The relationship between urinary kidney injury molecule-1 and blood bone metabolism markers in patients with chronic kidney disease
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OBJECTIVE: The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers. MATERIALS AND METHODS: This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr). RESULTS: Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D. CONCLUSION: UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).

99mTc-MIBI SPECT/CT imaging had high sensitivity in accurate localization of parathyroids before parathyroidectomy for patients with secondary hyperparathyroidism.

Purpose: Accurate preoperative parathyroid localization is important for successful parathyroidectomy (PTX). The aim of our study was to investigate whether SPECT/CT has enhanced effect in preoperative localization of parathyroids. Methods: In our retrospective cohort study, we evaluated the effects of technetium-99m methoxyisobutylisonitrile-single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) on preoperative parathyroid localization for 645 secondary hyperparathyroidism (SHPT) patients. Among them, 569 successful PTX patients were divided into group A (received 99mTc-MIBI scintigraphy, n = 175) and group B (received 99mTc-MIBI scintigraphy and SPECT/CT imaging, n = 394). Sensitivity, specificity, and consistency of two imaging methods in preoperative localization of parathyroids were compared. Results: Overall sensitivity and consistency were higher in group B, while there was no difference in specificity between the two groups. In group A, the sensitivity of 99mTc-MIBI was 50.00%, 77.11%, 61.76%, and 76.54% in the right upper gland (RU), right lower gland (RL), left upper gland (LU), and left lower gland (LL) subgroups, while the consistency was 52.00%, 76.57%, 61.71%, and 75.43%, respectively. In group B, the sensitivity of 99mTc-MIBI with SPECT/CT was 69.39%, 90.03%, 78.07%, and 84.27%, and the consistency was 69.54%, 88.32%, 78.43%, and 84.26%, respectively. The sensitivity and consistency in lower glands were higher than in upper glands in both groups. Sensitivity for eutopic parathyroid was higher in group B, while there was no difference for ectopic parathyroid. Conclusions: 99mTc-MIBI SPECT/CT can increase the sensitivity and consistency of preoperative localization of eutopic parathyroid glands, and it can accurately locate ectopic parathyroid without sensitivity improvement.

Sixty-Two-Year-Old Male Suffering From Uremic Leontiasis Ossea Caused by Severe Secondary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) is a long-term complication of chronic kidney disease-mineral and bone disorder (CKD-MBD). SHPT is characterized by hyperplasia of the parathyroid glands and abnormal secretion of parathyroid hormones (PTH), calcium and phosphorous metabolic disorders, renal osteodystrophy, vascular and soft tissue calcification, malnutrition, and other multiple system complications, which can seriously affect the quality of life of the patient and increase the risk of cardiovascular disease and mortality rate. Uremic leontiasis ossea (ULO) is a medical condition only rarely encountered clinically. SHPT causes craniofacial bone deformity accompanied by lesions of the nerve, cardiovascular, respiratory, bone, or other systems within the body. The case discussed here is related to severe SHPT. A 62-year-old male patient was suffering from leontiasis ossea, pectus excavatum, vascular calcification, spontaneous bone fractures, and lower limb deformities. He was undergoing hemodialysis and given total parathyroidectomy (TPTX) with autotransplantation (AT). We further analyzed the multivariate therapeutic effects of TPTX on this patient in order to provide clinical data for standardized treatment of individuals with CKD-MBD.

Effects of parathyroidectomy on blood bone markers and heart rate variability in patients with stage 5 chronic kidney disease.

PURPOSE: Decreased heart rate variability (HRV) is closely related to abnormal cardiac autonomic nervous function, especially sympathetic hyperactivity, which intensifies the risk of cardiovascular events and sudden death. HRV parameters are lower in chronic kidney disease (CKD) and parathyroidectomy (PTX) can improve these abnormalities in severe secondary hyperparathyroidism (SHPT) patients. However, few studies have evaluated correlations between circulating bone markers and HRV in CKD patients. METHODS: We conducted a cross-sectional study including 134 stage 5 CKD patients with 100 controls and a prospective study of 29 PTX patients with follow-up. Circulating bone biomarkers included: (1) intact parathyroid hormone (iPTH) as bone remodeling regulator; (2) bone-specific alkaline phosphatase (BAP), representing bone formation; (3) tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption; and (4) bone-derived hormone, fibroblast growth factor 23 (FGF23). RESULTS: Stage 5 CKD patients had higher circulating iPTH, BAP, TRACP-5b, and FGF23 than controls and these bone markers were significantly elevated in SHPT patients. Baseline iPTH, BAP, and lnFGF23 were independently associated with HRV in CKD patients. After PTX with a follow-up (median interval: 6.7 months), high blood iPTH, BAP, TRACP-5b, FGF23, and attenuated HRV were ameliorated. Furthermore, improved HRV indices were associated with reduced iPTH, BAP, TRACP-5b, and FGF23. CONCLUSIONS: Circulating bone markers are correlated with HRV in CKD 5 patients and PTX can improve decreased HRV, which are associated with corrected bone markers in severe SHPT patients. Thus, we propose that PTH increases sympathetic tone and both high circulating PTH levels and sympathetic hyperactivity increase bone turnover, and that the products of bone turnover influence HRV.

Effects of Parathyroidectomy on Plasma iPTH and (1-84) PTH Levels in Patients with Stage 5 Chronic Kidney Disease.

Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1-84)PTH levels, respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1-84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5 (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.

Parathyroid Hormone Fragments: New Targets for the Diagnosis and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

As a common disorder, chronic kidney disease (CKD) poses a great threat to human health. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complication of CKD characterized by disturbances in the levels of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D; abnormal bone formation affecting the mineralization and linear growth of bone; and vascular and soft tissue calcification. PTH reflects the function of the parathyroid gland and also takes part in the metabolism of minerals. The accurate measurement of PTH plays a vital role in the clinical diagnosis, treatment, and prognosis of patients with secondary hyperparathyroidism (SHPT). Previous studies have shown that there are different fragments of PTH in the body's circulation, causing antagonistic effects on bone and the kidney. Here we review the metabolism of PTH fragments; the progress being made in PTH measurement assays; the effects of PTH fragments on bone, kidney, and the cardiovascular system in CKD; and the predictive value of PTH measurement in assessing the effectiveness of parathyroidectomy (PTX). We hope that this review will help to clarify the value of accurate PTH measurements in CKD-MBD and promote the further development of multidisciplinary diagnosis and treatment.