Sclerosing encapsulating peritonitis: a case successfully treated with immunosuppression.

Perit Dial Int. 1999 Sep-Oct;19(5):478-81. Sclerosing encapsulating peritonitis: a case successfully treated with immunosuppression. Martins LS, Rodrigues AS, Cabrita AN, Guimaraes S. SourceDepartment of Nephrology, Hospital de Santo António, Porto, Portugal

Encapsulating Peritoneal Sclerosis in the Netherlands: A study on incidence, risk factors and clinical consequences

Patients with chronic renal failure have an accumulation of extracellular fluid and waste products (uremic toxins) which are normally excreted by the kidney. There are diff erent renal replacement therapies, which can partially correct these abnormalities. Peritoneal dialysis (PD) is one of these modalities. Since the introduction of continuous ambulatory peritoneal dialysis (CAPD) in 1976, the use of PD has increased steadily and is now used worldwide. On January 1st 2009, 6292 patients were on dialysis in The Netherlands, of which 18.1 % (n=1139) were on PD (source:RENINE www.renine.nl). In PD the peritoneal membrane is used as a dialyzer membrane. By gravity a sterile dialysis solution is instilled in the peritoneal cavity via an intra-abdominal catheter. Through a combination of diff usion and convection waste products and fl uid are transported between the peritoneal capillaries and the dialysis fluid. After a few hours an equilibration is reached, and the effl uent is drained. In the regular CAPD scheme, this cycle is performed 4 times a day for 4 hours with a long night dwell. Dialysis solutions contain varying concentrations of glucose in order to provide an osmotic gradient necessary for the transport and removal of excess body water. The glucose is absorbed by the peritoneal capillaries, which leads to a decrease of the osmotic gradient. In the early nineties icodextrin was introduced as a new dialysis fl uid. This is a glucose polymer derived from starches, which is absorbed slowly by the capillaries. Therefore it is very eff ective for ultrafi ltration, particularly in long dwells. Although, the side eff ects of icodextrin appear to be limited, sterile peritonitis due to icodextrin has been reported. Normal peritoneum comprises diff erent components; a thin layer of mesothelial cells and a submesothelial layer with vessels and fi broblasts. The inner abdominal wall is lined with a parietal membrane, where as a visceral membrane covers the intestines. Continuous exposure to dialysis solutions and other exogenous factors results in changes of the peritoneal membrane. In long term PD there is mesothelial denudation, the submesothelial layer becomes thicker and new vessels develop

Local membrane versus systemic consequences of peritoneal dialysis treatment

The primary intent of this thesis is to delineate the relative roles of local membrane and systemic consequences of peritoneal dialysis therapy, with particular reference to the role of inflammation and a severe, uncommon complication, encapsulating peritoneal sclerosis (EPS). Data sources comprised observational cohort studies as well as registry data: the Stoke PD study, a single centre study with clinical data, the Global Fluid Study (GFS), a multinational study with clinical data and repeated dialysate and plasma samples, and Scottish Renal Registry (SRR) and AnzData registry data. Through a cross sectional analysis of dialysate and plasma samples from GFS for inflammatory cytokines, we demonstrated that peritoneal and systemic inflammation are mostly separate processes although there is an association for IL-6 along with a steep concentration gradient from dialysate to plasma. Peritoneal inflammation, though IL-6, is the strongest determinant of peritoneal solute transport, and systemic inflammation, though IL-6, is a strong predictor of patient survival although peritoneal may contribute to systemic inflammation. Through a nested case control study of GFS we showed that inflammatory cytokines are upregulated within the peritoneum prior to developing EPS. With a nested case control design from the Stoke PD study, we showed that a decrease in ultrafiltration, likely due to increased fibrosis causing a reduction in osmotic conductance to glucose, also predisposes to EPS. A competing risks analysis of SRR and AnzData showed that patients at a high risk of death, have a low risk of EPS. These findings provide supporting evidence for the theory that the risk of EPS develops through the accumulation of inflammation-driven fibrosis due to dialysate exposure over a long period of time. Dialysate contains high concentrations of glucose and absorption of this drives impairment of systemic glucose metabolism, demonstrated through a cross sectional analysis of GFS

CCL18 y su implantación en esclerosis peritoneal: validación clínica de un nuevo marcador diagnóstico y pronóstico de alteraciones de la función peritoneal

