Efeito da inflamação sobre os biomarcadores do distúrbio mineral ósseo na lesão renal aguda

Abstract

Introduction: Patients with chronic kidney disease and on dialysis have a high prevalence of bone mineral disorders. Recently, the inflammation have been associated to cause abnormalities in bone and mineral metabolism in end stage renal disease (ESRD) patients. These are linked with morbidity and mortality in this population. The Fibroblast Growth Factor 23 (FGF-23) a phosphaturic hormone, Sclerostin (SOST) (a protein that inhibit bone formation) and inflammation markers have been described as an important axis of the physiopathology of mineral bone disease (MBD). However, patients with acute kidney injury (AKI) which abruptly lose kidney function; have not been investigated to bone and mineral metabolism abnormalities. Objective: To investigate the effect of inflammation on mineral bone metabolism in patients with Acute Kidney Injury (AKI). Material and Methods: We included 77 severe patients without AKI (age 74±14) and 83 severe AKI patients (age 71±17) all admitted to the Intensive Care Unit. Patients with AKI were characterized by AKIN criteria that used a 0.3 mg/dL increase in serum creatinine within seven days of admission in the hospital. Serum markers of mineral bone metabolism and inflammation investigated were: FGF-23, SOST, Interleukin-6 (IL-6), Tumor Necrosis Factor Alpha (TNF-α) and Interleukin-10 (IL-10) (by enzyme-linked immunosorbent assay - ELISA), calcium and phosphorus (colorimetric method), parathyroid hormone and 25 vitamin D (by electrochemiluminescence immunoassay – ECLIA). Results were expressed on average or median. Test T and Mann-Whitney were used to analyze the groups. Results: We observed difference in serum levels of IL-6 (pg/mL) [AKI 21.2 (12.1-31.7) vs. No-AKI 11.8 (7.0-19.3); p<0.01], TNF-α (pg/mL) [AKI 8.0 (6.6 -10.6) vs. No-AKI 7.0 (6.0-8.0); p<0.01], IL-10 (pg/mL) [AKI 1.07 (0.95-1.54) vs. No-AKI 0.97 (0.91-1.08); p<0.01], phosphate (mg/dL) [AKI 4.5 ±1.7 vs. No-AKI 3.9 ±1.2; p=0.01] PTH (pg/mL) [AKI 7.8 (3.5-17.5) vs. No-AKI 5.5 (2.9-10.7); p=0.04], vitamin D (ng/mL) [AKI 13.6 ±7.6 vs. No-AKI 16.1 ±6.5; p=0.01] and sclerostin (pg/mL) [AKI 80.0 ±24.4 vs. No-AKI 15.2 ±4.8; p=0.01]. We did not observe difference in albumin (g/dL) [AKI 2.9 ±0.5 vs. No-AKI 3.1 ±0.6; p=0.09], C-reactive protein (mg/L) [AKI 6.4 (1.8-15.0) vs. No-AKI 6.2 (1.1-15.0); p=0.31], calcium (mg/dL) [AKI 7.9 ±1.1 vs. No-AKI 8.0 ±1.1; p=0.24] and FGF-23 (pg/mL) [AKI 48 (1.5-149) vs. No-AKI 58 (1.5-193); p=0.35]. In addition, we observed that patients with APACHE II presented higher serum levels of creatinine (mg/dL) [APACHE Abstract XII 1.8 ±1.4 vs. Não-APACHE 1.0 ±0.6; p<0.01], cystatin C (ng/mL) [APACHE 1.8 ±1.0 vs. Não-APACHE 1.1 ±0.6; p <0.01], TNF-α (pg/mL) [APACHE 9.2 ±4.9 vs. Não-APACHE 7.5 ±1.8; p <0.01] e PTH (pg/mL) [APACHE 13.9 ±18 vs. Não-APACHE 9.1 ±10.5; p=0.04] and patients who progressed to death had altered creatinine (mg/dL) [Death 2.1 ±1.4 vs. No-Death 1.3 ±1.0; p=0.03], cystatin C (ng/mL) [Death 2.4 ±1.2 vs. No-Death 1.3 ±0.7; p<0.01], IL-6 (pg/mL) [death 22 ±9 vs. No-Death 17 ±10; p=0.04], TNF-α (pg/mL) [Death 12.1 ±6.2 vs. No-Death 7.9 ±3.0; p<0.01], C-reactive protein (mg/L) [Death 15.9 ±13 vs. No-Death 8.4 ±8; p<0.01], IL-10 (pg/mL) [Death 7.3 ±24 vs. No-Death 2.0 ±8.4; p=0.01] and phosphate (mg/dL) [Death 5.1 ±2.4 vs. No-Death 4.1 ±1.4; p=0,01]. Conclusion: Sclerostin was higher in AKI patients As expected, AKI patients presented higher inflammation state characterized by increased serum levels of IL-6, TNF-α and IL-10. It is possible these cytokines signalizing sclerostin production from osteocytes. To our knowledge, this is the first study that detected high levels of sclerostin in AKI patients. However, the inflammatory mechanism and their impact on osteocyte associated to outcome, should be investigated.