In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group ...of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.
Background Acute kidney injury (AKI) is common in hospitalized patients. The impact of AKI on long-term outcomes is controversial. Study Design Systematic review and meta-analysis. Setting & ...Participants Persons with AKI. Selection Criteria for Studies MEDLINE and EMBASE databases were searched from 1985 through October 2007. Original studies describing outcomes of AKI for patients who survived hospital discharge were included. Studies were excluded from review when participants were followed up for less than 6 months. Predictor AKI, defined as acute changes in serum creatinine level or acute need for renal replacement therapy. Outcomes Chronic kidney disease (CKD), cardiovascular disease, and mortality. Results 48 studies that contained a total of 47,017 participants were reviewed; 15 studies reported long-term data for patients without AKI. The incidence rate of mortality was 8.9 deaths/100 person-years in survivors of AKI and 4.3 deaths/100 patient-years in survivors without AKI (rate ratio RR, 2.59; 95% confidence interval, 1.97 to 3.42). AKI was associated independently with mortality risk in 6 of 6 studies that performed multivariate adjustment (adjusted RR, 1.6 to 3.9) and with myocardial infarction in 2 of 2 studies (RR, 2.05; 95% confidence interval, 1.61 to 2.61). The incidence rate of CKD after an episode of AKI was 7.8 events/100 patient-years, and the rate of end-stage renal disease was 4.9 events/100 patient-years. Limitations The relative risk for CKD and end-stage renal disease after AKI was unattainable because of lack of follow-up of appropriate controls without AKI. Conclusions The development of AKI, defined as acute changes in serum creatinine level, characterizes hospitalized patients at increased risk of long-term adverse outcomes.
Background In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. Study Design Longitudinal cohort study. Setting & ...Participants 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. Predictors Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. Outcomes & Measurements Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N -acetyl-β- d -glucosaminidase (NAG), and albumin; serum creatinine–based estimated glomerular filtration rate (eGFR). Results Mean eGFR was 113 mL/min/1.73 m2 and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non–field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, −0.6 to 6.7) mL/min/1.73 m2 , respectively. Limitations Surrogate exposure measure, loss to follow-up. Conclusions Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury.
Abstract Background Acute kidney injury (AKI) is common after cardiac surgery and is associated with post-operative mortality. Perioperative cardiac biomarkers may predict AKI and mortality. ...Objective We evaluated whether cardiac biomarkers were associated with severe AKI, defined as a doubling in serum creatinine or requiring renal replacement therapy during hospital stay after surgery, and mortality. Methods In a prospective multicenter cohort of adults undergoing cardiac surgery, we measured the following biomarkers in pre- and post-operative banked plasma: high-sensitivity troponin T (hs-cTnT), troponin I (cTnI), CK-MB and NT-proBNP. Results In the patients who were discharged alive, severe AKI occurred in 37/960 (3.9%) and 43/960 (4.5%) died within 1 year of follow-up. NT-proBNP was the only pre-operative biomarker that was independently associated with severe AKI (with log transformation, adjusted OR=1.4, 95% CI (1.0, 1.9)). Biomarkers measured within 6 hours of surgery (Day 1) were all associated with severe AKI. Pre-operative NT-proBNP was also independently associated with 1-year mortality (with log transformation, adjusted OR=1.7, 95% CI (1.2-2.2)). Patients in the highest tertile for NT-proBNP pre-operatively (>1006.4 ng/L) had marked increases in their risk for 1-year mortality (adjusted OR=27.2, 95%CI (3.5-213.5)). Day 1 NT-proBNP was associated with mortality independently of change in serum creatinine from pre-operative baseline. Conclusion Of the studied biomarkers, NT-proBNP was the only pre-operative biomarker independently associated with severe AKI and mortality. Early increases in post-operative cardiac biomarkers were associated with severe AKI after cardiac surgery. Future research should focus on whether interventions that lower NT-proBNP can impact upon post-operative outcomes.
Background Intravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. ...Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown. Study Design Retrospective population-based cohort study. Setting & Participants We studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity. Predictor Outpatient prescription for oral acyclovir, valacyclovir, or famciclovir. Outcomes The primary outcome was hospital admission with AKI in the 30 days after the initial prescription. Measurements We assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements. Results 76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 IQR, 71-81 years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 0.27% events with acyclovir or valacyclovir vs 238 0.28% events with famciclovir relative risk, 0.97; 95% CI, 0.81-1.17). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements. Limitations Diagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available. Conclusions In this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir.
Background Monocyte chemotactic protein-1 (MCP-1; chemokine C-C ligand-2 CCL-2) is upregulated in ischemia-reperfusion injury and is a promising biomarker of inflammation in cardiac operations. ...Methods We measured preoperative and postoperative plasma MCP-1 levels in adults undergoing cardiac operations to evaluate the association of perioperative MCP-1 levels with acute kidney injury (AKI) and death in Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI), a prospective, multicenter, observational cohort. Results Of the 972 participants in the study, AKI developed in 329 (34%), and severe AKI developed in 45 (5%). During a median follow-up of 2.9 years (interquartile range, 2.2 to 3.5 years), 119 participants (12%) died. MCP-1 levels were significantly higher in those who developed AKI and died than in those without AKI and death. Participants with a preoperative MCP-1 level in the highest tertile (>196 pg/mL) had an increased AKI risk than those in the lowest tertile (<147 pg/mL; odds ratio OR, 1.43l; 95% confidence interval CI, 1.00 to 2.05). The association appeared similar but was not significant for the severe AKI outcome (OR, 1.48; 95% CI, 0.62 to 3.54). Compared with participants with preoperative MCP-1 level in the lowest tertile, those in the highest tertile had higher adjusted risk of death (hazard ratio, 1.82; 95% CI, 1.40 to 2.38). Similarly, participants in the highest tertile had a higher adjusted risk of death (hazard ratio, 1.95; 95% CI, 1.09–3.49) than those with a postoperative MCP-1 level in the lowest tertile. Conclusions Higher plasma MCP-1 is associated with increased AKI and risk of death after cardiac operations. MCP-1 could be used as a biomarker to identify high-risk patients for potential AKI prevention strategies in the setting of cardiac operations.
Background Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and ...may increase earlier in AKI than serum creatinine level. Study Design Prospective cohort study. Settings & Participants The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents at 8 institutions in 2007-2009. Index Test Urinary CysC (in milligrams per liter) within the first 12 hours after surgery. Outcome Serum creatinine–based AKI was defined as AKI Network stage 1 (mild AKI) and doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization (severe AKI). Other Measurements Analyses were adjusted for characteristics used clinically for AKI risk stratification, including age, sex, race, estimated glomerular filtration rate, diabetes, hypertension, heart failure, nonelective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time longer than 120 minutes. Results Urinary CysC level measured in the early postoperative period (0-6 and 6-12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However, after analyses were adjusted for other factors, the effect was attenuated for both forms of AKI in both cohorts. Limitations Limited numbers of patients with severe AKI and in-hospital dialysis treatment. Conclusions Urinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children.
Background The primary aim of this study was to compare the sensitivity and rapidity of acute kidney injury (AKI) detection by cystatin C level relative to creatinine level after cardiac surgery. ...Study Design Prospective cohort study. Settings & Participants 1,150 high-risk adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. Predictor Changes in serum creatinine and cystatin C levels. Outcome Postsurgical incidence of AKI. Measurements Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1-5. To allow comparisons between changes in creatinine and cystatin C levels, AKI end points were defined by the relative increases in each marker from baseline (25%, 50%, and 100%) and the incidence of AKI was compared based on each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine levels. Results Overall, serum creatinine level detected more cases of AKI than cystatin C level: 35% developed a ≥25% increase in serum creatinine level, whereas only 23% had a ≥25% increase in cystatin C level ( P < 0.001). Creatinine level also had higher proportions meeting the 50% (14% and 8%; P < 0.001) and 100% (4% and 2%; P = 0.005) thresholds for AKI diagnosis. Clinical outcomes generally were not statistically different for AKI cases detected by creatinine or cystatin C level. However, for each AKI threshold, patients with AKI confirmed by both markers had a significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine level alone ( P = 0.002). Limitations There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based on their definitions of AKI. Conclusions In this large multicenter study, we found that cystatin C level was less sensitive for AKI detection than creatinine level. However, confirmation by cystatin C level appeared to identify a subset of patients with AKI with a substantially higher risk of adverse outcomes.
