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.

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.

Calidad de cuidado médico en una clínica de enfermedad renal avanzada con estrategia multi-causal / Medical care quality in an advanced kidney disease clinic

En enfermedad renal crónica etapa IV (ERC-IV) es alta la mortalidad y progresión a insuficiencia renal extrema (IRE). Objetivo: Valorar la calidad asistencial en una Clínica de Enfermedad Renal Crónica Avanzada (CERCA). Métodos: Estudio prospectivo de pacientes ERC- IV asistidos con un equipo multidisciplinario formal mediante estrategia de educación, asesoramiento nutricional, seguimiento clínico mensual, y tratamiento según metas de presión arterial (<130/80) reducción de proteinuria, uso de inhibidores de enzima de conversión (IECA) y/o Bloqueantes de receptores de angiotensina (BRA), tratamiento de dislipemia, y preparación para diálisis. Resultados: Se analizaron 150 pacientes, 50% masculino, 62,0 ± 14,4 años, Nefropatías vascular 20,4%, diabética 34,2% y 62,5% proteinúricos, con Indice de Charlson 3,67±1,57. En seguimiento de 1,4 años (IQ: 0,6-2,4) disminuyó la PA (147±35 a 132 ± 28mm), colesterol (210±55 a 179±50 mg/dL) y LDL (129±52 a 108±37 mg/dL) con aumento del uso de IECA/BRA (55,9 a 60,6 %) y estatinas (32,2 a 63,3%). La tasa de Mortalidad fue 5,3 e IRE 14,5/100 Pt- año. El Riesgo pérdida de FG mayor a la mediana o IRE aumentó con HTA, Pru >1 g/d y glomerulopatias y se redujo 90% con IEC/BRA (p<0.001). Al ingreso a diálisis la Hemoglobina ≥10g%, vacunación hepatitis B y acceso permanente fueron más frecuentes que en la población general. Conclusiones: En una Clínica multidisciplinaria con estrategia de control de riesgos se alcanzó mejor las metas de tratamiento, disminuyendo los factores de riesgo de progresión y mejorando el cuidado médico al ingreso a diálisis.(AU)

In stage IV chronic kidney disease (stage-IV CKD), mortality and progression to extreme renal failure (ERF) are high. Objective: Assessing the quality of health care in an Advanced Kidney Disease Clinic (AKDC). Methods: Prospective study of patients with stage-IV CKD treated by a multidisciplinary formal team through an educational strategy, nutritional advice, clinical nephrology follow-up, aimed at achieving blood pressure goals (<130/80), proteinuria reduction, use of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), dyslipidemia treatment and preparation for dialysis. Results: 150 patients were analyzed, 50% were males, of 62.0 ± 14.4 years of age, 20.4% had vascular kidney diseases, 34.2% had diabetes and 62.5% had proteinuria with a Charlson index of 3.67 ± 1.57. In the 1.4-year follow-up (IQ: 0.6- 2.4), there were decreases in the BP (147±35 to 132±28 mm), cholesterol (210±55 to 179±50 mg/ dl) and LDL (129±52 to 108±37 mg/dl), and there was an increase in the use of ACEI/ARB (55.9to 60.6%) and statins (32.2 to 63.3%). The mortality rate was 5.3 and the ERF rate was 14.5/100 patient-years. The glomerular function loss risk, which was higher than the median or ERF, increased with HTN, Pru >1 g/d and glomerular diseases, and had a 90% decrease with ACEI/ARB(p<0.001). At dialysis entry, hemoglobin levels of≥10g%, hepatitis B vaccination and permanent access were more frequent than in the general population. Conclusions: Treatment goals were best achieved in a multidisciplinary clinic with a riskcontrol strategy, reducing progression risk factors and improving medical care upon dialysis entry.(AU)

Calidad de cuidado médico en una clínica de enfermedad renal avanzada con estrategia multi-causal / Medical care quality in an advanced kidney disease clinic

