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.     

IgA-Dominant Postinfectious Glomerulonephritis: Not Peculiar to Staphylococcal Infection and Diabetic Patients

Background: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. Methods: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. Results: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1?mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group (p?=?0.007). There were no significant differences in other clinical parameters and outcome between the two groups. Conclusions: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.     

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.     

Analysis of 4931 renal biopsy data in central China from 1994 to 2014

The purpose of this study is to investigate the changing spectrum and clinicopathologic correlation of biopsy-proven renal diseases in central China. We retrospectively analyzed data of 4931 patients who underwent renal biopsy in ten hospitals between September 1994 and December 2014. Among them, 81.55% were primary glomerular diseases (GD), and 13.02% were secondary GD. IgA nephropathy (IgAN) was the most common primary GD (43.45%), followed by focal glomerulonephritis (16.79%), mesangial proliferative glomerulonephritis (MsPGN, 14.35%), and membranous nephropathy (MN, 13.28%). IgAN was leading primary GD in patients under 60 years old, while MN was the leading one over 60 years old. The most frequent secondary GD was lupus nephritis (LN) (47.35%). The prevalence of IgAN, MN and minimal change disease was found to increase significantly (p?<?0.001, p?<?0.001, and p?<?0.01, respectively), while that of MsPGN, membranoproliferative glomerulonephritis and LN decreased significantly (p?<?0.001, p?<?0.001, and p?<?0.05, respectively). The main indication for renal biopsy was proteinuria and hematuria (49.03%), followed by nephrotic syndrome (NS, 20.36%). IgAN was the most common cause in patients with proteinuria and hematuria, chronic-progressive kidney injury, hematuria and acute kidney injury; and MN was the leading cause of NS. Primary GD remained the predominant renal disease in central China. IgAN and LN were the most prevalent histopathologic lesions of primary and secondary GD, respectively. The spectrum of biopsy-proven renal disease had a great change in the past two decades. Proteinuria and hematuria was the main indication for renal biopsy.     

Rapidly Progressive Renal Failure in Type 2 Diabetes in the Tropical Environment: A Clinico-Pathological Study

Background. Rapid decline of renal function in a diabetic suggests the presence of a nondiabetic kidney disease (NDKD). We designed a prospective study to evaluate the factors associated with a rapid decline in renal function in patients with type 2 diabetes. Methods. Over a 2 and a half year period, all patients with type 2 diabetes who presented with documented doubling of serum creatinine in less than 4 weeks or recently diagnosed advanced renal failure were identified. Patients with prerenal causes, urinary tract obstruction, or systemic disease causing renal failure were not included. Renal histology was studied in all cases. Results. A total of 26 patients satisfied the inclusion criteria. Over 75% had serum creatinine > 4 mg/dL at presentation and 62% were dialysis dependent. Renal histology showed mixed lesions of diabetic nephropathy (DN) and NDKD in 11 cases, only DN in nine, and pure NDKD in six. Diffuse proliferative glomerulonephritis (DPGN) was the commonest NDKD (27% cases), all on a background of DN. History of preceding cutaneous or pharyngeal infection was available in five cases. The proportion of postinfectious glomerulonephritis in diabetics with rapidly progressive renal failure was over six times that of the nondiabetic adult RPRF population during the study period. Four patients had acute interstitial nephritis and three showed crescentic glomerulonephritis. Other lesions included amyloidosis, atheroembolic disease, and renal papillary necrosis (one each). The frequency of microscopic hematuria and retinopathy was similar in those with pure DN and NDKD. Four out of seven cases with DPGN showed partial recovery whereas the other three remained unchanged. Conclusions. About two-thirds of patients with type 2 diabetes presenting with rapid decline of renal function in a tropical environment show NDKD. The high incidence of postinfectious glomerulonephritis in this group is possibly related to the high prevalence of skin and soft tissue infections; and could contribute to progressive kidney disease.     

Apoptosis and proliferation in childhood acute proliferative glomerulonephritis

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p <0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03±2% versus 0.32±0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4±1.9 versus 1.52±0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89±0.8 versus 0.73±0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.     

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.     

