Hepatitis C virus infection and renal disease after renal transplantation

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease after renal transplantation (RT). It is considered in some series to be a risk factor for graft loss and patient death. Also, HCV has been implicated in the pathogenesis of glomerular diseases in native and transplanted kidneys. The presence of membranoproliferative (MP) or membranous (M) glomerulonephritis (GN) in HCV-positive patients has been well documented after RT, but there is no clear data concerning the real prevalence of HCV-induced glomerulonephritis. MPGN with or without cryoglobulinemia and MGN have been described in HCV RNA-positive patients in general without severe liver disease. Also, there is a possible association between HCV infection and acute/chronic transplant glomerulopathy. Renal thrombotic microangiopathy has been described in HCV-positive patients with positive anti-cardolipin antibodies. The pathogenesis of MPGN and MGN in HCV patients after RT seems to be similar to that which occurs in native kidneys: the deposition of immune complexes containing HCV proteins in the glomeruli. Renal biopsy, using light microscopy, immunofluorescence techniques, and electron microscopy, is useful to achieve a correct diagnosis. Unfortunately, interferon is not recommended due to the significant risk of rejection. The possibility of pegylated interferon needs to be tested. Ribavirin can improve proteinuria but HCV RNA remains positive. Finally, recent data suggest that the use of interferon in HCV patients on dialysis can negate HCV RNA and prevent associated glomerulonephritis after RT.     

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.     

Intermediate-term outcomes of hepatitis C-positive compared with hepatitis C-negative deceased-donor renal allograft recipients

BACKGROUND: Prior studies have yielded conflicting results concerning the impact of HCV on renal transplant outcomes. METHODS: We examined outcomes in comparable groups of predominantly African American hepatitis C virus (HCV)-positive (n = 34) and HCV-negative (n = 111) kidney transplant patients receiving contemporary immunosuppression. RESULTS: There was no difference in patient survival or acute rejection, but new-onset diabetes (NODM) was increased and graft survival decreased in the HCV-positive group, with increased graft loss secondary to noncompliance and Type I MPGN. The incidence of NODM among patients undergoing early corticosteroid withdrawal was 11% in both groups, while among those on prednisone, it was 47% in HCV-positive versus 25% in HCV-negative recipients. CONCLUSIONS: Deceased-donor HCV-positive renal allograft recipients have equivalent patient but decreased graft survival. Noncompliance and Type I MPGN play a role in producing this negative effect on graft outcome. Steroids may be required for HCV to exert its diabetogenicity in kidney transplant patients.     

A comprehensive study of the association between hepatitis C virus and glomerulopathy.

BACKGROUND: Hepatitis C virus (HCV)-related infection is commonly associated with a wide range of glomerulonephritides (GN) including membranoproliferative glomerulonephritis (MPGN). The causal link between HCV infection and renal disease has been postulated through the induction of cryoglobulinaemia and secondary GN. However, the detection of viral particles or genomes within the kidneys of HCV-infected patients has proved to be difficult. With that in mind, we have studied a population of Egyptian HCV-positive patients with associated GN in an attempt to detect viral particles, antigens or RNA within their kidneys. METHODS: Fifty patients were found to be HCV positive out of 303 who presented with a glomerulopathy between 1998 and 1999 at the Mansoura Urology and Nephrology Center, Egypt. Comprehensive investigations of these 50 patients were undertaken including an evaluation of their clinical, biochemical, histological, virological and immunological parameters. In addition, their kidney biopsy material was analysed by electron microscopy (EM) to detect viral particles, by immunohistochemistry to detect a viral core antigen and by RT-PCR to detect RNA. This was compared with 50 HCV-negative controls. RESULTS: Positivity for HCV antibodies was higher among patients with GN (38%) compared with healthy blood donors (16%). Genotype 4 was sequenced in 70% of the HCV-positive samples examined. MPGN was the most common type of GN accounting for 54% of patients. Extrarenal manifestations were absent in the majority (80%) of patients even though 54% had cryoglobulinaemia. EM revealed virus-like particles in 50% of biopsies. Immunohistochemistry failed to reveal HCV-related antigens in kidney sections. HCV RNA was detected in the cryoprecipitates in 66% of patients and 22% of frozen renal sections. Control sections were negative. CONCLUSION: Our findings suggest a causal link between HCV and GN based on the observation of virus-like particles as well as viral RNA within the kidney sections of patients with HCV-associated glomerulopathies.     

