The impact of peritoneal dialysis on oxypurinol and urate elimination in people with gout.

Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.

Pharmacokinetics of ferric pyrophosphate citrate administered via dialysate and intravenously to pediatric patients on chronic hemodialysis.

BACKGROUND: Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients. METHODS: The pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to <18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 µM (110 µg/L) iron via dialysate during hemodialysis session no. 2. RESULTS: Mean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline by 10 h after the start of hemodialysis for both routes. Iron exposure was greater after administration via dialysate than after IV administration. The absolute amount of absorbed iron after administration via dialysate roughly doubled with increasing age, but the weight-normalized amount of absorbed iron was relatively constant across age groups (~ 0.06-0.10 mg/kg). FPC was well tolerated in the small number of patients studied. CONCLUSIONS: FPC iron can be administered to pediatric patients with CKD-5HD via dialysate or by the IV route. Further study of FPC administered to maintain hemoglobin concentration is indicated.

Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis.

Transforming growth factor-ß1 (TGF-ß1) is a major mediator of peritoneal fibrosis and reportedly affects expression of the H3K4 methyltransferase, SET7/9. SET7/9-induced H3K4 mono-methylation (H3K4me1) critically activates transcription of fibrosis-related genes. In this study, we examined the effect of SET7/9 inhibition on peritoneal fibrosis in mice and in human peritoneal mesothelial cells (HPMCs). We also examined SET7/9 expression in nonadherent cells isolated from the effluent of peritoneal dialysis (PD) patients. Murine peritoneal fibrosis was induced by intraperitoneal injection of methylglyoxal (MGO) into male C57/BL6 mice over 21 days. Sinefungin, a SET7/9 inhibitor, was administered subcutaneously just before MGO injection (10 mg/kg). SET7/9 expression was elevated in both MGO-injected mice and nonadherent cells isolated from the effluent of PD patients. SET7/9 expression was positively correlated with dialysate/plasma ratio of creatinine in PD patients. Sinefungin was shown immunohistochemically to suppress expression of mesenchymal cells and collagen deposition, accompanied by decreased H3K4me1 levels. Peritoneal equilibration tests showed that sinefungin attenuated the urea nitrogen transport rate from plasma and the glucose absorption rate from the dialysate. In vitro, sinefungin suppressed TGF-ß1-induced expression of fibrotic markers and inhibited H3K4me1. These findings suggest that inhibiting the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis.

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

UNLABELLED: ♦ BACKGROUND: The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ METHODS: This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ RESULTS: The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ CONCLUSIONS: On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration.

Is it useful to increase dialysate flow rate to improve the delivered Kt?

BACKGROUND: Increasing dialysate flow rates (Qd) from 500 to 800 ml/min has been recommended to increase dialysis efficiency. A few publications show that increasing Qd no longer led to an increase in mass transfer area coefficient (KoA) or Kt/V measurement. Our objectives were: 1) Studying the effect in Kt of using a Qd of 400, 500, 700 ml/min and autoflow (AF) with different modern dialysers. 2) Comparing the effect on Kt of water consumption vs. dialysis time to obtain an individual objective of Kt (Ktobj) adjusted to body surface. METHODS: This is a prospective single-centre study with crossover design. Thirty-one patients were studied and six sessions with each Qd were performed. HD parameters were acquired directly from the monitor display: effective blood flow rate (Qbe), Qd, effective dialysis time (Te) and measured by conductivity monitoring, final Kt. RESULTS: We studied a total of 637 sessions: 178 with 500 ml/min, 173 with 700 ml/min, 160 with AF and 126 with 400 ml/min. Kt rose a 4% comparing 400 with 500 ml/min, and 3% comparing 500 with 700 ml/min. Ktobj was reached in 82.4, 88.2, 88.2 and 94.1% of patients with 400, AF, 500 and 700 ml/min, respectively. We did not find statistical differences between dialysers. The difference between programmed time and Te was 8' when Qd was 400 and 500 ml/min and 8.8' with Qd = 700 ml/min. Calculating an average time loss of eight minutes/session, we can say that a patient loses 24' weekly, 312' monthly and 62.4 hours yearly. Identical Kt could be obtained with Qd of 400 and 500 ml/min, increasing dialysis time 9.1' and saving 20% of dialysate. CONCLUSIONS: Our data suggest that increasing Qd over 400 ml/min for these dialysers offers a limited benefit. Increasing time is a better alternative with demonstrated benefits to the patient and also less water consumption.

