Nephrol Dial Transplant (2006) 21: 1663 1668 doi:10.1093/ndt/gfl006 Advance Access publication 6 February 2006 Original Article Application of NKF-K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease: changes of clinical practices and their effects on outcomes and quality standards in three haemodialysis units M. Dolores Arenas 1, Fernando Alvarez-Ude 2, M. Teresa Gil 1, Antonio Soriano 1, Juan Jose Egea 1, Isabel Milla n 1, M. Luisa Amoedo 1, Salomé Muray 1 and M. Antonia Carreto n 1 1 Hospital Perpetuo Socorro, Alicante, Elche y Elda, Spain and 2 Hospital General de Segovia, Segovia, Spain Abstract Background. The K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease was published in October 2003. The objective of this study was to analyse the effect of the application of those guidelines on clinical practices and on the achievement of bone disease targets and quality standards. Methods. We included in the study 342 patients dialysed in our three HD units during 2003 and 2004. Starting October 2003, the K-DOQI recommendations were introduced into practice. Parathyroid hormone (PTH) was measured every 3 months and the serum Ca and P levels, monthly. In patients whose medications were modified, PTH was measured monthly and Ca and P levels, weekly or biweekly. Results. The following are the main findings for 2004 (post-k/doqi): an increased use of dialysates with a Ca concentration of 2.5 meq/l (27.2 50.9%, P<0.001) and a reduced use of a dialysate calcium of 3.0 meq/l (44.6 39.6%, P: NS) and 3.5 meq/l (28 9.4%, P<0.001); a reduced use of calcium-based phosphate binders (891.9 565.5 mg Ca/day, P<0.001) and increased use of sevelamer hydrochloride (800 mg) (from 4.86 to 7.51 mg, tablets/day, P<0.001) lower serum Ca levels (9.7 9.4 mg/dl, P<0.01), and higher intact PTH levels (201.4 311.8 pg/ml, P<0.001), without changes in serum P levels; an increased proportion of patients with serum Ca levels within the K/DOQI target range (38.7 46.6%, P<0.01), resulting mainly from the reduced percentage of patients with hypercalcaemia (55 44.4%, P<0.01); a decreased proportion of patients with PTH<150 pg/ml (53.8 31.4%, Correspondence and offprint requests to: M. Dolores Arenas, Hospital Perpetuo Socorro, Alicante, Elche y Elda, Spain. Email: arenasd@perpetuosocorro.nehos.com; lola@olemiswebs.com P<0.001) but an increased proportion of patients with PTH>300 pg/ml, with no change in the proportion of patients with PTHs within the K/DOQI target range. Phosphorus levels and targets did not show significant differences between 2003 and 2004 (56.9 56.2%, P: NS). Conclusions: The only way to ensure that K/DOQI guidelines actually improve medical outcomes is to emphasize implementation strategies and also the scientific evaluation of their effectiveness in clinical settings. In spite of the application of the K-DOQI recommendations, a large proportion of our patients stayed outside the proposed targets, which points to the need for more effective therapeutic options. Keywords: bone metabolism; clinical performance measures; clinical practice guidelines; NKF-K/DOQI target; quality management system Introduction Clinical practice guidelines have long been used in clinical medicine, having been developed by physicians as a means of improving quality of care and objective medical decision making, and also for optimizing the use of resources [1]. The National Kidney Foundation- Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice Guidelines established a widely accepted set of recommendations for high quality dialysis care [2]. Nevertheless, a number of serious deficiencies in the application of the guidelines to clinical practice have been pointed out [3], their validity in changing physician practices and modifying patient outcomes remains largely untested, and there are considerable variations in their impact on medical (or clinical) practice [4,5]. ß The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
1664 M. D. Arenas et al. The only way of ensuring that clinical practice guidelines actually improve health care outcomes is to increase the emphasis placed on implementation strategies and on the scientific evaluation of their effectiveness in clinical settings. This approach could include the development of implementation support systems in individual dialysis centrers, clinical audit programmes and methods of gathering and feeding back information regarding practices. In this context, clinical performance measures (CPMs), based on the targets established by the Guidelines, are important tools for assessing and improving the quality of care in haemodialysis (HD) units [6]. Since 2001, our three HD units have implemented a quality management system (QMS) that includes the routine use of CPMs and quality standards. The objective of this study was to analyse the effect of the K/DOQI Guidelines for Bone Metabolism and Disease on changing clinical practices in the three HD units and its effect on bone disease targets and quality standards in haemodialysis. Methods Patients We included in this study 342 patients dialysed in our three HD units during 2003 and 2004. Of them, 62.1% were men and 37.8% were women. All patients received regular haemodialysis sessions, lasting between 3.5 and 4 h, three times per week, with 1.8 2.1 m 2 polysulphone dialysers of varying permeability. All were maintained on a stable haemodialysis regimen during 2003 and 2004. Their mean body weight was 64.2±13.3 kg. Objectives, quality standards and treatments The objectives and quality standards in 2003, i.e. those in effect prior to the publication of the K/DOQI guidelines in October 2003, were as follows: the maintenance of serum parathyroid hormone (PTH) levels between 120 and 250 pg/ml, predialysis serum calcium (Ca) between 10 and 10.5 mg/dl, phosphorus (P) levels between 3.5 and 5.5 mg/dl, and the calcium phosphorus product (CaP) below 60 mg 2 /dl 2. Starting October 2003, the K-DOQI recommendations were applied. The objectives in 2004 were to maintain PTH between 150 and 300 pg/ml, serum Ca between 8.4 and 9.5 mg/dl, P between 3.5 and 5.5 mg/dl, and CaP below 55 mg 2 /dl 2 (Guideline 6.5) [12]. In both the periods, drug dose adjustments were made based on serum Ca, P, PTH and Ca P values. During 2003, vitamin D administration was discontinued if serum Ca exceeded 11 mg/dl, P 6 mg/dl, Ca P 60, or if PTH levels fell below 120 pg/ml. Dialysate calcium content was determined individually, based on particular serum Ca levels and the dose of vitamin D administered. A dialysate calcium content of 3 meq/l was preferentially used. A bath containing 2.5 meq/l of Ca was used, in some cases to maintain serum Ca levels within the target range and preventively in patients treated with higher doses of vitamin D or in patients whose serum P levels required increasing the doses of calcium-containing phosphate binders. In 2004, vitamin D administration was discontinued if serum Ca exceeded 10.2 mg/dl (Guideline 6.3), P 5.5 mg/dl or Ca P product 55, or if PTH levels fell below150 pg/ml. In accordance with DOQI recommendations (Guideline 9.1), a dialysate calcium content of 2.5 meq/l was preferentially used; a higher dialysate Ca content was used when serum Ca was less than 8.4 mg/dl. In both the periods, patients were treated with intravenous pulses of (for them) the same vitamin D derivatives (Alphacalcidol, Etalpha Õ, Leo Pharma, in unit A, and Calcitriol, Calcijex Õ, Abbott, in units B and C) given immediately after haemodialysis sessions. Variable doses of calcium acetate or calcium carbonate and sevelamer were used to achieve the target serum P level, being adjusted according to patient response until the target PTH was achieved, which was then kept at the dose necessary to maintain it. Monitoring Routinely, PTH was measured every 3 months, and serum Ca and P monthly. In patients whose drug doses were modified, PTH, Ca and P measurements were made more frequently (PTH monthly, and calcium and phosphorus weekly or biweekly). All blood samples were drawn immediately before the mid-week