Ron Wald

Chronic dialysis and death among survivors of acute kidney injury requiring dialysis.

CONTEXT Severe acute kidney injury among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who survive to hospital discharge. OBJECTIVE To assess the risk of chronic dialysis and all-cause mortality in individuals who experience an episode of acute kidney injury requiring dialysis. DESIGN, SETTING, AND PARTICIPANTS We conducted a population-based cohort study of all adult patients in Ontario, Canada, with acute kidney injury who required in-hospital dialysis and survived free of dialysis for at least 30 days after discharge between July 1, 1996, and December 31, 2006. These individuals were matched with patients without acute kidney injury or dialysis during their index hospitalization. Matching was by age plus or minus 5 years, sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury requiring dialysis. Patients were followed up until March 31, 2007. MAIN OUTCOME MEASURES The primary end point was the need for chronic dialysis and the secondary outcome was all-cause mortality. RESULTS We identified 3769 adults with acute kidney injury requiring in-hospital dialysis and 13 598 matched controls. The mean age was 62 years and median follow-up was 3 years. The incidence rate of chronic dialysis was 2.63 per 100 person-years among individuals with acute kidney injury requiring dialysis, and 0.91 per 100 person-years among control participants (adjusted hazard ratio, 3.23; 95% confidence interval, 2.70-3.86). All-cause mortality rates were 10.10 and 10.85 per 100 person-years, respectively (adjusted hazard ratio, 0.95; 95% confidence interval, 0.89-1.02). CONCLUSIONS Acute kidney injury necessitating in-hospital dialysis was associated with an increased risk of chronic dialysis but not all-cause mortality.

Declining Mortality in Patients with Acute Renal Failure, 1988 to 2002

Despite improvements in intensive care and dialysis, some experts have concluded that outcomes associated with acute renal failure (ARF) have not improved significantly over time. ARF was studied in hospitalized patients between 1988 and 2002 using the Nationwide Inpatient Sample, a nationally representative sample of discharges from acute-care, nonfederal hospitals. During a 15-yr period, 5,563,381 discharges with ARF and 598,768 with ARF that required dialysis (ARF-D) were identified. Between 1988 and 2002, the incidence of ARF rose from 61 to 288 per 100,000 population; the incidence of ARF-D increased from 4 to 27 per 100,000 population. Between 1988 and 2002, in-hospital mortality declined steadily in patients with ARF (40.4 to 20.3%; P < 0.001) and in those with ARF-D (41.3 to 28.1%; P < 0.001). Compared with 1988 to 1992, the multivariable-adjusted odds ratio (OR) of death was lower in 1993 to 1997 (ARF: OR 0.62, 95% confidence interval [CI] 0.61 to 0.64; ARF-D: OR 0.63, 95% CI 0.59 to 0.66) and 1998 to 2002 (ARF: OR 0.40, 95% CI 0.39 to 0.41; ARF-D: OR 0.47, 95% CI 0.45 to 0.50). The percentage of patients who had ARF with a Deyo-Charlson comorbidity index of 3 or more increased from 16.4% in 1988 to 26.6% in 2002 (P < 0.001). This study provides evidence from an administrative database that the incidence of ARF and ARF-D is rising. Despite an increase in the degree of comorbidity, in-hospital mortality has declined.

Urinary N-Acetyl-β-(D)-Glucosaminidase Activity and Kidney Injury Molecule-1 Level Are Associated with Adverse Outcomes in Acute Renal Failure

