Adherence to multidisciplinary care in a prospective chronic kidney disease cohort is associated with better outcomes.

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.

Mineral and bone disorder and longterm survival in a chronic kidney disease grade 3b-4cohort.

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.

Recomendaciones sobre la vacunación contra SARS-CoV-2 / COVID-19 en pacientes con enfermedad renal y trasplante renal / Recommendations for the SARS-CoV-2 vaccination of patients with kidney disease and transplant recipients / Recomendações sobre vacinação contra SARS-CoV-2 / COVID-19 em pacientes com doença renal e transplante renal

Resumen: Este documento de recomendaciones tiene como objetivo orientar a médicos nefrólogos y no nefrólogos que asisten a pacientes con enfermedad renal crónica (ERC) en todas las etapas de la misma, en el proceso de vacunación contra el SARS-CoV-2. Como consecuencia de la situación epidemiológica y de los tiempos del proceso de elaboración de las vacunas disponibles, no se ha generado evidencia lo suficientemente potente, por lo que las recomendaciones no se acompañan del nivel de evidencia. Se fundamenta la necesidad de priorizar la vacunación en este grupo de pacientes en el mayor riesgo de adquirir la infección por SARS-CoV-2, desarrollar la enfermedad COVID-19 con mayor gravedad y presentar una mortalidad más elevada que la población general. Las recomendaciones se organizan por grupos de pacientes considerando pacientes con ERC no dialítica, diálisis y trasplante renal, y pacientes bajo tratamiento inmunosupresor.

Summary The objective of this document containing recommendations is to provide guidelines for nephrologists and non-nephrologists who assist patients with chronic kidney disease (CKD) at all stages of the disease on the vaccination process against SARS-CoV-2. As a consequence of the current epidemiological situation and the timing of the COVID-19 vaccine development -for available vaccines- there is no solid evidence, and thus, recommendations are not accompanied by the due medical proof. The need to prioritize vaccination in this group of patients is based on the increased risk of acquiring the SARS-CoV-2 infection, developing the COVID-19 disease with greater severity and presenting higher mortality rates than the general population. The recommendations are organized by groups of patients, considering patients with non-dialytic CKD, dialysis and kidney transplantation, and patients under immunosuppressive treatment.

Resumo: O objetivo deste documento de recomendações é orientar os nefrologistas e não nefrologistas que atendem pacientes com doença renal crônica (DRC) em todas as fases da doença, no processo de vacinação contra a SARS-CoV-2. Como consequência da situação epidemiológica e do momento do processo de produção das vacinas disponíveis, não foram geradas evidências suficientemente potentes, de modo que as recomendações não são acompanhadas de seu nível de evidência. A necessidade de priorizar a vacinação neste grupo de pacientes baseia-se no maior risco de adquirir a infecção pelo SARS-CoV-2, desenvolver a doença COVID-19 com maior gravidade e apresentar mortalidade superior à da população em geral. As recomendações são organizadas por grupos de pacientes, considerando pacientes com DRC não dialítica, em diálise, com transplante renal, e pacientes em tratamento imunossupressor.

Is Chronic Kidney Disease Progression Influenced by the Type of Renin-Angiotensin-System Blocker Used?

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.

Riesgo cardiovascular en la enfermedad renal crónica / Cardiovascular risk in chronic kidney disease

