Safety and efficacy of nivolumab therapy in patients with metastatic renal cell carcinoma and impaired kidney function.

INTRODUCTION: Patients with renal insufficiency, usually defined as those with creatinine clearance < 40 mL/min, were excluded from pivotal clinical trials, especially in studies involving nivolumab therapy in patients with renal cell carcinoma (RCC). The aim of the study is to evaluate the efficacy and safety of nivolumab in patients with metastatic RCC (mRCC) stratified according to creatinine clearance. MATERIAL AND METHODS: Data from mRCC patients treated with nivolumab were retrospectively analyzed. Patients were classified into two categories according to their estimated glomerular filtration rate (eGFR); the first category (C1) included patients with eGFR < 40 mL/min/1.73 m2 and the second category (C2) included those with eGFR ≥ 40 mL/min/1.73 m2. RESULTS: Of the 95 patients enrolled, 1. group included 26 patients (27.4%) and 2. group included 69 patients (72.6%). None of the pts in category 1 were on hemodialysis. Overall incidence of adverse events was not statistically different between the two groups (P = .469). The overall response rate ORR was 50% in the first group and 42.0% in the second group (P = .486). Median overall survival (OS) was longer with 23.3 months in the 2. group versus 11 months in the 1. group (P = .415). CONCLUSION: Renal insufficiency is a common problem in patients with advanced renal cancer since they often undergo nephrectomy and their renal function may also worsen while receiving tyrosine kinase inhibitor therapy. We found that there is no significant difference in the safety and efficacy of nivolumab treatment between two groups. Nivolumab appears to be a safe and effective agent in patients with renal impairment.

The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis / Seguridad y eficacia de tolvaptan en el tratamiento de los pacientes con enfermedad renal poliquística autosómica dominante: Revisión sistemática y metaanálisis

Background The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. Methods Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. Result We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=−3.32, 95% CI (−4.57, −2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=−69.99, 95% CI (−91.05, −48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. Conclusions This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions (AU)

Antecedentes La progresión irreversible de la enfermedad renal poliquística autosómica dominante (ERPAD) a enfermedad renal en etapa final (ESRD) es demorada por tolvaptan. Por tanto, nuestro objetivo fue estimar y calcular sistemáticamente la eficacia y seguridad de tolvaptan en el tratamiento de ERPAD. Métodos Dos revisores buscaron de manera independiente todos los estudios publicados sobre ensayos controlados aleatorizados en las bases de datos de PubMed, Embase, Web of Science y Cochrane, extrayendo datos, evaluando el riesgo de sesgo y calificando la calidad de la evidencia. Los datos fueron analizados utilizando el software RevMan. Resultados Identificamos ocho ensayos, que incluyeron 2.135 pacientes. Tanto la reducción de la tasa de filtración glomerular estimada (eGFR) [MD=1,89, IC 95% (0,74, 3,04), p=0,001] como el volumen renal total (VRT) [MD=−3,32, IC 95% (−4,57, −2,07), p<0,001] se demoraron en el grupo tolvaptan, en comparación con el grupo placebo en los pacientes con ERPAD. El uso de tolvaptan demoró la progresión del VRT en los subgrupos de diferentes meses [MD=−69,99, IC 95% (−91,05, −48,94), p<0,001]. Tolvaptan redujo el dolor renal [RR=0,66, IC 95% (0,54, 0,81), p<0,001] y los episodios de hematuria [RR=0,55, IC 95% (0,41, 0,74), p<0,001] en los pacientes con ERPAD. Sin embargo, la prevalencia de episodios de sed [RR=2,75, IC 95% (2,34, 3,24), p<0,001] y nocturia [RR=3,01, IC 95% (1,27, 7,11), p=0,01] se incrementó en el grupo tolvaptan. No existe diferencia significativa en cuanto a episodios de hipertensión [RR=0,92, IC 95% (0,82, 1,03), p=0,13] en el grupo tolvaptan, en comparación con el grupo placebo. Conclusiones Este metaanálisis sugiere que tolvaptan puede mejorar la progresión clínica en los pacientes con ERPAD, sin incrementar significativamente el riesgo de reacciones adversas (AU)

The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis.

BACKGROUND: The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. METHODS: Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. RESULTS: We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=-3.32, 95% CI (-4.57, -2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=-69.99, 95% CI (-91.05, -48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. CONCLUSIONS: This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions.

Primeras recomendaciones de consenso SLANH - COLABIOCLI / Primeiras Recomendações de Consenso SLANH - COLABIOCLI / (Sociedad Latinoamericana de Nefrología e Hipertensión - Confederación Latinoamericana de Bioquímica Clínica) / Informe de la tasa de filtración glomerular estimada junto a la determinación de la creatininemia en población adulta / First SLANH-COLABIOCLI Consensus Recommendations

Resumen La enfermedad renal crónica (ERC) es de alta prevalencia en América Latina y en todo el mundo. Se estima que entre 10 y 20% de la población adulta es portadora de ERC y su prevalencia va en aumento. La ERC progresa en forma silenciosa. Su diagnóstico temprano y oportuno permite iniciar un tratamiento efectivo, en la mayoría de los casos, para detener la enfermedad. Desde hace mucho tiempo, el análisis de la creatininemia es la principal prueba utilizada para valorar la función renal, pero su confiabilidad es limitada. De acuerdo con las recomendaciones de las GUIAS KDOQI del año 2002 la tasa de filtración glomerular estimada (TFGe) obtenida a través de fórmulas, se estableció como una de las herramientas principales para detectar la enfermedad renal de manera precoz, ya que alerta de forma precisa al médico y al equipo de salud sobre el nivel de función renal del paciente. La detección de una TFGe disminuida (menor de 60 mL/min/1,73 m2) es clínicamente relevante, ya que permite establecer el diagnóstico de enfermedad renal en adultos. En el año 2022, en una encuesta realizada por SLANH y COLABIOCLI dirigida a los laboratorios de análisis clínicos de América Latina (n: 237), el 49% de los mismos no informaban la TFGe rutinariamente. En base a esta realidad SLANH y COLABIOCLI elaboraron estas recomendaciones de consenso en referencia al uso de la TFGe.

Abstract Chronic kidney disease (CKD) has a high prevalence worldwide and in Latin America (10 to 20% of the adult population) and is increasing. CKD progresses silently. Opportune diagnosis and treatment are effective in most cases to improve outcomes. Serum creatinine was the main test to assess kidney function, but its reliability is limited. Through the KDOQI Guidelines 2002, the estimated glomerular filtration rate (eGFR) obtained from equations was established as one of the main tools for the early detection of kidney disease in clinical practice. The detection of a decreased eGFR (less than 60 mL/min/1.73 m2) is clinically relevant. This cut-off level establishes the diagnosis of kidney disease in adults. In 2022 SLANH and COLABIOCLI conducted a survey among the clinical laboratories from Latin America. The survey included 237 laboratories, 49% of which did not routinely report the eGFR. Based on this situation, SLANH and COLABIOCLI have elaborated the following consensus recommendations regarding the use of eGFR.

Resumo A doença renal crônica (DRC) é altamente prevalente na América Latina e em todo o mundo. Estima-se que entre 10 e 20% da população adulta seja portadora de DRC e sua prevalência esteja aumentando. A DRC progride silenciosamente. Seu diagnóstico precoce e oportuno permite iniciar um tratamento eficaz, na maioria dos casos, para estancar a doença. Faz muito tempo, a análise da creatinina tem sido o principal teste usado para avaliar a função renal mas sua confiabilidade é limitada. De acordo com as recomendações dos GUIAS KDOQI do ano de 2002, a estimativa da taxa de filtração glomerular (eGFR), obtida por meio de fórmulas, consolidou-se como uma das principais ferramentas para a detecção precoce da doença renal, visto que alerta com precisão ao médico e ao equipe de saúde sobre o nível de função renal do paciente. A detecção de uma eGFR diminuída (inferior a 60 mL/min/1,73 m2) é clinicamente relevante, pois permite estabelecer o diagnóstico de doença renal em adultos. No ano de 2022, em pesquisa realizada pela SLANH e COLABIOCLI dirigida a laboratórios de análises clínicas da América Latina (n: 237), 49% deles não relataram rotineiramente eGFR. Com base nessa realidade, SLANH e COLABIOCLI prepararam essas recomendações de consenso sobre o uso de eGFR.

Consecuencias de la selección inadecuada de la ecuación de estimación de la tasa de filtración glomerular / Consequences of inadequate selection of estimated glomerular filtration rate equation / Consequências da seleção inadequada da equação de estimação da taxa de filtração glomerular

El objetivo del trabajo consistió en evaluar, en una muestra de estudiantes, las consecuencias sobre la Tasa de Filtración Glomerular estimada (TFGe) por MDRD-4, MDRD-4 IDMS y CKD-EPI producidas por la selección inadecuada de las fórmulas según la trazabilidad de la creatininemia utilizada y valorar el efecto sobre la categorización por estadio G de TFG al utilizar valores numéricos de MDRD-4 y MDRD-4 IDMS≥60 mL/min/1,73 m². Se realizó un estudio descriptivo, analítico, de corte transversal con 100 alumnos de bioquímica, que participaron voluntariamente. Se determinó la creatininemia por métodos Jaffé cinéticos, valores trazables y no trazables al Isotopic Dilution Mass Spectroscopy (IDMS). La TFGe se calculó por las fórmulas MDRD-4, MDRD-4 IDMS y CKD-EPI introduciendo en cada fórmula valores de creatinina trazables y no trazables a IDMS. Los estudiantes se clasificaron por categoría G según los resultados. El mal empleo de las ecuaciones respecto a la trazabilidad de la creatininemia según fueron diseñadas cambió sensiblemente los valores de TFGe (p<0,05) y la proporción de jóvenes por estadio G respecto a lo hallado con el empleo adecuado (MDRD-4. G1: 67,4% vs. 53,7%; G2: 32,6% vs. 45,3%; G3a: 0,0% vs. 1,0%. MDRD-4 IDMS. G1: 37,9% vs. 59,0%; G2: 56,8% vs. 40,0%; G3a: 5,3% vs. 1,0%. CKD-EPI. G1: 70,5% vs. 85,3%; G2: 29,5% vs. 14,7%). El uso de valores numéricos para TFGe por MDRD-4 y MDRD-4 IDMS≥60 mL/min/1,73 m² infraestimó lo obtenido con CKD-EPI, que puede informarse numéricamente en ese rango. Ambas situaciones conllevan errores que afectan la categorización funcional renal de pacientes y la prevalencia en estudios epidemiológicos.

The objective of this work was to evaluate the consequences on the estimated Glomerular Filtration Rate (eGFR) by MDRD-4, MDRD-4 IDMS and CKD-EPI produced by the inadequate equation selection according to the creatinine traceability in a sample of biochemistry students and to assess the effect on G categorization if numerical values of the MDRD-4 and MDRD-4 IDMS equations≥60 mL/ min/1.73 m² were used. A descriptive, analytical, cross-sectional study was performed between 2014- 2016, 100 volunteer students of biochemistry were studied. Creatininemia was determined by kinetic Jaffé methods, traceable and non-traceable to Isotopic Dilution Mass Spectroscopy (IDMS). The eGFR was estimated by the MDRD-4, MDRD-4 IDMS and CKD-EPI formula, by feeding each formula with traceable and non traceable creatinine values to IDMS. Students were classified by category G according to the results obtained. Inappropriate equation use regarding the traceability of the creatinine for which they were designed significantly changed eGFR values (p<0.05) and the proportion of young people per G stage compared to what was found with adequate use (MDRD-4. G1: 67.4% vs. 53.7%; G2: 32.6% vs. 45.3%; G3a: 0.0% vs. 1.0%. MDRD-4 IDMS. G1: 37.9% vs. 59.0%; G2: 56.8% vs. 40.0%; G3a: 5.3% vs. 1.0%. CKD-EPI. G1: 70.5% vs. 85.3%; G2: 29.5% vs. 14.7%). The use of numerical values for eGFR by MDRD-4 and MDRD-4 IDMS≥60mL/min/1.73 m² underestimated what was obtained with CKD-EPI, which can be reported numerically in that range. Both situations involve errors that affect patient renal functional categorization and prevalence in epidemiological studies.

Este trabalho teve como objetivo avaliar as consequências sobre a Taxa de Filtração Glomerular estimada (TFGe) por MDRD-4, MDRD-4 IDMS e CKD-EPI produzidas pela seleção inadequada das fórmulas, segundo a rastreabilidade da creatininemia utilizada e o efeito sobre a categorização por estágio G de TFG ao utilizar valores numéricos de MDRD-4 e MDRD-4 IDMS≥60 mL/min/1,73 m². Este é um estudo descritivo, analítico e de corte transversal com 100 alunos de bioquímica, que participaram em forma voluntária. Foi determinada a creatininemia através do métodos Jaffé cinéticos, valores rastreáveis e não rastreáveis ao Isotopic Dilution Mass Spectroscopy (IDMS). A TFGe foi estimada pela fórmula MDRD-4, MDRD-4 IDMS e CKD-EPI introduzindo em cada fórmula valores de creatinina rastreáveis e não rastreáveis a IDMS. Os estudantes foram classificados por categoria G conforme os resultados. Uso indevido das equações a respeito da rastreabilidade da creatinina conforme foram desenhadas, mudou sensivelmente os valores de TFGe (p<0,05) e a proporção de jovens por estágio G em relação ao encontrado com o uso adequado adecuado (MDRD-4. G1: 67,4% vs. 53,7%; G2: 32,6% vs. 45,3%; G3a: 0,0% vs. 1,0%. MDRD-4 IDMS. G1: 37,9% vs. 59,0%; G2: 56,8% vs. 40,0%; G3a: 5,3% vs. 1,0%. CKD-EPI. G1: 70,5% vs. 85,3%; G2: 29,5% vs. 14,7%). Utilizar valores numéricos para TFGe por MDRD-4 e MDRD-4 IDMS≥60mL/min/1,73 m² infraestimou o obtido com CKD-EPI, que pode informar-se numericamente nesse intervalo. Ambas as situações conduzem a erros que afetam a categorização funcional renal de pacientes e a prevalência em estudos epidemiológicos.

Relationship between Early Life Factors and Renal Function in Afro-Caribbean Young Adults: Analysis from the Jamaica 1986 Birth Cohort Study / Relación entre los factores de los primeros años de vida y la función renal en adultos jóvenes afrocaribeños: análisis del Estudio de Cohorte de Nacimientos de Jamaica en 1986

ABSTRACT Objective: To investigate the relationship between intrauterine growth and renal function among Jamaican young adults. Methods: Data from 744 participants from the Jamaica 1986 Birth Cohort Study were analysed. We evaluated the relationship between infant characteristics (birthweight and gestational age), maternal characteristics at child's birth (age and socio-economic status), and renal function at ages 18-20 years (using estimated glomerular filtration rate (eGFR), calculated using the Schwartz-Lyon equation and urine albumin excretion), or prevalent chronic kidney disease (CKD; defined as eGFR < 60 ml/minute/1.73 m2 or urinary albumin ≥ 30 mg/g creatinine). Associations were examined using multi-level mixed effects regression models. Results: The mean eGFR was 86.3 ml/minute/1.73 m2 among males and 102.4 ml/minute/1.73 m2 among females (p < 0.001). The prevalence of CKD was 8.3% (7.4% males, 9.1% females, p = 0.387). Birthweight was not significantly associated with eGFR in unadjusted models, but after adjustment for potential confounders/mediators (gender, blood pressure, body mass index, maternal occupation and education), individuals born with a low birthweight (< 2.5 kg) had a 5.1% lower eGFR compared to those with a normal birthweight (β = −0.052, p = 0.002). Furthermore, a one standard deviation increase in birthweight was associated with a 2.2% increase in eGFR (β = 0.022, p = 0.044). No statistically significant associations were observed between early life factors and urinary albumin or CKD in adjusted models. Conclusion: There was a high prevalence of CKD in this Afro-Caribbean young population. Lower birthweight was associated with reduced renal function in early adulthood, which may result in an increased risk of CKD later on in adulthood. Early life interventions may also be warranted in addressing the CKD epidemic.

RESUMEN Objetivo: Investigar la relación entre el crecimiento intrauterino y la función renal entre los adultos jóvenes jamaicanos. Métodos: Se analizaron los datos de 744 participantes en el Estudio de Cohorte de Nacimientos de Jamaica en 1986. Se evaluó la relación entre las características infantiles (peso al nacer y edad gestacional), las características maternas a la hora del nacimiento del niño (edad y estado socioeconómico), y la función renal a la edad de 18 a 20 años (utilizando la tasa de filtración glomerular estimada (TFGe), calculada usando la ecuación Schwartz-Lyon y la excreción de albúmina urinaria), o la enfermedad renal crónica prevalente (ERC; definida como TFGe < 60 ml/min/1.73 m2 o albúmina urinaria ≥ 30 mg/g creatinina). Las asociaciones se examinaron mediante modelos multinivel de regresión de efectos mixtos. Resultados: El TFGe fue de 86.3 ml/min/1.73 m2 entre los varones y 102.4 ml/min/1.73 m2 entre las mujeres (p < 0.001). La prevalencia de ERC fue 8.3% (7.4% varones, 9.1% hembras, p = 0.387). El peso al nacer no se asoció significativamente con la TFGe en los modelos no ajustados, pero después de ajustar los factores de confusión/mediación potenciales (género, presión sanguínea, índice de masa corporal, ocupación y educación materna), los individuos con bajo peso al nacer (< 2.5 kg) tenían un TFGe 5.1% más bajo en comparación con aquellos con un peso normal al nacer (β = −0.052, p = 0.002). Además, un aumento de la desviación estándar en el peso al nacer estuvo asociado con un aumento de 2.2% en TFGe (β = 0.022, p = 0.044). No se observaron asociaciones estadísticamente significativas entre los factores de los primeros años de vida y la albúmina urinaria o ERC en los modelos ajustados. Conclusión: Hubo una alta prevalencia de ERC en esta población de jóvenes afrocaribeños.Un peso más bajo al nacer estuvo asociado con una reducción de la función renal en la edad adulta temprana, lo que puede llevar a un mayor riesgo de ERC más tarde en la edad adulta. Las intervenciones en los primeros años de vida también pueden explicarse al abordar la epidemia de ERC.

Enfermedad renal crónica determinada mediante la creatinina sérica / Chronic kidney disease as measured by serum creatinine

La enfermedad renal crónica se relaciona con un mayor riesgo de enfermedad renal crónica terminal, de enfermedades cardiovasculares y de muerte, por lo que se requiere sudiagnóstico desde las primeras etapas de la enfermedad. Para ello, se disponen de un gran número de ecuaciones para estimar la tasa de filtración glomerular basadas en la concentración de creatinina sérica. Si bien la creatinina no es el analito ideal para estimar la filtración glomerular, ésta continuará empleándose hasta que haya una amplia disponibilidad en el medio de otros marcadores, como la cistatina C, por lo que el laboratorio clínico debe velar por la calidad analíticade los resultados y por lo tanto, debe determinar la creatinina a través de un método estandarizado frente a los procedimientos de medida de referencia. El objetivo de este módulo es revisar ladetección de la enfermedad renal crónica desde sus etapas iniciales, a partir de la creatinina sérica y de la estimación de la tasa de filtración glomerular.

Chronic kidney disease is associated with an increased risk of end-stage renal disease,cardiovascular diseases and death; hence, it is necessary to make a diagnosis in the early phasesof the disease. Many equations for estimating glomerular filtration rates are available for thispurpose, and are based on serum creatinine concentration. Although creatinine is not the idealanalyte to gauge glomerular filtration rate, it will be used until there is extensive availability of othermarkers, such as cystatin C. On these grounds, clinical laboratories must offer results with highstandards of quality control, and accordingly, they must measure serum creatinine with suitablemethods, previously standardized by reference measurement procedures. The aim of this moduleis to assess early diagnosis of chronic kidney disease through serum creatinine quantification andglomerular filtration rate estimation.