Incidence and risk factors of acute kidney injury in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

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.

Neutrophil-to-Lymphocyte ratio as a prognostic marker of mortality and disease severity in septic Acute kidney injury Patients: A retrospective study.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of sepsis associated with increased mortality and morbidity. The neutrophil-to-lymphocyte ratio (NLR) has been shown as a risk factor for septic AKI. In this study, we aimed to further evaluate NLR's prediction value on the prognosis of septic AKI patients. METHODS: Septic AKI patients at a tertiary university-affiliated medical center were retrospectively enrolled from August 2015 to August 2021. The primary outcomes were 30-day and 90-day mortality, and secondary outcomes were disease severity, length of stay, and rehospitalization in survivors. Kaplan-Meier curves, Cox proportional hazards, cubic spline and logistics regression analyses were performed for adverse outcomes basing on NLR. The predictive value of NLR on morality was also estimated by the area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 309 septic AKI patients were included with a mean age of 57.8 ± 18.1 years and 92 (29.8 %) being female. The 30-day mortality was 43.4 % and 90-day morality was 61.8 %. When divided by the median of NLR at hospital admission, patients in the high NLR group were associated with an increased 30-day/90-day mortality. After adjusting for multiple covariates, the predictive value of NLR remained significant for 30-day mortality (HR: 2.96, 95 % CI: 1.48-5.92, p = 0.002) and 90-day mortality (HR: 1.88, 95 % CI: 1.11-3.16, p = 0.018). NLR at admission had the highest AUROC (0.618) for 30-day mortality compared with other parameters such as white blood cell (0.573), neutrophil (0.579), lymphocyte (0.567), platelet (0.546), BUN (0.580), albumin (0.545), C-reactive protein (0.571) and procalcitonin (0.534). A similar predictive value on mortality was also observed for NLR measured at septic AKI diagnosis. For secondary outcomes, high NLR was associated with increased risk of transfer to ICU, mechanical ventilation, stage-3 AKI and renal replacement therapy, but not with length of hospital/ICU stay or long-term rehospitalization. CONCLUSION: High NLR is independently associated with 30-day/90-day mortality and disease severity in septic AKI patients. NLR may serve as an economic and widely available biomarker of septic AKI prognosis.

Blood Pressure Variability and the Progression of Chronic Kidney Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor prognosis including cardiovascular events, chronic kidney disease, and mortality, independent of elevated BP. METHODS: We searched PubMed/Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 23, 2022. Cohort studies reporting the association between BPV and chronic kidney disease (CKD) progression were selected. Hazard ratios were pooled using a random-effects model. Meta-regression, subgroup analyses, and sensitivity analyses were conducted. RESULTS: A total of 23 studies were included in this systematic review and meta-analysis. Increased BPV was associated with progression of CKD (HR: 1.21, 95% CI: 1.09-1.33) and incidence of ESRD (HR: 1.08, 95% CI: 1.08-1.30). Among the different BPV metrics, high variation independent of mean (VIM), coefficient of variation (CV), standard deviation (SD), and average real variability (ARV) were indicated as predictors of CKD progression. DISCUSSION: Increased BPV was associated with CKD progression.

Phospholipase A2 induces acute kidney injury by complement mediated mitochondrial apoptosis via TNF-α/NF-κB signaling pathway.

OBJECTIVE: Acute kidney injury (AKI) is one of common complications of wasp/bee stings. Phospholipase A2 (PLA2) is a vital pathogenic composition of wasp/bee venom. We aimed to investigate the role of complement mediated mitochondrial apoptosis in PLA2 induced AKI. MATERIALS AND METHODS: PLA2 induced AKI model was established by injecting PLA2 into via tail vein on mice. The pathological changes and the microstructural changes of kidney, complement activation, inflammation and apoptosis were detected in vitro and in vivo respectively. RESULTS: The results showed that PLA2 induced AKI models were successfully established in vivo and vitro. Compared with control, serum creatinine and urea nitrogen levels were elevated. Complement system activation and mitochondrial damage were observed. Expressions of IL-6, TNF-α, cleaved caspase-3 and cleaved caspase-9, and Bax/Bcl-2 increased in PLA2 induced AKI models. TNF-α/NF-κB signaling pathway activation in AKI models. CONCLUSION: In the present study, PLA2 induced AKI model was first successfully established to our knowledge. The role of complement mediated mitochondrial apoptosis pathway in renal tubular epithelial cells in PLA2 induced AKI were verified in vitro and vivo.

Kidney health in the COVID-19 pandemic: An umbrella review of meta-analyses and systematic reviews.

Background: This umbrella review aims to consolidate evidence from systematic reviews and meta-analyses investigating the impact of the coronavirus disease-2019 (COVID-19) on kidney health, and the associations between kidney diseases and clinical outcomes in COVID-19 patients. Methods: Five databases, namely, EMBASE, PubMed, Web of Science, the Cochrane Database of Systematic Reviews and Ovid Medline, were searched for meta-analyses and systematic reviews from January 1, 2020 to June 2, 2022. Two reviewers independently selected reviews, identified reviews for inclusion and extracted data. Disagreements were resolved by group discussions. Two reviewers independently assessed the methodological quality of all included reviews using ROBIS tool. A narrative synthesis was conducted. The characteristics and major findings of the included reviews are presented using tables and forest plots. The included meta-analyses were updated when necessary. The review protocol was prospectively registered in PROSPERO (CRD42021266300). Results: A total of 103 reviews were identified. Using ROBIS, 30 reviews were rated as low risk of bias. Data from these 30 reviews were included in the narrative synthesis. Ten meta-analyses were updated by incorporating 119 newly available cohort studies. Hospitalized COVID-19 patients had a notable acute kidney injury (AKI) incidence of 27.17%. AKI was significantly associated with mortality (pooled OR: 5.24) and severe conditions in COVID-19 patients (OR: 14.94). The pooled prevalence of CKD in COVID-19 patients was 5.7%. Pre-existing CKD was associated with a higher risk of death (pooled OR: 2.21) and disease severity (pooled OR: 1.87). Kidney transplant recipients were susceptible to SARS-CoV-2 infection (incidence: 23 per 10,000 person-weeks) with a pooled mortality of 18%. Conclusion: Kidney disease such as CKD or recipients of kidney transplants were at increased risk of contracting COVID-19. Persons with COVID-19 also had a notable AKI incidence. AKI, the need for RRT, pre-existing CKD and a history of kidney transplantation are associated with adverse outcomes in COVID-19. Systematic review registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266300, identifier: CRD42021266300.