SummaryBackground and objectives The burden of AKI around the globe has not been systematically examined.Design, setting, participants, & measurements A systematic review (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their economies. AKI definitions were reclassified according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Randomeffects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity.Results There were 312 studies identified (n=49,147,878) , primarily in hospital settings. Most studies originated from North America, Northern Europe, and Eastern Asia, from high-income countries, and from nations that spent $5% of the gross domestic product on total health expenditure. Among the 154 studies (n=3,585,911) that adopted a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% confidence interval [95% CI], 19.3 to 24.1) and 33.7% in children (95% CI, 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI, 22.1 to 25.7) and 13.8% in children (95% CI, 8.8 to 21.0). The AKIassociated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure.Conclusions Using the KDIGO definition, 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care. This analysis provides a platform to raise awareness of AKI with the public, government officials, and health care professionals.

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IntroductionLittle is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series to examine the clinical characteristics and outcomes of patients with secondary oxalate nephropathy.MethodsElectronic databases were searched for case reports and case series of individual cases or cohorts of patients with biopsy-proven oxalate nephropathy in native or transplanted kidneys from 1950 until January 2018.ResultsFifty-seven case reports and 10 case series met the inclusion criteria, totaling 108 patients. The case series were meta-analyzed. Mean age was 56.4 years old, 59% were men, and 15% were kidney transplant recipients. Fat malabsorption (88%) was the most commonly attributed cause of oxalate nephropathy, followed by excessive dietary oxalate consumption (20%). The mean baseline serum creatinine was 1.3 mg/dl and peaked at 4.6 mg/dl. Proteinuria, hematuria, and urinary crystals was reported in 69%, 32%, and 26% of patients, respectively. Mean 24-hour urinary oxalate excretion was 85.4 mg/d. In addition to universal oxalate crystal deposition in tubules and/or interstitium, kidney biopsy findings included acute tubular injury (71%), tubular damage and atrophy (69%), and interstitial mononuclear cell infiltration (72%); 55% of patients required dialysis. None had complete recovery, 42% had partial recovery, and 58% remained dialysis-dependent. Thirty-three percent of patients died.ConclusionSecondary oxalate nephropathy is a rare but potentially devastating condition. Renal replacement therapy is required in >50% of patients, and most patients remain dialysis-dependent. Studies are needed for effective preventive and treatment strategies in high-risk patients with hyperoxaluria-enabling conditions.

Differences in race/ethnicity can significantly affect the results obtained from MDRD-based eGFR equation. It is highly recommended that each population should validate eGFR equations before applying the equation in epidemiologic studies or clinical use.

BackgroundCalciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case series, and cohort studies to synthesize the available treatment modalities and outcomes of calciphylaxis in patients with CKD.MethodsElectronic databases were searched for studies that examined the uses of sodium thiosulfate, surgical parathyroidectomy, calcimimetics, hyperbaric oxygen therapy, and bisphosphonates for calciphylaxis in patients with CKD, including end-stage renal disease. For cohort studies, the results were synthesized quantitatively by performing random-effects model meta-analyses.ResultsA total of 147 articles met the inclusion criteria and were included in the systematic review. There were 90 case reports (90 patients), 20 case series (423 patients), and 37 cohort studies (343 patients). In the pooled cohorts, case series, and case reports, 50.3% of patients received sodium thiosulfate, 28.7% underwent surgical parathyroidectomy, 25.3% received cinacalcet, 15.3% underwent hyperbaric oxygen therapy, and 5.9% received bisphosphonates. For the subset of cohort studies, by meta-analysis, the pooled risk ratio for mortality was not significantly different among patients who received sodium thiosulfate (pooled risk ratio [RR] 0.89; 95% confidence interval [CI] 0.71–1.12), cinacalcet (pooled RR 1.04; 95% CI 0.75–1.42), hyperbaric oxygen therapy (pooled RR 0.89; 95% CI 0.71–1.12), and bisphosphonates (pooled RR 0.77; 95% CI 0.44–1.32), and those who underwent surgical parathyroidectomy (pooled RR 0.88; 95% CI 0.69–1.13).ConclusionThis systematic review found no significant clinical benefit of the 5 most frequently used treatment modalities for calciphylaxis in patients with CKD. Randomized controlled trials are needed to test the efficacy of these therapies.

Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.

Background Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design Meta-analysis. Setting & Population MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”. Selection Criteria for Studies Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded. Intervention Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD. Outcomes Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary). Results We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications. Limitations Paucity of randomized controlled trials. Conclusions Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed.