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Aim: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment., Methods: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries., Results: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors., Conclusion: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Mineral and bone disorder biomarkers 'normal ranges' are controversial. The aim of the study was to evaluate the association between serum calcium (Ca), phosphate (P), intact parathyroid hormone (iPTH), and 25(OH) vitamin D levels and mortality risk, in a chronic kidney disease (CKD) grade (G) 3b-4 cohort. The Uruguayan National Renal Healthcare Program (NRHP-UY) CKD patients' cohort, included between 1 October 2004 and 1 March 2020 and followed-up until 1 March 2021, was analyzed with the Ethics Committee approval. A total of 6473 patients were analyzed: 56% men, median age 73 (65-79) years, 55% on CKD G3b. At the end of the follow-up, 2459 (37.7%) patients had died (6.4/100 patient-year). There were iPTH data on 2013 patients (younger, with lower estimated glomerular filtration rate (eGFR) and lesser comorbidities). By bivariate Cox analysis the lowest death risk was observed with mean Ca between 9.01 and 10.25 mg/dl, P between 2.76 and 4.0 mg/dl, iPTH ≤ 105 pg/ml, and 25(OH) vitamin D >10 ng/ml. The multivariate Cox regression mortality risk adjusted to age, sex, CKD etiology, diabetes, smoking, cardiovascular comorbidity, blood pressure, proteinuria, eGFR, renin-angiotensin system blockers and vitamin D treatments, serum Ca, P, iPTH, and 25(OH) vitamin D ( n  = 964) showed that a higher mortality risk was associated with p  > 4.00 mg/dl (HR 1.668, CI 95%: 1.201-2.317), iPTH >105 pg/ml (HR 1.386, CI 95%: 1.012-1.989), and 25(OH) vitamin D ≤ 10 ng/ml (HR 1.958, CI 95%: 1.238-3.098) and a lower mortality risk with 1,25(OH) 2 vitamin D treatment (HR 0.639, CI 95%: 0.451-0.906). These data may contribute to the precise G3b-4 CKD-MBD biomarkers levels definition.

Introduction: The Renal Healthcare Program Uruguay (NRHP-UY) is a national, multidisciplinary program that provides care to chronic kidney disease (CKD) patients. In this study, we report the global results of CKD patient outcomes and a comparison between those treated at the NRHP-UY Units, with those patients who were initially included in the program but did not adhere to follow up., Methods: A cohort of not-on dialysis CKD patients included prospectively in the NRHP-UY between October 1st 2004 and September 30th 2017 was followed-up until September 30th 2019. Two groups were compared: a) Nephrocare Group: Patients who had at least one clinic visit during the first year on NRHP-UY (n = 11174) and b) Non-adherent Group: Patients who were informed and accepted to be included but had no subsequent data registered after admission (n = 3485). The study was approved by the Ethics Committee and all patients signed an informed consent. Outcomes were studied with Logistic and Cox´s regression analysis, Fine and Gray competitive risk and propensity-score matching tests., Results: 14659 patients were analyzed, median age 70 (60-77) years, 56.9% male. The Nephrocare Group showed improved achievement of therapeutic goals, ESKD was more frequent (HR 2.081, CI 95%1.722-2.514) as planned kidney replacement therapy (KRT) start (OR 2.494, CI95% 1.591-3.910), but mortality and the combined event (death and ESKD) were less frequent (HR 0.671, CI95% 0.628-0.717 and 0.777, CI95% 0.731-0.827) (p = 0.000) compared to the Non-adherent group. Results were similar in the propensity-matched group: ESKD (HR 2.041, CI95% 1.643-2.534); planned kidney replacement therapy (KRT) start (OR 2.191, CI95% 1.322-3.631) death (HR 0.692, CI95% 0.637-0.753); combined event (HR 0.801, CI95% 0.742-0.865) (p = 0.000)., Conclusion: Multidisciplinary care within the NRHP-UY is associated with timely initiation of KRT and lower mortality in single outcomes, combined analysis, and propensity-matched analysis., Competing Interests: The authors have declared that no competing interests exist

