J.G Cotorruelo

Creatinine Reduction Ratio on Post-Transplant Day Two as Criterion in Defining Delayed Graft Function

Delayed graft function (DGF) is a common complication after renal transplant, affecting its outcome. A common definition of DGF is the need for dialysis within the first week of transplantation, but this criterion has its drawbacks. We tried to validate an earlier and better defined parameter of DGF based on the creatinine reduction ratio on post‐transplant day 2 (CRR2). We analyzed the clinical charts of 291 cadaver kidney recipients to compare the outcome of patients with immediate graft function (IGF), dialyzed patients (D‐DGF) and nondialyzed CRR2‐defined DGF patients (ND‐DGF) and to identify risk factors for D‐DGF and ND‐DGF.

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell, Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.

Ecstasy-induced brain death and acute hepatocellular failure: multiorgan donor and liver transplantation.

Background. Ecstasy is a neurotoxic and hepatotoxic drug. Brain edema and fulminant hepatic failure are two of the most serious complications associated with the consumption of ecstasy. Acute ecstasy intoxication can transform a patient into an organ donor or a hepatic graft recipient. Materials and Methods. In the last 5 years in our centers, we have had two multiorgan donors who died from ecstasy-induced brain edema and three patients who required urgent orthotopic liver transplantation for treatment of severe acute hepatocellular failure induced by this drug. We performed eight transplantations using the organs of these two brain-dead donors: one heart, one bipulmonary, three kidneys, one kidney-pancreas, and two livers. Results. Toxicity caused by ecstasy was not observed in any of the eight patients who underwent transplantation. The clinical state and the graft function of the heart, two liver, renopancreatic, and three kidney recipients were normal for a follow-up period that ranged between 7 months and 4.5 years. The lung recipient died from multiorgan failure secondary to bilateral pneumonia 5 days after the transplantation, and one of the kidney transplant patients died as a result of intestinal lymphoma 6 months after transplantation. The three liver transplantations in the three patients with ecstasy-induced fulminant hepatic failure were performed successfully using orthotopic transplantation. These three recipients are asymptomatic and have normal-functioning hepatic grafts after follow-up of 3.5 years, 15 months, and 11 months, respectively. Conclusions. The thoracic and abdominal organs of people dying from ecstasy intoxication can be viable for transplantation. The short- and medium-term survival of the graft and of the recipient have been similar to that of other organ donors. Urgent liver transplantation is an effective therapeutic option in patients with ecstasy-induced acute hepatocellular failure.

Impact of restrictive fluid balance focused to increase lung procurement on renal function after kidney transplantation

BACKGROUND Restrictive management of fluid status has been proposed to increase the rates of lung grafts available for transplant. However, no studies have supported the effect of this negative fluid balance in the kidney graft recipients. METHODS We evaluated the effect of restrictive fluid balance in brain-dead donors and their impact in 404 kidney recipients using Kaplan-Meier curves and Cox regression for long-term effects, and logistic regression for short-term effects. Our primary interest was graft survival and the second was occurrence of delayed graft function (DGF). RESULTS A negative or equalized fluid balance with a central venous pressure (CVP) <6 mm Hg affects neither graft survival in kidney recipients (P = 0.983) nor the development of DGF (P = 0.573). A positive fluid balance between brain death and organ retrieval does not reduce either the risk of graft survival or the risk of DGF. CONCLUSION We concluded that restrictive management of fluid balance in a multiorgan donor supports adequate perfusion to vital organ systems even with a CVP <6 mm Hg. A strict fluid balance could avoid volume overload and lung neurogenic oedema, increasing the rate of lung grafts available for transplant without impacting either kidney graft survival or DGF development.

Glioblastoma multiforme of donor origin after renal transplantation: Report of a case

A case of transmission of a glioblastoma multiforme from the donor to a kidney transplant recipient in the absence of previous ventriculosystemic shunt is described. The recipient was a 48-year-old woman who developed a fever with no other associated symptoms 17 months posttransplant. Physical examination revealed a large nonpulsatile mass on the upper graft pole. Histopathologic examination showed a highly cellular neoplasm with fusiform and globoid cells, a high grade of nuclear pleomorphism and mitosis, necrosis with pseudopalisading, and vascular proliferation. Immunohistochemistry of the cells showed them to contain glial fibrillary acidic and S-100 proteins, consistent with a glioblastoma multiforme. We conclude that the risk of tumor transmission from donors with primary central nervous system tumors to kidney transplant recipients, is real and should be considered when evaluating a graft mass in such patients.