The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in acute renal failure (ARF) has not been well described. The relationship between urinary N-acetyl-beta-(D)-glucosaminidase activity (NAG) and kidney injury molecule-1 (KIM-1) level and adverse clinical outcomes was evaluated prospectively in a cohort of 201 hospitalized patients with ARF. NAG was measured by spectrophotometry, and KIM-1 was measured by a microsphere-based Luminex technology. Mean Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score was 16, 43% had sepsis, 39% required dialysis, and hospital mortality was 24%. Urinary NAG and KIM-1 increased in tandem with APACHE II and Multiple Organ Failure scores. Compared with patients in the lowest quartile of NAG, the second, third, and fourth quartile groups had 3.0-fold (95% confidence interval [CI] 1.3 to 7.2), 3.7-fold (95% CI 1.6 to 8.8), and 9.1-fold (95% CI 3.7 to 22.7) higher odds, respectively, for dialysis requirement or hospital death (P < 0.001). This association persisted after adjustment for APACHE II, Multiple Organ Failure score, or the combined covariates cirrhosis, sepsis, oliguria, and mechanical ventilation. Compared with patients in the lowest quartile of KIM-1, the second, third, and fourth quartile groups had 1.4-fold (95% CI 0.6 to 3.0), 1.4-fold (95% CI 0.6 to 3.0), and 3.2-fold (95% CI 1.4 to 7.4) higher odds, respectively, for dialysis requirement or hospital death (P = 0.034). NAG or KIM-1 in combination with the covariates cirrhosis, sepsis, oliguria, and mechanical ventilation yielded an area under the receiver operator characteristic curve of 0.78 (95% CI 0.71 to 0.84) in predicting the composite outcome. Urinary markers of kidney injury such as NAG and KIM-1 can predict adverse clinical outcomes in patients with ARF.

Epidemiology and Outcomes of Acute Renal Failure in Hospitalized Patients: A National Survey

The aim of this study was to provide a broad characterization of the epidemiology of acute renal failure (ARF) in the United States using national administrative data and describe its impact on hospital length of stay (LOS), patient disposition, and adverse outcomes. Using the 2001 National Hospital Discharge Survey, a nationally representative sample of discharges from nonfederal acute care hospitals in the United States, new cases of ARF were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Multivariate regression analyses were used to explore the relation of ARF to hospital LOS and mortality as well as discharge disposition. Review of discharge data on a projected total of 29,039,599 hospitalizations identified 558,032 cases of ARF, with a frequency of 19.2 per 1000 hospitalizations. ARF was more commonly coded for in older patients; men; black individuals; and the setting of chronic kidney disease, congestive heart failure, chronic lung disease, sepsis, and cardiac surgery. ARF was associated with an adjusted prolongation of hospital LOS by 2 d (P < 0.001) and an adjusted odds ratio of 4.1 for hospital mortality and of 2.0 for discharge to short- or long-term care facilities. In a US representative sample of hospitalized patients, the presence of an ICD-9-CM code for ARF in discharge records is associated with prolonged LOS, increased mortality, and, among survivors, a greater requirement for posthospitalization care. These findings suggest that in the United States, ARF is associated with increased in-hospital and post-hospitalization resource utilization.

Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure

Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis

IntroductionOur aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI).MethodsSystematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Science and Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July 2010. Eligible studies selected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI.ResultsWe identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494 citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). There was significant heterogeneity among the 15 pooled studies (I2 = 78%). In subgroup analyses, stratifying by patient population (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there was no impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (Acute Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported greater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studies showed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however, significantly affect the odds of dialysis dependence beyond hospitalization (OR 0.62 0.34 to 1.13, I2 = 69.6%).ConclusionsEarlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence of new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made.

