Salvage of the peritoneal dialysis catheter in Candida peritonitis using amphotericin B catheter lock.

Candida species form biofilms, facilitating adherence to peritoneal dialysis (PD) catheters and making them less susceptible to antifungal therapy. Therefore, the International Society for Peritoneal Dialysis recommends immediate PD catheter removal in case of Candida peritonitis. However, in 2007, our institution showed that Candida peritonitis could be successfully treated without catheter removal with a treatment strategy including amphotericin B as catheter lock. To confirm the efficacy and safety of this lock-based protocol, we evaluated the outcome of Candida peritonitis episodes since then. A retrospective, single-centre study was conducted in which we analysed all Candida peritonitis episodes in PD patients, treated with the lock-based protocol between July 2006 and March 2018. Eleven non-relapse Candida peritonitis episodes in 10 patients were treated with the lock-based protocol. Seven of the 11 episodes (64%) were cured without PD catheter removal (5 episodes cured immediately, 1 episode cured after an early relapse and 1 episode cured after a late relapse), in 2 episodes (18%) the catheter had to be removed, and two patients died (18%). This study confirms our previous findings that an amphotericin B lock-based protocol has potential to cure Candida peritonitis without PD catheter removal. However, further research is needed given the limitations of this study. Until that time, the lock-based Candida protocol could be used in patients who are not severely ill and in whom PD catheter removal is not desirable.

Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats.

The key to success in developing a wearable dialysis device is a technique to safely and efficiently regenerate and reuse a small volume of dialysate in a closed-loop system. In a hemodialysis model in goats, we explored whether urea removal by electro-oxidation (EO) could be effectively and safely applied in vivo. A miniature dialysis device was built, containing 1 or 2 "EO units," each with 10 graphite electrodes, with a cumulative electrode surface of 585 cm2 per unit. The units also contained poly(styrene-divinylbenzene) sulfonate beads, FeOOH beads, and activated carbon for respective potassium, phosphate, and chlorine removal. Urea, potassium, and phosphate were infused to create "uremic" conditions. Urea removal was dependent on total electrode surface area [removal of 8 mmol/h (SD 1) and 16 mmol/h (SD 2) and clearance of 12 ml/min (SD 1) and 20 ml/min (SD 3) with 1 and 2 EO units, respectively] and plasma urea concentration but not on flow rate. Extrapolating urea removal with 2 EO units to 24 h would suffice to remove daily urea production, but for intermittent dialysis, additional units would be required. EO had practically no effects on potassium and phosphate removal or electrolyte balance. However, slight ammonium releasewas observed, and some chlorine release at higher dialysate flow rates. Minor effects on acid-base balance were observed, possibly partly due to infusion of chloride. Mild hemolysis occurred, which seemed related to urea infusion. In conclusion, clinically relevant urea removal was achieved in vivo by electro-oxidation. Efficacy and safety testing in a large-animal model with uremia is now indicated.

Absence of Post-Transplantation Encapsulating Peritoneal Sclerosis after Relatively Short Exposure to Peritoneal Dialysis: Prospective Analysis Using Repeated Abdominal CT Scanning.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is the most severe complication of peritoneal dialysis (PD). Several retrospective reports published between 2007 and 2009 have suggested an increasing incidence of EPS occurring after kidney transplantation. We conducted a prospective observational study to determine the incidence of post-transplantation EPS and identify possible risk factors. METHODS: Consecutive PD patients undergoing kidney transplantation between 2009 and 2013 were included. Encapsulating peritoneal sclerosis was defined as gastrointestinal obstruction combined with radiological evidence of EPS. Gastrointestinal symptoms were assessed using a self-administered Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Abdominal computed tomography (CT) was performed prospectively at 6 and 18 months post-transplantation. The primary end point was EPS during follow-up. RESULTS: Fifty-three PD patients were included (age 51 ± 14 years). Mean PD duration was 31.3 months. Peritoneal dialysis solutions low in glucose degradation products and icodextrin were used by 86.8% of patients. A fast or average-fast transport status was documented in 83.0%. After a median follow-up of 19 months, complete data of 47 patients were available for analysis. None of the patients developed clinical or radiological signs of EPS. The GSRS score improved from 1.87 to 1.55 (p = 0.024) and body weight increased from 75.9 to 78.3 kg (p = 0.003). Only 1 patient had new onset localized (< 20%) peritoneal thickening on CT 22 months post-transplantation. CONCLUSION: Post-transplantation EPS did not develop in this cohort of patients with a relatively short time of PD exposure. This suggests that these patients can be transplanted safely without concern for the development of EPS, at least within the follow-up period of 19 months.

