Glomerular lesions and final outcome in children with glomerulonephritis of acute onset.

131 children with nephritic syndrome of acute onset were studied by renal biopsy and were followed clinically from 2 to 13 years. 87 patients (66%) with proliferative endocapillary glomerulonephritis all recovered. 21 (16%) had focal extracapillary and diffuse endocapillary glomerulonephritis. Eleven (52%) of these recovered. Six patients (5%) had diffuse extra and endocapillary glomerulonephritis, 13 (10%) had membrano-proliferative glomerulonephritis and four had diffuse glomerular fibrosis. All 23 patients of the latter groups progressed to renal insufficiency. A correlation between morphology and prognosis was apparent in this study.     

Two cases of rapidly progressive nephritic syndrome complicated with alcoholic liver cirrhosis

It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA (IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR)were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three courses of steroid semi-pulse therapy and post therapy with steroids and MZR were combined, his proteinuria and serum Cre level decreased and stagnated ascites markedly decreased. The two cases were diagnosed as having secondary IgA nephropathy induced by the deposition of the IgA1 derived mainly from the intestinal tract, which had increased in the blood due to alcoholic liver cirrhosis. Active use of immune system suppressor therapy was effective.     

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.     

Glomerular T cell and monocyte populations in patients with IgA nephropathy

Renal tissues from 19 patients with the minimal or slight stage of IgA nephropathy were examined for evidence of glomerular T cell or monocyte infiltration using monoclonal antibodies to identify T cells (OKT3, OKT11), T cell subsets (OKT4, OKT8), and monocytes and null cells (OKM1) by indirect immunofluorescence. Renal tissues from 12 patients at the same stage of mesangial proliferative glomerulonephritis without IgA deposition were also investigated by these procedures. Light microscopic examination of the same renal tissues was also performed. Reactive glomerular mononuclear cells were found to be numerous in patients with IgA nephropathy. The most prominent type of glomerular cells was OKT8 positive. T cell subsets and OKM1 positive cells in glomeruli from patients with IgA nephropathy were significantly increased as compared to those from patients with mesangial proliferative glomerulonephritis. Focal segmental proliferation of mesangial cells was observed in glomeruli which showed an accumulation of OKT8 positive cells. It is concluded that the immuno-regulatory mechanism involving T cells and/or monocytes might be one of the exacerbating factors in patients with IgA nephropathy.     

Peculiar renal endarteritis in a patient with acute endocapillary proliferative glomerulonephritis

Acute glomerulonephritis (AGN) is one of the most common renal diseases. They are often associated with infections and can result in diffuse proliferative glomerulonephritis (GN). This case report reviews an interesting case in which renal endarteritis coexisted in AGN with diffuse endocapillary proliferation. The discussion highlights important pathological findings and clinical aspects in acute endocapillary proliferative GN with renal endarteritis. Coexisting endarteritis should be in the differential diagnosis of AGN in patients with persistent clinical courses.     

Mesangiocapillary glomerulonephritis caused by Puumala hantavirus infection.

Nephropathia epidemica induced by Puumala hantavirus typically causes acute reversible renal function impairment. A typical renal biopsy finding is acute tubulointerstitial nephritis with slight glomerular mesangial changes. We describe here 5 patients who developed the nephrotic syndrome during the convalescent phase of an otherwise typical acute febrile nephropathia epidemica. Renal biopsy of all patients disclosed type I mesangiocapillary glomerulonephritis (MCGN). A clinical remission of the nephrotic syndrome was observed in 4 patients during the follow-up period, and 1 entered into chronic renal failure. Three patients had microscopic hematuria and proteinuria and 2 elevated blood pressure at the latest assessment visit. No patient had clinical or laboratory findings compatible with chronic bacterial, parasitic or viral infections (hepatitis B or C), malignancies, or other disorders known to be associated with MCGN. In conclusion, Puumala hantavirus has to be added to the list of potential agents associated with type I MCGN. Further studies are necessary to establish the incidence of MCGN caused by various hantavirus infections.     

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.     

Canine chronic renal disease: prevalence and types of glomerulonephritis in the dog

In a prospective survey, one hundred and eleven dogs with canine chronic renal disease, presenting to 24 veterinary practices in East Anglia and the West Midlands (geographical area 8,600 square miles) were identified. More than 20 different breeds were represented. In 76 cases, clinical details, blood and urine biochemistry, serology and kidney tissue for light and electron microscopy, and immunohistochemistry were obtained. Forty (52%) had glomerular (GN) and 36 (48%) non-glomerular (NGN) disease. Types of GN identified were (W.H.O. classification, number of cases in brackets): focal glomerulonephritis (gn) (5), diffuse mesangial proliferative gn (8), diffuse endocapillary proliferative gn (2), mesangiocapillary gn type I (8), diffuse crescentic gn (1), diffuse sclerosing gn (7), amyloid (6), unclassifiable gn (3). Eight dogs with GN and 13 with NGN had extra-renal lesions. In only one GN case (bacterial endocarditis) was the etiology clear. Proteinuria, but not age, breed, sex, serum creatinine or hematuria, discriminated between GN and NGN groups. This prospective survey identifies GN, with morphological types as found in humans, as a common cause of canine chronic renal disease.     

