Renal Osteodystrophy ( paraclinical evaluation ) Dr. Y. Ataipour Hashemi Nejad Hospital TUMS

56 Y/O man on regular hemodialysis is transferred to another dialysis center. Previous records showing values from the past year are as following. In new dialysis center he is continued on the same dialysis regimen. New chemistry values are as following: Ca: 9P: 5.4 PTH: 610Alk Pho: 112

The sudden increase in PTH is likely due to which one of the following?  A: Lower dialyzate calcium  B: Pt noncompliance  C: Progression of hyperparathyroidism  D: A change in PTH assay  E: Access insufficiency

FGF – 23 Produced by Osteocyte (Osteoblast)  Decreases renal phosphate reabsorption  Decreases the production of 1.25 DH Vit D  In CRF phosphate retention many result progressive increase in FGF-23 level and finally results hyperparathyroidism.

FGF – 23 as an adaptive mechanism (trade off) FGF-23 level increases to maintain normal serum phosphate while decreasing Vit D level as initial trigger for hyperparathyroidism. FGF-23 levels are also an independent risk factor of LV hypertrophy.

PTH PTH a polypeptide of 84 amino acids is secreted in response to hypocalcemia with a half life of few minutes. Stimulating osteoclast and bone resorption Renal reabsorption of Ca Renal excretion of P Stimulates synthesis of Vit D Increases Intestinal absorption of Ca

PTH exerts its biological effects through the first 34 (N-terminal) amino acids,which binds to the type I PTH receptor. The cacboxyl © terminal (last 50 aa,) has no direct influence on PTH receptor.

PTH Fragments Accumulated in CKD patients. (7-84)fragment is the largest proportion of non PTH (1-84) fragment (80% of circulation PTH) (7- 84) fragment exerts opposite biological effect on bone compared with (1-84) PTH

Clinical Importance of PTH (1-84) and (7- 84) fragment PTH (1- 84)PTH (7- 84) Stimulates bone resorption to increase serum Ca produced in response to hypercalcemia Stimulates activity of 1, 25 Vit D High serum level in CKD due to decreased excretion Decreases serum POpposite effects to PTH (1- 84) Stimulates bone formation through a G-protein receptorsHalf life times PTH (1- 84) Half life 2- 4 min

First Generation of RIAs for PTH  Directed Ab against c-terminal  Directed Ab against N- terminal

Limitations of First Generation RIA  Measures both PTH (1- 84) & PTH fragment  Overestimates PTH level  Inaccurate estimation of PTH due to impaired renal excretion  Poor sensitivity at low concentration  Not highly reliable

PTH Assay 2 nd Generation Immunometric assay (IMAs) of intact PTH Dose not measure C- terminal or mid fragment. iPTH assay brings advantages over RIAs but is associated with several limitations  Overestimates PTH in CKD  Limited sensitivity & specificity for assessing bone turnover in CKD patients.

3 rd generation of PTH assay (IMAs) Elecys PTH (1-84) Immunometric assay of whole PTH (1- 84)  Anti-C-terminal Ab  Anti- N- terminal Ab  Does not measure PTH (7- 84)  No over estimation of PTH level

Advantages  High specificity & sensitivity for PTH (1- 84)  % lower serum level  Intera surgical Diagnosis of resection sufficiency Limitation: Not yet widely available

Bone mineral density: BMD is measured by dual energy x-ray absorptomety in general population. BMD is lower in CKD than a GP. The utility of this test in CKD is limited.

Other Indicators of BMD  Vit K activity correlates with BMD & risk of Fx  Possible efficacy & safety of Vit K supplement in dialysis patients has not yet been documented to reduce Fx  Bone morphogenic protein- 7

The gold standard test for DX the various types of bone disease in CKD patients but it is an invasive test which is recommended in following conditions : Unexplained FX Unexplained hypercalcemia Unexplained hyperphosphatemia Persistant bone pain Possible aluminum toxicity Before therapy with biphosphonate Bone Biopsy