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.     

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.     

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.     

Percutaneous renal biopsy results: a retrospective analysis of 511 consecutive cases

To determine the patterns of the prevalent glomerulonephritis (GN) in our region, we studied the results of 511 consecutive renal biopsies performed on patients with proteinuria, hematuria and mild to moderate renal impairment at the Aga Khan University Hospital during a period of 18 years from January 1990 to December 2008. Primary glomerular disease accounted for two-thirds of the glomerular diseases, which in turn constituted 49% of all renal biopsies. The most common histological lesion was membranoproliferative disease (28%). Membranous GN was the second most common lesion (19%), followed by minimal change disease (16%) and focal segmental GN (11%). Secondary glomerular disease comprised 30% of glomerular diseases (21% of all the renal biopsies), with lupus nephritis forming the most common lesion (34%) followed by amyloidosis (22%), diabetic nephropathy (10%), Wagener's granulomatosus and post-infectious GN (9% each). Tubulointerstitial diseases accounted for 16% of all the renal biopsies. We conclude that there exists a wide variability in the different categories of primary and secondary glomerular diseases in our region as compared with different parts of the world. Future studies should be directed to analyze the causes for these variations.     

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.     

IgA肾病520例临床病理分析

目的研究IgA肾病(IgAN)的临床和病理特点及其相互关系。方法对1992年11月～2003年6月温州医学院附属第一医院肾内科病理室肾活检诊断的原发性IgAN520例进行临床与病理分型关系的分析。结果520例IgAN临床表现以无症状性尿检异常最常见,占346例(66.5%),其次是慢性肾炎和肾病综合征,分别占77例(14.8%)和66例(12.7%)。病理类型以局灶节段硬化性肾小球肾炎最常见,占186例(35.8%),其次是系膜增生性肾小球肾炎、轻微病变肾小球肾炎和局灶节段增生性肾小球肾炎,分别为116例(22.3%)、104例(20%)和63例(12.1%)。结论IgAN的临床病理表现多样化并具有一定特点。临床表现最常见为无症状性尿检异常,在病理上最常见的是局灶性肾小球病变类型。     

Expression of macrophage migration inhibitory factor in human glomerulonephritis

BACKGROUND: We have recently demonstrated that macrophage migration inhibitory factor (MIF) plays a pathogenic role in experimental glomerulonephritis (GN). The aim of the current study was to investigate MIF expression in human GN. METHODS: MIF expression was examined by in situ hybridization and immunohistochemistry staining in 65 biopsies from a variety of glomerulonephridities. RESULTS: There is constitutive expression of MIF mRNA and protein in normal human kidney that is largely restricted to tubular epithelial cells and to some glomerular epithelial cells. There was little change in the pattern of MIF expression in nonproliferative forms of GN such as minimal change disease and membranous GN. However, there was a marked increase in both glomerular and tubular MIF expression in proliferative forms of GN, including focal segmental glomerulosclerosis (FGS), lupus nephritis, crescentic GN, and mesangiocapillary proliferative GN. The prominent macrophage and T-cell infiltrate in these diseases were largely restricted to areas with marked up-regulation of MIF expression, contributing to glomerular hypercellularity, glomerular focal segmental lesions, crescent formation, tubulitis, and granulomatous lesions. De novo MIF expression was evident in glomerular endothelial cells and mesangial cells in proliferative forms of GN. In addition, many infiltrating macrophages and T cells showed MIF mRNA and protein expression. Quantitative analysis found that increased glomerular and tubular MIF expression gave a highly significant correlation with macrophage and T-cell accumulation, the severity of histologic lesions, and the loss of creatinine clearance. CONCLUSIONS: Renal MIF expression is markedly up-regulated in proliferative forms of human GN, and this correlates with leukocyte infiltration, histologic damage, and renal function impairment. These results suggest that MIF may be an important mediator of renal injury in progressive forms of human GN. Based on these findings, together with the known pathogenic role of MIF in experimental GN, we propose that MIF is an attractive therapeutic target in the treatment of progressive forms of GN.     

A five-year analysis of the incidence of glomerulonephritis at Cairo University Hospital-Egypt

Our study aimed to obtain a comprehensive review of the incidence of biopsy-proven glomerulonephritis (GN) at the Cairo University Hospitals, Egypt, over the last five years. We analyzed the clinical and pathological data of all renal biopsy samples that were performed during the period from July 2003 to July 2008. Renal biopsy samples of 924 patients were referred for pathological assessment during the period of the study [437 male and 487 female patients; their mean age was 26.5 ± 14.6 years (range: 2.5-71 years)]. Focal segmental glomerulo-nephritis was the most frequent cause of primary GN (21.21%), followed by mesangial proliferative GN (18.93%), diffuse proliferative GN (13.96%), focal proliferative GN (12.77%) and membranous GN (10.93%). The results could be explained by the high incidence of lupus nephritis among the study subjects as well as the relatively young age of the study group.     

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.     

Glomerular distribution and gelatinolytic activity of matrix metalloproteinases in human glomerulonephritis.

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the development of glomerular injury in rat experimental glomerulonephritis (GN). However, the significance of MMPs in human GN remains obscure. In order to evaluate the role of MMPs in human GN, we examined the glomerular distribution and gelatinolytic activities of MMP-2 and MMP-9 in human GN. METHODS: We performed immunohistochemistry with polyclonal anti-MMP-2 and MMP-9 antibodies, and analysed gelatin zymograms of five isolated glomeruli from various types of human renal disease. The renal specimens investigated were from normal kidneys (n=5), IgA nephritis (n=20), Henoch-Sch?nlein nephritis (n=4), non-IgA mesangial proliferative GN (n=9), lupus nephritis (n=6), acute poststreptococcal GN (APSGN) (n=4) and diabetic nephropathy (DN) (n=4). RESULTS: MMP-2 immunoreactivity was not detected in normal controls or in any type of GN. MMP-9 staining, which was almost negative in normal glomeruli, was increased mainly in the mesangial region and corresponded to the level of glomerular cell proliferative changes in mesangial proliferative GN (IgA nephritis, Henoch-Sch?nlein nephritis, non-IgA mesangial proliferative GN and lupus nephritis). Positive but weak staining for MMP-9 was observed in mesangial areas in DN. In addition, double immunostaining showed that MMP-9 is colocalized in scattered neutrophils within diseased glomeruli in APSGN. MMP-9 gelatinolytic activity in five normal glomeruli was weakly detected. Consistent with the levels of immunostaining, MMP-9 glomerular activity was dramatically increased in nephritic glomeruli with IgA nephritis, lupus nephritis and DN. The gelatinolytic activity of MMP-2 was occasionally detectable in nephritic glomeruli. CONCLUSION: These results strongly suggest that MMP-9 plays an important role in abnormal mesangial proliferative changes in human GN.     

Intraglomerular monocytes in human glomerulonephritis.

A total of 246 cases of 166 primary glomerulonephritis (GN) and 80 secondary GN were examined for the presence of intraglomerular monocytes using nonspecific esterase reaction of alpha-naphthyl butyrate methods. The high score of monocyte index (MI) as the numbers of monocytes per glomerulus was found in crescentic GN (n = 5, MI = 3.72 +/- 1.98), endocapillary proliferative GN (n = 8, MI = 2.17 +/- 2.13), lupus nephritis (n = 43, MI = 2.21 +/- 3.35), and cryoglobulinemia-related GN (n = 1, MI = 11.5). The intermediate score of MI was observed in IgA nephropathy (IgA-N, n = 64, MI = 0.63 +/- 0.42) and Henoch-Sch?nlein purpura nephritis (HSP-N, n = 11, MI = 1.09 +/- 0.87). Out of IgA-N and HSP-N, the scores of MI in patients with more severe proliferation and/or with segmental lesions were higher than those without this histological finding. However, there was not a significant correlation between the glomerular monocytic infiltration and clinical findings in each group. In primary GN including minor glomerular abnormalities, focal glomerular sclerosis and membranous GN, and in secondary renal diseases except for SLE, HSP, and cryoglobulinemia, the score of intraglomerular monocytic infiltration was of little value. The participation of monocytes was predominant in extra- and intracapillary GN, lupus nephritis, and cryoglobulinemia-related GN, as previously reported. Moreover, in some types of proliferative GN, especially IgA-N and HSP-N, some parts of glomerular hypercellularity result from the participation of monocyte-macrophage series, although the main parts of cell proliferation are intrinsic mesangial cells.     

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).     

The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades

This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries.     