Nephrotic syndrome in Namibian children.

BACKGROUND AND OBJECTIVES: Patterns of nephrotic syndrome vary between regions and countries, and influence approaches to management. In the mid-1970s the University of Stellenbosch became involved in providing tertiary care to Namibia, including a paediatric nephrology service. The aim of this study was to document the clinical, pathological and outcome features of nephrotic syndrome in Namibian children. SUBJECTS: Seventy black Namibian children with nephrotic syndrome were managed from 1975 to 1988. Sixty-eight renal specimens (67 biopsies and 1 autopsy specimen) were evaluated. RESULTS: Twenty-nine of the 70 children (41.4%) were hepatitis B virus (HBV) carriers, of whom 25 (86.2%) were male. Of the 29, 26 had predominantly membranous glomerulonephritis (MGN), 1 mesangiocapillary glomerulonephritis (MCGN), and 1 focal segmental glomerulosclerosis (FSGS); 1 child in advanced renal failure was not biopsied. Five children (7.4%) showed minimal change disease (MCD), 11 (16.2%) FSGS and 15 (22.1%) diffuse mesangial proliferative glomerulonephritis (DMP). The remaining 10 children showed diffuse glomerulosclerosis (6), MCGN (3) and endocapillary proliferative GN (1). Four of the 5 children with MCD went into remission on immunosuppressive treatment. Of the 15 with DMP, 4 improved spontaneously and only 1 of those treated did not improve. Only 2 of those with FSGS improved on treatment. The children with HBV-associated MGN and MCGN were offered symptomatic rather than specific treatment. Thirteen children presented with degrees of chronic renal failure. Eight are known to have died, 3 of relentless nephrotic syndrome and 4 (of whom 3 were HBV carriers) of end-stage renal failure. One child died of penicillin anaphylaxis. CONCLUSIONS: The pattern of nephrotic syndrome in black Namibian children differed greatly from the non-African pattern elsewhere in that MCD was uncommon and HBV-associated GN was the most common single group. The most frequent pattern of HBV-associated GN was MGN with some mesangiocapillary features showing marked male predominance. MCD and DMP were potentially treatable and could only be identified by biopsy. HBV carrier rates exert a major influence on the proportions of morphological subgroups of nephrotic syndrome in children. As these HBV carrier rates alter in future due to the influence of vaccination and urbanisation, the relative size of nephrotic subgroups seems likely to alter.     

Discrimination between postinfectious IgA-dominant glomerulonephritis and idiopathic IgA nephropathy

Background: A unique form of postinfectious glomerulonephritis (PIGN) with IgA-dominant deposition mimicking IgA nephropathy has been increasingly reported. Methods: We compared the clinical and histological features of 12 patients with postinfectious IgA-dominant glomerulonephritis to 134 patients with idiopathic IgA nephropathy. Results: In addition to hypocomplementemia and subepithelial hump-shaped deposits characteristic of PIGN, patients with postinfectious IgA-dominant glomerulonephritis had older age (62.3 ± 16.9 vs. 37.9 ± 16.3 years; p < 0.001) and more frequently presented with acute renal failure (83.3% vs. 10.4%; p < 0.001) than patients with idiopathic IgA nephropathy. Moreover, glomerular changes including endocapillary proliferation, neutrophil infiltration, and capillary loops deposits by immunofluorescence were more commonly present in postinfectious IgA-dominant glomerulonephritis group (p < 0.001). Conclusions: PIGN could be characterized by glomerular IgA-dominant deposition resembling idiopathic IgA nephropathy. It is essential to differentiate postinfectious IgA-dominant glomerulonephritis from idiopathic IgA nephropathy because of the different treatments and prognosis of the two diseases.     

Patient with diffuse mesangial and endocapillary proliferative glomerulonephritis with hypocomplementemia and elevated anti-streptolysin O treated with prednisolone, angiotensin-converting enzyme inhibitor, and angiotensin II receptor antagonist