Imaging of the peritoneum evaluated by 99mTc-icodextrin scintigraphy in peritoneal dialysis patients: preliminary data.

AIM: In this study, we proposed a peritoneal scintigraphy with a different marker, the 99mTechnetium-Icodextrin, to evaluate the distribution of the dialysate within the peritoneal cavity in peritoneal dialysis (PD) patients. METHODS: 99mTc-Icodextrin scintigraphy was performed in 16 PD patients. 0.5 ml of 7.5% Icodextrin solution was labeled with 74 megabecquerel (MBq) of 99mTc and then added to 2,000 ml of dialysate solution (2.5% dextrose). The peritoneum scintigraphy was performed by a SPECT gamma camera with the peritoneal cavity filled and after the complete drainage of the radio compound-dialysate mixture. The images were reviewed for evidence of peritoneal leaks, hernias, loculated fluid collections, and peritoneal membrane adhesions. RESULTS: Abnormal findings were detected by 99mTc-Icodextrin scintigraphy in 4 (25%) out of 16 patients and included retroperitoneal (n = 1), diaphragmatic (n = 1) and inguinal (n = 1) leakages and peritoneal membrane adhesions (n = 1). CONCLUSIONS: Peritoneum scintigraphy with 99mTc-Icodextrin is a useful method to detect some complications occurring during peritoneal dialysis; it offers excellent imaging to assess these complications.

Peritoneal solute transport rate as an independent risk factor for total and cardiovascular mortality in a population of peritoneal dialysis patients.

The aim of the present study was to assess the influence of peritoneal permeability expressed as the dialysate-to-plasma ratio of creatinine (D/P Cr) on total and cardiovascular (CV) mortality in a population of peritoneal dialysis (PD) patients during a 6-year observation period. The study recruited 55 patients (mean age: 53 years) treated with PD for a median of 24 months. Hematology parameters and serum albumin were determined using routine methods. Tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta1) were determined by high-sensitivity ELISA. Peritoneal transport characteristics were identified using D/P Cr reference values after a peritoneal equilibration test. During the 6-year observation period, 22 patients (40%) died, mostly from CV complications (77% of deaths). In multiple Cox regression, D/P Cr and dialysate volume at PD initiation predicted total [hazard ratio (HR): 1.57; p = 0.02; and HR: 1.20; p = 0.04 respectively] and CV mortality (HR: 1.65; p = 0.02; and HR: 1.23; p = 0.05 respectively) independent of age, dialysis therapy duration, serum albumin concentration, dialysis adequacy measures, TGF-beta1, and TNF-alpha. Additionally, TNF-alpha was independently associated with all-cause and CV mortality, and albumin, with all-cause mortality. Baseline D/P Cr was a strong independent marker of survival in PD patients. Baseline D/P Cr and dialysate volume were independent risk factors for total and CV mortality in the PD population and could be significant for assessing CV risk in this population.

Hyperosmolality-mediated peritoneal microvascular vasodilation is linked to aquaporin function.

Glucose-based peritoneal dialysis (PD) solutions dilate the parietal and visceral peritoneal microvasculature by endothelium-dependent mechanisms that primarily involve hyperosmolality. This PD-mediated dilation occurs by active intracellular glucose uptake and adenosine Al receptor activation, and by hyperosmolality-stimulated glibenclamide-sensitive potassium channels. Both pathways invoke NO as a second messenger for vasodilation. We hypothesized that during crystalloid-induced osmosis, the osmotic water flux through the transendothelial water-exclusive aquaporin 1 (AQP1) channels is the primary mechanism whereby the endothelium is being stimulated to instigate hyperosmolality-driven vasodilation. Four microvascular levels (diameters in the range 6 - 100 microm) were visualized by intravital videomicroscopy of the terminal ileum in anesthetized rats. Microvascular diameters and flow were measured after topical exposure to a 5% hypertonic mannitol or 2.5% glucose-based PD solution, at baseline and after brief tissue pre-treatment (with 0.1% glutaraldehyde for 10 seconds) or after combined tissue pre-treatment and pharmacologic blockade of AQP1 with HgCl2 (100 micromol/L). Vascular endothelial integrity was verified by the response to acetylcholine (10(-4) mol/L) and sodium nitroprusside (10(-4) mol/L). The hyperosmolar solutions both caused rapid and sustained vasodilation at all microvascular levels, which was not altered by tissue pre-treatment. Inhibition of AQP1 completely abolished the mannitol-induced vasodilation and markedly attenuated the PD fluid-mediated vasodilation. Neither glutaraldehyde pre-treatment nor HgCl2 affected tissue integrity or endothelial cell function. We conclude that the peritoneal microvascular vasodilation caused by hyperosmolar PD fluid is instigated by the osmotic water flux through AQP1. Clinical PD solutions have components other than hyperosmolality that can induce endothelium-dependent peritoneal microvascular vasodilation independent of the AQP1-mediated osmosis.

