Safety and Tolerability of Tolvaptan in an Autosomal Dominant Polycystic Kidney Disease Spanish Cohort: A Real-World Experience.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited disorder of the kidneys. A vasopressin V2-receptor antagonist (tolvaptan) was recently approved for the treatment of ADPKD. This study aims to analyze the safety and tolerability of tolvaptan for the management of ADPKD patients in a real-world setting. METHODS: We conducted a descriptive retrospective study in ADPKD patients in an outpatient clinic setting in Spain from 2018 to 2019. Descriptive statistical analysis of demographics and clinical data, at baseline and one year after tolvaptan initiation, was assessed. Data are presented as median and interquartile range, and as frequencies for categorical variables. RESULTS: Ten patients with ADPKD were identified. At baseline median age was 49.5 (38.5-63.5) years and 60% were males. During treatment with tolvaptan, no significant aquaresis-related symptoms or hepatotoxicity were described. No serious adverse events, discontinuation, or deaths were reported during the study. CONCLUSION: Tolvaptan was well-tolerated without severe adverse events in patients with ADPKD who showed rapid disease progression criteria. Longer follow-up is required to learn about the long-term effects of this treatment.

Initiating renal replacement therapy through incremental haemodialysis: Protocol for a randomized multicentre clinical trial.

BACKGROUND: Thrice-weekly haemodialysis is the usual dose when starting renal replacement therapy; however, this schedule is no longer appropriate since it does not consider residual renal function. Several reports have suggested the potential benefit of beginning haemodialysis less frequently and incrementally increasing the dose as the residual renal function decreases. However, all the data published so far are from observational studies. Thus, this clinical trial avoids any potential selection bias and will assess the possible benefits that have been observed in observational studies. METHODS/DESIGN: This report describes the study protocol of a randomized prospective multi-centre open-label clinical trial to evaluate whether starting renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than the standard thrice-weekly regimen. We also explore other clinical parameters, such as concentrations of uremic toxins, dialysis doses, control of anaemia, removal of medium-weight uremic toxins, nutritional status, quality of life, hospital admissions and mortality. Only incident haemodialysis patients who can maintain a urea clearance rate KrU ≥ 2.5 mL/min/1.73 m2 are eligible. Patient recruitment began on 1 January 2017 and will last for 2 years or until the required sample size has been recruited to ensure the established statistical power has been reached. The minimum follow-up period will be 1 year. Anuric patients with acute renal failure and patients who return to haemodialysis after a kidney transplant failure are excluded. It has been calculated that 44 patients should be recruited into each group to achieve a power of 80% in a two-sided comparison of means with a usual significance level of 0.05. A time-to-event analysis will estimate the probability of kidney function survival in both groups using the Kaplan-Meier method. Survival curves will be compared with log-rank tests. This survival analysis will be complemented with a proportional hazard model to estimate the hazard ratio of kidney function survival adjusted for any confounding factors. Analyses will be carried out in accordance with the intention-to-treat principle. DISCUSSION: The incremental initiation of dialysis may preserve residual renal function better than the conventional treatment, with similar or higher survival rates, as reported by observational studies. To our knowledge, this is the first clinical trial to evaluate whether initiating renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than beginning with the standard thrice-weekly regimen. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03302546. Registered on 5 October 2017.

Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis.

The role of steroid treatment in drug-induced acute interstitial nephritis (DI-AIN) is controversial. We performed a multicenter retrospective study to determine the influence of steroids in 61 patients with biopsy-proven DI-AIN, 52 of whom were treated with steroids. The responsible drugs were antibiotics (56%), non-steroidal anti-inflammatory drugs (37%) or other drugs. The final serum creatinine was significantly lower in treated patients while almost half of untreated patients remained on chronic dialysis. Among treated patients, over half showed a complete recovery of baseline renal function, whereas the rest remained in renal failure. There were no significant initial differences between these two subgroups in terms of duration or dosage of steroids. After withdrawal of the presumed causative drug, we found that when steroid treatment was delayed (by an average of 34 days) renal function did not return to baseline levels compared to those who received steroid treatment within the first 2 weeks after withdrawal of the offending agent. We found a significant correlation between the delay in steroid treatment and the final serum creatinine. Renal biopsies, including three patients who underwent a second biopsy, showed a progression of interstitial fibrosis related to the delay in steroid treatment. Our study shows that steroids should be started promptly after diagnosis of DI-AIN to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function.

[Differences in the synthesis pattern of vasoactive factors in gestational hypertension and preeclampsia]. / Diferencias en el patrón de síntesis de factores vasoactivos en la hipertensión gestacional y en la preeclampsia.

BACKGROUND AND OBJECTIVE: The gestational hypertension -HG- and preeclampsia -P- are hypertensive diseases whose pathogenic mechanism has not been determined yet. The aim of this work is to define some patterns of vasoactive factors release that allow to explain the origin of the differences between both entities. DESIGN: Prospective case-control study. MATERIAL AND METHODS: Two groups of target patients were consecutively selected, GH (n=21) and P patients (n=21). Every patient was matched with a pregnant of similar age and week of pregnancy. Two control groups were obtained, one respect to the GH and another one respect to the P group. A biochemistry, blood cell count, coagulation and quantification of vasoactive factors endothelin, nitrites and GMPc were performed in every woman. Results of GH and P groups were compared with their respective control group with the paired Student's t Test. RESULTS: Both systolic and diastolic arterial pressures were higher in hypertensive pregnants (GH and P) than in their respective controls. Moreover, blood endothelin and GMPc were higher in GH and P. GH pregnants showed decreased norepinephrine and increased epinephrine urinary excretion , as well as an increased plasma nitrites concentration than control group. P patients did not show statistically significant differences in catecholamines urinary excretion nor in plasma nitrites concentration respect their control group. CONCLUSION: There are relevant differences in the synthesis patterns of vasoactive factors between gestational hypertension and preeclampsia. These differences could account for a decreased tissue perfusion in preeclampsia and could also contribute to the genesis of the renal dysfunction of this entity.

