Charuhas V. Thakar

A Clinical Score to Predict Acute Renal Failure after Cardiac Surgery

The risk of mortality associated with acute renal failure (ARF) after open-heart surgery continues to be distressingly high. Accurate prediction of ARF provides an opportunity to develop strategies for early diagnosis and treatment. The aim of this study was to develop a clinical score to predict postoperative ARF by incorporating the effect of all of its major risk factors. A total of 33,217 patients underwent open-heart surgery at the Cleveland Clinic Foundation (1993 to 2002). The primary outcome was ARF that required dialysis. The scoring model was developed in a randomly selected test set (n = 15,838) and was validated on the remaining patients. Its predictive accuracy was compared by area under the receiver operating characteristic curve. The score ranges between 0 and 17 points. The ARF frequency at each score level in the validation set fell within the 95% confidence intervals (CI) of the corresponding frequency in the test set. Four risk categories of increasing severity (scores 0 to 2, 3 to 5, 6 to 8, and 9 to 13) were formed arbitrarily. The frequency of ARF across these categories in the test set ranged between 0.5 and 22.1%. The score was also valid in predicting ARF across all risk categories. The area under the receiver operating characteristic curve for the score in the test set was 0.81 (95% CI 0.78 to 0.83) and was similar to that in the validation set (0.82; 95% CI 0.80 to 0.85; P = 0.39). In conclusion, a score is valid and accurate in predicting ARF after open-heart surgery; along with increasing its clinical utility, the score can help in planning future clinical trials of ARF.

Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study.

Objectives:To examine the effect of severity of acute kidney injury or renal recovery on risk-adjusted mortality across different intensive care unit settings. Acute kidney injury in intensive care unit patients is associated with significant mortality. Design:Retrospective observational study. Setting:There were 325,395 of 617,927 consecutive admissions to all 191 Veterans Affairs ICUs across the country. Patients:Large national cohort of patients admitted to Veterans Affairs ICUs and who developed acute kidney injury during their intensive care unit stay. Measurements and Main Results:Outcome measures were hospital mortality, and length of stay. Acute kidney injury was defined as a 0.3-mg/dL increase in creatinine relative to intensive care unit admission and categorized into Stage I (0.3 mg/dL to <2 times increase), Stage II (≥2 and <3 times increase), and Stage III (≥3 times increase or dialysis requirement). Association of mortality and length of stay with acute kidney injury stages and renal recovery was examined. Overall, 22% (n = 71,486) of patients developed acute kidney injury (Stage I: 17.5%; Stage II: 2.4%; Stage III: 2%); 16.3% patients met acute kidney injury criteria within 48 hrs, with an additional 5.7% after 48 hrs of intensive care unit admission. Acute kidney injury frequency varied between 9% and 30% across intensive care unit admission diagnoses. After adjusting for severity of illness in a model that included urea and creatinine on admission, odds of death increased with increasing severity of acute kidney injury. Stage I odds ratio = 2.2 (95% confidence interval, 2.17–2.30); Stage II odds ratio = 6.1 (95% confidence interval, 5.74, 6.44); and Stage III odds ratio = 8.6 (95% confidence interval, 8.07–9.15). Acute kidney injury patients with sustained elevation of creatinine experienced higher mortality risk than those who recovered. Interventions:None. Conclusions:Admission diagnosis and severity of illness influence frequency and severity of acute kidney injury. Small elevations in creatinine in the intensive care unit are associated with increased risk-adjusted mortality across all intensive care unit settings, whereas renal recovery was associated with a protective effect. Strategies to prevent even mild acute kidney injury or promote renal recovery may improve survival.

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.

KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury

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.

ARF after open-heart surgery: Influence of gender and race.

BACKGROUND Both acute renal failure (ARF) and female sex are strongly associated with mortality after open-heart surgery. This study analyzes the effect of sex and race on the incidence of ARF after open-heart surgery and its influence on mortality. METHODS A total of 24,660 patients underwent open-heart surgery at the Cleveland Clinic Foundation (Cleveland, OH) from 1993 to 2000. The primary outcome was ARF defined as ARF requiring dialysis, 50% or greater decline in glomerular filtration rate (GFR) not requiring dialysis, or 50% or greater decline in GFR relative to baseline or requirement of dialysis. The secondary outcome was all-cause hospital mortality. RESULTS The overall frequency of ARF requiring dialysis after open-heart surgery was 1.82%. The frequency was greater in women (2.36%) than men (1.60%; P < 0.0001) and blacks (2.94%) than nonblacks (1.70%; P < 0.0001) by univariate analysis. By multivariate analysis, risk for ARF requiring dialysis in women was 1.61 (confidence interval [CI], 1.27 to 2.05; P < 0.0001), but race was not a risk factor. The overall postoperative mortality rate was 2.2%, and for patients with ARF requiring dialysis, it was 61.2% (women, 68.6% versus men, 56.5%; P = 0.01) with an odds ratio of 49.29, whereas in patients with ARF not requiring dialysis, it was 14.1% (women, 13.3% versus men 14.6%; P = 0.63) with an odds ratio of 7.18. CONCLUSION Female sex is an independent risk factor for developing ARF after open-heart surgery. The influence of race on risk for ARF is less clear. Regardless of its definition, ARF is strikingly associated with a high risk for mortality.