Molecular mechanisms of peritoneal dialysis-induced microvascular vasodilation.

Peritoneal dialysis (PD) solutions dilate microvessels by undefined mechanisms. This vasodilation directly affects ultrafiltration and solute exchange during a PD dwell and is thought to account for the variable mass transfer area coefficient for small solutes during a glucose-based hypertonic dwell. We hypothesized that PD-mediated vasodilation occurs by endothelium-dependent mechanisms that involve endothelium energy-dependent K+ channels (K(ATP)), adenosine A1 receptor activation, and NO release. We used intravital videomicroscopy to study 3 levels of microvessels (A1 inflow arterioles about 100 microm diameter to pre-capillary A3 arterioles 10 - 15 microm diameter) in the terminal ileum of anesthetized rats under control conditions in vivo in a tissue bath. Ileum was bathed with hypertonic mannitol or 2.5% glucose-based PD solution (Delflex: Fresenius Medical Care North America, Waltham, MA, U.S.A.) with or without topical application of individual or combined specific inhibitors of the endothelium-dependent dilation pathways.: NO (L-NMMA), prostaglandin I2 (mefenamic acid), endothelium hyperpolarizing factor (glibenclamide), and adenosine A1 receptor antagonist (DPCPX). The mannitol and PD solutions induced rapid and sustained peritoneal vasodilation whose magnitude depended on microvascular level and osmotic solute. Combined inhibition of endothelium-dependent dilation pathways completely abolished the mannitol-induced hyperosmolality-mediated dilation at all microvascular levels, but selectively eliminated the PD solution-mediated A3 dilation. The K(ATP) and adenosine receptor antagonists, individually or combined, remarkably attenuated dilation in the smaller pre-capillary arterioles; NO inhibition, alone or combined with K(ATP) and adenosine receptor antagonists, eliminated the PD solution-induced dilation. The cyclooxygenase pathway is not involved in PD-induced dilation. Solutions for PD dilate the visceral peritoneal microvasculature by endothelium-dependent mechanisms, primarily the NO pathway. Adenosine receptor-activated NO release and K(ATP) channel-mediated endothelium hyperpolarization significantly contribute to vasodilation in the smaller peritoneal pre-capillary arterioles.

Fisiologia do transporte de fluidos e solutos atraves da membrana peritoneal / Physiology of fluid and solute transport across the peritoneal membrane

Nesta revisão, são explicados os fenômenos envolvidos nas trocas de fluidos e solutos através da membrana peritoneal, tanto na situação fisiológica quanto no contexto da diálise peritoneal. Para tanto, são utilizados os modelos matemáticos desenvolvidos para estudo do transporte pela membrana, tais como o "Modelo de Poros" e o "Modelo Distributivo". Os ganhos científicos com as pesquisas nesse campo são contemplados e as áreas que merecem pesquisas adicionais também são citadas. Assim, o estado atual do conhecimento fisiológico a respeito dessa modalidade de terapia renal substitutiva, no que se refere aos eventos relacionados à membrana peritoneal, encontra-se sintetizado nesse manuscrito.

In this review, phenomena involved in fluid and solute exchange through the peritoneal membrane, both in the physiologic and in the peritoneal dialysis settings, are explained. For that purpose, mathematical models developed for the study of molecule transport through the membrane, such as the "Pore Model" and the "Distributive Model" are used. Scientific accomplishments in the field are described and areas that require additional research are also cited. Knowledge about the physiologic mechanisms involved in this renal replacement therapy modality, concerning events directly related to the peritoneal membrane itself, is synthesized in this manuscript.

