Talat Alp Ikizler

Estimating Baseline Kidney Function in Hospitalized Patients with Impaired Kidney Function

BACKGROUND AND OBJECTIVES Inaccurate determination of baseline kidney function can misclassify acute kidney injury (AKI) and affect the study of AKI-related outcomes. No consensus exists on how to optimally determine baseline kidney function when multiple preadmission creatinine measurements are available. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The accuracy of commonly used methods for estimating baseline serum creatinine was compared with that of a reference standard adjudicated by a panel of board-certified nephrologists in 379 patients with AKI or CKD admitted to a tertiary referral center. RESULTS Agreement between estimating methods and the reference standard was highest when using creatinine values measured 7-365 days before admission. During this interval, the intraclass correlation coefficient (ICC) for the mean outpatient serum creatinine level (0.91 [95% confidence interval (CI), 0.88-0.92]) was higher than the most recent outpatient (ICC, 0.84 [95% CI, 0.80-0.88]; P<0.001) and the nadir outpatient (ICC, 0.83 [95% CI, 0.76-0.87; P<0.001) serum creatinine. Using the final creatinine value from a prior inpatient admission increased the ICC of the most recent outpatient creatinine method (0.88 [95% CI, 0.85-0.91]). Performance of all methods declined or was unchanged when the time interval was broadened to 2 years or included serum creatinine measured within a week of admission. CONCLUSIONS The mean outpatient serum creatinine measured within a year of hospitalization most closely approximates nephrologist-adjudicated serum creatinine values.

Patient Dialysis Knowledge Is Associated with Permanent Arteriovenous Access Use in Chronic Hemodialysis

BACKGROUND AND OBJECTIVES Patient knowledge about chronic hemodialysis (CHD) is important for effective self-management behaviors, but little is known about its association with vascular access use. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Prospective cohort of adult incident CHD patients from May 2002 until November 2005 and followed for 6 mo after initiation of hemodialysis (HD). Patient knowledge was measured using the Chronic Hemodialysis Knowledge Survey (CHeKS). The primary outcome was dialysis access type at: baseline, 3 mo, and 6 mo after HD initiation. Secondary outcomes included anemia, nutritional, and mineral laboratory measures. RESULTS In 490 patients, the median (interquartile range) CHeKS score (0 to 100%) was 65%[52% to 78%]. Lower scores were associated with older age, fewer years of education, and nonwhite race. Patients with CHeKS scores 20 percentage points higher were more likely to use an arteriovenous fistula or graft compared with a catheter at HD initiation and 6 mo after adjustment for age, sex, race, education, and diabetes mellitus. No statistically significant associations were found between knowledge and laboratory outcome measures, except for a moderate association with serum albumin. Potential limitations include residual confounding and an underpowered study to determine associations with some clinical measures. CONCLUSIONS Patients with less dialysis knowledge may be less likely to use an arteriovenous access for dialysis at initiation and after starting hemodialysis. Additional studies are needed to explore the impact of patient dialysis knowledge, and its improvement after educational interventions, on vascular access in hemodialysis.

Early Intervention Improves Mortality and Hospitalization Rates in Incident Hemodialysis Patients: RightStart Program

BACKGROUND AND OBJECTIVES Annualized mortality rates of chronic hemodialysis (CHD) patients in their first 90 d of treatment range from 24 to 50%. Limited studies also show high hospitalization rates. It was hypothesized that a structured quality improvement program (RightStart), focused on medical needs and patient education and support, would improve outcomes for incident CHD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 918 CHD incident patients were prospectively enrolled in a multicenter RightStart Program, and compared with a time-concurrent group of 1020 control patients from non-RightStart clinics. RightStart patients received 3 mo of intervention in management of anemia, dosage of dialysis, nutrition, and dialysis access and a comprehensive educational program. Outcomes were tracked for up to 12 mo. RESULTS At 3 mo, RightStart patients had higher albumin and hematocrit values. Dose of dialysis and permanent access placement were not statistically significantly different from control subjects. Compared with baseline, Mental Composite Score for RightStart patients improved significantly. Mean hospitalization days per patient year were reduced with RightStart versus control subjects. Mortality rates at 3, 6, and 12 mo were 20, 18, and 17 for RightStart patients versus 39, 33, and 30 deaths per 100 patient-years for control subjects, respectively. CONCLUSIONS A structured program of prompt medical and educational strategies in incident CHD patients results in improved morbidity and mortality that last up to 1 yr.

Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease.

Insulin resistance (IR), the reciprocal of insulin sensitivity is a known complication of advanced chronic kidney disease (CKD) and is associated with a number of metabolic derangements. The complex metabolic abnormalities observed in CKD such as vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of “uremic toxins” are believed to contribute to the etiology of IR and acquired defects in the insulin‐receptor signaling pathway in this patient population. Only a few investigations have explored the validity of commonly used assessment methods in comparison to gold standard hyperinsulinemic hyperglycemic clamp technique in CKD patients. An important consequence of insulin resistance is its role in the pathogenesis of protein energy wasting, a state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, insulin resistance has been associated with accelerated protein catabolism. Among end‐stage renal disease (ESRD) patients, enhanced muscle protein breakdown has been observed in patients with Type II diabetes compared to ESRD patients without diabetes. In the absence of diabetes mellitus (DM) or severe obesity, insulin resistance is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, primarily mediated by the ubiquitin‐proteasome pathway. Recent epidemiological data indicate a survival advantage and better nutritional status in insulin‐free Type II DM patients treated with insulin sensitizer thiazolidinediones. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, insulin resistance may represent an important modifiable target for intervention in the ESRD population.

Comparison of methods for estimating glomerular filtration rate in critically ill patients with acute kidney injury

BACKGROUND In critically ill patients with acute kidney injury, estimates of kidney function are used to modify drug dosing, adjust nutritional therapy and provide dialytic support. However, estimating glomerular filtration rate is challenging due to fluctuations in kidney function, creatinine production and fluid balance. We hypothesized that commonly used glomerular filtration rate prediction equations overestimate kidney function in patients with acute kidney injury and that improved estimates could be obtained by methods incorporating changes in creatinine generation and fluid balance. METHODS We analysed data from a multicentre observational study of acute kidney injury in critically ill patients. We identified 12 non-dialysed, non-oliguric patients with consecutive increases in creatinine for at least 3 and up to 7 days who had measurements of urinary creatinine clearance. Glomerular filtration rate was estimated by Cockcroft-Gault, Modification of Diet in Renal Disease, Jelliffe equation and Jelliffe equation with creatinine adjusted for fluid balance (Modified Jelliffe) and compared to measured urinary creatinine clearance. RESULTS Glomerular filtration rate estimated by Jelliffe and Modification of Diet in Renal Disease equation correlated best with urinary creatinine clearances. Estimated glomerular filtration rate by Cockcroft-Gault, Modification of Diet in Renal Disease and Jelliffe overestimated urinary creatinine clearance was 80%, 33%, 10%, respectively, and Modified Jelliffe underestimated GFR by 2%. CONCLUSION In patients with acute kidney injury, glomerular filtration rate estimating equations can be improved by incorporating data on creatinine generation and fluid balance. A better assessment of glomerular filtration rate in acute kidney injury could improve evaluation and management and guide interventions.

Determinants of C‐reactive protein in chronic hemodialysis patients: Relevance of dialysis catheter utilization

Biomarkers of inflammation, especially C‐reactive protein (CRP), have been consistently shown to predict poor outcomes in chronic hemodialysis (CHD) patients. However, the determinants of CRP and the value of its monitoring in CHD patients have not been well defined. We conducted a retrospective cohort study to evaluate possible determinants of the inflammatory response in CHD patients with a focus on dialysis catheter utilization. Monthly CRP were measured in 128 prevalent CHD patients (mean age 56.6 years [range 19–90], 68% African Americans, 39% diabetics [DM]) over a mean follow‐up of 12 months (range 2–26 months). There were a total of 2405 CRP measurements (median 5.7 mg/L; interquartile range [IQR] 2.4–16.6 mg/L). The presence of a dialysis catheter (p<0.002), cardiovascular disease (p=0.01), male gender (p=0.005), higher white blood cell count (p<0.0001), elevated phosphorus (p=0.03), and lower cholesterol (p=0.02) and albumin (p<0.0001) concentrations were independent predictors of elevated CRP in the multivariate analysis. Additionally, CRP levels were significantly associated with the presence of a catheter, when comparing the levels before and after catheter insertion (p=0.002) as well as before and after catheter removal (p=0.009). Our results indicate that the presence of a hemodialysis catheter is an independent determinant of an exaggerated inflammatory response in CHD patients representing a potentially modifiable risk factor.

