Viral nephropathy

Viral infections can cause many glomerular diseases. The diagnostic criteria for virus-related nephropathy include detailed clinical and laboratory data, and tissue molecular analysis. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including tropism of the virus in the kidney, induction of abnormal immune complexes, direct cytopathogenic effects, and multiorgan failure. Hepatitis B virus is associated with membranous nephropathy and mesangiocapillary glomerulonephritis in endemic areas. Hepatitis C virus causes various forms of glomerulonephritis, including cryoglobulinemia-mediated glomerulonephritis. Infection with HIV is associated with a collapsing focal segmental glomerulosclerosis, a distinctive disease that affects mainly Africans and African Americans. In the course of HIV infection, other types of immune complex glomerulonephritis can occur, most frequently in whites. Recent reports indicate a role for parvovirus B19 in 'idiopathic' collapsing focal segmental glomerulosclerosis. Both hantaviruses, and coronaviruses associated with severe acute respiratory syndrome, can lead to acute renal failure. Renal biopsy followed by appropriate serological and molecular testing is essential for defining virus-related glomerular lesions and guiding prognostic and therapeutic evaluation.     

Collapsing glomerulopathy

Collapsing glomerulopathy is a morphologic variant of focal segmental glomerulosclerosis (FSGS) characterized by segmental and global collapse of the glomerular capillaries, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. The cause of this disorder is unknown, but nearly identical pathologic findings are present in idiopathic collapsing glomerulopathy and human immunodeficiency virus (HIV)-associated nephropathy, and collapsing glomerulopathy has been associated with parvovirus B19 infection and treatment with pamidronate. The pathogenesis of collapsing glomerulopathy involves visceral epithelial cell injury leading to cell cycle dysregulation and a proliferative phenotype. Clinically, collapsing glomerulopathy is characterized by black racial predominance, a high incidence of nephrotic syndrome, and rapidly progressive renal failure. Collapsing glomerulopathy also may recur after renal transplantation or present de novo, often leading to loss of the allograft. The optimal treatment for collapsing glomerulopathy is unknown. Treatments may include steroids or cyclosporine in addition to aggressive blood pressure control, angiotensin converting enzyme inhibitors and/or angiotensin II receptor blockers, and lipid lowering agents. The role of other immunosuppressive agents such as mycophenolate mofetil in the treatment of collapsing FSGS remains to be defined. Prospective clinical trials are needed to define optimal therapy of this aggressive form of FSGS.     

Long-term response to peginterferon in hepatitis C virus-associated nephrotic syndrome from focal segmental glomerulosclerosis

Abstract

Hepatitis C virus (HCV) infection is a global public health problem. Chronic HCV infection is an important cause of chronic liver disease. Since the first reported association between HCV and membranoproliferative glomerulonephritis (MPGN) in 1993, HCV has been described with other types of glomerular diseases, although less frequently. Focal segmental glomerulosclerosis (FSGS) is one such glomerular disease that has been rarely reported in association with HCV. Antiviral therapy with interferon and ribavirin has been shown to be beneficial in HCV-associated MPGN. The optimal therapy of HCV-associated FSGS is not currently known. To our knowledge, long-term response to pegylated interferon monotherapy in treatment of HCV-associated FSGS has not been reported. We report an adult patient with HCV-associated FSGS who presented with nephrotic syndrome and renal failure. Treatment with pegylated interferon alfa-2a monotherapy resulted in sustained virological response with a clinical remission of nephrotic syndrome and stabilization of renal function. Patient continued to remain in clinical remission of nephrotic syndrome with stable renal function, 5 years after treatment. We also briefly review the literature on HCV-associated glomerular diseases, particularly HCV-associated FSGS.     

Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies

It is well known that lesions morphologically identical with focal segmental glomerulosclerosis (FSGS) may appear in IgA nephropathy (IgAN). Capsular adhesions without underlying abnormalities in the tuft, often the first sign of FSGS, are frequent in IgAN. In this retrospective study, a new cohort of 128 adult patients with IgAN was used to validate the new Oxford classification system of IgAN, and shown to have highly significant associations with clinical and outcome parameters. We then used these patients to determine the extent to which IgAN could be accounted for in terms of FSGS. Some form of lesion consistent with FSGS, notably hyalinosis and collapsing glomerulopathy, was found in 101 of these patients. No glomerular lesions were found in 16 patients, and 11 had mild lesions not definable as FSGS. Those with FSGS had significantly worse renal survival at 80 months than those without. Comparison of pure forms of FSGS (excluding collapsing glomerulopathy) with cases of FSGS having other glomerular lesions (mesangial hyperplasia, endocapillary hypercellularity, glomerular necroses, extracapillary proliferation) revealed that those with FSGS and other superimposed lesions did significantly worse than cases of pure FSGS at 80 months following diagnosis. Importantly, patients with pure FSGS had relatively poor survival even without other superimposed glomerular abnormalities. Thus, the majority of cases of IgAN can be interpreted as representing one or another variant of FSGS. Hence, interpreting IgAN in terms of FSGS emphasizes the role that podocyte lesions may play in the pathogenesis and progression of this disease.     

Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?

AIMS: Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979-1999. METHODS: The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. RESULTS: We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979-1983), 23.7% (1984-1988), 35.7% (1989-1993), 33.9% (1994-1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994-1999. CONCLUSIONS: FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.     

Lupus-like nephritis in an HIV-positive patient: report of a case and review of the literature

The most common manifestation of HIV/AIDS in the kidney is the collapsing variant of focal segmental glomerular sclerosis, HIV-associated nephropathy (HIVAN). Other forms of renal disease in HIV-infected patients include mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, IgA nephropathy, minimal change disease and proliferative immune-complex GN. We present the case of a 42-year-old Caucasian male with HIV infection, treatment associated peripheral neuropathy, nephrotic syndrome and progressive renal failure. The initial and subsequent kidney biopsies showed diffuse proliferative glomerulonephritis resembling diffuse proliferative (WHO class IV) lupus nephritis. There was no clinical or serological evidence of systemic lupus erythematosus (SLE). Proteinuria improved with ACE-inhibitors, and renal function remained relatively stable while receiving highly active antiretroviral therapy (HAART). A precipitous decline in renal function to end-stage renal disease followed a brief period of withdrawal from potent antiretroviral therapy during which the viral load rebounded. Considering previously reported cases, it appears that lupus-like nephritis is a rare but well-defined pattern of immune-complex-induced renal injury seen in HIV-infected patients. It appears to be markedly responsive to HAART.     

Glomerular pathology of allograft kidneys in Hong Kong

AIMS: Our goal was to define the spectrum of glomerular diseases in allograft kidneys and to correlate them with clinical parameters. METHODS: Eight hundred ninety-one renal graft biopsies and 43 graft nephrectomies from 1980 to 2004 were obtained from 442 allografts transplanted to 425 patients. RESULTS: Glomerular diseases were diagnosed in 33% of kidney grafts. Indications for biopsy were baseline assessment (23 biopsies, 2.5%); renal dysfunction (790 biopsies, 88.7%); proteinuria (154 biopsies, 17.3%); hematuria (11 biopsies, 1.2%); and study protocol (four biopsies, 0.4%). The median time to take a biopsy was less than 8 months posttransplant. The mean time posttransplant when the biopsy diagnosis was made was 70 months for IgA nephropathy (IgAN); 66 months for transplant glomerulopathy (TG); 65 months for focal segmental glomerulosclerosis (FSG); 55 months for mesangiocapillary glomerulonephritis (MCGN); 45 months for membranous glomerulonephritis (GN); 49 months for mesangial proliferative GN; and 101 months for diabetic nephropathy. Recurrent glomerular disease was documented in 31 (7.0%) grafts. Specific glomerular diseases were diagnosed by biopsies in 106 (89.1%) of 119 proteinuric allografts. CONCLUSIONS: Glomerulopathy was common in allografted kidneys. IgAN, TG, FSG, mesangial proliferative GN, and membranous GN were the majority. A higher proportion of grafts from donors related to the recipients than from unrelated donors showed IgAN (P < .05), suggesting that genetic factors might play a role in the pathogenesis of IgAN. Recurrence of glomerulopathy underlying ESRD was frequent for IgAN, FSG, and MCGN, but this was rarely seen in membranous GN.     

