The recent publication of the novel KDIGO chronic kidney disease (CKD) guidelines in 2009 [1] clearly underlined the importance of bone and vascular health for patients with CKD. Our understanding is rapidly increasing of how closely disturbances in mineral metabolism are linked to bone and vascular disease (the so-called bone–vascular axis). A decade ago, the first published studies on this deleterious interplay focused upon dialysis patients [2,3]. However, it has recently become evident that patients in the early stages of CKD also exhibit profound pathological changes in the bone–vascular axis, termed CKD–mineral bone disorder (CKD–MBD) [4]. CKD–MBD is a descriptive term that encompasses serum biochemistry changes such as hyperphosphataemia or hyperparathyroidism, renal osteodystrophy, and the problem of vascular calcification [5]. Our current understanding of these disorders has switched the focus of interest towards patients with earlier forms of CKD, as prevention of occurrence (primary prevention) might be easier than prevention of progression. In the light of overall rather disappointing results of interventional trials in patients with end-stage renal disease (ESRD), the idea that primary prophylaxis may be promising is fascinating. This concept is supported by the data from lipid modification trials indicating that statin therapy in ESRD is not effective and probably starts too late [6]. In contrast, statin therapy in patients with moderate CKD lowers cardiovascular risk comparable to patients with normal renal function. The data from the Pravastatin Pooling Project (PPP) demonstrated that pravastatin significantly reduced the incidence of cardiovascular events in people with or at risk for coronary disease and concomitant moderate CKD [7]. In this respect, we are awaiting the SHARP trial results. In line with these data, in patients with moderately reduced kidney function, ‘subclinical’ or modestly elevated serum phosphorus levels may pose an appreciable threat to patients [8,9]. In a recent issue of theNewEngland Journal of Medicine, we found of interest the review article by Tonelli et al. [10] on the use of oral phosphate binders in CKD patients undergoing dialysis. The revision of the literature in the field appears to be complete. However, we would like to discuss critically the authors' conclusions on considering calcium-based phosphate binders to be the first-line therapy for dialysis patients. In contrast to the strict focus on available evidence-based medicine data as chosen by Tonelli et al., we suggest a more integrative and translational approach to this crucial question. In our opinion, several issues have not been sufficiently appreciated by Tonelli et al. [10]: for example, the data regarding occurrence of hypercalcaemic episodes, the development of vascular calcifications as a surrogate for cardiovascular disease [11], and the deleterious interaction of inflammation, dyslipidaemia and vascular disease. Although prolonged hypercalcaemia is not a common event in dialysis patients [12], any serum calcium levels below overt hypercalcaemia do not necessarily mean a well-balanced calcium metabolism given the poor reflection of serum spot measurements with overall total body calcium and with direction of calcium flux. In our opinion, several issues have not been sufficiently appreciated by Tonelli et al. [10]: for example, the data regarding occurrence of hypercalcaemic episodes, the development of vascular calcifications as a surrogate for cardiovascular disease [11], and the interaction of inflammation, dyslipidaemia and vascular disease. Serum phosphate levels in uraemic patients can be controlled by the reduction of oral phosphate intake, an adequate dialysis schedule and the use of intestinal phosphate binders. During homeostasis, ~60% of the ingested phosphate is absorbed via the gut. This amount is increased by (active) vitamin D. Strict dietary counselling may reduce daily oral intake of phosphate. However, following daily dietary protein recommendations of 1000–1200 g/kg/body weight, CKD patients ingest a consistent amount of at least 900–1000 mg phosphate per day [13]. It is a common observation that rigid dietary phosphorus restriction is rarely followed by most patients in the long term. Moreover, the
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Jan 12, 2016
P.H Cutini + 2
Open Access