La enfermedad renal crónica (ERC) tiene elevada prevalencia y morbimortalidad cardiovascular (CV). Objetivos: analizar la prevalencia de factores de riesgo y tratamientos en la población del Programa de Salud Renal del Uruguay (PSRU) y su asociación con eventos CV y supervivencia. Método: estudio retrospectivo de la cohorte del registro del PSRU, que representa 58% de la población del país, entre 29/9/2006 y 31/12/2014. Los criterios de inclusión son: personas ³ 20 años, con alteraciones renales por más de tres meses, filtrado glomerular estimado (FGe) < 60 ml/min/1,73 m² o proteinuria >300 mg/día o albuminuria >30 mg/día en diabéticos, con seis o más meses en control. Se incluye registro de nuevos eventos cardiovasculares (NECV), ingreso a tratamiento de sustitución renal (TSR) y fallecimientos. Resultados: se incluyeron 8.407 individuos, edad 68 ± 14 años, 56% hombres, 66,6% > 65 años. Se observó elevada prevalencia de factores de riesgo CV. Se reportaron 2.245 NECV no fatales en 1.439 individuos (18,9%), tasa 10,1 por 100 pacientes-año (pac-año). Fallecieron 1.380 pacientes, 32,7% de causa CV. La tasa de ingreso a tratamiento de sustitución renal (TSR) fue de 1,94, la de mortalidad global de 6,2 y de causa CV de 2,03 por 100 pac-año. Se demostró la asociación de NECV y mortalidad con factores de riesgo tradicionales y vinculados a ERC, así como disminución con control glucídico y tratamiento con inhibidores de la enzima convertidora de angiotensina (IECA). Conclusiones: la población con ERC presenta múltiples factores de riesgo CV con elevada morbimortalidad, lo que amerita detección precoz y tratamiento.

Chronic kidney disease (CKD) is a highly prevalent condition with high cardiovascular morbidity and mortality. Objectives: the aim of the study was to analyze risk factors and treatments in the Uruguayan National Renal Healthcare Program (NRHP) and their association with cardiovascular events (CVE) and survival. Methods: this is a cohort study of patients included in the Uruguayan NRHP Registry, from 29/9/2006 to 31/12/2014. The inclusion criteria were age ³ 20 years, kidney disease for more than 3 months, estimated glomerular filtration rate (eFG) < 60 ml/min/1.73 m² and/or proteinuria >300 mg/day or albuminuria >30 mg/day in diabetics, with ³ 6 months under surveillance. The end-points were a new CV event, renal replacement therapy (RRT) or death. Results: 8.407 patients were included, mean age 68 ± 14 years, 56% males, 66,6% >65 years. Cardiovascular risk factors were highly prevalent. 2.245 new CVE were registered in 1.439 (18.9%) patients who survived (10.1/100 patient-year (pt-yr). 1.380 patients died, 32.7% of them from a CVE. RRT rate was 1.94 / 100 pt-yr, global mortality rate 6.2 and CV mortality rate 2.03 / 100 pt-yr. There was significant association between new CVE and traditional and CKD related risk factors, as well as a better outcome with good glycemic control and treatment with angiotensin converting enzyme inhibition Conclusion: CKD patients have many CV risk factors and high mortality, so early detection and treatment strategies are important.

Importancia del examen médico preventivo para el diagnóstico precoz de enfermedad renal en Uruguay.: Programa Nacional de Salud Renal / Importance of preventive medical examination for early diagnosis of renal disease in Uruguay.: The National Renal Health Program

Introducción: El Programa Nacional de Salud Renal (PNSR) mostró que la enfermedad renal crónica (ERC) puede estabilizarse en la evolución. Objetivo: evaluar el tamizaje de Enfermedad Renal Crónica presuntiva (ERCp) en población ambulatoria de una Clínica Preventiva con tirilla reactiva para proteinuria (TPu) y determinación de creatinina. Método. Estudio observacional, descriptivo, de corte transversal, entre 1/1/2008 y 31/12/2012 en 83.912 personas que se realizaron Carné de Salud (edad media =34.4años). Se consideró proteinuria positiva (Pu+) si TPu ≥1+ o ≥ 0.3 g/l. Se realizó TPu a todos y dosificación de creatinina para estimación Filtrado Glomerular (TFGe) en subpoblación con factores de riesgo (FR) como hipertensión o diabetes. Se evaluó proteinuria según edad y presencia o no de FR. En 11.161 individuos con determinación de creatinina se estimó el TFGe por fórmula CKD-EPI, (edad media=44.7años) se estimó prevalencia de ERCp mediante Pu+ TFGe<60 ml/min aisladas o en conjunto según grupos con FR, en base de datos no identificados de la Clínica Preventiva. Se utilizó el software estadístico SPSS 15.0 y regresión logística para análisis multivariado. Resultados: La prevalencia total de Pu+ fue de 6% (5.5% en grupo sin FR, 6.7% en hipertensión-sin-diabetes, 9.2% en diabetes-sin-hipertensión y 13.6% con ambos FR). Se desconocen falsos positivos. La prevalencia de TFGe<60 ml/min fue de 1.8%, siendo edad e hipertensión FR independientes para TFGe descendido. Considerados en conjunto Pu+ y TFGe<60 ml/min la prevalencia de ERCp alcanza 9.2%. Los FR aumentan la frecuencia de ERCp (p<0.05). Con Pu+ aislada se detecta ERCp entre el 85-90% según tengan o no FR; por grupos etarios la Pu+ aislada detecta el 100% de individuos con ERCp <20 años, es >90% en <50 años y cae a 30% en >70 años, donde cobra importancia la TFGe: 21.9% en con FR. Conclusiones: La población del Carné de Salud es útil para el tamizaje de ERCp temprana. Este estudio permitió identificar los mejores marcadores de ERCp para segmentos diferentes de población: la Pu+ aislada detecta ERCp en más del 90% de las personas <50 años y la TFGe adquiere importancia en añosos.

