Diagnostic Accuracy of Serum Parathyroid Hormone Levels in Kidney Transplant Recipients with Moderate-to-Advanced CKD

Abstract

Background/Aims: Elevated parathyroid hormone (PTH) is used to diagnose high turnover bone disease in chronic kidney disease (CKD). The diagnostic accuracy of PTH in kidney transplant recipients with CKD is unknown. Methods: We examined kidney transplant recipients with CKD stages 3 (n = 498) and 4 (n = 141) to determine the sensitivity and specificity of the Kidney/Dialysis Outcome Quality Initiative (K/DOQI)-recommended PTH levels in detecting elevated serum β-CrossLaps (CTX) or osteocalcin (OC) levels. We performed receiver-operator curve analyses to determine CKD stage-specific PTH levels that provide optimal diagnostic accuracy. Results: PTH below the lower limits of the K/DOQI ranges (35 and 70 pg/ml in CKD stages 3 and 4, respectively) showed sensitivity of >90% in diagnosing increases in biochemical markers. The upper limits (70 and 110 pg/ml), however, showed poor specificity. A specificity of >90% for detecting increased biochemical markers was seen with PTH of >140 and >240 pg/ml in CKD stages 3 and 4, respectively. Conclusion: Currently applied cutoffs for PTH in kidney transplant recipients with CKD stages 3 and 4 do not appear to adequately detect increased biochemical markers of bone turnover. Diagnostic uncertainty exists in patients with CKD stage 3 and PTH between 35 and 140 pg/ml, and CKD stage 4 and PTH between 70 and 240 pg/ml.

Vitamin K Dependent Proteins in Kidney Disease

“…As a common complication in CKD, the secondary hyperparathyroidism was assessed in a large cohort by parathyroid hormone and OC as marker of bone turnover. The higher levels of OC reported in post-renal transplant patients with CKD stage IV versus those with CKD III [46] are in agreement with the findings of Holden et al [9], even when they assessed %ucOC. In addition, post-renal transplant patients with higher levels of serum OC showed an increase bone turnover [50].…”

“…In addition, serum GRP levels were decreased in advanced stages of CKD [86]. Serum OC levels were found elevated in more advanced CKD of post renal transplant patients [46], as well as both cOC and ucOC in HD patients [10]. Gas6 levels were inversely correlated with eGFR, serum levels of Gas6 increasing as CKD stage became more advanced [70].…”

“…Most of the studies either did not identify the specific etiology of the kidney disease [9,14,17,18,45,46,80,86] or in the study protocol the authors included multiple etiologies that were all considered as CKD [15,38] Moreover, the statistics used for the assessment of association between VKDPs and etiologies of CKD are missing. Most of the studies found associations between VKDPs and CKD progression or parameters of kidney damage [9,15,41], but did not perform any correlations with the etiology itself or at least with subgroup of etiologies.…”

“…The process of identification, selection, screening and inclusion of the studies are depicted in Figure 1. The following studies were included: MGP [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]; OC [9,10,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69]; Gas6 [70,71,72,73,74,75,76,77,78,79,80,8...…”

Management of mineral and bone disorder after kidney transplantation

“…Both pre-transplant63 and post-transplant39 serum PTH level are associated with unfavorable outcomes including worse graft function. However, it is important to note that two studies that assessed bone biopsy samples in kidney transplant recipients did not find a correlation between serum PTH levels and bone turnover,18,38 and the diagnostic accuracy of PTH is not quite clear 64. Treatment options for hyperparathyroidism are summarized below.…”