Cola-colored dialysate as a gastrointestinal sequelae of cardiac surgery in a patient who underwent peritoneal dialysis.

The discoloration of effluent peritoneal dialysate, which is transparent in origin, is seen in some particular conditions including chyloperitoneum, calcium channel blocker usage, hemoperitoneum, perforated cholecystitis, iron administration, and hemorrhagic pancreatitis. We report a case of a 60-year-old woman who underwent peritoneal dialysis for 3 years and presented with conspicuous cola-colored (brownish-black) dialysate after a cardiac surgery. The findings of the dialysate analysis and the abdominal computed tomography showed that this discoloration could be due to the presence of methemalbumin caused by pancreatitis (not hemorrhagic) combined with intra-abdominal bleeding-both of which are rare gastrointestinal complications of cardiac surgery. She eventually died of pulseless electrical activity due to severe sepsis with profound shock. Therefore, the rare event of cola-colored peritoneal dialysate could present as severe gastrointestinal sequelae of cardiac surgery and may indicate a poor prognosis.

Association between VEGF receptors and baseline peritoneal transport status in new peritoneal dialysis patients.

BACKGROUND: Peritoneal transport status is important not only for prescription, but also as a prognostic index. Flt-1 and Flk-1, the major vascular endothelial growth factor receptors involved in angiogenesis and hyperpermeability, may play a potent role in determining peritoneal transport characteristics. However, the relationship between them has not been studied to date. We hypothesized that Flt-1 and Flk-1 expression in the peritoneal vasculature of uremic patients could be closely related to baseline peritoneal transport status. METHODS: Thirty-six new patients without a previous history of peritonitis were enrolled. Clinical parameters such as age, sex, height, weight, causes of renal failure, and residual renal function were assessed. Parietal peritoneal biopsies were obtained during implantation of peritoneal dialytic catheters. Flt-1 and Flk-1 were semi-quantitatively evaluated by immunohistochemical staining. Peritoneal microvascular density (MVD) was counted. Within 6 weeks after commencing peritoneal dialysis, a standard peritoneal equilibration test was performed, and the dialysate-to-plasma concentration ratio for creatinine at 4 h (D4/P Cr) was determined. The patients were divided into two groups based on the D4/P Cr: more than 0.65 (Group H, n = 22) and less than or equal to 0.65 (Group L, n = 14). The 24-h peritoneal protein excretion (PPE) was assayed. Flt-1 and Flk-1 were correlated with peritoneal MVD, D4/P Cr, and PPE. RESULTS: Flt-1 and Flk-1 were detected in the peritoneal vasculature of uremic patients. Flt-1 expression was similar between the two groups, but Flk-1 expression in Group H was significantly higher than that in Group L (p = 0.001). Flt-1 expression did not show significant correlations with peritoneal MVD, D4/P Cr, and PPE. However, Flk-1 expression showed significant correlations with the above three parameters (p < 0.001 for all). CONCLUSIONS: For the first time, the expressions of Flt-1 and Flk-1 in peritoneal vasculature of uremic patients were detected. Flk-1 expression in peritoneal vasculature of uremic patients is closely correlated with the number of peritoneal microvessels, peritoneal small solute transport rate, and PPE. Our findings strongly suggest that Flk-1 may be a crucial determinant of baseline peritoneal transport characteristics. Further interventional studies are needed.

The plasma permeability factor in nephrotic syndrome: indirect evidence in pediatric peritoneal dialysis.

