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      Impacto de la acidosis en la evolución de la cohorte de pacientes del Programa de Salud Renal del Uruguay

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          Abstract

          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 por seis 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 tenía proteinuria. 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 observar desde estadios iniciales de ERC y es un factor independiente de progresión y muerte, por lo que se recomienda su detección precoz y corrección.

          Translated abstract

          Summary 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 control groups 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 were considered final events. Statistical analysis: t test, chi2, ANOVA, Kaplan-Meier and multivariate analysis using Cox 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 of chronic kidney disease. In stages I-II bicarbonatemia was lower in the presence of proteinuria. Seven point three 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 independently correlated with the combined final event (entering the renal substitution treatment/death). Conclusions: metabolic acidosis may be observed since initial stages of the chronic kidney disease and it constitutes an independent factor of progression and death. Thus, early detection and correction are advisable.

          Translated abstract

          Resumo 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 considerados como 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 análise multivariado de Cox (significativo p < 0,05). Resultados: foram analisados 921 pacientes com pelo menos uma bicarbonatemia, dos quais 232 tinham dois ou mais resultados. A creatininemia foi maior nas nefropatias túbulo intersticiales e nos grupos com bicarbonatemia menor a 23 mEq/l (acidose) ou maior a 32 mEq/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 maior e 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.

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          Most cited references 50

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          Bicarbonate supplementation slows progression of CKD and improves nutritional status.

          Bicarbonate supplementation preserves renal function in experimental chronic kidney disease (CKD), but whether the same benefit occurs in humans is unknown. Here, we randomly assigned 134 adult patients with CKD (creatinine clearance [CrCl] 15 to 30 ml/min per 1.73 m(2)) and serum bicarbonate 16 to 20 mmol/L to either supplementation with oral sodium bicarbonate or standard care for 2 yr. The primary end points were rate of CrCl decline, the proportion of patients with rapid decline of CrCl (>3 ml/min per 1.73 m(2)/yr), and ESRD (CrCl <10 ml/min). Secondary end points were dietary protein intake, normalized protein nitrogen appearance, serum albumin, and mid-arm muscle circumference. Compared with the control group, decline in CrCl was slower with bicarbonate supplementation (5.93 versus 1.88 ml/min 1.73 m(2); P < 0.0001). Patients supplemented with bicarbonate were significantly less likely to experience rapid progression (9 versus 45%; relative risk 0.15; 95% confidence interval 0.06 to 0.40; P < 0.0001). Similarly, fewer patients supplemented with bicarbonate developed ESRD (6.5 versus 33%; relative risk 0.13; 95% confidence interval 0.04 to 0.40; P < 0.001). Nutritional parameters improved significantly with bicarbonate supplementation, which was well tolerated. This study demonstrates that bicarbonate supplementation slows the rate of progression of renal failure to ESRD and improves nutritional status among patients with CKD.
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            Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.

            In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.
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              Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR.

              Metabolic acidosis often accompanies low glomerular filtration rate and induces secretion of endothelin, which in turn might mediate kidney injury. Here we tested whether treatment of metabolic acidosis in patients with low glomerular filtration rate reduced the progression of kidney disease. Fifty-nine patients with hypertensive nephropathy and metabolic acidosis had their blood pressure reduced with regimens that included angiotensin-converting enzyme inhibition. Thirty patients were then prescribed sodium citrate, and the remaining 29, unable or unwilling to take sodium citrate, served as controls. All were followed for 24 months with maintenance of their blood pressure reduction. Urine endothelin-1 excretion, a surrogate of kidney endothelin production, and N-acetyl-beta-D-glucosaminidase, a marker of kidney tubulointerstitial injury, were each significantly lower, while the rate of estimated glomerular filtration rate decline was significantly slower. The estimated glomerular filtration rate was statistically higher after 24 months of sodium citrate treatment compared to the control group. Hence it appears that sodium citrate is an effective kidney-protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition.
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                Author and article information

                Contributors
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                Journal
                rmu
                Revista Médica del Uruguay
                Rev. Méd. Urug.
                Sindicato Médico del Uruguay (Montevideo )
                1688-0390
                March 2013
                : 29
                : 1
                : 04-11
                Affiliations
                [1 ] Universidad de la República Uruguay
                [2 ] Comisión Honoraria de Salud Renal Uruguay
                [3 ] Universidad de la República Uruguay
                [4 ] Universidad de la República Uruguay
                [5 ] Universidad de la República Uruguay
                Article
                S1688-03902013000100002
                Product
                Product Information: website
                Categories
                MEDICAL LABORATORY TECHNOLOGY
                MEDICINE, GENERAL & INTERNAL
                MEDICINE, LEGAL
                MEDICINE, RESEARCH & EXPERIMENTAL
                ONCOLOGY
                SURGERY

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