Introduction: The National Renal Health Program showed that chronic kidney disease (CKD) can be stabilized in the outcome. Objective: To assess screening Chronic Kidney Disease presumptive (pCKD) in an outpatient population of a Preventive Clinic with dipstick proteinuria (TPu) and/or eGFR <60 ml/min. Method: It is an observational, descriptive and cross sectional study. Between 1/1/2008 and 12/31/2012 was performed medical check to 83.912 individual (average age=34.4 years) from a Preventive Clinic with a proteinuria by TPu. In a selective population with predominant hypertension and diabetes (n 11.161 individuals, age 44.7 years odl) was performed determination of creatina and eGFR was estimated by CKD-EPI formula. pCKD prevalence was assessed by Pu + and/or eGFR<60 ml/min/1.73m2 alone or combined. We analyzed the risk factors (RF) for pCKD with SPSS 15.0 statistical software and logistic regression was used for multivariate analysis. Results: The prevalence of Pu + in total population was 6% (5.5% in the reference group, 6.7% in hypertension-without-diabetes, 9.2% in diabetes-without-hypertension and 13.6% in both RF group); the risk of Pu+ was increased in the previous groups (p < 0.05). Pu + false positives were unknown. The prevalence of eGFR< 60 ml/min was 1.8%, and age and hypertension were independent risk factors. When Pu + and/or eGFR<60 ml/min are considered together, the prevalence of pCKD reaches 9.2%. RF increases the frequency of pCKD (p < 0.05). With isolated Pu +, pCKD is detected between 85-90% according to whether or not they have RF; by age groups the isolated Pu + detects 100% of individuals with pCKD <20 years, is > 90% in those with <50 years and drop to 30% at 70 years or more, where is relevant the eGFR: 21.9% in RF group. Conclusions: The Preventive Clinic population is a useful place for screening early pCKD. This study identified renal markers of pCKD for different population segments: isolated Pu + detects pCKD in more than 90% of people < 50 years and the eGFR makes it in aged people.

Impacto de la acidosis en la evolución de la cohorte de pacientes del Programade Salud Renal del Uruguay / Impact of acidosis in the evoluton of the patients cohort in the renal health program of Uruguay

Objetivo: evaluar la frecuencia de acidosis metabólica en la enfermedad renal crónica (ERC) y su impacto en la evolución. Material y método: se realizó un estudio retrospectivo de pacientes del Programa de Salud Renal del Uruguay (octubre de 2004 a octubre de 2011) con dos controles separados porseis o más meses y al menos un dato de bicarbonatemia. Se analizaron: creatininemia, proteinuria, bicarbonatemia venosa y tratamiento alcalinizante. Se consideró evento final el ingreso a diálisis o trasplante y/o fallecimiento. Análisis estadístico: test de t, chi2, ANOVA, Kaplan-Meier y análisis multivariado de Cox (significativo p < 0,05). Resultados: se analizaron 921 pacientes con al menos un dato de bicarbonatemia (232 pacientes con dos o más datos). La creatininemia fue mayor en las nefropatías túbulo intersticiales y en los grupos con bicarbonatemia menor a 23 mEq/l(acidosis) o mayor a 32 mEq/l versus grupo intermedio. La bicarbonatemia fue menor en los estadios IV-V versus I-II de ERC. En estadios I-II, la bicarbonatemia fue menor si teníaproteinuria. Recibían alcalinizantes al inicio 7,3% y al final 31%. En el grupo con acidosis, el aumento de creatininemia/año (n = 232) fue mayor y la sobrevida (combinada) fue menor. Los niveles de bicarbonatemia, creatininemia y proteinuria se correlacionaron independientemente con el evento final combinado (ingreso a tratamiento de sustitución renal /muerte). Conclusiones: la acidosis metabólica se puede observardesde estadios iniciales de ERC y es un factor independiente de progresión y muerte, por lo que se recomienda sudetección precoz y corrección.