Off-Pump Coronary Artery Bypass Surgery and Acute Kidney Injury: A Meta-analysis of Randomized and Observational Studies

BACKGROUND Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with significant morbidity and mortality. Controversy exists regarding whether an off-pump technique can reduce post-CABG renal injury. STUDY DESIGN Systematic review and meta-analysis. SETTING & POPULATION Adult patients undergoing CABG. SELECTION CRITERIA FOR STUDIES MEDLINE, EMBASE, Cochrane Renal Library, and Google Scholar were searched in May 2008 for randomized controlled trials (RCTs) and observational studies comparing off-pump CABG (OPCAB) with conventional CABG (CAB) for renal outcomes. Studies involving patients on long-term renal replacement therapy (RRT) were excluded. INTERVENTION OPCAB. OUTCOMES Primary outcomes were overall AKI and AKI requiring RRT. RESULTS 22 studies (6 RCTs and 16 observational studies) comprising 27,806 patients met the inclusion criteria. The pooled effect from both study cohorts showed a significant reduction in overall AKI (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.43 to 0.76; P for effect < 0.001; I(2) = 67%; P for heterogeneity < 0.001) and AKI requiring RRT (OR, 0.55; 95% CI, 0.43 to 0.71; P for effect < 0.001; I(2) = 0%; P for heterogeneity = 0.5) in the OPCAB group compared with the CAB group. In RCTs, overall AKI was significantly reduced in the OPCAB group (OR, 0.27; 95% CI, 0.13 to 0.54); however, no statistically significant difference was noted in AKI requiring RRT (OR, 0.31; 95% CI, 0.06 to 1.59). In the observational cohort, both overall AKI (OR, 0.61; 95% CI, 0.45 to 0.81) and AKI requiring RRT (OR, 0.54; 95% CI, 0.40 to 0.73) were significantly less in the OPCAB group. RCTs were noted to be underpowered and biased toward recruiting low-risk patients. Sensitivity analysis restricted to good-quality studies showed a significant reduction in AKI. LIMITATIONS Lack of uniform AKI definition in the included studies, heterogeneity for overall AKI outcome. CONCLUSIONS Analysis of the current evidence suggests a reduction in AKI using the OPCAB technique; however, studies lack consistency in defining AKI. Available RCTs are underpowered to detect a difference in AKI requiring RRT; evidence from observational studies suggests a reduction in RRT requirement. Future studies should apply a standard definition of AKI and target a high-risk population.

Acute Kidney Injury after Gastric Bypass Surgery

Gastric bypass surgery is a common treatment for morbid obesity. The presence of comorbid conditions and drugs that are used to treat them can adversely influence kidney function. Risk factors and outcomes of acute kidney injury (AKI) after gastric bypass surgery are not well understood, however. A total of 504 patients underwent gastric bypass between January 2003 and 2005. Primary outcome was AKI, defined as a > or =50% increase in serum creatinine relative to baseline or requirement of dialysis. Secondary outcomes were duration of hospitalization, all-cause hospital mortality, and readmissions within 30 d after surgery. Demographic, comorbid, and laboratory variables and preoperative medication use were examined as potential risk factors for AKI. A total of 42 (8.5%) patients developed postoperative AKI. Hyperlipidemia, preoperative use of angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB), intraoperative hypotension, and higher body mass index were associated with increased frequency of AKI. By multivariable analyses, the independent risk factors for AKI were body mass index (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.00 to 1.06), hyperlipidemia (OR 2.53; 95% CI 1.21 to 5.28), and preoperative use of ACE-I or ARB (OR 2.06; 95% CI 1.05 to 4.04). The postoperative mortality was 0.45% (n = 2), both of whom had AKI. Duration of hospitalization was greater in patients with AKI versus no AKI (4.0 versus 2.7 d; P = 0.0003). Postoperative AKI is not infrequent after gastric bypass surgery. Certain comorbid conditions and their commonly prescribed treatments, ACE-I or ARB, are independently associated with increased risk for postoperative AKI.

