Hyperuricemia has been reported to be associated with chronic kidney disease (CKD). However whether an elevated serum uric acid level is an independent risk factor for new-onset CKD remained controversial. A systematic review and meta-analysis using a literature search of online databases including PubMed, Embase, Ovid and ISI Web/Web of Science was conducted. Summary adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were calculated to evaluate the risk estimates of hyperuricemia for new-onset CKD. Thirteen studies containing 190,718 participants were included. A significant positive association was found between elevated serum uric acid levels and new-onset CKD at follow-up (summary OR, 1.15; 95% CI, 1.05–1.25). Hyperuricemia was found be an independent predictor for the development of newly diagnosed CKD in non-CKD patients (summary OR, 2.35; 95% CI, 1.59–3.46). This association increased with increasing length of follow-up. No significant differences were found for risk estimates of the associations between elevated serum uric acid levels and developing CKD between males and females. With long-term follow-up of non-CKD individuals, elevated serum uric acid levels showed an increased risk for the development of chronic renal dysfunction.

Rationale: Sepsis is a severe clinical syndrome featured through organ dysfunction due to infection, while the accompanying acute kidney injury (AKI) is linked to significant incidence of morbidity as well as mortality. Recently, emerging evidence has revealed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is implicated in various renal diseases, while its role and modulation in septic acute kidney injury (S-AKI) remains largely unknown.

Sepsis-associated acute kidney injury (S-AKI) is a common complication in hospitalized and critically ill patients, which increases the risk of multiple comorbidities and is associated with extremely high mortality. Maresin 1 (MaR1), a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid has been reported to protect against inflammation and promote the regression of acute inflammation. This study proposed to systematically investigate the renoprotective effects and potential molecular mechanism of MaR1 in septic acute kidney injury. We established a S-AKI animal model by a single intraperitoneal injection of lipopolysaccharide (LPS), 10 mg/kg, on male C57BL/6J mice. LPS-stimulated (100 μg/ml) mouse kidney tubular epithelium cells (TCMK-1) were used to simulate septic AKI in vitro. The results showed that pretreatment with MaR1 significantly reduced serum creatinine and blood urea nitrogen levels as well as tubular damage scores and injury marker neutrophil gelatinase-associated lipocalin in septic AKI mice. Meanwhile, MaR1 administration obviously diminished pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1), downregulated BAX and cleaved caspase-3 expression, and upregulated BCL-2 expression in the injured kidney tissues and TCMK-1 cells. In addition, MaR1 reduced malondialdehyde production and improved the superoxide dismutase activity of renal tissues while inhibiting reactive oxygen species (ROS) production and protecting the mitochondria. Mechanistically, LPS stimulated the expression of the NOX4/ROS/NF-κB p65 signaling pathway in S-AKI kidneys, while MaR1 effectively suppressed the activation of the corresponding pathway. In conclusion, MaR1 attenuated kidney inflammation, apoptosis, oxidative stress, and mitochondrial dysfunction to protect against LPS-induced septic AKI via inhibiting the NOX4/ROS/NF-κB p65 signaling pathway.

Background: The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application.Objective: This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs.Methods: We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted.Results: In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00–1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65–5.11), ipilimumab (OR: 2.66, 95% CI: 1.42–4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40–4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88–2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90–3.57), fluindione (OR: 6.48, 95% CI: 2.72–15.46), diuretic (OR: 1.78, 95% CI: 1.32–2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15–2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study.Conclusion: The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.