Mitochondrial dysfunction is considered to be an important mediator of the pro‐aging process in chronic kidney disease, which is continuously increasing worldwide. Although PTEN‐induced kinase 1 (PINK1) regulates mitochondrial function, its role in renal aging remains unclear. We investigated the association between PINK1 and renal aging, especially through the cGAS‐STING pathway, which is known to result in an inflammatory phenotype. Pink1 knockout (Pink1^−/−) C57BL/6 mice and senescence‐induced renal tubular epithelial cells (HKC‐8) treated with H₂O₂ were used as the renal aging models. Extensive analyses at transcriptomic‐metabolic levels have explored changes in mitochondrial function in PINK1 deficiency. To investigate whether PINK1 deficiency affects renal aging through the cGAS‐STING pathway, we explored their expression levels in PINK1 knockout mice and senescence‐induced HKC‐8 cells. PINK1 deficiency enhances kidney fibrosis and tubular injury, and increases senescence and the senescence‐associated secretory phenotype (SASP). These phenomena were most apparent in the 24‐month‐old Pink1^−/− mice and HKC‐8 cells treated with PINK1 siRNA and H₂O₂. Gene expression analysis using RNA sequencing showed that PINK1 deficiency is associated with increased inflammatory responses, and transcriptomic and metabolomic analyses suggested that PINK1 deficiency is related to mitochondrial metabolic dysregulation. Activation of cGAS‐STING was prominent in the 24‐month‐old Pink1^−/− mice. The expression of SASPs was most noticeable in senescence‐induced HKC‐8 cells and was attenuated by the STING inhibitor, H151. PINK1 is associated with renal aging, and mitochondrial dysregulation by PINK1 deficiency might stimulate the cGAS‐STING pathway, eventually leading to senescence‐related inflammatory responses.

Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.

Most eukaryotic cells have mitochondrial networks that can change in shape, distribution, and size depending on cellular metabolic demands and environments. Mitochondrial quality control is critical for various mitochondrial functions including energy production, redox homeostasis, intracellular calcium handling, cell differentiation, proliferation, and cell death. Quality control mechanisms within mitochondria consist of antioxidant defenses, protein quality control, DNA damage repair systems, mitochondrial fusion and fission, mitophagy, and mitochondrial biogenesis. Defects in mitochondrial quality control and disruption of mitochondrial homeostasis are common characteristics of various kidney cell types under hyperglycemic conditions. Such defects contribute to diabetes-induced pathologies in renal tubular cells, podocytes, endothelial cells, and immune cells. In this review, we focus on the roles of mitochondrial quality control in diabetic kidney disease pathogenesis and discuss current research evidence and future directions.

Kang JM, et al. J Korean Med Sci. 2020 Aug;35(36):e305. https://doi.org/10.3346/jkms.2020.35.e305

Background: Online hemodiafiltration (OL-HDF) offers considerable advantages in clearance of molecules of various sizes. However, evidence of clinical effects of OL-HDF is scarce in Korea. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. Methods: Adult patients with end-stage renal disease undergoing hemodialysis (HD) were prospectively enrolled in a K-cohort (CRIS no. KCT0003281) from 6 tertiary hospitals in South Korea. We recruited 435 patients, 339 of whom were on HD at enrollment. One hundred eighty-two patients were followed for more than 24 months. Among them, 44 were switched to OL-HDF for more than 12 months without conversion to HD. We used a paired t test to compare baseline and 24-month follow-up results. Results: The mean age of the subjects was 61.2 +/- 12.2 years, and 62.6% were male. The baseline hemoglobin level was not significantly different between HD and OL-HDF group (10.61 +/- 1.15 vs. 10.46 +/- 1.03 g/dL, P = 0.437). However, the baseline serum protein and albumin levels were significantly lower in the OL-HDF group (6.82 +/- 0.49 vs. 6.59 +/- 0.48 g/dL, P= 0.006; 3.93 +/- 0.28 vs. 3.73 +/- 0.29 g/dL, P< 0.001). In patients switched to OL-HDF, levels of hemoglobin and serum albumin significantly increased (10.46 +/- 1.03 vs. 11.08 +/- 0.82 g/dL, P= 0.001; 3.73 +/- 0.29 vs. 3.87 +/- 0.30 g/dL, P = 0.001). The normalized protein catabolic rate decreased after 24 months, but the change was not significant (1.07 +/- 0.25 vs. 1.03 +/- 0.21 g/kg/day, P = 0.433). Although the dose of erythropoiesis-stimulating agent was lower in patients who converted to HDF, it was not significantly different (-115.7 +/- 189.7 vs. -170.5 +/- 257.1 P = 0.206). Conclusion: OL-HDF treatment over more than 12 months was associated with no harmful effects on anemia and nutritional status.

Kim SK, et al. Korean J Adult Nurs. 2018 Apr;30(2):149-160. https://doi.org/10.7475/kjan.2018.30.2.149