A 24-year-old woman was admitted to Toyosaka Hospital with proteinuria, hematuria, lymphopenia, hypocomplementemia, positive anti-nuclear antibody (ANA), and elevation of anti-streptolysin O (ASO). Renal biopsy specimen revealed diffuse mesangial and endocapillary glomerulonephritis with crescent formation and duplication of the capillary loop on light microscopic examination. Mild to moderate proliferation of mesangial matrix and cells were observed. On immunofluorescence (IF) examination, deposition of IgG, IgA, IgM, C1q, C3, and C4 to the mesangium and capillary wall were observed. By electron microscopy (EM), mesangial, subendothelial, and subepithelial deposits were recognized. However, microtubular structure in glomerular endothelial cells, fingerprint structures, and circumferential mesangial interposition were not observed by EM. The patient was referred to our hospital, but there was no change in her proteinuria 3 weeks after admission. The elevation of ASO, hypocomplementemia, and endocapillary proliferation suggested acute glomerulonephritis, while lymphocytopenia, positive ANA, the persistent hypocomplementemia, and various deposits detected by IF and EM suggested lupus nephritis; however, she did not fulfill the classification criteria of systemic lupus erythematosus. We started prednisolone (40mg/day) with the diagnosis of chronic glomerulonephritis revealing diffuse mesangial and endocapillary proliferative glomerulonephritis, but it was not effective for the proteinuria. Quinapril (10mg/day) and losartan (25 to 50mg/day) were administered and the proteinuria decreased. It is possible that this use of an angiotensin converting-enzyme inhibitor and an angiotensin II receptor antagonist was effective in reducing the proteinuria in this patient.     

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.     

Psoriasis vulgaris associated with mesangiocapillary glomerulonephritis

A patient experienced the concomitant onset of psoriasis vulgaris and mesangiocapillary glomerulonephritis (MCGN) with massive proteinuria. Laboratory examination revealed reduced glomerular filtration rate (GFR), elevated serum IgG, IgA and circulating immune complex (CIC) levels. Both diseases responded promptly to combined therapy with prednisolone, urokinase and plasma exchange. CIC and GFR were normalized with histological improvement. To our knowledge, this is the first case of glomerulonephritis, which can be related to psoriasis vulgaris through an immune mechanism.     

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.     

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.     

Idiopathic IgA nephropathy with diffuse crescent formation

OBJECTIVE: To investigate the clinicopathological features and outcome of idiopathic IgA nephropathy with diffuse crescent formation in Chinese patients. METHODS: Twenty-five patients with diffuse crescentic IgA nephropathy (DCIgAN), 15 males and 10 females with median age of 28.5, and median disease duration of 5.1 months, were studied. Their clinical, laboratory and pathological features and outcome were investigated. Twenty-one were administered pulse immunosuppressive therapy, and 15 were followed up for more than 6 months. RESULTS: 1.14% had total IgA nephropathy, and 16.4% total diffuse crescentic glomerulonephritis. Clinically, most of patients (88%) showed rapidly progressive glomerulonephritis associated with a high level of serum creatinine (418 +/- 264 micromol/l). Gross hematuria was noted in 72%, hypertension in 64%, and nephrotic syndrome in 48%. Pathologically, except for diffuse crescent formation (a median 65% and range 50-95%), we observed segmental necrosis of glomerular capillaries in 60%, glomerular infiltrating cells in 48%, endothelial cells proliferation in 32%, and rupture of Bowmans' capsule in 24%. Severe tubular interstitial damage was also found, tubular atrophy in 64%, interstitial fibrosis in 60%, diffuse interstitial infiltrating cells in 74%, and interstitial vasculitis in 40%. Immunopathologically, four phenotypes were observed; however, IgA associated with IgM deposition was higher than that in patients with general IgA nephropathy (IgAN). In addition, the infiltrating CD4+, CD8+, CD68+ and PCNA+ cells in renal tissue were significantly high compared with that in controls. In a follow-up study, 66.7% of patients had life-sustaining renal function, 4 of them had normal range of serum creatinine (<124 micromol/l), and only 5 were dialysis-dependent. CONCLUSIONS: The patients with crescentic IgA nephropathy mostly show rapidly progressive nephritis associated with more severe pathological changes including glomerular, tubular interstitial and vascular lesions than in patients with general IgAN. The infiltrates in glomeruli may contribute to the crescentic formation, and the intensive immune suppressing treatment is useful to improve renal damage in patients with DCIgAN.     

A case of glomerulopathy showing podocytic infolding in association with Sjögren’s syndrome and primary biliary cirrhosis

A 49-year-old man was admitted to our hospital with mild proteinuria. Prior to admission, he had been diagnosed as having Sjögren’s syndrome in association with primary biliary cirrhosis. Examination of a renal biopsy under light microscopy revealed diffuse and global mesangial cell proliferation and a spike and/or bubbling formation of the glomerular basement membrane (GBM), resembling membranoproliferative glomerulonephritis. In contrast, immunofluorescent studies showed marked immunoglobulin and complement depositions in the mesangial areas; however, only faint granular IgG and IgA deposition was observed along the GBM. Interestingly, electron microscopy revealed that a microtubular structure, derived from podocytes, was present in the GBM. We present a case of glomerulopathy showing podocytic infolding in association with Sjögren’s syndrome and primary biliary cirrhosis.     

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.