Hypertension and circulating mRNA for 11beta-hydroxysteroid dehydrogenase type II.

Circulating DNA and mRNA for 11beta-hydoxysteroid dehydrogenase (HSD) type II were measured in patients with hypertension and in healthy subjects. DNA and RNA levels in hypertensive patients and controls were quantified using real-time RT-PCR. Messenger RNA for 11beta-HSD type II was significantly lower in the hypertensive patients (median: 0.18) (P= 0.032) than in healthy subjects (median: 0.42). Plasma DNA was also significantly lower (P= 0.016) in hypertension. It is suggested that measurement of mRNA for 11beta-HSD type II in hypertension may identify subjects who may be salt-sensitive.

Advanced glycation end product free adducts are cleared by dialysis.

Plasma advanced glycation end product (AGE) free adducts are increased up to 50-fold among patients on dialysis. We examined the ability of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) to clear these compounds. The AGE free adducts Nepsilon-carboxymethyl-lysine (CML) and Nepsilon-(1-carboxyethyl)lysine (CEL) and the hydroimidazolones derived from glyoxal (G-H1), methylglyoxal (MG-H1), and 3-deoxyglucosone (3DG-H) were determined by LC-MS/MS and pentosidine by HPLC with fluorimetric detection in ultrafiltrates of plasma, urine, or PD effluent as appropriate from patients on HD (n = 8) or PD (n = 8), and from healthy controls (n = 8). Among patients on HD, all free AGEs predialysis were significantly higher than in controls and were decreased with dialysis. The removal of MG-H1 and 3DG-H was comparable to that of urea, whereas that of CML and pentosidine was some 20% higher; in contrast, the removal of CEL and G-H1 was 25% lower. Among patients on CAPD, free AGEs in PD effluent increased with increasing dwell time. The combined renal and peritoneal 24-h excretion rates of CML (4.7 micromol), CEL (6.5 micromol), 3DG-H (16.6 micromol), and pentosidine (0.08 micromol) were twofold higher than the amount excreted in healthy controls, whereas MG-H1 was ninefold higher (59 micromol); the combined clearances of all free AGEs except pentosidine were lower than in healthy controls. Impaired renal clearance contributes to increased plasma free AGEs in uremia, but the increased excretion rate among patients on PD demonstrates that there was also an increased synthesis of free AGEs. Both HD and PD are able to remove free AGEs.

Removal of advanced glycation end products in clinical renal failure by peritoneal dialysis and haemodialysis.

AGEs (advanced glycation end products) accumulate markedly in the plasma of human subjects with renal failure. We investigated the efficiency of removal of AGEs from the circulation by PD (peritoneal dialysis) and HD (haemodialysis) therapy. Free AGEs were measured by LC-MS/MS in blood plasma before dialysis, in dialysis fluid effusate after a 2-12 h dwell time in the peritoneal cavity of PD subjects, and in the HD dialysate before and after HD therapy. In clinical uraemia, the concentrations of free AGEs in blood plasma were increased up to 50-fold. For example, levels of MG-H1 (methylglyoxal-derived hydroimidazolone) were: normal controls, 110+/-46 nM; PD subjects, 1876+/-676 ( P <0.01); HD subjects, 5496+/-1138 nM ( P <0.001). In PD subjects, the AGE concentration in the effusate increased with increasing dwell time, reaching a maximum at a concentration higher than that in plasma for some AGEs at 4-12 h. This may reflect AGE formation in the peritoneal cavity. In HD, AGE concentrations in HD fluid were decreased markedly from the start to the end of a dialysis session, except that levels of the methylglyoxal-derived AGEs N (epsilon)-(1-carboxyethyl)lysine and MG-H1, and of pentosidine, remained 5-fold higher than control levels. Inadequate clearance of free AGEs may be linked to the increased risk of cardiovascular disease in patients with renal failure.