Diferencias en el patrón de síntesis de factores vasoactivos en la hipertensión gestacional y en la preeclampsia / Differences in the synthesis pattern of vasoactive factors in gestational hypertension and preeclampsia

Introducción y objetivos: La Hipertensión gestacional -HG-y la preeclampsia -P- son estados hipertensivos del embarazo cuyo mecanismo patogénico no se conoce. Este estudio pretende definir patrones de comportamiento que expliquen el origen de las diferencias entre embarazadas hipertensas y con preeclampsia mediante el análisis de determinados factores vasoactivos. Diseño del estudio: Estudio caso-control basado en casos incidentes. Material y métodos: Se seleccionaron de forma consecutiva dos grupos de pacientes, HG (n = 21) y P (n = 21). Por cada paciente problema se incluyó una gestante normal de similar edad y semana de gestación. Se obtuvieron dos grupos control, uno con respecto al grupo de pacientes HG y otro en relación a las pacientes P. A cada mujer se le realizó estudio de bioquímica, hemograma, coagulación, y cuantificación de los factores vasoactivos endotelina, nitritos y GMPc, así como la excreción urinaria de adrenalina y noradrenalina. Se compararon los resultados de cada grupo de pacientes (HG y P) con su respectivo grupo control. Resultados: La tensión arterial sistólica y diastólica fueron superiores en las pacientes con hipertensión (HG y P) en comparación con sus controles. Igualmente, en las pacientes con HG y en las P se observó un aumento de las concentraciones plasmáticas de endotelina y GMPc. Las pacientes con HG mostraron una eliminación urinaria disminuida de noradrenalina e incrementada de adrenalina, así como una mayor concentración plasmática de nitritos que su grupo control. En las pacientes con P no se observaron diferencias estadísticamente significativas en la eliminación urinaria de catecolaminas ni en la concentración de nitritos en relación con sus controles. Conclusiones: Existen diferencias relevantes en el patrón de síntesis de mediadores vasoactivos en la HG y la P. Estas diferencias condicionarían una perfusión tisular disminuida en la preeclampsia y podrían contribuir a la génesis de las alteraciones renales de este proceso

Background and objetive: The gestational hypertension -HG- and preeclampsia -P- are hypertensive diseases whose pathogenic mechanism has not been determined yet. The aim of this work is to define some patterns of vasoactive factors release that allow to explain the origin of the differences between both entities. Design: Prospective case-control study. Material and methods: Two groups of target patients were consecutively selected, GH (n = 21) and P patients (n = 21). Every patient was matched with a pregnant of similar age and week of pregnancy. Two control groups were obtained, one respect to the GH and another one respect to the P group. A biochemistry, blood cell count, coagulation and quantification of vasoactive factors endothelin, nitrites and GMPc were performed in every woman. Results of GH and P groups were compared with their respective control group with the paired Student’s t Test. Results: Both systolic and diastolic arterial pressures were higher in hypertensive pregnants (GH and P) than in their respective controls. Moreover, blood endothelin and GMPc were higher in GH and P. GH pregnants showed decreased norepinephrine and increased epinephrine urinary excretion, as well as an increased plasma nitrites concentration than control group. P patients did not show statistically significant differences in catecholamines urinary excretion nor in plasma nitrites concentration respect their control group. Conclusion: There are relevant differences in the synthesis patterns of vasoactive factors between gestational hypertension and preeclampsia. These differences could account for a decreased tissue perfusion in preecalmpsia and could also contribute to the genesis of the renal dysfunction of this entity

[Renal aging]. / Envejecimiento renal.

Frequently underestimated, the deterioration of the renal function characteristic of the aging has very prominent clinical consequences. In the present article some aspects of the cellular and molecular biology of this process are analysed. The critical role of the oxidative stress and of TGFbeta are underlined. Determinant genetic factors are also mentioned. Such a knowledge can contribute to develop therapeutical strategies to prevent the decline of the.renal function that happens with the aging.

Envejecimiento renal / Renal aging

Frecuentemente infraestimado, el deterioro de la función renal característico delenvejecimiento tiene consecuencias clínicas muy relevantes. En el presente artículose analizan algunos aspectos de la biología celular y molecular de este proceso,subrayándose el papel crítico del stress oxidativo y del TGF ��, así como tambiénprobablemente de condicionantes genéticos. Estos conocimientos pueden contribuira desarrollar estrategias terapéuticas útiles para prevenir el declinar de la funciónrenal que acontece con el envejecimiento

Frequently underestimated, the deterioration of the renal function characteristicof the aging has very prominent clinical consequences. In the present article someaspects of the cellular and molecular biology of this process are analysed. The criticalrole of the oxidative stress and of TGF �� are underlined. Determinant geneticfactors are also mentioned. Such a knowledge can contribute to develop therapeuticalstrategies to prevent the decline of the renal function that happens withthe aging