[Intracellular pH changes induced by sclerosing agents in peritoneal fibroblasts]. / Alteraciones del pH intracelular en fibroblastos peritoneales inducida por factores implicados en la esclerosis peritoneal.

UNLABELLED: Sclerosing encapsulating peritonitis secondary to peritoneal dialysis has been associated to acetate-containing dialysis fluids, hypertonic glucose and disinfectants. Physiopathologic mechanisms of fibrotic proliferation that implicate those agents are not totally explained. With an experimental approach using cultured peritoneal fibroblasts, we have studied intracellular pH changes and Na+/H+ antiporter activity under cells perfusion with peritoneal dialysis liquids containing acetate, lactate, hypertonic glucose and interleukin-1. All experiments were performed at extracellular pH 7.4 and physiologic HCO3/CO2 concentration. RESULTS: 35 mM acetate produced a huge intracellular acidosis (ipH = 6.80 +/- 0.08). Lactate effect was less important (6.95 +/- 0.07), with a slow ipH recovery in about 30 min in both cases. IL-1, 10(-6) M also reduced ipH to 7.10 +/- 0.03. Acidosis was linked to Ca2+ outflow via Ca/H exchange and was blocked with Cd 20 nM. Extracellular Na = 0 and amiloride totally inhibited ipH recovery after acetate, lactate, or interleukin-induced acidosis. Hypertonic glucose perfusion increased ipH (7.31 +/- 0.06) for 5-7 min. This increase was also inhibited by amiloride or extracellular Na absence. Na+/H+ exchanger activity increased to 58%, and kept activated after ipH recovery. In conclusion, acetate, hypertonic glucose and IL-1 showed the common effect of stimulating the sodium-proton exchanger by different mechanisms, giving a possibility of potentiation. Activated Na+/H+ exchanger may act as a signal-transduction increasing fibroblast proliferation and explaining the cellular mechanism of sclerosing peritonitis.

Factors influencing serum aluminum in CAPD patients.

The aim of this study was to find out the relationship between body iron stores and serum aluminum levels among 82 stable CAPD patients. The influence of other factors such as time on CAPD and residual renal function was also considered. Thirty-three patients received aluminum hydroxide as a phosphate binder, and they had significantly higher aluminum levels (36.45 microg/l) than the patients who were not taking aluminum preparations (17.2 microg/l, p = 0.001). A statistically-significant correlation between serum aluminum levels and residual renal function and time on CAPD was also observed (p <0.05). However, there was no relationship between serum aluminum levels and serum iron, ferritin and transferrin saturation, neither between body iron stores and total excretion of aluminum (p >0.05). In previous reports, low serum iron levels were associated with high serum aluminum concentration among hemodialysis patients. However, this effect was not observed in the CAPD population under study. The highest risk of hyperaluminemia was found in the patients who were taking aluminum hydroxide, had worse residual renal function and had been longer on CAPD.

Is there a lesser hyperparathyroidism in diabetic patients with chronic renal failure?

Diabetic patients on dialysis have lower levels of parathyroid hormone (PTH); however, there is no data regarding PTH levels with different degrees of chronic renal failure (CRF). We compared 58 diabetic patients with different degrees of CRF with 268 non-diabetic patients with CRF (serum creatinine >1.2 mg/dl). In both groups, we investigated the main biochemical parameters together with plasma calcium, phosphorus, magnesium, PTH and calcitriol. Diabetic patients showed lower levels of PTH than non-diabetics (P=0.003). The differences were observed in patients with creatinine clearance <70ml/min. We also observed differences in phosphorus, magnesium and tubular resorption of phosphate. In the group of diabetic patients, serum glucose correlated inversely with PTH. Our study suggests that poor control of diabetes (hyperglycaemia) may play a role in the pathogenesis of the hypoparathyroidism observed in patients with diabetes and CRF.

Reversibility of parathyroid gland suppression in CAPD patients with low i-PTH levels.

The i-PTH response to changes in the peritoneal calcium balance was studied prospectively in a group of 13 stable CAPD patients, who presumably had adynamic bone disease, with low or normal i-PTH values and low aluminum in plasma. Five days after the reduction of dialysate calcium concentration from 1.75 mmol/l to 1 mmol/l, there was a significant elevation in the serum i-PTH. These increased PTH levels returned to baseline values when patients were changed to the 1.75 mmol/l Ca solution (p = 0.004). The changes in i-PTH mirrored the changes in peritoneal calcium balances. These results support the notion that the low or normal levels of i-PTH frequently seen in peritoneal dialysis patients are due to the hypercalcemic effects of the standard peritoneal dialysis solutions; in these patients, the parathyroid hormone production is normal since negative peritoneal balances of calcium are associated with an increase in serum i-PTH.