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Ryan D Kilpatrick

Publications and source records attributed to Ryan D Kilpatrick.

10 recordsLinked to original sources

Association between serum lipids and survival in hemodialysis patients and impact of race.

Despite the enormous cardiovascular disease epidemic among maintenance hemodialysis (MHD) patients, total hypercholesterolemia seems paradoxically to be associated with better survival. It was hypothesized that similar paradoxic associations also exist for serum LDL, HDL, and triglycerides. A 3-yr (July 2001 through June 2004) cohort of 15,859 MHD patients was studied in the United States from DaVita dialysis clinics where lipid profile was measured in at least 50% of all outpatients during a given calendar quarter. Cox proportional hazard models were adjusted for case mix and surrogates of malnutrition-inflammation complex. Both total and LDL hypercholesterolemia showed a paradoxic association with better survival. Hypertriglyceridemia (>200 mg/dl) also showed a similar trend, but serum HDL cholesterol did not have any clear association with survival. The association between a low serum LDL <70 mg/dl, which was prevalent among almost 50% of all MHD patients, and a higher all-cause death risk was robust to multivariate adjustment. In the subgroup analyses, these paradoxic associations persisted among most subgroups, although they tended to be stronger among hypoalbuminemic (<3.8 mg/dl) patients and those with a lower dietary protein intake (<1 g/kg per d). However, in black patients, a high serum LDL (>100 mg/ml) was associated with adjusted cardiovascular death hazard ratio of 1.94 (95% confidence interval 1.12 to 2.38; P = 0.02). Despite inverse associations between hyperlipidemia and survival, black MHD patients with high LDL show almost two-fold increase in cardiovascular death risk. Although these associations may not be causal, they call into question whether specific subgroups of dialysis patients are better targets for cholesterol-lowering therapy.

Aged↗

Longitudinal associations between dietary protein intake and survival in hemodialysis patients.

BACKGROUND: Decreased dietary protein intake may be associated with increased mortality risk in individuals with kidney failure undergoing maintenance hemodialysis (MHD). We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in MHD patients. METHODS: The relation between urea kinetic-based normalized protein nitrogen appearance (nPNA) and all-cause and cardiovascular mortality was examined in a 2-year (July 2001 to June 2003) cohort of 53,933 MHD patients from virtually all DaVita dialysis clinics in the United States, using both conventional and time-dependent (repeated-measure) Cox models to estimate death hazard ratios for quarterly averaged nPNA categories controlled for case-mix, comorbidity, dialysis dose (Kt/V), and available markers of malnutrition-inflammation complex syndrome (MICS). RESULTS: The best survival was associated with nPNA between 1.0 and 1.4 g/kg/d, whereas nPNA less than 0.8 or greater than 1.4 g/kg/d was associated with greater mortality in almost all models. Adjustment for MICS mitigated the associations substantially. A decrease in protein intake during the first 6 months in patients with an nPNA in the 0.8- to 1.2-g/kg/d range was associated incrementally with greater death risks in the subsequent 18 months, whereas an increase in nPNA tended to correlate with reduced death risk. CONCLUSION: Low daily protein intake or decrease in its magnitude over time is associated with increased risk for death in MHD patients. Whether the association between time-varying protein intake and survival is causal or a consequence of anorexia secondary to MICS or other factors needs to be explored further in interventional trials.

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Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients.

Although treating anemia of chronic kidney disease by erythropoiesis-stimulating agents (ESA) may improve survival, most studies have examined associations between baseline hemoglobin values and survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in hemoglobin or administered ESA have meaningful associations with survival after adjustment for time-varying confounders. With the use of time-dependent Cox regression models, longitudinal associations were examined between survival and quarterly (13-wk averaged) hemoglobin values and administered ESA dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States. After time-dependent and multivariate adjustment for case mix, quarterly varying administered intravenous iron and ESA doses, iron markers, and nutritional status, hemoglobin levels between 12 and 13 g/dl were associated with the greatest survival. Among prevalent patients, the lower range of the recommended Kidney Disease Quality Outcomes Initiative hemoglobin target (11 to 11.5 g/dl) was associated with a higher death risk compared with the 11.5- to 12-g/dl range. A decrease or increase in hemoglobin over time was associated with higher or lower death risk, respectively, independent of baseline hemoglobin. Administration of any dose of ESA was associated with better survival, whereas among those who received ESA, requiring higher doses were surrogates of higher death risk. In this observational study, greater survival was associated with a baseline hemoglobin between 12 and 13 g/dl, treatment with ESA, and rising hemoglobin. Falling hemoglobin and requiring higher ESA doses were associated with decreased survival. Randomized clinical trials are required to examine these associations.

