Abstract
Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not ...widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is ‘solved’ by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020–2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true.
El KDRI y su variante KDPI son dos herramientas utilizadas para la valoración del donante renal. Se ha propuesto la utilidad del KDPI como sustituto/complementario a la biopsia renal preimplantación. ...Estos scores no están validados en España.
1) Investigar la concordancia entre los scores KDPI e histológico (biopsia renal preimplantación), y 2) valorar la relación entre el KDRI, KDPI y la puntuación histológica sobre la supervivencia del injerto, en donantes con criterios expandidos (ECD).
Estudio de cohortes, unicéntrico, retrospectivo desde el 1 de enero de 1998 hasta el 31 de diciembre de 2010.
Se reclutaron 120 donantes y 220 biopsias preimplantación. Ciento cuarenta y cuatro (65,5%) injertos fueron aptos para trasplante. Setenta y seis (34,5%) fueron descartados. Tiempo medio de seguimiento 6,4 años (ds 3,9). Edad media de los donantes 63,1 años (ds 8,2), varones (145; 65,9%), no diabéticos (191; 86,8%) y sin otros factores de riesgo cardiovascular (173; 78,6%). Causa de muerte mayoritaria ACV hemorrágico (153; 69,5%). La puntuación KDPI media entre los grupos riñón válido (1,56/89; ds 0,22) y no válido (1,66/93; ds 0,15) es estadísticamente significativa (p < 0,01). El KDPI mostró una concordancia y correlación moderadas con el score histológico (AUC 0,64/coeficiente de correlación 0,24, p < 0,01). Los scores KDPI (HR 24,3, p < 0,01) y KDRI (HR 23,3, p < 0,01) están relacionados con la supervivencia del injerto en el análisis multivariante.
1) Los scores KDPI e histológico presentan una concordancia moderada. 2) Las puntuaciones KDPI, y sobre todo KDRI, son válidas para estimar la supervivencia de los injertos y pueden ser utilizadas de forma combinada con la biopsia para la toma de decisiones individualizadas en el grupo de donantes con criterios expandidos.
KDRI / KDPI are tools use in kidney donor evaluation. It has been proposed as a substitute of, or complementary to preimplantation renal biopsy. These scores has not been validated in Spain.
1) To investigate the concordance between KDPI and histological scores (preimplantation renal biopsy) and 2) To assess the relationship between KDRI, KDPI and histological score on graft survival in the expanded criteria donors group.
Retrospective cohort study from 1 January 1998 until 31 December 2010.
During the study 120 donors were recruited, that resulted in 220 preimplantation renal biopsies. 144 (65%) grafts were considered suitable for kidney transplantation. 76 (34.5%) were discarded. Median follow up has been 6.4 years (sd 3.9). Median age 63.1 years (sd 8.2), males (145; 65.9%), non-diabetic (191; 86.8%) and without another cardiovascular risk factors (173; 78.6%). 153 (69.5%) donors died of cerebrovascular disease. There were significant differences in KDRI/KDPI score in both groups 1.56/89 (sd 0.22) vs 1.66/93 (sd 0.15), p<0.01). The KDPI showed moderate concordance and correlation with the histological score (AUC 0.64 / correlation coefficient 0.24, p <0.01). KDPI (HR 24.3, p<0.01) and KDRI (HR 23.3, p<0.01) scores were associated with graft survival in multivariate analysis.
1) KPDI and histological scores show moderate concordance. The utility of both scores as combined tools it has to be determined. 2) KDPI score, and especially KDRI score, are valid for estimating graft survival and combined with the biopsy can help to individualized decision making in the expanded criteria donors pool.
Although studies have shown that mycophenolate mofetil (MMF) with cyclosporine (CsA) and prednisone can reduce the incidence of acute rejection and increase the half-life of the graft, the effects of ...MMF on established chronic allograft nephropathy (CAN) are controversial.
We studied 121 patients with biopsy-proven CAN, 59 treated with CsA and prednisone and 62 treated with triple-drug therapy with azathioprine. At inclusion, each group received 2 g per day of MMF and azathioprine was stopped. Renal function was measured by the glomerular filtration rate (GFR) obtained by creatinine clearance (Cockcroft-Gault) and monitored by the slope of the GFR, adjusted using linear regression.