Improved Outcome of Enteric Peritonitis in Peritoneal Dialysis Patients Aged 50 Years and Older with Temporary Discontinuation of Peritoneal Dialysis and Intravenous Meropenem.

♦ BACKGROUND: Peritonitis is a major cause of morbidity, mortality, and technique failure in peritoneal dialysis (PD) patients, especially when caused by enteric microorganisms (EM). We have implemented a treatment protocol specifically aimed at improving the outcome in EM peritonitis. The adapted protocol was applied in all PD patients 50 years and older presenting with peritonitis who were considered to be at risk of EM peritonitis and involves 3 interventions: 1) temporary discontinuation of PD without removing the catheter (peritoneal rest), 2) intravenous meropenem, and 3) meropenem intracatheter as lock (Mero-PerRest protocol). ♦ METHODS: In this observational study, we compared the outcome of 203 peritonitis episodes in 71 patients treated with the Mero-PerRest protocol, with 217 episodes in 104 patients treated with a more traditional intraperitoneal gentamicin-rifampicin-based regimen. ♦ RESULTS: In EM peritonitis episodes, the Mero-PerRest protocol resulted in a higher primary cure rate (90.0% vs 65.3%, adjusted odds ratio [OR] 4.54 [95% confidence interval (CI) 1.46 - 14.15]) and better technique survival (90.0% vs 69.4%, adjusted OR 3.41 [95% CI 1.07 - 10.87]). This effect was most distinct in patients with polymicrobial EM peritonitis (cure rate 87.5% vs 34.8%, p = 0.0003). Interestingly, primary cure rate (95.6% vs 84.7%, adjusted OR 3.92 [95% CI 1.37 - 11.19]) and technique survival (95.6% vs 85.6%, adjusted OR 3.60 [95% CI 1.25 - 10.32]) were also excellent in non-EM peritonitis episodes. Patient survival did not differ significantly. ♦ CONCLUSION: The poor outcome of peritonitis caused by EM in PD patients aged 50 years and older could be improved by applying a treatment protocol involving temporary discontinuation of PD without catheter removal and intravenous and intracatheter meropenem.

A regenerable potassium and phosphate sorbent system to enhance dialysis efficacy and device portability: a study in awake goats.

BACKGROUND: Patients on standard intermittent haemodialysis suffer from strong fluctuations in plasma potassium and phosphate. Prolonged dialysis with a wearable device, based on continuous regeneration of a small volume of dialysate using ion exchangers, could moderate these fluctuations and offer increased clearance of these electrolytes. We report in vivo results on the efficacy of potassium and phosphate adsorption from a wearable dialysis device. We explore whether equilibration of ion exchangers at physiological Ca 2+ , Mg 2+ and hypotonic NaCl can prevent calcium/magnesium adsorption and net sodium release, respectively. Effects on pH and HCO3- were studied. METHODS: Healthy goats were instrumented with a central venous catheter and dialysed. Potassium and phosphate were infused to achieve plasma concentrations commonly observed in dialysis patients. An adsorption cartridge containing 80 g sodium poly(styrene-divinylbenzene) sulphonate and 40 g iron oxide hydroxide beads for potassium and phosphate removal, respectively, was incorporated in a dialysate circuit. Sorbents were equilibrated and regenerated with a solution containing NaCl, CaCl 2 and MgCl 2 . Blood was pumped over a dialyser and dialysate was recirculated over the adsorption cartridge in a countercurrent direction. RESULTS: Potassium and phosphate adsorption was 7.7 ± 2.7 and 4.9 ± 1.3 mmol in 3 h, respectively. Adsorption capacity remained constant during consecutive dialysis sessions and increased with increasing K + and PO43-. Equilibration at physiological Ca 2+ and Mg 2+ prevented net adsorption, eliminating the need for post-cartridge calcium and magnesium infusion. Equilibration at hypotonic NaCl prevented net sodium release Fe 2+ and arterial pH did not change. Bicarbonate was adsorbed, which could be prevented by equilibrating at HCO3- 15 mM. CONCLUSION: We demonstrate clinically relevant, concentration-dependent, pH-neutral potassium and phosphate removal in vivo with small volumes of regenerable ion exchangers in our prototype wearable dialysis device. Application of the selected ion exchangers for potassium and phosphate removal in a wearable dialysis device appears to be effective with a low-risk profile.

The importance of intake: a gut feeling.

Limiting enteric sodium absorption is an attractive option when renal sodium excretion is disturbed. An effective approach in the gut appears to be inhibition of the electroneutral Na(+)/H(+) exchangers (NHE), in particular NHE3. Recently, fluid retention, blood pressure and target organ injury were limited in rats with cardiorenal syndrome when treated with the NHE3 inhibitor tenapanor. The downside was that the osmotic fecal load leads to watery feces. Tenapanor also induced marked reductions in enteric phosphorus absorption in rats with cardiorenal syndrome on a high phosphorus intake and resulted in marked reductions in renal injury and practically prevented vascular calcification. We have yet to discover the clinical relevance in volume terms and vascular calcifications in patients in relation to the tolerated dose. However, even if the tenapanor-induced reduction in sodium adsorption is limited in humins, combination of tenapanor therapy with diuretics may be an interesting option in selected patients.

CD4-Positive T Cells and M2 Macrophages Dominate the Peritoneal Infiltrate of Patients with Encapsulating Peritoneal Sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Previously, it has been shown that infiltrating CD4-positive T cells and M2 macrophages are associated with several fibrotic conditions. Therefore, the characteristics of the peritoneal cell infiltrate in EPS may be of interest to understand EPS pathogenesis. In this study, we aim to elucidate the composition of the peritoneal cell infiltrate in EPS patients and relate the findings to clinical outcome. STUDY DESIGN, SETTING, AND PARTICIPANTS: We studied peritoneal membrane biopsies of 23 EPS patients and compared them to biopsies of 15 PD patients without EPS. The cellular infiltrate was characterized by immunohistochemistry to detect T cells (CD3-positive), CD4-positive (CD4+) and CD8-positive T cell subsets, B cells (CD20-positive), granulocytes (CD15-positive), macrophages (CD68-positive), M1 (CD80-positive), and M2 (CD163-positive) macrophages. Tissues were analysed using digital image analysis. Kaplan-Meier survival analysis was performed to investigate the survival in the different staining groups. RESULTS: The cellular infiltrate in EPS biopsies was dominated by mononuclear cells. For both CD3 and CD68, the median percentage of area stained was higher in biopsies of EPS as opposed to non-EPS patients (p<0.001). EPS biopsies showed a higher percentage of area stained for CD4 (1.29% (0.61-3.20)) compared to CD8 (0.71% (0.46-1.01), p = 0.04), while in the non-EPS group these cells were almost equally represented (respectively 0.28% (0.05-0.83) versus 0.22% (0.17-0.43), p = 0.97). The percentage of area stained for both CD80 and CD163 was higher in EPS than in non-EPS biopsies (p<0.001), with CD163+ cells being the most abundant phenotype. Virtually no CD20-positive and CD15-positive cells were present in biopsies of a subgroup of EPS patients. No relation was found between the composition of the mononuclear cell infiltrate and clinical outcome. CONCLUSIONS: A characteristic mononuclear cell infiltrate consisting of CD4+ and CD163+ cells dominates the peritoneum of EPS patients. These findings suggest a role for both CD4+ T cells and M2 macrophages in the pathogenesis of EPS.

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-ß1, and vascular endothelial growth factor.

INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFß1 and VEGF, in different stages of peritoneal fibrosis. MATERIALS AND METHODS: Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. RESULTS: Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFß1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFß1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. CONCLUSIONS: Peritoneal expression of CCN2, TGFß1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Removal of urea in a wearable dialysis device: a reappraisal of electro-oxidation.

A major challenge for a wearable dialysis device is removal of urea, as urea is difficult to adsorb while daily production is very high. Electro-oxidation (EO) seems attractive because electrodes are durable, small, and inexpensive. We studied the efficacy of urea oxidation, generation of chlorine by-products, and their removal by activated carbon (AC). EO units were designed. Three electrode materials (platinum, ruthenium oxide, and graphite) were compared in single pass experiments using urea in saline solution. Chlorine removal by AC in series with EO by graphite electrodes was tested. Finally, urea-spiked bovine blood was dialyzed and dialysate was recirculated in a dialysate circuit with AC in series with an EO unit containing graphite electrodes. Platinum electrodes degraded more urea (21 ± 2 mmol/h) than ruthenium oxide (13 ± 2 mmol/h) or graphite electrodes (13 ± 1 mmol/h). Chlorine generation was much lower with graphite (13 ± 4 mg/h) than with platinum (231 ± 22 mg/h) or ruthenium oxide electrodes (129 ± 12 mg/h). Platinum and ruthenium oxide electrodes released platinum (4.1 [3.9-8.1] umol/h) and ruthenium (83 [77-107] nmol/h), respectively. AC potently reduced dialysate chlorine levels to < 0.10 mg/L. Urea was removed from blood by EO at constant rate (9.5 ± 1.0 mmol/h). EO by graphite electrodes combined with AC shows promising urea removal and chlorine release complying with Association for the Advancement of Medical Instrumentation standards, and may be worth further exploring for dialysate regeneration in a wearable system.

A regenerable potassium and phosphate sorbent system to enhance dialysis efficacy and device portability: an in vitro study.

BACKGROUND: Continuous dialysis could provide benefit by constant removal of potassium and phosphate. This study investigates the suitability of specific potassium and phosphate sorbents for incorporation in an extracorporeal device by capacity and regenerability testing. METHODS: Capacity testing was performed in uraemic plasma. Regenerability was tested for potassium sorbents, with adsorption based on cationic exchange for sodium, with 0.1 M and 1.0 M NaCl. To regenerate phosphate sorbents, with adsorption based on anionic exchange, 0.1 M and 1.0 M NaHCO3 and NaOH were used. Subsequently, sodium polystyrene divinylbenzene sulphonate (RES-A) and iron oxide hydroxide (FeOOH) beads were incorporated in a cartridge for testing in bovine blood using a recirculating blood circuit and a dialysis circuit separated by a high-flux dialyzer (dynamic setup). Preloading was tested to assess whether this could limit calcium and magnesium adsorption. RESULTS: In the batch-binding assays, zirconium phosphate most potently adsorbed potassium (0.44 ± 0.05 mmol/g) and RES-A was the best regenerable potassium sorbent (92.9 ± 5.7% with 0.1 M NaCl). Zirconium oxide hydroxide (ZIR-hydr) most potently adsorbed phosphate (0.23 ± 0.05 mmol/g) and the polymeric amine sevelamer carbonate was the best regenerable sorbent (85.7 ± 5.2% with 0.1 M NaHCO3). In the dynamic setup, a potassium adsorption of 10.72 ± 2.06 mmol in 3 h was achieved using 111 g of RES-A and a phosphate adsorption of 4.73 ± 0.53 mmol in 3 h using 55 g of FeOOH. Calcium and magnesium preloading was shown to reduce the net adsorption in 3 h from 3.57 ± 0.91 to -0.29 ± 1.85 and 1.02 ± 0.05 to -0.31 ± 0.18 mmol, respectively. CONCLUSION: RES-A and FeOOH are suitable, regenerizable sorbents for potassium and phosphate removal in dialysate regeneration. Use of zirconium carbonate and ZIR-hydr may further increase phosphate adsorption, but may compromise sorbent regenerability. Use of polymeric amines for phosphate adsorption may enhance sorbent regenerability. Calcium and magnesium preloading considerably reduced net adsorption of these ions.

High incidence of mild hyponatraemia in females using ecstasy at a rave party.