dialysis session. As part of our QMS, we calculate and register, either monthly or every 3 months, the following CPMs: the means of all measurements of serum Ca, P, PTH and Ca P; the percentages of patients whose serum Ca was <8.4 mg/dl, between 8.4 and 9.5 mg/dl or >9.5 mg/dl, whose serum P was <3.5 mg/dl, between 3.5 and 5.5 mg/dl or >5.5 mg/dl, whose serum PTH was <150 pg/ml, between 150 300 pg/ml or >300 mg/dl, and of those whose Ca P was <55 mg 2 /dl 2. We established the percentages of patients using dialysates with Ca concentrations of 2.5 meq/l (sodium [Na] 140 meq/l, potasium [K] 1.5 meq/l, magnesium [Mg] 1 meq/l, chlorine [Cl] 108.0 meq/l, acetate 3 meq/l, glucose 1.0 meq/l, bicarbonate 34 meq/l), 3 meq/l (Na 140 meq/l, K 1.5 meq/l, Mg 1 meq/l, Cl 108.5 meq/l, acetate 3 meq/l, glucose 1.0 meq/l, bicarbonate 34 meq/l) or 3.5 meq/l (Na 140 meq/l, K 2 meq/l, Mg 1 meq/l, Cl 109.5 meq/l, acetate 3 meq/l, glucose 1.5 meq/l, bicarbonate 34 meq/l). We also established the average consumption of calcium-based phosphate binders (expressed as milligrams of calcium element/day), and the average dose of a non-calcium, nonaluminium, non-magnesium-containing phosphate binding agent (sevelamer hydrochloride, expressed as the number of 800 mg tablets of sevelamer/day). Laboratory tests Serum calcium (UV Vis spectrophotometry, normal laboratory values: 8.6 10.4 mg/dl), phosphorus (UV Vis spectrophotometry, normal laboratory values: 2.7 4.5 mg/dl) and intact PTH (electrochemoluminescence technique, normal laboratory values: 10 65 pg/ml) were assayed on blood samples obtained immediately before the mid-week dialysis session.
NKF-K/DOQI clinical practice guidelines for bone metabolism and disease 1665 Statistical analysis Clinical practices Dialysate calcium concentrations. As shown in Table 3, during 2004 (post-k/doqi) the percentage of patients using a dialysate Ca concentration of 2.5 meq/l increased and the percentage of those using a concentration of 3.5 meq/l decreased significantly. Although there was a reduction in the percentage of those using a Ca dialysate of 3.0 meq/l, the difference between the two periods did not reach statistical significance (P ¼ 0.1). The Student s unpaired t-test was used to compare the 2003 and 2004 means of all PTH, Ca, P and Ca P values, as well as the means of the monthly percentages of patients with Ca levels between 8.4 and 9.5 mg/dl, P levels between 3.5 and 5.5 mg/dl, PTH levels between 150 and 300 pg/ml and (Ca P)<55. We also compared the means of the monthly percentages of patients using different dialysate calcium concentrations, as well as the average total dose of elemental calcium provided by the calcium-containing phosphate binders used (expressed as mg of calcium element/day) and the average dose of the non-calcium, non-aluminium, non-magnesium-containing phosphate binding agent (expressed as the number of 800 mg tablets of sevelamer hydrochloride/day). Correlations among the monthly percentages of patients using different dialysate calcium concentrations and the monthly means or target levels of PTH and serum Ca were assessed using Pearson correlation coefficients or Spearman rank order coefficients, as appropriate. A value of P<0.05 was considered statistically significant. Results Demographics The demographics of the patients studied are summarized in Tables 1 and 2. There were no significant differences in mean spkt/v levels between 2003 (1.48±0.08) and 2004 (1.48±0.47) (P ¼ 0.69). Mean haemoglobin values were lower in 2003 (12.1±0.4 g/dl) than in 2004 (12.3±0.4 g/dl) (P ¼ 0.02). Table 1. Demographic characteristics of the patient population studied in 2003 Use of phosphate binders As shown in Table 3, the prescription of calcium-based phosphate binders was significantly reduced during 2004 (post-k/doqi), whereas that of a non-calcium, non-aluminium, non-magnesium-containing phosphate binding agent (sevelamer hydrochloride) increased significantly. K/DOQI targets As can be seen in Table 3, compared with 2003, during 2004 (post-k/doqi), the