Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.

To maintain the oxygen supply, the production of red blood cells (erythrocytes) is promoted under low-oxygen conditions (hypoxia). Oxygen is carried by hemoglobin in erythrocytes, in which the majority of the essential element iron in the body is contained. Because iron metabolism is strictly controlled in a semi-closed recycling system to protect cells from oxidative stress caused by iron, hypoxia-inducible erythropoiesis is closely coordinated by regulatory systems that mobilize stored iron for hemoglobin synthesis. The erythroid growth factor erythropoietin (EPO) is mainly secreted by interstitial fibroblasts in the renal cortex, which are known as renal EPO-producing (REP) cells, and promotes erythropoiesis and iron mobilization. Intriguingly, EPO production is strongly induced by hypoxia through iron-dependent pathways in REP cells. Here, we summarize recent studies on the network mechanisms linking hypoxia-inducible EPO production, erythropoiesis and iron metabolism. Additionally, we introduce disease mechanisms related to disorders in the network mediated by REP cell functions. Furthermore, we propose future studies regarding the application of renal cells derived from the urine of kidney disease patients to investigate the molecular pathology of chronic kidney disease and develop precise and personalized medicine for kidney disease.

Prognostic factors for acute ischemic stroke in patients undergoing hemodialysis.

BACKGROUND: Acute ischemic stroke (AIS) is a critical complication in patients undergoing dialysis. Although the improvement of AIS management is an urgent requirement, few studies have evaluated the prognostic factors of AIS in these patients. This study aimed to assess the relationship between clinical factors in patients undergoing dialysis and the prognosis of AIS. METHODS: Among 1267 patients who were hospitalized for AIS in Sendai City Hospital from January 2015 to June 2020, 81 patients undergoing hemodialysis were retrospectively enrolled. Multivariate analysis was performed to evaluate the effect of baseline characteristics, dialysis factors, and neurological severity of patients at admission [National Institutes of Health Stroke Scale (NIHSS) score] on in-hospital mortality, physical disability, and the need for rehabilitation transfer. RESULTS: A higher NIHSS score was a critical risk factor for each outcome and the only significant factor for in-hospital mortality [odds ratio (OR)/point 1.156, 95% confidence interval (CI) 1.054-1.267]. The risk factors of physical disability were NIHSS score (OR/point 1.458, 95% CI 1.064-1.998), older age (OR/year 1.141, 95% CI 1.022-1.274), diabetic nephropathy (OR 7.096, 95% CI 1.066-47.218), and higher premorbid modified Rankin scale (mRS) score (OR/grade 2.144, 95% CI 1.155-3.978); while those of rehabilitation transfer were a higher NIHSS score (OR/point 1.253, 95% CI 1.080-1.455), dialysis vintage (OR/year 1.175, 95% CI 1.024-1.349), and intradialytic hypotension before onset (OR 5.430, 95% CI 1.320-22.338). CONCLUSIONS: Along with neurological severity, dialysis vintage, intradialytic hypotension, and diabetic nephropathy could worsen the prognosis of patients with AIS undergoing hemodialysis.

Tubulointerstitial Nephritis after Using a Sodium-glucose Cotransporter 2 Inhibitor.

We herein report a case of acute kidney injury (AKI) due to tubulointerstitial nephritis (TIN) after starting empagliflozin in a diabetic patient. The patient developed stage 1 AKI with proteinuria and elevated tubulointerstitial markers. A renal biopsy showed acute TIN with lymphocytic infiltration into the interstitium. The patient's renal function improved after discontinuation of empagliflozin and steroid administration. Sodium-glucose cotransporter 2 (SGLT2) inhibitor-induced AKI has been reported, but the underlying mechanism remains unclear, potentially because few patients with SGLT2-inhibitor-induced AKI have undergone a renal biopsy. We report the present case in the hope that it will help clarify the mechanism.