BACKGROUND: Globally, millions of subjects regularly use ecstasy, a drug popular due to its empathogenic and entactogenic effects. Dilutional hyponatraemia, mainly caused by direct stimulation of antidiuretic hormone (ADH) secretion by ecstasy, is among the many side effects of the drug (active substance 3, 4-methylenedioxymethamphetamine, MDMA). Severe, symptomatic hyponatraemia related to the use of MDMA has been reported in more than 30 cases. The mortality of this complication is high and mainly females are involved. Dramatic cases that reach the literature probably represent the tip of the iceberg. We decided to study the incidence of hyponatraemia in subjects using MDMA at an indoor rave party. METHODS: The study was performed at the indoor event 'Awakenings', held in Amsterdam in the fall of 2010. The plasma sodium concentration was measured at the party using a point of care method in 63 subjects using MDMA and 44 controls. The use of MDMA was confirmed by a urine test. RESULTS: The plasma sodium concentration in subjects using MDMA was significantly lower than in those not using the drug (138 ± 2 mmol/L versus 140 ± 2 mmol/L, respectively, P < 0.001). The overall incidence of hyponatraemia, defined as a plasma sodium concentration <136 mmol/L, was 14.3% in MDMA users (9/63 subjects). Most cases of hyponatraemia occurred in females, in whom the incidence was 26.7% (8 of 30 females), with lowest values of 133 mmol/L. The number of ecstasy pills ingested by the females developing hyponatraemia was not different from that ingested by those who did not develop this complication. Fluid intake in ecstasy users exceeded that of non-users, suggesting a dipsogenic effect of the drug. CONCLUSIONS: Only 3% of males, but no less than ∼25% of females attending a rave party and using MDMA developed mild hyponatraemia during the event. Especially females are therefore probably also at risk of developing severe symptomatic hyponatraemia. Not using MDMA is obviously the best option to prevent MDMA-induced hyponatraemia. However, accepting the fact that millions use the drug every weekend, strategies should also be developed to prevent hyponatraemia in subjects choosing to take MDMA. This would include matching the electrolyte content of the fluids and food ingested to that of the fluids that are lost during the use of MDMA, mainly by perspiration. Users of MDMA and emergency health care workers should become more aware of the relatively high incidence of MDMA-induced hyponatraemia and of potential strategies to prevent this complication.

[The wearable artificial kidney: a promise for the future?]. / De draagbare kunstnier: belofte voor de toekomst?

Portable or wearable dialysis devices could increase treatment flexibility and dialysis patients' independence. Current renal replacement therapies such as intermittent haemodialysis extend life but are a burden, are time-consuming and immobilize patients. An additional disadvantage is the discontinuous nature of the treatment. Peritoneal dialysis is a good alternative, but is associated with relatively limited toxin clearance and a need for high glucose concentrations in the dialysate. Portable dialysis devices could be used as a replacement or to support existing dialysis techniques. At the moment several initiatives, including some started in the Netherlands, aim at the development of a portable device. Some of them are so far into development that they are at a preclinical phase, but as yet none has been approved for regular use in patients. To achieve the ultimate goal, an implantable artificial kidney, a lot of hurdles still have to be surmounted.

Solid renal tumours of collecting duct origin in patients on chronic lithium therapy.

BACKGROUND: Lithium (Li) is an invaluable drug for the treatment of bipolar disorder. Long-term Li use is associated with renal complications including the formation of uncomplicated renal cysts caused by proliferation and expansion of collecting duct (CD) cells. We report six patients with complicated renal cysts in the context of Li nephropathy. METHODS: Over a time period of 15 years, we have identified six patients with one or more solid renal tumours in our population of approximately 50 patients with chronic Li nephropathy. In this study we describe the clinical and pathological characteristics of these Li-related tumours. RESULTS: All patients were on Li therapy for over 10 years and suffered from varying degrees of Li nephropathy. The tumours were all of CD origin and comprised both oncocytomas and collecting duct carcinomas. The CD carcinomas differed from the very rare "classical" CD cell carcinomas in histological appearance, multifocal presentation and non-aggressive clinical behaviour. CONCLUSIONS: The increased incidence of CD derived tumours and atypical presentation of CD cell carcinomas in patients with chronic Li nephropathy suggests that Li predisposes to the development of these tumours. We hypothesize that prolonged stimulation of CD cell proliferation and expansion by Li not only causes cyst formation, but can eventually induce the formation of adenomas and carcinomas. Increased awareness of a possible relationship between chronic Li therapy and renal neoplasms, will enhance the knowledge on epidemiology, clinical behavior and optimal therapy for the Li-related renal neoplasms.

