Our study shows that IEA are more common in DN, when compared with other types of glomerulopathy. In DN, IEA are associated with the severity of IFTA but not with prescribed medications or clinical history of allergy. This suggests that in DN IEA are often associated with chronic tubulointerstitial injury and are not diagnostic of an allergic interstitial nephritis.

Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.

Levamisole is an antihelminthic agent widely used as an adulterant of illicit cocaine recently implicated as a cause of antineutrophil cytoplasmic antibody (ANCA)–associated microscopic polyangiitis in cocaine abusers. An isolated case of membranous nephropathy (MN) associated with levamisole exposure has also been reported. We report the first case, to our knowledge, of a patient with both microscopic polyangiitis manifest as a pauci-immune necrotizing and crescentic glomerulonephritis and concurrent MN in the setting of chronic cocaine abuse and presumed levamisole exposure, raising the hypothesis that levamisole was the causative agent in the development of this rare dual glomerulopathy.

Transpl Infect Dis. 2020;22:e13288.| 1 of 4 https://doi.org/10.1111/tid.13288 wileyonlinelibrary.com/journal/tid | INTRODUC TI ONPolyomavirus-associated nephropathy in solid organ transplantations is rarely caused by JC virus, with BK viremia being the more common cause. There are few cases of JC virus-associated nephropathy in kidney transplant patients, and even fewer cases in recipients of other solid organ transplants. We present a case of JC virus-associated nephropathy in a dual heart-kidney transplant recipient, which to our knowledge is the first case reported in the literature. | C A S E REP ORTA 79-year-old Caucasian male with a history of left nephrectomy in 1981 for an infected congenital atrophic kidney underwent a heart-kidney transplant in October 2011 for restrictive cardiomyopathy secondary to wild-type TTR amyloidosis and end-stage renal disease from presumed cardiorenal syndrome. As per our program's protocol with dual organ transplants, the patient received rabbit anti-thymocyte globulin (rATG) dosed at 1.5 mg/kg daily with standard premedication for 5 days immediately after surgery. A month after his transplantation, the patient had a negative serum polyoma BK virus PCR as part of routine screening after transplantation.The patient did well after heart-kidney transplantation with no episodes of rejection or infection requiring hospitalization. By 1-year post-transplant, his immunosuppressive regimen consisted of tacrolimus 1 mg twice daily titrated to a goal level 5-10 ng/mL and mycophenolate mofetil 500 mg twice daily. The patient was weaned to prednisone 10 mg daily at 3 months and 5 mg daily at 6 months. However, 7 years after heart-kidney transplantation, he presented with progressive renal dysfunction, with creatinine rising from 1.3 to 2.0 mg/dL over the course of 2 months. A urinalysis revealed a bland sediment without protein or leukocytes. Screening for decoy cells in urine is not routinely done at our center and thus was not done for our patient. The patient had no complaints of dysuria, flank pain, or hematuria. He denied use of NSAIDs, had not recently received intravenous iodinated contrast, and was on no new medications. Tacrolimus trough level was 7.3 ng/mL. A renal biopsy was performed.The renal biopsy showed tubulointerstitial inflammation and evidence of polyomavirus (SV40) in tubular epithelial cells by immunohistochemical (IHC) staining (Figure 1), changes consistent with polyomavirus nephropathy. There was also acute tubular injury with focal isometric cytoplasmic vacuolization ( Figure 1B) and a "striped" pattern of interstitial fibrosis (Figure 2A) suggestive of acute and chronic calcineurin inhibitor toxicity, respectively. Electron microscopy demonstrated paracrystalline array arrangement of polyomavirus particles ( Figure 2B). Despite the positive IHC staining for SV40, AbstractJC virus-associated nephropathy is rare in kidney transplant recipients, and even rarer in recipients of other solid organ transplants. We present a case of JC virus-associated nephropathy in ...

Polyomavirus associated nephropathy (PyVAN) continues to be a burden in renal transplantation leading to allograft insufficiency or graft failure. A presumptive diagnosis of PyVAN is made based on the presence of BK polyomavirus in patients' plasma; however, kidney biopsy remains the gold standard to establish a definitive diagnosis. The Banff Working Group on PyVAN proposed a novel classification of definitive PyVAN based on polyomavirus replication/load level and the extent of interstitial fibrosis. The aim of our study was to test the newly defined classes of PyVAN using independent cohorts of 124 kidney transplant patients with PyVAN with respect to the initial presentation and outcome, and to compare our analysis to that previously reported. Detailed analysis of our cohort revealed that the proposed classification of PyVAN did not stratify or identify patients at increased risk of allograft failure. Specifically, while class 3 was associated with the worst prognosis, there was no significant difference between the outcomes in classes 1 and 2. We also found that the timing posttransplantation and inflammation in areas of interstitial fibrosis and tubular atrophy might be additional factors contributing to an unfavorable allograft outcome in patients with PyVAN.