Clinicopathological study of originally non-lupus “full-house” nephropathy

Background: Glomerular “full-house” immunofluorescence staining commonly indicates lupus nephritis. However, some non-lupus nephropathy also can present with a “full-house” immunofluorescence pattern mimicking lupus nephritis. The goal of this study is to define the clinicopathological spectrum of originally non-lupus “full-house” nephropathy. Methods: Records of 24 patients with “full-house” nephropathy in the absence of clinical or serological evidence of systemic lupus erythematosus (SLE) at the time of renal biopsy were abstracted for demographics, clinical presentation, laboratory data, renal biopsy findings, and clinical follow-up. Results: The clinicopathological diagnoses included membranous glomerulonephritis (GN) (46%), IgA nephropathy (21%), membranoproliferative GN (12.5%), postinfectious GN (12.5%), C1q nephropathy (4%), and unclassified mesangial GN (4%). No one had endothelial tubuloreticular inclusions. One patient originally diagnosed as IgA nephropathy developed anti-DNA antibody and another one patient with membranous GN developed hypocomplementemia 8 months and 10 months after renal biopsy, respectively. The two patients also developed clinical symptoms of lupus subsequently. Conclusions: There was a broad spectrum of glomerular histological findings in non-lupus “full-house” nephropathy. The possibility of “full-house” nephropathy preceding the emergence of overt systemic lupus erythematosus remained to be elucidated.     

Acute endocapillary proliferative glomerulonephritis associated with human parvovirus B19 infection

A 36-year-old female developed acute nephritic syndrome associated with human parvovirus B19 (HPVB19) infection. Laboratory data showed proteinuria, hypocomplementemia, mild pancytopenia, the presence of immunoglobulin (Ig) M and IgG antibodies to HPVB 19 and positive reaction of serum HPVB19 DNA using a polymerase chain reaction (PCR). A renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental apparent mesangiolytic change; fine granular IgM, IgG and C3 deposits were noted by immunofluorescence microscopy; relatively small electron-dense deposits were observed in the widened subendothelial spaces and the mesangium, and loosening of the mesangial matrix varied from place to place electron microscopically. PCR of HPVB19 DNA in the renal biopsy tissue was positive as well as in the peripheral blood. The histological findings suggested that immune-complex-mediated endocapillary proliferative glomerulonephritis is caused by acute HPVB 19 infection. We discuss the differences from poststreptococcal glomerulonephritis and the possible pathogenesis of acute endocapillary proliferative glomerulonephritis associated with HPVB19 infection.     

Mycoplasma pneumoniae-associated nephritis in children

 Mycoplasma pneumoniae infection is a rare cause of acute nephritis. Six children (2 girls) aged 5–10 years, admitted for nephritis, had serological tests showing recent Mycoplasma pneumoniae infection. The diagnosis of Mycoplasma pneumoniae infection was based on the presence of serum IgM, detected either by immunofluorescence (IF) (n=1) or enzyme-linked immunosorbent assay (n=5). Four children had a renal biospy, with analysis of parenchymal Mycoplasma pneumoniae components by indirect IF and polymerase chain reaction. Extrarenal symptoms were: respiratory (n=3), ear, nose, and throat (n=2), gastrointestinal (n=3), hepatic (n=1), neurological (n=1), articular (n=1), and hematological (n=3). The patients presented with acute nephritis (1 had a nephrotic syndrome) or with acute renal failure and proteinuria. Pathological findings included type 1 membranoproliferative glomerulonephritis (MPGN, n=1), proliferative endocapillary glomerulonephritis (n=2), and minimal change disease (n=1). The patient with type 1 MPGN progressed rapidly towards end-stage renal failure because of a congenital solitary kidney. Among the patients with endocapillary glomerulonephritis, 1 relapsed 6 months later and remained proteinuric, while the other recovered, as did the child with minimal change disease. The search for Mycoplasma pneumoniae antigens and nucleic acids in renal tissue was negative. However, the absence of the microorganism in the kidney is a common feature of post-streptococcal glomerulonephritis. We conclude that Mycoplasma pneumoniae is a rare yet potential cause of acute glomerulonephritis. Received: 13 September 1996 / Revised: 16 June 1998 / Accepted: 18 June 1998     

Three elderly cases of endocapillary glomerulonephritis and nephrotic syndrome

Three patients aged over 60 with endocapillary proliferative glomerulonephritis and nephrotic syndrome were reported. Immunofluorescence and electron microscopical findings were similar in all of them: granular deposits of IgG and C 3 along the capillary loops, electron dense deposits in the subendothelial area, and partial mesangial interposition. The levels of CH 50 were slightly suppressed in two of them, but neither preceding infection nor elevation in ASLO were noticed. None of then responded to steroid therapy. One patient fell in renal failure in spite of intensive steroid therapy, and died of bronchopneumonia. In another patient, proteinuria was remitted with systemic treatment against high blood pressure. The remaining patient took a favorable course during the admission without any special treatment, but proteinuria recurred after the discharge. These clinical manifestations and clinical courses were not compatible with the diagnoses of acute glomerulonephritis, mesangiocapillary glomerulonephritis, or vasculitis. We concluded that the endocapillary proliferative glomerulonephritis in adults over 60 years might be different form of glomerulonephritis from that of AGM, MPGN, and vasculitis, in which diffuse endocapillary proliferative changes in the glomeruli are seen in younger people.     

Glomerulonephritis induced by methicillin-sensitive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> infection

A 57-year-old woman developed exacerbation of atopic dermatitis, fever, and nephrotic syndrome with microscopic hematuria. By bacteriological study, methicillin-sensitive Staphylococcus aureus (MSSA) was detected from each culture of pharyngeal mucus, stool, and blood samples. Renal biopsy specimens showed endocapillary proliferative glomerulonephritis with massive IgA deposition in the mesangium and along the capillary loops. After antistaphylococcal therapy with antibiotics, MSSA was negative for each culture and urinary protein decreased. Nine months after the first renal biopsy, a re-biopsy was performed, which revealed apparent disappearance of both endocapillary cell proliferation and IgA deposition. It is known that methicillin-resistant S. aureus (MRSA) infection causes glomerulonephritis through T-cell stimulation by superantigen presented by MRSA. The present results suggest that not only MRSA but also MSSA can cause this type of glomerulonephritis.     

Renal involvement of monoclonal immunoglobulin deposition disease associated with an unusual monoclonal immunoglobulin A glycan profile

A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-κ gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-κ deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient’s serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-κ staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient’s serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.     

Pattern of glomerular diseases among adults in Rajshahi, the Northern Region of Bangladesh

To obtain a recent and comprehensive insight into the pattern of glomerular diseases in the Bangladeshi population, we studied 95 adequate renal biopsies done during July 2008 to June 2009, by light and direct immunofluorescence microscopy in the Department of Pathology, Rajshahi Medical College, Northern Region of Bangladesh. Of these, 38 (40%) were males and 57 (60%) were females, with a male to female ratio of 1:1.5. The most frequent clinical presentation was nephrotic syndrome (67.37%). Primary glomerular disease accounted for 91.25% of all glomerular disease and, of them, focal and segmental mesangial proliferative glomerulonephritis was the most common histological lesion in 29.47%. Diffuse mesangial proliferative glomerulonephritis (GN) was the second most common lesion (15.79%), followed by focal segmental GN (11.58%), minimal change disease (10.53%), membranous GN (7.37%), IgA nephropathy (6.85%), chronic sclerosing GN (2.11%) and crescentic GN (2.11%). Lupus nephritis was the most prevalent among secondary GN.     