Aged↗

Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.

BACKGROUND: Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different. METHODS: Associations between 3-month averaged serum albumin levels, measured in a single laboratory using bromocresol green, and CV mortality were studied longitudinally in a 2-year cohort of 58,058 MHD patients. Mortality predictability of fixed baseline and trimonthly-varying serum albumin concentrations were compared. RESULTS: Hazard ratios (HRs) of CV death strictly increased across decrements of baseline serum albumin, whereas the HR for time-varying serum albumin decrements below 3.8 g/dl did not differ. A drop in serum albumin in the first 6 months was associated with increasing all-cause and CV death risks in the subsequent 18 months, while a rise in serum albumin was a predictor of better survival independent of baseline serum albumin. The multivariate adjusted population-attributable fraction of death due to baseline serum albumin <3.8 g/dl was 19%. CONCLUSIONS: Time-varying hypoalbuminaemia predicts all-cause and CV death differently from fixed measures of serum albumin in MHD patients. An increase in serum albumin over time is associated with better survival independent of baseline serum albumin or other MICS surrogates. If this association is causal, an intervention that could increase serum albumin >3.8 g/dl might reduce the number of MHD deaths in the USA by approximately 10,000 annually. Nutritional interventions examining benefits of increasing serum albumin in MHD patients are urgently needed.

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Reverse epidemiology of hypertension and cardiovascular death in the hemodialysis population: the 58th annual fall conference and scientific sessions.

Maintenance hemodialysis patients in the United States have a high prevalence (approximately 80%) of systolic hypertension and a high mortality (approximately 20% per year). Some reports indicate a paradoxical association between hypertension and mortality in hemodialysis patients (ie, a normal to low blood pressure is associated with poor outcome), whereas high pressure confers survival advantages, a phenomenon referred to as "reverse epidemiology." We hypothesized that malnutrition-inflammation complex syndrome may be a cause of this paradoxical association. We studied a 15-month cohort of 40 933 hemodialysis patients in the United States whose predialysis and postdialysis blood pressure values were recorded routinely during each hemodialysis treatment. Patients were 59.8+/-15.3 years old; 54% were women and 46% diabetics. Cox proportional hazard models were used for blood pressure categories (systolic <110, > or =190 mm Hg; diastolic <50, > or =110; and increments of 10 mm Hg in between). Unadjusted, case-mix and dialysis dose-adjusted, and additional malnutrition-inflammation-adjusted hazard ratios of all-cause and cardiovascular death showed progressively increasing all-cause and cardiovascular death risk for decreasing blood pressure values. The lowest mortality was associated with predialysis systolic pressure of 160 to 189 mm Hg, whereas normal to low predialysis pressure values were associated with significantly increased mortality. Adjustment for the malnutrition-inflammation mitigated only a small portion of paradoxical associations between the low blood pressure and mortality. Predialysis systolic hypertension remained a significant predictor of highest all-cause and cardiovascular survival rate. Although these associations may not be causal, they call into question whether treatment goals for the general population can be applied to dialysis patients or other similar populations.

Aged↗

Association of morbid obesity and weight change over time with cardiovascular survival in hemodialysis population.

BACKGROUND: In maintenance hemodialysis (MHD) outpatients, a reverse epidemiology is described, ie, baseline obesity appears paradoxically associated with improved survival. However, the association between changes in weight over time and prospective mortality is not known. METHODS: Using time-dependent Cox models and adjusting for changes in laboratory values over time, the relation of quarterly-varying 3-month averaged body mass index (BMI) to all-cause and cardiovascular mortality was examined in a 2-year cohort of 54,535 MHD patients from virtually all DaVita dialysis clinics in the United States. RESULTS: Patients, aged 61.7 +/- 15.5 (SD) years, included 54% men and 45% with diabetes. Time-dependent unadjusted and multivariate-adjusted models, based on quarterly-averaged BMI controlled for case-mix and available time-varying laboratory surrogates of nutritional status, were calculated in 11 categories of BMI. Obesity, including morbid obesity, was associated with better survival and reduced cardiovascular death, even after accounting for changes in BMI and laboratory values over time. Survival advantages of obesity were maintained for dichotomized BMI cutoff values of 25, 30, and 35 kg/m2 across almost all strata of age, race, sex, dialysis dose, protein intake, and serum albumin level. Examining the regression slope of change in weight over time, progressively worsening weight loss was associated with poor survival, whereas weight gain showed a tendency toward decreased cardiovascular death. CONCLUSION: Weight gain and both baseline and time-varying obesity may be associated with reduced cardiovascular mortality in MHD patients independent of laboratory surrogates of nutritional status and their changes over time. Morbidly obese patients have the lowest mortality. Clinical trials need to verify these observational findings.