A clinicopathologic study of forty-eight infants with nephrotic syndrome

The clinical and histopathologic features of 48 children presenting with the nephrotic syndrome during the first year of life were analyzed. Proteinuria was discovered soon after birth to 3 months of age in 39 infants (congenital nephrotic syndrome), and nine infants had an infantile onset presenting between 4 and 12 months of age. Neither histologic parameters--microglomeruli, epithelial, or mesangial proliferation, focal segmental or global sclerosis, fibrinoid necrosis, or tubular microcysts--nor histologic classification--microcystic disease, mesangial proliferative glomerulonephritis, focal segmental glomerular sclerosis/hyalinosis-predicted the outcome. Rather, age at presentation was found to predict outcome: One of 39 infants with a congenital onset and seven of nine infants with an infantile onset underwent a complete remission (P less than 0.0001).     

Dense intramembranous deposit disease: new pathologic features

The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tubulointerstitial nephritis, and two had focal segmental mesangial proliferative glomerulonephritis. The patients with membranoproliferative glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis had easily recognizable dense intramembranous deposits by optical microscopy. The patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis did not have recognizable peripheral loop dense intramembranous deposits even under oil immersion. In patients with membranoproliferative glomerulonephritis ultrastructural examination revealed extensive capillary wall dense intramembranous deposits. Immunofluorescence revealed diffuse double linear staining along the capillary walls and "mesangial rings" of C3. In the patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis the immunofluorescence study suggested a diagnosis of dense intramembranous deposit disease because of the segmental double linear staining of the capillary walls and "mesangial rings" of C3, but the diagnosis was only established by fine structural analysis where occasional peripheral loop and prominent paramesangial basement membrane dense intramembranous deposits and mesangial nodular deposits were identified. Clinical features prior to biopsy included nephrotic syndrome in eight patients, an acute nephritic syndrome in six patients, and asymptomatic proteinuria and hematuria in two patients. Five of six patients with an acute nephritic presentation had focal segmental necrotizing glomerulonephritis. The acute renal insufficiency in these patients was transitory and appeared to be related to a prominent acute tubulointerstitial nephritis present in four of the biopsy specimens. Depressed serum C3 levels were present in patients with membranoproliferative glomerulonephritis; patients with focal segmental lesions were normocomplementemic. Because of the "atypical" light microscopic features in six of our patients, we support the suggestion that membranoproliferative glomerulonephritis, type II be replaced by the term 'dense intramembranous deposit disease' for this glomerulopathy with variable clinical and histologic features.     

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.     

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.     

肾小球系膜增生机制的免疫组化研究

以单抗Ｍａｃ３８７作为单核细胞或中性粒细胞标志，以增殖细胞核抗原（ＰＣＮＡ）单抗作为细胞增殖指标，应用ＡＢＣ免疫酶标法对８７例各型肾小球肾炎肾穿刺组织进行了免疫组化研究，结果发现肾小球Ｍａｃ３８７阳性细胞数除紫癜性肾炎外，各型增生性肾炎显著高于非增生性肾炎（Ｐ〈０．０５）；ＰＣＮＡ阳性细胞数除ＩｇＡ肾炎外，各型增生性肾炎也均显著高于非增生性肾炎组（Ｐ〈０．０５）；肾小球Ｍａｃ３８７和ＰＣＮＡ阳性细     

Renal involvement in canine leishmaniasis. A light-microscopic, immunohistochemical and electron-microscopic study

In a prospective survey in the Isle of Elba, 413 dogs affected by naturally acquired Leishmania infantum infection were identified out of a controlled population of 1,500 resident mongrel dogs. In all the 34 randomly selected dogs of different breed, age, and duration of disease, the presence of glomerular lesions which defined mainly two categories of glomerulonephritis (GN) was observed. The first group was characterized by mesangial-cell proliferation either with focal features (11 dogs), or with a diffuse pattern (10 dogs). The second group (12 dogs) showed the typical findings of segmental membrano-proliferative GN; amyloid deposits were seen in the glomerular tuft and interstitium in 1 dog. Immunohistochemical investigation revealed granular deposits of IgG, IgM, and C3 both in mesangial areas as well as on glomerular capillary walls. Granular immune deposits om the tubular basement membrane were also found in 31 out of 34 dogs examined. With ultrastructural investigation, subendothelial and mesangial electron-dense deposits were revealed. Age, sex, serum creatinine, BUN, duration of disease, anti-Leishmania antibody titers, and immune complexes did not discriminate between the types of observed GN, while proteinuria did. The study shows that the renal involvement is the natural sequela in dogs infected with L. infantum, and that the kidney lesions are characterized by immunologically mediated glomerular and tubular damage.