Identification of thrombospondin 1 (TSP-1) as a novel mediator of cell injury in kidney ischemia

Thrombospondin 1 (TSP-1) is a matricellular protein that inhibits angiogenesis and causes apoptosis in vivo and in vitro in several cancerous cells and tissues. Here we identify TSP-1 as the molecule with the highest induction level at 3 hours of IR injury in rat and mouse kidneys subjected to ischemia/reperfusion (IR) injury using the DNA microarray approach. Northern hybridizations demonstrated that TSP-1 expression was undetectable at baseline, induced at 3 and 12 hours, and returned to baseline levels at 48 hours of reperfusion. Immunocytochemical staining identified the injured proximal tubules as the predominant sites of expression of TSP-1 in IR injury and showed colocalization of TSP-1 with activated caspase-3. Addition of purified TSP-1 to normal kidney proximal tubule cells or cells subjected to ATP depletion in vitro induced injury as demonstrated by cytochrome c immunocytochemical staining and caspase-3 activity. The deleterious role of TSP-1 in ischemic kidney injury was demonstrated directly in TSP-1 null mice, which showed significant protection against IR injury-induced renal failure and tubular damage. We propose that TSP-1 is a novel regulator of ischemic damage in the kidney and may play an important role in the pathophysiology of ischemic kidney failure.

Perioperative Acute Kidney Injury

The incidence of acute kidney injury (AKI) is generally 5-7.5% in all acute care hospitalizations and accounts for up to 20% of admissions to intensive care units (ICUs). Of all of the cases of AKI during hospitalization, approximately 30-40% are observed in operative settings. AKI is a serious morbidity that is associated with greater length of hospital stay, high risk of hospital mortality, and increased risk of incident and progressive chronic kidney disease. The incidence of AKI is variable depending on the specific surgical setting under consideration. Much of our knowledge regarding the epidemiology of AKI is derived from studies related to cardiac or vascular surgery. With limited treatment options, prevention of AKI and amelioration of its severity remain important cornerstones of improving patient outcomes. The magnitude of the problem and the unique set of patient characteristics calls for a multidisciplinary approach for the perioperative management of renal complications. The purpose of the review presented here is to discuss the current knowledge regarding the epidemiology and risk factors, outcomes, diagnoses, and prevention and treatment of AKI during the perioperative period in cardiovascular and noncardiovascular surgical settings.

Effect of off-pump coronary artery bypass graft surgery on postoperative acute kidney injury and mortality

Objective:Risk of mortality after cardiac surgery is associated with severity of acute kidney injury. The aim of this study is to examine the effect of off-pump coronary artery bypass surgery on the risk of postoperative acute kidney injury and its association with mortality. Design:Observational cohort study. Setting:Tertiary care center. Patients:Some 10,061 patients underwent coronary artery bypass surgery (1998–2002), of which 1,365 patients underwent off-pump surgery. Interventions:Acute kidney injury was defined as either requirement of dialysis or ≥50% decline in postoperative glomerular filtration rate but not requiring dialysis. We compared on- and off-pump surgeries and used propensity score matching to examine the effect of off-pump surgery on acute kidney injury and mortality. Measurements and Main Results:We found that 2.6% on-pump and 1.2% off-pump patients developed acute kidney injury requiring dialysis among the 2,370 matched subjects (relative risk, 2.06; 95% confidence interval [CI], 1.36–3.36); 5.0% of on-pump patients suffered a ≥50% decline in glomerular filtration rate compared with 2.5% in off-pump group (relative risk, 2.00; 95% CI, 1.48–2.82). The mortality rate in the matched cohort was 2.3% for on-pump group vs. 0.6% in off-pump group (relative risk, 3.88; 95% CI, 2.29–9.50). Among matched patients with acute kidney injury, the risk of mortality was 13.14 (95% CI, 8.43–30.50) in patients requiring dialysis and 9.33 (95% CI, 4.83–19.00) in those with ≥50% decline in glomerular filtration rate but not requiring dialysis. Conclusions:Off-pump surgery is associated with a lower risk of developing acute kidney injury (regardless of its definition). The risk of mortality is incremental with worsening degrees of acute kidney injury. Lower risk of acute kidney injury may be one of the factors that offer a survival advantage after off-pump surgery.