IL-1β, TNF-α, TGF-β, and bFGF expression in bone biopsies before and after parathyroidectomy

IL-1β, TNF-α, TGF-β, and b FGF expression in bone biopsies before and after parathyroidectomy.BackgroundThere is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-lβ (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and basic fibroblast growth factor (bFGF) in bone biopsies taken from uremic patients before and 1 year after parathyroidectomy (PTX) was evaluated. Biochemical features and histomorphometric outcome were also studied.MethodsIliac bone biopsies were taken before and 1 year after PTX in nine uremic patients with severe hyperparathyroidism (HPT). Immunohistochemical techniques were used to identify the expression of IL-1β, TNF-α, TGF-β, and bFGF in these bone samples.ResultsAt the time of the second bone biopsy, the mean serum total alkaline phosphatase activity was normal, whereas mean serum intact parathyroid hormone (iPTH) level was slightly above the upper limit of normal values. Histomorphometric analysis showed a decrease in resorption parameters and static bone formation parameters after PTX. Dynamically, mineral apposition rate (MAR) and mineralization surface (MS/BS) decreased significantly. There was a marked local expression of IL-1β, TNF-α, TGF-β, and bFGF in bone biopsies before PTX, particularly in fibrous tissue and resorption areas. One year after PTX, IL-1β decreased from 23.6 ± 7.5% to 9.9 ± 3.1%, TNF-α from 4.5 ± 1.5% to 0.7 ± 0.8%, TGF-β from 49.6 ± 9.8% to 15.2 ± 4.6%, and bFGF from 50.9 ± 12.7% to 12.9 ± 7.9% (P < 0.001). A significant correlation was documented between cytokines and growth factors expression in bone with iPTH levels before and after PTX (P < 0.05).ConclusionsBased on these results, we suggest that IL-1β, TNF-α, TGF-β, and bFGF are involved in bone remodeling regulation, acting as local effectors, possibly under the control of PTH

Phosphate Removal During Conventional Hemodialysis: a Decades-Old Misconception

Background/Aims: Hyperphosphatemia is associated with high mortality rate in patients on dialysis. Conventional hemodialysis (HD) is a limit technique in removing phosphate (P). There is a widespread belief that P is removed mainly in the first hour of HD. The aim of this study was to certify the percentage of 1-hour removal of P as compared to the entire procedure. Methods: data from the first dialysis of the week of 21 patients (13 men, age 44±15 years), for 3 consecutive dialysis sessions were evaluated. Fresh dialysate samples were collected at 1 hour and at the end of the session from a partial spent dialysate collection method. Results: Pre dialysis serum P was 4.7±1.7 mg/dl. Reduction rate of serum P was 47.4 ± 14.3 and 45.1 ± 10.8% in 1- and 4-hour of HD, respectively (p=0.322). P removal was 194 (145, 242) mg in 1-hour (p&#x3c;0.0001), which represents 25.0 ± 0.2% of the total removed during the entire HD. Patients with pre dialysis P ≥ 5.5mg/dl had higher P removal during HD than those with P &#x3c; 5.5mg/dl [975 (587, 1354) vs. 776 (580, 784) mg, p=0.025], although the percentage of removal in 1 hour was not different from those with P &#x3c; 5.5mg/d (24.9 ± 0.3 vs. 25.0 ± 0.1%, p=0.918). P removal during dialysis correlated with pre dialysis serum P (r=0.455, p=0.001), parathormone (r=0.264, p=0.037) and ultrafiltration volume (r=0.343, p=0.019). Conclusion: despite the P serum concentration normalizing in the first hour of hemodialysis, the removal in the same period reaches only 25% of the entire session

FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy

Background and objectives Fibroblast growth factor 23 (FGF-23) has emerged as a new factor in mineral metabolism in chronic kidney disease (CKD). An important regulator of phosphorus homeostasis, FGF-23 has been shown to independently predict CKD progression in nondiabetic renal disease. We analyzed the relation between FGF-23 and renal outcome in diabetic nephropathy (DN). Design, setting, participants, & measurements DN patients participating in a clinical trial (enalapril+placebo versus enalapril+losartan) had baseline data collected and were followed until June 2009 or until the primary outcome was reached. Four patients were lost to follow-up. The composite primary outcome was defined as death, doubling of serum creatinine, and/or dialysis need. Results At baseline, serum FGF-23 showed a significant association with serum creatinine, intact parathyroid hormone, proteirturia, urinary fractional excretion of phosphate, male sex, and race. Interestingly, FGF-23 was not related to calcium, phosphorus, 25OH-vitamin D, or 24-hour urinary phosphorus. Mean follow-up time was 30.7 +/- 10 months. Cox regression showed that FGF-23 was an independent predictor of the primary outcome, even after adjustment for creatinine clearance and intact parathyroid hormone (10 pg/ml FGF-23 increase = hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P = 0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of >70 pg/ml. Conclusions FGF-23 is a significant independent predictor of renal outcome in patients with macroalbuminuric DN. Further studies should clarify whether this relation is causal and whether FGF-23 should be a new therapeutic target for CKD prevention. Clin J Am Soc Nephrol 6: 241-247, 2011. doi: 10.2215/CJN.04250510FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paul

Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4

Hemodynamic Behavior During Hemodialysis: Effects of Dialysate Concentrations of Bicarbonate and Potassium

Background/Aims: Ultrafiltration that occurs during hemodialysis (HD) promotes profound alterations in a relatively short period of time. The dialysate content of bicarbonate (DBic) and potassium (DK) may have impact over intradialytic hemodynamics, which goes beyond ultrafiltration, and its impact was evaluated in a prospective cohort. Methods: 30 patients under HD were submitted to hemodynamic assessment (HA) at the beginning and at the end of HD sessions, through a non-invasive method. Serum minus dialysate potassium concentration was expressed as K-Gap. Cardiac index (CI) and peripheral arterial resistance (PAR) variation (post-HD minus pre-HD) were expressed as &#x0394;CI and &#x0394;PAR. Dialysate content of sodium and calcium were expressed as DNa and DCa, respectively. Results: Mean DNa, DK and DBic were, respectively, 136.4 ± 1.1, 2.1 ± 0.6 and 38.2 ± 2.1 mEq/L. In 15 patients, DCa was >1.5 mmol/L and in the other 15 patients ≤ 1.5 mmol/L. The K-Gap ranged from 1.4 to 5.1 mEq/l (median 3.0 mEq/L). There was a reduction in post-HD CI and systolic blood pressure (&#x0394;CI = -0.72l/min/m2 and -11.3±15.1mmHg, respectively, p5, pConclusion: We confirmed that Na and Ca dialysate content exerts and important role on hemodynamic during HD. In addition, our findings pointed out that higher dialysate concentrations of bicarbonate and potassium promote lower cardiac performance at the end of hemodialysis session