END-DIALYSIS OVERWEIGHT AND CHRONIC INFLAMMATION. A DANGEROUS CONNECTION

INTRODUCTION AND AIMS: Attaining dry body weight is paramount in dialysis practice, but this goal is not always reached. We hypothesized that the amount of enddialysis overweight (edOW), could be associated to increased chronic inflammation and mortality. Aim of the study: to evaluate the effect of edOW on serum C-reattive protein(hsCRP) concentrations and on survival in a cohort of 182 prevalent HD patients (pts) followed for 36 months. METHODS: In 182 pts (117 men, age 65612 years, vintage 48 months; range 6-336), edOW was present in 98/182 (54%) pts. Mean value was 0.460.2 Kg (range: 0.1-1.4). In the 98 pts with edOW (Group 1) and in the other 84 (Group 2) we evaluated: Ultrafiltration rate(UFR), hsCRPdry body weight (dBW), Kt/V, protein catabolic rate (PCRn), interdialytic weight gain (IDWG), mean arterial pressure (MAP). Unpaired Student’s t test was employed to compare groups, linear regression analysis to test correlations, log-rank test and Kaplan-Meier curves to evaluate survival. RESULTS: Mean UFR was 11.762.8 ml/Kg/hour, dBW 64612 Kg, hsCRP 6.6 (0.2-36) mg/L, Kt/V 1.2760.09, PCRn 1.0660.10 g/Kg/day, IDWG 2.860.4 Kg, MAP 9766.5 mmHg. edOW and hsCRP were directly and significantly correlated (r= 0.67; p<0.0001). Comparison between pts with (Group 1) and without (Group 2) edOW showed significant differences in: UFR (12.762.6 vs 10.962.6 ml/Kg/hour; p< 0.0001), hsCRP (13.068.1 vs 5.265.3 mg/L; p< 0.0001), and PCRn (1.0360.09 vs 1.0860.10 g/Kg/day; p<0.004). 98 pts (54%) died during follow-up for cardiovascular complications in 69% of cases. Survival curves showed significantly greater mortality in Group 1 vs Group 2 in relation to the amount of edOW, and hsCRP (p<0.0001). CONCLUSIONS: : edOW and chronic inflammation are directly correlated in HD pts, and both are associated to a greater long-term risk of mortality

The clinical features of juvenile dermatomyositis: A single-centre inception cohort

Introduction: Juvenile Dermatomyositis (JDM), a severe and rare autoimmune disease, is the most common idiopathic inflammatory myopathy in children. We describe the clinical features of a large single-centre cohort.Methods: We studied an inception cohort (0-18 years old) referred for diagnosis to the JDM clinic at The Hospital for Sick Children (SickKids), between January 1989 and September 2017. Probable or definite diagnosis of JDM was done according to the 2017 ACR/EULAR Criteria. We excluded children who had treatment started at another hospital. The data were collected retrospectively from clinical charts and the SickKids JDM database.Results: 172/230 (74.8%) patients were included. They were most often female (female:male = 1.8:1); the age at diagnosis was 8.5 +/- 4.3 years. There was a positive family history for autoimmune disease in 52%, mainly rheumatoid arthritis. No patient died. The most common signs at inception were muscle weakness (85.5%), nailfold capillary abnormalities (83.4%), Gottron papules (78.5%), heliotrope rash (66.3%), abnormal gait (55.8%), and malar/facial rash (54.7%). The prevalence of Gottron papules, heliotrope rash, facial/malar rash, nailfold capillary abnormalities, Raynaud phenomenon, dysphonia/dysphagia (a frequent cause of hospitaliza-tion), mouth ulcers, calcinosis, eye problems, joint involvement, acanthosis nigricans and lipodystrophy increased during follow-up. Muscle enzymes, namely CK, ALT, AST, were often normal or only slightly raised despite active muscle disease; conversely LD was often high. Anti-Nuclear Autoantibodies were positive in 49.7% of patients at diagnosis. The course of the disease was: 29.1% monocyclic, 5.3% polycyclic, 33.1% chronic. The course of 56 patients (32.5%) was not classifiable due to length of follow-up. Corticosteroids were used as treatment in almost all our patients and 30% required intravenous therapy due to the severity of the presen-tation; methotrexate was added in 64%, more often in recent years. Unresponsive patients were treated mostly with intravenous immunoglobulins (IVIG).Conclusions: The information obtained from this relatively large number of patients adds to the growing knowledge base of this rare disease. Trial registration: SickKids Research Ethics Board approved the study

