Prognostic Value of Isolated High Serum Cystatin C Levels Without Glomerular Filtration Rate Reduction. / Valor pronóstico de la elevación aislada de los niveles de cistatina C sin reducción del filtrado glomerular.

OBJECTIVES: Cystatin C is increasingly used as a marker of renal function as a complement to serum creatinine and glomerular filtration rate (GFR). We have assessed its efficacy as a predictor of mortality in a group of patients with increased cystatin C but GFR> 60mL/min. DESIGN AND METHODS: We included 608 patients, 65.9% male, 34.6% had diabetes mellitus. The mean age was 58.5±14.5 years and a mean GFR of 64.1±33.5mL/min. Patients were divided into 3 groups: CONTROL (normal cystatin C and GFR> 60mL/min, age 53.3±12.8years, GFR 96.6±22.4mL/min,n=193), INCREASED CYSTATIN (cystatin C>1.03mg/l and GFR>60mL/min, age 58.9±13,1years, GFR 72.2±10.4mL/min, n=40) and CKD (chronic kidney disease, increased cystatin C and GFR <60mL/min, age 61.4±14.8years, GFR 36.0±12.7mL/min, n=160). The relationship with overall mortality was analyzed using the Kaplan-Meier method. RESULTS: Mean cystatin C was 0.75±0.13 versus 1.79±0.54 in CKD group and 1.14±0.14mg/l, p <0.001). In CONTROL group survival was 93.9% at 5y, compared to 78.8% in the ERC group and 82.3% in the INCREASED CYSTATIN group (p <0.001) Five-year survival before renal replacement therapy was also different for the ERC group (73%, p <0.001 Log Rank) but not between the other two groups (CONTROL 99.0%, INCREASED CYSTATIN 94.3% p=0.08). CONCLUSIONS: Increased plasmatic levels of cystatin C in patients with GFR> 60mL/min was a predictor of increased mortality but not of progression to end-stage renal failure. These results confirm the interest of routinely measuring cystatin C.

Antiretroviral Treatment and Antihypertensive Therapy.

The presence of hypertension among the population with human immunodeficiency virus (HIV) has become a new threat to the health and well-being of people living with this disease, in particular, among those who received antiretroviral therapy. The estimated prevalence of high blood pressure in HIV-infected patients is significantly higher than the rate observed in HIV-uninfected subjects. The approach to the HIV-positive patient requires the assessment of individual cardiovascular risk and its consideration when designing the individualized target. On the other hand, the numerous pharmacological interactions of antiretroviral (ARV) drugs are essential elements to take into account. Serum levels of any kind of antihypertensive drugs may be influenced by the coadministration of protease inhibitors, non-nucleoside reverse transcriptase inhibitor, or other antiretroviral. Similarly, plasma concentrations of antiretroviral drugs can be increased by the concomitant use of calcium channel blockers or diuretics. In this regard, the treatment of high blood pressure in HIV patients should be preferentially based on ACE inhibitors or thiazide/thiazide-like diuretics or their combination.

Alfa-1-microglobulina: valor pronóstico en la enfermedad renal crónica / Alpha-1-microglobulin: Prognostic value in chronic kidney disease

Objetivos: La alfa-1-microglobulina (α1M) es una proteína tubular usada para detectar lesiones agudas del túbulo proximal. Se ha evaluado el uso de α1M como marcador de progresión de la enfermedad renal crónica (ERC) y de supervivencia vital.Diseño y métodosSe seleccionaron 163 pacientes (90 hombres), con una edad media de 61,6±16,4 años. La excreción de α1M en orina se analizó por nefelometría. Los pacientes se dividieron en 2 grupos según la excreción de α1M (valor de corte: 32,85mg/24h).ResultadosLa supervivencia libre de ERC terminal fue del 94,2% a los 5 años en pacientes con α1M baja. Para pacientes con una excreción más elevada la supervivencia fue del 72,7% (p=0,011). La supervivencia fue del 94,4% en pacientes con α1M baja; para los pacientes con una excreción elevada de α1M, la supervivencia fue del 54,2% (p=0,001). La regresión de Cox mostró una asociación independiente de la α1M con la progresión de la ERC.ConclusionesLa excreción urinaria de α1M se asoció con una progresión más rápida de la ERC y una mayor mortalidad. Serán precisos estudios más amplios para confirmar la relación causal entre α1M y mortalidad general. (AU)

Objectives: α1-microglobulin (α1M) is a tubular protein used for detecting acute lesions of proximal tubules. This study evaluated the use of urine α1M excretion as a marker of chronic kidney disease (CKD) progression and life survival.Design and methodsIn all 163 patients were recruited (90 men), mean age 61.6±16.4 years. Urinary α1M was evaluated using an immunonephelometric assay. Patients were divided into 2 groups according to urinary α1M excretion (cut-off value: 32.85mg/24h).ResultsEnd stage renal disease-free survival was 94.2% at 5 years for patients with lower α1M. For patients in the highest percentile, renal function survival was 72.7% (P=.011). Life survival was 94.4% for patients with α1M in the lower percentiles. For patients in the upper percentile, live survival was 54.2% (P=.001). The Cox regression analysis showed an independent association of CKD progression with high α1M excretion (P=.043).Conclusionsα1M urinary excretion was associated with faster CKD progression and higher mortality. Further studies are needed to determine whether the association between α1M urinary excretion and excess mortality risk represents a causal link. (AU)

Alpha-1-microglobulin: Prognostic value in chronic kidney disease. / Alfa-1-microglobulina: valor pronóstico en la enfermedad renal crónica.

OBJECTIVES: α1-microglobulin (α1M) is a tubular protein used for detecting acute lesions of proximal tubules. This study evaluated the use of urine α1M excretion as a marker of chronic kidney disease (CKD) progression and life survival. DESIGN AND METHODS: In all 163 patients were recruited (90 men), mean age 61.6±16.4 years. Urinary α1M was evaluated using an immunonephelometric assay. Patients were divided into 2 groups according to urinary α1M excretion (cut-off value: 32.85mg/24h). RESULTS: End stage renal disease-free survival was 94.2% at 5 years for patients with lower α1M. For patients in the highest percentile, renal function survival was 72.7% (P=.011). Life survival was 94.4% for patients with α1M in the lower percentiles. For patients in the upper percentile, live survival was 54.2% (P=.001). The Cox regression analysis showed an independent association of CKD progression with high α1M excretion (P=.043). CONCLUSIONS: α1M urinary excretion was associated with faster CKD progression and higher mortality. Further studies are needed to determine whether the association between α1M urinary excretion and excess mortality risk represents a causal link.

Sacubitril-Valsartan Improves Anemia of Cardiorenal Syndrome (CRS).

BACKGROUND AND AIMS: Anemia is a common complication of heart failure and Chronic Kidney Disease (CKD). Sacubitril-valsartan is a novel therapy for the treatment of chronic Heart Failure with a reduced Ejection Fraction (HFrEF). We have evaluated the short-term effects of sacubitril- valsartan on the anemia of CRS. METHODS: The study group comprised 39 patients with HFrEF, who were followed-up for three months. The study is a retrospective analysis of clinical data. Data of 3 months' and baseline visits were recorded including plasmatic creatinine, glomerular filtration rate, cystatin C, kaliemia, haemoglobin, pro-BNP, and albuminuria. RESULTS: In all, 34 patients ended the follow-up. Mean sacubitril-valsartan dosage at baseline was 101 ± 62 mg/day and 126 ± 59 mg/day at end. Mean hemoglobin increased from 12.2 ± 1.1 g/dl at baseline to 12.9 ± 1.0 g/dl (p = 0.001,). Prevalence of anemia was 64.7% (95%CI, 47.9-78.5%) at baseline and 38.4 (95%CI, 23.9-55.0%) after the follow-up (p = 0.016). Serum cystatin C levels decreased from 2.71 ± 1.0 to 2.48 ± 1.0 mg/l (p = 0.028). Serum K levels remained unchanged (baseline 4.94 ± 0.60, three months visit 4.94 ± 0.61 mmol/l, p = 0.998). CONCLUSION: Sacubitril-valsartan improves anemia in CRS patients. An improvement in serum cystatin levels was observed. Few untoward effects were detected. These findings should be confirmed in wider clinical trials.

Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada / Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease

INTRODUCCIÓN: La acidosis metabólica (AM) es una alteración frecuente en la enfermedad renal crónica (ERC) que se asocia a numerosas complicaciones, por lo que su corrección es recomendable. El bicarbonato sódico oral es actualmente el tratamiento de elección. OBJETIVOS: Describir la prevalencia de AM en la ERC avanzada, y determinar cuáles son las características clínicas y bioquímicas que se asocian a una corrección adecuada. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadio 4-5. Los criterios de inclusión fueron: no estar siendo tratado con alcalinos en el momento de la inclusión y tener al menos 3 medidas consecutivas de filtrado glomerular (FG) y parámetros bioquímicos durante un periodo > 3 meses. Los pacientes con un bicarbonato sérico < 22 mEq/l se incluyeron en el estudio de seguimiento, siendo tratados con bicarbonato sódico oral. Se consideró que la corrección fue adecuada cuando más de la mitad de las muestras y la media de los niveles de bicarbonato durante el seguimiento individual fueron ≥ 22 mEq/l. RESULTADOS: Se incluyeron 969 pacientes (edad 65± 14 años, 507 hombres) con FG medio 14,8± 4,5 ml/min/1,73 m2. Basalmente 530 pacientes (55%) que mostraron un bicarbonato sérico < 22 mEq/l fueron tratados con bicarbonato sódico y seguidos durante 15 meses. En tan solo 133 pacientes (25%) se alcanzó una corrección satisfactoria de la AM. Por regresión logística multivariable las principales características en los que se logró el control adecuado de la AM fueron: edad (OR = 1,03; IC. 95%1,01-1,05), FG basal (OR = 1,07; 1,02-1,12) y tratamiento con inhibidores de bomba protones (OR = 1,61; IC 95%: 1,06-2,44). En aquellos en los que se logró corrección de AM tuvieron progresión más lenta de ERC (-1,67± 3,71 vs. -4,36± 4,56 ml/min/1,73 m2/año, p < 0,0001) y menor concentración de potasio sérico promedio (5,1± 0,5 vs. 5,3± 0,5, p < 0,0001) que los del resto de pacientes, aunque no se observaron diferencias en la tasa de ingresos hospitalarios y ni en la mortalidad. CONCLUSIÓN: La AM es una alteración frecuente en la ERC avanzada, pero de difícil corrección con los tratamientos actuales. Debido al importante beneficio que puede suponer el control de la AM se deberían investigar nuevas terapias más efectivas

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate < 22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were ≥ 22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8 ± 4.5 ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate < 22 mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR = 1.03; 95% CI 1.01 - 1.05), baseline GFR (OR = 1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR = 1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67 ± 3.71 vs -4.36 ± 4.56 ml/min/1.73 m2/year, P < .0001), and lower average serum potassium concentration (5.1 ± 0.5 vs 5.3 ± 0.5, P < .0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched

Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia / Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia

INTRODUCCIÓN: La hipercaliemia (HK) es un hallazgo frecuente en la enfermedad renal crónica (ERC), sobre todo en sus estadios más avanzados. El mecanismo patogénico más común de esta alteración es la ingesta-absorción de potasio que sobrepasa la capacidad excretora renal. La investigación sobre el papel relativo de cada uno de los elementos patogénicos en el desarrollo de HK podría ayudar a su tratamiento. OBJETIVO: Analizar el manejo renal de potasio en pacientes con ERC avanzada prediálisis, y establecer qué diferencias existen entre los que presentan o no HK. MATERIAL Y MÉTODOS: Estudio transversal de observación en pacientes adultos con ERC estadio 4-5 prediálisis. Entre los pacientes incidentes en la consulta ERCA se seleccionaron aquellos clínicamente estables con capacidad para recoger adecuadamente la orina de 24horas. Se midieron parámetros bioquímicos en sangre y orina que incluyeron las concentraciones de sodio y potasio (K). Se calculó la fracción de excreción de K (FEK) y la carga de K relativa al filtrado glomerular (Ko/FG). Se definió la HK como una concentración de K sérico ≥ 5,5 mmol/l. RESULTADOS: Se incluyeron 212 pacientes (edad 65 ± 14 años, 92 mujeres) con un FG 15,0 ± 4,2 ml/min/1,73 m2. Sesenta y tres pacientes (30%) presentaban HK. Los pacientes con HK tenían un bicarbonato sérico más bajo (20,3 ± 3,1 vs. 22,8 ± 3,2 mEq/l, p < 0,0001), y un menor filtrado glomerular (14,1 ± 3,3 vs. 15,4 ± 4,4 ml/min/1,73 m2, p = 0,028), pero no mostraban diferencias en la excreción urinaria total de sodio o K. La FEK era inferior en los pacientes con HK con respecto a los que presentaban normocaliemia (32,1 ± 12,1% vs. 36,4 ± 14,3%, p = 0,038), mientras que la Ko/FG fue mayor (4,2 ± 1,5 vs. 3,7 ± 1,4 mmol por cada ml/min, p = 0,049). Existía una fuerte correlación lineal entre Ko/FG y FEK (R2 = 0,74), y en regresiones parciales se observó que a igual carga de K, la FEK era inferior en los pacientes con HK. Mediante regresión lineal y regresión logística multivariable, tanto la FEK como la Ko/FG fueron los principales determinantes del K sérico y de la HK. CONCLUSIONES: Aunque la carga de K relativa a la función renal (Ko/FG) se asocia de forma relevante a la HK de la ERC, la principal característica asociada a esta alteración bioquímica es la incompleta excreción renal compensatoria de K, expresada como una menor FEK

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24 hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥ 5.5 mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65 ± 14 years, 92 females) with a mean GFR of 15.0 ± 4.2 ml/min/1.73 m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3 ± 3.1 vs. 22.8 ± 3.2 mEq/l, P < .0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1 ± 12.1% vs. 36.4 ± 14.3%, P = .038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2 ± 1.5 vs. 3.7 ± 1.4 mmol/ml/min, P = 0,049). FEK showed a strong linear correlation with Ku/GFR (R2 = 0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK

Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis? / Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?

INTRODUCCIÓN: El efecto renoprotector de los fármacos inhibidores del sistema renina-angiotensina (ISRA) ha sido cuestionado en la enfermedad renal crónica (ERC) avanzada. La combinación de tratamiento ISRA (doble bloqueo) puede, además, acelerar el deterioro de la función renal en algunas poblaciones de riesgo. Sin embargo, se desconoce si este efecto adverso está relacionado con la dosis total prescrita de ISRA o más específicamente con una interacción farmacológica. OBJETIVO: Investigar si la tasa de reducción de función renal en la ERC avanzada se asocia a la dosis total de ISRA, y si el doble bloqueo SRA deteriora la función renal independientemente de los principales factores de confusión. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadios 4-5 prediálisis, tratados con ISRA desde al menos 3 meses antes de la inclusión en el estudio. Otros criterios de inclusión fueron: tener al menos 3 medidas consecutivas de filtrado glomerular durante un periodo superior a 3 meses. Las dosis equipotentes de ISRA fueron normalizadas (DEN-ISRA) a un peso corporal de 70 kg o a una superficie corporal de 1,73 m2. La asociación de DEN-ISRA o doble bloqueo con la progresión de ERC fue analizada mediante modelos de regresión lineal uni- y multivariante, tomando en cuenta las principales variables de confusión. RESULTADOS: Se incluyeron 813 pacientes (edad media: 64 ± 14 años; 430 hombres) con un filtrado glomerular medio de 14,9 ± 4,2 ml/min/1,73 m2; 729 pacientes eran tratados con ISRA monoterapia y 84 pacientes con doble bloqueo. La mediana de la DEN-ISRA en el grupo total de estudio fue de 0,91 (rangos IQ: 0,69-1,20). Los pacientes con doble bloqueo tenían una DEN-ISRA significativamente mayor que el resto (1,52 ± 0,49 vs. 0,93 ± 0,44; p < 0,0001). Mediante regresión lineal univariable, DEN-ISRA se correlacionó significativamente con la tasa de progresión de la ERC (R = -0,149; p < 0,0001). Los pacientes con doble bloqueo mostraron un deterioro más acelerado de la función renal que el resto (-6,19 ± 5,57 vs. -3,04 ± 5,37 ml/min/1,73 m2/año, p < 0,0001). Mediante regresión lineal multivariante, el tratamiento con doble bloqueo SRA mantuvo la asociación significativa e independiente con el deterioro de la función renal (beta = -0,094; p = 0,005), mientras que la DEN-ISRA no alcanzó significación estadística. CONCLUSIÓN: La DEN-ISRA se asocia de forma significativa con la tasa de progresión en pacientes con ERC avanzada. Sin embargo, el efecto negativo del doble bloqueo SRA sobre la progresión de la ERC parece independiente de la DEN-ISRA y de otros factores relevantes de confusión

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period > 3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70 kg or a body surface area of 1.73 m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64 ± 14 years, 430 males) with a mean eGFR 14.9 ± 4.2 ml/min/1.73 m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52 ± 0.49 vs. 0.93 ± 0.44; p < 0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R = -0.149; p < 0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19 ± 5.57 vs. -3.04 ± 5.37 ml/min/1.73 m2/year, p < 0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta = -0.094; p = 0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors

Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment? / Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis?

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70kg or a body surface area of 1.73m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64±14 years, 430 males) with a mean eGFR 14.9±4.2ml/min/1.73m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52±0.49 vs. 0.93±0.44; p<0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R=-0.149; p<0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19±5.57 vs. -3.04±5.37ml/min/1.73m2/year, p<0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta=-0.094; p=0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors.

Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease. / Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada.

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate<22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were≥22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8±4.5ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate<22mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR=1.03; 95% CI 1.01 - 1.05), baseline GFR (OR=1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR=1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67±3.71 vs -4.36±4.56ml/min/1.73 m2/year, P<.0001), and lower average serum potassium concentration (5.1±0.5 vs 5.3±0.5, P<.0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched.

Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia. / Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia.

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥5.5mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65±14 years, 92 females) with a mean GFR of 15.0±4.2ml/min/1.73m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3±3.1 vs. 22.8±3.2 mEq/l, P<.0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1±12.1% vs. 36.4±14.3%, P=.038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2±1.5 vs. 3.7±1.4 mmol/ml/min, P=0,049). FEK showed a strong linear correlation with Ku/GFR (R2=0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK.

Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada / Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease

INTRODUCCIÓN: Los pacientes con enfermedad renal crónica (ERC) tienen un alto riesgo de desarrollo de hiperkaliemia (HK). La relación entre HK y una mala evolución (mortalidad o progresión de la insuficiencia renal) en la ERC avanzada es controvertida. OBJETIVOS: Determinar la incidencia, prevalencia, y factores relacionados con la HK en una cohorte de pacientes con ERC, y su relación con la mortalidad, tasa de hospitalización, progresión de la ERC, y necesidad de inicio de diálisis. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadio 4-5. Los criterios de inclusión fueron: tener al menos 3 medidas consecutivas de filtrado glomerular (FG) durante un periodo superior a 3 meses. HK se definió como un K sérico ≥ 5,5 mmol/l. La asociación entre HK y las variables de evolución fue ajustada a los principales factores de confusión mediante análisis mutivariantes. RESULTADOS: Se incluyeron 1079 pacientes (574 hombres, edad media: 65 ± 14 años) con un FG basal 14,8 ± 4,5 ml/min/1,73 m2. El tiempo medio de seguimiento fue de 15 meses y se determinaron una mediana de 7 muestras por paciente. Basalmente un 26% de pacientes tenía HK, un 68% en al menos una muestra durante el periodo individual de seguimiento, y un 33% de forma crónica (HK > 50% del seguimiento individual). Mediante regresión logística multivariable los mejores determinantes de la HK fueron: sexo masculino (OR = 1,529; IC 95% [1,154-2,025], p = 0,003), bicarbonato sérico (OR = 0,863, [0,829-0,900], p < 0,0001), tratamiento diurético (OR = 0,743, [0,556-0,992], p = 0,044), y tratamiento con inhibidores del sistema renina-angiotensina (OR = 4,412, [2,915-6,678], p < 0,0001). Estos pacientes con HK mostraron una progresión de la ERC significativamente más acelerada (−4,05 ± 5,22 vs. −2,69 ± 5,61 ml/min/1,73 m2/año, p < 0,0001), e inicio más frecuente de diálisis (63% vs. 57%, p = 0,115), pero menos mortalidad (9% vs. 17%, p = 0,003), y tasa de hospitalización (2,68 ± 5,94 vs. 3,16 ± 6,77 días/año, p = 0,301) que el resto de los pacientes estudiados. Sin embargo en el análisis multivariante, HK no se asoció de forma independiente con ninguna de las variables de evolución investigadas. CONCLUSIÓN: HK es un hallazgo bioquímico muy frecuente en la ERC avanzada, que se asocia con algunos medicamentos de uso habitual. Sin embargo, HK no se asocia de forma independiente con ninguna de las variables de mala evolución clínica estudiadas

INTRODUCTION: Patients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AIMS: To determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. MATERIAL AND METHODS: A retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period > 3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥ 5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. RESULTS: The study group consisted of 1079 patients (574 males, mean age: 65 ±14 years) with mean baseline eGFR 14.8 ± 4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (-4.05±5.22 vs. -2.69 ± 5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68 ± 5.94 vs. 3.16 ± 6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. CONCLUSION: HK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes

Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease. / Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada.

INTRODUCTION: Patients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AIMS: To determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. MATERIAL AND METHODS: A retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. RESULTS: The study group consisted of 1079 patients (574 males, mean age: 65±14 years) with mean baseline eGFR 14.8±4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (-4.05±5.22 vs. -2.69±5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68±5.94 vs. 3.16±6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. CONCLUSION: HK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes.