Glomerular disease in cirrhosis of the liver: low frequency of IgA deposits

Twelve HBsAg-negative patients with histologically documented cirrhosis of the liver of either alcoholic (8 of 12) or cryptogenic (4 of 12) origin underwent renal biopsy to investigate proteinuria, hematuria and/or renal failure. Immunofluorescence was positive for IgA in 2 patients with mesangiocapillary glomerulonephritis (MCGN) and could not be performed in 2 additional patients with the same diagnosis. However, in the remaining 8 patients, immunofluorescence was negative for IgA and frequently positive for C3, IgG, IgM and/or fibrinogen. These 8 patients without IgA were classified as follows: MCGN with subendothelial electron-dense deposits (2 cases), IgM-IgG cryoglobulinemia with diffuse endocapillary glomerulonephritis (1 case), membranous nephropathy (1 case), diffuse endocapillary proliferative glomerulonephritis (1 case), vasculitis with focal segmental necrotizing glomerulitis and crescentic glomerulonephritis (2 cases). These results show that cirrhosis of the liver can be associated with a wide variety of glomerular disorders. Contrary to previous belief, IgA is absent in two thirds of patients with cirrhosis and glomerulopathy. Therefore, the pathogenetic importance of IgA in the development of glomerular disease in such patients is doubtful.     

C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome?

C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.     

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.     

Diffuse proliferative glomerulonephritis after bone marrow transplantation

A 15-year-old boy developed nephrotic syndrome and acute renal failure 4 years after allogenic bone marrow transplantation (BMT) for lymphoid crisis of chronic myelocytic leukemia. On admission, he presented with clinical features of chronic GVHD including transient exacerbation of cholestatic liver injury. Renal biopsy showed diffuse proliferative glomerulonephritis with cellular crescents. The patient was treated with methylprednisolone pulse therapy (1 g/day, for 3 days) followed by oral prednisolone. Renal function gradually improved but nephrotic state was persistent. A second renal biopsy showed improvement of acute tubular necrosis and endocapillary proliferation and transformation of crescents into a fibrous form. After tapering of oral prednisolone, cyclophosphamide was started, which resulted in a gradual improvement of proteinuria. Several cases of nephrotic syndrome occurring after BMT have already been reported, but most cases had membranous nephropathy. In our case, renal biopsy revealed diffuse proliferative glomerulonephritis with findings of active cellular immunity, and aggressive treatment resulted in attenuation of these findings. Moreover, chronic GVHD-related liver injury was noted at the time of this episode. Our findings suggest that chronic GVHD may be complicated with diffuse proliferative glomerulonephritis through unknown cellular immune mechanism.     

Primary antiphospholipid antibody syndrome and mesangial IgA glomerulonephritis

The antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis, fetal loss, multiorgan involvement, and the presence of lupus anticoagulant and/or anticardiolipin antibody. When not associated with systemic lupus erythematosus, other collagen diseases, or ingestion of medications, the condition is called primary APS. The kidney may be involved in the APS syndrome with acute nephritis and renal failure. The cases with renal biopsy studies have shown variable glomerular morphology, ranging from mild mesangial changes to a diffuse endocapillary proliferative glomerulonephritis. The most frequent lesion is thrombotic microangiopathy or features seen in the hemolytic uremic syndrome. Apart from fibrin thrombus deposition, only a few cases have shown focal and segmental deposits of IgG and/or IgM and/or C3. We describe a patient with primary APS who had thrombosis with lower limb amputation and acute renal failure. The renal biopsy specimen showed a focal proliferative glomerulonephritis with endothelial proliferation and damage, with diffuse heavy mesangial deposits of IgA and fibrinogen. This case with diabetes mellitus, but without diabetic nephropathy, represents the occurrence of primary APS and mesangial IgA nephropathy which potentiated the renal injury, leading to acute renal failure. The relationship to the Henoch-Sch?nlein syndrome is discussed.     

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.     

Paulista Registry of glomerulonephritis: 5-year data report.

BACKGROUND: The Paulista Registry of Glomerulopathies was created in May 1999 and comprises several centres of S?o Paulo, the most populous Brazilian State, that concentrates people from all regions of the country who look for health care. METHODS: This report includes data from 2086 patients from Brazil submitted to renal biopsy due to the presumed diagnosis of glomerular diseases, registered prospectively since May 1999 until January 2005. Data were collected by the integrants of the 11 centres involved, utilizing a standardized questionnaire. RESULTS: The mean age of the patients was 34.5+/-14.6 years. Primary glomerular diseases were more frequent in males (55.1%) than in females; on the other hand, secondary glomerular diseases were more frequent in females (71.8%). The most common clinical presentation was nephrotic syndrome and the frequency of hypertension, at this time, was 55.5%. There was a predominance of indication of biopsies in the third, fourth and fifth decades of life. The most common primary glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%). The most frequent secondary glomerular disease was lupus nephritis, corresponding to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%), diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%), hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary focal segmental glomerulosclerosis (0.6%) and others (0.9%). CONCLUSION: Focal segmental glomerulosclerosis was the most frequent primary glomerular disease, followed by membranous nephropathy and IgA nephropathy. Lupus nephritis predominated over all the other secondary glomerular diseases.     

Renal survival rate of IgA nephropathy

In an attempt to identify prognostic indicators in IgA nephropathy, we evaluated the relationship between clinical and histological findings and changes in renal function in 81 patients with IgA nephropathy whose creatinine clearance was more than 80 ml/min at the time of renal biopsy. The incidence of patients whose creatinine clearance decreased to less than 60 ml/min during the follow-up period was calculated with the life table method to designate the renal survival rate. This rate was compared according to the clinical and histological findings at the time of renal biopsy. In conclusion, a statistically significant decrease in the renal survival rate was observed in patients with proteinuria of more than 1.0 g/day, hypertension, severe diffuse proliferative glomerulonephritis, diffuse proliferative glomerulonephritis with focal crescents and glomerular deposition of IgM and/or fibrinogen-related antigen.     

Pathology, clinical presentations, and outcomes of C1q nephropathy

C1q nephropathy is an uncommon glomerular disease with characteristic features on immunofluorescence microscopy. In this report, clinicopathologic correlations and outcomes are presented for 72 patients with C1q nephropathy. The study comprised 82 kidney biopsies from 28 children and 54 adults with male preponderance (68%). Immunofluorescence microscopy showed dominant or co-dominant staining for C1q in the mesangium and occasional glomerular capillary walls. Electron-dense deposits were observed in 48 of 53 cases. Light microscopy revealed no lesions (n = 27), focal segmental glomerulosclerosis (FSGS; n = 11), proliferative glomerulonephritis (n = 20), or various other lesions (n = 14). Clinical presentations in the patients who had no lesions histology were normal urine examination (7%), asymptomatic hematuria and/or proteinuria (22%), and nephrotic syndrome (minimal change-like lesion; 63%), which frequently relapsed. All patients with FSGS presented with nephrotic syndrome. Those with proliferative glomerulonephritis usually presented with chronic kidney disease (75%) or asymptomatic urine abnormalities (20%). Of the patients with sufficient follow-up data, complete remission of the nephrotic syndrome occurred in 77% of those with a minimal change-like lesion, progression to end-stage renal disease occurred in 33% of those with FSGS, and renal disease remained stable in 57% of those with proliferative glomerulonephritis. In conclusion, this study identified two predominant clinicopathologic subsets of C1q nephropathy: (1) Podocytopathy with a minimal change-like lesion or FSGS, which typically presents with nephrotic syndrome, and (2) a typical immune complex-mediated glomerular disease that varies from no glomerular lesions to diverse forms of glomerular proliferation, which typically presents as chronic kidney disease. Clinical presentation, histology, outcomes, and presumably pathogenesis of C1q nephropathy are heterogeneous.     

Histology and immunohistology of IgA nephropathy

IgA nephropathy is a histologically diverse glomerular disease characterized by mesangial or mesangial plus peripheral glomerular capillary immune complex deposits that contain IgA as the dominant or co-dominant immunoglobulin type. The most common histologic manifestation of IgA nephropathy is mesangial proliferative glomerulonephritis (GN), most often focal but not infrequently diffuse. However, the light microscopic appearance of IgA nephropathy spans the entire range from histologically normal to diffuse proliferative and crescentic glomerulonephritis, much as is the case with lupus nephritis. This review examines the histologic diversity as well as the immunohistologic features of IgA nephropathy.     

Glomerulonephritis in ankylosing spondylitis

There have been a few reports suggesting the association between glomerulonephritis (GN) and ankylosing spondylitis (AS). The reported glomerulonephritides include IgA nephropathy, mesangial proliferative GN and membranous nephropathy. From January 1983, through December 1984, we observed 5 cases of GN among 116 cases of definite AS. Three of them were IgA nephropathy. The other two were mesangial proliferative GN, with IgM deposit in one case and isolated C3 deposit in another. Microscopic hematuria was observed in all of them. The renal function and 24-hour urine protein excretion were all within normal limits. Serum IgA level increased in all but the case of mesangial proliferative GN with IgM deposit. All except one had the antigen of HLA-B27. Serum IgA level was determined in 78 cases (86 estimations) of AS. The mean value was 399.6 +/- 15.0 mg/dl (mean +/- SE) (normal range: 100-350 mg/dl). Fifty-four of them (63%) had a value higher than 350 mg/dl. The interrelationship of AS and IgA nephropathy was discussed.     

Extrarenal cytokines modulate the glomerular response to IgA immune complexes.

Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC-BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis.     

Therapy of IgA nephropathy with mycophenolate mofetil--report of 3 cases

Mycophenolate mofetil is an immunosuppressive agent in transplantation which inhibits the purin neogenesis. Proliferating lymphocytes are suppressed and antibody production is decreased. Many cases of successful therapy in different kidney diseases are reported, such as diffuse proliferative lupus nephritis, pauci-immune necrotizing glomerulonephritis, focal segmental glomerular sclerosis and IgA nephropathy. We report 3 patients with IgA nephropathy who were treated with mycophenolate mofetil for more than 1 year. In all patients, proteinuria decreased significantly and the renal function remained stable. In 2 patients, kidney biopsy was repeated after 12 months and 18 months, respectively. There were no histological signs of progression of the disease. Two patients developed infections during treatment. One patient had a pneumonia, and a second patient an infection with varizella zoster. Based on our data, mycophenolate mofetil can be a potential treatment of IgA nephropathy. Further controlled studys are warranted to investigate the role of mycophenolate mofetil in IgA nephropathy.     

De-novo anti-GBM-antibody-induced glomerulonephritis in a renal transplant

We report a case of de-novo anti-glomerular basement membrane antibody induced glomerulonephritis (anti-GBM GN) in a renal cadaveric transplant. The 52 year old male patient had developed end-stage renal failure secondary to malignant hypertension. His initial renal transplant lost function within two months because of severe allograft rejection without evidence of anti-glomerular basement membrane (anti-GBM) antibody formation. Eight months after his second cadaveric transplant he developed the nephrotic syndrome. This was followed by a rapid deterioration in graft function associated with the development of diffuse proliferative glomerulonephritis with 100% crescent formation. Linear staining of the GBM with IgG and C3 and the presence of circulating anti-GBM antibodies confirmed the anti-GBM antibody etiology of the glomerular lesion. Thus anti-GBM antibody induced glomerulonephritis can occur de-novo in a transplanted kidney despite routine immunosuppression. This represents either coincidental autoantibody production after transplantation or specific alloantibody production, stimulated by the introduction, by transplantation, of GBM neoantigens.     

Digital subtraction venography in the diagnosis of renal vein thrombosis.

Fifteen cases of renal vein thrombosis were seen in patients with nephrotic syndrome, both adult and pediatric, and all had kidney biopsies. Six patients were found to have membranoproliferative glomerulonephritis, 3 membranous nephropathy, 2 focal segmental glomerulosclerosis, 2 renal amyloidosis and one each minimal change disease and diffuse mesangial proliferative glomerulonephritis. The diagnosis of renal vein thrombosis was made in all patients by utilizing digital subtraction venography. This method is simple, safe, noninvasive and quite efficient.     

Acute poststreptococcal glomerulonephritis superimposed on IgA nephropathy

Superimposition of poststreptococcal glomerulonephritis (PSGN) on the course of IgA nephropathy (IgAN) is uncommon. A case of PSGN during IgA nephropathy is presented. A 30-year-old man who had alternating gross and microscopic hematuria for 7 months underwent a renal biopsy. The first renal biopsy revealed IgAN with mesangial deposits of IgA and C3. Two months later, the patient suffered generalized edema, proteinuria, hematuria, an increased ASO titer and a decreased C3 level. A second renal biopsy revealed diffuse endocapillary proliferative glomerulonephritis with epimembranous hump-like electron-dense deposits of C3, but the original mesangial IgA deposits had disappeared. A diagnosis of acute PSGN was indicated. Two months after the onset of acute nephritic syndrome, the patient remained asymptomatic, except for microscopic hematuria and proteinuria. Some cases with persistent proteinuria or hematuria after PSGN are probably related to preexisting IgAN.     

Acute renal failure associated with hematuria in IgA nephropathy

Severe acute deterioration of renal function, which occurred during the episode of massive gross hematuria, is described in two patients with IgA nephropathy (IgAN). The renal failure abated gradually after dialytic support. Renal pathology in each case revealed focal proliferative glomerulonephritis with less than 14% of the glomeruli affected by crescents or sclerosis. In contrast to the mild glomerular lesions, acute tubular cell injury in relation to phagocytosis of erythrocytes or pigments and/or tubular obstruction was prominent. We think our observations support the previous reports that tubular lesions in relation to heavy glomerular bleeding may be a cause of severe acute renal failure in patients with IgAN.     

原发性肾病综合征并发急性肾损伤48例临床病理分析

目的探讨原发性肾病综合征合并急性肾损伤的临床及病理特点,提高此类并发症的防治水平。方法对我院原发性肾病综合征合并急性肾损伤患者的临床和病理改变进行回顾性分析。结果原发性肾病综合征合并急性肾损伤的临床特征表现为大量蛋白尿、高度水肿,常合并胸腹腔积液。肾脏病理类型：系膜增生性肾小球肾炎、肾小球微小病变及IgA肾病多见。其中系膜增生性肾小球肾炎22例,占46%;微小病变型10例,IgA肾病9例。所有患者均依据病理分型给予激素和（或）细胞毒药物,同时行利尿、控制感染、抗凝等综合治疗,其中5例进行血液透析治疗,肾损伤大多好转,但增生硬化型肾炎等预后较差。结论原发性肾病综合征并发急性肾损伤临床并不少见,多发生于系膜增生性肾小球肾炎、肾小球微小病变及IgA肾病,尽早明确病理诊断和去除诱因,并予相应治疗,大多患者预后良好,肾功能可恢复正常。     

Fibrillary glomerulonephritis and renal failure in a child with systemic lupus erythematosus

Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerulopathy characterized by randomly arranged immunoglobulin (Ig) deposits on electron microscopy. Only seven pediatric cases have been reported, and the incidence in adults is about 1.5%. A 12-year-old boy presented with systemic lupus erythematosus (SLE) with World Health Organization Class IV lupus nephritis. A repeat biopsy carried out due to a poor response to standard immunosuppressive therapy and worsening renal functions revealed diffuse proliferative glomerulonephritis with fibrillary deposits. Despite aggressive immunosuppression with plasmapheresis and rituximab, the patient developed end stage renal disease. This is an atypical pediatric case characterized by SLE-associated FGN and a poor prognosis.     

996例肾活检临床病理分析

目的 回顾性分析本院肾脏内科近10年肾活检病理类型及疾病谱变化.方法 收集2006年2月至2016年2月期间996例肾活检患者临床病理资料,分析肾脏疾病临床病理特点.结果 996例肾活检患者中,原发性肾小疾病760例,占76.31％,继发性肾小球疾病211例,占21.18％,肾小管间质性疾病22例,占2.21％,遗传性肾病3例,占0.30％.原发性肾小球疾病最常见病理类型为IgA肾病238例,占31.32％,其次为系膜增生性肾炎199例,占26.18％,膜性肾病127例,占16.71％.继发性肾小球疾病最常见为狼疮性肾炎76例,占36.02％,其次为紫癜性肾炎56例,占26.54％,乙肝相关性肾炎24例,占11.37％.原发性肾小球疾病临床表现最常见为肾病综合征446例,占58.68％,其次为慢性肾炎223例,占29.34％,隐匿性肾小球肾炎69例,占9.08％.结论 原发性肾小球疾病是目前临床最常见肾小球疾病,其病理类型以IgA肾病最为常见,近年来膜性肾病所占比例明显增高.继发性肾小球疾病以狼疮性肾炎最为常见,乙肝相关性肾炎所占比例较前增高.