World incidence of AKI: a meta-analysis.
BACKGROUND AND OBJECTIVES The burden of AKI around the globe has not been systematically examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic review (2004-2012) 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. Random-effects 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 AKI-associated 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.
Calciphylaxis from nonuremic causes: a systematic review.
BACKGROUND AND OBJECTIVES Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes. This systematic review was designed to characterize etiologies, clinical features, laboratory abnormalities, and prognosis of nonuremic calciphylaxis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic review of literature for case reports and case series of nonuremic calciphylaxis was performed. Cases included met the operational definition of nonuremic calciphylaxis-histopathologic diagnosis of calciphylaxis in the absence of end-stage kidney disease, renal transplantation, or acute kidney injury requiring renal replacement therapy. RESULTS We found 36 cases (75% women, 63% Caucasian, aged 15 to 82 yr) of nonuremic calciphylaxis. Primary hyperparathyroidism, malignancy, alcoholic liver disease, and connective tissue disease were the most common reported causes. Preceding corticosteroid use was reported for 61% patients. Protein C and S deficiencies were seen in 11% of patients. Skin lesions were morphologically similar to calcific uremic arteriolopathy. Mortality rate was 52%, with sepsis being the leading cause of death. CONCLUSION Calciphylaxis should be considered while evaluating skin lesions in patients with predisposing conditions even in the absence of end-stage kidney disease and renal transplantation. Nonuremic calciphylaxis is reported most often in white women. Mineral abnormalities that are invoked as potential causes in calcific uremic arteriolopathy are often absent, suggesting that heterogeneous mechanisms may contribute to its pathogenesis. Nonuremic calciphylaxis is associated with high mortality, and there is no known effective treatment.
Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus.
BACKGROUND AND OBJECTIVES Prior studies have examined long-term outcomes of a single acute kidney injury (AKI) event in hospitalized patients. We examined the effects of AKI episodes during multiple hospitalizations on the risk of chronic kidney disease (CKD) in a cohort with diabetes mellitus (DM). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 4082 diabetics were followed from January 1999 until December 2008. The primary outcome was reaching stage 4 CKD (GFR of <30 ml/min per 1.73 m(2)). AKI during hospitalization was defined as >0.3 mg/dl or a 1.5-fold increase in creatinine relative to admission. Cox survival models examined the effect of first AKI episode and up to three episodes as time-dependent covariates, on the risk of stage 4 CKD. Covariates included demographic variables, baseline creatinine, and diagnoses of comorbidities including proteinuria. RESULTS Of the 3679 patients who met eligibility criteria (mean age = 61.7 years [SD, 11.2]; mean baseline creatinine = 1.10 mg/dl [SD, 0.3]), 1822 required at least one hospitalization during the time under observation (mean = 61.2 months [SD, 25]). Five hundred thirty of 1822 patients experienced one AKI episode; 157 of 530 experienced ≥2 AKI episodes. In multivariable Cox proportional hazards models, any AKI versus no AKI was a risk factor for stage 4 CKD (hazard ratio [HR], 3.56; 95% confidence interval [CI], 2.76, 4.61); each AKI episode doubled that risk (HR, 2.02; 95% CI, 1.78, 2.30). CONCLUSIONS AKI episodes are associated with a cumulative risk for developing advanced CKD in diabetes mellitus, independent of other major risk factors of progression.
Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury.
BACKGROUND AND OBJECTIVES Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury (AKI). Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase. The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospective study of 123 adults undergoing cardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth factor (HGF), π-glutathione-S-transferase (π-GST), α-GST, and fractional excretions of sodium and urea were all measured at preoperative baseline, postoperatively, and at the time of the initial clinical diagnosis of AKI. Receiver operator characteristic curves were generated and the areas under the curve (AUCs) were compared. RESULTS Forty-six (37.4%) subjects developed AKI Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1 and α-GST were able to predict the future development of stage 1 and stage 3 AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1 AKI (AUC = 0.70, P < 0.001); the 6-hour ICU NGAL (AUC = 0.88; P < 0.001) best detected early stage 3 AKI. π-GST best predicted the progression to stage 3 AKI at the time of creatinine increase (AUC = 0.86; P = 0.002). CONCLUSION Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.
Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury.
BACKGROUND AND OBJECTIVES Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury (AKI). Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase. The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospective study of 123 adults undergoing cardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth factor (HGF), π-glutathione-S-transferase (π-GST), α-GST, and fractional excretions of sodium and urea were all measured at preoperative baseline, postoperatively, and at the time of the initial clinical diagnosis of AKI. Receiver operator characteristic curves were generated and the areas under the curve (AUCs) were compared. RESULTS Forty-six (37.4%) subjects developed AKI Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1 and α-GST were able to predict the future development of stage 1 and stage 3 AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1 AKI (AUC = 0.70, P < 0.001); the 6-hour ICU NGAL (AUC = 0.88; P < 0.001) best detected early stage 3 AKI. π-GST best predicted the progression to stage 3 AKI at the time of creatinine increase (AUC = 0.86; P = 0.002). CONCLUSION Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.
Ascertainment and epidemiology of acute kidney injury varies with definition interpretation.
BACKGROUND AND OBJECTIVES Differences in defining acute kidney injury (AKI) may impact incidence ascertainment. We assessed the effects of different AKI definition interpretation methods on epidemiology ascertainment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Two groups were studied at Texas Children's Hospital, Houston, Texas: 150 critically ill children (prospective) and 254 noncritically ill, hospitalized children receiving aminoglycosides (retrospective). SCr was collected for 14 d in the prospective study and 21 d in the retrospective study. Children with known baseline serum creatinine (bSCr) were classified by the pediatric Risk, Injury, Failure, Loss, End-Stage Kidney Disease (pRIFLE) AKI definition using SCr change (pRIFLE(DeltaSCr)), estimated creatinine clearance (eCCl) change (pRIFLE(DeltaCCl)), and the Acute Kidney Injury Network (AKIN) definition. In subjects without known bSCr, bSCR was estimated as eCCl = 100 (eCCl(100)) and 120 ml/min per 1.73 m(2) (eCCl(120)), admission SCr (AdmSCr) and lower/upper normative values (NormsMin, NormsMax). The differential impact of each AKI definition interpretation on incidence estimation and severity distribution was evaluated. RESULTS pRIFLE(DeltaSCr) and AKIN led to identical AKI distributions. pRIFLE(DeltaCCl) resulted in 14.5% (critically ill) and 11% (noncritical) more patients diagnosed with AKI compared to other methods (P 0.05). Different bSCr estimates led to differences in AKI incidence, from 12% (AdmSCr) to 87.8% (NormsMin) (P 0.05) in the critically ill group and from 4.6% (eCCl(100)) to 43.1% (NormsMin) (P 0.05) in the noncritical group. CONCLUSIONS AKI definition variation causes interstudy heterogeneity. AKI definition should be standardized so that results can be compared across studies.
Low urine pH: a novel feature of the metabolic syndrome.
BACKGROUND AND OBJECTIVES The metabolic syndrome is associated with alterations in renal function. An overly acidic urine has been described as a renal manifestation of the metabolic syndrome in patients with kidney stone disease. This study examined the association between the metabolic syndrome and urine pH in individuals without a history of nephrolithiasis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 148 adults who were free of kidney stones were evaluated in this outpatient cross-sectional study. Height, weight, BP, fasting blood, and 24-h urine chemistries were obtained. Urine pH was measured by pH electrode. The following features of the metabolic syndrome were evaluated: BP; body mass index; and serum triglyceride, glucose, and HDL cholesterol concentrations. The degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance. RESULTS Participants with the metabolic syndrome had a significantly lower 24-h urine pH compared with participants without the metabolic syndrome. Mean 24-h urine pH, adjusted for age, gender, creatinine clearance, and 24-h urine sulfate, decreased from 6.15, 6.10, 5.99, 5.85, to 5.69 with increasing number of metabolic syndrome abnormalities. An association was observed between 24-h urine pH and each metabolic feature. After adjustment for age, gender, creatinine clearance, urine sulfate, and body mass index, a significant inverse relationship was noted between 24-h urine pH and the degree of insulin resistance. CONCLUSIONS An unduly acidic urine is a feature of the metabolic syndrome and is associated with the degree of insulin resistance.
Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES Addition of aldosterone antagonists (AA) might provide renal benefits to proteinuric chronic kidney disease (CKD) patients over and above the inhibition of renin-angiotensin system blockers (RAS). We evaluated the benefits and harms of adding selective and nonselective AA in CKD patients already on RAS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS MEDLINE, EMBASE, and Renal Health Library were searched for relevant randomized clinical trials in adult CKD patients. Results were summarized using the random-effects model. RESULTS Eleven trials (991 patients) were included. In comparison to angiotensin- converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) plus placebo, nonselective AA along with ACEi and/or ARB significantly reduced 24 h proteinuria (seven trials, 372 patients, weighted mean difference [WMD] -0.80 g, 95% CI -1.27, -0.33) and BP. This did not translate into an improvement in GFR (WMD -0.70 ml/min/1.73m(2), 95% CI -4.73, 3.34). There was a significant increase in the risk of hyperkalemia with the addition of nonselective AA to ACEi and/or ARB (relative risk 3.06, 95% CI 1.26, 7.41). In two trials, addition of selective AA to ACEi resulted in an additional reduction in 24 h proteinuria, without any impact on BP and renal function. Data on cardiovascular outcomes, long-term renal outcomes and mortality were not available in any of the trials. CONCLUSIONS Aldosterone antagonists reduce proteinuria in CKD patients already on ACEis and ARBs but increase the risk of hyperkalemia. Long-term effects of these agents on renal outcomes, mortality, and safety need to be established.
Mortality in kidney disease patients treated with phosphate binders: a randomized study.
BACKGROUND AND OBJECTIVES Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification (CAC) that may contribute to high mortality of dialysis patients. CAC has been found in patients in early stages of nondialysis-dependent CKD. In this population, no study has evaluated the potential role of phosphorus binders on mortality. This study aimed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients randomized to different phosphate binders; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This is a randomized, multicenter, nonblinded pilot study. Consecutive outpatients (n=212; stage 3-4 CKD) were randomized to either sevelamer (n=107) or calcium carbonate (n=105). Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3-4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD. The CAC score was assessed by computed tomography at study entry and after 6, 12, 18, and 24 months. All-cause mortality, dialysis inception, and the composite end point were recorded for up to 36 months. RESULTS In patients randomized to sevelamer, all-cause mortality and the composite end point were lower; a nonsignificant trend was noted for dialysis inception. CONCLUSIONS Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception. Larger studies are needed to confirm these results.
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