mean serum PTH was significantly higher, the mean serum Ca was significantly lower, and there was no significant change in the mean serum P. The proportion of patients who had PTHs >300 pg/ml increased significantly; at the same time, there was a reduction in the percentage of those with a PTH <150. The proportion of those meeting the K/DOQI target for PTH (between 150 and 300 pg/ml) decreased, although the difference did not reach statistical significance. Unit 1 Unit 2 Unit 3 Number of patients dialysed 195 46 35 Number of prevalent patients 152 38 30 Number of incident patients 68 7 9 Mean age of prevalent patients 63.8±14.8 66.9±15.1 65.1±14.7 Mean age of incident patients 67.2±15 71±12 57.1±15.3 Mean time on HD (months) 75.7±98.9 44±60.9 43.6±127.2 Mean serum albumin (g/dl) 3.8±0.1 3.8±0.0 3.9±0.1 % of diabetic patients 25.3 13.8 21.6 Table 2. Demographic characteristics of the patient population studied in 2004 Unit 1 Unit 2 Unit 3 Number of patients dialysed 200 46 46 Number of prevalent patients 157 38 32 Number of incident patients 52 8 16 Mean age of prevalent patients 61.6±14.8 67.3±14.7 64.4±15.1 Mean age of incident patients 61.2±14 64.7±13.2 56.9±15.4 Mean time on HD (months) 83.4±98.2 65.6±59.7 97.5±128.9 Mean serum albumin (g/dl) 3.8±0.1 3.9±0.1 3.8±0.1 % of diabetic patients 25 15.3 34.4
1666 M. D. Arenas et al. During 2004 (post-k/doqi), there was a significant reduction in the proportion of patients with hypercalcaemia (calcium >9.5 mg/dl), as well as a significant increase in the percentage of patients who had Ca levels within the K/DOQI target range (between 8.4 and 9.5 mg/dl). We found no significant changes in the percentage of patients within or outside the targets for P. In the analysis of CPMs, a higher proportion of patients with a dialysate calcium concentration of 3.5 meq/l was significantly and independently associated with higher mean serum Ca (r ¼ 0.53; P<0.001), patients with a greater proportion of hypercalcaemia (r ¼ 0.40; P<0.001), with a lower mean PTH (r ¼ 0.8; P<0.001), with a lower proportion of patients with PTH >300 pg/ml (r ¼ 0.7; P<0.001) and with a higher percentage of patients with PTH <150 pg/ml (r ¼ 0.7; P<0.001). A higher proportion of patients with a calcium dialysate concentration of 2.5 meq/l was significantly associated with higher mean serum PTH (r ¼ 0.7; P<0.001), with a higher proportion of patients with PTH>300 pg/ml (r ¼ 0.5; P<0.001), and with a lower percentage of patients with PTH<150 pg/ml (r ¼ 0.7; P<0.001). Discussion The main findings in our three HD units during 2004 (post-k/doqi) were the following: (1) The use of a dialysate with a Ca concentration of 2.5 meq/l increased, while that of a concentration of 3.5 meq/l decreased significantly. At the same time, we observed a significant reduction in the use of calcium-based phosphate binders and a significant increase in the use of non-calcium, nonaluminium, non-magnesium-containing phosphate binding agents (sevelamer hydrochloride). (2) Lower serum Ca levels, higher PTH levels and no changes in serum P levels. (3) The proportion of patients with serum Ca levels within the K/DOQI target range was significantly increased, mainly due to a reduction in the percentage of patients with hypercalcaemia. (4) The proportion of patients with PTH levels within the K/DOQI target range did not change significantly. In fact, the proportion of patients with PTH <150 pg/ml decreased, but the proportion of patients with PTH>300 pg/ml increased significantly. (5) Serum P levels were not significantly different between 2003 and 2004, with 28 29% patients above and 15% below the recommended target range. Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease (CKD), and their long term presence have become a source of growing concern in the care of these patients. For example, cardiovascular calcifications secondary to increases in phosphate and calcium load could make Table 3. Evolution of the quality indicators in the patients of the three haemodialysis units between 2003 (pre-k/doqi) and 2004 (post-k/doqi) Pre-K/DOQI (2003) Post-K/DOQI (2004) P Proportion of patients were within K/DOQI guideline ranges targets serum Ca, phosphorus, and ipth 0 target 14.5% 11.5% <0.05 1 target 47.2% 39.3% <0.01 2 targets 31.5% 38.1% <0.05 3 targets 6.6% 10.9% <0.01 Serum PTH (pg/ml) Mean±SD 201.4±43.1 311.8±64.5 <0.001 % of patients between 150 and 300 25.6 18.7 NS % of patients >300 20.5 45.0 <0.001 % of patients <150 53.8 31.4 <0.001 Serum calcium (mg/dl) Mean±SD 9.7±0.3 9.4±0.2 <0.01 % of patients between 8.4 and 9.5 38.7 46.6 <0.01 % of patients >9.5 55.0 44.4 <0.01 % of patients <8.4 6.2 7.4 NS Serum phosphate (mg/dl) Mean±SD 4.8±0.2 4.9±0.3 NS % of patients between 3.5 and 5.5 56.9 56.2 NS % of patients P>5.5 27.8 28.8 NS % of patients P<3.5 15.2 14.6 NS Calcium in dialysate (meq/l) % of patients with Ca 2.5 27.2 50.9 <0.001 % of patients with Ca 3.0 44.6 39.6 NS % of patients with Ca 3.5 28.0 9.4 <0.001 Phosphate binders Calcium-containing (mg Ca/day) 891.9±665.5 565.5±550.0 <0.001 Sevelamer (800 mg tablets/day) 4.8±4.4 7.5±4.6 <0.001 NS, not significant.
NKF-K/DOQI clinical practice guidelines for bone metabolism and disease 1667 an important contribution to excess cardiovascular mortality and morbidity in dialysis patients [8,9]. In fact, it has been shown [10] that all-cause and cardiovascular mortality are significantly and independently associated with serum Ca levels and even more consistently with serum P [11]. In October 2003, the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in CKD, was published [12] to provide information and to assist in decision-making in this complex problem. Nevertheless, many European clinicians were not entirely convinced of the value of another set of prescriptive US guidelines, and a group of European nephrologists gathered to discuss the guidelines and comment on potential differences in practice [13]. The only way of ensuring that those guidelines actually improve health care outcomes is to emphasize implementation strategies and also the scientific evaluation of their effectiveness in clinical settings. Up until the publication of the K/DOQI Guidelines, there was greater permissiveness regarding acceptable calcium values in patients on dialysis, and serum Ca values between 10 and 10.5 mg/dl were considered normal for the purpose of avoiding the stimulating effect of low plasma concentrations on PTH secretion and on PTH mrna levels and parathyroid cell proliferation [14]. Among the most important changes in practice that the K/DOQI Guidelines put forward were the recommendations that the corrected total serum Ca should be maintained within the normal range for the testing laboratory, preferably towards its lower limit (between 8.4 and 9.5 mg/dl), that the serum (Ca P)<55 mg 2 /dl 2, and that a corrected total serum Ca >10.2 mg/dl should be considered as hypercalcaemia (Guidelines 6.2, 6.5 and 6.3). In order to reach these objectives, a reduction in oral calcium dosing (by reducing the use of phosphorusbinding agents containing calcium and increasing the use of binders that do not contain calcium, Guideline 6.3a) and the use of dialysates containing less Ca þ (Ca 2.5 meq/l) were proposed. We applied these measures in our three HD units: during 2004, the use of a dialysate with a calcium concentration of 2.5 meq/l and of non-calcium, non-aluminium, nonmagnesium-containing phosphate-binding agents was increased, whereas the use of dialysates with calcium concentrations of 3.0 3.5 meq/l and calcium-based phosphate binders was reduced. The consequence of these actions was an improvement in the achievement of the K/DOQI Ca targets. In fact, the mean serum Ca levels decreased, as did the proportion of patients with serum Ca >9.5 mg/dl, whereas no significant change was recorded in the percentage of patients with hypocalcaemia. Maintaining serum Ca levels at the lower end of the normal range, and the use of a low-calcium dialysate are controversial measures [14]. It has been postulated that keeping calcium at the