Infection-Related Hospitalizations After Simultaneous Pancreas-Kidney Transplantation Compared to Kidney Transplantation Alone.

The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, p = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups.

The first 10 years of simultaneous pancreas-kidney transplantation in Finland.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is an option for patients with type 1 diabetes (T1D) and kidney failure but can be associated with a high complication rate. Here we describe our 10-year experience since the launch of the SPK program. METHODS: This retrospective study included consecutive patients with T1D receiving SPK from March 14, 2010 to March 14, 2020 at Helsinki University Hospital. Portocaval anastomosis (i.e., systemic venous drainage) and enteric exocrine drainage were used. A specific team was trained for both pancreas retrieval and transplantation, postoperative care was standardized to include somatostatin analogues, antimicrobial treatment, and preoperatively initiated chemothrombopropylaxis. During program maturation donor criteria were expanded and logistical processes improved to minimize cold ischemia time. Clinical data were collected from a nationwide transplantation registry and patient records. RESULTS: A total of 166 SPKs were performed (median 2 per year in the first 3 years, 17.5 per year for the following 4 years, and 23 per year for the past 3 years). Seven patients (4.1%) died with a functioning graft with a median 43 months follow-up. One-year pancreas graft survival was 97.0%, 3-year pancreas graft survival was 96.1% and 5-year was 96.1%. Mean HbA1c was 36 mmol/mol (SD 5.57) and creatinine was 107 µmol/L (SD 34.69) at 1-year after transplantation. All kidney grafts were functioning at the end of follow-up. Complications required re-laparotomy in 39 (23%) patients, mostly due to a pancreas graft related problem (N = 28). No pancreas or kidney graft failure from thrombosis occurred. CONCLUSION: A planned, step-wise development of an SPK program offers a safe and effective treatment for patients with T1D and kidney failure.

Availability of assisted peritoneal dialysis in Europe: call for increased and equal access.

BACKGROUND: Availability of assisted PD (asPD) increases access to dialysis at home, particularly for the increasing numbers of older and frail people with advanced kidney disease. Although asPD has been widely used in some European countries for many years, it remains unavailable or poorly utilized in others. A group of leading European nephrologists have therefore formed a group to drive increased availability of asPD in Europe and in their own countries. METHODS: Members of the group filled in a proforma with the following headings: personal experience, country experience, who are the assistants, funding of asPD, barriers to growth, what is needed to grow and their top three priorities. RESULTS: Only 5 of the 13 countries surveyed provided publicly funded reimbursement for asPD. The use of asPD depends on overall attitudes to PD, with all respondents mentioning the need for nephrology team education and/or patient education and involvement in dialysis modality decision making. CONCLUSIONS AND CALL TO ACTION: Many people with advanced kidney disease would prefer to have their dialysis at home, yet if the frail patient chooses PD most healthcare systems cannot provide their choice. AsPD should be available in all countries in Europe and in all renal centres. The top priorities to make this happen are education of renal healthcare teams about the advantages of PD, education of and discussion with patients and their families as they approach the need for dialysis, and engagement with policymakers and healthcare providers to develop and support assistance for PD.

First-day plasma amylase detects patients at risk of complications after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) carries a high risk of major postoperative complications, but knowledge on early warning signs and surrogate markers for postoperative complications is scarce. AIMS: Our aim was to analyze the complication-predictive value of different laboratory tests in pancreas transplantation. MATERIALS & METHODS: All SPKs in Finland between January 2010 and February 2020 were retrospectively analyzed. Levels of first three-day plasma amylase, drain fluid amylase, C-reactive protein, C-peptide, plasma trypsinogen, and white blood cell count were assessed for their performance predicting cumulative postoperative complications (assessed using the Comprehensive Complication Index) within 90 days from transplantation by using ROC analyses. RESULTS: Of the 164 SPK patients included, 39 suffered at least one complication requiring laparotomy. First-day plasma amylase had the best value in predicting complications based on its high AUC value and easy clinical applicability, with an optimum cutoff of six times the upper normal limit. Negative predictive values (NPVs) and positive predictive values of this cutoff were 0.81 and 0.71 for any relaparotomy, and 0.91 and 0.71 for the Comprehensive Complication Index >47.7 (which equals the morbidity of two relaparotomies), respectively. CONCLUSION: In conclusion, first-day plasma amylase could be able to detect patients at risk of complications after SPK.

