Lilia R. Lukowsky

Mortality Prediction by Surrogates of Body Composition: An Examination of the Obesity Paradox in Hemodialysis Patients Using Composite Ranking Score Analysis

In hemodialysis patients, lower body mass index and weight loss have been associated with higher mortality rates, a phenomenon sometimes called the obesity paradox. This apparent paradox might be explained by loss of muscle mass. The authors thus examined the relation to mortality of changes in dry weight and changes in serum creatinine levels (a muscle-mass surrogate) in a cohort of 121,762 hemodialysis patients who were followed for up to 5 years (2001-2006). In addition to conventional regression analyses, the authors conducted a ranking analysis of joint effects in which the sums and differences of the percentiles of change for the 2 measures in each patient were used as the regressors. Concordant with previous body mass index observations, lower body mass, lower muscle mass, weight loss, and serum creatinine decline were associated with higher death rates. Among patients with a discordant change, persons whose weight declined but whose serum creatinine levels increased had lower death rates than did those whose weight increased but whose serum creatinine level declined. A decline in serum creatinine appeared to be a stronger predictor of mortality than did weight loss. Assuming residual selection bias and confounding were not large, the present results suggest that a considerable proportion of the obesity paradox in dialysis patients might be explained by the amount of decline in muscle mass.

Impact of race on hyperparathyroidism, mineral disarrays, administered vitamin D mimetic, and survival in hemodialysis patients

Blacks have high rates of chronic kidney disease, are overrepresented among the US dialysis patients, have higher parathyroid hormone levels, but greater survival compared to nonblacks. We hypothesized that mineral and bone disorders (MBDs) have a bearing on survival advantages of black hemodialysis patients. In 139,328 thrice‐weekly treated hemodialysis patients, including 32% blacks, in a large dialysis organization, where most laboratory values were measured monthly for up to 60 months (July 2001 to June 2006), we examined differences across races in measures of MBDs and survival predictabilities of these markers and administered the active vitamin D medication paricalcitol. Across each age increment, blacks had higher serum calcium and parathyroid hormone (PTH) levels and almost the same serum phosphorus and alkaline phosphatase levels and were more likely to receive injectable active vitamin D in the dialysis clinic, mostly paricalcitol, at higher doses than nonblacks. Racial differences existed in mortality predictabilities of different ranges of serum calcium, phosphorus, and PTH but not alkaline phosphatase. Blacks who received the highest dose of paricalcitol (>10 µg/week) had a demonstrable survival advantage over nonblacks (case‐mix‐adjusted death hazard ratio = 0.87, 95% confidence level 0.83–0.91) compared with those who received lower doses (<10 µg/week) or no active vitamin D. Hence, in black hemodialysis patients, hyperparathyroidism and hypercalcemia are more prevalent than in nonblacks, whereas hyperphosphatemia or hyperphosphatasemia are not. Survival advantages of blacks appear restricted to those receiving higher doses of active vitamin D. Examining the effect of MBD modulation on racial survival disparities of hemodialysis patients is warranted.

Patterns and predictors of early mortality in incident hemodialysis patients: new insights.

Background: Incident hemodialysis patients have the highest mortality in the first several months after starting dialysis treatments. We hypothesized that the patterns and risk factors associated with this early mortality differ from those in later dialysis therapy periods. Methods: We examined mortality patterns and predictors during the first several months of hemodialysis treatment in 18,707 incident patients since the first week of hemodialysis therapy and estimated the population attributable fractions for selected time periods in the first 24 months. Results: The 18,707 incident hemodialysis patients were 45% women and 54% diabetics. The standardized mortality ratios (95% confidence interval) in the 1st to 3rd month of hemodialysis therapy were 1.81 (1.74–1.88), 1.79 (1.72–1.86), and 1.34 (1.27–1.40), respectively. The standardized mortality ratio reached prevalent mortality only by the 7th month. No survival advantage for African Americans existed in the first 6 months. Patients with low albumin <3.5 g/dl had the highest proportion of infection-related deaths while patients with higher albumin levels had higher cardiovascular deaths including 76% of deaths during the first 3 months. Use of catheter as vascular access and hypoalbuminemia <3.5 g/dl explained 34% (17–54%) and 33% (19–45%) of all deaths in the first 90 days, respectively. Conclusions: Incident hemodialysis patients have the highest mortality during the first 6 months including 80% higher death risk in the first 2 months. The presence of a central venous catheter and hypoalbuminemia <3.5 g/dl each explain one third of all deaths in the first 90 days.

An update on the comparisons of mortality outcomes of hemodialysis and peritoneal dialysis patients.