Guideline 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. ( practice point )., Guideline 2a: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. ( practice point ) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) ( GRADE 1A ) and subsequently when clinically indicated. ( practice point )., Guideline 2b: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. ( GRADE 1A ) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. ( GRADE 1A ) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. ( GRADE 1A ) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. ( practice point )., Guideline 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), ( GRADE 1B ) and/or (b) the daily UF is insufficient to maintain adequate fluid status. ( practice point ) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR., Guideline 4a: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. ( GRADE 2B )., Guideline 4b: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. ( practice point )., Guideline 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and 'lymphatic' reabsorption are not recommended for routine clinical practice but remain valuable research methods. ( practice point )., Guideline 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. ( practice point ).

Background: Optimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in patients who are high risk. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy., Methods: In this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3, and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6)., Results: At 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation., Conclusions: Replacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4, and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020&#95;09&#95;24&#95;KID0002802020.mp3., Competing Interests: All authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Background: Patients on dialysis report high levels of symptom burden. The association of these symptoms may have an increased deleterious effect on the patients' well-being., Objective: This study aimed to assess the prevalence of symptoms, to identify symptom clusters, and to describe the impact of concurrent symptoms on physical and emotional well-being in a sample of dialysis patients., Methods: Data of the first assessment of a longitudinal study aimed to assess patient-reported outcomes in dialysis were included here. The KDQOL-36 PCS, MCS and Symptom Subscale, the Hospital Anxiety and Depression Scales and the Epworth Sleepiness Scale were analyzed. The ICLUST procedure was followed for hierarchical cluster analyses., Results: Of the 512 eligible patients, 493 accepted to participate, 43.6 % were female, with mean age of 60.9 (SD=16.7). Treatment modality was HD in 87.6% of patients. Most prevalent and severe symptoms were muscle sores, cramps, "washed out", dry skin, and itchy skin, Moderate to severe pain was reported by 25%, and daily somnolence by 12.4% of the patients. Five first level symptom clusters were identified as cutaneous, cardiac, digestive, sensory-motor, energy. Both, the presence of any cluster and cluster scores were significantly associated with lower physical and mental quality of life and a higher psychological distress., Conclusions: Our study confirms the presence of high symptom burden in dialysis patients in Uruguay. Several symptom clusters were identified having significant impact on the patients' well-being. The identification of symptom clusters can help to understand common underlying pathways. It is possible that the management of symptom clusters may reduce symptom burden in these patients., (Copyright © 2018 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Background: Peritonitis is a major complication and the main cause of peritoneal dialysis (PD) failure. The aim of the present study was to evaluate peritonitis risk factors and its prevention with a new peritoneal educational program (NPEP)., Methods: We performed a retrospective analysis of a cohort of chronic PD patients, older than 16 years, who began PD in the period 1 January 1999 to 31 December 2015 at a Uruguayan PD center, with follow-up until 31 December 2016., Results: The population included 222 cases (219 patients, 128 men), median age 59 (interquartile range [IQR] 47.0 - 72.0) years, median time on PD 17.5 (IQR 6.0 - 36.2) months. Ninety-five patients suffered 1 or more episodes of peritonitis, and they had been on PD for a longer period and had nasal-positive culture more frequently. A NPEP started in September 2008; patients who trained with it, as well as younger patients, had longer peritonitis-free survival. After the NPEP, global peritonitis rates decreased significantly (from 0.48 to 0.29 episodes/patient-year, respectively), particularly gram-positive bacteria and Staphylococcus aureus / coagulase-negative (CoNS) (from 0.26 to 0.12 and 0.21 to 0.07 episodes/patient-year, respectively). In the multivariate Cox analysis of peritonitis risk factors, survival to first peritonitis was significantly associated only with age (hazard ratio [HR] 1.024, 95% confidence interval [CI] 1.007 - 1.397, p = 0.007) and the NPEP (HR 0.600, 95% CI 0.394 - 0.913, p = 0.017)., Conclusion: A multidisciplinary peritoneal educational program may improve peritonitis rates, independently of other risk factors., (Copyright © 2019 International Society for Peritoneal Dialysis.)

Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria and slow renal disease progression more effectively than other therapies in patients with chronic kidney disease (CKD). However, differences regarding efficacy and safety between these therapies remain controversial., Objectives: Aim of this study was to analyze the different treatment effect of ACEI, ARB, and non-ACEI/ARB in CKD progression. The primary outcome was survival to end-stage renal disease (ESRD) and/or death and to ESRD censored by all-cause death, secondary outcomes were proteinuria reduction and hyperkalemia., Methods: We analyzed data from 1,120 patients extracted from the National Renal Healthcare Program cohort, which included 17,238 CKD nondialysis subjects who were successively monitored between -September 1, 2004 and August 31, 2016. Inclusion criteria were at least a 1-year follow-up, 3 clinical visits, and no previous treatment with ACEI or ARB. From the baseline visit onward, patients continued with 3 different treatment schemes: no ACEI/ARB, started on ACEI or ARB, but while avoiding both treatments in combination. Chi2, t test, binary logistic regression, and multivariate regression models (Cox proportional Hazard model and competing risk Fine and Gray model were used for statistical analysis., Results: Mean age and follow-up were 67.9 (± 15) and 3.8 (± 2) years, respectively. Estimated glomerular filtration rate averaged 42.1 ± 23 mL/min/1.73 m2 and 300 (27%) patients were diabetics. Progression to ESRD was significantly worse in the no ACEI/ARB group (hazard ratio [HR] 4.23, 95% CI 1.28-13.92) versus ACEI (reference group; p = 0.01). The analysis by competing-risks' regression showed significantly higher risk of ESRD in the no ACEI/ARB group (HR 3.63, 95% CI 1.34-9.85) versus ACEI (p = 0.01). There were no significant differences between ACEI and ARB groups (HR 1.31, 95% CI 0.37-4.66) regarding the risk of progression to ESRD. Survival was similar in all 3 groups (p = 0.051). Statistically significantly more patients experienced reductions in proteinuria/albuminuria in ACEI and ARB groups (together) versus no ACEI/ARB group (p = 0.016, OR 1.82, 95% CI 1.12-2.94). No difference in hyperkalemia frequency was found between them (p = 0.17)., Conclusions: In patients with CKD, treatment with ACEI or ARB had a superior effect than no ACEI or ARB treatment on slowing kidney disease progression and on proteinuria reduction. Efficacy of ACEI and ARB was comparable., (© 2019 S. Karger AG, Basel.)

Background and Objectives: Drug-induced acute interstitial nephritis represents an emerging cause of acute kidney disease, especially among polymedicated elderly patients. Although corticosteroids are frequently used, controversy exists about the timing of initiation, efficacy, safety, and duration of treatment., Design, Setting, Participants, & Measurements: We performed a retrospective study of 182 patients with biopsy-proven drug-induced acute interstitial nephritis from 13 Spanish centers. Exposure was defined as the length of corticosteroid treatment. The main outcome was the level of serum creatinine at month 6, with respect to baseline values., Results: The most common offending agents were nonsteroidal anti-inflammatory drugs (27%). In 30% of patients, the offending drug could not be identified. The median time to suspected drug withdrawal was 11 days (interquartile range, 5-22). All patients presented with acute kidney disease and were treated with corticosteroids. The mean initial dose of prednisone was 0.8±0.2 mg/kg per day. High-dose corticosteroid treatment was maintained for 2 weeks (interquartile range, 1-4). After 6 months, the mean recovered GFR was 34±26 ml/min per 1.73 m 2 and ten patients required maintenance dialysis. Use of high-dose corticosteroids for 3 weeks or treatment duration >8 weeks were not associated with better recovery of kidney function. In the multivariable analysis, delayed onset of steroid treatment (odds ratio, 1.02; 95% confidence interval, 1.0 to 1.04) and the presence of interstitial fibrosis of >50% on the kidney biopsy specimen (odds ratio, 8.7; 95% confidence interval, 2.7 to 27.4) were both associated with serum creatinine level at month 6 of >75%, with respect to baseline values., Conclusions: High-dose corticosteroid treatment for 3 weeks or prolonged treatment for >8 weeks were not associated with greater kidney function recovery in drug-induced acute interstitial nephritis. A delay in the initiation of corticosteroids resulted in worse recovery of kidney function., (Copyright © 2018 by the American Society of Nephrology.)