The median follow-up, after incorporation of MMF, was 36 (13-36) months, with 103 (85.1%) having a full 3-year follow-up. Before the introduction of MMF, there was progressive deterioration in renal function (GFR: 54.8+/-20.9 vs. 39.7+/-14.0 mL/min, P<0.001). After introduction of MMF, renal function remained stable (GFR: 39.7+/-14.0 vs. 41.3+/-10.8 mL/min, P=NS), with a significant change in the slope of the GFR (-0.0144 vs. +0.00045, P<0.001). In 65 patients in whom CsA blood levels remained unchanged during follow-up (148.0+/-65.6 vs. 154.1+/-58.2, P=NS), the slope of the GFR showed a reduction in loss of renal function (-0.0147 vs. -0.0001, P<0.001).
Treatment with MMF reduced the progressive deterioration of renal function in patients with CAN, independently of the blood levels of CsA.
To determine the incidence of postintensive care syndrome in a cohort of critically ill patients admitted to the intensive care unit and to identify risk factors related to its development in the ...physical, cognitive and mental health areas.
This was a prospective observational cohort study developed in the intensive care unit of a university hospital. Patients with intensive care unit stays equal to or longer than one week and the need for mechanical ventilation for more than 3 days, shock or delirium were included in the study. Demographic variables, reasons for admission, diagnoses, sedation, type of mechanical ventilation used, complications and length of stay were recorded. A univariate analysis was performed to identify risk factors related to postintensive care syndrome. The scales used for the assessment of the different spheres were Barthel, Pfeiffer, Hospital Anxiety and Depression Scale and Impact of Event Scale-6. The main variables of interest were postintensive care syndrome incidence overall and by domains. Risk factors were examined in each of the health domains (physical, cognitive and mental health).
Eighty-seven patients were included. The mean Acute Physiology and Chronic Health Evaluation II score was 16.5. The mean number of intensive care unit days was 17. The incidence of global postintensive care syndrome was 56.3% (n = 49, 95%CI 45.8 - 66.2%). The incidence of postintensive care syndrome in each of the spheres was 32.1% (physical), 11.5% (cognitive), and 36.6% (mental health).
The incidence of postintensive care syndrome is 56.3%. The mental health sphere is the most frequently involved. The risk factors are different depending on the area considered.
Endothelin 1 (Et1) is widely expressed in the kidney and is related to several functions and to pathological conditions with progression towards sclerosis. The function of endothelin 3 (Et3) at the ...renal level is debatable, but it could have an important regulatory function in the reabsorption of water through its action on tubular type B receptors. Angiotensin II has recently been implicated as the principal factor responsible for the progression of interstitial fibrosis induced by cyclosporin A (CsA). We investigated this relationship in vivo and analyzed the modifications induced by CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day of CsA for 28 and 56 days. Immunohistochemical methods and molecular analysis were used to study the expression of Et1 and Et3 and immunohistochemistry alone to determine the intrarenal expression of angiotensin II. Rats treated with CsA developed chronic nephrotoxicity lesions; semiquantitative analyses of hyaline arteriolopathy revealed that the passage of time affected the extent of this lesion and led to the diminution of the total glomerular area. Immunohistochemical results showed that chronic CsA treatment induced moderate secretion of Et1 and Et3 at tubular and glomerular levels and that the local expression of angiotensin II in the treatment groups was more evident than in control animals. Besides, the mRNA levels of preproEt3 showed a dramatic increase from 28 days after CsA treatment (control group 0.07+/-0.11 vs. CsA group 0.48+/-0.11, p<0.01), while the mRNA levels of preproEt1 increased from 56 days (control group 0.15+/-0.05 vs. CsA group 0.34+/-0.09, p< 0.05). At 28 days, renal lesions correlated strongly with the mRNA levels of Et3 (r>0.50, p<0.01). However, at 56 days, the key finding was the strong correlation of the most important analytical, histological, and immunohistochemical parameters of CsA nephrotoxicity with Et1 mRNA levels (r>0.50, p<0.01). These results support the hypothesis that the clinical and morphological phenomena linked with CsA nephrotoxicity are related to hypersecretion of endothelins and local expression of angiotensin II in the outer medulla and medullary rays; Et3 and angiotensin II are the first to act, followed subsequently by Et1.
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