A Comparison of Novel and Commonly-Used Indices of Insulin Sensitivity in African American Chronic Hemodialysis Patients

BACKGROUND Insulin resistance (IR) is highly prevalent in chronic hemodialysis (CHD) patients and is associated with poor cardiovascular outcomes. Hyperinsulinemic euglycemic glucose clamp (HEGC) is the gold standard for measuring IR. The comparison of commonly-used indirect indices of IR to HEGC has not been adequately performed in this population. Furthermore, the validity of newly proposed adipokine-based IR indices has not been explored. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This is an observational study performed in a single center, involving 12 prevalent CHD patients (50 ± 9 years old, 100% African American, 33% women, body mass index of 34.4 ± 7.6 kg/m(2)) who were studied three consecutive times. IR was assessed by HEGC (glucose-disposal rate [GDR]), homeostatic model assessment of IR (HOMA-IR), HOMA-IR corrected by adiponectin (HOMA-AD), leptin adiponectin ratio (LAR), QUICKI, and the McAuleys index at each time point. RESULTS Eighty-three percent of the subjects displayed either glucose intolerance or overt insulin resistance by HEGC (GDR median, 5.71; interquartile range [IQR], 4.16, 6.81). LAR and HOMA-AD were the best correlates of IR measured by HEGC (r=-0.72, P<0.001, and -0.67, P<0.001), respectively. Fat percentage, interleukin-6, and adipokines (leptin, adiponectin, and resistin) were strongly associated with GDR. HEGC, LAR, and HOMA-AD had the best intraclass correlation coefficients. CONCLUSION IR is common in CHD patients. Adipokine-based indices are the best correlates of IR measurements by HEGC. HOMA-IR and QUICKI are reasonable alternatives. Use of these indices may allow better detection of alterations in insulin sensitivity in CHD patients.

Predictors of Recurrent AKI

Recurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19-167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted.

Patient knowledge of blood pressure target is associated with improved blood pressure control in chronic kidney disease.

OBJECTIVE To describe patient hypertension knowledge and associations with blood pressure measurements. METHODS Patients with chronic kidney disease (CKD) were asked about the impact of high blood pressure on kidneys and their target blood pressure goal. Systolic blood pressure was measured using automated sphygmomanometers. RESULTS In 338 adults with hypertension and pre-dialysis CKD, the median [IQR] age was 59 [47,68] years, 45% [n = 152] were women, and 18% [n = 62] were non-white. Lower systolic blood pressure (SBP) was associated with female sex (SBP mmHg median [IQR] 132 [117,149] women vs. 137 [124,152] men; p = 0.04), less advanced CKD (SBP 134 [122,147] stages 1-2 vs. 132 [118,148] stage 3 vs. 140 [125,156] stages 4-5; p = 0.01), and patient ability to correctly identify SBP goal (SBP 134 [119,150] correct vs. 141 [125,154] incorrect; p = 0.05). In adjusted analysis, knowledge of blood pressure goal remained independently associated with lower SBP (-9.96 mmHg [-19.97, -1.95] in correct respondents vs. incorrect; p<0.001). CONCLUSION Patient knowledge of goal blood pressure is independently associated with improved blood pressure control. PRACTICE IMPLICATIONS Interventions to improve patient knowledge of specific blood pressure targets may have an important role in optimizing blood pressure management.

Review Articles: Uremic Malnutrition: New Insights Into an Old Problem

ABSTRACT Uremic malnutrition is highly prevalent and is associated with poor clinical outcomes in end‐stage renal disease (ESRD) patients. Inadequate diet and a state of persistent catabolism play major roles in predisposing these patients to uremic malnutrition and appear to have an additive effect on overall outcome. Recent studies highlight the existence of a complex syndrome involving chronic inflammation, metabolic abnormalities, and hormonal derangements contributing to the increased morbidity and mortality observed in ESRD patients. Novel strategies such as appetite stimulants, anti‐inflammatory drugs, and anabolic hormones along with conventional nutritional supplementation may provide potential interventions to improve clinical outcome in ESRD patients.