Chronic nasal Staphylococcus aureus carriage identifies a subset of newly diagnosed granulomatosis with polyangiitis patients with high relapse rate.

Objective: The aim of this study was to evaluate whether chronic nasal carriage of Staphylococcus aureus (SA) is related to relapses in patients with newly diagnosed ANCA-associated vasculitis (AAV). Methods: In two clinical trials (n = 200), for early systemic (n = 83) and generalized (n = 117) AAV, nasal swabs were obtained monthly and at the time of a relapse. Chronic nasal SA carriage (CNSAC) was defined as ⩾ 75% of cultures being SA positive, with non-carriers being SA negative in all cultures and remaining patients being intermittent carriers. Fifty-five of 200 (27.5%) patients received prophylactic trimethoprim/sulfamethoxazole (T/S) against Pneumocystis jirovecii . Results: Of the total AAV patients, 24/200 (12%) were chronic, 102/200 (51%) intermittent and 74/200 (37%) non-carriers. Of 65 relapsing patients, 10/24 (41.7%) were chronic, 32/102 (31.4%) intermittent and 23/74 (31.1%) non-carriers (P = 0.59). For all AAV patients, CNSAC was not associated with an increased relapse risk [odds ratio (OR) = 1.57, 95% CI: 0.66, 3.76; P = 0.31]. However, 23/24 chronic carriers had granulomatosis with polyangiitis (GPA). In the 73 patients with generalized GPA (hazard ratio = 4.10, 95% CI: 1.37, 12.25; P = 0.01) and the 78 patients with early systemic GPA during immunosuppression (hazard ratio = 2.73, 95% CI: 0.95, 7.87; P = 0.06), relapse rates were higher for chronic SA carriers. Prophylactic T/S was not associated with a reduced relapse risk (OR = 0.71, 95% CI: 0.36, 1.41; P = 0.33). Nevertheless, prophylactic T/S reduced CNSAC (OR = 0.19, 95% CI: 0.04, 0.91; P = 0.04). Conclusion: The frequency of CNSAC in newly diagnosed GPA paralleled that in the general population. This subset of GPA patients (23/151, 15.2%) has a high relapse rate despite immunosuppression and prophylactic T/S treatment, requiring further investigations on pathogenesis and therapy.

The evolving treatment of ANCA-associated vasculitides.

Prevention of organ damage and maintenance of long-term remission are the principal goals for treatment of ANCA-associated vasculitides. This can be accomplished by early diagnosis and swift initiation of remission-inducing agents. Outcome has improved but relapses and glucocorticoid- and cyclophosphamide-related toxicity are still major concerns. For remission induction in generalized disease a combination of glucocorticoids and cyclophosphamide or rituximab is used. Rituximab is suitable especially for younger patients with fertility concerns and when cyclophosphamide avoidance otherwise is desirable. In the treatment of relapses and refractory disease, rituximab has proved effective. As maintenance treatment rituximab prevents relapses more effectively than azathioprine.

Characteristics and Outcomes of Granulomatosis With Polyangiitis (Wegener) and Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the European Renal Association-European Dialysis and Transplant Association Registry.