Denosumab for treatment of immobilization-related hypercalcaemia in a patient with advanced renal failure.

We describe the case of a young adult with immobilization-related hypercalcaemia and advanced renal insufficiency. Because of the uncertain safety profile of bisphosphonates in such patients, only a low dose of pamidronate was administered twice. This did not result in a sufficient decrease in the serum calcium concentration nor was the decrease sustained. We decided to administer a single dose of denosumab, a monoclonal antibody against the receptor activator of nuclear factor-κB ligand, a new antiresorptive agent registered for use in osteoporosis. This resulted in rapid and sustained decrease in the serum calcium concentration. Transient hypocalcaemia ensued with normalization after vitamin D supplementation. Furthermore, we summarize what is known about hypercalcaemia caused by immobilization.

No influence of haemodialysis on interferon production in the QuantiFERON-TB Gold-In-Tube test.

BACKGROUND: Immunodeficiency in end-stage renal disease (ESRD) can be aggravated by haemodialysis (HD). This results in an increased incidence of reactivation of tuberculosis (TB) in HD patients. The tuberculin skin test to detect a latent TB infection (LTBI) has its limitations in these patients because of a high rate of false negative results due to anergy of T cells. Data on the influence of HD on the performance of interferon-gamma release assays are limited. The aim of this study was to determine the effect of HD on the performance of the QuantiFERON-TB Gold (QFT-G) assay in ESRD patients before, during and after the HD session. METHODS: In HD patients older than 18 years without immunosuppressive medication or other immunocompromising conditions, the QFT-G assay was performed just before starting HD, 30 minutes after start and immediately after the finish of the HD session. RESULTS: Twenty patients were included. No statistically significant differences were found in interferon-gamma production in the nil- and antigen tubes between pre-HD, during and after HD. In 1 patient the predialysis result was indeterminate (one of 60 samples, 1.67%). In all 3 patients with a history of LTBI, the QFT-G test tube results were positive at all time points. In the other 16 patients, all test tubes showed negative results. CONCLUSIONS: The QFT-G assay could be a useful test for the evaluation of the immunological response against Mycobacterium tuberculosis in HD patients. The time point of blood sampling does not seem to affect the interpretation of test results.

Progenitor cells and vascular function are impaired in patients with chronic kidney disease.

BACKGROUND: Endothelial dysfunction contributes to accelerated atherosclerosis in chronic kidney disease (CKD). Bone marrow-derived endothelial progenitor cells (EPC) constitute an endogenous vascular repair system protecting against atherosclerosis. Smooth muscle progenitor cells (SPC) may stimulate atherosclerosis development. We hypothesized that an imbalance in EPC and SPC occurs in CKD, which may contribute to the increased cardiovascular disease (CVD) risk. METHODS: EPC and SPC outgrowth from mononuclear cells (MNC), EPC migratory function and circulating CD34(+)KDR(+)-EPC were measured in 49 patients with varying degrees of CKD on regular therapy and 33 healthy volunteers. Renal function, CKD cause, CVD history and endothelial dysfunction parameters were determined as factors of influence on progenitor cells. RESULTS: Patients had reduced EPC outgrowth compared to controls [9 (2-22) vs 12 (1-38) cells/10(3) MNC, P = 0.026], independent of CKD cause and degree, whereas SPC outgrowth levels were higher in patients with more impaired kidney function (r = -0.397, P = 0.008). Patients had lower CD34(+)KDR(+)-EPC compared to controls [9 (0-52) vs 19 (4-110) cells/10(5) granulocytes, P = 0.004]. CVD history and increased endothelial dysfunction markers were related to lower EPC levels. Progenitor cell outgrowth was shifted towards SPC with progression of endothelial damage. Reduction in EPC could not be attributed to decreases in progenitor cell-mobilizing factors SDF-1 alpha and VEGF as levels increased with progressive kidney and endothelial dysfunction, while EPC remained low. CONCLUSIONS: Our data suggest that, already in mild CKD, EPC-mediated endogenous vascular regeneration is impaired, while SPC levels increase with declining kidney function.

