1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.

Peritoneal transport characteristics in CAPD patients are often assessed by the peritoneal equilibration test (PET), which uses a four hour dwell with glucose 2.27% dialysate. From the test, the dialysate/plasma ratio of creatinine (D/PCr), the dialysate/initial dialysate ratio of glucose (D/Do) and net ultrafiltration (NUF, drained minus instilled volume) are calculated. The standard peritoneal permeability analysis (SPA) is a modification and extension of the PET: glucose 1.36% dialysate is used, to which dextran 70 (1 g/liter) is added for the calculation of fluid kinetics. Mass transfer area coefficients (MTAC's) of low molecular weight solutes, clearances of proteins and the change in intraperitoneal volume (delta IPV) can be assessed. In this study the SPA was analyzed, and a comparison with the PET was made. A total number of 138 SPA's was analyzed in 86 different clinically stable patients. Normal values were calculated for both SPA and PET parameters in the same tests. Median (ranges) of comparable transport parameters from SPA and PET were: MTACCr, 10.4 ml/min (5.7 to 19.3); glucose absorption, 61% (35 to 87); delta IPV, 9.5 ml (-761 to 310); D/PCr, 0.76 (0.53 to 1.14); D/D0, 0.37 (0.13 to 0.56); NUF, -75 ml (-675 to 450). The agreement between SPA and PET was analyzed using the method of Bland and Altman. A fairly good agreement was present between NUF and delta IPV. Systematic errors were found when D/PCr and MTACCr were compared: D/P overestimated MTAC mainly in the low range, whereas in the high range values were underestimated. A similar pattern was seen for the transport parameters of glucose. In 40 patients negative net ultrafiltration was present, and possible reasons for this were assessed. In 9 patients no reason could be identified. It can be concluded that the SPA provides useful and extensive information on peritoneal transport parameters. Compared to the PET, the SPA has better discriminative power for the transport of glucose and creatinine.

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Osmotic-induced fluid and solute transport was studied in ten stable CAPD patients, who were examined twice within one week, using dialysate with 1.36% glucose on the first and 3.86% glucose on the second day. Peritoneal fluid kinetics were determined using intraperitoneally administered dextran 70 as a volume marker. After a four-hour dwell period, an increase in mean transcapillary ultrafiltration rate (TCUFR) with 3.86% glucose compared to 1.36% glucose was found (3.40 +/- 0.62 ml/min vs. 1.20 +/- 0.57, P < 0.001), but the lymphatic absorption was unchanged (1.32 +/- 0.10 ml/min vs. 1.42 +/- 0.15). The increased TCUFR resulted in a higher clearance of beta 2-microglobulin, but no differences were present in the clearances of albumin, transferrin, IgG, IgA and alpha 2-macroglobulin. This is consistent with the two pore theory for transcapillary transport with a small pore size of less than 40 A. The contribution of osmotic induced convection to the total transport of beta 2-microglobulin was small (6% during 1.36% glucose, 16% during 3.86% glucose), suggesting that macromolecules are mainly transported by diffusion or hydrostatic convection. The peritoneal restriction coefficient was 2.37 +/- 0.04, indicating restricted diffusion for macromolecules. In contrast, the restriction coefficient for low-molecular weight solutes was 1.24 +/- 0.03, in accordance with a process of mainly unrestricted diffusion for solutes smaller than 16 A. Higher values of protein clearances were found during the first hour of dialysis compared with the subsequent hours.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective two year follow-up study of the functional characteristics of the peritoneal membrane was conducted in 61 CAPD patients. Peritoneal transport of solutes, calculated by mass transfer area coefficients for urea and creatinine, peritoneal clearances for proteins, percentage of absorption of glucose, as well as net ultrafiltration were measured every four months. After five months on CAPD a decrease was found for the transport of most solutes (P < 0.05, mean values, ml/min/1.73 m2): urea 18.1 to 16.2, creatinine 9.5 to 8.4, IgG 0.049 to 0.040 and alpha 2-macroglobulin 0.020 to 0.015, as well as for the absorption of glucose (57.9 to 53.2%, P < 0.05). Net ultrafiltration increased simultaneously from 44.6 to 100.5 ml/4 hr/1.73 m2, P < 0.05. From five months to two years on CAPD a significant increase in the transport of all solutes except alpha 2-macroglobulin was found, as well as a decrease in net ultrafiltration. Peritoneal transport at the end of the study was not significantly different from the starting values. Our findings indicate an initial effect of CAPD itself on peritoneal transport, probably due to the recent start of the treatment. Baseline values were reached after five months on CAPD. Thereafter a gradual increase in peritoneal solute transport occurred during two years of treatment. This can be explained by an increase in the effective peritoneal surface area.

