RESUMEN
BACKGROUND: The sodium-glucose cotransporter type 2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease, with and without type 2 diabetes. Whether its effects are uniform across the spectrum of age and among men and women is unknown. OBJECTIVE: We performed a pre-specified analysis in DAPA-CKD to evaluate efficacy and safety of dapagliflozin according to baseline age and sex. DESIGN: Prospective randomized placebo-controlled trial. PARTICIPANTS: A total of 4304 adults with chronic kidney disease (estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio 200-5000 mg/g) with and without type 2 diabetes. INTERVENTION: Dapagliflozin 10 mg versus placebo once daily. MAIN MEASURES: Primary endpoint was a composite of ≥ 50% sustained eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included kidney composite endpoint (same as primary composite endpoint but without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. KEY RESULTS: Median follow-up was 2.4 years. Absolute risks of cardiovascular composite endpoint and all-cause mortality were higher in older patients. Absolute risk of kidney composite endpoint was highest in patients < 50 years (10.7 and 6.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively) and lowest in patients ≥ 80 years (3.0 and 1.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively). There was no evidence of heterogeneity of the effects of dapagliflozin on the primary or secondary endpoints based on age or sex. Neither age nor sex modified the effects of dapagliflozin on total or chronic eGFR slope. CONCLUSIONS: Dapagliflozin reduced the risks of mortality, cardiovascular events, and CKD progression in older patients, including in septuagenarians and octogenarians who comprised 25% of participants. Ageism and/or therapeutic nihilism should not discourage the use of dapagliflozin in older women and men who are likely to experience considerable benefit. TRIAL REGISTRY: clinicaltrials.gov NIH TRIAL REGISTRY NUMBER: NCT03036150.
Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Glucósidos/uso terapéutico , Glucósidos/efectos adversos , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Masculino , Femenino , Insuficiencia Renal Crónica/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Factores de Edad , Factores Sexuales , Tasa de Filtración Glomerular/efectos de los fármacos , Adulto , Método Doble Ciego , Resultado del Tratamiento , Estudios de Seguimiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).
Asunto(s)
COVID-19 , Colecalciferol , Método Doble Ciego , Hospitalización , Hospitales , Humanos , SARS-CoV-2 , Resultado del Tratamiento , Vitamina DRESUMEN
BACKGROUND: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. METHODS: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). RESULTS: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). CONCLUSIONS: Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/tratamiento farmacológico , Glucósidos/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/patología , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , PronósticoRESUMEN
End-stage kidney disease (ESKD) represents a major challenge for Latin America (LA). The Latin American Dialysis and Renal Transplantation Registry (LADRTR) has published several reports, and its continuity has implied a sustained effort of the nephrology community to improve care of ESKD in the region; this paper summarizes results of the year 2014. Methods have been reported previously; participant countries complete annual surveys collecting data on incident and prevalent patients undergoing renal replacement therapy (RRT) in all modalities. 20 countries participated in the surveys (more than 90% of the region). Prevalence of treated ESKD in RRT increased from 119 patients per million population (pmp) in 1991 to 709 pmp in 2014; hemodialysis continues to be the treatment of choice in the region (68%). A wide variation was observed in the incidence rate, from 421 pmp in Jalisco (Mexico) to 23 pmp in Paraguay; diabetes was the cause of 36% of incident cases. Additionally, great heterogeneity was observed in the number of nephrologists by country, from 2 pmp in Colombia to 53 pmp in Uruguay. Heterogeneity, or even absence of registries in some LA countries, is concordant with inequities in RRT access as well as with the limited availability of qualified personnel. The LADRTR is leading the personnel training to develop and strengthen national dialysis and transplant registries in LA within the frame of the Pan-American Health Organization (PAHO) - Sociedad Latinoamericana de Nefrología e Hipertension (SLANH) cooperation program.