Sodium profiling, but not cool dialysate, increases the absolute plasma refill rate during hemodialysis.

Intradialytic hypotension is often caused by a discrepancy between ultrafiltration and plasma refilling. Increasing the plasma refill rate could therefore reduce intradialytic hypotension. We used a recently developed method to measure the effect of cool dialysate and sodium (Na) profiling on refill during hemodialysis (HD). Using a Gambro AK200 with blood volume (BV) sensor plus computer-guided external pump, a high ultrafiltration rate quickly induced a preset BV reduction. A software feedback mechanism subsequently adjusted the ultrafiltration rate continuously to maintain BV between very narrow preset boundaries. The continuously changing, software-generated ultrafiltration rate then quantitatively equalled refill. Absolute plasma refill rate was measured in six stable patients without intradialytic hypotension, undergoing HD without intervention, with cool dialysate (1 degrees C below core temperature), and with Na profiling (gradually declining from 150 to 140 mmol/l). Baseline refill rate was 20.1 + or - 4.0 ml/min (mean + or - SD). Although cool dialysate did not affect refill (22.2 + or - 4.1 ml/min, p = 0.27 vs. baseline), Na profiling induced a significant improvement (26.8 + or - 3.7 ml/min, p = 0.006 vs. baseline). Using our method to measure absolute plasma refill rate during HD, we demonstrated that Na profiling indeed improves the plasma refill rate. A potential effect of cool dialysate could not be established.

Continuous, online measurement of the absolute plasma refill rate during hemodialysis using feedback regulated ultrafiltration: preliminary results.

Methods to continuously measure absolute refill during dialysis are not available. It would be useful to have such a method because it would allow investigating the mechanism of refill the effect of interventions. We designed a feedback algorithm that adjusts ultrafiltration rate (QUF) according to hemoglobin (Hb) concentration changes in such a way that relative blood volume (BV) remains constant within a narrow target range. In this situation, the generated QUF quantitatively reflects refill. Refill patterns were studied in five hypotension prone patients. In addition, on separate occasions, we studied the effect of antiembolism stockings (AES) and infusion of hydroxy-ethylated starch (HAES) on refill in these patients. Refill during the first hour fell significantly from 21 +/- 3 ml/min to 9 +/- 2 ml/min (p < 0.05). In the second hour, refill decreased further and became zero in four out of five patients. Neither AES nor HAES measurably affected refill. The marked and rapid fall in refill in the early stages of dialysis suggests untimely depletion of the interstitial compartment and underestimation of dry weight. We propose that continuous, online measurement of refill patterns may be of value for accurate estimation of dry weight in dialysis patients.

Posttransplant encapsulating peritoneal sclerosis: a worrying new trend?

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication in patients on peritoneal dialysis (PD). We describe a cluster of 13 EPS cases occurring in 2 university hospitals in The Netherlands. Most of these cases were diagnosed after recent kidney transplantation, when the patients developed severe symptoms of bowel obstruction. This accumulation raised the question as to whether other than known risk factors, such as duration of PD treatment, could be involved in the development or course of EPS after transplantation. According to various publications, EPS has been diagnosed often after withdrawal from PD, suggesting that cessation in itself may be a risk factor. In addition, transplantation-related management should be considered to play a role, including the use of the profibrotic calcineurin inhibitors and the trend to reduce the load of corticosteroids in treatment regimes. To identify risk factors, further multicenter studies are required, paying special attention to alterations in immunosuppressive treatment regimens as well as PD prescriptions, including PD fluid characteristics. Transfer from PD to hemodialysis should be under serious consideration in patients eligible for kidney transplantation as soon as there are indications of ultrafiltration failure.