The risk factors influencing the natural course of chronic kidney disease (CKD) are complex and heterogeneous, and few systematic reviews to date have focused on this issue. The aim of the study is to identify the risk factors for disease development and progression in each stage of CKD. We conducted electronic literature searches of PubMed, MEDLINE, Scopus, and the Cochrane Library up to October 15, 2012, for observational studies evaluating the risk factors on the development or progression of CKD. Eligible studies should have collected repeated information that could evaluate changes in renal function. Extracted information from all the included studies was synthesized narratively. Quality assessments were performed using the Newcastle-Ottawa Scale. An exploratory random-effects meta-analysis was performed where feasible to pool effect sizes across studies for a specific risk factor in a specific outcome. We identified 38 cohort studies and 2 case-control studies from 40 articles, with a total of 318,898 participants from 14 countries. The follow-up duration ranged from 1.5 to 16 years. The majority of the included studies were of high quality. The baseline CKD stages of the included studies ranged from normal to later stages, and only 19 studies could be classified into a specific range of CKD stages during follow-up. Three risk factors from studies of the same baseline and follow-up CKD stages were eligible for the exploratory meta-analysis, including male sex, substantial proteinuria, and diabetes. The hazard ratios for the progression from CKD stages 3-5 to end-stage renal disease (ESRD) were 1.37 (95% confidence interval 1.17-1.62), 1.64 (1.01-2.66), and 1.16 (0.98-1.38) for male sex, substantial proteinuria, and diabetes, respectively. In conclusion, our analyses comprehensively summarize the initiating and perpetuating factors for CKD. Male sex and substantial proteinuria are significant perpetuating factors for the progression from late stage CKD to ESRD, and diabetes may play a minor role for the outcome of ESRD among patients with later stages of CKD.

Quiz Ref ID Chronic kidney disease (CKD) is a global epidemic, and it leads to higher risks of dialysis, cardiovascular morbidity, and mortality.^1-3 The prevalence of CKD varies from 8% to 16% worldwide, with nondiabetic CKD accounts for most of the CKD population.^4-7 The development and progression of nondiabetic CKD are closely interrelated to hypertension, and blood pressure (BP) control is able to decrease the risk of decline in renal function and cardiovascular mortality.^7-11 However, the optimal BP target for preventing kidney disease progression remain debated.

Introduction: Inhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS. Methods: A systematic review of databases was performed to identify RCTs which compared iNO with controls up to September 2014. Effect estimates for risk ratio (RR) of acute kidney injury (AKI) were pooled using a random-effects model. Results: Ten RCTs involving 1363 participants were included. Inhaled nitric oxide significantly increased the risk of AKI compared with controls (RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02). In the stratified analysis, a high cumulative-dose of iNO significantly increased the risk of AKI (RR, 1.52, 95%CI, 1.14 to 2.02, p = 0.004), whereas medium and low cumulative-doses did not (RR, 0.64, 95%CI, 0.23 to 1.81 and RR, 0.56, 95%CI, 0.11 to 2.86 respectively). In subgroup analysis by study population, an increased risk of AKI was observed in patients with ARDS (RR, 1.55, 95%CI, 1.15 to 2.09, p = 0.005) but not in those without (RR, 0.90, 95%CI, 0.49 to 1.67, p = 0.75). Conclusions: The available data show that iNO therapy may increase the risk of renal dysfunction, especially with prolonged use and in patients with ARDS. The risk in pediatric population is unknown owing to limited data. We suggest monitoring renal function during iNO therapy, and that future trials of iNO should evaluate renal safety.

Uremic pruritus is one of the most common and bothersome symptoms in patients with end-stage renal disease. Most patients withuremic pruritus experience a prolonged and relapsing course and significant impairments of quality of life. The pathophysiology of uremicpruritus is not completely understood. A complex interplay among cutaneous biology and the nervous and immune systems hasbeen implicated, with the involvement of various inflammatory mediators, neurotransmitters, and opioids. Uremic pruritus treatmentoutcomes are often unsatisfactory. Clinical trials have mostly been small in scale and have reported inconsistent results. Recent evidenceshows that gabapentinoids, nalfurafine, and difelikefalin are effective for relieving uremic pruritus in hemodialysis patients.This review provides an overview of the epidemiology and proposed mechanisms of uremic pruritus, then highlights the manifestationsof and clinical approach to uremic pruritus. Current evidence regarding treatment options, including topical treatments, treatmentof underlying disease, phototherapy, and systemic treatments, is also outlined. With a better understanding of uremic pruritus,more therapeutic options can be expected in the near future.

Objectives: To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. Methods: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI. Results: We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m ² /year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion. Conclusions: Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD. PROSPERO registration number: CRD42021239807.