BACKGROUND: This study describes the incidence and outcomes of European patients requiring renal replacement therapy (RRT) for kidney failure due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 12 renal registries providing individual RRT patient data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry in 1993-2012 participated. PREDICTOR: Cause of primary kidney disease: AAV (ie, granulomatosis with polyangiitis [Wegener] and microscopic polyangiitis) versus 3 separate matched control groups without AAV: (1) primary glomerulonephritis, (2) diabetes mellitus, and (3) disease other than diabetes mellitus as the cause of primary kidney disease, including glomerulonephritis (termed "nondiabetes"). OUTCOMES: Incidence, causes of death, and survival. MEASUREMENTS: ERA-EDTA primary renal disease codes. RESULTS: 2,511 patients with AAV (1,755, granulomatosis with polyangiitis; 756, microscopic polyangiitis) were identified, representing an incidence of 1.05 per million population (pmp) for granulomatosis with polyangiitis (predominating in Northern Europe) and 0.45 pmp for microscopic polyangiitis (prevailing in Southern Europe). Kidney transplantation was performed in 558 (22.2%) patients with vasculitis. The 10-year probability for survival on RRT after day 91 was 32.5% (95% CI, 29.9%-35.1%) in patients with vasculitis. Survival on RRT after day 91 did not differ between AAV and matched nondiabetes patients. Patient and transplant survival after kidney transplantation, adjusted for time period and country, was better in AAV than in matched nondiabetes patients (HRs of 0.81 [95% CI, 0.67-0.99] and 0.82 [95% CI, 0.69-0.96], respectively). LIMITATIONS: No data for extrarenal manifestations, treatment, and relapses. CONCLUSIONS: Geographical differences in the incidence of RRT for kidney failure due to granulomatosis with polyangiitis and microscopic polyangiitis copied their distribution in the general population. Overall survival on RRT after day 91 for patients with AAV was similar to that for patients with nondiabetes diagnoses. Our results suggest that patients with AAV are suitable candidates for kidney transplantation with favorable survival outcomes.

Activation of endothelium, coagulation and fibrinolysis is enhanced and associates with renal anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: While the incidence of thromboembolism in anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) is high, the coagulation and fibrinolysis profile in AAV patients remains poorly characterized. We aimed at studying this profile in association with vasculitis activity and renal function. METHODS: This prospective study included 21 AAV patients with renal disease and 40 controls with other chronic kidney disease. Platelet count, antithrombin, FVIII : C, von Willebrand factor (VWF) activities (VWF : RCo) and antigen (VWF : Ag), fibrinogen, prothrombin fragments (F1 + 2), fibrin degradation product d-dimer and the presence of antiphospholipid antibodies were measured during the active and remission states of the AAV and at the baseline in controls. Occurrence of thromboembolic events was recorded. RESULTS: F1 + 2 was 2.6-fold and D-dimer was 5-fold higher during the active AAV than its remission (median 563 versus 212 pM and 3.0 versus 0.6 mg/L, P = 0.001 for both). FVIII : C (median 228%), VWF : RCo (198%) and VWF : Ag (222%) were the highest among the patients with active AAV and remained elevated also under remission. In active AAV, both F1 + 2 and d-dimer clearly associated with impaired renal function (r = -0.67, P = 0.001 and r = -0.66, P = 0.001). In AAV patients, two thromboembolic events occurred during the follow-up. CONCLUSIONS: In active renal AAV, thrombin formation and especially fibrin turnover prevail compared both with remission and other kidney diseases. Overall, AAV is characterized by an enhanced coagulation, especially FVIII activity, which continues partly in remission.

[Four years of simultaneous pancreas-kidney transplantations in Finland]. / Neljä vuotta samanaikaisia haiman- ja munuaisensiirtoja Suomessa.

The first simultaneous pancreas-kidney transplantation in Finland was performed in 2010. On a global scale, already more than 45,000 pancreatic transplantations have been performed. Pancreatic transplantation restores the blood glucose level to normal, but only at the cost of possible adverse effects due to surgery and anti-rejection drugs. Based on our experience with 24 patients, this operation has met the expectations and shown that simultaneous pancreas-kidney transplantation is a good alternative for selected type 1 diabetics instead of mere kidney transplantation. In the future we aim to conduct approximately 15 combined transplantations per year.

Assisted PD throughout Europe: advantages, inequities, and solution proposals.

BACKGROUND: Peritoneal dialysis provides several benefits for patients and should be offered as first line kidney replacement therapy, particularly for fragile patients. Limitation to self-care drove assisted peritoneal dialysis to evolve from family-based care to institutional programs, with specialized care givers. Some European countries have mastered this, while others are still bound by the availability of a volunteer to become responsible for treatment. METHODS: A group of leading nephrologists from 13 European countries integrated real-life application of such therapy, highlighting barriers, lessons learned and practical solutions. The objective of this work is to share and summarize several different approaches, with their intrinsic difficulties and solutions, which might helpperitoneal dialysis units to develop and offer assisted peritoneal dialysis. RESULTS: Assisted peritoneal dialysis does not mean 4 continuous ambulatory peritoneal dialysis exchanges, 7 days/week, nor does it exclude cycler. Many different prescriptions might work for our patients. Tailoring PD prescription to residual kidney function, thereby maintaining small solute clearance, reduces dialysis burden and is associated with higher technique survival. Assisted peritoneal dialysis does not mean assistance will be needed permanently, it can be a transitional stage towards individual or caregiver autonomy. Private care agencies can be used to provide assistance; other options may involve implementing PD training programs for the staff of nursing homes or convalescence units. Social partners may be interested in participating in smaller initiatives or for limited time periods. CONCLUSION: Assisted peritoneal dialysis is a valid technique, which should be expanded. In countries without structural models of assisted peritoneal dialysis, active involvement by the nephrologist is needed in order for it to become a reality.