CHRONIC INFLAMMATION AND END-DIALYSIS OVERWEIGHT. A 36 MONTH PROSPECTIVE OBSERVATIONAL STUDY

Introduction and Aims: Attaining dry body weight is paramount in dialysis practice, but this goal is not always reached.We hypothesized that the amount of end-dialysis overweight (edOW), could be associated to increased chronic inflammation and mortality. Aim of the study: to evaluate the effect of edOWon serum C-reattive protein (hsCRP) concentrations and on survival in a cohort of 182 prevalent HD patients ( pts) followed for 36 months. Methods: In 182 pts (117 men, age 65±12 years, vintage 48 months; range 6-336), edOWwas present in 98/182 (54%) pts. Mean value was 0.4±0.2 Kg (range: 0.1-1.4). In the 98 pts with edOW(Group 1) and in the other 84 (Group 2) we evaluated: Ultrafiltration rate(UFR), hsCRPdry body weight (dBW), Kt/V, protein catabolic rate (PCRn), interdialytic weight gain (IDWG), mean arterial pressure (MAP). Unpaired Student’s t test was employed to compare groups, linear regression analysis to test correlations, log-rank test and Kaplan-Meier curves to evaluate survival. Results: Mean UFR was 11.7±2.8 ml/Kg/hour, dBW 64±12 Kg, hsCRP 6.6 (0.2-36) mg/L, Kt/V 1.27±0.09, PCRn 1.06±0.10 g/Kg/day, IDWG 2.8±0.4 Kg, MAP 97±6.5 mmHg. edOWand hsCRP were directly and significantly correlated (r= 0.67; p<0.0001). Comparison between pts with (Group 1) and without (Group 2) edOW showed significant differences in: UFR (12.7±2.6 vs 10.9±2.6 ml/Kg/hour; p< 0.0001), hsCRP (13.0±8.1 vs 5.2±5.3 mg/L; p< 0.0001), and PCRn (1.03±0.09 vs 1.08±0.10 g/Kg/day; p<0.004). 98 pts (54%) died during follow-up for cardiovascular complications in 69% of cases. Survival curves showed significantly greater mortality in Group 1 vs Group 2 in relation to the amount of edOW, and hsCRP (p<0.0001). Conclusions: edOWand chronic inflammation are directly correlated in HD pts, and both are associated to a greater long-term risk of mortality

Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas

Use of renin-angiotensin system blockers increases serum potassium in anuric hemodialysis patients.

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are increasingly used in uremic patients (pts). However, their effect on serum potassium (sK) concentrations in anuric pts on chronic hemodialysis treatment (HD) is controversial. The aim of the study was to evaluate sK before and after the start of ACEi/ARB therapy. In the period 1/1/2015 - 31/12/2015, 112 out of 240 prevalent HD pts on thrice weekly HD treatment followed at our institution started the ACEi/ARB therapy. The mean age was 67 ± 14 years, 67/112 were men, dialysis vintage was 6-212 months. In the 3 months before (PRE; N° 36 HD sessions) and after (POST; N° 36 HD sessions) the start of ACEi/ARB therapy, the following variables were evaluated in pre dialysis after the long interdialysis interval: sK (mean of 12 determinations; mmol/L), maximum sK (maximum K value observed during observations; sKmax; mmol/L), serum sodium (sNa; mmol/L), pre dialysis systolic blood pressure (SBP; mm Hg) and diastolic blood pressure (DBP; mm Hg), body weight (BW; Kg), interdialytic weight gain (IWG; Kg), Kt/V, serum bicarbonate concentrations (sBic; mmol/L), protein catabolic rate (PCRn; g/KgBW/day). SBP, DBP, IWG are the mean of the 24 HD sessions. Out of 112 patients, 102 were on antihypertensive therapy. The duration of HD and blood and dialysate flow rates were kept constant. Data are expressed as mean ± SD. Student t test for paired and unpaired data for normally distributed variables, Mann-Whitney test for medians, χ2 test for categorical data were employed to compare groups. A significant difference was defined as p < 0.05. sK increased from 5.0 ± 0.4 mmol/L PRE to 5.7 ± 0.5 mmol/L POST (p < 0.0001). sKmax increased from 5.3 ± 0.5 mmol/L PRE to 6.2 ± 0.6 mmol/L POST (p < 0.0001). The percentage of pts with normal sK concentrations decreased from 82% PRE to 29% POST (p < 0.0001). Mild hyperkalemia increased from 18 to 52% (p < 0.001); in 31% of the patients, it was necessary to reduce the K dialysate concentration. None of the patients had severe hyperkalemia PRE, but 19% developed severe hyperkalemia POST (p < 0.0001) necessitating treatment withdrawal. Mean sK in these pts varied from 5.2 ± 0.3 mmol/L PRE to 6.5 ± 0.2 mmol/L at the moment of withdrawal (p < 0.0001) and sKmax from 5.5 ± mmol/L PRE to 6.9 ± 0.3 mmol/L (p< 0.0001). After withdrawal of ACEi/ARB, sK and sKmax concentrations decreased to basal levels within 1 month. There were no significant changes of BW, IWG, SBP, DBP, Na, Hb, Kt/V, sBic, and PCRn in both periods. ACEi/ARB therapy is associated with an increased risk of hyperkalemia in anuric hemodialysis patients. The proportion of patients with normal sK concentrations decreased from 82 to 29% and with mild hyperkalemia increased from 18 to 52%. Severe hyperkalemia necessitating the interruption of ACEi/ARB therapy developed in 19% of patients. This suggests great caution in the widest utilization of this class of drugs in HD patients

Total Convection Affects Serum β2 Microglobulin and C-Reactive Protein but Not Erythropoietin Requirement following Post-Dilutional Hemodiafiltration

BACKGROUND: Inflammation and increased erythropoiesis stimulating agents (ESA) requirement are frequently associated in patients on dialysis. On-line hemodiafiltration (ol-HDF), putting together high levels of diffusion, and convection could improve both conditions. However, it is still not known which depurative component plays a major role in determining this result. The aim of the study was to evaluate the role of convection and diffusion on long-term variations of serum β2 microglobulin (Δβ2M), high-sensitive C-reactive protein (ΔhsCRP) concentrations, and ESA requirement (ΔESA) in ol-HDF. METHODS: Seventy-three patients prevalent on high flux HD (hfHD) were studied. Thirty-eight patients were switched from hfHD to post-dilutional ol-HDF (Study group); the other 35 patients were considered the Control group. At 6 and 12 months, the effects of ol-HDF and hfHD on ΔhsCRP, ΔB2M, and ΔESA (U/kg/week) were evaluated. Other variables considered were body weight (BW), serum albumin (sAlb), hemoglobin (Hb), and equilibrated Kt/V (eKt/V). Iron therapy and ESA were administered intravenously according to the K/DOQI guidelines in order to maintain transferrin saturation between 20 and 40%, serum ferritin between 150 and 500 ng/ml and Hb between 11 and 12 g/dl. Qb, treatment time and Qd remained constant. Ol-HDF and hfHD were performed using membranes of size 1.9-2.1 sqm. Ultrapure dialysate and substitution fluid were employed in both HDF and HD treatments. Data are expressed as mean ± SD. Paired t test, Mann-Whitney U test, and simple and multiple regression analyses were employed for statistical evaluation. RESULTS: STUDY GROUP: total convective volume (TCV) was 22.1 ± 1.9 l/session. A significant reduction of hsCRP: from 6.8 ± 7.1 to 2.3 ± 2.4 mg/dl (p < 0.001), β2M: from 36.5 ± 14.4 to 24.7 ± 8.6 mg/dl (p < 0.0001) and ESAdose: from 107 ± 67 to 65 ± 44 U/kg/week (p < 0.005) was observed. No significant variations of Hb, BW and sAlb were seen. A significant inverse correlation was found between TCV and Δβ2M (r = -0.627; p < 0.0001), and TCV and ΔhsCRP (r = -0.514; p < 0.0001); no correlation between TCV and ΔESAdose was observed. No correlation was found between eKt/V and Δβ2M, ΔhsCRP, and ΔESAdose. Multiple regression analysis with ΔESAdose as dependent variable showed ΔhsCRP as the only significantly associated independent factor (p < 0.01). CONTROL GROUP: no significant variations of hsCRP, β2M, and ESAdose were observed over time. CONCLUSIONS: Ol-HDF induces a long-term significant reduction in pre-dialysis β2M and hsCRP concentrations. The magnitude of reduction is directly correlated to the amount of TCV achieved but not on eKt/V. The observed reduction in ESAdose requirement is independent either on convection or diffusion, but is directly associated to the concomitant reduction of inflammation

Total Convection Affects Serum β2 Microglobulin and C-Reactive Protein but Not Erythropoietin Requirement following Post-Dilutional Hemodiafiltration

BACKGROUND: Inflammation and increased erythropoiesis stimulating agents (ESA) requirement are frequently associated in patients on dialysis. On-line hemodiafiltration (ol-HDF), putting together high levels of diffusion, and convection could improve both conditions. However, it is still not known which depurative component plays a major role in determining this result. The aim of the study was to evaluate the role of convection and diffusion on long-term variations of serum β2 microglobulin (Δβ2M), high-sensitive C-reactive protein (ΔhsCRP) concentrations, and ESA requirement (ΔESA) in ol-HDF. METHODS: Seventy-three patients prevalent on high flux HD (hfHD) were studied. Thirty-eight patients were switched from hfHD to post-dilutional ol-HDF (Study group); the other 35 patients were considered the Control group. At 6 and 12 months, the effects of ol-HDF and hfHD on ΔhsCRP, ΔB2M, and ΔESA (U/kg/week) were evaluated. Other variables considered were body weight (BW), serum albumin (sAlb), hemoglobin (Hb), and equilibrated Kt/V (eKt/V). Iron therapy and ESA were administered intravenously according to the K/DOQI guidelines in order to maintain transferrin saturation between 20 and 40%, serum ferritin between 150 and 500 ng/ml and Hb between 11 and 12 g/dl. Qb, treatment time and Qd remained constant. Ol-HDF and hfHD were performed using membranes of size 1.9-2.1 sqm. Ultrapure dialysate and substitution fluid were employed in both HDF and HD treatments. Data are expressed as mean ± SD. Paired t test, Mann-Whitney U test, and simple and multiple regression analyses were employed for statistical evaluation. RESULTS: STUDY GROUP: total convective volume (TCV) was 22.1 ± 1.9 l/session. A significant reduction of hsCRP: from 6.8 ± 7.1 to 2.3 ± 2.4 mg/dl (p < 0.001), β2M: from 36.5 ± 14.4 to 24.7 ± 8.6 mg/dl (p < 0.0001) and ESAdose: from 107 ± 67 to 65 ± 44 U/kg/week (p < 0.005) was observed. No significant variations of Hb, BW and sAlb were seen. A significant inverse correlation was found between TCV and Δβ2M (r = -0.627; p < 0.0001), and TCV and ΔhsCRP (r = -0.514; p < 0.0001); no correlation between TCV and ΔESAdose was observed. No correlation was found between eKt/V and Δβ2M, ΔhsCRP, and ΔESAdose. Multiple regression analysis with ΔESAdose as dependent variable showed ΔhsCRP as the only significantly associated independent factor (p < 0.01). CONTROL GROUP: no significant variations of hsCRP, β2M, and ESAdose were observed over time. CONCLUSIONS: Ol-HDF induces a long-term significant reduction in pre-dialysis β2M and hsCRP concentrations. The magnitude of reduction is directly correlated to the amount of TCV achieved but not on eKt/V. The observed reduction in ESAdose requirement is independent either on convection or diffusion, but is directly associated to the concomitant reduction of inflammation

Magnitude of End-Dialysis Overweight is Associated with All-Cause and Cardiovascular Mortality: A 3-Year Prospective Study.

9Background: We hypothesized that the difference between the prescribed end-dialysis body weight, defined end-dialysis over-weight (edOW; kg), and the body weight which is actually attained could impact survival in hemodialysis (HD) patients. The aim of this prospective observational study was to evaluate if edOW could influence survival in a cohort of prevalent HD patients, controlled for multiple dialysis and clinical risk factors and followed for 3 years. Methods: One hundred and eighty-two patients (117 men, age 65 ± 13 years) on regular HD treatment for at least 6 months [median 48 months (range: 6-366)] were followed from January 1, 2008 to December 31, 2010. Eighty-four patients (46%) did not achieve their prescribed dry body weight (dBW); their median edOW was 0.4 kg (range: 0.1-1.4). Ninety-eight died during observation, mainly from cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized to evaluate the effect edOW, ultrafiltration rate (UFR), interdialytic weight gain (IDWG), age, sex, dialytic vintage, cardiovascular disease, antihypertensive therapy, diabetes, duration of HD, dBW, BMI, mean arterial blood pressure, Kt/V, and protein catabolic rate (PCRn) had on mortality. Results: Age (HR: 1.04; CI: 1.03-1.05; p <0.0001), IDWG (HR: 2.62; CI: 2.06-3.34; p < 0.01), UFR (HR: 1.13; CI: 1.09-1.16; p< 0.01), PCRn (HR: 0.02; CI: 0.01-0.04; p <0.001), and edOW (HR: 2.71; CI: 1.95-3.75; p < 0.02) were independently correlated to survival. The relative receiver operating characteristic curve identified a cutoff value of 0.3 kg for edOW in predicting death. Conclusions: High edOW is independently associated with an increased long-term risk of all-cause and cardiovascular mortality in HD patients. Better survival was observed in patients with edOW <0.3 kg. For patients with higher edOW, longer or more frequent dialysis sessions should be considered in order to prevent the deleterious consequences of excessive body fluid expansionreservedmixedMovilli, E.; Camerini, C.; Gaggia, P.; Zubani, R.; Feller, P.; Poiatti, P.; Pola, A.; Carli, O.; Cancarini, G.Movilli, Ezio; Camerini, Corrado; Gaggia, Paola; Zubani, Roberto; Feller, P.; Poiatti, P.; Pola, A.; Carli, O.; Cancarini, Giovann