SummaryBackground and objectives The kidney is the organ most commonly involved in systemic amyloidosis. This study reports the largest clinicopathologic series of renal amyloidosis.

Background and objectives: Dense deposit disease (DDD) is a rare disorder that most commonly affects children. This study reports the largest North American series addressing clinicopathologic and outcome differences in children and adults.Design, setting, participants, & measurements: Thirty-two patients with DDD were analyzed from the archives of Columbia University between 1977 and 2007. Characteristic intramembranous electron-dense deposits defined all diagnoses.Results: The cohort included 14 children (<16 yr) and 18 adults, with 39% of adults >60 yr. The female/male ratio was 1.9. At presentation, the mean 24-h urine protein was 4.6 g, nephrotic syndrome was present in 33%, renal insufficiency in 59%, and hematuria in 87% of patients. Compared with adults, children had lower incidence of renal insufficiency and were more likely to have reduced C3. Histologic pattern included membranoproliferative, mesangial, endocapillary, and crescentic glomerulonephritis. Treatment included immunosuppression (IS) alone in seven, renin angiotensin system (RAS) blockade alone in six, and combined IS/RAS blockade in 11. On follow-up (mean 63 mo) available in 27 patients, 26% had complete response, 48% had persistent renal dysfunction, and 26% had ESRD. Correlates of ESRD were older age and higher creatinine at biopsy, the absence of combined IS/RAS blockade therapy and the presence of subepithelial humps, but not histologic pattern. On multivariate analysis, age and creatinine emerged as the only independent predictors of ESRD.Conclusions: DDD is clinically and pathologically heterogeneous. Adults have worse outcome than children, despite similar treatment. Combined IS/RAS blockade appears superior to either agent alone.

Background and objectives: The most common bariatric surgery is Roux-en-Y gastric bypass (RYGB), which has been associated with hyperoxaluria and nephrolithiasis. We report a novel association of RYGB with renal insufficiency as a result of oxalate nephropathy.Design, setting, participants, & measurements: Eleven cases of oxalate nephropathy after RYGB were identified from the Renal Pathology Laboratory of Columbia University. The clinical features, pathologic findings, and outcomes are described.Results: Patients were predominantly white (72.7%) with a mean age of 61.3 yr. Indications for RYGB included morbid obesity (eight patients) and reconstruction after total gastrectomy for gastric cancer (three patients). All 11 patients had a history of hypertension, and 9 were diabetic. Patients presented with acute renal failure, often superimposed on mild chronic renal insufficiency (n ‫؍‬ 7), at a median of 12 mo after RYGB. The mean creatinine at baseline, at discovery of acute renal failure, and at biopsy was 1.5, 5.0, and 6.5 mg/dl, respectively. Renal biopsies revealed diffuse tubular degenerative changes, abundant tubular calcium oxalate deposits, and varying degrees of tubulointerstitial scarring. In addition, seven biopsies had underlying diabetic glomerulosclerosis and two had glomerulosclerosis attributable to obesity and hypertension. Eight of 11 patients rapidly progressed to ESRD and required hemodialysis at a mean of 3.2 wk after renal biopsy. The remaining three patients were left with significant chronic kidney disease.Conclusions: Oxalate nephropathy is an underrecognized complication of RYGB and typically results in rapid progression to ESRD. Patients with pre-existing renal disease may be at higher risk for this complication.

IntroductionFibrillary glomerulonephritis (FGN) is a rare disease with unknown pathogenesis and a poor prognosis. Until now, the diagnosis of this disease has required demonstration of glomerular deposition of randomly oriented fibrils by electron microscopy that are Congo red negative and stain with antisera to Igs. We recently discovered a novel proteomic tissue biomarker for FGN, namely, DNAJB9.MethodsIn this work, we developed DNAJB9 immunohistochemistry and tested its sensitivity and specificity for the diagnosis of FGN. This testing was performed on renal biopsy samples from patients with FGN (n = 84), amyloidosis (n = 21), a wide variety of non-FGN glomerular diseases (n = 98), and healthy subjects (n = 11). We also performed immunoelectron microscopy to determine whether DNAJB9 is localized to FGN fibrils.ResultsStrong, homogeneous, smudgy DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN. The 2 cases that did not stain for DNAJB9 were unique, as they had glomerular staining for IgG only (without κ or λ) on immunofluorescence. DNAJB9 staining was not observed in cases of amyloidosis, in healthy subjects, or in non-FGN glomerular diseases (with the exception of very focal staining in 1 case of smoking-related glomerulopathy), indicating 98% sensitivity and > 99% specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules.ConclusionDNAJB9 immunohistochemistry is sensitive and specific for FGN. Incorporation of this novel immunohistochemical biomarker into clinical practice will now allow more rapid and accurate diagnosis of this disease.