Our aim is to describe variations in the incidence rates of glomerular disease diagnosed by renal biopsies performed in Uruguay over the last 25 years in relation to sex, age, clinical presentation and histological diagnosis. We analyzed all renal biopsies performed in Uruguay during the 25 years period and estimated incidence rates per million people per year (pmp/yr) for the population older than 14 years. Mann Kendall's trend analysis was used to assess incidence trends. In order to identify changes in trends, we compared annual incidence rates with the Joinpoint method. From 1990 to 2014, 3390 biopsies of native kidneys corresponding to glomerular disease were performed in patients older than 14 years. The average biopsy rate was 58 per pmp/yr. The glomerular disease incidence rate increased progressively over the period (p<0.05). Trends analysis over five-year periods demonstrated a progressive increase of IgA nephropathy (3.08 pmp/yr 1990-1994 to 12.53 pmp/yr 2010-2014 p<0.05), membranous nephropathy (2.38 pmp/yr 1990-1994 to 8.04 pmp/yr 2010-2014 p< 0.05) and lupus nephritis (4,23 pmp/yr 1990-1994 to 7,81 pmp/yr 2010-2014 p<0.05). There was a change in the trend of focal segmental glomerular sclerosis (FSGS) which increased until 1996 and decreased afterwards. The incidence rates of glomerular disease have doubled globally in the last quarter of a century in Uruguay, mainly related to the increase of IgA nephropathy, membranous nephropathy and lupus nephritis. There was a change in the slope of the incidence rate of FSGS., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Because of their rarity in men, systemic lupus erythematous and lupus nephritis (LN) are poorly understood in men. Our aim was to analyze the clinical presentation and course of histology-proven systemic lupus erythematous and LN in males and to determine the risk factors for progression to end-stage renal disease., Methods: Fifty patients from 2 historical cohorts in Spain (Hospital 12 de Octubre) and Uruguay were retrospectively analyzed and compared with a female cohort matched for age and disease characteristics., Results: The median age at the time of renal biopsy was 27 years (range, 8-79 years). The main forms of presentation were nephrotic syndrome in 26 of 50 patients (52%), and class IV LN in 34 of 50 (68%). After treatment, 21 patients (45.6%) achieved complete renal remission. During follow-up, 12 patients required renal replacement therapy, and 3 patients died of infectious causes. When patients who required renal replacement therapy were compared with those who did not require it, several parameters showed significant differences ( P  < 0.05) at the time of renal biopsy: estimated glomerular filtration rate < 60 ml/min, hypertension, hypoalbuminemia, and concomitant visceral involvement (neurologic, cardiovascular, and/or pulmonary). In the multivariate analysis, only estimated glomerular filtration rate < 60 ml/min persisted as a risk factor for progression to end-stage renal disease. When compared with a cohort of female patients with LN, there were no significant differences in remission or renal survival., Discussion: LN in males usually presents as nephrotic syndrome, and type IV LN is the most frequent form. An estimated glomerular filtration rate < 60 ml/min at the time of renal biopsy is associated with poor renal outcomes. There were no differences in remission or progression of LN in males when compared with a cohort of female patients with LN.

Rhabdomyolysis results from acute necrosis of skeletal muscle fibers and consequent leakage of muscle constituents into the circulation. It ranges from an asymptomatic state to a severe condition associated with extreme elevations in creatine kinase and acute renal failure. Reported etiologies of rhabdomyolysis include alcohol abuse, drugs, muscle trauma and muscle overexertion. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, toxins and endocrine disorders. Hypokalemia is a rare cause of rhabdomyolysis. We report six patients aged 31 to 57 years (three women) with a severe hypokalemic rhabdomyolysis, secondary to chronic diarrhea in two patients, treatment with loop diuretics in one and Gitelman syndrome in three. Rhabdomyolysis may be underdiagnosed in the context of hypokalemia, because the neuromuscular symptoms can be attributed solely to the electrolyte disorder.

Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m(2)) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m(2) higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m(2) was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m(2).

Objectives: The present study evaluated the tool used to assess patients' skills and the impact on peritonitis rates of a new multidisciplinary peritoneal dialysis (PD) education program (PDEP)., Methods: After the University Hospital Ethics Committee approved the study, the educational and clinical records of PD patients were retrospectively analyzed in two phases. In phase I, an Objective Structured Assessment (OSA) was used during August 2008 to evaluate the practical skills of 25 patients with adequate Kt/V and no mental disabilities who had been on PD for more than 1 month. Test results were correlated with the prior year's peritonitis rate. In phase II, the new PDEP, consisting of individual lessons, a retraining schedule, and group meetings, was introduced starting 1 September 2008. Age, sex, years of education, time on PD, number of training sessions, and peritonitis episodes were recorded. Statistical analyses used t-tests, chi-square tests, and Poisson distributions; a p value of less than 0.05 was considered significant., Results: In phase I, 25 patients [16 men, 9 women; mean age: 54 ± 15 years (range: 22 - 84 years); mean time on PD: 35 ± 30 months (range: 1 - 107 months)] were studied. The OSA results correlated with peritonitis rates: patients who passed the test had experienced significantly lower peritonitis rates during the prior year (p < 0.05). In phase II, after the new PDEP was introduced, overall peritonitis rates significantly declined (to 0.28 episodes/patient-year from 0.55 episodes/patient-year, p < 0.05); the Staphylococcus peritonitis rate also declined (to 0.09 episodes/patient-year from 0.24 episodes/patient-year, p < 0.05)., Conclusions: The OSA is a reliable tool for assessing patients' skills, and it correlates with peritonitis rates. The multidisciplinary PDEP significantly improved outcomes by further lowering peritonitis rates.

Introduction: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it., Methods: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant., Results: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production., Conclusions: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

Uruguay is a South American country (3241003 inhabitants) where renal replacement treatment is universally available. The aim of this study was to analyze the incidence and outcome of peritonitis, and the causative organisms and their sensitivity, in order to recommend an empiric initial antibiotic treatment. A retrospective descriptive study of all peritonitis during the period 2004-2005 was performed (144 peritonitis, 44% due to gram-positive bacteria). We conclude that the high prevalence of methicillin-resistant coagulase-negative staphylococci justifies the use of vancomycin in the national empiric initial antibiotic protocols.

Background: Metabolic acidosis is a consequence of chronic renal failure and it may produce bone demineralization, muscle proteolysis, and progression of chronic renal failure. The aim of this study was to evaluate the effects of correction of metabolic acidosis with calcium citrate in an experimental model of renal mass ablation., Methods: Wistar rats were subjected to 5/6 nephrectomy and were randomly assigned to one of 4 groups: nontreated (NFX); treated with calcium citrate (1.45 g/100 g feed) (NFX-CIT); treated with captopril (500 mg/L water) (NFX-CAP); or treated with both (NFX-CAP-CIT) during 1, 10, or 20 weeks. Body weight, systolic blood pressure, proteinuria, arterial bicarbonate concentration, urine citrate excretion, plasma calcium, and inulin clearance were measured. Histologic glomerular and tubulointerstitial damage scores were measured at 1, 10, and 20 weeks, and glomerular and tubular proliferating cell nuclear antigen (PCNA)-positive cells, alpha-smooth muscle actin, and desmin staining were studied by immunohistochemistry at 1 and 10 weeks., Results: The treated groups showed significantly less glomerular and tubulointerstitial cellular proliferation in the first week (P < 0.05), less glomerular cell transdifferentiation and higher plasma bicarbonate at 10 weeks (P < 0.05), as well as diminished histologic glomerular and tubulointerstitial damage scores at 20 weeks (P < 0.05). Inulin clearances were higher (P < 0.05), and urine protein excretion rates were lower (P < 0.05) than in the NFX non-treated group, but arterial blood pressure was not significantly different in the NFX-CIT group., Conclusion: Calcium citrate slows the progression of chronic renal injury in the 5/6 NFX model. It improves metabolic acidosis and diminishes cell proliferation and transdifferentiation without changes in systolic blood pressure.