BACKGROUND: Nephrotic syndrome (NS) in children has been associated with a systemic circulating permeability factor. Therefore, once peritoneal dialysis (PD) has been started, peritoneal protein losses should be higher in the nephrotic than in the non-nephrotic population. OBJECTIVE: We compared peritoneal protein losses in children with and without NS on PD. METHODS: Our retrospective 4-year study analyzed Hispanic patients with NS under PD. Data at dialysis entry and 6 months later were compared. Nutritional support was given according to recommended dietary allowances and recommendations from the Kidney Disease Outcomes Quality Initiative. Clinical and biochemical data were obtained, and 24-hour dialysate and urine samples were collected to measure protein losses. Dialysis dose (Kt/V), daily protein intake (DPI), normalized protein equivalent of nitrogen appearance (nPNA), peritoneal equilibration test (PET), and peritonitis rate were determined. All measurements took place at least 4 weeks after resolution of a peritonitis episode. All patients received automated PD using a HomeChoice PD System cycler (Baxter Healthcare Corporation, Deerfield, IL, USA), with an exchange volume of 1100 mL/m(2) and a dextrose concentration of 1.5% - 2.5%. A control group of non-NS children on PD matched by age and sex were also studied. Data are reported as mean ± standard deviation. Differences between groups were calculated using the Mann-Whitney U-test, and p < 0.05 was considered significant. RESULTS: Each study group consisted of 10 patients [NS patients: 4 boys, mean age of 7.3 ± 4.1 years; control patients: 6 boys, mean age of 7.2 ± 4.7 years (p = nonsignificant)]. In the group with NS, 8 patients were diagnosed by biopsy as having focal segmental glomerulosclerosis, and 2 as having minimal-change disease. At study entry, patients with NS had hourly urinary protein losses of 398 ± 313 mg/m(2) and daily peritoneal protein losses of 3.4 ± 1.9 g/m(2), compared with 29.9 ± 31 mg/m(2) and 1.5 ± 1.1 g/m(2) respectively in the control group (p < 0.05). The same statistical difference was found 6 months later. We observed no statistical differences in PET results, daily exchange volume, and mean dextrose concentration of dialysate. Similarly, no significant between-group differences were observed for Kt/V, DPI, nPNA, and biochemical parameters. CONCLUSIONS: Hispanic children with NS on PD show higher peritoneal protein losses than do their control counterparts. Such differences could be secondary to increased peritoneal permeability caused by a systemic permeability factor.

Aluminum toxicokinetics in peritoneal dialysis patients.

CONTEXT: Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition. METHODS: Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion. RESULTS: After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues. CONCLUSION: This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.

Peritoneal macrophage infiltration is correlated with baseline peritoneal solute transport rate in peritoneal dialysis patients.

BACKGROUND: High baseline peritoneal solute transport rate is reportedly associated with reduced patient and technique survival in continuous peritoneal dialysis (PD) patients. However, the determinants of baseline peritoneal solute transport rate remain uncertain. The aim of this study was to investigate the relationship between peritoneal local inflammation, angiogenesis and systemic inflammation and baseline peritoneal permeability. METHODS: Peritoneal biopsy specimens from 42 pre-dialysis uraemic patients and 11 control individuals were investigated. Immunohistochemistry for CD68-positive macrophages, chymase- and tryptase-positive mast cells, interleukin-6 (IL-6)-positive cells, CD3-positive T cells, CD20-positive B cells, neutrophils and CD31- and pathologische anatomie Leiden-endothelium (PAL-E)-positive blood vessels in the peritoneum was performed. Baseline dialysate-to-plasma ratio for creatinine (D/P Cr) was determined within 6 months of PD induction. Clinical and laboratory parameters were measured at the time of peritoneal biopsy. Factors associated with peritoneal permeability were assessed by multiple linear regression analysis. RESULTS: Pre-dialysis uraemic peritoneum showed infiltration by CD68-positive macrophages, and mast cells, as compared with controls. Baseline D/P Cr was correlated with density of CD68-positive macrophages (P < 0.001), IL-6-positive cells (P < 0.001), CD31-positive (P < 0.05) and PAL-E-positive blood vessels (P < 0.05) and serum albumin (P < 0.05). However, baseline peritoneal permeability was not correlated with infiltration by mast cells, B cells, T cells, neutrophils, serum C-reactive protein or other clinical factors. On multiple linear regression analysis, the number of CD68-positive macrophages in peritoneum was an independent predictor for baseline peritoneal permeability (P = 0.009). CONCLUSIONS: Peritoneal macrophage infiltration is predominant in uraemic patients and is an important factor in predicting baseline peritoneal permeability.

[99mTc-MAA peritoneal scintigraphy in pleuroperitoneal comunication in peritoneal dialysis patients]. / Gammagrafía peritoneal con 99mTc-MAA en las comunicaciones pleuroperitoneales en pacientes en diálisis peritoneal.

