Ashita Tolwani

Septic Acute Kidney Injury in Critically Ill Patients: Clinical Characteristics and Outcomes

Sepsis is the most common cause of acute kidney injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective, observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753 patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters, greater severity of illness, and higher need for mechanical ventilation and vasoactive therapy. There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy (RRT; 72 versus 71%; P = 0.83). Oliguria was more common in septic AKI (67 versus 57%; P < 0.001). Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI (70.2 versus 51.8%; P < 0.001). After adjustment for covariates, septic AKI remained associated with higher odds for death (1.48; 95% confidence interval 1.17 to 1.89; P = 0.001). Median (IQR) duration of hospital stay for survivors (37 [19 to 59] versus 21 [12 to 42] d; P < 0.0001) was longer for septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to 184] mumol/L; P = 0.01) and RRT dependence (9 versus 14%; P = 0.052) at hospital discharge for septic AKI. Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology. Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT.

Standard versus High-Dose CVVHDF for ICU-Related Acute Renal Failure

The effect of dosage of continuous venovenous hemodiafiltration (CVVHDF) on survival in patients with acute renal failure (ARF) is unknown. In this study, 200 critically ill patients with ARF were randomly assigned to receive CVVHDF with prefilter replacement fluid at an effluent rate of either 35 ml/kg per h (high dosage) or 20 ml/kg per h (standard dosage). The primary study outcome, survival to the earlier of either intensive care unit discharge or 30 d, was 49% in the high-dosage arm and 56% in the standard-dosage arm (odds ratio 0.75; 95% confidence interval 0.43 to 1.32; P = 0.32). Among hospital survivors, 69% of those in the high-dosage arm recovered renal function compared with 80% of those in the standard-dosage arm (P = 0.29); therefore, a difference in patient survival or renal recovery was not detected between patients receiving high-dosage or standard-dosage CVVHDF.

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.

Efficacy and Safety of Renal Tubule Cell Therapy for Acute Renal Failure

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.

A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury

BACKGROUND The RIFLE classification scheme for acute kidney injury (AKI) is based on relative changes in serum creatinine (SCr) and on urine output. The SCr criteria, therefore, require a pre-morbid baseline value. When unknown, current recommendations are to estimate a baseline SCr by the MDRD equation. However, the MDRD approach assumes a glomerular filtration rate of approximately 75 mL/min/1.73 m(2). This method has not been validated. METHODS Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. RESULTS Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 micromol/L (79-150) for oSCr and 88 micromol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. CONCLUSIONS While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

Outcomes of critically ill children requiring continuous renal replacement therapy

PURPOSE Acute kidney injury in the pediatric intensive care unit (PICU) is associated with significant morbidity, with continued mortality greater than 50%. Previous studies have described an association between percentage of fluid overload (%FO) less than 20% and improved survival. We reviewed our continuous renal replacement therapy (CRRT) experience to evaluate for factors associated with mortality as well as secondary outcomes. MATERIALS AND METHODS This is a retrospective chart review of pediatric CRRT intensive care unit patients from January 2000 to September 2005. RESULTS Seventy-six admissions required CRRT during the study period. Overall survival was 55.3%. Median patient age was 5.8 years (range, 0-18.9). Median %FO at the time of CRRT initiation was 7.3% in survivors vs 22.3% in nonsurvivors (P = .0001). Presence of sepsis was significantly associated with mortality (P = .0001). All nonsurvivors had multiple organ dysfunction syndrome (MODS); only 69% of survivors had MODS (P = .0003). For survivors, there was a significant relationship between %FO and time to renal recovery (P = .0038). Greater %FO was also associated with significantly prolonged days of mechanical ventilation (P = .0180), PICU stay (P = .0425), and duration of hospitalization (P = .0123). CONCLUSIONS For patients with acute kidney injury who require CRRT, the presence of sepsis, MODS, and FO greater than 20% at the time of CRRT initiation are significantly associated with higher mortality. In addition, we report that duration of mechanical ventilation, PICU stay, hospitalization, and time to renal recovery were all significantly prolonged for survivors who had FO greater than 20%.

Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study*

Objectives:To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes. However, there is lack of information on how and under what conditions continuous renal replacement therapy is discontinued. Design:Post hoc analysis of a prospective observational study. Setting:Fifty-four intensive care units in 23 countries. Patients:Five hundred twenty-nine patients (52.6%) who survived initial therapy among 1006 patients treated with continuous renal replacement therapy. Interventions:None. Measurements and Main Results:Three hundred thirteen patients were removed successfully from continuous renal replacement therapy and did not require any renal replacement therapy for at least 7 days and were classified as the “success” group and the rest (216 patients) were classified as the “repeat-RRT” (renal replacement therapy) group. Patients in the “success” group had lower hospital mortality (28.5% vs. 42.7%, p < .0001) compared with patients in the “repeat-RRT” group. They also had lower creatinine and urea concentrations and a higher urine output at the time of stopping continuous renal replacement therapy. Multivariate logistic regression analysis for successful discontinuation of continuous renal replacement therapy identified urine output (during the 24 hrs before stopping continuous renal replacement therapy: odds ratio, 1.078 per 100 mL/day increase) and creatinine (odds ratio, 0.996 per &mgr;mol/L increase) as significant predictors of successful cessation. The area under the receiver operating characteristic curve to predict successful discontinuation of continuous renal replacement therapy was 0.808 for urine output and 0.635 for creatinine. The predictive ability of urine output was negatively affected by the use of diuretics (area under the receiver operating characteristic curve, 0.671 with diuretics and 0.845 without diuretics). Conclusions:We report on the current practice of discontinuing continuous renal replacement therapy in a multinational setting. Urine output at the time of initial cessation of continuous renal replacement therapy was the most important predictor of successful discontinuation, especially if occurring without the administration of diuretics.

A Practical Citrate Anticoagulation Continuous Venovenous Hemodiafiltration Protocol for Metabolic Control and High Solute Clearance

Obstacles to the widespread use of continuous renal replacement therapy (CRRT) include the need for anticoagulation, customized solutions, and complex protocols that carry an attendant risk for error, raise cost, and increase pharmacy and nursing workload. However, high solute clearance using CRRT with an effluent rate of 35 ml/kg per h has also recently been associated with improved survival in critically ill patients with acute renal failure. No published CRRT protocols using dilute regional citrate anticoagulation have achieved adequate metabolic control, effective anticoagulation, and high solute clearance in a practical, user-friendly, and economical manner. The safety and the efficacy of continuous venovenous hemodiafiltration at effluent rates of 35 ml/kg per h in critically ill acute renal failure patients were evaluated prospectively using a standardized bicarbonate-based dialysate; a systemic calcium infusion; and two separate trisodium citrate replacement solutions, a 0.67% solution and a 0.5% solution. All patients achieved adequate metabolic control, the desired effluent rate of 35 ml/kg per h, and high solute clearance. Use of the 0.67% citrate replacement solution resulted in mild alkalosis, whereas the 0.5% solution maintained appropriate acid-base balance. There was no difference in dialyzer survival between the 0.67 and 0.5% citrate groups (80 versus 82%; P = 0.60, Kaplan-Meier analysis). Dilute regional citrate as part of a CRRT protocol with a standard 25-mmol/L bicarbonate dialysate provides adequate metabolic control, high diffusive and convective clearance, and excellent dialyzer patency in a practical and cost-effective manner.

Hepatorenal syndrome: the 8th international consensus conference of the Acute Dialysis Quality Initiative (ADQI) Group

IntroductionRenal dysfunction is a common complication in patients with end-stage cirrhosis. Since the original publication of the definition and diagnostic criteria for the hepatorenal syndrome (HRS), there have been major advances in our understanding of its pathogenesis. The prognosis of patients with cirrhosis who develop HRS remains poor, with a median survival without liver transplantation of less than six months. However, a number of pharmacological and other therapeutic strategies have now become available which offer the ability to prevent or treat renal dysfunction more effectively in this setting. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies.MethodsWe undertook a systematic review of the literature using Medline, PubMed and Web of Science, data provided by the Scientific Registry of Transplant Recipients and the bibliographies of key reviews. We determined a list of key questions and convened a two-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research.ResultsOf the 30 questions considered, we found inadequate evidence for the majority of questions and our recommendations were mainly based on expert opinion. There was insufficient evidence to grade three questions, but we were able to develop a consensus definition for acute kidney injury in patients with cirrhosis and provide consensus recommendations for future investigations to address key areas of uncertainty.ConclusionsDespite a paucity of sufficiently powered prospectively randomized trials, we were able to establish an evidence-based appraisal of this field and develop a set of consensus recommendations to standardize care and direct further research for patients with cirrhosis and renal dysfunction.

Continuous Renal-Replacement Therapy for Acute Kidney Injury

Acute kidney injury develops in a 20-year-old man with Marfans syndrome after aortic-valve replacement complicated by thoracic aortic dissection. Continuous renal-replacement therapy rather than intermittent hemodialysis is recommended because of hemodynamic instability.