The role of sulfatides in autoimmunity in children with various glomerular disease]

Previous studies have suggested that autoimmunity to a number of kidney antigens may exist in glomerular disease. Our own work suggested that sulfatide which is one of the major acidic glycolipids of human kidney may be antigenic. Glycolipids were isolated from lipid extract of human kidney using thin-layer chromatography (TLC). As the major acidic glycolipids, sulfatide, CDH-sulfate, GM3, GD3 were identified. Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining. Sera from patients with IgA nephropathy (IgAN) and Henoch-Sch?nlein purpura nephritis (HSPN) contained antibody to the sulfatide of human kidney as determined by the direct binding of antibody to TLC. In addition, we measured the presence of sulfatide antibodies by enzyme linked immunosorbent assay (ELISA) in sera of patients with various glomerular disease: IgAN, HSPN, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), focal and segmental glomeruosclerosis (FSGS), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), acute post streptococcal glomerulonephritis (PSAGN), and lupus nephritis (LN). IgM class sulfatide antibody were demonstrated in many cases of them. The incidence of IgA class sulfatide antibody in HSPN and IgAN was significantly high, and also the high incidence of IgG class sulfatide antibody occurred in IgAN. On the other hand, we evaluated cellular hypersensitivity to sulfatide in IgAN, HSPN, and FSGS using an active E-rosette assay. Positive results occurred in IgAN and HSPN. It was suggested that delayed hypersensitivity to sulfatide may generate an autoimmune inflammatory process. It has been reported that laminin binds specifically to sulfatide. Autoimmunity to sulfatide may disturb the laminin binding and consequently interfere with renal function. These results suggested sulfatide antigen may play important role in occurrence and aggravation of glomerular disease.     

Human immunodeficiency virus and IgA nephropathy

Summary: IgA nephropathy (IgAN) in human immunodeficiency virus (HIV)-infected patients has been described with increasing frequency. In contrast to HIV-associated nephropathy, with collapsing variant of focal and segmental glomerulosclerosis and prominent tubular cell changes, a disorder which is more common in black persons, IgAN is a disease mainly of white patients. Most are asymptomatic carriers of HIV although few have acquired immunodeficiency syndrome (AIDS) or ARC at the time the renal disorder is discovered. The clinical manifestations are generally of haematuria, sometimes with proteinuria. In some patients, the finding of IgA reactive with anti-HIV IgG or IgM in circulating immune complexes and in glomerular eluates strongly suggests this glomerulopathy to be an HIV-associated immune complex disorder. Because of the demographic factors, IgAN may evolve to be an important renal lesion in HIV infection.     

Hepatitis B virus associated focal and segmental glomerular sclerosis: report of two cases and review of literature

The hepatitis B virus (HBV) is estimated to have infected about 350 million people worldwide, making it one of the most common human pathogens. Renal involvement is among its most common extra hepatic manifestations and usually manifests in the form of immune complex mediated glomerulopathy, such as membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), mesangioproliferative glomerulonephritis and immunoglobulin A (IgA) nephropathy. Occurrence of focal and segmental glomerular sclerosis (FSGS) with HBV infection is rare and only five cases have been reported earlier. We report two cases of hepatitis B associated FSGS. In both the cases, HBsAg was demonstrated in the renal tissue and both the cases showed response to treatment with lamivudine, thus indicating a possible causal association between the viral infection and occurrence of nephrotic syndrome.     

Effect of organic solvent exposure on chronic kidney disease progression: the GN-PROGRESS cohort study

It has been suggested that solvent exposure may have a role in the progression of glomerulonephritis (GN) to ESRD, but this has never been tested with an appropriate cohort study design. A total of 338 non-ESRD patients with a first biopsy for primary GN between 1994 and 2001 were included: 194 IgA nephropathies (IgAN), 75 membranous nephropathies (MN), and 69 FSGS. ESRD, defined as an estimated GFR <15 ml/min per 1.73 m2 or dialysis, was registered during a mean follow-up period of 5 yr. Patients' lifelong solvent exposures before and after diagnosis were recorded by interview and assessed by industrial hygienist experts. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Overall, 15 and 14% of the patients had been exposed at a low and a high level before diagnosis, respectively. Forty-two with IgAN, 12 with MN, and 22 with FSGS reached ESRD. A graded relationship was observed for MN (age- and gender-adjusted HR [95% confidence interval] for low exposure versus none was 3.1 [0.5 to 18.2] and for high exposure versus none was 8.2 [1.9 to 34.7]) and for IgAN (1.6 [0.7 to 3.9] and 2.2 [1.0 to 4.8]) but not for FSGS. Solvent risk was mediated only partly by baseline proteinuria: Adjusted HR for high exposure versus none was 5.5 (1.3 to 23.9) for MN and 1.8 (0.8 to 3.9) for IgAN. In patients with IgAN, there was a trend in increasing HR with exposure duration before and its persistence after diagnosis. These findings support the hypothesized association of solvent exposure with the progression of GN to ESRD. They should prompt clinicians to give greater attention to patients' occupational exposures and possibly to consider professional reclassification.     

肾小球疾病患者尿沉渣足细胞分子podocin和podocalyxin分析

目的：以ELISA法检测尿沉渣足细胞podocin,podocalyxin排泌并观察其与不同肾小球疾病的关系。方法：共收集我院自2010年5月～8月以来行肾活检证实为肾小球疾病的患者,收集其临床资料,并以ELISA法检测尿沉渣足细胞分子podocin,podocalyxin。结果：共40个患者,男15例,女25例,平均年龄（38.27±16.33）岁,增殖性肾小球疾病患者19例：IgA肾病10例,新月体性肾炎2例,IgM肾病2例,Ⅳ（A/G）型狼疮性肾炎5例;非增殖性肾小球疾病患者19例：微小病变型（MCD）5例,局灶节段硬化性肾小球肾炎（FSGS）8例,膜性肾病（MN）6例,另原发性肾淀粉样变性2例,对照健康自愿者10例。尿podocin分子排泌在正常对照组最低,在增殖性肾小球疾病和非增殖性肾小球疾病间差异无统计学意义（P〉0.05）,增殖性肾小球疾病尿podocin排泌高于肾淀粉样变性患者（P〈0.05）。新月体肾炎的尿podocin排泌显著高于其他肾小球疾病（P〈0.05）,后依次FSGS,IgA肾病,狼疮性肾炎,MN,IgM肾病,MCD;尿沉渣podocalyxin排泌在正常对照组最低,而增殖性肾小球肾炎和非增殖性肾小球肾炎间差异无统计学意义（P〉0.05）。新月体肾炎尿podocalyxin排泄量最高,其后依次为FSGS,IgA肾病,MN,狼疮性肾炎,MCD,IgM肾病,以肾淀粉样变性最低。尿podocalyxin与podocin呈正相关,尿podocin与血C3呈负相关。结论：ELISA法检测尿沉渣足细胞分子检测可对肾小球疾病患者的肾病理类型提供参考,以正常人尿podocin,podocalyxin排泌最少,增殖性肾小球疾病和非增殖性肾小球疾病间差异无统计学意义,新月体性肾炎尿沉渣podocin及Podocalyxin高于其他疾病患者,FSGS患者的尿沉渣podocin及Podocalyxin排泌量也较多,肾淀粉样变性患者的尿沉渣podocin及Podocalyxin最低,血清C3与尿podocin的排泌呈负相关。     

The clinico-pathological studies of hepatitis B virus nephropathy in adults

The purpose of this study is to clarify the clinical and pathological features of glomerulonephritis associated with hepatitis B virus infection (HBV-GN) in adults. Of the 47 adult cases with HBV-GN, 7 cases were diagnosed as minor glomerular abnormalities, 19 as mesangial proliferative GN (mild 13, moderate 4, severe 2), 11 as membranous GN, 10 as membranoproliferative GN (type I 2, type III 8). Indirect immunoperoxidase method using monoclonal antibody raised against HBV related antigens (HBsAg and HBeAg) revealed glomerular deposition of only HBsAg in 10 cases, only HBeAg in 2, and both antigens in 10. Deposition of HBeAg was observed dominantly along the capillary walls in comparison with that of HBsAg (p less than 0.01). Additionally, in 4 cases diagnosed as the IgA-GN because of the IgA dominant mesangial deposition and normal liver function, HBV related antigens were detected in the mesangial areas. Aggravation of renal function with respect to serum creatinine level, only 0.6-0.8 mg/dl increased, was demonstrated in 4 of 27 cases followed up for more than a year. These results suggest that the high incidence of membranous GN and membrano-proliferative GN was observed in HBV-GN in adults. HBsAg as well as HBeAg may contribute to the pathogenesis of this glomerulonephritis, and then HBsAg may play in capillary walls and mesangial areas, whereas HBeAg in capillary walls mainly. And the possibility exists that HBV related antigens are the responsible antigenic agents in some cases of IgA-GN.     

