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. In vitro, SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably via 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.

Angiogenesis plays an important role in the pathogenesis of diabetic nephropathy (DN). In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with antiangiogenic activity in DN. In a type 1 diabetic rat model, resveratrol treatment blunted the increases of urine albumin excretion, kidney weight and creatinine clearance rate. The increases of glomerular diameter, mesangium accumulation, glomerular basement membrane thickness and renal fibrosis in diabetic rats were also reduced by resveratrol treatment. In the diabetic kidney, increased expression of vascular endothelial growth factor (VEGF), Flk-1 and angiopoietin 2, and reduced expression of Tie-2 were observed. These changes in angiogenic hormones and associated receptors were attenuated by resveratrol treatment. No changes in angiopoietin 1 expression were detected among each group of rats. Resveratrol also significantly downregulated high glucose-induced VEGF and Flk-1 expressions in cultured mouse glomerular podocytes and endothelial cells, respectively. These effects were attenuated by knocking-down silent information regulator 1 (Sirt1) expression. In contrast, upregulation of Sirt1 in cultured endothelial cells reduced Flk-1 expression. Increased permeability and cellular junction disruption of cultured endothelial cells caused by VEGF were also inhibited by resveratrol pretreatment. Taken together, the present study demonstrated that resveratrol may attenuate DN via modulating angiogenesis.

Background: Animal and human studies suggest that inflammation and malnutrition are common in acute kidney injury (AKI) patients. However, only a few studies reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol, markers of nutritional status were associated with the prognosis of AKI patients. No study examined whether the combination of inflammatory and nutritional markers could predict the mortality of AKI patients. Methods: 155 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. C-reactive protein (CRP), and the nutritional markers (albumin, prealbumin and cholesterol) measured at nephrology consultation were analyzed in relation to all cause mortality of these patients. In addition, CRP and prealbumin were also measured in healthy controls (n = 45), maintenance hemodialysis (n = 70) and peritoneal dialysis patients (n = 50) and then compared with AKI patients. Results: Compared with healthy controls and end-stage renal disease patients on maintenance hemodialysis or peritoneal dialysis, patients with AKI had significantly higher levels of CRP/prealbumin (p < 0.001). Higher level of serum CRP and lower levels of albumin, prealbumin and cholesterol were found to be significant in the patients with AKI who died within 28 days than those who survived >28 days. Similarly, the combined factors including the ratio of CRP to albumin (CRP/albumin), CRP/prealbumin and CRP/cholesterol were also significantly higher in the former group (p < 0.001 for all). Multivariate analysis (Cox regression) revealed that CRP/prealbumin was independently associated with mortality after adjustment for age, gender, sepsis and sequential organ failure assessment (SOFA, p = 0.027) while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and CRP/cholesterol) became non-significantly associated. The hazard ratio was 1.00 (reference), 1.85, 2.25 and 3.89 for CRP/prealbumin increasing according to quartiles (p = 0.01 for the trend). Conclusions: Inflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to independent of the severity of illness and it may be a valuable addition to SOFA score to predict the prognosis of AKI patients.

Background: SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology. Summary: SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity. With regard to the kidney, SIRT1 attenuates diabetic albuminuria, reduces blood pressure and related cardiovascular diseases, resists acute kidney injury, delays kidney fibrogenesis, promotes cyst formation and benefits renal ageing. Key Messages: This review summarizes the biology of SIRT1 and focuses on the latest studies concerning SIRT1 as a potential therapeutic target for kidney diseases.

Coronary 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. Adult 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. A 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. Hyperphosphatemia 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.