Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

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.

A low baseline body fat percentage and fat loss over time are independently associated with higher mortality in MHD patients even after adjustment for demographics and surrogates of muscle mass and inflammation, whereas a tendency toward a worse QoL is reported by MHD patients with a higher body fat percentage. Obesity management in dialysis patients may need reconsideration.

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.

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Lym pho cyte per cent age, mal nu tri tion-in flam ma tion and di al y sis out come Ab stract. Ob jec tives: Lym pho cyte percent age (LYM%), an in de pend ently measured value to re flect pe riph eral lym pho cyte count and a pos si ble nu tri tional marker, may be re lated to clin i cal out come in main te nance di al y sis (MHD) pa tients. Study de sign and set ting: We ex am ined the as so ci a tions of the base line white blood cell count (WBC) and LYM% with 12-month mor tal ity and three mea sures of hos pi tal iza tion in a co hort of 1,283 MHD pa tients from 10 out pa tient DaVita di al y sis clin ics in Los An geles County, as well as in a subcohort of 372 MHD pa tients with ad di tional mea sures of in flamma tion, nu tri tion and comorbidity. Multivariate Cox and Pois son mod els that in cluded 13 co-vari ates in clud ing case-mix fea tures, di al y sis dose, blood he mo glo bin and se rum al bu min were ex plored. Re sults: Pa tients, aged 57.8 ± 15.2 years, in cluded 49% men and 49% di a bet ics. Base line WBC was 7,353 ± 2.427 per µl, and LYM% was 21.2 ± 7.3%. LYM% had sig nif i cant cor re la tions with "malnutrition-inflam mation score" and inverse cor re la tions with se rum interleukin-6. The WBC and LYM% had sig nif i cant but oppo site pre dict ing va l ues for mor tal ity and hos pi tal iza tion, in di cat ing that a high WBC and a low LYM% were each in de pend ently as so ci ated with in creased mor tality. Af ter divid ing each vari able into four quartiles, only the high est WBC quar tile (≥ 8,500) but not the other mid dle two quartiles, pre dicted increased mor tal ity. How ever, all three lower quartiles of LYM% vs. the high est quar tile (based on quar tile cut offs of 16%, 20.3% and 25.5%) were sig nif i cantly and pro gres sively as so ci ated with greater risks of mor tal ity and hos pi tal iza tions. The ab so lute lym pho cyte count (LYM% times WBC/100) ex hib ited some what sim i lar trends but its out come predict abil ity was not as strong as LYM%. Conclu sions: A high WBC and a low LYM% are as so ci ated with sig nif i cant in crease in mor tal-ity and hos pi tal iza tion in MHD pa tients. Lym pho cyte per cent age, com pared to ab solute lym pho cyte count, ap pears to be a better nu tri tional and anti-in flammatory marker and a more sen si tive pre dic tor of mor tal ity and hos pi tal iza tion in MHD pa tients. Key words white blood cell countlym pho cyte per cent age-mor tal ity-hos pi tal ization-hemodialysis Re ceived Jan u ary 9, 2004; ac cepted in re vised form

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