Objective: to evaluate the prevalence of metabolic acidosis in chronic kidney disease and its impact on the evolution of the condition. Method:we conducted a retrospective study of patients in the Renal Health Program of Uruguay (from October, 2004 through October, 2011) with two controlgroups six months or longer apart, and at least one bicarbonatemia datum. We analysed: creatininemia, proteinuria, venous bicarbonatemia and alcalinizing treatment. The start of dialysis, transplant and/or death wereconsidered final events. Statistical analysis: t test, chi2, ANOVA, Kaplan-Meier and multivariate analysis usingCox method (meaningful p < 0,05).Results: we analyzed 921 patients with at least one bicarbonatemia datum (232 patients with two or more data). Creatininemia was greater in the tubulo-interstitial nephritis and in the groups with bicarbonatemia lower than 23 mEq/l (acidosis) or greater than 32 mEq/l, rather than in the intermediate group. Bicarbonatemia was lower in the IV-V stages than in the I-II stages ofchronic kidney disease. In stages I-II bicarbonatemia was lower in the presence of proteinuria. Seven pointthree percent of patients received alkalinizers at the start, and 31% at the end. In the group with acidosis, increase of creatininemia/year (n = 232) was greater and survival (combined) was lower. Bicarbonatemia, creatininemia and proteinuria levels were independentlycorrelated with the combined final event (entering the renal substitution treatment/death). Conclusions:metabolic acidosis may be observedsince initial stages of the chronic kidney disease and it constitutes an independent factor of progression anddeath. Thus, early detection and correction are advisable.

Objetivo: avaliar a frequência da acidose metabólica na doença renal crônica (DRC) e o impacto desta na evolução dessa patologia. Material e método: um estudo retrospectivo de pacientes do Programa de Saúde Renal do Uruguai no período outubro de 2004 a outubro de 2011, como dois controles separados por seis ou mais meses e com pelo menos um dado de bicarbonatemia foi realizado. Foram analisados: creatininemia, proteinuria, bicarbonatemia venosa e tratamento alcalinizante. Foram consideradoscomo evento final a entrada a tratamento de substituição da função renal (diálise ou transplante) ou morte. A analise estatística foi realizada empregando teste de t, chi-quadrado, ANOVA, Kaplan-Meier e análisemultivariado de Cox (significativo p < 0,05). Resultados: foram analisados 921 pacientes compelo menos uma bicarbonatemia, dos quais 232 tinham dois ou mais resultados. A creatininemia foi maior nasnefropatias túbulo intersticiales e nos grupos com bicarbonatemia menor a 23 mEq/l (acidose) ou maior a 32mEq/l comparado com o grupo intermediário. A bicarbonatemia foi menor nos estádios IV-V quando comparados com I-II de DRC. Nos estádios I-II a bicarbonatemia foi menor se havia proteinuria. No inicio 7,3 % receberam alcalinizantes e 31% ao final. No grupo com acidose, o aumento da creatininemia/ano (n=232) foi maiore a sobrevida (combinada) foi menor. Os níveis de bicarbonatemia, creatininemia e proteinuria estavam correlacionados de forma independente com o evento final combinado (ingresso a tratamento de substituição renal/morte). Conclusões: a acidose metabólica pode ser observada desde estádios iniciais da DRC e é um fator independente de progressão e morte, por essa razão se recomenda sua detecção precoce e correção.