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Background : Uric acid levels are linked to cardiovascular outcomes and mortality, especially in chronic kidney disease (CKD). However, their impact across varying kidney function remains unclear. Methods : We conducted a retrospective cohort study using the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database from a single center. Adult patients with at least one serum uric acid measurement between 2002 and 2021 were included and categorized by estimated glomerular filtration rate (eGFR): normal kidney function (≥90 mL/min/1.73 m 2 ), mild dysfunction (60-89 mL/min/1.73 m 2 ), moderate dysfunction (30-59 mL/min/1.73 m 2 ), and advanced dysfunction (<30 mL/min/1.73 m 2 ). The primary outcome was all-cause mortality with secondary outcomes being myocardial infarction (MI) and heart failure (HF). Results : A total of 242,793 participants were analyzed. Uric acid levels showed a U-shaped association with all-cause mortality in advanced kidney dysfunction, where both low (<3 mg/dL) and high (>10 mg/dL) levels increased mortality risk. In mild kidney dysfunction, lower uric acid levels were linked to better survival. HF risk increased linearly with higher uric acid, particularly in normal kidney function, while no significant association was found between uric acid and MI in any group. Conclusions : Uric acid levels are associated with mortality in a U-shaped pattern for advanced kidney dysfunction, while lower levels appear protective in mild dysfunction. These findings suggest the need for personalized uric acid management in CKD patients based on their kidney function.

Deteriorating kidney function is frequently observed in the elderly population, as well as vulnerability to acute kidney failure, such as ischemic/reperfusion injury (IRI), and inadequate recovery from IRI is one of the mechanisms of kidney dysfunction in the elderly. The potential mediators in the progression of kidney dysfunction in the aging kidney have not yet been clearly revealed. In this study, we investigated the role of nuclear factor erythroid 2-related factor 2 (NRF2), which is an essential regulator of cellular redox homeostasis, in restoring kidney function after IRI in the aging kidney. NRF2 expression decreased significantly in the kidneys of old mice, as well as histologic and functional renal recovery after IRI; 45-min renal pedicle clamping was retarded in old compared with young mice. Persistent renal injury during the recovery phase after IRI was aggravated in NRF2 knockout (KO) mice compared to wild-type mice. Oxidative stress occurred in NRF2 KO old mice during the IRI recovery phase along with decreased expression of mitochondrial OXPHOS-related proteins and a reduction in mitochondrial ATP content. In vitro, hypoxia/reoxygenation (H/R) injury was aggravated in senescent human proximal tubuloepithelial cells after NRF2 restriction using NRF2 siRNA, which also increased the level of oxidative stress and deteriorated mitochondrial dysfunction. Treating the mice with an NRF2 activator, CDDO-Me, alleviated the injury. These results suggest that NRF2 may be a therapeutic target for the aging kidney.

Contrast-induced nephropathy (CIN) is an impairment of renal function that occurs after the administration of an iodinated contrast medium (CM). Kidney dysfunction in CIN is considered transient and reversible in most cases. However, it is the third most common cause of hospital-acquired acute kidney injury and is associated with increased morbidity and mortality, especially in high-risk patients. Diagnostic and interventional procedures that require intravascular CM are being used with increasing frequency, especially among the elderly, who can be particularly susceptible to CIN due to multiple comorbidities. Therefore, identifying the exact mechanisms of CIN and its associated risk factors is crucial not only to provide optimal preventive management for at-risk patients, but also to increase the feasibility of diagnostic and interventional procedure that use CM. CM induces kidney injury by impairing renal hemodynamics and increasing the generation of reactive oxygen species, in addition to direct cytotoxicity. Periprocedural hydration is the most widely accepted preventive strategy to date. Here, we review the latest research results on the pathophysiology and management of CIN.

Osteoporosis is a major public health concern, especially in women. This study aims to identify early biomarkers from biochemical measurements of serum and urine for recognizing the development of osteoporosis and osteopenia in premenopausal and postmenopausal women. From the Korean Genome and Epidemiology Study (KoGES) cohort, longitudinal study participants with normal bone density were enrolled and assessed for the association of baseline clinical and biochemical factors with osteoporosis development over 4 years. In addition, a cross-sectional study between normal bone density and osteopenia/osteoporosis was conducted to validate the risk factors found in the longitudinal cohort. Of the 5272 female participants in the KoGES cohort, 813 women (501 premenopausal and 312 menopausal) who had normal bone density at baseline were included in the longitudinal study. During the 4 years of follow-up, 64 patients developed osteoporosis and 354 developed osteopenia. In a multivariate logistic regression analysis, serum calcium and urine uric acid levels were significantly associated with elevated osteoporosis risk in premenopausal and postmenopausal women, respectively (risk of osteoporosis by serum calcium levels in premenopausal women: 4.03 (1.09-14.93), p = 0.037; risk of osteoporosis by urine uric acid levels in postmenopausal women: 24.08 (1.79-323.69), p = 0.016). For the cross-sectional study, serum and urine parameters were compared between women with osteopenia or osteoporosis at baseline and those with normal bone density. Urine uric acid levels were found to be significantly higher in both premenopausal and postmenopausal women with bone loss than in women with normal bone density ( p < 0.001 and p = 0.004, respectively). Uric acid level in urine may be an early marker for the development of osteoporosis in women, especially after menopause.

Endocan, a potential biomarker of endothelial dysfunction, is associated with increased cardiovascular risk. We investigated the utility of plasma endocan for predicting cardiovascular risk in end-stage renal disease (ESRD) patients undergoing hemodialysis. Of the 452 patients in the K-cohort, 354 with available plasma endocan levels were enrolled. The correlation between plasma endocan levels and the clinical characteristics of a study population were analyzed. We divided patients into two groups, according to plasma endocan levels, and investigated the predictive value of endocan for the occurrence of cardiovascular events. In a multiple linear regression analysis, plasma endocan levels were positively correlated with previous cardiovascular events and negatively correlated with body mass index, albumin, and triglyceride. Patients with higher plasma endocan levels experienced more frequent cardiovascular events than those with lower plasma endocan levels (12.9% in the lower group vs. 22.7% in the higher group, p = 0.016). Cox proportional hazard models showed that higher plasma endocan levels were an independent predictor of cardiovascular events in ESRD patients on hemodialysis ((hazard ration) HR 1.949, 95% (confidence interval) CI 1.144-3.319, p = 0.014). Our results suggest that plasma endocan level might be a useful biomarker for predicting cardiovascular events in ESRD patients on hemodialysis.