Effects of candesartan on glomerular hemodynamics and permselectivity in patients with favorable renal allograft function.

BACKGROUND: Distinct effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers on glomerular perfusion and permselectivity are important determinants of the substances nephroprotective quality. In renal allograft recipients, however, specific effects of angiotensin antagonism on glomerular function have not been evaluated so far. METHODS: Twenty patients with favorable allograft function were included into a prospective study within the first year after renal transplantation. Glomerular filtration rate, renal plasma flow, albuminuria, and the fractional clearances of neutral dextrans were determined at baseline and after 3 months of treatment with candesartan. Ten individuals after renal donation served as controls for the baseline evaluation. RESULTS: Compared with the control group, the allograft recipients had a higher renal-vascular resistance and a lower glomerular filtration rate. Albuminuria was significantly higher; however, the difference in the dextran sieving curve was not statistically significant. Apart from mild changes in biochemical parameters, the therapy with candesartan led to a rise in serum creatinine along with a nonsignificant drop in the glomerular filtration rate. There was a highly significant drop in filtration fraction and albuminuria. Glomerular permselectivity clearly improved for a range of dextran molecular diameters from 43 Angstrom up to 73 Angstrom. CONCLUSION: A therapy with candesartan has distinct effects on glomerular function in patients after renal transplantation. A drop in filtration fraction along with an improvement in glomerular permselectivity and albuminuria point to a nephroprotective quality that should lead to a systematic clinical evaluation of candesartan even in patients with favorable renal allograft function.

Effluent CA 125 concentration in chronic peritoneal dialysis patients: influence of PD duration, peritoneal transport and PD regimen.

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 +/- 11.2 vs. 20.7 +/- 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 +/- 11.0 vs. 21.6 +/- 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid.

Peritoneal fluid and solute transport: influence of treatment time, peritoneal dialysis modality, and peritonitis incidence.

The integrity of the peritoneal membrane in peritoneal dialysis (PD) is of major importance for adequate dialysis and fluid balance. However, alterations in peritoneal fluid transport, such as ultrafiltration failure, often develop during long-term PD. To investigate peritoneal solute and fluid transport and to analyze the influence of treatment time, peritonitis incidence, and PD modality (continuous ambulatory PD [CAPD] or automated PD [APD]), a cross-sectional study with an extended peritoneal transport test that used dextran 70 in 2 L of glucose was performed in 23 nonselected chronic PD patients. Compared were long-term (>40 mo) with short-term PD patients (<40 mo), CAPD with APD patients, and those with a peritonitis incidence of >0.25/yr to those with an incidence of <0.25/yr. Dialysate/plasma (D/P) ratio and mass transfer area coefficient of creatinine, lymphatic absorption rate (LAR), transcapillary ultrafiltration, and effective ultrafiltration were measured. Long-term PD patients had higher D/P ratio of creatinine (73.5 +/- 2.3% versus 65.9 +/- 2.2%; P < 0.01) and higher LAR (243 +/- 69 ml/4 h versus 96 +/- 31 ml/4 h; P < 0.03), both resulting in lower effective ultrafiltration (242 +/- 35 ml/4 h versus 324 +/- 30 ml/4 h; P < 0.05). D/P ratio (r = 0.66) and LAR (r = 0.67) were positively correlated to PD duration. Patients on APD compared with those on CAPD and patients with a history of peritonitis compared with those without did not differ in terms of D/P ratio, mass transfer area coefficient, LAR, transcapillary ultrafiltration, and effective ultrafiltration. Lower ultrafiltration after long-term PD is both the result of increased small solute transport and increased lymphatic absorption. APD or CAPD modality and peritonitis incidence do not have a significant influence on small solute transport or fluid kinetics.