Peritoneal dialysis is a fully-contrasted alternative for the treatment of end-stage renal disease although it is not exempt of complications. Peritonitis and exit-site infections are among the most frequent complications found. Pleural effusion secondary to pleuroperitoneal communication (PPC) is a serious and uncommon complication in these patients. We present the case of a 50-year old man diagnosed of end-stage renal disease undergoing treatment with peritoneal dialysis who presented progressive dyspnea and right pleural effusion. The peritoneal scintigraphy with (99m)Tc-MAA makes it possible to confirm communication of intraperitoneal dialysis fluid to the pleural cavity.

Serum cystatin C: a surrogate marker for the characteristics of peritoneal membrane in dialysis patients.

To evaluate whether cystatin C levels can be a surrogate marker of creatinine clearance and reflect the characteristics of peritoneal membrane in dialysis patients, we performed peritoneal equilibration tests (PET) in 18 anuric adult chronic peritoneal dialysis (PD) patients with a mean age of 39.7 +/- 20 years. All the samples were analyzed for urea, creatinine, and cystatin C. Peritoneal transport, mass transfer, and peritoneal clearance of cystatin C were calculated. Correlation and regression analysis was done using cystatin C as a dependent variable and age, sex, height, weight, body surface area, and creatinine as independent variables. Cystatin C demonstrated a significant time dependent increase of dialysate concentration and decline in the serum concentrations during PET, and a strong correlation between serum creatinine and serum cystatin C concentrations(r: 0.62, p= 0.008). The trans-peritoneal clearance (mL/min/1.73 m 2 ) of cystatin C was related to its serum concentration and was similar to creatinine in its pattern but of smaller magnitude. Peritoneal mass transfer (mg/4 hr per 1.73 m 2 ) for cystatin C serum creatinine was 1.68 +/- 0.67 and 73.3 +/- 29.8, respectively. The dialysis/plasma D/P cystatin C concentration was > or = 0.1 at 4 hrs of PET denoted high peritoneal transport, while the values of < 0.1 denoted low transport type. We conclude that cystatin C follows the same pattern of peritoneal exchange as creatinine but the magnitude of transfer is many folds lower than creatinine. At present clinical utility of cystatin C in the evaluation of solute clearance is probably limited due to the minute amounts transferred across the membrane and the high renal clearance in the presence of residual renal function.

Effects of interleukin-6 T15A single nucleotide polymorphism on baseline peritoneal solute transport rate in incident peritoneal dialysis patients.

OBJECTIVE: To study the genetic effects of various inflammatory cytokines on peritoneal solute transport rate (PSTR) in incident Korean peritoneal dialysis (PD) patients. DESIGN: Case-control association study. METHODS: 132 patients with baseline peritoneal equilibration test within 1-3 months after starting PD were enrolled. We analyzed the influence of single nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6; -572G/C, T15A), tumor necrosis factor-alpha (TNF-alpha; -1031C/T, -863C/A, -308G/A), and IL-10 (-1082A/G, -592A/C) on baseline PSTR. Clinical parameters such as age, gender, presence of diabetes mellitus, comorbidity, C-reactive protein, and residual renal function were also included as covariates. RESULTS: The T15A SNP of IL-6 (rs13306435) was associated with PSTR. Patients with TA genotype (n=18) had significantly lower D4/P creatinine (0.65+/-0.087 vs 0.73+/-0.110, p=0.0046) and higher D4/D0 glucose (0.39+/-0.174 vs 0.31+/-0.119, p=0.027) than patients with TT genotype (n=114). The log value of the dialysate appearance rate of IL-6 had a strong positive correlation with D4/P creatinine (r2=0.1294, p<0.0001) and was significantly lower in the TA genotype than the TT genotype (201.7+/-14.42 vs 116.8+/-88.91 pg/minute, p=0.0358). By multiple logistic regression, TA genotype was negatively associated with a higher PSTR (high or high average; odds ratio 0.18; 95% confidence interval 0.048-0.666). CONCLUSIONS: In incident Korean PD patients, T15A polymorphism of IL-6 is associated with dialysate IL-6 concentration and baseline PSTR.