Specific changes in plasma concentrations of matrix metalloproteinase-2 and -9, TIMP-1 and TGF-beta1 in patients with distinct types of primary glomerulonephritis.

BACKGROUND: Dysregulated renal expression of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMP) and TGF-beta1 contribute to the development of tubulo-interstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). There is little information on the circulating levels of these proteins in human GNs. Here, we assessed whether different histopathological GN types could be associated with distinct plasma patterns of MMPs and regulatory proteins. METHODS: Protein levels of MMP-2, MMP-9, TGF-beta1 and TIMP-1 were measured by ELISA in plasma from venous blood of 108 untreated patients with various types of primary GN defined by kidney biopsy, namely IgAN (n=63), membranous GN (MN, n=26), minimal change nephrotic syndrome (MCNS, n=12) and focal and segmental glomerular sclerosis (FSGS, n=7), and were compared with levels in 50 healthy subjects. Plasma samples were assayed for gelatinolytic activity (zymography). RESULTS: Zymography detected the proforms of MMP-2 and MMP-9. Compared with controls, IgAN patients exhibited a significant, parallel decrease in plasma levels of MMP-2, MMP-9 and TGF-beta1. In MN patients, decreased MMP-9 level contrasted with a high MMP-2 level and a normal TGF-beta1 level. In the MCNS/FSGS group, increased MMP-2 level contrasted with unchanged MMP-9 and decreased TGF-beta1 levels. Plasma concentration of TIMP-1 was elevated in all GN groups. There was no correlation between baseline MMP-2/MMP-9/TIMP-1/TGF-beta1 levels and the degree of renal dysfunction or with progression toward ESRD. CONCLUSIONS: Plasma concentrations of MMP-2, MMP-9 and TGF-beta1 significantly differed between the various histopathological types of primary GNs, thus suggesting the involvement of different underlying mechanisms in the regulation of glomerular and tubulointerstitial fibrosis in these renal diseases.     

The spectrum of children's kidney diseases—9925 renal biopsy-proven cases from a single center of China between 2004 and 2017

Objective To analyze the spectrum of children's kidney pathology by renal biopsy. Methods The clinical and pathological data of the cases in Jinling Hospital involving the patients younger than 18 years old who received renal biopsy from April 1st, 2004 to December 31th, 2017 were retrospectively collected, and compared with the renal pathological data of 1611 children aged 0-18 years from June 1982 to March 2004. Results This study included 9925 cases of kidney diseases proven by renal biopsy. The ratio of male to female was 1.79∶1. Primary glomerulonephritis (PGN) accounted for 66.14%, and secondary glomerulonephritis (SGN) accounted for 28.00%. Top five of the PGN were IgA nephropathy (IgAN, 19.11%), mesangial proliferative glomerulonephritis (MsPGN, 16.07%), minimal change disease (MCD, 14.20%), focal segmental glomerulosclerosis (FSGS, 6.19%) and membranous nephropathy (MN, 4.70%) in whole children, IgAN (13.12%), MsPGN (11.20%), MCD(10.63%), FSGS (4.55%) and MN (2.54%) in males, and IgAN (5.99%), MsPGN (4.87%), MCD (3.57%), MN (2.16%) and FSGS (1.63%) in females. Top three of the SGN were Henoch-Schonlein purpura nephritis (HSPN, 17.74%), lupus nephritis (LN, 8.23%) and vasculitis nephropathy (1.82%). The male was in a dominant position in all kinds of pathologic types than female except LN. HSPN was the most frequent type in adolescents between 6-13 years old. LN was the commonest one in 14-18-year-old girls, while IgAN was the the most common in 14-18-year-old boys. Post infective nephritis was the most popular in 12-14-year-old teenagers. It was also found that MN ascended in female. When compared with the data before 2004, HSPN and LN accounted for a greater proportion in SGN, post infective nephritis displayed a smaller proportion. Conclusions PGN is the mainly kind of glomerular disease as before, and immune disorder related to glomerular diseases increase and post infective nephritis decreases in proportion. This study provides the reference and epidemic data for diagnosis, treatment and prevention of children's renal diseases.     

Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy

BACKGROUND: Collapsing glomerulopathy (CG), a disorder with severe glomerular and tubular involvement, occurs either as an idiopathic lesion or in some patients with human immunodeficiency virus (HIV) infection known as HIV-associated nephropathy (HIVAN). We previously reported a renal transplant recipient with de novo CG and red cell aplasia in association with persistent parvovirus B19 (PVB19) infection. This prompted us to look for an association between PVB19 infection and CG. METHODS: DNA from archived biopsies of patients with CG was analyzed for PVB19 by polymerase chain reaction (PCR). Results were compared with HIVAN, idiopathic focal segmental glomerulosclerosis (FSGS), and controls. In situ hybridization (ISH) was done to localize PVB19 in renal biopsies. Peripheral blood specimens of patients with CG, HIV infection, healthy controls, and randomly selected hospitalized patients (sick controls) were also analyzed for PVB19. RESULTS: PVB19 DNA was detected in renal biopsies of 18 out of 23 (78.3%) patients with CG, 3 out of 19 (15.8%) with HIVAN, 6 out of 27 (22.2%) with FSGS, and 7 out of 27 (25.9%) controls (P < 0.01, CG vs. HIVAN, FSGS, and controls). PVB19 was detected in peripheral blood of 7 out of 8 (87.5%) CG patients, 3 out of 22 (13.6%) with HIV infection, 4 out of 133 (3%) healthy controls, and 2 out of 50 (4%) sick controls (P < 0.001, CG vs. HIV infected, healthy, and sick controls). PVB19 was identified in glomerular parietal and visceral epithelial and tubular cells by ISH. CONCLUSIONS: The significantly higher prevalence of PVB19 DNA in renal biopsies and peripheral blood of CG patients suggests a specific association between PVB19 infection and CG. In susceptible individuals, renal epithelial cell infection with PVB19 may induce CG.     

Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA?

Over the past decade, focal segmental glomerulosclerosis (FSGS) has emerged as the most common primary glomerulopathy in adults in the USA. However in our practice, we became aware of increased numbers of patients with IgA nephropathy (IgAN). In order to further examine this, a retrospective analysis of renal biopsy diagnoses from adults was done from our biopsy database. Adult renal biopsies received from 3/1/2001 to 2/28/2005 were analyzed to determine the frequency of common primary glomerulopathies, which included FSGS, IgAN, membranous nephropathy (MN), minimal change disease, and membranoproliferative glomerulonephritis Type I (MPGN). The patients were grouped as all adults (>or=20 years) and young adults (20-39 years). The distribution of common primary glomerulopathies among the two age groups, expressed as a percentage of all non-transplant diagnoses (n = 4,504), was IgAN 6.9/3.4%, FSGS 9.6/3.2%, MN 6.8/1.6%, minimal change disease 2.5/0.9%, MPGN 1.2/0.2%. IgAN was as common as FSGS in young adults in our biopsy population (IgAN/FSGS 154/143 1.08:1). IgAN was the most common primary glomerulopathy in young adult Caucasians (IgAN/FSGS 2.1:1). IgAN was also the most common cause of end-stage renal disease (ESRD) in young adult Caucasians. In contrast, IgAN was rare in African Americans in whom FSGS remains more common (FSGS/IgAN 9.7:1). These findings from a large renal biopsy referral center serving 24 Midwestern and Southern states suggest that IgAN may be the most common primary glomerulopathy and the most common cause of ESRD in young adult Caucasians in the USA.     

