Bone and mineral disorders in pre-dialysis CKD

Abstract

Disorders in calcium, phosphorus, and parathyroid hormone (PTH) are common in chronic kidney disease (CKD) and may be associated with poor outcomes including a higher rate of CKD progression and increased death risk. Although these abnormalities have been examined extensively in patients with CKD stage 5 who are receiving chronic maintenance dialysis, they have not been studied to the same extent at earlier stages of CKD, in spite of the much larger numbers of patients in the early CKD population. We summarize the available literature on outcomes associated with bone and mineral disorders in patients with CKD not yet receiving maintenance dialysis. We have reviewed novel data linking fibroblast growth factor 23 (FGF-23) to phosphorus and vitamin D homeostasis. More rapid CKD progression is linked to hyperphosphatemia and its associated hyperparathyroidism and vitamin D deficiency. Hence, hyperphosphatemia may play a central role in the diverse disorders characterizing CKD. We provide a brief overview of the available treatment recommendations for bone and mineral disorders, with an emphasis on areas needing further research.

Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

“…Moreover, in the MHD patient, serum phosphorus concentration will also fluctuate in response to net bone reabsorption; i.e. the degree and type of a patient's bone mineral disease, and the serum calcium level as well as the use of intestinal phosphate binders and the magnitude of net intestinal phosphorus absorption (48). Thus, predialysis serum phosphorus can be considered to provide only a rough and short-term estimate of whether there is excess phosphorus concentration in plasma, and whether dietary phosphorus intake might be excessive.…”

Clinical Outcomes with Active versus Nutritional Vitamin D Compounds in Chronic Kidney Disease

“…The first series of KDOQI Mineral and Bone Disorder (MBD) guidelines recommended that in all NDD-CKD patients who suffer from SHPT, total circulating 25(OH)D level, which usually includes both D 2 and D 3 in the plasma, should be measured if intact PTH level is above 70 pg/ml in stage 3 or above 110 pg/ml in stage 4 CKD (10). If blood 25(OH)D level is below 30 ng/ml, then first a nutritional vitamin D compound, e.g., ergocalciferol 50,000 units per week, is to be administered according to the severity of vitamin D deficiency, followed by a VDRA if SHPT persists (3,10).…”

“…T he kidney is the most abundant source of 1-alpha hydroxylase in the body for the conversion of 25(OH) vitamin D 3 , to active vitamin D hormone (calcitriol), i.e., 1,25(OH) 2 D 3 (1). While 1-alpha hydroxylase also exists in many nonrenal tissues for paracrine activation of vitamin D (see below), the circulating level of 1,25(OH) 2 D 3 decreases significantly with diminishing renal function across worsening stages of chronic kidney disease (CKD) contributing to hypocalcemia, secondary hyperparathyroidism (SHPT) and subsequent renal osteodystrophy (2).…”

“…While 1-alpha hydroxylase also exists in many nonrenal tissues for paracrine activation of vitamin D (see below), the circulating level of 1,25(OH) 2 D 3 decreases significantly with diminishing renal function across worsening stages of chronic kidney disease (CKD) contributing to hypocalcemia, secondary hyperparathyroidism (SHPT) and subsequent renal osteodystrophy (2). Hence, replacement of active vitamin D has been considered an essential step in the management of SHPT and its associated disorders in CKD (3).…”

Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease

“…The progressive deterioration of kidney function in CKD leads to retention of many substances, including phosphorus (P), that are normally excreted by the kidney. Serum P concentration, however, is usually maintained within the normal range of 2.5 to 4.5 mg/dl by a variety of compensatory mechanisms until renal disease has progressed to approximately stage 5 CKD or ESRD (2). An effective mechanism is the reduction in renal tubular absorption of phosphate (PO 4 ; i.e., increased fractional excretion of P regulated by parathyroid hormone [PTH] and the phosphatonin fibroblast growth factor 23) (3,4).…”