Increased Risk of All-Cause Mortality and Renal Graft Loss in Stable Renal Transplant Recipients With Hyperparathyroidism

Abstract

Hyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

“…3 Persistent hyperparathyroidism has been associated with both chronic allograft nephropathy 4 and cardiovascular morbidity and mortality after kidney transplantation. 5,6 Secondary hyperparathyroidism is a common complication in CKD. Parathyroid glands are committed to secrete parathyroid hormone (PTH) to correct calcium and phosphate serum levels.…”

More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients

“…Mediated via an elegant mechanism, i.e ., direct inhibition of sodium-dependent transport of phosphorus in the small intestine[21], this consistent phosphorus-lowering effect mandates surveillance of serum phosphorus levels in patients on chronic oral NAM/NA to avoid the theoretical development of clinical hypophosphatemia[21]. But such potential toxicity might be counterbalanced by a distinctly positive clinical phenomenon: Since baseline serum phosphorus concentrations appear to predict total and/or cardiovascular disease (CVD) mortality in CKD and KTR populations[27-31], as well as native kidney, or kidney graft failure[27,30-32], conceivably, NAM-induced phosphorus-lowering could reduce such hard outcomes in these patients. Moreover, as NAM does not induce prostaglandin-mediated flushing, cause hyperuricemia, or adversely affect glucose tolerance, we believe it will have a better tolerability and safety profile relative to NA, confirming a substantive, decades old body of clinical evidence[33,34] from non-SOTR patient populations-now updated to include those studied on oral NAM therapy in the recent phase 2 and 3 Australian AK/NMSC prevention trials[11-13].…”

“…Moreover, notwithstanding abnormalities, particularly hyperparathyroidism (with resultant increased fractional excretion of urinary phosphorus/decreased tubular reabsorption of phosphorus)[37], which may persist long term despite successful transplantation, and excellent kidney graft function, chronic KTRs whose GFR subsequently declines to stage 4 (15-29 mL/min per 1.73 m 2 ) to 5 (< 15 mL/min per 1.73 m 2 ), or even 3b (30-44 mL/min per 1.73 m 2 ) CKD, are prone to the hyperphosphatemia, inadequate vitamin D status ( i.e ., deficiencies of 25-hydoxy vitamin D3, and/or 1,25-dihydroxy vitamin D3), elevated concentrations of parathyroid hormone (PTH), and increased levels of the phosphatonin fibroblast growth factor 23 (FGF23), characteristic of stage 3b to 5 CKD in the native kidneys of non-KTRs[28-31,37,38]. …”

“…Recently, a novel assay of serum calcification propensity, the transformation time (“T50”) from primary calciprotein particles to secondary calciprotein particles, has been validated, and appears to reflect the pathophysiological milieu engendered by derangement of calcium-phosphorus metabolism which may predispose to ectopic, including vascular, calcification[29,30]. These interrelated perturbations-hyperphosphatemia, inadequate status of vitamin D, elevations in PTH and FGF23, and more recently, greater calcification propensity (reduced T50)-are of epidemiological, and potentially, clinical relevance, because they have been associated, with fatal CVD[26,35], graft failure[30-32,40] or rapid decline in eGFR[38], and total mortality[28-31,40], among KTRs.…”

“…Pihlstrøm et al[31], for example, investigated the association between baseline phosphorus concentrations and major CVD events, kidney graft loss, and all-cause mortality by proportional hazard survival analyses in 1840 stable KTRs derived from the Assessment of LEscol in Renal Transplantation (ALERT) trial, a multicenter randomized, double-blind, placebo-controlled study examining the effect of fluvastatin (40-80 mg daily) on CVD (primarily coronary heart disease, CHD), and renal outcomes in 2102 KTRs. Patients were recruited a mean of 5.1 years after transplantation, and followed for 6 to 7 years.…”