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Background. The vast majority of polyomavirus nephropathy (PVN) is due to BK virus, but rare cases result from JC virus reactivation. To date, only a handful of biopsy-proven JC-PVN cases have been reported. Here, we describe the clinical and pathologic findings in 7 patients with biopsy-proven JC-PVN. Methods. Search of the pathology archives at 2 institutions found 7 cases of JC-PVN. Clinical data were extracted from the electronic medical records, and the biopsies were reviewed. Results. Four cases were diagnosed at 6 y posttransplant or later. The remaining 3 cases presented within approximately 2 y posttransplant, of which 2 showed subclinical JC-PVN on surveillance biopsy. Two early presenting patients were treated for acute rejection just before acquiring JC-PVN. Late presenting patients had higher chronicity, which correlated to worse outcome. All but 1 biopsy showed nonspecific inflammation within areas of interstitial fibrosis without significant inflammation in unscarred cortex. The earliest presenting patient was the exception and showed active inflammation with tubulitis. Viral cytopathic changes were detected in all cases with moderate or high-histologic viral load (pvl), showing preference for the distal tubules and medulla. The 2 cases with low pvl did not demonstrate cytopathic changes but were SV40 positive. Conclusions. JC-PVN can be insidious in presentation, which may cause delayed or missed diagnosis. Unlike BK-PVN, which typically occurs early in the posttransplant period, JC-PVN can occur both early and late following transplant. Overreliance on negative plasma and urine BK viral loads to exclude PVN can be a pitfall.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have revolutionized our armamentarium for kidney and heart protection in patients with or without diabetes. Based on early reports of a limited number of cases, a concern for increased risk of urinary tract infections arose, which has become one of the main areas of concern for some clinicians. However, data from large randomized clinical trials and real-world population-based studies have not shown a significantly increased risk of UTI in patients on SGLT2 inhibitors. The goal of this brief review article is to review the literature and provide reassurance to the patients and prescribers for the broader use of these agents.

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Aims/Hypothesis: Diabetic kidney disease (DKD) remains a significant cause of morbidity and mortality in people with diabetes. Though animal models have taught us much about the molecular mechanisms of DKD, translating these findings to human disease requires greater knowledge of the molecular changes caused by diabetes in human kidneys. Establishing this knowledge base requires building carefully curated, reliable, and complete repositories of human kidney tissue, as well as tissue proteomics platforms capable of simultaneous, spatially resolved examination of multiple proteins. Methods: We used the multiplexed immunofluorescence platform CO-Detection by indexing (CODEX) to image and analyze the expression of 21 proteins in 23 tissue sections from 12 individuals with diabetes and healthy kidneys (DM, 5 individuals), DKD classes IIA, and IIB (2 individuals per class), IIA-B intermediate (2 individuals), and III (one individual). Results: Analysis of the 21-plex immunofluorescence images revealed 18 cellular clusters, corresponding to 10 known kidney compartments and cell types, including proximal tubules, distal nephron, podocytes, glomerular endothelial and peritubular capillaries, blood vessels, including endothelial cells and vascular smooth muscle cells, macrophages, cells of the myeloid lineage, broad CD45+ inflammatory cells and the basement membrane. DKD progression was associated with co-localized increase in collagen IV deposition and infiltration of inflammatory cells, as well as loss of native proteins of each nephron segment at variable rates. Compartment-specific cellular changes corroborated this general theme, with compartment-specific variations. Cell type frequency and cell-to-cell adjacency highlighted (statistically) significant increase in inflammatory cells and their adjacency to tubular and aSMA+ cells in DKD kidneys. Finally, DKD progression was marked by substantial regional variability within single tissue sections, as well as variability across patients within the same DKD class. The sizable intra-personal variability in DKD severity impacts pathologic classifications, and the attendant clinical decisions, which are usually based on small tissue biopsies. Conclusions/Interpretations: High-plex immunofluorescence images revealed changes in protein expression corresponding to differences in cellular phenotypic composition and microenvironment structure with DKD progression. This initial dataset demonstrates the combined power of curated human kidney tissues, multiplexed immunofluorescence and powerful analysis tools in revealing pathophysiology of human DKD.