The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline for Bone Metabolism and Disease in CKD: association with mortality in dialysis patients

BACKGROUND: In 2003, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) published a guideline recommending tight control of serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone levels in patients with chronic kidney disease. Within the context of this guideline, we explored associations of these plasma concentrations with all-cause mortality risk in incident dialysis patients in The Netherlands. METHODS: In a large, prospective, multicenter, cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis), we included 1,629 patients new on hemodialysis or peritoneal dialysis therapy between 1997 and 2004. Multivariate Cox regression models containing calcium level, phosphorus level, intact parathyroid hormone level, age, comorbidity, primary kidney disease, nutritional status, albumin level, dialysis dose, and hemoglobin level were used to examine mortality risks. RESULTS: Mean age was 60 +/- 15 (SD) years, 61% were men, and 64% were treated with hemodialysis. In adjusted time-dependent survival analysis, all-cause mortality risk increased in hemodialysis patients by 40% (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1 to 1.7) and in peritoneal dialysis patients by 60% (HR, 1.6; 95% CI, 1.1 to 2.4) for plasma phosphorus levels greater than the target. In addition, having elevated plasma Ca x P product levels increased mortality risk by 40% (HR, 1.4; 95% CI, 1.1 to 1.8) in hemodialysis patients and 50% in peritoneal dialysis patients (HR, 1.5; 95% CI, 1.0 to 2.2). In both patient groups, no significant effects were observed for plasma levels less than the targets. CONCLUSION: In time-dependent survival analysis, the presence of plasma phosphorus and Ca x P product concentrations greater than K/DOQI targets increased all-cause mortality risk in hemodialysis and peritoneal dialysis patient

Disordered mineral metabolism is not a risk factor for loss of residual renal function in dialysis patients

BACKGROUND: Recent studies showed that mineral metabolism disorders are associated with renal function loss in pre-dialysis patients, but their effects in dialysis patients are less well established. We examined associations between parameters of mineral metabolism and loss of residual renal function (RRF) in dialysis patients. METHODS: We included 1468 incident haemodialysis (HD) and peritoneal dialysis (PD) patients who were not anuric at dialysis initiation from NECOSAD, a prospective multicentre cohort study. We studied the effects of plasma calcium, phosphorus, calcium-phosphorus product and intact PTH concentrations on loss of RRF. Cox regression models were applied to calculate relative risks of total loss of RRF, defined as anuria during the first 3 years of dialysis. The rate of decline of RRF over time was calculated using general linear mixed models. RESULTS: The mean (SD) age was 59 (15), 62% were men and 59% were treated with HD. We found that both HD and PD patients with the highest phosphorus (P < 0.0001) and calcium-phosphorus product (P < 0.0001) levels had the lowest baseline residual glomerular filtration rate (rGFR) values. During follow-up, 136 HD (15%) and 67 PD patients (12%) became anuric. After adjustment for baseline rGFR, there were no significant associations between parameters of mineral metabolism and the risk of becoming anuric. There were also no differences in the rate of decline in RRF between categories of plasma concentrations. CONCLUSION: Disordered mineral metabolism was neither associated with the risk of becoming anuric, nor with the rate of decline in RRF in dialysis patients. Differences in decline were mainly attributable to the baseline rGFR valu

Mineral metabolism and cardiovascular morbidity and mortality risk: peritoneal dialysis patients compared with haemodialysis patients

BACKGROUND: The K/DOQI guideline for bone metabolism and disease in chronic kidney disease is predominantly based on studies in haemodialysis (HD) patients. However, in clinical practice, this guideline is also applied to peritoneal dialysis (PD) patients. To validate the implementation of this guideline in PD patients, we evaluated the associations between plasma concentrations outside the K/DOQI-targets and the risk of cardiovascular morbidity and mortality in incident PD patients compared with HD patients. METHODS: In a large prospective multicentre study in the Netherlands (The Netherlands Cooperative Study on the Adequacy of Dialysis, NECOSAD), we included patients starting PD or HD between 1997 and 2004. Relative risk of cardiovascular morbidity and mortality were estimated using time-dependent Cox regression modelling. RESULTS: We included 586 PD patients with mean age 52 +/- 15 years (66% males) and 1043 HD patients with mean age 63 +/- 14 years (58% males). Cardiovascular disease (CVD) was the reason for hospitalization in 102 PD and 271 HD patients. In HD patients, the relative risk of CVD-related hospitalization increased with elevated plasma calcium concentrations (hazard ratio: 1.4; 95% CI: 1.1-1.9). Cardiovascular mortality was significantly higher for phosphorus concentrations above the K/DOQI-threshold in PD (2.4; 95% CI: 1.3-4.2) and HD patients (1.5; 95% CI: 1.1-2.1), and for elevated Ca x P in PD (2.2; 95% CI: 1.3-3.8) and HD patients (1.5; 95% CI: 1.1-2.1). CONCLUSIONS: Plasma calcium concentrations above the K/DOQI-threshold increase the relative risk of CVD-related hospitalization in HD patients. Associations with cardiovascular mortality were more pronounced. Both in PD and HD patients with elevated plasma phosphorus and Ca x P concentrations, the cardiovascular mortality risk is increased. Therefore, it seems appropriate to adopt the current guideline in PD patient

Disturbed mineral metabolism is associated with muscle and skin complaints in a prospective cohort of dialysis patients

BACKGROUND: Disturbed mineral metabolism is associated with increased morbidity and mortality, however, its influence on physical symptoms is less clear. We explored the effects of disordered plasma calcium, phosphorus, calcium-phosphorus (Ca x P) product and intact parathyroid hormone (iPTH) concentrations according to the K/DOQI guideline for bone metabolism and disease on the risk of muscle and skin complaints in dialysis patients. METHODS: As part of NECOSAD, a prospective multicentre study in the Netherlands, we included 1469 consecutive patients who started haemodialysis or peritoneal dialysis between 1997 and 2004. Muscle pain, cramps and itching (pruritus) and dry (xerosis) skin were repeatedly measured using the Kidney Disease Quality of Life-Short Form questionnaire. Odds ratios (OR) for the risk of complaints over time were calculated by generalized estimating equations (GEE) models. RESULTS: Mean age was 59 +/- 15 years, 61% of the patients were male and 63% were on haemodialysis. At baseline >65% of the patients had muscle and skin complaints. Compared with patients who met the target, the risk of muscle pain was increased in patients with hyperphosphataemia [OR: 1.2; 95% confidence interval (CI): 1.1-1.5] iPTH concentrations below the target range were associated with lower risk of cramps (OR 0.8, 95%CI: 0.6-0.9). The risk of pruritus was increased in patients with severely elevated plasma calcium (OR 1.4; 95%CI: 1.1-1.7), phosphorus (OR 1.4; 95%CI: 1.1-1.7) and Ca x P product levels (OR 1.6; 95%CI: 1.3-2.0). Finally, increased plasma calcium concentrations were associated with an elevated risk of xerosis (OR 1.4; 95%CI: 1.1-1.9). CONCLUSIONS: Disturbed mineral metabolism according to the K/DOQI guideline is associated with more muscle and skin complaints in dialysis patients. These findings emphasize the importance of keeping mineral metabolism in dialysis patients in tight contro