Impact of Hospital-Associated Hyponatremia on Selected Outcomes

BACKGROUND Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. METHODS We evaluated whether hospital-associated hyponatremia has an independent effect on all-cause mortality, hospital length of stay (LOS), and patient disposition. This cohort study included all adult hospitalizations at an academic medical center occurring between 2000-2007 for which an admission serum sodium concentration ([Na(+)]) was available (N = 53 236). We examined community-acquired hyponatremia (admission serum [Na(+)], <138 mEq/L [to convert to millimoles per liter, multiply by 1.0]), hospital-aggravated hyponatremia (community-acquired hyponatremia complicated by worsening in serum [Na(+)]), and hospital-acquired hyponatremia (nadir serum [Na(+)], <138 mEq/L with a normal admission serum [Na(+)]). The independent associations of these hyponatremic presentations with in-hospital mortality, LOS, and patient disposition were evaluated using generalized estimating equations adjusted for age, sex, race, admission service, and Deyo-Charlson Comorbidity Index score. RESULTS Community-acquired hyponatremia occurred in 37.9% of hospitalizations and was associated with adjusted odds ratios (ORs) of 1.52 (95% confidence interval [CI], 1.36-1.69) for in-hospital mortality and 1.12 (95% CI, 1.08-1.17) for discharge to a short- or long-term care facility and a 14% (95% CI, 11%-16%) adjusted increase in LOS. Hospital-acquired hyponatremia developed in 38.2% of hospitalizations longer than 1 day in which initial serum [Na(+)] was 138 to 142 mEq/L. Hospital-acquired hyponatremia was associated with adjusted ORs of 1.66 (95% CI, 1.39-1.98) for in-hospital mortality and 1.64 (95% CI, 1.55-1.74) for discharge to a facility and a 64% (95% CI, 60%-68%) adjusted increase in LOS. The strength of these associations tended to increase with hyponatremia severity. CONCLUSIONS Hospital-associated hyponatremia is a common occurrence. All forms of hyponatremia are independently associated with in-hospital mortality and heightened resource consumption.

Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass

The purpose of this study was to compare the performance of six candidate urinary biomarkers, kidney injury molecule (KIM)-1, N-acetyl-β-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, cystatin C and α-1 microglobulin, measured 2 h following cardiopulmonary bypass (CPB) for the early detection of acute kidney injury (AKI) in a prospective cohort of patients undergoing cardiac surgery. A total of 103 subjects were enrolled; AKI developed in 13%. Urinary KIM-1 achieved the highest area under-the-receiver-operator-characteristic curve (AUC 0.78, 95% confidence interval 0.64–0.91), followed by IL-18 and NAG. Only urinary KIM-1 remained independently associated with AKI after adjustment for a preoperative AKI prediction score (Cleveland Clinic Foundation score; p = 0.02), or CPB perfusion time (p = 0.006). In this small pilot cohort, KIM-1 performed best as an early biomarker for AKI. Larger studies are needed to explore further the role of biomarkers for early detection of AKI following cardiac surgery.

Effects of Regional Dysfunction and Late Gadolinium Enhancement on Global Right Ventricular Function and Exercise Capacity in Patients With Repaired Tetralogy of Fallot

Background— The underlying mechanisms that contribute to global right ventricular (RV) dysfunction in patients with repaired tetralogy of Fallot are incompletely understood. We therefore sought to quantify regional RV abnormalities and to determine the relationship of these to global RV function and exercise capacity. Methods and Results— Clinical and cardiac magnetic resonance data from 62 consecutive patients with repaired tetralogy of Fallot were analyzed (median age at follow-up 23 years [limits 9 to 67 years]). Using cardiac magnetic resonance data, 3D RV endocardial surface models were reconstructed from segmented contours, and a correspondence between end diastole and end systole was computed with a novel algorithm. Regional RV abnormalities were quantified and expressed as segmental ejection fraction, spatial extent of dyskinetic area, displacement of dyskinetic area, and score of extent of late gadolinium enhancement. Regional abnormalities of function and hyperenhancement were greatest in the RV outflow tract (RVOT). These regional RVOT abnormalities correlated with global RV ejection fraction: RVOT ejection fraction r=0.64, P<0.0001; RVOT dyskinetic area r=−0.51, P<0.0001; RVOT displacement of dyskinetic area r=−0.49, P<0.0001; and RVOT late gadolinium enhancement score r=−0.33, P=0.01. Peak oxygen consumption during exercise correlated best with RVOT ejection fraction (r=0.56, P=0.0002) compared with the remainder of the RV (r=0.35, P=0.03). The only cardiac magnetic resonance variable independently predictive of aerobic capacity was RVOT ejection fraction (P=0.02). Conclusion— A greater extent of regional abnormalities in the RVOT adversely affects global RV function and exercise capacity after tetralogy of Fallot repair. These regional measures may have important implications for patient management, including RVOT reconstruction, at the time of pulmonary valve replacement.

Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.