Mineral bone disorders (MBD) in patients on peritoneal dialysis
- 77 Downloads
Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism. In patients undergoing peritoneal dialysis (PD), serum levels of calcium (Ca), phosphate (P), and parathyroid hormone (PTH) remain relatively constant, irrespective of the timing of treatment. This is because PD is a continuous blood purification procedure, and in this respect differs greatly from hemodialysis (HD), where the serum levels of these factors change following each dialysis session, and so pre-dialysis values are considered baseline values. Nevertheless, the target values for serum P, Ca, and PTH in PD patients are the same as those in HD patients. In PD patients, however, it is plausible to initiate correction of any of these values once any tendency towards worsening is observed, even if they are still within the upper limit of normal for HD patients. Restriction of dietary P intake, conservation of residual renal function for excretion of P, and prescription of an appropriate P binder are recommended to maintain the blood P level in the appropriate range. The use of a 2.5-mEq/L Ca concentration dialysate reduces the risk of hypercalcemia and allows correction of adynamic bone disease. Meanwhile, secondary hyperparathyroidism may progress in such cases. It is thus recommended that this factor be considered in prescribing this type of dialysate.
KeywordsPeritoneal dialysis Mineral bone disorder Dialysate Adynamic bone disease Vascular calcification
Abdominal aortic calcification
Adynamic bone disease
Chronic kidney disease-mineral bone disorder
Kidney Disease: Improving Global Outcomes
Kidney Disease Outcomes Quality Initiative
Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic condition that manifests as abnormalities in parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and vitamin D metabolism, with associated bone abnormalities and ectopic calcification ; it is a major complication in patients undergoing peritoneal dialysis (PD) . CKD-MBD is associated with vascular calcification and cardiovascular disease (CVD), and these conditions are closely related to an increased mortality rate . Guidelines for the treatment of CKD-MBD have been published by Disease Outcomes Quality Initiative (DOQI)  and Kidney Disease: Improving Global Outcomes (KDIGO) . Clinical practice guideline for the management of CKD-MBD for Japanese dialysis patients was recently published and was made applicable to Japanese PD patients . At the end of 2015, the number of PD patients in Japan was 9322, slightly higher than in 2014 . The clinical relevance of CKD-MBD has led to the identification of clinical biochemistry targeted to be achieved to improve the outcome of PD patients. The purpose of this paper was to review the literature concerning the management of CKD-MBD in PD patients.
Assessment of serum levels of Ca, P, and PTH
Dialysis dose and metabolism of Ca and P
Adynamic bone disease in PD patients
Adynamic bone disease (ABD) resulting from low serum levels of PTH is now recognized as a common complication in PD patients . Carmen Sánchez et al. reported that ABD was found in 63.2% of PD patients and that PTH levels less than 150 pg/mL in patients with ABD showed a sensitivity of 91.6% and specificity of 95.2% . Moreover, de Oliveira et al. have recently shown that sclerostin, a Wnt/β-catenin pathway inhibitor that decreases osteoblast action and bone formation, seems to participate in the pathophysiology of ABD, and bone alkaline phosphatase was the sensitive serum marker of bone turnover in these patients .
With this background, the use of a dialysate with a Ca concentration of 3.5-mEq/L should be considered, particularly in order to avoid hypocalcemia in the introductory phase of dialysis. Prescription of a dialysate with a Ca concentration corresponding to the serum level in each patient undergoing PD is feasible, unlike with HD where the access is via the central vein. Mineral management should therefore take advantage of the characteristics of PD, in which personalized therapy is readily practicable. For example, the efficacy of cinacalcet for secondary hyperparathyroidism during the maintenance phase has been also demonstrated in PD patients .
Vascular calcification in PD patients
The most important methods for the prevention and treatment of vascular calcification are dietary P restriction and adequate use of P binders for hyperphosphatemia. The severe vascular calcification associated with hyperphosphatemia is a result of the phenotypic conversion of smooth muscle cells to osteoblasts . The KDOQI recommends a target of P < 5.5 mg/dL, while KDIGO recommends normalization. There are several commercially available P binders that are invariably equally effective. These can either be Ca-containing (Ca carbonate, Ca acetate) or Ca-free (sevelamer hydrochloride, lanthanum carbonate, magnesium carbonate). Furthermore, the iron-containing P binder such as ferric citrate hydrate and sucroferric oxyhydroxide has recently been marketed.
Hypomagnesemia has also been found to be associated with increased mortality in PD patients . Molnar et al. have recently shown that lower serum magnesium is associated with vascular calcification in PD patients . Magnesium carbonate may thus be useful to inhibit vascular calcification in PD patients with hypomagnesemia.
