Membranous nephropathy with crescents: a series of 19 cases.

Membranous nephropathy (MN) with crescents is rare and, in the absence of lupus, usually is associated with anti-glomerular basement membrane (anti-GBM) nephritis or antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis. Only rare cases of crescentic MN without ANCA or anti-GBM have been reported. Case series. 19 patients with ANCA- and anti-GBM-negative crescentic MN and no clinical evidence of systemic lupus. Clinical features, kidney biopsy findings, laboratory results, treatment, and follow-up of patients with crescentic MN. Mean age was 55 (range, 5-86) years. All patients presented with proteinuria (mean protein excretion, 11.5 [range, 3.3-29] g/d) and nearly all had hematuria; 16 of 19 (84%) patients had decreased estimated glomerular filtration rates (eGFRs; mean serum creatinine, 2.9 [range, 0.4-10] mg/dL; mean eGFR, 39.7 [range, 4 to >100] mL/min/1.73 m2). Glomeruli showed on average 25% (range, 2%-73%) involvement by crescents. All showed a membranous pattern; 7 showed mesangial and 2 showed segmental endocapillary proliferation. By immunofluorescence, all cases showed granular subepithelial immunoglobulin G (IgG) and κ and λ light chains, and all but one showed C3; 5 showed C1q or IgA. Electron microscopy revealed stages I-III MN; 38% of cases were M-type phospholipase A2 receptor (PLA2R) associated, indicating that at least some were primary MN. Follow-up clinical data were available for all patients (mean, 22 [range, 1.5-138] months). 14 patients received immunosuppressive therapy, and 2, only angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy. 4 patients (21%) progressed to end-stage renal disease, at 0-9 months postbiopsy. Mean serum creatinine level of those without end-stage renal disease at follow-up was 1.7 (range, 0.5-4.1) mg/dL; mean eGFR was 53.3 (range, 16-103) mL/min/1.73 m2. 67% of patients had proteinuria with protein excretion≥1 (mean, 3.2) g/d at follow-up. Retrospective study. Crescentic MN is a rare variant of MN that usually presents with heavy proteinuria, hematuria, and decline in GFR. The prognosis is variable and the disease may respond to therapy, but most patients develop a long-term decline in GFR.

Rodriguez EF ，Nasr SH ，Larsen CP ，Sethi S ，Fidler ME ，Cornell LD ... -  《-》

ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits.

Haas M ，Jafri J ，Bartosh SM ，Karp SL ，Adler SG ，Meehan SM ... -  《-》

Clinical features and outcomes of anti-glomerular basement membrane disease in older patients.

Anti-glomerular basement membrane (GBM) disease is being recognized increasingly in older patients. Disease presentation and outcomes of these patients are unclear. Case series. 221 consecutive Chinese patients with anti-GBM disease diagnosed in 1998-2008 in our tertiary referral center. Anti-GBM disease was defined as positive anti-GBM antibodies in circulation and/or linear immunoglobulin G deposition along the GBM on kidney biopsy. Older age, defined as 65 years or older, and antineutrophil cytoplasmic antibody, detected using immunofluorescence and enzyme-linked immunosorbent assay, at presentation. Clinical features, kidney pathologic characteristics, end-stage renal disease (ESRD), and mortality. Multivariate Cox proportional hazard models were used to assess the contribution of age, sex, clinical measures, and treatments to ESRD and mortality. 50 of 221 (22.6%) patients were 65 years or older. Older patients had a male predominance (male/female ratio, 1.9:1). They had a higher proportion of positive antineutrophil cytoplasmic antibody results (46.0% vs 14.6%; P < 0.001), lower prevalence of hemoptysis (26.0% vs 46.2%; P = 0.01), lower urine protein excretion (1.4 ± 1.0 vs 3.9 ± 3.3 g/d; P = 0.001), and higher estimated glomerular filtration rate (eGFR) at presentation (8.4 vs 5.1 mL/min/1.73 m(2); P = 0.007) compared with younger patients. During follow-up, 30 of 37 (81.1%) and 21 of 37 (56.8%) patients developed ESRD and died in the older group compared with 115 of 139 (82.7%) and 35 of 139 (25.2%) in the younger group (P = 0.1 and P = 0.001, respectively). For older patients, multivariate Cox regression analysis showed that higher initial eGFR was an independent predictor for both ESRD (HR, 0.86; 95% CI, 0.78-0.96; P = 0.005) and death (HR, 0.79; 95% CI, 0.66-0.94; P = 0.008). Not all patients underwent kidney biopsy, especially those with very old age or ESRD at presentation. Older patients with anti-GBM disease had milder kidney damage and less pulmonary involvement. Outcomes were predicted by initial eGFR. Thus, early diagnosis was crucial to improve outcomes.

Cui Z ，Zhao J ，Jia XY ，Zhu SN ，Zhao MH ... -  《-》

Rare case of exostosin 1/exostosin 2-related membranous lupus nephritis concomitant with dual ANCA- and anti-GBM antibody-associated crescentic glomerulonephritis effectively diagnosed by mass spectrometry: a case report.

Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.

Yamazaki T ，Takahashi H ，Takeuchi K ，Sakamoto E ，Tominaga K ，Sakurabayashi S ，Abe T ，Sano T ，Wada Y ，Kuwahara N ，Shimizu A ，Takeuchi Y ... -  《BMC Nephrology》

Etiology and Outcome of Crescentic Glomerulonephritis From a Single Center in China: A 10-Year Review.

The disease spectrum of crescentic glomerulonephritis (GN) has been described in only a few previous studies, and detailed epidemiologic data from China are unavailable to date. Case series. 528 patients with biopsy-proven crescentic GN in 2003 to 2013 from a single center. Crescentic GN was classified into 3 types according to immunofluorescence findings: type I was defined as linear deposition of immunoglobulins along the glomerular basement membrane; type II, as glomerular deposition of immune complex; and type III, as pauci-immune deposition. Demographic, clinical, and serologic characteristics. Of 528 cases identified, 208 (39.4%) were men, with a mean age of 37.6±16.4 (SD) years at kidney biopsy. 61 (11.6%) patients had type I crescentic GN, 331 (62.7%) had type II (lupus nephritis, 34.3%; immunoglobulin A [IgA] nephropathy, 17.4%), and 136 (25.8%) had type III. Proportions of patients with acute kidney injury (AKI), acute kidney diseases and disorders without AKI, and chronic kidney disease were 86.9%, 0%, and 13.1% for type I; 42.0%, 19.6%, and 38.4% for type II; and 84.6%, 2.9%, and 12.5% for type III crescentic GN, respectively. Serum antineutrophil cytoplasmic antibodies were detected in 11 (18.0%) patients with type I, 15 (4.5%) with type II, and 117 (86.0%) with type III. Anti-glomerular basement membrane antibodies were found in 60 (98.4%) patients with type I, 3 (0.9%) with type II, and 5 (3.7%) with type III. 5-year cumulative renal survival rates for patients with types I, II, and III were 17.6%, 70.1%, and 44.3%, respectively. Retrospective study, single-center experience. Lupus nephritis may be the most common type of crescentic GN in China, followed by pauci-immune crescentic GN and IgA nephropathy. Almost half the patients presented with AKI, whereas 28.8% of cases showed chronic kidney disease. Clinical manifestations and outcomes varied according to crescentic GN type. The distinction between subtypes based on immunofluorescence and serologic findings has important implications for therapy and outcome.

Chen S ，Tang Z ，Xiang H ，Li X ，Chen H ，Zhang H ，Hu W ，Zeng C ，Liu Z ... -  《-》