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Early protocol renal allograft biopsies and graft outcome. To evaluate whether biopsies performed early after transplantation in stable grafts can predict graft failure due to chronic transplant nephropathy, a protocol biopsy was performed at three months in 98 patients treated with antilymphocytic antibodies, cyclosporine and prednisone. Patients were followed for 58 ± 16 months. Histological diagnosis according to the Banff schema were: normal ( N = 41), borderline changes ( N = 12), chronic transplant nephropathy (CTN; N = 30), CTN associated to borderline changes ( N = 11) and acute rejection ( N = 4). Biopsies displaying acute rejection were not considered for statistical analysis. Since clinical characteristics of patients with normal histology and borderline changes, as well as characteristics of patients displaying CTN either with or without tubulitis were not different, biopsies were grouped as presence or absence of CTN. Patients displaying CTN had an increased incidence of acute rejection before performing biopsy (24.3 vs. 3.9%, P = 0.003), a higher mean cyclosporine level until biopsy (242 ± 74 vs. 214 ± 59 ng/ml, P = 0.049) and a lower actuarial graft survival (80.5% vs. 94.4%, P = 0.024). We conclude that early protocol biopsies are useful to detect patients at risk of losing their graft due to chronic transplant nephropathy.

Renal ischemia—reperfusion injury is a complex sequence of events that leads to organ lesion. Ischemia depletes cells of energetic adenosine nucleotides, altering the membrane ionic ATP-dependent pumps which favours the entry of calcium, sodium and water to the cytoplasma. The catabolism of adenine nucleotides results in an accumulation of hypoxanthine. The supply of molecule oxygen during blood reperfusion generates oxygen free radicals which are highly reactive for lipidic cellular membranes in the same sites in which they are produced. The increase in intracellular calcium is thought to activate membrane phospholipase A2 which leads to the activation of arachidonic acid cascade and the generation of platelet activating factor. As a result, polimorphonuclear cells interact with endothelial cells. This interaction is regulated by selectins, platelet activating factor and integrins. Polymorphonuclear cells become activated and produce oxygen free radicals via the respiratory burst, and proteases. The altered endothelium in ischemia-reperfusion injury results in an imbalance of the ratio between endothelin and nitric oxide that entails a vasoconstrictory state which impairs renal function [1, 2]. Thus, ischemia-reperfusion injury may be considered an inflammatory and vasomotor phenomenon. In renal transplantation, ischemia-reperfusion injury hampers organ function recovery. The absence of immediate renal allograft function is usually known as delayed graft function (DGF), and commonly defined as the need for dialysis during the first week of transplantation.

Short-term results after kidney transplantation have dramatically improved over the last decade. The introduction of new drugs such as cyclosporin (CsA) has decreased the incidence of acute rejection episodes and, consequently, the proportion of grafts lost during the first year after transplantation [1]. However, longterm results have not reflected the same progress since, in most registries, the yearly rate of grafts lost beyond the first year has remained unchanged [2].

Interstitial surface is a quantitative measure of chronic renal damage that correlates with renal function at the time of biopsy and correlates with the prognosis of renal disesase. Calculation of this parameter is very time consuming and depends on the ability of the observer. Renal interstitium can be viewed as a texture. For this reason, we study the utility of grey level granulometry as a quick and objective method to measure chronic renal damage.

Achieving an adequate dialysis dose is one of the key goals for dialysis treatments. Here we assessed whether patients receiving the current cleared plasma volume (Kt), individualized for body surface area per recommendations, had improved survival and reduced hospitalizations at 2 years of follow-up. Additionally, we assessed whether patients receiving a greater dose gained more benefit. This prospective, observational, multicenter study included 6129 patients in 65 Fresenius Medical Care Spanish facilities. Patients were classified monthly into 1 of 10 risk groups based on the difference between achieved and target Kt. Patient groups with a more negative relationship were significantly older with a higher percentage of diabetes mellitus and catheter access. Treatment dialysis time, effective blood flow, and percentage of on-line hemodiafiltration were significantly higher in groups with a higher dose. The mortality risk profile showed a progressive increase when achieved minus target Kt became more negative but was significantly lower in the group with 1 to 3 L clearance above target Kt and in groups with greater increases above target Kt. Additionally, hospitalization risk appeared significantly reduced in groups receiving 9 L or more above the minimum target. Thus, prescribing an additional 3 L or more above the minimum Kt dose could potentially reduce mortality risk, and 9 L or more reduce hospitalization risk. As such, future prospective studies are required to confirm these dose effect findings.

Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsies.BackgroundChronic allograft nephropathy (CAN) progresses rapidly during the first few months and slowly thereafter. Although the presence of CAN in protocol renal biopsies is a predictor of outcome, the reliability of this diagnosis according to Banff criteria has not been characterized.MethodsRenal lesions were evaluated according to the Banff criteria in sequential protocol biopsies performed at 4 and 14 months in 310 biopsies obtained from 155 patients.ResultsCAN progressed from 40 to 53% (P = 0.001) while serum creatinine remained stable (146 ± 44 vs. 147 ± 48 μmol/L, P = NS). Graft survival in patients with and without CAN in the first biopsy was 74 versus 91% (P < 0.05), and in the second biopsy 75 versus 94% (P < 0.05). In 54 patients (35%) no CAN was present in both biopsies, 39 (25%) showed progression to CAN, 19 (12%) showed regression of CAN, and 43 (28%) showed CAN in both biopsies. Graft survival was: 100%, 81.6%, 82.6% and 69.4%, respectively (P < 0.01). Assuming that CAN does not regress and sampling error is normally distributed, we estimated that 25% of biopsies cannot be properly classified.ConclusionsThe increase in the incidence of CAN between the 4th and 14th month is lower than the proportion of misclassified biopsies. Thus, monitoring the progression of CAN by means of two sequential biopsies at 4 and 14 months is inaccurate. We suggest that progression of scarring be monitored by means of a donor and a protocol biopsy performed during the first year evaluated with a quantitative approach.

ResumenIntroducciónEl estudio ESHOL ha demostrado que la hemodiafiltración on line (HDF-OL) posdilución reduce la mortalidad por todas las causas respecto a la hemodiálisis (HD) en pacientes prevalentes. Sin embargo, durante el periodo de observación, 355 pacientes finalizaron prematuramente el estudio, de acuerdo con el diseño del mismo. Estos pacientes fueron censurados en el momento de la finalización prematura.ObjetivosEl objetivo de este estudio fue investigar los eventos de los pacientes que abandonaron el estudio.MétodosReanalizar los datos de supervivencia utilizando la población por intención de tratar en los 3 años de seguimiento. Los datos fueron analizados considerando también el trasplante renal como evento competitivo de la muerte del paciente.ResultadosDurante el seguimiento, 207 pacientes fallecieron durante el tratamiento y 47 después de abandonar el estudio. Comparados con aquellos pacientes que se mantuvieron en HD, los que fueron aleatorizados a HDF-OL tuvieron una mortalidad total menor (12,4 vs. 9,46 por 100/pacientes/año, hazard ratio [HR] e IC 95%: 0,76 [0,59-0,98]; p=0,031). La mortalidad total por todas las causas, teniendo en consideración el riesgo competitivo del trasplante renal y tiempo-dependiente, mostró en el análisis de Cox tiempo-dependiente resultados similares al análisis principal con un HR de 0,77 (0,60-0,99; p=0,043).ConclusionesLos resultados del reanálisis del estudio ESHOL se confirman cuando se aplica el análisis en la población por intención de tratar sin censurar ninguna observación y considerando la mortalidad por todas las causas dependiente del tiempo y del riesgo competitivo del trasplante renal.AbstractBackgroundThe ESHOL study showed that post-dilution online haemodiafiltration (OL-HDF) reduces all-cause mortality versus haemodialysis. However, during the observation period, 355 patients prematurely completed the study and, according to the study design, these patients were censored at the time of premature termination.MethodsThe aim of this study was to investigate the outcome of patients who discontinued the study.ResultsDuring follow-up, 207 patients died while under treatment and 47 patients died after discontinuation of the study. Compared with patients maintained on haemodialysis, those randomised to OL-HDF had lower all-cause mortality (12.4 versus 9.46 per 100 patient-years, hazard ratio and 95%CI: 0.76; [0.59-0.98], P= 0.031). For all-cause mortality by time-dependent covariates and competing risks for transplantation, the time-dependent Cox analysis showed very similar results to the main analysis with a hazard ratio of 0.77 (0.60-0.99, P= 0.043).ConclusionThe results of this analysis of the ESHOL trial confirm that post-dilution OL-HDF reduces all-cause mortality versus haemodialysis in prevalent patients. The original results of the ESHOL study, which censored patients discontinuing the study for any reason, were confirmed in the present ITT population without censures and when all-cause mortality was considered by time-dependent and competing risks for transplantation.

The extraction of circulating antiglomerular basement membrane (GBM) antibodies by plasmapheresis (PP) has allowed the prognosis of Goodpasture's disease to markedly improve. Immunoabsorption (IA) may improve the results of PP upon allowing more effective immunoglobulin extraction. Two patients with Goodpasture disease were treated with IA. A rapid decrease was observed in the serum levels of anti GBM antibodies and improvement in respiratory failure. In one of the patients this regimen was administered following the observation of a lack of clinical response of pulmonary hemorrhage in three PP sessions (9 liters of treated plasma). In this patient, the IA processed 39 liters of plasma and the method was found to be equally effective on reinstatement (29 liters) on the occasion of a relapse in the pulmonary symptoms presented at three weeks after the first treatment. Both cases showed renal involvement. In one case this was incipient and the treatment was associated with non progression of the kidney disease, normalization of the urine sediment and preservation of renal function. In the second case treatment was initiated at an advanced disease state with no changes in dialysis needs. Immunoadsorption has shown to be effective in the treatment of pulmonary hemorrhage in Goodpasture's disease. Onset of treatment at an early stage of the kidney disease may avoid progression to renal failure.

Symptomatic hypotension is the most frequent acute complication affecting patients during chronic hemodialysis treatment sessions. Many reports have demonstrated that the use of cool dialysate has a protective effect on blood pressure during hemodialysis treatments. In the present study, we investigated whether preventing the hyperthermic response had favourable effects on hemodynamic stability during the hemodialysis procedure while affording good tolerance to patients.We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients in our center. Patients were eligible for the study if they had symptomatic hypotensive episodes (3/12session/ month) during the screening phase. The study was designed with two phases for the same selected patients and two treatment arms, each phase lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36 masculineC for 12 sessions (cold dialysis) and in the second phase we used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature unchanged (isothermic dialysis).Nine HD patients were enrolled and completed the study. During the screening phase the mean ultrafiltration was 4 1% of dry weight, and blood pressure decreased from 9916 to 8016 mm Hg (p0.001). In 5.01.7 sessions of 12 treatments were complicated by hypotension. In the first and second phase we observed a decrease of complicated treatments with symptomatic hypotension (5.01.7 versus 2.71.6 y 2.81.7; p0.01). Both procedures: Cold dialysis and Isothermic dialysis was well tolerated by patients.Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients.

This paper proposes a new technique for the analysis of renal biopsies stained with Sirius red and digitized under non-polarized light. The renal interstitial space, the cortex area and the tubules should be segmented to allow the estimation of the renal cortical interstitial volume fraction and the parameters characterizing the tubule distribution. In this paper, a totally automatic algorithm is proposed that relies on mathematic morphology tools. The proposed algorithm has been assessed in a large number of biopsies leading to similar results to those obtained by the manual approach.

To segment renal interstitial space in order to automatically quantify renal cortical interstitial volume fraction (Vvint/cortex) by means of image analysis techniques.The study group consisted of 35 renal biopsies with different degrees of chronic interstitial damage. Biopsies were stained with Sirius red and digitized under polarized light. Two methods were employed to segment interstitial space: (1) interstitial bright particles were thresholded, and afterwards interstitial space was reconstructed with a morphologic operation, and (2) the texture of the surroundings of each pixel was quantified by means of local granulometry, and this information was employed as the input of a neural network in order to classify interstitial and tubular pixels.The correlation between Vvint/cortex obtained manually and both methods was r = .92. The first method produced some deformation of tubular contours and underestimated Vvint/cortex (beta = .70) when compared to the second approach (beta = .95) (P.05).Two different algorithms based on image analysis techniques allow the classification of renal interstitial and tubular structures and consequently allow the automated and precise estimation of renal Vvint/cortex.

Background Infections, new onset diabetes mellitus (NODAT) and rejection are frequent complications after renal transplantation and may be related to innate immunity alterations. We evaluate the relationship between serum mannosebinding lectin (MBL) levels, chronic inflammation, infection, NODAT and subclinical rejection after renal transplantation.