCV negative. Light and immunofluorescence microscopy were performed on all biopsies and clinical and laboratory findings reviewed. Fifteen (34%) of the 44 HCV positive patients showed de novo GN (4 membranous, 11 membranoproliferative) at a mean of 47 +/- 22 months. But only 8 (6.6%) of 121 HCV negative patients showed de novo GN (5 anti-glomerular basement membrane nephritis in recipients with Alport's disease, 2 membranous GN, 1 membranoproliferative GN) at a mean of 60 +/- 39 months. The risk of development of de novo GN was higher among patients with HCV infection (P < .001). The presence of de novo GN in HCV positive patients impaired graft survival compared with HCV positive patients without de novo GN (P < .01). The incidence of recurrence of primary disease, mainly focal segmental glomerulosclerosis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and IgA nephropathy, was higher in HCV negative patients (29%) compared with HCV positive patients (6.8%; P = .001), namely, 50%, 57.6%, 25%, and 69%, respectively. In conclusion, HCV infection showed a strong influence on the development of de novo GN. For this reason, it is important to follow HCV positive recipients with a renal biopsy even when there are no significant clinical or laboratory findings.     

Absence of hepatitis B and C viruses in pediatric idiopathic membranoproliferative glomerulonephritis

The blood-borne hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV), have similar epidemiological features. The association of chronic HBV infection and glomerulonephritis is well established, particularly in children. Recent reports have shown an association between HCV infection and glomerulonephritis in adults. In order to assess the role of these hepatotropic viruses in membranoproliferative glomerulonephritis (MPGN) we screened 34 children with idiopathic MPGN for the presence of HBV and HCV infection using highly sensitive polymerase chain reaction techniques for the detection of HBV DNA and HCV RNA. Also, enzyme-linked immunosorbent assays were used to detect the presence of antibody to hepatitis B surface antigen and antibody to HCV. No evidence of HBV or HCV infection was demonstrated in any of the patients. We conclude that HBV and HCV are not significant causes of idiopathic MPGN in children in the United States.     

Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis

Background

Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established.

Methods

We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed.

Results

Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04).

Conclusions

C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.     

Outcome of hepatitis C virus-associated membranoproliferative glomerulonephritis after liver transplantation.

BACKGROUND: Hepatitis C virus was the most frequent cause of liver failure requiring liver transplantation in our series. Hepatitis C virus infection has been associated with glomerulonephritis and, more frequently, type I membranoproliferative glomerulonephritis. Renal disease in patients with liver failure is often clinically silent and difficult to diagnose; thus, biopsy is required to establish the diagnosis. Our aim was to study the evolution of six patients diagnosed with membranoproliferative glomerulonephritis some months before liver transplantation. METHODS: Liver transplantation alone was performed in four patients and combined liver-kidney transplantation in the remaining two, who were on hemodialysis for kidney failure. These patients were followed for a mean of 38.3+/-7.8 months. Evolution of proteinuria, renal function, hepatic function, and hepatitis C virus activity was studied. RESULTS: In the four patients who underwent liver transplantation alone, proteinuria became negative initially and renal function remained stable. Proteinuria reappeared and renal function was altered in two of these patients at 17 and 36 months of follow-up, respectively, coinciding with a recurrence of active chronic hepatitis. In the two patients who received a combined liver-kidney transplant, proteinuria became negative, and their renal grafts currently maintain normal renal function. CONCLUSIONS: Membranoproliferative glomerulonephritis does not constitute an absolute contraindication for liver transplantation alone; combined liver-kidney transplantations are reserved for patients with end-stage kidney failure. Proteinuria is reversed after liver transplantation, and recurrence seems to be associated with severe hepatitis C virus hepatic allograft disease relapse.     

Type I membranoproliferative glomerulonephritis in an HIV-infected individual without hepatitis C co-infection

Type I membranoproliferative glomerulonephritis (MPGN) is an uncommon manifestation of human immunodeficiency virus (HIV)-associated renal disease in patients co-infected with hepatitis C virus (HCV). We describe a case of Type I MPGN in an HIV-positive diabetic man with nephrotic-range proteinuria and renal insufficiency who was not co-infected with HCV. Tubuloreticular inclusions were present but there was no evidence for either cryoglobulinemia or cryoglobulin deposits in the kidney. This finding suggests that Type I MPGN may represent a reaction of the kidney to HIV independent of the effects of HCV co-infection. Clinical suspicion must be maintained for Type I MPGN in all HIV infected patients presenting with significant proteinuria regardless of HCV infection status.     

Persistent low C3 levels associated with meningococcal meningitis and membranoproliferative glomerulonephritis

Recurrent meningococcal meningitis is usually related to terminal complement factor deficiencies (C5-C8); however it is not frequent with isolated primary C3 deficiency. Similarly, membranoproliferative glomerulonephritis has been described in association with primary C3 deficiencies and the presence of C3 nephritic factor. We present a case of an 18-year-old woman with relapsing meningococcal meningitis in whom membranoproliferative glomerulonephritis and persistent low serum C3 levels were found. A detailed immunological study was performed, but no other abnormalities in the complement components were found. C3 Nef was also negative. Moreover, the familiar complement studies showed an asymptomatic C4 deficiency in her mother and borderline C3 levels in her sister. The presence of persistent low serum C3 levels in the absence of other immunological abnormalities suggests that this is the cause of the relapsing meningococcal infections and the glomerular disease of this patient. We suggest that a complement deficiency, including isolated C3 deficiency, should be ruled out in all cases of relapsing meningitis. Further, the possibility of glomerular disease should be carefully considered in these patients.