Orfeas Liangos

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.

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.

NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position -262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype-phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype-phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P = 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P = 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P = 0.01). This association persisted with 2.0- to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P = 0.03), the Multiple Organ Failure score (P = 0.01), or presence of sepsis (P = 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position +242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.

Effect of intra-dialytic, low-intensity strength training on functional capacity in adult haemodialysis patients: a randomized pilot trial

BACKGROUND Kidney failure is associated with muscle wasting and physical impairment. Moderate- to high-intensity strength training improves physical performance, nutritional status and quality of life in people with chronic kidney disease and in dialysis patients. However, the effect of low-intensity strength training has not been well documented, thus representing the objective of this pilot study. METHODS Fifty participants (mean +/- SD, age 69 +/- 13 years) receiving long-term haemodialysis (3.7 +/- 4.2 years) were randomized to intra-dialytic low-intensity strength training or stretching (attention-control) exercises twice weekly for a total of 48 exercise sessions. The primary study outcome was physical performance assessed by the Short Physical Performance Battery score (SPPB) after 36 sessions, if available, or carried forward from 24 sessions. Secondary outcomes included lower body strength, body composition and quality of life. Measurements were obtained at baseline and at completion of 24 (mid), 36 (post) and 48 (final) exercise sessions. RESULTS Baseline median (IQR) SPPB score was 6.0 (5.0), with 57% of the participants having SPPB scores below 7. Exercise adherence was 89 +/- 15%. The primary outcome could be computed in 44 participants. SPPB improved in the strength training group compared to the attention-control group [21.1% (43.1%) vs. 0.2% (38.4%), respectively, P = 0.03]. Similarly, strength training participants exhibited significant improvements from baseline compared to the control group in knee extensor strength, leisure-time physical activity and self-reported physical function and activities of daily living (ADL) disability; all P < 0.02. Adverse events were common but not related to study participation. CONCLUSIONS Intra-dialytic, low-intensity progressive strength training was safe and effective among maintenance dialysis patients. Further studies are needed to establish the generalizability of this strength training program in dialysis patients.

Serum cystatin C for prediction of dialysis requirement or death in acute kidney injury: a comparative study.

BACKGROUND Serum cystatin C has emerged as a new and potentially more reliable marker of kidney function. However, its utility and performance in patients with acute kidney injury (AKI), particularly for the prediction of dialysis requirement, is not well known. STUDY DESIGN Prospective cohort study. SETTINGS & PARTICIPANTS Adult patients with AKI enrolled at 2 academic medical centers, at time of nephrology consultation. PREDICTORS Serum cystatin C (primary predictor), serum creatinine, and serum urea nitrogen levels and 24-hour urine output measured at enrollment. OUTCOMES The composite of dialysis requirement or in-hospital death. COVARIATES: Acute Physiology and Chronic Health Evaluation II (APACHE II) score, liver disease, sepsis, and mechanical ventilation. RESULTS 200 participants were enrolled for this analysis. Mean age was 65 years, 55% were men, and mean APACHE II score was 20. In unadjusted analyses, increases in serum cystatin C (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.36 to 2.59), serum creatinine (OR, 1.53; 95% CI, 1.12 to 2.09), and serum urea nitrogen levels (OR, 1.84; 95% CI, 1.34 to 2.54) were associated with a higher odds (per 1-SD increase) for the composite outcome, whereas greater urine output (OR, 0.56; 95% CI, 0.39 to 0.80) was associated with lower odds. These associations persisted after adjustment for APACHE II score. The addition of serum cystatin C, serum creatinine, and serum urea nitrogen levels or urine output to a basic model entailing APACHE II score, liver disease, sepsis, and assisted mechanical ventilation improved its prediction, evidenced by increases in areas under a receiver operator characteristic curve from 0.816 to 0.829, 0.826, 0.837, and 0.836, respectively. However, there was no significant difference between each of these models. LIMITATIONS Observational study, single serum cystatin C measurement. CONCLUSION In patients with AKI, serum cystatin C level performs similarly to serum creatinine level, serum urea nitrogen level, and urine output for predicting dialysis requirement or in-hospital death. Larger studies are needed to confirm these findings.

Plasma Cystatin C and Acute Kidney Injury after Cardiopulmonary Bypass

BACKGROUND AND OBJECTIVES Little is known about the performance of plasma cystatin C (CysC) in patients undergoing cardiopulmonary bypass (CPB) and its utility in the early diagnosis of acute kidney injury (AKI). In this post hoc analysis, the goal was to determine whether plasma cystatin C, measured 2 hours after the conclusion of CPB, is a reliable marker of AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Plasma CysC was measured in 150 patients undergoing CPB at the following times: preoperatively, 2 hours after the conclusion of CPB, postoperative day 1, and postoperative day 2. Plasma CysC levels were related to the development of AKI as defined by an increase in serum creatinine of >or=50% or >or=0.3 mg/dl from baseline up to 3 days postoperative. Mixed linear models were used to evaluate the relationship of serial plasma CysC values with AKI. The discriminatory capacity of plasma CysC was estimated using receiver operating characteristic curves. Logistic regression was utilized to assess the adjusted relationship between plasma CysC and subsequent AKI. RESULTS AKI developed in 47 (31.3%) patients. Plasma CysC was higher at all times among patients who developed AKI compared with those who did not (P < 0.0001). The discriminatory capacity of plasma CysC measured preoperatively and 2 hours after the conclusion of CPB was modest. CONCLUSIONS Serial measures of plasma CysC are highly correlated with the development of AKI. However, the discriminatory capacity of plasma CysC as an early marker of AKI remains limited.

Predicting acute renal failure after cardiac surgery: validation and re-definition of a risk-stratification algorithm.

Background:  Acute renal failure (ARF) after cardiac surgery is associated with significant morbidity and mortality, irrespective of the need for dialysis. Previous studies have attempted to identify predictors of ARF and develop risk stratification algorithms. This study aims to validate the algorithm in an independent cohort of patients that includes a significant proportion of female and black patients and compares two different definitions of renal outcome.

Long-term management of the tunneled venous catheter.

Despite their propensity for significant complications, tunneled central venous catheters have become a common means of vascular access in the United States for patients requiring maintenance hemodialysis for end‐stage renal disease (ESRD). Reasons for their use include advanced patient age, peripheral vascular disease (arterial and venous), late referral for creation of vascular access, and more importantly, the lack of an interdisciplinary service line on vascular access among vascular surgeons, radiologists, and nephrologists. This review article summarizes complications commonly encountered in dialysis patients who use tunneled central venous catheters for vascular access—mainly thrombosis, stenosis, and infection. Special attention is given to novel approaches for the prevention of catheter‐associated infections. Effective prevention and timely treatment of common catheter‐associated complications can reduce the substantial morbidity associated with the use of these devices. However, these measures should not detract from the goal of avoiding or limiting the long‐term use of catheters, thereby optimizing vascular access management by ensuring the timely availability of functioning arteriovenous fistulas.