Renal transplantation offers a better survival in HCV-infected ESRD patients

Sezer S, Ozdemir FN, Akcay A, Arat Z, Boyacioglu S, Haberal M. Renal transplantation offers a better survival in HCV-infected ESRD patients. Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00252.x Copyright Blackwell Munksgaard, 2004Abstract: The presence of hepatitis C virus (HCV) infection has been found to adversely affect the morbidity and mortality rates in the dialysis population. Renal transplantation is a treatment option after a careful pre-transplant evaluation. We designed this study to find the impact of HCV infection on patient survival, co-morbidity and allograft survival in a selected group of hemodialysis (HD) and transplant population. We retrospectively analyzed 116 renal transplant patients (94 HCV-negative, 22 HCV-positive) and 136 HD patients (106 HCV-negative, 30 HCV-positive) who had renal transplantation or underwent dialysis before 1996. The HCV-infected patients were evaluated by liver biopsy for the absence of advanced liver disease before transplantation. There was no clinical or laboratory decompensation of liver disease in transplant and dialysis patient groups. The overall 5-yr survival rates were 85.2% for renal transplant recipients and 74.5% for those on HD. The comparison results revealed a significant difference between HCV-infected patients with and without transplantation. The 3-yr renal allograft survival rates were comparable in HCV-positive and -negative patients, but the risk of chronic allograft nephropathy (CAN) and graft failure were higher at the fifth year in HCV-positive patients. In conclusion, renal transplantation should the preferred therapy in HCV-infected dialysis patients as it improves the survival rates. The presence of HCV infection increases the CAN rate and the influence on allograft survival is evident at the fifth year of assessment.     

Idiopathic nephrotic syndrome of the adult with asymptomatic thrombosis of the renal vein

Twenty-six adult patients with idiopathic nephrotic syndrome, ages ranging from 16 to 62 years, were prospectively evaluated with selective renal venogram for the presence of renal vein thrombosis (RVT). Ten patients had membranoproliferative glomerulonephritis (MPGN); 5, membranous nephropathy (MGN); 3, diffuse proliferative glomerulonephritis (DGPG), and 1 focal glomerulonephritis (FPG). Renal vein thrombosis was observed in 11 patients. The primary nephropathies in these patients were: MPGN in 4, MGN in 3, FGS in 2, FPG in 1, and DGPG in 1. All patients were asymptomatic. The clinical and renal pathology features were similar in patients with and without RVT. Other thromboembolic complications were observed in 4 patients. In conclusion, renal vein thrombosis was observed in 42% of our patients and MPGN was the most frequent nephropathy associated with RVT.     

Impact of hepatitis C virus on renal transplantation: association with poor survival

Data concerning the effect of hepatitis C virus (HCV) infection on the long-term outcome of patient and allograft survival are conflicting. We performed a retrospective study including all renal transplant recipients who underwent the procedure at our center between July 1983 and December 2004. We compared HCV-positive (n = 155) versus HCV-negative (n = 1044) recipients for the prevalence of anti-HCV, patient/donor characteristics, and graft/patient survival. The prevalence of HCV-positive patients was 12%. The anti-HCV positive recipients displayed a longer time on dialysis (P < .001), more blood transfusions prior to transplant (P < .001), and a higher number of previous transplants (P < .001). There were no differences in the incidence of acute rejection between the two groups. Patient (P = .006) and graft survival (P = .012) were significantly lower in the HCV-positive than the HCV-negative group. Graft survival censored for patient death with a functioning kidney did not differ significantly between HCV-positive and HCV-negative recipients (P = .083). Death from infectious causes was significantly higher among the HCV-positive group (P = .014). We concluded that HCV infection had a significant detrimental impact on patient and renal allograft prognosis. Death from infectious causes was significantly more frequent among HCV-positive than the non-HCV population.     

Long-term effect of hepatitis C virus chronic infection on patient and renal graft survival