Transcapillary ultrafiltration during CAPD is determined by the ultrafiltration coefficient of the peritoneal membrane and by Starling forces, the latter being mainly determined by the osmolality of the dialysate. Dialysate sodium concentration decreases during a dwell, implying that: (1) sodium passes the peritoneal membrane to a lesser extent than H2O, and (2) more H2O than sodium is removed in overhydrated patients. We therefore compared two dialysate solutions with similar osmolality, but different sodium concentration (Na+ 129 mmol/liter and 102 mmol/liter). Two peritoneal permeability tests (2 x 6 hrs, dextran 70 as volume marker) with an interval of two days were performed in 10 CAPD patients. Transcapillary ultrafiltration rate was higher with ultralow sodium dialysate (USD) than normal sodium dialysate (NSD): 1.80 +/- 0.16 ml/min versus 1.58 +/- 0.18 (P < 0.01). It was especially higher during the last two hours of the dwell: 0.49 +/- 0.12 ml/min (USD) versus 0.27 +/- 0.13 (NSD). The effective lymphatic absorption rate was not different: 1.01 +/- 0.12 ml/min (USD) versus 1.05 +/- 0.09 (NSD). Using two different kinetic models, the reflection coefficients for glucose, sodium and chloride were 0.032, 0.029 and 0.027 (for the convection model) and 0.033, 0.030 and 0.027 (for the diffusion model). As a consequence the decline in osmotic pressure was more gradual during the exchange with USD. The peritoneal membrane characteristics, that is the effective peritoneal surface area and the peritoneal restriction coefficient, were not altered by the composition of the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of an increased intraperitoneal pressure on fluid and solute transport was studied in eight stable CAPD patients. Two permeability tests of two hours each with continuous registration of the intraperitoneal pressure were performed while patients were in supine position. The intra-abdominal pressure was raised by means of a tightening girdle with inflatable cuffs in one of the experiments. Intraperitoneally administered dextran 70 was used as a volume marker in order to determine the peritoneal fluid kinetics. The increment in the intra-abdominal pressure of 10.0 +/- 1.0 mm Hg caused a decline in the net ultrafiltration. This was mainly determined by an increase in the lymphatic absorption: 1.07 +/- 0.18 ml/min (without compression) versus 1.86 +/- 0.25 ml/min (with compression; P < 0.01), whereas the transcapillary ultrafiltration rate tended to decrease: 2.02 +/- 0.23 versus 1.73 +/- 0.27 ml/min (P = 0.08). External compression also diminished solute transport from the circulation to the peritoneal cavity. The decline in the mass transfer area coefficient of urea, creatinine, urate and beta 2-microglobulin was 13%, indicating a smaller effective peritoneal surface area caused by external compression probably due to a decrease in the number of the perfused peritoneal capillaries. The fall in the peritoneal protein clearances was more pronounced the higher the molecular weight of the protein, consistent with a decline in the intrinsic permeability of the peritoneum. Kinetic modeling using computer simulations was used to analyse these effects in terms of the pore theory, using a convection model (large pore radius 184 +/- 14 A) and a diffusion model (large pore radius 1028 +/- 218 A) for the transport of macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)

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