Asunto(s)
Fallo Renal Crónico/terapia , Terapia de Reemplazo Renal/estadística & datos numéricos , Costo de Enfermedad , Humanos , América Latina/epidemiología , Prevalencia , Sistema de RegistrosRESUMEN
Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality. Mutations associated with factor H, factor B and complement C3 show the worst prognosis. Even though plasma therapy is occasionally useful, eculizumab is effective both for treatment and prevention of post-transplant recurrence. We describe here an adult case of congenital aHUS (C3 mutation) under preventive treatment with eculizumab after renal transplantation, with neither disease recurrence nor drug-related adverse events after a 36-months follow-up.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/etiología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/cirugía , Adolescente , Femenino , Rechazo de Injerto/tratamiento farmacológico , HumanosRESUMEN
Patients receiving sub-optimal dose of hemodialysis have increased morbidity and mortality. The objectives of this study were to identify predisposing factors and causes of inadequate dialysis, and to design a practical algorithm for the management of these patients. A cross-sectional study was conducted. Ninety patients in chronic hemodialysis at Hospital Privado Universitario de Córdoba were included, during September 2015. Twenty two received sub-optimal dose of hemodialysis. Those with urea distribution volume (V) greater than 40 l (72 kg body weight approximately) are 11 times more likely (OR = 11.6; CI 95% = 3.2 to 51.7, p < 0.0001) to receive an inadequate dose of hemodialysis, than those with a smaller V. This situation is more frequent in men (OR = 3.5; 95% CI 1.01-15.8; p = 0.0292). V greater than 40 l was the only independent predictor of sub-dialysis in the multivariate analysis (OR = 10.3; 95% CI 2.8-37; p < 0.0004). The main cause of suboptimal dialysis was receiving a lower blood flow (Qb) than the prescribed (336.4 ± 45.8 ml/min vs. 402.3 ± 28.8 ml/min respectively, p < 0.0001) (n = 18). Other causes were identified: shorter duration of the session (n = 2), vascular access recirculation (n = 1), and error in the samples (n = 1). In conclusion, the only independent predisposing factor found in this study for sub-optimal dialysis is V greater than 40 l. The main cause was receiving a slower Qb than prescribed. From these findings, an algorithm for the management of these patients was developed.
Asunto(s)
Fallo Renal Crónico/terapia , Diálisis Renal/normas , Algoritmos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal/métodos , Factores de RiesgoRESUMEN
INTRODUCTION: End-stage renal disease (ESRD) represents a major challenge for Latin America (LA). Epidemiological information needed to assist in the development of ESRD care in the region. The Latin American Dialysis and Renal Transplant Registry (RLADTR), has published several reports and its continuity has implied a sustained effort of the entire LA Nephrology community. This paper summarizes the results corresponding to year 2012. METHODS: Our methods have been reported previously. Participant countries complete an annual survey collecting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities. RESULTS: 20 countries participated in the surveys, more than 90% of the Latin America. The prevalence of ESRD under RRT in LA increased from 119 patients Per million population (pmp) in 1991 to 661 pmp in 2012. HD continues to be the treatment of choice in the region (82%). A wide rate variation in incidence is observed: from 472.7 in Jalisco (Mexico) to 14 pmp in Guatemala. Diabetes remained the leading cause of ESRD. The most frequent cause of death was cardiovascular. There is a wide rate variation of nephrologist by country, from 1.8 pmp in Honduras to 45.2 pmp in Cuba. DISCUSSION: The heterogeneity or even absence of registries in some LA countries is congruent with the inequities in access to RRT in such countries, as well as the availability of qualified personnel. The SLANH is currently running training programs as well as cooperation programs between LA countries to help the least developed start ESRD programs. In this spirit, RLADTR is training personnel to carry out dialysis and transplant registries in LA.