Effect of Pretransplant Dialysis Modality on Outcomes After Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND Pretransplant dialysis modality may affect outcome after simultaneous pancreas-kidney transplantation (SPKT), and it has been suspected that peritoneal dialysis (PD) is associated with more postoperative complications compared to hemodialysis (HD). The aim of this study was to evaluate whether pretransplant dialysis modality affects the risk for postoperative complications in SPKT recipients. MATERIAL AND METHODS This was a retrospective longitudinal cohort study of all patients undergoing SPKT from 2010 to 2017, during which 99 simultaneous pancreas-kidney transplantations were performed. Three pre-emptive transplantations were excluded. Patient groups receiving PD (n=59) or HD (n=37) were similar regarding baseline characteristics. All complications occurring during the first 3 months after transplantation, as well as patient and graft survival, were analyzed. RESULTS There were no significant differences in postoperative complications between groups, with similar rates of intra-abdominal infections (8% in HD vs. 10% in PD), pancreatitis (16% in HD vs. 17% in PD), gastrointestinal bleedings (22% in HD vs. 10% in PD), and relaparotomies (27% in HD vs. 24% in PD). None of the patients had venous graft thrombosis. Past peritonitis was not associated with increased risk for postoperative complications in PD patients. Patient and graft survival were similar between PD and HD groups. CONCLUSIONS Peritoneal dialysis is not a risk factor for postoperative complications after SPKT.

Prognostic Factors for Survival and Relapse in ANCA-Associated Vasculitis with Renal Involvement: A Clinical Long-Term Follow-Up Study.

AIM: We describe the clinical pattern of ANCA-associated vasculitis (AAV) and assess long-term prognostic factors of patients and renal survival and relapse. METHODS: Data from 85 patients with renal biopsy-proven AAV at a single center with up to 20-year [median 16.2 years (95% CI 14.9-17.7)] follow-up were retrospectively collected. RESULTS: Overall, 55% of the patients had microscopic polyangiitis (MPA) and 45% had granulomatosis with polyangiitis (GPA). The histopathological classes were focal in 35%, crescentic in 26%, mixed in 20%, and sclerotic glomerulonephritis in 19% of the patients. As induction treatment, a combination of cyclophosphamide and corticosteroids was given to 82%, while a combination of azathioprine and corticosteroids was maintenance therapy in 79%. The twenty-year patient survival was 45%. In a multivariable analysis, age ≥58 years [hazard ratio (HR) 7.64, 95% CI 3.44-16.95] and myeloperoxidase (MPO) ANCA (HR 2.12, 95% CI 1.08-4.17) were associated with shorter patient survival time. Renal survival was 68% overall: 88% in focal, 71% in crescentic, 56% in mixed, and 37% in sclerotic class (p=0.01). Female sex (HR 0.26, 95% CI 0.10-0.73) was a predictor of improved renal survival, whereas GFR <30 ml/min and MPO-ANCA were associated with worse renal survival (HR 4.10, 95% CI 1.35-12.49 and HR 3.10, 95% CI 1.21-7.95, respectively). Relapse-free survival at 20 years was 10%. MPA was associated with a lower risk for relapse (HR 0.48, 95% CI 0.28-0.82). CONCLUSION: We confirmed the improved patient and renal survival in AAV patients with glomerulonephritis, while relapse remained the primary challenge. Histopathological classification may be relevant for survival.

A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies.

BACKGROUND: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission. METHODS: We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point. RESULTS: Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03). CONCLUSIONS: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.

Glucose-free dialysis solutions: inductors of inflammation or preservers of peritoneal membrane?