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 13-12-2016Esta tesis tiene embargado el acceso al texto completo hasta el 13-06-2018El proceso de remodelado de la membrana peritoneal se ve mediado por una interacción inflamatoria y profibrótica que deriva en el fallo de membrana peritoneal (PMF) y en última estancia en su complicación más grave, la EPS. Dada la implicación de los macrófagos peritoneales alternativamente activados (M2) en el proceso de fibrosis peritoneal, se plantea la implicación fisiopatogénica de su citoquina CCL18 en dicha fibrosis y sus consecuencias funcionales derivadas. Objetivos del estudio: validar los niveles de CCL18, en suero y efluente peritoneal, como marcadores de alteraciones funcionales y estructurales profibróticas de la membrana peritoneal y explorar potenciales inhibidores del sistema profibrótico M2-CCL18. Métodos: Mediante un estudio longitudinal sobre 43 pacientes durante los 3 primeros años de DP y un corte transversal sobre 61 pacientes de >3 años en DP, valoramos CCL18 en suero y efluente estableciendo su asociación con PMF, EPS y factores de riesgo peritoneal. Estudiamos la implicación de CCL18 en efluente en PE secundaria a hipersensibilidad por clorhexidina. Relacionamos CCL18 con otras moléculas asociadas a EPS como PAI-1. Evaluamos CCL18 como diana terapéutica y su respuesta a inhibidores de la fibrosis como paricalcitol. Resultados y Discusión: Valores bajos y estables de CCL18 en efluente (<2.2ng/ml) se asocian con la ausencia de presentación posterior de PMF o EPS. Incrementos de CCL18 se asociaron significativamente con desarrollo de PMF. Valores de CCL18 en efluente <3.15ng/ml en el tercer año de DP presentaron un valor predictivo negativo del 89.5% y superiores a dicho umbral un riesgo mayor de PMF. La asociación de CCL18 en efluente y el desarrollo posterior de PMF se mostró independiente del abordaje clásico de transporte peritoneal. CCL18 en PE se confirma como agente fisiopatogénico de fibrosis peritoneal y fallo funcional asociado. CCL18 y PAI-1 en efluente se correlacionaron entre sí. Paricalcitol inhibe CCL18 en efluente. Conclusiones: Nuestro estudio muestra CCL18 en efluente como un marcador de riesgo de desarrollo de PMF con implicación fisiopatogénica en el modelo de fibrosis peritoneal en situación basal y en modelos inflamatorios como el de la PE, proporcionando además una potencial nueva diana terapéutica. Palabras clave: Diálisis peritoneal, efluente peritoneal, CCL18, función peritoneal, fallo de membrana peritoneal, esclerosis peritoneal encapsulante.The fibrotic remodeling of the peritoneal membrane is mediated by inflammatory and profibrotic interaction, resulting in the failure of peritoneal membrane (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS). Given the involvement of alternatively activated peritoneal macrophages (M2) in the process of peritoneal fibrosis, we hypostasized that its cytokine CCL18 has a physiopathogenic involvement in peritoneal fibrosis and its derived functional consequences. Objectives: validate CCL18 levels in serum and peritoneal effluent as a marker of fibrotic structural and functional alterations of the peritoneal membrane and explore potential inhibitors of profibrotic system M2 - CCL18. Methods: Through a longitudinal study of 43 patients during the first 3 years of PD and a cross section of 61 long-term PD patients (>3 years) , we analyze serum and effluent CCL18 and its association with PMF, EPS and peritoneal risk factors. We study the involvement of effluent CCL18 in chlorhexidine hypersensitivity secondary PE and CCL18 interaction with other molecules associated with EPS as PAI-1. Paricalcitol was studied as a CCL18 therapeutic agent. Results and discussion: Low and stable values of CCL18 in effluent (< 2.2ng/ml) are associated with the absence of subsequent presentation of PMF or EPS. An increase in CCL18 levels at any time was a predictive factor for PMF development. At year 3 of PD, CCL18 values in effluent under 3.15ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF. The association of effluent CCL18 and the subsequent development of PMF was shown independent from the classical approach of peritoneal transport. CCL18 in PE is confirmed as a physiopathogenic agent of peritoneal fibrosis and its associated membrane functional failure. Effluent CCL18 and PAI -1 correlated with each other. Paricalcitol inhibits CCL18 production by M2 macrophagues. Conclusions: Our study shows CCL18 in effluent as a marker of risk of development of PMF with physiopathogenic involvement in the model of peritoneal fibrosis at baseline and inflammatory models such as the PE, also providing a potential new therapeutic target. Key words: Peritoneal dialysis, peritoneal effluent, CCL18, peritoneal function, peritoneal membrane failure, encapsulating peritoneal sclerosis

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes