The rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD Supplementation with nicotinamide mononucleotide (NMN), an NAD precursor, restored renal SIRT1 activity and NAD content in 20-month-old mice and further increased both in 3-month-old mice. Moreover, supplementation with NMN significantly protected mice in both age groups from cisplatin-induced AKI. SIRT1 deficiency blunted the protective effect of NMN, and microarray data revealed that c-Jun N-terminal kinase (JNK) signaling activation associated with renal injury in SIRT1 heterozygotes. , SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably the deacetylation of a JNK phosphatase, DUSP16. Taken together, our findings reveal SIRT1 as a crucial mediator in the renal aging process. Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI.

BackgroundCoronary artery calcification (CAC) is associated with cardiovascular mortality in end-stage renal disease (ESRD) patients. The present study aimed to identify modifiable risk factors for CAC progression in peritoneal dialysis (PD) patients.MethodsAdult patients who received regular PD for more than 6 months and underwent a series of coronary artery calcification score (CaCS) measurements by multislice spiral computed tomography (MSCT) with an interval of ≥ 6 months were included in this observational cohort study. The demographic characteristics and clinical data, including laboratory data and adequacy of PD, were collected. Curve estimation was used to fit the straight line and obtain the slope. Binary logistic regression was performed to identify the independent risk factors for CAC progression in the PD patients, and multivariate linear regression was conducted to identify factors associated with hyperphosphatemia.ResultsA total of 207 adult patients on PD (116 men, 56.0 %) with a mean age of 59.8 ± 15.9 years were recruited to this study, and 157 of them (75.8 %) received three or more CaCS assessments. The patients were divided into a slow group (n = 137) and a rapid group (n = 70) according to the linear regression slope or the average speed of development. The follow-up time was 33.0 ± 18.8 months. Multivariate logistic regression revealed that age and serum phosphate level were independent risk factors for CAC progression after adjustments. Multivariate linear regression revealed that hyperphosphatemia was associated with elevations in the transferrin and serum albumin levels and normalized protein catabolic rate (nPCR) and reductions in the hemoglobin level, residual Ccr, and PD Ccr.ConclusionsHyperphosphatemia is an independent risk factor for CAC progression, and the serum phosphate level may be associated with protein intake and PD adequacy. These results provide important information for the clinical management of ESRD patients.

♦ Background: This study aimed to examine whether the coronary artery calcification score (CaCS) was associated with the prognosis of peritoneal dialysis (PD) patients. ♦ Methods: Adult PD patients who were clinically stable for at least 2 months were recruited for this prospective, observational cohort study. Coronary artery calcification was assessed using multislice spiral computed tomography and was recorded according to the Agatston score. The endpoints including all-cause mortality, cardiovascular events, and cardiovascular mortality were assessed. Multivariate Cox regression was used to identify independent predictors of all-cause mortality, cardiovascular events (CVEs), and cardiovascular mortality. ♦ Results: A total of 179 PD patients (86 men) with a mean age of 63.5 ± 14.8 years were recruited for this study. Coronary artery calcification scores ranging from 0 to 5,257 were stratified as follows: no (CaCS = 0, n = 54), low (0 < CaCS < 400, n = 72), and high (CaCS ≥ 400, n = 53) calcification. The follow-up duration was 30.6 ± 16.2 (24 -63) months. Compared with the no calcification group, patients with a higher CaCS were older and had lower diastolic blood pressure, residual renal function, and serum albumin, and higher HbA 1 C and serum insulin. Multivariate Cox regression revealed that the CaCS was an independent predictor for all the 3 endpoints after adjustment in PD patients. ♦ Conclusions: CaCS was an independent predictor of allcause mortality, cardiovascular events, and cardiovascular mortality in patients receiving peritoneal dialysis.