Rapidly progressive glomerulonephritis in a patient with Chlamydia pneumoniae infection: a possibility of superantigenic mechanism of its pathogenesis

Herein we describe a case of a patient with rapidly progressive glomerulonephritis after Chlamydia pneumoniae infection. An 88-year-old woman who had had C. pneumoniae infection two months previously was admitted to our hospital with complaints of dyspnea and generalized edema. Laboratory tests revealed acute renal failure, polyclonal hypergammaglobulinemia, highly increased level of C-reactive protein, and hematoproteinuria. A renal biopsy revealed mesangial and endocapillary proliferative glomerulonephritis with crescents. She responded to high-dose steroids, cyclophosphamide, minocycline, and plasma exchange treatment with the remission of oliguric renal failure. The percentage of the subset of CD3+ TCR+ Vbeta11+ cells markedly increased to 9.6% (normal range: < 1.04%) at the onset of the disease and decreased to 0.1% after the treatment. These clinicopathological features were similar to those of superantigen-associated glomerulonephritis after methicillin-resistant Staphylococcus aureus infection. We suggest that the superantigenic mechanism is one of the possible pathomechanisms of this glomerulonephritis.     

Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient

Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.     

Histological features of IgA glomerulonephritis as predictors of pregnancy outcome

116 pregnancies undertaken by 70 women with IgA glomerulonephritis and their diagnostic renal biopsies have been reviewed. An IgA diffuse mesangial proliferative lesion with superimposed focal and segmental proliferative lesions (IgA FSP) on diagnostic renal biopsy was associated with a greater incidence of maternal complications than IgA diffuse mesangial proliferative glomerulonephritis with no superimposed lesions (IgA DMP) and IgA diffuse mesangial proliferative glomerulonephritis with superimposed focal and segmental hyalinosis and sclerosis (IgA FSHS) (p less than 0.025). Patients with severe vessel lesions had a significantly greater incidence of fetal loss than those with only mild to moderate lesions (p less than 0.025).     

Superimposition of poststreptococcal acute glomerulonephritis on the course of IgA nephropathy

A 17-year-old male with poststreptococcal acute glomerulonephritis (PSAGN) superimposed on the course of IgA nephropathy is presented. The histological findings of the first renal biopsy showed mild IgA nephropathy with a mesangial deposition of IgA and C3. Eighteen months later, acute nephritic syndrome with hypocomplementemia and rising antihyaluronidase titer occurred 10 days following the onset of an upper respiratory infection. The second renal biopsy revealed severe diffuse endocapillary proliferative and exudative glomerulonephritis with cellular crescents in 70% of the glomeruli. Immunofluorescence showed granular staining of C3 alone along the capillary walls. The pre-existing IgA deposits had disappeared. Typical 'humps' were observed by electron microscopy. The symptoms were gradually resolved by intensive steroid and anticoagulant therapy. Five months after the episode of acute nephritic syndrome, the patient was clear of symptoms except for mild proteinuria and hematuria. The third renal biopsy at that time showed morphologic changes similar to those of the first renal biopsy with mild mesangial IgA deposits.     

强直性脊柱炎肾损害的临床病理特点

目的探讨强直性脊柱炎（AS）合并肾损害的临床及病理特点。方法回顾性分析18例经肾脏活体组织检查的AS患者的临床及肾脏病理表现。结果18例患者中,9例呈隐匿性肾小球肾炎表现,5例呈慢性肾小球肾炎表现,1例呈肾病综合征表现,3例为慢性肾功能不全;4例血压增高,14例血压正常。24h尿蛋白定量平均为（1．17±1．39）g。15例肾功能正常,3例肾功能异常患者血肌酐平均为（153．2±36．8）umol／L。8例患者血清IgA水平升高,10例c反应蛋白升高,13例红细胞沉降率（EsR）增快,且血清IgA水平和C反应蛋白呈正相关（r=0．707,P=0．001）,血清IgA水平和ESR呈正相关（r=0．858,P〈0．001）。病理检查结果发现15例为IgA肾病（其中10例为轻度系膜增生性肾炎,1例为轻度系膜增生性肾炎并慢性肾小管间质肾病,2例为局灶增生性肾炎,1例为局灶增生坏死性肾炎,1例为局灶节段性肾小球硬化症）,1例为膜性肾病,1例为局灶增生性肾炎伴慢性肾小管间质肾病,1例为慢性。肾小管间质肾病。有慢性肾小管间质肾病者均有服中药史。结论AS相关性肾损伤的病理改变多样,但主要为IgA肾病,也可表现为膜性肾病、局灶增生性肾炎和慢性肾小管间质。肾病,其肾损伤可能与AS疾病本身和（或）治疗用药相关。