Asunto(s)
Costo de Enfermedad , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Humanos , Incidencia , Trasplante de Riñón , América Latina/epidemiología , Prevalencia , Diálisis RenalRESUMEN
INTRODUCTION: Chronic kidney disease (CKD) represents a major challenge for Latin America (LA), due to its epidemic proportions and high burden to the population affected and to public health systems. METHODS: Our methods have been reported previously: This paper shows the data for the last 10 years until 2010, from the Latin American Dialysis and Renal Transplantation Registry (RLADTR). RESULTS: 20 countries participated in the surveys, covering 99% of Latin America (LA). The prevalence of end-stage renal disease (ESRD) under renal replacement therapy (RRT) in LA increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (hemodialysis (HD) 413 pmp, peritoneal dialysis (PD) 135 pmp, and LFG 111 pmp). HD proportionally increased more than PD and transplant and continues to be the treatment of choice in the region (75%). The kidney transplant rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of transplants in 2010 was 10,397, with 58% being deceased donors. The total RRT prevalence correlated positively with gross national income (GNI) (r = 0.86; p < 0.05) and life expectancy at birth (r = 0.58; p < 0.05). The global incidence rate correlated significantly only with GNI (r = 0.56; p < 0.05). Diabetes remained the leading cause of ESRD. CONCLUSION: The prevalence and incidence of RRT continues to increase. In countries with 100% public health or insurance coverage for RRT the rates are comparable to those displayed by developed countries with better GNI. PD is still an underutilized strategy for RRT in the region. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost effective forms of RRT are needed in the region.
Asunto(s)
Costo de Enfermedad , Predicción , Fallo Renal Crónico/economía , Fallo Renal Crónico/epidemiología , Sistema de Registros , Femenino , Humanos , Incidencia , América Latina/epidemiología , Masculino , Prevalencia , Estudios RetrospectivosRESUMEN
The Strategic Plan of the Pan American Health Organization, 2014-2019, Championing Health: Sustainable Development and Equityrecognizes that "Chronic kidney disease, caused mainly by complications of diabetes and hypertension, has increased in the Region." This Plan includes the first concrete goal on chronic kidney disease: to achieve a prevalence rate for renal replacement therapy of at least 700 patients per million population by 2019. National dialysis and transplant registries (DTR) are a useful tool for epidemiological research, health care planning, and quality improvement. Their success depends on the quality of their data and quality control procedures. This article describes the current situation of national DTRs in the Region and the content of their information and health indicators, and it offers recommendations for creating and maintaining them. It points to their heterogeneity or absence in some countries, in line with the inequities that patients face in access to renal replacement therapy. The complete lack of information in Caribbean countries prevents their inclusion in this communication, which requires immediate attention.
Asunto(s)
Sistema de Registros , Región del Caribe/epidemiología , Humanos , Fallo Renal Crónico/epidemiología , Trasplante de Riñón , América Latina/epidemiología , Prevalencia , Diálisis RenalRESUMEN
For patients with chronic renal failure (CRF), kidney transplant (KT) is a better alternative to dialysis in terms of survival, life quality and costs. We studied the general characteristics, causes and survival rate of the dialysis population in 2010. We evaluated broader criteria for acceptance of transplants has affected the results of the procedure in that period. A total of 118 dialysis patients were included; mean age 56.9 ± 18.4 years, dialysis duration 45.5 ± 59.6 months, main cause of CRF was diabetes in 35 (30%), and 58 (49%) were included in waiting list for KT. Of the 34 patients who finished dialysis in 2010, 18 (53%) were KT, while 12 (35%) died (cardiovascular 50%, infectious 17%). Survival at 12 months was 85% for the total group, 98% on waiting list and 72% those who were not enrolled. During 2010 there were 88 KT, 62 with cadaveric donors (CD), 18 with living donors and 8 with double pancreas-kidney transplants. Recipients of CD were 50.7 years old, with 67 months on dialysis, 8 (13%) diabetics, and 12 (20%) with previous KT. Donors had a mean age of 45 years, 28 (45%) expanded criteria, and 27.7 hours of cold ischemia time. During an approximate follow-up of 11.4 months, 13 (21%) suffered acute graft rejection, survival was 88% for graft and 93% for patients. We emphasize KT as the main cause of success as regards dialysis. No differences in risk factors were found to significantly affect graft or patient survival.