Amyloidosis derived from leukocyte chemotactic factor 2 (ALECT2) is a recently described disease. Here, we report the characteristics and outcome of 72 patients with renal ALECT2, which included 19 who had another kidney disease on biopsy. Ninety-two percent of patients were Hispanics and over half were elderly. Three had other organ, but not cardiac, amyloidosis involvement. All patients without concurrent disease, except three, presented with chronic renal insufficiency. Proteinuria was variable and absent in a third, whereas nephrotic syndrome and hematuria were rare. After a median follow-up of 26 months, one-third developed end-stage renal disease (ESRD). The median renal survival was 62 months. Independent predictors of renal survival were serum creatinine at diagnosis, with a value of 2.0 mg/dl being the best cutoff for predicting ESRD, percentage global glomerulosclerosis, and presence of diabetes. Only four patients died and four had received chemotherapy for an erroneous diagnosis of immunoglobulin light chain-derived amyloidosis. Five patients underwent kidney transplantation; none had graft loss but one had disease recurrence. Patient survival is superior to renal immunoglobulin light chain-derived amyloidosis and reactive amyloidosis largely due to the absence of cardiac involvement. Thus, renal ALECT2 mainly affects elderly Hispanics who typically present with chronic renal insufficiency and bland urine sediment, with or without proteinuria.

Acute postinfectious glomerulonephritis (APIGN) is uncommon in adults, and its incidence is progressively declining in developed countries. To our knowledge there are no modern North American series addressing epidemiology and outcome. Here we report the clinical and pathologic findings in 86 cases of adult APIGN diagnosed by renal biopsy in a large New York referral center between 1995 and 2005. The male:female ratio was 2:1, and mean age was 56 years, with 33.7% aged older than 64 years. Of the patients, 38.4% had an immunocompromised background, including diabetes (29.1%), malignancy (4.7%), alcoholism (2.3%), acquired immunodeficiency syndrome (AIDS) (2.3%), and intravenous drug use (1.2%). The most common sites of infection were upper respiratory tract (23.3%), skin (17.4%), lung (17.4%), and heart/endocarditis (11.6%). The 2 most frequently identified infectious agents were streptococcus (27.9%) and staphylococcus (24.4%). Hypocomplementemia was present in 73.9% of patients. The most common histologic patterns were diffuse (72.1%), focal (12.8%), and mesangial (8.1%) proliferative glomerulonephritis. Outcome analysis was performed on the 52 patients with a follow-up of >/=3 months (mean, 25 mo). Among the 41 patients without underlying diabetic glomerulosclerosis, 23 (56.1%) achieved complete remission, 11 (26.8%) had persistent renal dysfunction, and 7 (17.1%) progressed to end-stage renal disease (ESRD). Of the 11 patients with underlying diabetic glomerulosclerosis, 2 (18.2%) had persistent renal dysfunction, and the remaining 9 (81.8%) progressed to ESRD (p < 0.001). In patients without underlying diabetic glomerulosclerosis, correlates of complete remission were younger age, female sex, lower serum creatinine at biopsy, and absence of immunocompromised state. By multivariate analysis, age and serum creatinine at biopsy inversely correlated with complete remission, and serum creatinine at biopsy was the only correlate with ESRD. Outcome did not correlate with any pathologic feature (including crescents) or steroid treatment. Diabetes and aging have emerged as major risk factors for adult APIGN. Full recovery of renal function can be expected in just over half of patients, and prognosis is dismal in those with underlying diabetic glomerulosclerosis.

Little is known about the rare entities of heavy- and light-chain amyloidosis (AHL) and heavy-chain amyloidosis (AH). Here, we report the renal and hematological characteristics, pathology, and outcome of 16 patients with renal AH/AHL (5 with AH and 11 with AHL) and compare them with 202 patients with renal light-chain amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) on 12 patients or by immunofluorescence on four patients. All patients with renal AH/AHL were Caucasians, with a male/female ratio of 2.2 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal immunoglobulin, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematological response to chemotherapy was comparable with renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. Thus, renal AH/AHL is an uncommon and underrecognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications.

Conclusions: MGN with ANCA-associated NCGN is a rare dual glomerulopathy seen in patients with heavy proteinuria, acute renal failure, and active urine sediment. Prognosis is variable, with 50% of patients reaching endpoints of ESRD or death.