Mortality Risk for Dialysis Patients With Different Levels of Serum Calcium, Phosphorus, and PTH: The Dialysis Outcomes and Practice Patterns Study (DOPPS)

Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and are an important cause of morbidity, decreased quality of life, and extraskeletal calcification that have been associated with increased cardiovascular mortality. These disturbances have traditionally been termed renal osteodystrophy and classified based on bone biopsy. Kidney Disease: Improving Global Outcomes (KDIGO) sponsored a Controversies Conference on Renal Osteodystrophy to (1) develop a clear, clinically relevant, and internationally acceptable definition and classification system, (2) develop a consensus for bone biopsy evaluation and classification, and (3) evaluate laboratory and imaging markers for the clinical assessment of patients with CKD. It is recommended that (1) the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD, which can be further assessed by histomorphometry, and the results reported based on a unified classification system that includes parameters of turnover, mineralization, and volume, and (2) the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD, which is manifested by abnormalities in bone and mineral metabolism and/or extra-skeletal calcification. The international adoption of these recommendations will greatly enhance communication, facilitate clinical decision-making, and promote the evolution of evidence-based clinical practice guidelines worldwide.

Logistic regression analysis was applied to a sample of more than 12,000 hemodialysis patients to evaluate the association of various patient descriptors, treatment time (hours/treatment), and various laboratory tests with the probability of death. Advancing age, white race, and diabetes were all associated with a significantly increased risk of death. Short dialysis times were also associated with high death risk before adjustment for the value of laboratory tests. Of the laboratory variables, low serum albumin less than 40 g/L (less than 4.0 g/dL) was most highly associated with death probability. About two thirds of patients had low albumin. These findings suggest that inadequate nutrition may be an important contributing factor to the mortality suffered by hemodialysis patients. The relative risk profiles for other laboratory tests are presented. Among these, low serum creatinine, not high, was associated with high death risk. Both serum albumin concentration and creatinine were directly correlated with treatment time so that high values for both substances were associated with long treatment times. The data suggest that physicians may select patients with high creatinine for more intense dialysis exposure and patients with low creatinine for less intense treatment. In a separate analysis, observed death rates were compared with rates expected on the basis of case mix for these 237 facilities. The data suggest substantial volatility of observed/expected ratios when facility size is small. Nonetheless, a minority of facilities (less than or equal to 2%) may have higher rates than expected when compared with the pool of all patients in this sample. The effect of various laboratory variables on mortality is substantial, while relatively few facilities have observed death rates that exceed their expected values. Therefore, we suggest that strategies designed to improve the overall mortality statistic for dialysis patients in the United States would be better directed toward improving the quality of care for all patients, particularly high-risk patients, within their usual treatment settings rather than trying to identify facilities with high death rate for possible regulatory intervention.