Asunto(s)
Trasplante de Riñón/mortalidad , Diálisis Renal/mortalidad , Tasa de Supervivencia , Adulto , Argentina/epidemiología , Cadáver , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Unidades de Hemodiálisis en Hospital/estadística & datos numéricos , Humanos , Incidencia , Trasplante de Riñón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/mortalidad , Prevalencia , Diálisis Renal/estadística & datos numéricos , Donantes de Tejidos , Listas de EsperaRESUMEN
We present a patient with a rare systemic autoinflammatory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in extremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymphadenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and proteinuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclophosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid progression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenomenon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient's clinical manifestations.
Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Mevalonato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenomegalia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias mostrando nefropatía por IgA alternando actividad y cronicidad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatillos para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para generar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.
Asunto(s)
Glomerulonefritis por IGA , Necrosis de la Corteza Renal , Humanos , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/patología , Necrosis de la Corteza Renal/etiología , Necrosis de la Corteza Renal/patología , Masculino , Femenino , AdultoAsunto(s)
Enfermedades Renales , Nefrólogos/tendencias , Nefrología/tendencias , Sociedades Médicas/tendencias , Accesibilidad a los Servicios de Salud/tendencias , Necesidades y Demandas de Servicios de Salud/tendencias , Disparidades en Atención de Salud/tendencias , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/epidemiología , Enfermedades Renales/terapia , América Latina/epidemiología , Evaluación de Necesidades/tendencias , Nefrólogos/educación , Nefrólogos/estadística & datos numéricos , Nefrología/educación , Pronóstico , Factores de TiempoRESUMEN
A considerable percentage of patients exhibit anemia post kidney transplant. Its origin is multifactorial and the main causes involved depend on the post transplant period considered. We studied in a group of 134 consecutive patients the associated factors and the clinical implications of "late anemia" (6 months post transplant). Multiple regression analysis showed that post transplant oliguria and acute rejection episodes were significantly associated with anemia. Graft survival at 36 months was significantly reduced in the anemic group (83 % versus 96%, p < 0.01). No differences in patients survival or rate of cardiovascular events were observed. We concluded that anemia at 6 months post transplant is independently and significantly associated with events that reduced functioning renal mass and kidney survival.
Asunto(s)
Anemia/etiología , Funcionamiento Retardado del Injerto/etiología , Trasplante de Riñón/efectos adversos , Adulto , Anemia/mortalidad , Argentina/epidemiología , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Oliguria/etiología , Análisis de Regresión , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
There is no consensus on the best equation to estimate glomerular filtration rate (eGFR) in obese patients (OP). Objective: to evaluate the performance of the current equations and the new Argentinian Equation ("AE") to estimate GFR in OP. Two validation samples were used: internal (IVS, using 10-fold cross-validation) and temporary (TVS). OP whose GFR was measured (mGFR) with clearance of iothalamate between 2007/2017 (IVS, n = 189) and 2018/2019 (TVS, n = 26) were included. To evaluate the performance of the equations we used: bias (difference between eGFR and mGFR), P30 (percentage of estimates within ±30% of mGFR), Pearson's correlation (r) and percentage of correct classification (%CC) according to the stages of CKD. The median age was 50 years. Sixty percent had grade I obesity (G1-Ob), 25.1% G2-Ob and 14.9% G3-Ob, with a wide range in mGFR (5.6-173.1 mL/min/1.73 m2). In the IVS, AE obtained a higher P30 (85.2%), r (0.86) and %CC (74.4%), with lower bias (-0.4 mL/min/1.73 m2). In the TVS, AE obtained a higher P30 (88.5%), r (0.89) and %CC (84.6%). The performance of all equations was reduced in G3-Ob, but AE was the only one that obtained a P30 > 80% in all degrees. AE obtained better overall performance to estimate GFR in OP and could be useful in this population. Conclusions from this study may not be generalizable to all populations of obese patients since they were derived from a study in a single center with a very specific ethnic mixed population.
Asunto(s)
Obesidad , Insuficiencia Renal Crónica , Humanos , Persona de Mediana Edad , Tasa de Filtración Glomerular , Creatinina , Etnicidad , Organizaciones , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region. Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America. Results: The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48-1.00), 0.60 (0.43-0.85), 0.61 (0.43-0.86), and 0.51 (0.34-0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively). Conclusion: Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.
RESUMEN
The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore that mediates free water transport during peritoneal dialysis (PD). Proof-of-principle studies performed in rats have shown that treatment with corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries, causing a significant increase in free water transport. Whether such a beneficial effect could be observed in end-stage renal disease patients treated by PD remains unknown. Peritoneal transport parameters were evaluated in three patients on PD, shortly before and after living-donor renal transplantation and treatment with high-dose methylprednisolone (1.0-1.2 g/m(2)). As compared with pre-transplantation values, the post-transplantation test revealed an â¼2-fold increase in the sodium sieving and ultrasmall pore ultrafiltration volume, suggesting an effect on AQP1 water channels. In contrast, there was no change in the parameters of small solute transport. The direct involvement of AQP1 in these changes is suggested by the expression of glucocorticoid receptors in the human peritoneum and the presence of conserved glucocorticoid response elements in the promoter of the human AQP1 gene.
Asunto(s)
Glucocorticoides/administración & dosificación , Metilprednisolona/administración & dosificación , Diálisis Peritoneal , Peritoneo/efectos de los fármacos , Peritoneo/metabolismo , Agua/metabolismo , Niño , Femenino , Glucocorticoides/farmacología , Humanos , Trasplante de Riñón , Masculino , Metilprednisolona/farmacología , Persona de Mediana EdadRESUMEN
BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73m2) and 13.8% (60ml/min/1.73m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.
RESUMEN
BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73 m2) and 13.8% (60ml/min/1.73 m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73 m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.
RESUMEN
The ABO incompatible (ABOi) living donor (LD) kidney transplant allows increasing the number of donors and reducing the time on the waiting list. The objectives of this study were to compare graft survival, patient survival, rejection risk factors and complications during the first year p ost-transplantation in patients who received an ABOi LD kidney transplant between 2014 and 2019 in our institution, matched according to sex, age and immunological risk with a control group of ABO compatible (ABOc) LD kidney transplants in the same period. Thirteen patients were included in each group. No significant differences were found between ABOi and ABOc in the incidence of delayed graft function (n = 0 vs. 1), bleeding (0 vs. 0), infections (13 vs. 13), cellular rejection (1 vs. 3) and humoral rejection (4 vs. 3) in the first year after transplantation. The rejection rate in ABOi do not seem to be related to blood incompatibility. No risk factors associated with rejection were found. Overall survival of patients was 100% in both groups, and graft survival was 92.3% in ABOi and 100% in ABOc (p = 1). ABOi kidney transplantation is an adequate feasible option in our environment for those who do not have compatible donors.
El trasplante renal con donante vivo (DV) ABO incompatible (ABOi) permite aumentar el número de donantes y reducir el tiempo en lista de espera. Los objetivos de este estudio fueron: comparar la supervivencia del injerto, del paciente, los factores de riesgo de rechazo y las complicaciones durante el primer año post-trasplante en los pacientes que recibieron un trasplante DV ABOi entre 2014 y 2019 en nuestra institución, emparejados según sexo, edad y riesgo inmunológico con un grupo control de trasplantados DV ABO compatibles (ABOc) en el mismo periodo. Se incluyeron 13 pacientes en cada grupo. No se hallaron diferencias significativas entre los ABOi vs ABOc en la incidencia de retardo de la función del injerto (n = 0 vs. 1), sangrado (0 vs. 0), infecciones (13 vs. 13), rechazo celular (1 vs. 3) y rechazo humoral (4 vs. 3) en el primer año posttrasplante. La tasa de rechazo en los pacientes ABOi no parece tener relación con la incompatibilidad sanguínea, ni se hallaron otros factores de riesgo asociados a rechazo. La supervivencia global de los pacientes fue del 100% en ambos grupos, y la del injerto fue del 92.3% en ABOi y 100% en ABOc (p = 1). El trasplante renal ABOi es una adecuada opción factible en nuestro medio para quienes que no cuentan con donantes compatibles.