Phosphate binder pill burden, patient-reported non-adherence, and mineral bone disorder markers: Findings from the DOPPS.

Because of multiple comorbidities, hemodialysis (HD) patients are prescribed many oral medications, including phosphate binders (PBs), often resulting in a high "pill burden." Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we assessed associations between PB pill burden, patient-reported PB non-adherence, and levels of serum phosphorus (SPhos) and parathyroid hormone (PTH) using standard regression analyses. The study included data collected from 5262 HD patients from dialysis units participating in the DOPPS in 12 countries. PB prescription ranged from a mean of 7.4 pills per day in the United States to 3.9 pills per day in France. About half of the patients were prescribed at least 6 PB pills per day, and 13% were prescribed at least 12 PB pills per day. Overall, the proportion of patients who reported skipping PBs at least once in the past month was 45% overall, ranging from 33% in Belgium to 57% in the United States. There was a trend toward greater PB non-adherence and a higher number of prescribed PB pills per day. Non-adherence to PB prescription was associated with high SPhos (>5.5 mg/dL) and PTH (>600 pg/mL). Adherence to PB is a challenge for many HD patients and may be related to the number of PB pills prescribed. Prescription of a simplified PB regimen could improve patient adherence and perhaps improve SPhos and PTH levels.

Dialysate sodium prescription and blood pressure in hemodialysis patients.

BACKGROUND: Diffusive sodium removal has been recommended to control hypertension in hemodialysis patients. Recent evidence on hospitalizations and mortality, however, challenged the benefit of lower dialysate sodium prescriptions and ignited a debate in the dialysis community. We therefore studied the relationship between dialysate sodium and blood pressure over the longer term. METHODS: We used multiply adjusted linear mixed models to estimate the association between dialysate sodium and predialysis systolic blood pressure (SBP) as well as change in SBP (delta SBP; postdialysis minus predialysis) in 23,962 patients from the international Dialysis Outcomes and Practice Patterns Study. RESULTS: We found that 43% of hemodialysis facilities had variable (individualized) dialysate sodium prescriptions (125-155 mEq/L), whereas 57% had uniform dialysate sodium prescriptions (135-145 mEq/L) for ≥90% patients. Between-group comparisons of these 2 facility types suggested that dialysate sodium, when variably prescribed, might have been used to modify predialysis SBP (P interaction = 0.01) and perhaps delta SBP levels (P interaction = 0.08). Within facilities not prone to indication bias, because dialysate sodium was not variable, higher uniform dialysate sodium (per 2 mEq/L) was associated with slightly higher SBP (+0.9 mm Hg, 95% confidence interval (CI) = 0.1-1.6 among all patients; +1.7 mm Hg, 95% CI = 0.1-3.2 among patients not treated with blood pressure medication) and no increase in delta SBP. CONCLUSIONS: Patients assigned to hemodialysis facilities with uniformly higher dialysate sodium do not have markedly higher predialysis SBP, providing rather limited support for lowering dialysate sodium to control hypertension, particularly in view of hospitalization and mortality risks associated with lower dialysate sodium.

Phosphate binder use and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS): evaluation of possible confounding by nutritional status.

BACKGROUND: Poor nutritional status and both hyper- and hypophosphatemia are associated with increased mortality in maintenance hemodialysis (HD) patients. We assessed associations of phosphate binder prescription with survival and indicators of nutritional status in maintenance HD patients. STUDY DESIGN: Prospective cohort study (DOPPS [Dialysis Outcomes and Practice Patterns Study]), 1996-2008. SETTING & PARTICIPANTS: 23,898 maintenance HD patients at 923 facilities in 12 countries. PREDICTORS: Patient-level phosphate binder prescription and case-mix-adjusted facility percentage of phosphate binder prescription using an instrumental-variable analysis. OUTCOME: All-cause mortality. RESULTS: Overall, 88% of patients were prescribed phosphate binders. Distributions of age, comorbid conditions, and other characteristics showed small differences between facilities with higher and lower percentages of phosphate binder prescription. Patient-level phosphate binder prescription was associated strongly at baseline with indicators of better nutrition, ie, higher values for serum creatinine, albumin, normalized protein catabolic rate, and body mass index and absence of cachectic appearance. Overall, patients prescribed phosphate binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for serum phosphorus level and other covariates; further adjustment for nutritional indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However, this inverse association was observed for only patients with serum phosphorus levels ≥3.5 mg/dL. In the instrumental-variable analysis, case-mix-adjusted facility percentage of phosphate binder prescription (range, 23%-100%) was associated positively with better nutritional status and inversely with mortality (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment for nutritional indicators reduced this association to an HR of 0.95 (95% CI, 0.92-0.99). LIMITATIONS: Results were based on phosphate binder prescription; phosphate binder and nutritional data were cross-sectional; dietary restriction was not assessed; observational design limits causal inference due to possible residual confounding. CONCLUSIONS: Longer survival and better nutritional status were observed for maintenance HD patients prescribed phosphate binders and in facilities with a greater percentage of phosphate binder prescription. Understanding the mechanisms for explaining this effect and ruling out possible residual confounding require additional research.