OBJECTIVES: Glucose and other bioincompatible factors of conventional peritoneal dialysis solutions may damage the peritoneal membrane. The aim of our study was to investigate whether replacement of glucose with icodextrin (ID) or amino acids (AA) affects inflammatory parameters or cancer antigen 125 (CA125). DESIGN: Either ID or AA was used, in random order, in one daily exchange during an 8-week period. After the first study period, the patients entered a washout period and then switched to the other study solution for an 8-week period. C-reactive protein (CRP) was measured in serum, and CA125, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), and hyaluronan (HA) were measured in the overnight dwell dialysates at the beginning and end of the study periods. SETTING: A university hospital. PATIENTS: 22 patients with duration on peritoneal dialysis of 1.5 - 6.3 months. MAIN OUTCOME MEASURES: Levels of serum CRP and dialysate CA125, IL-6, HA, and sICAM-1 during use of ID and AA were compared to levels during use of glucose-only-based solutions. RESULTS: CRP increased significantly during use of ID. CA125 increased significantly during 8 weeks' use of AA, from 22.8 (5.4 - 89.0) to 42.9 (7.1 - 92.9) kU/L (p = 0.007). IL-6 increased during 8 weeks' use of AA, from 22.0 (9.0 - 108.0) to 36.5 (14.0 - 93.0) ng/L (p = 0.002) and ID, from 25.5 (8.0 - 82.0) to 40.0 (12.0 - 118.0) ng/L (p = 0.008). TNF-alpha also increased significantly during use of ID, but showed no significant changes during use of AA. CONCLUSIONS: The use of glucose-free solutions, especially AA, may lead to preservation of mesothelial cell mass and host defense. However, activation of systemic and peritoneal inflammation may appear during the use of ID and to a lesser extent during use of AA.

Do interleukin-6, hyaluronan, soluble intercellular adhesion molecule-1 and cancer antigen 125 in dialysate predict changes in peritoneal function? A 1-year follow-up study.

OBJECTIVE: Diminishing ultrafiltration and dialysis adequacy may limit the long-term use of peritoneal dialysis (PD). Inflammation may play a role in changes in peritoneal function. This study was designed to evaluate alterations in peritoneal function and soluble factors in dialysate during a 1-year follow-up period. MATERIAL AND METHODS: A personal dialysis capacity test was performed at the start of the study and after 6 and 12 months in 20 patients in order to determine dialysis adequacy and membrane characteristics. Dialysate was collected during the test days for analyses of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, hyaluronan and cancer antigen 125 (CA125). RESULTS: There were no significant changes in dialysis adequacy or membrane characteristics during the 1-year follow-up period. The appearance rate of IL-6 in dialysate increased significantly (419.8+/-63.3 at the start, 784.1+/-136.4 after 6 months and 1149.3+/-252.2 ng/24 h after 12 months; p=0.006) during follow-up. Furthermore, the appearance rate of CA125 increased throughout the study in patients using icodextrin, but decreased slightly in patients using only conventional dialysis solutions. CONCLUSIONS: There were no major changes in dialysis adequacy or membrane characteristics during the follow-up period, but increased IL-6 in dialysate may reflect peritoneal inflammation, which may lead to long-term alterations in the peritoneal membrane. Icodextrin may have a preventive effect on the longevity of the peritoneal membrane.

Benefit of glucose-free dialysis solutions on glucose and lipid metabolism in peritoneal dialysis patients.

BACKGROUND: Glucose absorbed from conventional peritoneal dialysis (PD) solutions contributes to unfavorable metabolic effects. Its replacement with a glucose-free osmotic agent such as icodextrin (ID) or amino acids (AA) may have some benefit on glucose and lipid metabolism. METHODS: Serum lipids, insulin sensitivity and substrate oxidation (calorimetry) were measured before and after 8 weeks use of ID or AA in 22 patients. Calorimetry and blood tests (HbA1c, lipids) were also performed after 8 weeks of simultaneous use of ID and AA in 8 patients. RESULTS: Cholesterol declined during the use of AA (4.8 +/- 0.3-4.5 +/- 0.3 mmol/l, p = 0.045). Triglycerides decreased during the use of both ID (2.2 +/- 0.2-1.9 +/- 0.1 mmol/l, p = 0.019) and AA (1.9 +/- 0.2-1.6 +/- 0.1 mmol/l, p = 0.024). Free fatty acids declined during the use of AA. There were no significant changes in insulin sensitivity. Glucose oxidation decreased and lipid oxidation increased during the use of ID, the changes in substrate oxidation were accentuated during the simultaneous use of ID and AA. CONCLUSION: Replacement of glucose with ID or AA had a benefit on glucose and lipid metabolism.

Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription.

BACKGROUND: Peritoneal dialysis is associated with changes in membrane function that can lead eventually to ultrafiltration (UF) failure. Factors driving these changes are thought to include hypertonic glucose exposure, but previously reported associations are confounded by the presence of residual renal function. METHODS: Longitudinal membrane function (solute transport and UF capacity) were measured annually in a prospective cohort of 177 functionally anuric patients as part of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS). Subgroup analysis was performed according to glucose exposure and icodextrin use at baseline. RESULTS: The whole cohort experienced an increase in solute transport and reduction in UF capacity at 12 and 24 months that could not be explained by informative censoring. These changes were accelerated and more severe in patients using either 2.27% or 3.86% glucose, or those not using icodextrin at baseline. These differences could not be explained by age, comorbidity score, previous time spent on renal replacement, differential dropout from the study, peritonitis rates, or, by definition, residual renal function. Patients using icodextrin at baseline had worse membrane function and were more likely to be diabetic. There was an association between membrane function changes and achieved 24-hour ultrafiltration over the 2-year study period. CONCLUSION: Anuric automated peritoneal dialysis (APD) patients experience significant detrimental changes in membrane function over a relatively short time period. Glucose appears to enhance these changes independent of residual renal function. Icodextrin use in these circumstances is associated with less deterioration in membrane function.

Cytokines and other soluble factors in dialysate -- indicators of altered peritoneal function?

OBJECTIVE: The bioincompatibility of dialysis solutions and recurrent episodes of peritonitis may alter peritoneal function. Cytokines and growth factors may play a role in inflammatory and fibrotic processes. We therefore investigated whether there is a correlation between peritoneal function and excretion of cytokines and other soluble factors in dialysate. MATERIAL AND METHODS: A personal dialysis capacity test was performed in 40 stable peritoneal dialysis patients. Tumour necrosis factor-alpha, interleukin-6 (IL-6), hyaluronan, soluble intercellular cell adhesion molecule-1 and transforming growth factor-beta1 were analysed from overnight and 24-h dialysates during the test. RESULTS: We found little evidence for a direct correlation between cytokines and other soluble factors in dialysate and dialysis adequacy. There was, however, a strong correlation between the measured soluble factors and characteristics of the peritoneal membrane. Furthermore, IL-6 correlated with the number of previous episodes of peritonitis. CONCLUSIONS: Soluble factors in dialysate may indicate ongoing inflammatory processes in the peritoneal membrane, which may gradually lead to alterations in peritoneal function.

Dialysate leukocytes, sICAM-1, hyaluronan and IL-6: predictors of outcome of peritonitis?

BACKGROUND/AIMS: Despite effective antibiotic therapy, peritonitis still remains a major problem in peritoneal dialysis (PD). The aim of the present study was to investigate changes of CRP, dialysate leukocytes and IL-6, hyaluronan (HA) and sICAM-1 in dialysate during and after peritonitis and their association to the outcome of peritonitis. METHODS: Dialysate IL-6, HA and sICAM-1 were measured at the onset and on day 4, at the end of the treatment and 2 months after onset of peritonitis. Furthermore, CRP and dialysate leukocytes were measured on days 1-4. RESULTS: All measured soluble factors were higher on the first and fourth day than at the end of the treatment. sICAM-1 and HA were lower at the end of the treatment in patients who later had a relapse/re-infection. IL-6 remained higher 2 months after clinically cured peritonitis. CRP and dialysate leukocytes were higher on day 4 in patients with poor outcome. CONCLUSIONS: Peritonitis causes increased excretion of soluble factors. Low concentrations of sICAM-1 and HA at the end of the treatment were negative prognostic indicators. Higher IL-6 levels after peritonitis could be a sign of ongoing inflammation in the peritoneal membrane. Delayed decrease in CRP and dialysate leukocytes may indicate poor outcome.