PD is a continuous blood purification procedure and differs greatly from HD, where the serum Ca, P, and PTH levels change following each dialysis session, and pre-dialysis values are taken as the baseline values. Nevertheless, the target values for these factors in PD patients are the same as those in HD patients. In PD patients, however, it is plausible to initiate correction of any of these values once any tendency towards worsening is observed, even if they are still within the upper limit of normal for HD patients. Restriction of dietary P intake, conservation of residual renal function for excretion of P, and prescription of an appropriate P binder are all recommended to maintain the blood P level in the appropriate range. The use of a 2.5-mEq/L Ca concentration dialysate reduces the risk of hypercalcemia and allows correction of ABD.
Future research in this field will shed light on several topics, including a comparison of CKD-MBD management across different countries and the relationship between dialysate Ca concentrations and vascular calcification in PD patients. These studies should be designed to overcome several weaknesses in the literature, such as a lack of information on gender, ethnicity, and prescription of P binders such as magnesium carbonate, all of which may influence the grade of vascular calcification and osteoporosis. In addition, high-glucose PD solution may lead to low-turnover bone, and further studies are needed to explore whether it is true or not. Moreover, continuous renal replacement therapy may be associated with a change in bone metabolism or vascular calcification. While a loss of circadian rhythm is a characteristic of secondary hyperparathyroidism, a continuous replacement therapy will affect the PTH level. Updated clinical practice guideline for the management of CKD-MBD in Japanese dialysis patients will be published in the near future.
The authors acknowledge all the medical staff who contributed to this work in the Departments of Nephrology and Blood Purification, Tokyo Women’s Medical University.
Availability of data and materials
Data sharing not applicable to this article as no data-sets were generated or analyzed during the current study.
KN searched the literature and prepared this article. KN, NH, and KT read, criticized, and approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- 1.Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G, Kidney Disease Improving Global Outcomes (KDIGO). Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2006;69:1945–53.CrossRefGoogle Scholar
- 4.K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1–201.Google Scholar
- 5.Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clnical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 2009;76(Suppl 113):S1–130.Google Scholar
- 6.Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Sgigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T For CKD-MBD Guideline Working Group, Japanese Society for Dialysis Therapy. Ther Apher Dial 2013;17:247–288.Google Scholar
- 7.Masakane I, Taniguchi M, Nakai S, Tsuchida K, Goto S, Wada A, Ogata S, Hasegawa T, Hamano T, Hanafusa N, Hoshino J, Minakuchi J, Nakamoto H, on behalf of the Japanese Society for Dialysis Therapy Renal Data Registry Committee. Annual Dialysis Data Report 2015, JSDT Renal Data Registry. Ren Replace Ther. 2018;4:19.CrossRefGoogle Scholar
- 17.Salusky IB, Goodman WG, Sahney S, Gales B, Perilloux A, Wang HJ, Elashoff RM, Juppner H. Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J Am Soc Nephrol. 2005;16:2501–8.CrossRefGoogle Scholar
- 20.Kawanishi H, Ishida M, Ishizaki M, Takuma Y, Tamura H, Kobayashi S, Tamura T, Ohashi H, Hiramatsu M, Minakuchi J, Hirakata H, Shigematsu T, Lanthanum Carbonate Study Group in Japan. Lanthanum carbonate treatment of patients with hyperphosphatemia undergoing CAPD. Perit Dial Int. 2008;28:673–5.PubMedGoogle Scholar
- 26.Weinreich T, Passlick-Deetjen J, Ritz E. Low dialysate calcium in continuous ambulatory peritoneal dialysis: a randomized controlled multicenter trial. The Peritoneal Dialysis Multicenter Study Group. Am J Kidney Dis 1995;25:452–460.Google Scholar
- 28.Yamamoto H, Kasai K, Hamada C, Hasegawa Hm Higuchi C, Hiramatsu M, Hosoya T, Itami N, Kawanishi H, Kubota M, Masakane I, Minakuchi J, Mitarai T, Nakao T, Suzuki H, Tomo T, Kawaguchi Y, Japan Peritoneal Dialysis-Mineral Bone Disorder (PD-MBD) Research Group. Differences in corrective mode for divalent ions and parathyroid hormone between standard- and low-calcium dialysate in patients on continuous ambulatory peritoneal dialysis—result of a nationwide survey in Japan. Perit Dial Int. 2008;28(Suppl 3):S128–30.PubMedGoogle Scholar
- 29.Lindberg JS, Culleton B, Wong G, Borah MF, Clark RV, Shapiro WB, Roger SD, Husseri FE, Klassen PS, Guo MD, Albizem MB, Cobum JW. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind multicenter study. J Am Soc Nephrol. 2005;16:800–7.CrossRefGoogle Scholar
- 31.Makela S, Asola M, Hadimeri H, Heaf J, Heiro M, Kauppila L, Ljungman S, Ots-Rosenberg M, Povisen JV, Rogland B, Roessel P, Uhlinova J, Vainlotalo M, Svensson MK, Huhtala H, Saha H. Abdominal aortic calcifications predict survival in peritoneal dialysis patients. Perit Dial Int. 2018;38:366–73.CrossRefGoogle Scholar
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.