Evaluation of bone remodeling in hemodialysis patients: serum biochemistry, circulating cytokines and bone histomorphometry.
BACKGROUND
To optimize the noninvasive evaluation of bone remodeling, we evaluated, besides routine serum markers, serum levels of several cytokines involved in bone turnover.


METHODS
A transiliac bone biopsy was performed in 47 hemodialysis patients. Serum levels of intact parathyroid hormone (iPTH; 1-84), total alkaline phosphatases (tAP), calcium, phosphate and aluminum (Al) were measured. Circulating levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1Ra) and soluble IL-6 receptor (sIL-6r) were determined using ELISA. Circulating IL-1beta, IL-6, IL-8, IL-10, IL-12p70 and tumor necrosis factor-alpha (TNF-alpha) were simultaneously quantified by flow cytometric immunoassay.


RESULTS
Patients with low/normal bone formation rate (L/N-BFR) had significantly lower serum iPTH (p<0.001) and tAP (p<0.008) and significantly higher Al (p<0.025) than patients with high BFR. Serum calcium and phosphorus, however, did not differ (p=NS). An iPTH >300 pg/mL in association with tAP >120 U/L showed low sensitivity (58.8%) and low negative predictive value (44.0%) for the diagnosis of high BFR disease. An iPTH <300 pg/mL in association with normal or low tAP, <120 U/L, was associated with low sensitivity (66.7%) but high specificity (97.1%) for the diagnosis of L/N-BFR. Serum IL-1, IL-6, IL-12p70 and TNF-alpha were positively correlated with BFR, serum IL1-Ra and IL-10 with bone area, and by multiple regression analysis, tAP and IL-6 were independently predictive of BFR.


CONCLUSIONS
Significant associations were found between several circulating cytokines and bone histomorphometry in dialysis patients. The usefulness of these determinations in the noninvasive evaluation of bone remodeling needs to be confirmed in larger dialysis populations.
Ferreira
Aníbal
A
Department of Nephrology, Hospital Curry Cabral, Lisbon, Portugal. anibalferreira@netcabo.pt
Saraiva
Maria
M
Behets
Geert
G
Macedo
Ana
A
Galvão
Maria
M
D'Haese
Patrick
P
Drüeke
Tilman B
TB
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000535:Aluminum / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016723:Bone Remodeling; D002118:Calcium / Q000097:blood; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007085:Ilium / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D007378:Interleukins; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014409:Tumor Necrosis Factor-alpha; D000535:Aluminum; D000469:Alkaline Phosphatase; D002118:Calcium