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BackgroundImmune checkpoint inhibitors (ICPis) are associated with multi-organ immune-related adverse effects. Here, we examined the incidence rate, recovery rate, and risk factors of acute kidney injury complicated with ICPis (ICPi-AKI) and evaluted the association between ICPi-AKI and mortality in Japanese patients.MethodsWe analyzed 152 consecutive patients receiving ICPis between 2015 and 2019. A logistic regression analysis was performed to identify risk factors for ICPi-AKI incidence and Cox regression analysis was performed to evaluate the association between ICPi-AKI and mortality.ResultsThe mean patient age was 67 ± 10 years, with the median baseline serum creatinine level of 0.78 mg/dL. Twenty-seven patients (18%) developed ICPi-AKI, and 19 (73%) of them recovered. Pembrolizumab use and liver diseases were significant risk factors for the ICPi-AKI incidence. During the follow-up, 85 patients (59%) died, 17 patients (63%) with ICPi-AKI and 68 (54%) patients without ICPi-AKI, respectively. The ICPi-AKI incidence was not independently associated with mortality (adjusted hazard ratio, 0.85; 95% confidence intervals, 0.46–1.61).ConclusionsOur finding suggest that pembrolizumab use and liver diseases are associated with a higher risk of ICPi-AKI development, but ICPi-AKI did not affect mortality. Future multi-center studies are needed to develop optimal management and prevention strategies for this complication in patients receiving ICPis.

Background Fatty acid-binding protein 4 (FABP4) is secreted from adipocytes and macrophages in adipose tissue and acts as an adipokine. It has recently been reported that FABP4, but not liver-type FABP (L-FABP/FABP1), is also expressed in injured glomerular endothelial cells and infiltrating macrophages in the glomerulus and that urinary FABP4 (U-FABP4) is associated with proteinuria and kidney function impairment in nephrotic patients. However, the link between glomerular FABP4 and U-FABP4 has not been fully addressed in IgA nephropathy (IgAN). Methods We investigated the involvement of FABP4 in human and mouse IgAN. Results In patients with IgAN ( n  = 23), the ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area) and U-FABP4 were positively correlated with proteinuria and were negatively correlated with eGFR. In 4–28-week-old male grouped ddY mice, a spontaneous IgAN-prone mouse model, FABP4 was detected in glomerular endothelial cells and macrophages, and G-FABP4-Area was positively correlated with urinary albumin-to-creatinine ratio ( r  = 0.957, P  < 0.001). Endoplasmic reticulum stress markers were detected in glomeruli of human and mouse IgAN. In human renal glomerular endothelial cells, FABP4 was induced by treatment with vascular endothelial growth factor and was secreted from the cells. Treatment of human renal glomerular endothelial cells or mouse podocytes with palmitate-bound recombinant FABP4 significantly increased gene expression of inflammatory cytokines and endoplasmic reticulum stress markers, and the effects of FABP4 in podocytes were attenuated in the presence of an anti-FABP4 antibody. Conclusion FABP4 in the glomerulus contributes to proteinuria in IgAN, and U-FABP4 level is a useful surrogate biomarker for glomerular damage in IgAN.

Anti-glomerular basement membrane (GBM) disease causes rapidly progressive glomerulonephritis (RPGN) and has a high mortality rate from lung hemorrhage or infection as a side effect of immunosuppressive treatment. We report a case in which a patient with anti-GBM disease experienced severe jejunal bleeding due to cytomegalovirus (CMV) enteritis during immunosuppressive treatment. A previously healthy 74-year-old female was admitted to our hospital with severe acute kidney injury due to intrinsic kidney disease. The patient was anuric, and hemodialysis was started. The initial serum anti-GBM antibody level was elevated at 1880 U/mL. Kidney biopsy demonstrated global glomerulosclerosis and diffuse crescent formation on light microscopy. Immunofluorescence revealed focal deposition of IgG along the glomerular capillaries. The patient was diagnosed with RPGN secondary to anti-GBM disease, and oral prednisolone and double filtration plasmapheresis (DFPP) were begun. During treatment, the patient developed recurrent jejunal hemorrhage refractory to endoscopic clipping. Surgical resection of the intestine was performed to control bleeding. There were CMV-positive cells within the resected jejunum on immunohistochemistry. CMV antigens were also detected in the serum. The patient was diagnosed with CMV enteritis and treated with ganciclovir. Ultimately, the patient was discharged home without any neurologic problems on the 285th day of hospitalization. When treating severe anti-GBM antibody disease, there is a dilemma between the effectiveness and the side effects, especially infections, of immunosuppressive therapy. In this case, moderate immunosuppressive therapy with corticosteroids and DFPP without cyclophosphamide contributed to controlling the CMV enteritis and the patient's survival.

BackgroundSerum vitamin D level shows a seasonal variation, being lower in winter than in summer in healthy subjects. The aim of this study was to determine whether there is presence of such a seasonal variation in hemodialysis patients.MethodsA total of 102 patients on hemodialysis were enrolled in February 2017 (winter) for analyses of serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD). The examinations were repeated in August 2017 (summer). After exclusion of patients with malignancy, loss of follow-up and missing data, 78 patients contributed to the analyses.ResultsSerum level of 25(OH)D, but not that of 1,25(OH)2D, was significantly lower in winter (14.0 ng/mL) than in summer (15.5 ng/mL), though there was no significant difference in regimen for CKD-MBD treatment including vitamin D receptor activators (VDRAs) between the two seasons. Serum intact parathyroid hormone level tended to be higher and alkaline phosphatase was significantly higher in winter than in summer. Linear mixed-effects model analysis showed that level of 25(OH)D, but not that of 1,25(OH)2D, was significantly associated with season (winter and summer) after adjustment of age, sex, dialysis vintage, albumin level and use of drugs for CKD-MBD.ConclusionSerum 25(OH)D has a seasonal variation, being lower in winter than in summer, independent of CKD-MBD treatment including treatment with VDRAs in Japanese hemodialysis patients. The impact of the seasonal variation on risk of vitamin D deficiency and its effect on prognosis remain to be investigated.

Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function.

This manuscript presents a case report of type 2 papillary renal cell carcinoma presenting with persistent fever and abdominal tenderness after treatment for urinary tract infection. The purpose of this article is to aid physicians in understanding that papillary renal cell carcinomas should be considered in patients with a persistent fever after urinary tract infection and computed tomography was useful to diagnose this entity.

Background Fatty acid-binding protein 4 (FABP4), but not FABP1 (liver-type FABP), is ectopically induced in injured glomerular endothelial cells, and urinary FABP4 (U-FABP4) level is associated with proteinuria and renal dysfunction in a general population. Methods The clinical significance of U-FABP4 was investigated in 81 patients (male/female: 43/38, age: 57 ± 17 years) who underwent kidney biopsy. Results U-FABP4 was negatively correlated with estimated glomerular filtration rate (eGFR) ( r =  − 0.56, P  < 0.01) and was positively correlated with age, blood pressure, triglycerides, proteinuria ( r =  0.58, P  < 0.01), plasma FABP4 and urinary FABP1 (U-FABP1) ( r =  0.52, P <  0.01). Multivariable regression analysis showed that eGFR, proteinuria and U-FABP1 were independent predictors of U-FABP4. The level of U-FABP4, but not that of proteinuria, eGFR or U-FABP1, in minimal change nephrotic syndrome (MCNS) was significantly lower than the level in membranous nephropathy (MN) and that in diabetic nephropathy. Receiver operating characteristic curve analysis indicated that U-FABP4 level ≤ 0.78 μg/gCr predicted MCNS in patients who had nephrotic-range proteinuria with a high level of accuracy. When divided by the median value of U-FABP4 at baseline in 33 of the 81 patients who could be followed up, the yearly change (post–pre) in eGFR in the low U-FABP4 group was significantly greater than that in the high U-FABP4 group (median: 11.0 vs. -5.0 mL/min/1.73m 2 /year). Conclusions U-FABP4 level is independently associated with proteinuria and renal dysfunction in patients with glomerular kidney disease. A low U-FABP4 level may predict MCNS in patients with nephrotic syndrome and would be a useful biomarker for differential diagnosis of MCNS and MN, which are common causes of nephrotic syndrome.