lower end of the normal range may not be desirable; rather, a value in the middle range may be preferable. Serum Ca levels at the lower end of the normal range could make it more difficult to achieve control of the parathyroid function. The worsening of secondary hyperparathyroidism has been reported in patients dialysed with low calcium dialysates, probably due to the stimulation of PTH secretion resulting from a negative calcium balance during dialysis [15], and PTH levels have been inversely associated with calcium dialysate concentrations. In our HD units, the proportion of patients with PTH levels within the K/DOQI target range decreased, while the percentage of patients with PTH >300 pg/ml increased. The increase in PTH values after implementation of the K/DOQI guidelines did not seem to be related to a poorer control of phosphate levels, since P levels were not significantly different between 2003 and 2004. We, therefore, postulate that the stimulation of PTH secretion could be explained by the lower levels of serum Ca, in turn due to a more frequent use of calcium dialysate with a concentration of 2.5 meq/l (which was significantly associated with a higher serum PTH) and the reduced use of calcium salts. Current therapeutic strategies based on vitamin D compounds and calcium-containing phosphate binders are difficult to implement effectively, because both agents have substantial, and often dose-limiting, calcaemic actions that prevent the attainment of treatment targets. Dialysis against a 2.5 meq/l calcium dialysate, and reductions in the use of calciumcontaining phosphate binders, might improve the achievement of serum Ca targets, though at the price of worsened hyperparathyroidism as was our experience. Probably, an appropriate dialysate composition must be selected according to individual patient calcium and PTH levels and bone histology [16,17]. A lower calcium dialysate concentration might be considered when PTH is low, since therapeutic interventions associated with excessive lowering of parathyroid activity (parathyroidectomy, or excessive calcium or aluminium loading) favour lower bone turnover and adynamic bone disease, which in turn could influence the development and progression of vascular calcifications [20,21]. It is necessary to balance the potential adverse effects of calcium overload against the possible beneficial effect of PTH suppression. In our study, the proportion of patients with PTH <150 pg/ml decreased, though an increase was observed in the proportion of patients with uncontrolled hyperparathyroidism this probably being attributable to the sum of such factors as low calcium dialysates, the maintaining serum Ca levels at the lower end of the normal range and a decrease or suppression of the vitamin D dose in the face of calcium levels that were considered acceptable prior to the publication of the K/DOQI Guidelines. Despite the presumed benefits of maintaining PTH, calcium and phosphorus concentrations within the proposed ranges of the Guidelines, evidence suggests that the vast majority of dialysis patients are uncontrolled in this regard [18], and points to the need for more effective therapeutic options for example, vitamin D analogues with lower hypercalcaemic
1668 M. D. Arenas et al. potential [19], calcimimetic agents [20] or daily haemodialysis or thrice weekly, overnight dialysis. A recent study shows cinacalcet-treated patients to be more likely to achieve the K/DOQI recommended targets for PTH (56%), calcium (49%) and phosphorus (46%) [21]. In summary, the impact of the K/DOQI Guidelines on improving bone metabolism and disease among dialysis patients remains to be determined. As our study has shown, one way of doing so is to establish well-defined targets of physiologic parameters, determine the resources, means and time needed to reach such targets (planning), adopt corresponding guidelines on how to proceed (protocols), and know what to look for to ascertain that the approach is correct (CPMs). In any case, CPMs are only markers