Objective To validate the use of a modified three-pore model for predicting fluid transport during long dwell exchanges that use a 7.5% icodextrin solution. Design A nonrandomized, single group, repeated measures study. Patients Ten peritoneal dialysis patients underwent a single 8-hour exchange of a 7.5% icodextrin solution. All patients were naïve to icodextrin. Main Outcome Measures A modified three-pore model was used to model solute and fluid transport during each 8-hour exchange. Concordance correlation coefficients were used to estimate the level of agreement between modeled and measured values of net ultrafiltration (UF) and intraperitoneal volume. Methods Each patient underwent a modified 8-hour standard peritoneal permeability analysis using a 2-L 7.5% icodextrin exchange. Dextran 70 was added to the icodextrin solution as volume marker to estimate fluid transport kinetics. Transcapillary UF, fluid absorption, and intraperitoneal volumes were assessed via the volume marker at 0, 5, 15, 30, 60, 120, 240, 300, 360, 420, and 480 minutes. Results There was strong agreement (concordance correlation = 0.9856) between net UF as measured by the volume marker data and net UF as modeled using the modified three-pore model implemented in PD Adequest (Baxter Healthcare, Deerfield, Illinois, USA). Conclusions Net UF and intraperitoneal volumes for long dwell exchanges using a 7.5% icodextrin solution can be accurately modeled with a modified three-pore model. Steady state icodextrin plasma levels are needed to accurately predict net UF for chronic users of icodextrin.

Background and objectives Little is known about the functional course after initiating dialysis in elderly patients with ESKD. The aim of this study was to assess the association of the initiation of dialysis in an elderly population with functional status and caregiver burden. Design, setting, participants & measurements This study included participants aged $65 years with ESKD who were enrolled in the Geriatric Assessment in Older Patients Starting Dialysis study. All underwent a geriatric assessment and a frailty screening (Fried Frailty Index and Groningen Frailty Indicator) at dialysis initiation. Functional status (activities of daily life and instrumental activities of daily life) and caregiver burden were assessed at baseline and after 6 months. Decline was defined as loss of one or more domains in functional status, stable as no difference between baseline and follow-up, and improvement as gain of one or more domains in functional status. Logistic regression was performed to assess the association between the combined outcome functional decline/death and potential risk factors. Results Of the 196 included participants functional data were available for 187 participants. Mean age was 7567 years and 33% were women. At the start of dialysis, 79% were care dependent in functional status. After 6 months, 40% experienced a decline in functional status, 34% remained stable, 18% improved, and 8% died. The prevalence of high caregiver burden increased from 23%-38% (P=0.004). In the multivariable analysis age (odds ratio, 1.05; 95% confidence interval, 1.00 to 1.10 per year older at baseline) and a high Groningen Frailty Indicator compared with low score (odds ratio, 1.97; 95% confidence interval, 1.05 to 3.68) were associated with functional decline/death. Conclusions In patients aged $65 years, functional decline within the first 6 months after initiating dialysis is highly prevalent. The risk is higher in older and frail patients. Loss in functional status was mainly driven by decline in instrumental activities of daily life. Moreover, initiation of dialysis is accompanied by an increase in caregiver burden.

Nitroprusside is a nitric oxide (NO) donor. To investigate effects of nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed. Ten stable CAPD patients were studied twice within one week with glucose based dialysate (1.36% Dianeal) with and without addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in plasma and dialysate. The MTACs of low molecular weight solutes were greater with nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP) versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP) versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective peritoneal surface area with nitroprusside. Furthermore, the restriction coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23 (NP) (P = 0.02), suggesting some effect also on the size selectivity to these solutes. The effect of nitroprusside on the clearances of serum proteins was more pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70% for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in size selectivity was reflected in a decrease in the restriction coefficient for macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using computer simulations, was done to analyze these effects in terms of the pore theory, using a convection model and a diffusion model for the transport of macromolecules. Nitroprusside led to an increase of both the large pore radius and the small pore radius and of the unrestricted area over diffusion distance. These effects were more pronounced with the diffusion model. The MTAC CO2 was not different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than expected on the basis of the molecular weight during both dwells. The dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside: 0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its molecular weight (P < 0.001). This points to local generation of cGMP after the addition of nitroprusside, induced by NO. No differences were found in the dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha and thromboxane B2 after addition of nitroprusside. The transcapillary ultrafiltration rate and the net ultrafiltration rate during four hours were not different with nitroprusside. In conclusion, nitroprusside i.p. increased the effective peritoneal surface area and the intrinsic permeability, but the peritoneal blood flow did not change. The greater than expected D/P ratios of cGMP point to local generation of cGMP with nitroprusside, induced by NO.

Small solutes clearances cannot be increased by furosemide. Increasing the instilled volume of dialysis fluid and the number of exchanges both affect solute clearance. Studies are necessary on long-term effects of manipulation of the peritoneal membrane with nitroprusside.