Pharmacokinetics of sulfobutylether-beta-cyclodextrin and voriconazole in patients with end-stage renal failure during treatment with two hemodialysis systems and hemodiafiltration.

Sulfobutylether-beta-cyclodextrin (SBECD), a large cyclic oligosaccharide that is used to solubilize voriconazole (VRC) for intravenous administration, is eliminated mainly by renal excretion. The pharmacokinetics of SBECD and voriconazole in patients undergoing extracorporeal renal replacement therapies are not well defined. We performed a three-period randomized crossover study of 15 patients with end-stage renal failure during 6-hour treatment with Genius dialysis, standard hemodialysis, or hemodiafiltration using a high-flux polysulfone membrane. At the start of renal replacement therapy, the patients received a single 2-h infusion of voriconazole (4 mg per kg of body weight) solubilized with SBECD. SBECD, voriconazole, and voriconazole-N-oxide concentrations were quantified in plasma and dialysate samples by high-performance liquid chromatography (HPLC) and by HPLC coupled to tandem mass spectrometry (LC-MS-MS) and analyzed by noncompartmental methods. Nonparametric repeated-measures analysis of variance (ANOVA) was used to analyze differences between treatment phases. SBECD and voriconazole recoveries in dialysate samples were 67% and 10% of the administered doses. SBECD concentrations declined with a half-life ranging from 2.6 +/- 0.6 h (Genius dialysis) to 2.4 +/- 0.9 h (hemodialysis) and 2.0 +/- 0.6 h (hemodiafiltration) (P < 0.01 for Genius dialysis versus hemodiafiltration). Prediction of steady-state conditions indicated that even with daily hemodialysis, SBECD will still exceed SBECD exposure of patients with normal renal function by a factor of 6.2. SBECD was effectively eliminated during 6 h of renal replacement therapy by all methods, using high-flux polysulfone membranes, whereas elimination of voriconazole was quantitatively insignificant. The SBECD half-life during renal replacement therapy was nearly normalized, but the average SBECD exposure during repeated administration is expected to be still increased.

Cardiovascular problems on hemodialysis: current deficits and potential improvement.

High cardiovascular mortality is the major cause of reduced life expectancy of patients who are on hemodialysis. Classical risk factors cannot fully explain the magnitude of the risk. This article addresses some nontraditional approaches to deal with the excessive cardiovascular risk for patients who are on hemodialysis.

Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Abnormalities in serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. No clinical trials have been conducted to clearly identify categories of calcium, phosphorus, and PTH levels associated with the lowest mortality risk. Current clinical practice guidelines are based largely on expert opinions, and clinically relevant differences exist among guidelines across countries. We sought to describe international trends in calcium, phosphorus, and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international study of hemodialysis practices and associated outcomes. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I (1996-2001), DOPPS II (2002-2004), or DOPPS III (2005-2007). PREDICTORS: Serum calcium, albumin-corrected calcium (Ca(Alb)), phosphorus, and PTH levels. OUTCOMES: Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models. RESULTS: Distributions of mineral metabolism markers differed across DOPPS countries and phases, with lower calcium and phosphorus levels observed in the most recent phase of DOPPS. Survival models identified categories with the lowest mortality risk for calcium (8.6 to 10.0 mg/dL), Ca(Alb) (7.6 to 9.5 mg/dL), phosphorus (3.6 to 5.0 mg/dL), and PTH (101 to 300 pg/mL). The greatest risk of mortality was found for calcium or Ca(Alb) levels greater than 10.0 mg/dL, phosphorus levels greater than 7.0 mg/dL, and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium, phosphorus, and PTH. LIMITATIONS: Because of the observational nature of DOPPS, this study can only indicate an association between mineral metabolism categories and mortality. CONCLUSIONS: Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade. The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism.

Calcium load during administration of calcium carbonate or sevelamer in individuals with normal renal function.

BACKGROUND: Under steady-state conditions urinary calcium (Ca) excretion corresponds to the Ca load in healthy subjects. However, in chronic haemodialysis patients reliable data on Ca load are not available. In these patients Ca-containing phosphate binders are suspected to play a role in the progression of arteriosclerosis via increased but not quantified Ca load. The present study evaluated the effect of calcium carbonate (CC) and sevelamer hydrochloride (SEV), a calcium-free phosphate binder, on serum Ca and urinary Ca excretion in healthy individuals. METHODS: Twelve healthy male individuals were included in a monocentre, randomized, single-blind, placebo-controlled, three-way crossover phase I study. Concurrently with their meals, participants received 4 x 2 tablets of SEV (800 mg), CC (500 mg) or placebo for 6 days with 1-week washout between the treatment periods. During the study, weekly blood samples were taken and 24-h urine was collected each day for measurement of calcium, magnesium, phosphorus, chloride and iPTH. RESULTS: Mean daily urinary phosphorus excretion was significantly lower in subjects undergoing SEV treatment compared to those taking placebo (P < 0.001). Mean daily total urinary excretion of calcium was significantly higher in CC-treated participants compared to those receiving placebo (P < 0.001). Mean 24-h calcium excretion during the 6 treatment days was 6.60 +/- 2.62 mmol [265 +/- 105 mg] (CC) versus 5.15 +/- 2.16 mmol [206 +/- 87 mg] (SEV) versus 4.95 +/- 1.63 mmol [198 +/- 65 mg] (Placebo). Taking into account nutritional calcium intake estimated from dietary records fractional calcium absorption was 8.7% (CC), 13.3% (placebo) and 14.8% (sevelamer). CONCLUSION: Intake of calcium carbonate compared to placebo in contrast to sevelamer in healthy individuals was associated with increased total urinary calcium excretion indicating an increased calcium load due to increased intestinal calcium absorption.

Vitamin D receptor activator selectivity in the treatment of secondary hyperparathyroidism: understanding the differences among therapies.

Secondary hyperparathyroidism (SHPT) is a common and serious consequence of chronic kidney disease (CKD). SHPT is a complex condition characterised by a decline in 1,25-dihydroxyvitamin D and consequent vitamin D receptor (VDR) activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drugs used for treatment of SHPT: (i) nonselective VDR activators or agonists (VDRAs); (ii) selective VDRAs; and (iii) calcimimetics. The VDRAs act on the VDR, whereas the calcimimetics act on the calcium-sensing receptor. Calcimimetics are commonly used in conjunction with VDRA therapy. By virtue of the differences in their chemical structure, the nonselective and selective VDRAs differ in their effects on gene expression, and ultimately parathyroid gland, bone and intestine function. Medications in all three classes are effective in suppression of PTH; however, clinical studies show that calcimimetics are associated with an unfavourable tolerability profile and hypocalcaemia, whereas nonselective VDRAs, and to a lesser extent selective VDRAs, are associated with dose-limiting hypercalcaemia and hyperphosphataemia. Selective VDRAs also have minimal undesirable effects on calcium absorption in the intestine, and calcium and phosphorus mobilisation in the bone compared with nonselective VDRAs. Calcium load in patients with CKD can lead to vascular calcification, accelerated progression of cardiovascular disease and increased mortality. High serum phosphorus levels are also associated with adverse effects on cardiorenal function and survival. Recent evidence suggests that VDRAs are associated with a survival benefit in CKD patients, with a more favourable effect with selective VDRAs than nonselective VDRAs. Paricalcitol, a selective VDRA, is reported to exert specific effects on gene expression in various cell types that are involved in vascular calcification and the development of coronary artery disease. This article examines the molecular mechanisms that determine selectivity of VDRAs, and reviews the evidence for clinical efficacy, safety and survival associated with the three drug classes used for treatment of SHPT in CKD patients.

Improving outcomes for dialysis patients in the international Dialysis Outcomes and Practice Patterns Study.

