Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients

Abstract

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.

Alkaline Phosphatase and Mortality in Patients on Peritoneal Dialysis

“…A possible explanation for the described association between total serum ALP level and mortality is that ALP is a marker of high-turnover bone disease, which has been linked to higher mortality (15,16). However, ALP may be more than a marker of bone turnover.…”

“…Some studies have examined the association between ALP level and mortality in HD patients. Kalantar-Zadeh et al (15) showed a higher risk of all-cause mortality associated with higher baseline and time-varying ALP levels in HD patients using the DaVita database. However, these analyses were not adjusted for serum calcium and phosphorus levels, which have been associated with higher mortality risk.…”

Transition of care from pre-dialysis prelude to renal replacement therapy: the blueprints of emerging research in advanced chronic kidney disease

“…However, there are some inherent limitations in the USRDS dataset, in particular the lack of key pre-ESRD care data; hence, there is an urgent need for innovative linkage approaches to address this shortcoming. Similarly, whereas over the past decade some important contributions related to dialysis patient studies and outcomes have emerged as a result of epidemiologic analyses of large national dialysis databases in the USA such as those from the clinical care of Fresenius [36] and DaVita patients [37], these databases often lack pre-ESRD data. Hence, linking the pre-transition or prelude data to large national ESRD databases and analyzing the prelude variables as predictors of early ESRD outcomes enables better examination of the impact of pre-ESRD care on outcomes during the RRT.…”

Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

“…Whereas the traditional cardiovascular risk factors do not account for the increased mortality in CKD patients (3,4), measures of mineral and bone disorders (MBD), including hyperphosphatemia, are associated with increased death risk (5)(6)(7)(8)(9). Hyperphosphatemia may be involved in the pathogenesis of vascular calcification (10)(11)(12).…”