that alert us to the existence of possible areas open to improvement. They must be followed by more in-depth analyses to identify the causes and possible solutions for problems in patient management. In this sense, the results of our study are population-based and merely orientational, though presently we are conducting a more detailed analysis of only the patients dialysed in both 2003 and 2004. Acknowledgements. We are grateful to Thomas Stoyle, MD, for his valuable assistance in translating this text. Conflict of interest statement. None declared. References 1. Levin N, Eknoyan G, Pipp M, Steinberg E. National Kidney Foundation: Dialysis Outcome Quality Initiative-development of methodology for clinical practice guidelines. Nephrol Dial Transplant 1997; 12: 2060 2063 2. NKF-DOQI clinical practice guidelines for hemodialysis adequacy. National Kidney Foundation. Am J Kidney Dis 1997; 30 [Suppl 3]: S15 S66 3. Davis DA, Taylor-Vaisey A. Translating guidelines into practice. A systematic review of theoretic concepts, practical experience and research evidence in the adoption of clinical practice guidelines. CMAJ 1997; 157: 408 416 4. Walker RD, Howard MO, Lambert MD et al. Medical practice guidelines. West J Med 1994; 161: 39 44 5. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 1993; 342: 1317 1322 6. Sugarman JR, Frederick PR, Frankenfield DL, Owen WF Jr, McClellan WM. Dialysis Outcomes Quality Initiative Clinical Practice Guidelines. Developing clinical performance measures based on the Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: process, outcomes, and implications. Am J Kidney Dis 2003; 42: 806 812 7. Arenas MD, Alvarez-Ude F, Egea JJ et al. Impact of a quality program in hemodialysis. Nefrologia 2004; 24: 261 275 8. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731 1740 9. Tetta C, Gallieni M, Panichi V, Brancaccio D. Vascular calcifications as a footprint of increased calcium load and chronic inflammation in uremic patients: a need for a neutral calcium balance during hemodialysis? Int J Artif Organs 2002; 25: 18 26 10. Young EW, Albert JM, Satayathum S et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2005; 67: 1179 1187 11. Noordzij M, Korevaar JC, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT. Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) Study Group. The Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline for bone metabolism and disease in CKD: association with mortality in dialysis patients. Am J Kidney Dis 2005; 46: 925 932 12. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42 [Suppl 3]: S1 S201 13. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. With comments from: Cannata-Andía J, Coen G, Cuninghan J, London G, Olgaard K. Published by OCC Europe Ltd on behalf of Amgen (Europe). 2003 14. Silver J, Kilav R, Naveh-Many T. Mechanisms of secondary hyperparathyroidism. Am J Physiol Renal Physiol 2002; 283: 367 376 15. Fernandez E, Borras M, Pais B, Montoliu J. Low-calcium dialysate stimulates parathormone secretion and long-term use worsens secondary hyperparathyroidism. J Am Soc Nephrol 1995; 6: 132 135 16. Cunningham J. Calcium concentration in the dialysate and calcium supplements. Nephrol Dial Transplant 2000; 15 [Suppl 5]: 34 35 17. Malberti F, Ravani P. The choice of the dialysate calcium concentration in the management of patients on haemodialysis and haemodiafiltration. Nephrol Dial Transplant 2003; 18 [Suppl 7]: 37 40 18. Cannata-Andía J, Fernandez-Martin JL, Diaz-Corte C. Applying the K/DOQI guidelines cut-off levels to the dialysis population: how far are we from the target? (abstract SA-PO800) J Am Soc Nephrol 2003; 14: 474A 19. Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 2003; 63: 1483 1490 20. Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Nephrol Dial Transplant 2005; 20: 1311 1314 21. Moe SM, Chertow GM, Coburn JW et al. Achieving NKF-K/ DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int 2005; 67: 760 771 Received for publication: 29.9.05 Accepted in revised form: 10.1.06