The international Dialysis Outcomes and Practice Patterns Study (DOPPS) is well suited to evaluate levels of deviation from emerging and established guidelines to clinical practice of hemodialysis, over time and by country. The DOPPS can also evaluate whether the target levels that are chosen in the guidelines are in agreement with outcomes such as elevated risk for mortality, hospitalization, and vascular access failure. At a special DOPPS symposium during the 2004 congress of the American Society of Nephrology, the authors presented such findings; key points from that symposium are presented in this article, focusing on vascular access, mineral metabolism, dialysis dose, and anemia management. Although an observational study cannot prove causality, DOPPS suggests large opportunities to improve care and outcomes of dialysis patients. The international perspective of DOPPS assists in the new efforts for international guidelines. Some encouraging trends in recent years are documented in these areas.

Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl.

BACKGROUND: Patients with secondary hyperparathyroidism often require therapy that provides long-term control of parathyroid hormone concentrations without increasing calcium and phosphorus concentrations. Cinacalcet modulates the calcium-sensing receptor on the parathyroid gland to reduce secretion of parathyroid hormone and lower serum calcium, phosphorus and calcium-phosphorus product in haemodialysis patients. METHODS: Dialysis patients with secondary hyperparathyroidism [parathyroid hormone (PTH) level > or =300 pg/ml] who were enrolled in one of four phase 2 placebo-controlled studies were eligible to enroll in an open-label extension study in which all patients received cinacalcet. For this extension study, cinacalcet was initiated at 30 mg in all patients and the dose was escalated to a maximum of 180 mg once daily if PTH concentrations were >250 pg/ml. Use of concomitant vitamin D sterols and phosphate binders was not restricted. RESULTS: The analysis of all patients (n = 59) completing 100 weeks of cinacalcet treatment showed long-term control of PTH and calcium-phosphorus product. Approximately 55% achieved a PTH concentration < or =300 pg/ml at the week-100 study visit, and approximately 60% had at least a 30% reduction in PTH from baseline. Serum calcium, phosphorus and the calcium-phosphorus product did not increase during the study. Concomitant vitamin D sterol and phosphate binder therapy remained stable. Cinacalcet was safe and generally well tolerated at doses up to 180 mg/day. CONCLUSIONS: In this long-term study, cinacalcet effectively sustained reductions in PTH for up to 3 years without increasing concentrations of serum calcium, phosphorus or calcium-phosphorus product.

Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density.

BACKGROUND: Calcium-based phosphate binders may induce tissue calcification, and little is known about their effects on bone density. We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography. METHODS: Seventy-two adult haemodialysis patients were randomized to treatment with calcium carbonate (CC) or sevelamer (SEV) for 2 years. Electron beam CT scans were performed at baseline and at 6, 12 and 24 months. Serum phosphorus, calcium, calcium x phosphorus product and intact parathyroid hormone (iPTH) were measured and other routine laboratory tests were also carried out. RESULTS: The average calcium x phosphorus product was similar in the two treatment groups. However, patients receiving CC had significantly lower average iPTH (P<0.01), were more likely to have hypercalcaemic episodes (P = 0.03) and had significantly greater increases in coronary artery (CC median 484, P<0.0001, SEV median 37, P = 0.3118, between-group P = 0.0178) and aortic (CC median 610, P = 0.0003, SEV median 0, P = 0.5966, between-group P = 0.0039) calcification scores. The CC group also had a significant decrease in trabecular bone density (CC median -6%, P = 0.0049, SEV median +3%, P = 0.0296, between-group P = 0.0025). However, there was no significant difference in cortical bone density between the two groups. CONCLUSIONS: This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients. In addition, it suggests that it is also associated with decreased trabecular bone density. However, this latter finding requires confirmation by a study specifically devoted to this issue.

Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis.

UNLABELLED: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.

Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. METHODS: This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N= 307) and patients (N= 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001. RESULTS: Many patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P= 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg(2)/dL(2), P= 0.0001), PTH (1.01 per 100 pg/dL, P= 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P= 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P= 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P= 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration. CONCLUSION: This study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area.

Health-related quality of life in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Health-related quality of life (HRQOL), a validated system of measuring patients' physical, mental, and social well-being, can be of particular use in populations with chronic conditions, such as end-stage renal disease (ESRD). METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS) has used the Kidney Disease Quality of Life Short Form (KDQOL-SF) to measure ESRD patients' self-assessment of functioning and well-being, as measured by 3 component scores: physical component summary (PCS, 4 subscales), mental component summary (4 subscales), and kidney disease component summary (11 subscales). Several DOPPS studies examined HRQOL's associations with mortality and hospitalization by country, ethnicity (United States only), and in comparison with serum albumin levels; international variations in HRQOL of ESRD patients were also evaluated. RESULTS: Lower scores for all 3 summary scores were strongly associated with higher risk of death and hospitalization; these measures, especially PCS, may better identify patients at risk for death and hospitalization than serum albumin level. Japanese patients reported a greater burden of kidney disease but higher physical functioning than patients in Europe or the United States; many other significant regional differences in HRQOL were found. In the United States, all summary scores were significantly associated with mortality risk, regardless of ethnicity. Compared with whites, blacks had higher scores for all 3 summary scores, Asians and Hispanics had higher PCS scores, and Native Americans had lower mental component summary scores. CONCLUSION: Among ESRD patients, HRQOL displays an important predictive power for adverse events. Identifying effective interventions to improve the HRQOL of patients with ESRD should be viewed as a valued health care goal.

Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Experimental and some clinical data suggest that metabolic acidosis contributes to poor nutritional status, a strong predictor for mortality in hemodialysis patients. However, recent cross-sectional studies indicate that severe predialysis metabolic acidosis is associated with a greater normalized protein catabolic rate (nPCR) and greater serum albumin levels. Given this controversy, we analyzed data from the Dialysis Outcomes and Practice Pattern Study (DOPPS) for associations between predialysis serum bicarbonate and albumin concentrations, nPCR, and patient risk for mortality and hospitalization. METHODS: Data from more than 7,000 representative and randomly selected hemodialysis DOPPS patients from France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States were analyzed. Serum bicarbonate (total CO2 ) levels predialysis were corrected to the midweek interdialytic interval. RESULTS: The midweek predialysis serum bicarbonate level averaged 21.9 mEq/L (mmol/L) and correlated inversely with nPCR, serum albumin, and serum phosphorus values. Before and after adjusting for 15 comorbidities, nutrition, and equilibrated Kt/V, a U-curve best represented the association between predialysis serum bicarbonate level and risk for mortality or hospitalization. Patients with midweek predialysis serum bicarbonate levels of 20.1 to 21.0 mEq/L (mmol/L) faced the lowest risk for mortality, whereas those with bicarbonate levels of 21.1 to 22.0 mEq/L faced the lowest risk for hospitalization. Both high (>27 mEq/L) and low (< or =17 mEq/L) serum bicarbonate levels were associated with increased risk for mortality and hospitalization. CONCLUSION: Moderate predialysis acidosis seems to be associated with better nutritional status and lower relative risk for mortality or hospitalization than is observed in patients with normal ranges of midweek predialysis serum bicarbonate concentration (approximately 24 mEq/L) or severe acidosis (<16 mEq/L).

Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.

BACKGROUND: Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEpo), darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo. This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia. METHODS: In this multicentre, prospective, open-label study, 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [intravenous (i.v.), n = 900 or subcutaneous (s.c.), n = 602]. Subjects receiving rHuEpo two (n = 408, 27%) or three times (n = 884, 59%) a week were switched to darbepoetin alfa once a week, and those receiving rHuEpo once a week (n = 210, 14%) were switched to darbepoetin alfa once every 2 weeks. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations of 10-13 g/dl for 24 weeks. RESULTS: Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks. The overall mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was +0.10 g/dl [95% confidence interval (CI) 0.04+/- 0.17]. The mean haemoglobin concentration increased by 0.19 g/dl (95% CI 0.11+/-0.27) in subjects receiving i.v. darbepoetin alfa, and was unchanged (-0.02 g/dl; 95% CI -0.12 to 0.07) in patients treated with s.c. darbepoetin alfa. Subjects with baseline haemoglobin < 11 g/dl experienced a clinically relevant increase in mean haemoglobin concentration of 0.67 g/dl (95% CI 0.56+/-0.77) from baseline to the evaluation period. The mean weekly i.v. and s.c. darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week (95% CI 19.02+/-20.87) and 21.6 microg/week (95% CI 20.36+/- 22.94), respectively. Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects. CONCLUSIONS: Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated. Moreover, administration of darbepoetin alfa by both the i.v. and s.c. route is associated with stable haemoglobin concentrations.

Health-related quality of life among dialysis patients on three continents: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Assessing health-related quality of life (HRQOL) can provide information on the types and degrees of burdens that afflict patients with chronic medical conditions, including end-stage renal disease (ESRD). Several studies have shown important international differences among ESRD patients treated with hemodialysis, but no studies have compared these patients' HRQOL. Our goal was to document international differences in HRQOL among dialysis patients and to identify possible explanations of those differences. METHODS: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational, international study of hemodialysis patients. We performed a cross-sectional analysis of DOPPS data from the United States, five countries in Europe (France, Germany, Italy, Spain, and the United Kingdom), and Japan. Linear mixed models were used to analyze differences in HRQOL, using the KDQOL-SFTM. Norm-based scores were used to minimize cultural response bias. Linear regression analysis was used to adjust for confounding factors. Other variables included demographic variables, comorbidities, primary cause of ESRD, complications of ESRD and treatment, and socioeconomic status. RESULTS: In all generic HRQOL subscales, patients on all three continents had much lower scores than their respective population norm values. Patients in the United States had the highest scores on the mental health subscale and the highest mental component summary scores. Japanese patients reported better physical functioning than did patients in the United States or Europe, but they also reported the greatest burden of kidney disease. Overall, these differences remained even after adjusting for possible confounders. CONCLUSION: On all three continents, ESRD and hemodialysis profoundly affect HRQOL. In the United States, the effects on mental health are smaller than in other countries. Japanese hemodialysis patients perceived that their kidney disease imposes a greater burden, but their physical functioning was significantly higher. Different distributions of socioeconomic factors and major comorbid conditions could explain little of this difference in physical functioning. Other possible factors, such as quality of dialysis and related health care, deserve careful study.

Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: We investigated whether indicators of health-related quality of life (HRQOL) may predict the risk of death and hospitalization among hemodialysis patients treated in seven countries, taking into account serum albumin concentration and several other risk factors for death and hospitalization. We also compared HRQOL measures with serum albumin regarding their power to predict outcomes. METHODS: We analyzed data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international, prospective, observational study of randomly selected hemodialysis patients in the United States (148 facilities), five European countries (101 facilities), and Japan (65 facilities). The total sample size was composed of 17,236 patients. Using the Kidney Disease Quality of Life Short Form (KDQOL-SFTM), we determined scores for three components of HRQOL: (1) physical component summary (PCS), (2) mental component summary (MCS), and (3) kidney disease component summary (KDCS). Complete responses on HRQOL measures were obtained from 10,030 patients. Cox models were used to assess associations between HRQOL and the risk of death and hospitalization, adjusted for multiple sociodemographic variables, comorbidities, and laboratory factors. RESULTS: For patients in the lowest quintile of PCS, the adjusted risk (RR) of death was 93% higher (RR = 1.93, P < 0.001) and the risk of hospitalization was 56% higher (RR = 1.56, P < 0.001) than it was for patients in the highest quintile level. The adjusted relative risk values of mortality per 10-point lower HRQOL score were 1.13 for MCS, 1.25 for PCS, and 1.11 for KDCS. The corresponding adjusted values for RR for first hospitalization were 1.06 for MCS, 1.15 for PCS, and 1.07 for KDCS. Each RR differed significantly from 1 (P < 0.001). For 1 g/dL lower serum albumin concentration, the RR of death adjusted for PCS, MCS, and KDCS and the other covariates was 1.17 (P < 0.01). Albumin was not significantly associated with hospitalization (RR = 1.03, P> 0.5). CONCLUSION: Lower scores for the three major components of HRQOL were strongly associated with higher risk of death and hospitalization in hemodialysis patients, independent of a series of demographic and comorbid factors. A 10-point lower PCS score was associated with higher elevation in the adjusted mortality risk, as was a 1 g/dL lower serum albumin level. More research is needed to assess whether interventions to improve quality of life lower these risks among hemodialysis patients.

Prevalence and socio-economic aspects of chronic kidney disease.

The incidence and prevalence of end-stage renal disease (ESRD) are rising in Europe, the USA, and Japan. Prevalence is rising more steeply than incidence, due mostly to improved efficiency of treatment -patients are surviving longer. Hypertension and diabetes, the main causes of progression from chronic kidney disease (CKD) to ESRD, are becoming more frequent in the general population and make a large contribution to the rising incidence of ESRD. More effective therapies for other conditions have introduced new complications for patients with CKD, thereby also increasing the incidence of ESRD. Increased survival in the general population is reflected in the greater number of elderly people requiring care for ESRD. ESRD is a great economic burden and one that will increase as the incidence and prevalence of the disease increase. This needs to be considered when planning treatment. Prevention and early treatment of hypertension and diabetes will have the greatest impact on the future prevalence of ESRD and the costs associated with its treatment.