Utilization of advanced-age donors in renal transplantation.

The shortage of organ availability in recent years has made it necessary to use grafts from advanced-aged donors to maintain the rate of renal transplantation in our country. The objective of this study was to evaluate the graft function and patient survival using kidneys from deceased donors of over 65 year of age. From 2005 until 2010, we compared the outcomes of patients who received grafts from donors over 65 years old vs less than 65 years. We observed no significant difference in sex, time on dialysis, or cold ischemia time between the groups. As expected the recipient age was significantly different. For the analysis of survival, we used the Tablecloth-Haenzel test and the Kaplan-Meier survival estimator. Actuarial survivals at 3 years after transplantation showed 84.8% among patients transplanted with kidneys from donors over 65 years old versus 97.5% in the control group. The graft survival was 78.8% among expanded criteria versus 86.85% in the control group. When we analyzed graft survival using an "exitus-censured" analysis, we obtained graft survivals of 89.1% in the expanded criteria kidney group versus 88.6% among the controls. We concluded that the use of kidney from donors over 65 years of age allows us to increase the rate of renal transplantation to about 15 to 20 per million population, with good graft and patient survivals provided that the protocol for expanded criteria organs ensured proper macroscopic and microscopic evaluation of the organ for transplantation.

Conversion to everolimus in kidney transplant recipients with decreased renal function.

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1-3 mg/d that was sufficient to achieve the recommended levels of 3-8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.

Diuréticos en el fracaso renal agudo / Diuretics in acute renal failure

Los diuréticos y la dopamina a dosis renal, fármacos tradicionalmente utilizados en la «prevención» del FRA, han demostrado ser no efectivos e incluso deletéreos; por lo que se contraindica su utilización. En el manejo del FRA establecido los diuréticos aumentan la diuresis, pero no son beneficiosos en cuanto a la duración, necesidad de diálisis o supervivencia. Se les atribuyó un aumento de mortalidad que estudios posteriores no han confirmado. Su utilización en el tratamiento médico conservador puede considerarse después de haber conseguido un buen volumen circulante y una adecuada TA, pero obliga a una monitorización de la función renal que no difiera la consulta con el nefrólogo y el inicio de diálisis. La dopamina a dosis baja puede aumentar la diuresis en pacientes críticos, pero no previene ni mejora el FRA (puede incluso ocasionarlo en pacientes normo o hipovolémicos) por lo que su uso como renoprotector debe ser abandonado. La hipoperfusión, y en concreto la existencia de una PAM < 65 mmHg es un factor independiente asociado al riesgo de desarrolla FRA. Los vasopresores van a tener un papel importante en este contexto, pero deben iniciarse siempre después de haber asegurado un relleno vascular adecuado. En pacientes en shock séptico la noradrenalina (NA) consigue restaurar la PAM mejor que la dopamina a dosis alfa y es capaz de revertir la situación en pacientes que no han respondido a dopamina. Aunque en la actualidad no existen aun suficientes estudios controlados la vasopresina parece ser efectiva para revertir el shock cuando las catecolaminas no lo son, especialmente en el contexto séptico. Los estudios existentes han demostrado una importante mejoría hemodinámica, pero sin efecto positivo hasta la fecha en la mortalidad. El Péptido Natriurético Atrial, la Urodilatina y los bloqueantes de la endotelina demostraron eficacia en la prevención del FRA experimental, pero en los estudios clínicos randomizados son inferiores o similares al placebo por lo que actualmente se contraindica su utilización. El péptido natriurético atrial podría tener un papel en el contexto de FRA e insuficiencia cardíaca

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Indicaciones y aspectos logísticos de técnicas de depuración extracorpórea en el paciente agudo / Current indications of extracorporeal depuration in acute patients

Las técnicas de depuración extracorpórea que tenemos a nuestra disposición se pueden resumir en: Hemodiálisis Intermitente —HDI—, Diálisis Peritoneal —DP— y técnicas continuas —TCDE—; principalmente hemofiltración y hemodiafiltración continuas —HFVVC y HDFVVC—. Además de un conjunto de técnicas menos extendidas pero más sofisticadas encaminadas a tratar problemas concretos, como el fallo hepático (es el caso de la diálisis con albúmina —MARS®, Gambro-Hospal— o el sistema Prometheus®, de Fresenius Medical Care) o la sepsis con técnicas que comprenden la adsorción de moléculas. De estas últimas, se habla en extenso en el capítulo 6 de estas GUÍAS promovidas por la Sociedad Española de Nefrología. En la actualidad, la mayor incidencia de casos de pacientes con Fracaso Renal Agudo en un Hospital se presentan en Unidades de Cuidados Intensivos o Pacientes Críticos. En estas unidades, como lo evidencian los más recientes estudios epidemiológicos1- 3, se emplean mayoritariamente técnicas continuas. En el estudio multicéntrico y multinacional prospectivo sobre casi treinta mil ingresos en unidades de cuidados críticos, se observó que casi el 6% de los pacientes ingresados presentaban FRA y de entre ellos el 72% necesitaron tratamiento sustitutivo. Siendo tratados con TCDE el 80% de los casos, con HDI el 17% y tan solo el 3% de ellos con Diálisis Peritoneal1

Severe Acute Renal Failure (ARF) can be managed by intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT) or peritoneal dialysis (PD). The latter remains to be an alternative only in pediatrics and is anecdotic for adults in developed countries. Oliguria (urine output less than 200 mL/12h or 400 mL/day) seems to be the most frequent indication of renal replacement therapy, followed by uremia (blood urea greater than 33 mMol/L) and finally by electrolyte disturbances. Acute intoxications such as lithium, N-acetyl-procainamide, ethylenglycol or methanol can be effectively managed by these techniques. Whether or not CRRT compared with IHD improves outcome is controversial. At least in the most severely ill patients continuous therapies are better than intermittent ones and the former must be recommended if hemodynamic instability or cerebral edema are present. Regarding the dose: daily IHD seems to be better than the classical 3 per week scheme and in CRRT a dose of 35 mL·Kg-1·h-1 of effluent (convection only or ultrafiltration plus dialysis) is better than a lesser dose. CRRT have also been used in absence of acute renal failure in cases of sepsis, multiorgan failure syndrome, respiratory distress or fulminant hepatic failure. There is no strong evidence to support the use of these techniques on a regular basis to treat the aforementioned syndromes

Monitores de técnicas continuas de depuración renal / Monitoring devices of continuous techniques of renal depuration

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Equipment for continuous renal replacement therapies must provide efficiency and security. Every unithas four peristaltic roller pumps for: blood, reposition fluid, dialysis fluid and for effluent and an additionalsyring pump for anticoagulant (heparin). The most advanced monitors are provided with a fifth rollerpump to permit the use of citrate as anticoagulant or to permit the reinfusion in predilution (pre-hemofilter)and postdilution (post-hemofilter) simultaneously. And systems to check the pressure at differentpoints of the circuit: inlet (previous to the blood pump measuring negative pressures), pre-filter, outlet ofthe circuit (post-filter) and at the effluent. It is worthwhile that the software calculate several parameterssuch as the transmembrane pressure or the filtration fraction and desirable that it calculates de Kt/V ofurea. A detector (optic device) for blood leakage at the effluent line and other for air and foam (based onultrasounds or infrared emission) at the blood line previous to the patient entrance are mandatory. Nowadays,the most recent equipments are presented with tactile color TFT screens which show schemes thatfacilitate both the montage of the circuit kit and also the instruction of use of the different therapies: Continuoushemofiltration (CVVHF), Continuous hemodialysis (CVVHD), hemodiafiltration (CVVHDF), etc. It isalso of interest the ability of connecting this equipments with other computers. Devices that permit thewarming of fluids and/or blood line are also necessary

Problemas de coagulación de los circuitos extracorpóreos y estrategias para mejorar la duración de los filtros / Coagulation problems in extracorporeal circuits and strategies for improving filters duration

La coagulación de los filtros en técnicas de depuración extracorpórea continuas constituye uno de los principales problemas de su aplicación. Casi la mitad de los circuitos no llegan a cumplir el tiempo programado para su recambio. No existe consenso sobre lo que debe durar dicho circuito, aunque la mayoría de fabricantes recomiendan cambiar filtro y líneas cada 48 a 72 horas. Existen una serie de medidas encaminadas a mejorar la duración. La reposición prefiltro y el control de la fracción de filtración (mantenida por debajo del 20 ó 25%) son las más eficaces y las que mejor podemos controlar. Las emboladas con suero no han demostrado aumento en la eficacia. El correcto diseño de los circuitos y, lo que está más a nuestro alcance, un buen catéter proporcionan mayor duración y menos interrupciones de tratamiento. En la mayoría de los casos debemos optar por anticoagular el circuito, procurando que nuestra actuación tenga el menor efecto sistémico sobre el paciente y reduciendo al mínimo las complicaciones hemorrágicas. En algunas circunstancias se puede optar por no anticoagular, especialmente en casos de sangrado importante, coagulopatía, trombopenia severa o alteraciones en las pruebas de la coagulación; en este caso convendrá mantener a la baja la fracción de filtración y reponer prefiltro (en predilución). Sin embargo, en la mayor parte de las ocasiones emplearemos heparina no fraccionada a dosis bajas (5- 10 U/kg·h) controlando el APTT para obtener valores de entre 1 y 1,4 veces el control (menor de 45 segundos). En casos de TIH podremos utilizar antioagulación regional con citratos, prostaglandinas (sobre todo epoprostenol), fondaparinux o inhibidotes de la trombina. En casos de coagulación frecuente de filtros se pueden asociar prostaglandinas a heparina. El esquema de actuación queda resumido en el algoritmo de la figura 1. Los niveles de evidencia se describen en la tabla I

Filter coagulation is the cause of replacing kits in 40% to 70% of the cases. Furthermore, circuit coagulation represents loss of blood (around 200 mL), nursing workload, consumption of fungibles and temporary interruption of treatments. Anticoagulation of the extracorporeal circuit is generally required to prevent clotting of the circuit and preserve filter performance. On the other hand, anticoagulants can produce systemic effects and bleeding. Thus, there is a struggle between filter coagulation and hemorrhage. Circuit survival time is generally used to judge the effect of anticoagulation. Unfractionated sodium heparin (standard heparin) remains the most frequently used agent and the drug of choice for patients who require anticoagulation. It is cheap, and at low dosages (5-10 IU/kg per hour) the systemic effects are minor, providing an activated thromboplastin time less than 1.5 times the control. The drugs most often used apart from heparin in CRRT are prostaglandins and citrates. In patients with filter hypercoagulability heparin is frequently insufficient, and apart from physical maneuvers, such as reinfusion in pre-dilution and the reduction of the filtration fraction, we can add prostacyclin to heparin to increase filter life. Continued exposure to heparin may lead to the development of heparin-immunoglobulin G4 complexes and heparin-induced thrombocytopenia type II (TIH II), increasing the risk of both bleeding and thrombotic complications. In these cases there are several alternatives to heparin: regional citrate anticoagulation, prostaglandins, human recombinant hirudin (lepirudin), danaparoid and argatroban

Logística e implantación de programas de TCDE / Logistics and implementation of CTED schedules

La práctica clínica parece estar de acuerdo en que existe un incremento en la supervivencia de los pacientes con FRA debido al uso de técnicas continuas frente a la HD convencional. Los criterios de eficacia clínica indica que se debe de implantar un modelo abierto y colaborativo entre los servicios de nefrología y las unidades de cuidados intensivos tanto a nivel médico como de enfermería. Indicadores de la TCDE en los pacientes críticos: A. TCDE como tratamiento sustitutivo de la función renal 1. Corrección de las alteraciones hidroelectrolíticas • Acidosis metabólica • Hipercaliemia severa • Alteraciones del Na 2. Descenso del filtrado glomerular 3. Fallo renal agudo B. TCDE como tratamiento renal sustitutivo (con y sin FRA) 1. Síndrome de distres respiratorio del adulto (ARDS) 3. Síndrome de respuesta inflamatoria sistémica (SIRS) 4. Hipertermia o hipotermia incontrolable con medidas física 5. Venenos (litio, etilenglicol,biguanidas, etanol,metanol)

In the clinical praxis seems to exist a wide consensus regarding the increase of patients’ survival with FRA due to the using of continue techniques against conventional HDI. The clinical efficiency criteria prescribe that the implantation model might be “open” and collaborative between Nephrology and Acute Patients Unities both at the medical and nursing levels. The indications of TCDE are: INDICATIONS OF TCDE IN THE CRITICAL PATIENT A. TCDE as a substituted treatment of the renal function 1. Hydro-electrolytic alterations correction • Severe metabolic acidosis • Severe hyperkalemia • Sodium alterations 2. Glomerular filtration decrease (retention of nitrogen products) 3. Acute Renal Failure B. TCDE as a renal support (with or without FRA) 1. ARDS 3. SIRS 4. Hyperthermia or hypothermia non controlled by physical measures 5. Poisoning (litio, etilenglicol,biguanidas, etanol,metanol) ARDS (Adult respiratory distress syndrome) ; SIRS (Systemic inflamatory response syndrome)

Complicaciones de las técnicas renales sustitutivas / Complications renal replacement techniques

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Extracorporeal circuits for the management of acute renal failure entail a great deal of complications. The placement of a large double lumen central venous catheter (CVC) to provide enough blood flow together with the necessity of a continuous anticoagulation are the cause of the majority of the adverse events, such as puncture site bleeding, vascular complications, systemic hemorrhage, venous thrombosis and CVC-related infections. Hydro-electrolytic abnormalities regarding the use of fluids for reposition and dialysis, are frequently observed; mainly hypokalemia and hypophosphatemia. Liquids with lactate can produce hyperlactatemia or even exacerbate the lactic acidosis when lactate metabolism is altered

Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis.

Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant or recessive transmission are described. Mutations in the chloride-bicarbonate exchanger AE1 have recently been reported in four autosomal dominant dRTA kindreds, three of these altering codon Arg589. We have screened 26 kindreds with primary dRTA for mutations in AE1. Inheritance was autosomal recessive in seventeen kindreds, autosomal dominant in one, and uncertain due to unknown parental phenotype or sporadic disease in eight kindreds. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the one known dominant dRTA kindred, in one sporadic case, and one kindred with two affected brothers. In the dominant kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo mutation. In the third kindred, affected brothers both have an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1. These mutations were not detected in 80 alleles from unrelated normal individuals. These findings underscore the key role of Arg-589 and the C terminus in normal AE1 function, and indicate that while mutations in AE1 cause autosomal dominant dRTA, defects in this gene are not responsible for recessive disease.

Aminoglycoside-associated Fanconi's syndrome: an underrecognized entity.

The Fanconi syndrome is an array of multiple proximal renal tubular dysfunctions occurring in association with several exogenous toxins, such as aminoglycosides. These antibiotics remain the drugs of choice in most gram-negative infections, but nephrotoxicity is the main drawback for them. Furthermore, the nephrotoxic effects may be overlooked with routine analyses. With the purpose of making physicians aware of this underrecognized complication, we are reporting here 3 cases of Fanconi's syndrome related to the administration of high-dose aminoglycosides (ranging from 3.6 to 15 g) with normal serum urea nitrogen and creatinine levels. The pattern of aminoaciduria demonstrated high increases in neutral amino acids, followed by dibasic and near-normal acidic amino acids. We also report the urinary excretion rates of total protein and beta2-microglobulin and protein electrophoresis results. We compared these cases with others reported in the literature.

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartter's syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelman's syndrome represents the predominant subset of Bartter's patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelman's syndrome to the locus encoding the renal thiazide-sensitive Na-Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelman's syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.

Evaluation of complications due to percutaneous renal biopsy in allografts and native kidneys with color-coded Doppler sonography.

We studied 142 consecutive percutaneous renal biopsies (puncturing on 73 allografts and 69 native kidneys) which were performed under continuous ultrasonic guidance, on 133 adult patients. The patients were monitored, at least, during the next 24 hours. We compared the complication rate for biopsies recording clinical and biochemical data and, the day after the biopsy, the kidney was examined with a color-coded Doppler sonography (CCDS): in real-time survey of the kidney and with spectral wave form analysis. The diagnosis of arteriovenous (AV) fistula was achieved detecting increased color saturation toward white, high peak systolic flow velocity and low resistive index in the supplying artery. Three procedures were excluded of the analyses because of incomplete data recorded, although none of them showed any remarkable complication. There was a 94.3% rate of successful biopsies. The mean +/- SEM number of glomeruli under light microscopic examination was 8.5 +/- 0.6. Complications occurred 64 times in relation to 55 patients with a higher incidence in allografts (61%) than in native kidneys (31%). Renal transplant patients showed higher serum creatinine values (5.8 +/- 0.8 vs. 3.2 +/- 0.4; p > 0.0001) and lower hematocrit (31.3 +/- 1.1 vs. 34.4 +/- 0.9; p = 0.025) than the native-kidney patients at the time of biopsy. De novo hematuria occurred in 30% of the procedures. In transplant patients, the gross hematuria incidence (9.9%) more than doubled that showed by native-kidney patients. The incidence of serious complications (hematoma, hemoperitoneum and AV fistula) was 16.5% and these were more frequent in transplant than in native kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)