BACKGROUND: Hepatitis C virus (HCV) infection increases morbimortality in renal transplantation. The immune response against the HVC is not predictable in a great proportion of patients developing into chronic liver disease, glomerulonephritis, or both. PATIENTS: We analyzed the impact of posttransplant chronic hepatitis development on patient and graft survival in 200 HCV-positive/HBsAg-negative renal allograft recipients transplanted between 1981 and 2003. RESULTS: Ninety-eight patients developed chronic ALT elevation (ALT+), while 102 did not (ALT-). There was no difference in acute rejection episodes (ARE), acute tubular necrosis, donor and recipient age, gender, HLA mismatches, and number of previous renal transplants. Development of ALT+ was associated with a worse patient survival (90% vs 65% at 15 years of follow-up, P = .007; RR = 3.8, CI = 1.4-10.1), an effect that was independent of other variables as time on dialysis and age. The main causes of death among ALT+ were chronic liver disease (52%), cardiovascular (26%), and infection (13%), whereas in ALT- they were cardiovascular (33%), cancer (33%), and chronic liver disease (16%). Conversely, graft survival (censoring for patient death with a functioning graft) was higher among ALT+ (50% vs 35% at 15 years of follow-up, P = .04; RR = 1.5, CI = 1.19-2.22). Causes of graft loss in ALT- patients were chronic allograft nephropathy (CAN, 53%), glomerulonephritis (GN, 18%), acute rejection episode (AR, 22%), and death (5%), whereas among ALT+ they were CAN (36%), GN (31%), ARE (10%), and death (21%; P = .01). By multivariate analysis, ALT- (RR = 1.6, CI = 1.07-2.55, P = .02) and de novo GN (RR = 2, CI = 1.29-3.09, P = .002) were associated with worse renal allograft survival. CONCLUSION: Our results suggested that a better immune response against the HCV lead to greater patient survival but poorer graft survival.     

Virus-related glomerular diseases: histological and clinical aspects

Viral infections can be the causative agent in many glomerular diseases, and diagnostic criteria include clinical and laboratory data and tissue molecular analysis. Hepatitis B virus (HBV) is a well known cause of membranous glomerulonephritis (MGN), membranoproliferative GN (MPGN) and IgA nephropathy (IgAN), frequently in Asian populations. Hepatitis C virus (HCV), besides cryoglobulinemia-mediated glomerulonephritis (GN), is reported to cause other forms of GN. Human immunodeficiency virus (HIV) infection is closely related to a collapsing focal segmental glomerulosclerosis (FSGS), a distinct disease that affects mainly Africans and African-Americans. In the course of HIV infection other immune complex (IC) GN can occur, most frequently in whites. Nephrotic syndrome and progression to renal insufficiency are the main clinical manifestations. HIV-HCV co-infection is related to an IC glomerular disease, sometimes with immunotactoid deposits. Recent reports emphasize the role of parvovirus B19 (PV B19) for "idiopathic" collapsing FSGS and ICGN, and of Coxsackie B virus for IgAN. Renal biopsy is useful for defining virus-related glomerular lesions and a guide for prognostic and therapeutic evaluation.     

Pretransplant Interferon Prevents Hepatitis C Virus-Associated Glomerulonephritis in Renal Allografts by HCV-RNA Clearance

The purpose of this study was to examine the effect of pretransplant interferon administration on the occurrence of post-transplant de novo glomerulonephritis in hepatitis C virus (HCV)-positive renal allografts. From December 1992 to December 2000, 78 HCV-positive patients received a renal allograft in our unit. Fifteen out of 78 received pretransplant interferon for 1 year. Hepatitis C virus was investigated by serology and qualitative polymerase chain reaction (PCR). Hepatitis C virus-related de novo glomerulonephritis (membranoproliferative or membranous) was suggested by proteinuria (>1.5 g/24 h) and/or microhematuria and always diagnosed by renal biopsy. Of 15 HCV-positive recipients who received pretransplant interferon, 10 (67%) became HCV-RNA negative at the time of transplantation and only one out of the 15 (6.7%) developed de novo glomerulonephritis (this patient was HCV-RNA positive at transplantation). Among non-interferon-treated allograft recipients, 28.7% had negative HCV-RNA and 12 out of 63 (19%) developed de novo glomerulonephritis (9, membranoproliferative; 3 membranous), all 12 having positive HCV-RNA at transplantation (p < 0.0001). In conclusion, pretransplant interferon may reduce the occurrence of post-transplant HCV-related de novo glomerulonephritis. Our results suggest that the indication for pretransplant interferon should be extended to treat all HCV-RNA positive candidates for renal transplantation.     

Recurrence of membranoproliferative glomerulonephritis type II in renal allografts: The North American Pediatric Renal Transplant Cooperative Study experience

Membranoproliferative glomerulonephritis type II (MPGN II) is an uncommon form of complement-dependent acquired renal disease. Although it has been recognized since the 1970s that MPGN II recurs almost universally in renal transplants, data regarding the long-term consequences of disease recurrence are limited. Therefore, a retrospective comparative analysis of 75 patients with MPGN II contained in the North American Pediatric Renal Transplant Cooperative Study transplantation database was performed. Five-year graft survival for patients with MPGN II was significantly worse (50.0 +/- 7.5%) compared with the database as a whole (74.3 +/- 0.6%; P < 0.001). Living related donor organs had a significantly better 5-yr survival (65.9 +/- 10.7%) compared with cadaveric donor organs (34.1 +/- 9.8%; P = 0.004). The primary cause of graft failure in 11 (14.7%) patients was recurrent disease. Supplemental surveys were obtained on 29 (38%) of 75 patients. Analysis of these data indicated that recurrent disease occurred in 12 (67%) of the 18 patients with posttransplantation biopsies. Although there was no correlation between pretransplantation presentation, pre- or posttransplantation C3 levels, and either disease recurrence or graft failure, there was a strong association between heavy proteinuria and disease recurrence. The presence of glomerular crescents in allograft biopsies had a significant negative correlation with graft survival. At last follow-up, patients with recurrent disease had significantly higher serum creatinine and qualitatively more proteinuria than patients without biopsy-proven disease. These data indicate that recurrent MPGN II has a significant negative impact on renal allograft function and survival.     

Nephropathy associated with heroin abuse in Caucasian patients.

BACKGROUND: Renal disease is a complication of heroin addiction. Using renal biopsies in Caucasian patients, we studied the types of nephropathy associated with heroin abuse. METHODS: Nineteen renal biopsies were performed on heroin addicts between January 1993 and December 2001. The indications for renal biopsy included proteinuria with or without renal insufficiency. RESULTS: All 19 patients had serological evidence of hepatitis C virus (HCV) infection, one had hepatitis B virus surface antigen and three were HIV positive. Thirteen patients (68.4%) were found to have membranoproliferative glomerulonephritis (MPGN), 12 with type I and one with type III. Of the remaining patients, two had chronic interstitial nephritis, two had acute proliferative glomerulonephritis, one had amyloidosis and one had granulomatous glomerulonephritis with interstitial nephritis. No apparent decline in the incidence of renal disease was observed. CONCLUSIONS: In this cohort of male Caucasian heroin addicts, HCV-associated MPGN was the most frequent pattern of nephropathy, showing that the nephropathy associated with heroin abuse in Caucasians is not of the focal and segmental glomerulosclerosis type, in contrast to previous reports on African-Americans. This aspect may have important implications for patient management and prognosis.     

Membranoproliferative glomerulonephritis and circulating cryoglobulins

Background

Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN.

Patients and methods

Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease.

Results

In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative ‘idiopathic’ MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis.

Conclusion

Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.     

Hepatitis C virus infection and kidney transplantation

Hepatitis C virus (HCV) infection is an important problem in the patient with end-stage renal disease. After transplantation, liver disease is more frequent in HCV-positive patients than in HCV-negative patients. In the long run, this leads to important liver complications. The patients have a higher risk for developing proteinuria and infections. Long-term patient and graft survival rates are lower in HCV-positive patients than in HCV-negative graft recipients. Mortality is higher, mainly as a result of liver disease and infections. Despite this, transplantation is the best option for the HCV-positive patient with end-stage renal disease. Transplantation of HCV-positive kidneys should be offered to HCV-positive recipients in whom HCV RNA is detected in the serum. Finally, several measures after transplantation minimize the consequences of HCV infection. Adjustment of immunosuppression and careful follow-up in the outpatient clinic for early detection of proteinuria, infection, or worsening of liver disease are mandatory.     

Asymptomatic haematuria and proteinuria: Renal pathology and clinical outcome in 54 children

In a mass screening programme, 54 children with haematuria and proteinuria were detected and evaluated by clinical findings and renal histology. IgA glomerulonephritis (GN) occurred in 29 patients, diffuse mesangial proliferative GN (DPGN) in 16, membranous GN (MGN) in 4, membranoproliferative GN (MPGN) in 3, and focal segmental glomerular sclerosis (FSGS) was seen in 2. Of the 35 children with proteinuria less than or equal to 1 g/m² per day, 21 with IgA GN and 14 with DPGN had only mild to moderate glomerular changes. None of these children had developed renal impairment after a mean period of 6.5 years (range 5–10 years). On the other hand, 8 children with IgA GN, 2 with DPGN, 4 with MGN, 3 with MPGN, and 2 with FSGS had proteinuria that exceeded 1 g/m² per day. The biopsy specimens from these children showed moderate to severe glomerular changes, and 7 of these children had hypertension or renal impairment during the period of evaluation. This study suggests that a poor outcome correlates with the level of proteinuria and the severity of renal pathology in children with haematuria and proteinuria.     

Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV-infected renal allograft recipients

BACKGROUND: Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome. METHODS: Sera and fresh plasma from 31 HCV-RNA-positive patients after renal transplantation (group I) were studied for cryoglobulins, complement hemolytic activity (CH50), and complement split product C3d. In total, 80 HCV-negative renal transplant recipients (group II) and 72 untreated patients with chronic hepatitis C (group III) without renal transplantation served as controls. RESULTS: Cryoglobulins were detected in 45, 28, and 26% of the patients in group I, II, and III, respectively. A high cryocrit ( > 5%) was present only in patients of group III (p < 0.01%). Mean CH50 values were lower and C3d levels higher in HCV-positive patients (group I and III) compared with HCV-negative patients (p < 0.0001). Cryoglobulins were not associated with extrahepatic manifestations or graft dysfunction, except in five patients of group III demonstrating cryoglobulinemic vasculitis. HCV-positive renal transplant recipients with signs of complement activation showed a significantly greater increase of serum creatinine (0.88 +/- 1.14 mg/dL) when compared with baseline than patients without complement activation (0.34 +/- 0.37 mg/dL; p = 0.035). There was also a tendency toward a higher extent of proteinuria in patients with complement activation (1.38 +/- 2.17 g/d vs. 0.50 +/- 0.77 g/d; p = 0.25, NS). CONCLUSIONS: Cryoglobulins are common in renal allograft recipients, but do not affect graft function. However, complement activation appears to be involved in chronic allograft dysfunction in HCV-infected recipients.     

Outcome of kidney transplant in chronic hepatitis C virus patients: effect of pretransplantation interferon-alpha2b monotherapy

Hepatitis C virus (HCV) infection represents an important problem for hemodialysis patients especially following renal transplantation. We assessed the outcome of HCV-positive patients undergoing renal transplantation after treatment during the pretransplant period with alpha-interferon 2b (alpha-IFN2b). Data from all HCV-infected patients (n=38) undergoing renal transplantation from a cadaveric donor between January 1997 and June 2002 were retrospectively reviewed. Viral clearance was achieved in 7 of 13 patients receiving alpha-IFN2b monotherapy during the pretransplant period. Controls were HCV-negative renal transplantation recipients operated during the same period (n=273). HCV-positive compared to HCV-negative patients showed no differences in age, gender, underlying disease, donor type, or immunosuppressive regimen, but there were significant differences (P<.001) in the mean (+/-SD) time on dialysis (155+/-70 versus 43+/-47 months), retransplant incidence (26% versus 5%), immunization rate as assessed by panel reactive antibodies (PRA) peak >50% (55% versus 18%), or 1-year survival of recipients (88% versus 97%) and of grafts (76% versus 89%). In contrast, all seven HCV RNA-negative patients who were before transplantation survived to the end of follow up with functioning grafts in six subjects and remained with normal liver function and clearance of HCV RNA. We conclude that kidney transplantation in HCV-positive compared with HCV-negative patients shows lower recipient and graft survival rates, possibly due to the higher incidence of risk factors, such as duration of hemodialysis, higher retransplantation rate, or hyperimmunization. Responders to pretransplantation IFN therapy show an excellent prognosis of liver function and overall outcome close to HCV-negative renal transplant recipients.     

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.     

High prevalence and adverse effect of hepatitis C virus infection in type II diabetic-related nephropathy

Over a 4-yr period in the northeast region of Japan (Tohoku), 3643 patients for whom a renal biopsy was available were screened. In addition, 2370 biopsied patients for whom hepatitis C virus (HCV) serology was available were evaluated. The prevalence of HCV infection was investigated in the 2370 biopsied patients. The highest prevalence of HCV infection was found in type II diabetic-related glomerulosclerosis (II-DGS) (24 of 123; 19.5%). At renal biopsy, clinical and laboratory findings and histologic parameters were comparable between the HCV-positive and -negative II-DGS groups. After renal biopsy, the decline of renal function reflected by the slope of reciprocal serum creatinine (1/S(Cr)) was significantly greater in the HCV-positive group than in the HCV-negative group (P = 0.001). The log-rank test performed on the renal survival curves showed a significant difference in the two groups (P = 0.019). According to a multiple linear regression analysis adjusted for the effect of age, gender, BP, HbA1c, urinary protein excretion, and histologic parameters as covariates, urinary protein excretion (P = 0.011), severe arteriolar hyalinosis (P = 0.006), and HCV infection (P < 0.001) were significantly associated with 1/S(Cr) slope. Finally, HCV infection was randomly examined in 545 outpatients and inpatients with type II diabetes mellitus who did not undergo renal biopsy. Of these, 56 patients were positive for HCV antibody (10.3%), and their proteinuria was heavier than in 489 HCV-negative patients (P = 0.001). This study reveals that HCV infection is present at a high rate in type II diabetic-related nephropathy and may have an adverse effect on the progression of the disease.