Addition of the nitric oxide (NO) donor nitroprusside to 1.36% glucose dialysate enlarges the effective peritoneal surface area during four-hour dwells. The theoretical positive effect on ultrafiltration is, however, counteracted by an increase in glucose absorption. The absorption of the glucose polymer icodextrin is much lower in comparison with glucose-based dialysis solutions, due to its high molecular weight. In the present study 7.5% icodextrin dialysis solution with and without the addition of 4.5 mg/liter nitroprusside was studied during eight-hour CAPD dwells. Two Standard Peritoneal permeability Analyses, adapted for eight-hour dwells, were performed in 10 stable CAPD patients. Nitrate and cGMP were measured as parameters of NO synthesis. The transcapillary ultrafiltration increased in a linear way with icodextrin (ICO) and was even higher after the addition of nitroprusside (NP): 666 (ICO) versus 834 (NP) ml/8 hr, P = 0.03. The effective lymphatic absorption rate was not different. The resulting net ultrafiltration increased with nitroprusside: 344 (ICO) versus 540 (NP) ml/8 hr, P < 0.01. The mass transfer area coefficient of urea increased 15% and that of creatinine 26% with nitroprusside, consistent with the expected enlargement of the vascular peritoneal surface area. The increase in protein clearances was more pronounced the larger the protein: beta 2-microglobulin 19%, albumin 47%, IgG 63% and alpha 2-macroglobulin 95%. Dialysate/plasma (D/P) ratios of nitrate were not higher than the expected values on the basis of its molecular weight (P < 0.001). They increased 19% with nitroprusside. Also, the D/P ratio cyclic guanosine monophosphate (cGMP) after four hours increased with nitroprusside (0.39, range 0.13 to 0.55 ICO, and 0.82, range 0.36 to 1.39 NP, P = 0.01). With nitroprusside the D/P ratio cGMP was higher than expected after four and eight hours (P < 0.001). This points to local generation of NO after addition of nitroprusside. The nitroprusside induced increase in the mass transfer area coefficients (MTAC) of creatinine and in the ultrafiltration caused an increase in the creatinine clearance from 4.2 ml/min to 5.0 ml/min during the eight-hour dwell. This means that nitroprusside adds 3 liters/week to the peritoneal clearance of creatinine. The adequacy of peritoneal dialysis can therefore be improved by the addition of nitroprusside to 7.5% icodextrin, used for the long exchange.

No abstract

<b><i>Background and Objectives:</i></b> A geriatric assessment (GA) is a structural method for identifying frail patients. The relation of GA findings and risk of death in end-stage kidney disease (ESKD) is not known. The objective of the GA in OLder patients starting Dialysis Study was to assess the association of GA at dialysis initiation with early mortality and hospitalization. <b><i>Design, Setting, Participants, and Measurements:</i></b> Patients ≥65 years old were included just prior to dialysis initiation. All participants underwent a GA, including assessment of (instrumental) activities of daily living (ADL), mobility, cognition, mood, nutrition, and comorbidity. In addition, a frailty screening (Fried Frailty Index, [FFI]) was applied. Outcome measures were 6- and 12-month mortality, and 6-month hospitalization. Associations with mortality were assessed with cox-regression adjusting for age, sex, comorbidity burden, smoking, residual kidney function and dialysis modality. Associations with hospitalization were assessed with logistic regression, adjusting for relevant confounders. <b><i>Results:</i></b> In all, 192 patients were included, mean age 75 ± 7 years, of whom 48% had ≥3 geriatric impairments and were considered frail. The FFI screening resulted in 46% frail patients. Mortality rate was 8 and 15% at 6- and 12-months after enrolment, and transplantation rate was 2 and 4% respectively. Twelve-month mortality risk was higher in patients with ≥3 impairments (hazard ratio [HR] 2.97 [95% CI 1.19–7.45]) compared to less impaired patients. FFI frail patients had a higher risk of 12-month mortality (HR 7.22 [95% CI 2.47–21.13]) and hospitalization (OR 1.93 [95% CI 1.00–3.72]) compared to fit patients. Malnutrition was associated with 12-month mortality, while impaired ADL and depressive symptoms were associated with 12-month mortality and hospitalization. <b><i>Conclusions:</i></b> Frailty as assessed by a GA is related to mortality in elderly patients with ESKD. Individual components of the GA are related to both mortality and hospitalization. As the GA allows for distinguishing between frail and fit patients initiating dialysis, it is potentially of added value in the decision-making process concerning dialysis initiation.

The indomethacin induced inhibition of the synthesis of 6-keto-PGF1alpha and TxB2 did not lead to alterations in functional parameters of the peritoneal surface area, the intrinsic permeability to macromolecules and fluid kinetics. Therefore, these prostaglandins are not likely to be involved in the regulation of peritoneal transport during stable CAPD.