En enfermedad renal crónica etapa IV (ERC-IV) es alta la mortalidad y progresión a insuficiencia renal extrema (IRE). Objetivo: Valorar la calidad asistencial en una Clínica de Enfermedad Renal Crónica Avanzada (CERCA). Métodos: Estudio prospectivo de pacientes ERC- IV asistidos con un equipo multidisciplinario formal mediante estrategia de educación, asesoramiento nutricional, seguimiento clínico mensual, y tratamiento según metas de presión arterial (<130/80) reducción de proteinuria, uso de inhibidores de enzima de conversión (IECA) y/o Bloqueantes de receptores de angiotensina (BRA), tratamiento de dislipemia, y preparación para diálisis. Resultados: Se analizaron 150 pacientes, 50% masculino, 62,0 ± 14,4 años, Nefropatías vascular 20,4%, diabética 34,2% y 62,5% proteinúricos, con Índice de Charlson 3,67±1,57. En seguimiento de 1,4 años (IQ: 0,6-2,4) disminuyó la PA (147±35 a 132 ± 28mm), colesterol (210±55 a 179±50 mg/dL) y LDL (129±52 a 108±37 mg/dL) con aumento del uso de IECA/BRA (55,9 a 60,6 %) y estatinas (32,2 a 63,3%). La tasa de Mortalidad fue 5,3 e IRE 14,5/100 Pt- año. El Riesgo pérdida de FG mayor a la mediana o IRE aumentó con HTA, Pru >1 g/d y glomerulopatias y se redujo 90% con IEC/BRA (p<0.001). Al ingreso a diálisis la Hemoglobina ≥10g%, vacunación hepatitis B y acceso permanente fueron más frecuentes que en la población general. Conclusiones: En una Clínica multidisciplinaria con estrategia de control de riesgos se alcanzó mejor las metas de tratamiento, disminuyendo los factores de riesgo de progresión y mejorando el cuidado médico al ingreso a diálisis.

In stage IV chronic kidney disease (stage-IV CKD), mortality and progression to extreme renal failure (ERF) are high. Objective: Assessing the quality of health care in an Advanced Kidney Disease Clinic (AKDC). Methods: Prospective study of patients with stage-IV CKD treated by a multidisciplinary formal team through an educational strategy, nutritional advice, clinical nephrology follow-up, aimed at achieving blood pressure goals (<130/80), proteinuria reduction, use of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), dyslipidemia treatment and preparation for dialysis. Results: 150 patients were analyzed, 50% were males, of 62.0 ± 14.4 years of age, 20.4% had vascular kidney diseases, 34.2% had diabetes and 62.5% had proteinuria with a Charlson index of 3.67 ± 1.57. In the 1.4-year follow-up (IQ: 0.6- 2.4), there were decreases in the BP (147±35 to 132±28 mm), cholesterol (210±55 to 179±50 mg/ dl) and LDL (129±52 to 108±37 mg/dl), and there was an increase in the use of ACEI/ARB (55.9to 60.6%) and statins (32.2 to 63.3%). The mortality rate was 5.3 and the ERF rate was 14.5/100 patient-years. The glomerular function loss risk, which was higher than the median or ERF, increased with HTN, Pru >1 g/d and glomerular diseases, and had a 90% decrease with ACEI/ARB(p<0.001). At dialysis entry, hemoglobin levels of≥10g%, hepatitis B vaccination and permanent access were more frequent than in the general population. Conclusions: Treatment goals were best achieved in a multidisciplinary clinic with a riskcontrol strategy, reducing progression risk factors and improving medical care upon dialysis entry.

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. (AU)

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. (AU)

Objetivo: avaliar a frequência da acidose metabólica na doença renal crônica (DRC) e o impacto desta na evoluçäo 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 substituiçäo da funçäo 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 substituiçäo renal/morte). Conclusões: a acidose metabólica pode ser observada desde estádios iniciais da DRC e é um fator independente de progressäo e morte, por essa razäo se recomenda sua detecçäo precoce e correçäo. (AU)

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.