Background Recently, acute kidney injury defined by small changes in serum creatinine levels was associated with worse short-term outcomes; however, the precision and variability of this association ...was not fully explored. Study Design Systematic review and meta-analysis. Setting & Participants Hospitalized patients. Selection Criteria for Studies MEDLINE and EMBASE databases were searched for observational cohort studies and randomized controlled trials published from 1990 through February 2007 that provided information for small changes in serum creatinine levels. Predictor Small acute changes in serum creatinine levels by absolute and percentage of changes in serum creatinine levels (lower threshold for increase in serum creatinine <0.5 mg/dL or <25%). Outcome Short-term mortality (≤30 days). Results Compared with controls, patients with a 10% to 24% increase in creatinine levels had a relative risk (RR) of death of 1.8 (95% confidence interval CI, 1.3 to 2.5). By comparison, subjects with a 25% to 49% acute change in creatinine levels had an RR of death of 3.0 (95% CI, 1.6 to 5.8), and those with the largest change (≥50%) had the greatest RR of death (RR, 6.9; 95% CI, 2.0 to 24.5). Results were similar when absolute changes in creatinine levels were considered and when pooled estimates of adjusted RR were used. Limitations Individual patient data were unavailable; thus, only group-level data were pooled for meta-analysis. Results showed a significant degree of statistical heterogeneity that was only partially ameliorated by separating studies into subsets based on clinical setting. Conclusions Short-term mortality and acute decreases in renal function are associated through a graded relationship such that even mild changes in serum creatinine levels portend worse outcome in a variety of clinical settings and patient-types.
Background Acute kidney injury (AKI) after cardiac surgery is associated with worse outcomes. However, it is not known how adverse long-term consequences vary according to the duration of AKI. We ...sought to determine the association between duration of AKI and survival. Methods Medical records of 4,987 cardiac surgery patients from 2002 through 2007 with serum creatinine (SCr) collection at a medical center in northern New England were reviewed. Acute kidney injury was defined as at least a 0.3 (mg/dL) or at least a 50% increase in SCr from baseline and further classified into AKI Network stages. Duration of AKI was defined by the number of days AKI was present and categorized as no AKI and AKI for 1 to 2, 3 to 6, and at least 7 days. Results Thirty-nine percent of patients exhibited AKI. Long-term survival was significantly different by AKI duration ( p < 0.001). The proportion of patients with AKI duration, adjusted hazard ratio, and 95% confidence interval for mortality (no AKI as referent) were as follows: 1 to 2 days (18%; adjusted hazard ratio, 1.66; 95% confidence interval, 1.32 to 2.09), 3 to 6 days (11%; adjusted hazard ratio, 1.94; 95% confidence interval, 1.51 to 2.49), ≥7 days (9%; adjusted hazard ratio, 3.40; 95% confidence interval, 2.73 to 4.25). This graded relationship of duration of AKI with long-term mortality persisted when patients who died during hospitalization were excluded from analysis ( p < 0.001). Propensity-matched analysis confirmed results. Conclusions The duration of AKI after cardiac surgery is directly proportional to long-term mortality. This AKI dose-dependent effect on long-term mortality helps to close the gap between association and causation, whereby AKI stages and AKI duration have important implications for patient care and can aid clinicians in evaluating the risk of in-hospital and postdischarge death.
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