HIV-associated immune complex glomerulonephritis with "lupus-like" features: a clinicopathologic study of 14 cases

BACKGROUND: While the most common glomerular lesion associated with human immunodeficiency virus (HIV) infection is collapsing focal segmental glomerulosclerosis (FSGS) [HIV-associated nephropathy (HIVAN)], immune complex-mediated forms of glomerulonephritis have been increasingly reported. One form of glomerulonephritis that has been described in the HIV-infected population is immune complex glomerulonephritis with "lupus-like" features, characterized by histologic, immunohistologic, and ultrastructural features resembling lupus nephritis, but occurring in patients without evidence of systemic lupus erythematosus (SLE). Data regarding clinical outcomes in patients with this form of glomerulonephritis are very limited. METHODS: We reviewed pathology reports for all native renal biopsy specimens from HIV-positive patients processed at our center from January 1999 through December 2003. Of 77 total specimens, 14 met the following criteria for lupus-like glomerulonephritis: (1) immunofluorescence microscopy showed granular glomerular staining for IgG, IgA, IgM, C3 and C1q, with > or=1+ (0 to 4+ scale) staining for C1q; and (2) the patient's serum was negative for antinuclear antibodies (ANA), or weakly positive (titer < or =1:80) for ANA and negative for antidouble-stranded DNA. RESULTS: Clinically, ten of the 14 patients with lupus-like glomerulonephritis presented with nephrotic syndrome, all had microscopic hematuria, and nine had serum creatinine >3.0 mg/dL. All but one were African American. Histologically, seven biopsies showed diffuse proliferative glomerulonephritis, six focal proliferative glomerulonephritis, and one membranous nephropathy. All but two biopsies showed moderate or severe chronic change, and three showed concurrent HIVAN. Ten of the 14 patients developed end-stage renal disease (ESRD) within 1 year of the biopsy. Nine of these ten patients presented with proteinuria >5.0 g/24 hours and nephrotic syndrome, while three of four patients who did not develop ESRD had proteinuria < or =3.0 g/24 hours. CONCLUSION: Lupus-like glomerulonephritis, defined by immunohistologic features and absence of serologic evidence of SLE, is not an uncommon form of glomerular disease in HIV-infected patients undergoing a renal biopsy. Renal outcomes in these patients were poor, although this may be due largely to most patients presenting with advanced disease.     

Pathologic classification of focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is defined as a clinical-pathologic syndrome manifesting proteinuria and focal and segmental glomerular sclerosis with foot process effacement. The pathologic approach to the classification of FSGS is complicated by the existence of primary (idiopathic) forms and multiple subcategories with etiologic associations, including human immunodeficiency virus (HIV)-associated nephropathy, heroin nephropathy, familial forms, drug toxicities, and a large group of secondary FSGS mediated by structural-functional adaptations to glomerular hyperfiltration. A number of morphologic variants of primary and secondary focal sclerosis are now recognized, including FSGS not otherwise specified (NOS), perihilar, cellular, tip, and collapsing variants. The defining features of these morphologic variants and of the major subcategories of FSGS are discussed with emphasis on distinguishing light microscopic patterns and clinical-pathologic correlations.     

Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with renal manifestations, such as membranoproliferative glomerulonephritis (MPGN) with or without cryoglobulinaemia, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS). Standard treatment for HCV is interferon and ribavirin, but in renal insufficiency ribavirin has been contraindicated due to fear of side effects. METHODS: Seven patients, two with cryoglobulinaemia, vasculitic manifestations and glomerulonephritis (GN), four with MPGN and one with FSGS were treated with a combination of interferon and ribavirin. Two patients were given pegylated interferon and ribavirin. All patients had at presentation renal insufficiency, with a glomerular filtration rate (GFR) between 10 and 65 ml/min. One patient had HCV genotype 1, the remainder 2 and 3. Duration of therapy was according to genotype (6-12 months). Ribavirin in plasma was monitored by high-performance liquid chromatography (HPLC) to avoid over-dosing, aiming at a target concentration of 10-15 micromol/l. The main side effect of ribavirin, haemolytic anaemia, was monitored closely with haemoglobin controls. RESULTS: Six of seven patients became HCV-RNA-PCR negative and four of seven have maintained both virological and renal remission. One of seven has maintained virological and partial renal remission. One patient did not tolerate interferon, but is in renal remission with low-dose ribavirin. One vasculitis patient responded with complete remission, but relapsed virologically and had a minor vasculitic flare after 9 months. Only one patient with vasculitis had low-dose immunosuppression in addition to anti-viral therapy. Average daily ribavirin dose was 200-800 mg. Ribavirin-induced anaemia was managed in five of seven patients with low-dose iron and erythropoietin between 4000 and 20 000 IU/week. CONCLUSIONS: Interferon and ribavirin can with reasonable safety be used in HCV-related vasculitis and GN irrespective of renal function.