Adult↗

Survival advantages of obesity in dialysis patients.

In the general population, a high body mass index (BMI; in kg/m(2)) is associated with increased cardiovascular disease and all-cause mortality. However, the effect of overweight (BMI: 25-30) or obesity (BMI: >30) in patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis (MHD) is paradoxically in the opposite direction; ie, a high BMI is associated with improved survival. Although this "reverse epidemiology" of obesity or dialysis-risk-paradox is relatively consistent in MHD patients, studies in CKD patients undergoing peritoneal dialysis have yielded mixed results. Growing confusion has developed among physicians, some of whom are no longer confident about whether to treat obesity in CKD patients. A similar reverse epidemiology of obesity has been described in geriatric populations and in patients with chronic heart failure (CHF). Possible causes of the reverse epidemiology of obesity include a more stable hemodynamic status, alterations in circulating cytokines, unique neurohormonal constellations, endotoxin-lipoprotein interaction, reverse causation, survival bias, time discrepancies among competitive risk factors, and malnutrition-inflammation complex syndrome. Reverse epidemiology may have significant clinical implications in the management of dialysis, CHF, and geriatric patients, ie, populations with extraordinarily high mortality. Exploring the causes and consequences of the reverse epidemiology of obesity in dialysis patients can enhance our insights into similar paradoxes observed for other conventional risk factors, such as blood pressure and serum cholesterol and homocysteine concentrations, and in other populations such as those with CHF, advanced age, cancer, or AIDS. Weight-gaining interventional studies in dialysis patients are urgently needed to ascertain whether they can improve survival and quality of life.

Body Mass Index↗

A matched comparison of serum lipids between hemodialysis patients and nondialysis morbid controls.

The high incidence of cardiac and vascular disease in maintenance hemodialysis (MHD) patients has heightened interest in many investigations concerning the serum lipid levels of these patients. The prevalence and laboratory characteristics of serum lipid concentrations in MHD patients, however, are far from clear. We hypothesized that serum lipids are significantly lower in MHD patients compared to their matched nondialysis counterparts. We compared 2-year averaged serum levels of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL), and triglycerides in 285 MHD patients to the same averaged measurements during the same period of time in 285 nondialyzed outpatients from the same geographic area, whose lipid panels were measured in the same laboratory. Matching factors were sex, race and/or ethnicity, diabetes mellitus, and age (+/- 5 years). The MHD patients and their matched controls were 55.6 +/- 13.5 (SD) and 56.3 +/- 13.0 years old, respectively. Each group contained 51% women, 31% African Americans, 52% Hispanics, and 37% diabetics; 16% of MHD patients and 38% of controls were receiving statins. Body mass index (BMI) was significantly lower in MHD patients than in controls (26.2 vs. 31.5 kg/m2; p < 0.001). Serum cholesterol levels were significantly lower in MHD patients than in control subjects including after adjustment for BMI and statin use (TC, -51; LDL, -39; and HDL, -10 mg/dL; p < 0.001). Using conditional logistic regression for matched data and after controlling for BMI and statins, all odds ratios for predetermined hypercholesterolemic, but not hypertriglyceridemic, levels were significantly and substantially lower than 1.00, indicating much lower likelihood of hypercholesterolemia in MHD patients. Total and LDL hypercholesterolemia, although very common in nondialysis ambulatory outpatients, are substantially less prevalent in the MHD population, whereas hypertriglyceridemia is approximately equally prevalent between these populations.

Adult↗

Reverse epidemiology: a spurious hypothesis or a hardcore reality?

In maintenance hemodialysis (MHD) patients, associations between demographic, clinical and laboratory values and mortality, including cardiovascular death, are significantly different and, in some cases, in the opposite direction of those derived from the general population. This phenomenon, termed 'reverse epidemiology', is not limited to MHD patients but is also observed in populations that encompass an estimated 20 million Americans including those with an advanced age, heart failure, malignancies, and AIDS. A significant portion of this reversal may be due to the overwhelming effect of the malnutrition-inflammation complex syndrome (MICS). Since two thirds of MHD patients die within 5 years of initiation of dialysis treatment, traditional cardiovascular risk factors such as obesity, hypercholesterolemia and hypertension cannot exert a long-term deleterious impact, and instead, their short-term beneficial effects on MICS provides a survival advantage. In order to improve survival and quality of life in MHD patients, extrapolated ideal norms derived from the general population should be substituted with novel norms obtained from outcome-oriented epidemiologic analyses while accounting for the differential effect of MICS in different case-mix subgroups.

Cardiovascular Diseases↗