The number of dialysis patients continues to grow. In many parts of the world, peritoneal dialysis (PD) is a less expensive form of treatment. However, it has been questioned whether patients treated with PD can have as good a long-term outcome as that achieved with hemodialysis (HD). This skepticism has fueled ongoing comparisons of outcomes of patients treated with in-center HD and PD using data from national registries or prospective cohort studies. There are major challenges in comparing outcomes with two therapies when the treatment assignment is nonrandom. Furthermore, many of the intermodality comparisons include patients who started dialysis therapy in the 1990s. In many parts of the world, improvements in PD outcome have outpaced those seen with in-center HD. It is not surprising, then, that virtually all the recent observational studies from different parts of the world consistently show that long-term survival of HD and PD patients is remarkably similar. These studies support the case for a greater use of PD for the treatment of end-stage renal disease. This, in turn, could allow more patients to be treated for any given budgetary allocation to long-term dialysis.

Blood Pressure and Survival in Long-Term Hemodialysis Patients with and without Polycystic Kidney Disease

Background In maintenance dialysis patients, low blood pressure (BP) values are associated with higher death rates when compared with normal to moderately high values. This ‘hypertension paradox’ may be related to comorbid conditions. Dialysis patients with polycystic kidney disease (PKD) usually have a lower comorbidity burden and greater survival. We hypothesized that in PKD dialysis patients, a representative of a healthier dialysis patient population, high BP is associated with higher mortality. Methods Time-dependent survival models including after multivariate adjustment were examined to assess the association between prehemodialysis and posthemodialysis BP and all-cause mortality in a 5-year cohort of 67 085 non-PKD and 1579 PKD hemodialysis patients. Results In PKD patients, low prehemodialysis and posthemodialysis SBPs were associated with increased mortality, whereas high prehemodialysis DBP was associated with greater survival. Fully adjusted death hazard ratios (and 95% confidence levels) for prehemodialysis and posthemodialysis BP of less than 120 mmHg (reference 140 to <160 mmHg) were 1.30 (1.06–1.92) and 1.45 (1.04–2.02), respectively, and for prehemodialysis DBP of 80 mmHg or more (reference 70 to <80 mmHg) was 0.68 (0.49–0.93, all P values <0.05). Similar associations were observed in non-PKD patients. In pooled analyses, within each commensurate BP stratum, PKD patients exhibited superior survival to non-PKD patients. Conclusion Among hemodialysis patients, those with PKD display a similar BP paradox as those without PKD, even though within each BP category PKD patients maintain superior survival. Randomized clinical trials are needed to define optimal blood pressure targets in the hemodialysis population.

Dialysis modality and outcomes in kidney transplant recipients

BACKGROUND AND OBJECTIVES The influence of pretransplant dialysis modality on post-transplant outcomes is not clear. This study examined associations of pretransplant dialysis modality with post-transplant outcomes in a large national cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, 12,416 hemodialysis and 2092 peritoneal dialysis patients who underwent first kidney transplantation were identified. Mortality or graft failure and delayed graft function risks were estimated by Cox regression (hazard ratio) and logistic regression (odds ratio), respectively. RESULTS Recipients treated with peritoneal dialysis pretransplantation had lower (21.9/1000 patient-years [95% confidence interval: 18.1-26.5]) crude all-cause mortality rate than those recipients treated with hemodialysis (32.8/1000 patient-years [30.8-35.0]). Pretransplant peritoneal dialysis use was associated with 43% lower adjusted all-cause and 66% lower cardiovascular death. Furthermore, pretransplant peritoneal dialysis use was associated with 17% and 36% lower unadjusted death-censored graft failure and delayed graft function risk, respectively. However, after additional adjustment for relevant covariates, pretransplant peritoneal dialysis modality was not a significant predictor of death-censored graft failure delayed graft function, respectively. Similar trends were noted on analyses using a propensity score matched cohort of 2092 pairs of patients. CONCLUSIONS Compared with hemodialysis, patients treated with peritoneal dialysis before transplantation had lower mortality but similar graft loss or delayed graft function. Confounding by residual selection bias cannot be ruled out.

Serum creatinine level, a surrogate of muscle mass, predicts mortality in peritoneal dialysis patients

BACKGROUND In hemodialysis patients, higher serum creatinine (Cr) concentration represents larger muscle mass and predicts greater survival. However, this association remains uncertain in peritoneal dialysis (PD) patients. METHODS In a cohort of 10 896 PD patients enrolled from 1 July 2001 to 30 June 2006, the association of baseline serum Cr level and change during the first 3 months after enrollment with all-cause mortality was examined. RESULTS The cohort mean ± SD age was 55 ± 15 years old and included 52% women, 24% African-Americans and 48% diabetics. Compared with patients with serum Cr levels of 8.0-9.9 mg/dL, patients with serum Cr levels of <4.0 mg/dL and 4.0-5.9 mg/dL had higher risks of death {HR 1.36 [95% confidence interval (95% CI) 1.19-1.55] and 1.19 (1.08-1.31), respectively} whereas patients with serum Cr levels of 10.0-11.9 mg/dL, 12.0-13.9 mg/dL and ≥14.0 mg/dL had lower risks of death (HR 0.88 [95% CI 0.79-0.97], 0.71 [0.62-0.81] and 0.64 [0.55-0.75], respectively) in the fully adjusted model. Decrease in serum Cr level over 1.0 mg/dL during the 3 months predicted an increased risk of death additionally. The serum Cr-mortality association was robust in patients with PD treatment duration of ≥12 months, but was not observed in those with PD duration of <3 months. CONCLUSIONS Muscle mass reflected in serum Cr level may be associated with survival even in PD patients. However, the serum Cr-mortality association is attenuated in the early period of PD treatment, suggesting competing effect of muscle mass versus residual renal function on mortality.

Relationship of body size and initial dialysis modality on subsequent transplantation, mortality and weight gain of ESRD patients

BACKGROUND Whether peritoneal dialysis (PD) treatment leads to greater weight gain than with hemodialysis (HD) and if this limits access of obese end-stage renal disease patients to renal transplantation has not been examined. We undertook this study to determine the interrelationship between body size and initial dialysis modality on transplantation, mortality and weight gain. METHODS Time to transplantation, time to death and weight gain were estimated in a 1:1 propensity score-matched cohort of incident HD and PD patients treated in facilities owned by DaVita Inc. between 1 July 2001 through 30 June 2006 followed through 30 June 2007 (4008 pairs) in four strata of body mass index (BMI) (<18.5, 18.5-24.99, 25.00-29.99 and ≥ 30 kg/m(2)). RESULTS Transplantation was significantly more likely in PD patients [adjusted hazards ratio (aHR) 1.48, 95% confidence interval (95% CI) 1.29-1.70]; the probability of receiving a kidney transplant was significantly higher in each strata of BMI >18.5 kg/m(2), including with BMI ≥ 30 kg/m(2) (aHR 1.45, 95% CI 1.11-1.89). PD patients had significantly lower all-cause mortality for patients with BMI 18.50-29.99 kg/m(2). Both these findings were confirmed on analyses of the entire unmatched incident cohort (PD 4008; HD 58 471). The effect of dialysis modality on weight gain was tested in 687 propensity score-matched pairs; the odds of >2, >5 or >10% weight gain were significantly lower in PD patients. CONCLUSION Treatment with PD is less likely to be associated with a significant weight gain and does not limit the access of obese patients to renal transplantation.

Mineral and bone disorders and survival in hemodialysis patients with and without polycystic kidney disease

BACKGROUND Maintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential. METHODS Survival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients. RESULTS PKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to <300 pg/mL (reference) had the lowest risk for mortality, the death risk was higher in patients with PTH<150 [hazard ratio (HR): 2.16 (95% confidence interval 1.53-3.06)], 300 to <600 [HR: 1.30 (0.97-1.74)] and ≥600 pg/mL [HR: 1.46 (1.02-2.08)], respectively. Similar patterns were found in non-PKD patients. Fully adjusted death HRs of time-averaged serum phosphorous increments<3.5, 5.5 to <7.5 and ≥7.5 mg/dL (reference: 3.5 to <5.5 mg/dL) for PKD patients were 2.82 (1.50-5.29), 1.40 (1.12-1.75) and 2.25 (1.57-3.22). The associations of alkaline phosphatase and calcium with mortality were similar in PKD and non-PKD patients. CONCLUSION Bone-mineral disorder markers exhibit similar mortality trends between PKD and non-PKD MHD patients, although some differences are observed in particular in low PTH and phosphorus ranges.

Hemoglobin level and survival in hemodialysis patients with polycystic kidney disease and the role of administered erythropoietin

Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis-stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with minimal to no ESA administration as observed in some patients with polycystic kidney disease (PKD) is also associated with poor outcomes. Survival models were examined to assess the association between hemoglobin increments and mortality in a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus otherwise, respectively. Mortality risk was estimated by Cox proportional regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients with PKD were aged 58 ± 13 years and included 46% women 14% Blacks, respectively. Fully adjusted death HRs of time-averaged hemoglobin increments <11.0, 12.0 to <13.0 g/dL (reference: 11.0 to <12.0 g/dL) for frequent ESA therapy were 2.57 (1.48-4.48), 0.60 (0.43-0.82), and 0.81 (0.50-1.29), whereas for infrequent ESA therapy they were 1.33 (0.47-3.78), 0.28 (0.13-0.61), and 0.22 (0.09-0.57), respectively. Hence, in patients with PKD who require infrequent ESA, incrementally higher achieved hemoglobin including > 13.0 g/dL exhibits better survival; this incremental survival gain of higher hemoglobin is not observed in patients with PKD receiving frequent ESA administration, in whom hemoglobin concentration > 13 exhibits increased mortality.