Acute rejection in the elderly recipient: influence of age in the outcome of kidney transplantation.

Since the immune response in older recipientsis weaker they should be less likely to rejecta transplanted organ and should need lessaggressive immunosuppressive treatment. Our aimwas to record the incidence and severity ofepisodes of acute rejection (AR), estimate theinfluence of these events on graft survival ofelderly recipients (≥60) and to comparethese with that in younger ones.We performed 363 kidney transplants between1/94 and 12/98, and recorded clinical andimmunological data, incidence-severity of ARand cause of graft loss. Patients were dividedinto two groups, according to the age attransplantation: A (<60, n = 281/77.4%) and B(≥ 60, n = 82/22.6%). The percentage ofaging recipients and mean age of donors andrecipients increased throughout the period.Although the incidence of ATN was higher in theolder group (29% vs.19%, p < 0.0001) thenumber of graft biopsies was equal in bothgroups. The incidence of AR was similar, 33.4%vs. 26.8%, pNS. The number of AR episodes perpatient was 0.44 and 0.41 respectively. Theseverity of AR was: Banff grade I: A (40.3%)/B (45.7%) pNS; grade II: A (44.1%)/B(48.57) pNS; grade III: A (15.5%)/B (5.7%)pNS. Younger recipients presented a higherlevel of panel-reactive antibodies (PRA) (4.3%vs. 2.07%, p = 0.01). One-year patient survivalwas 96%/91% (p<0.05) and graft survivalwas 81%/78% (pNS) respectively.The age of recipient does not seem to haveinfluenced the incidence-severity of AR or thegraft survival. Thus immunosuppression shouldbe individualised for each patient and shouldnot depend on the age at transplantation.

Hyperparathyroidism is responsible for the increased levels of osteocalcin in patients with normally functioning kidney grafts.

Osteocalcin or bone Gla protein (BGP) is the most abundant noncollagenous protein of the skeleton. Serum BGP levels are thought to provide a valuable index of bone formation. We measured serum BGP and other parameters of mineral metabolism in 68 patients with functioning kidney grafts. The duration of the graft ranged from 1 to 131 months (mean 23). Serum BGP was positively correlated with parathyroid hormone (r = 0.56, p less than 0.001). BGP was inversely correlated with glomerular filtration rate (r = -0.44, p less than 0.001) and with the total cumulative dose of corticosteroids received after transplantation (r = -0.26, p less than 0.05). No correlation was observed between BGP and 1,25(OH)2D, nor between BGP and serum aluminum. All patients with increased BGP in the presence of normal renal function had persistent hyperparathyroidism. The activity of the parathyroid glands and corticosteroid treatment seem to be the main pathophysiological factors influencing BGP levels after successful kidney grafting.

Association Between Pulse Pressure and Cardiovascular Disease in Renal Transplant Patients

Elevated pulse pressure in general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effect that a wider pulse pressure range may have on cardiovascular disease after renal transplantation in 532 transplant patients with functioning graft for more than 1 year. Patients were classified into two groups depending on 1‐year pulse pressure (< or ≥65 mmHg) and we analyzed patient and graft survival, post‐transplant cardiovascular disease and main causes of death. Higher pulse pressure was associated with older recipient age (40.8 ± 10.8 vs. 50 ± 11.3), higher systolic blood pressure (132.7 ± 16.1 vs. 164.5 ± 16), lower blood diastolic pressure (84.5 ± 11.6 vs. 84.4 ± 11.2), higher prevalence of diabetes (12% vs. 23%) and total cardiovascular disease (20.9% vs. 33.6%). Five‐ and 10‐year patient survivals were lower in the group with higher pulse pressure, being vascular disease the main cause of death in both groups. In a Cox regression model increased pulse pressure was associated with higher cardiovascular disease (RR = 1.73, 95% CI: 1.13–2.32 p < 0.01). In conclusion, pulse pressure was an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.

Significance of age in the survival of diabetic patients after kidney transplantation

Background: In recent years acceptance ofdiabetic patients for renal replacement therapyhas increased. Renal transplantation for Type Idiabetic patients is widely accepted but theappropriate treatment for Type II diabeticpatients is still a matter of dispute. Ourstudy was done to determine whether the age ofType II diabetic patients constituted anadditional risk factor.Methods: We analyzed the outcome of renaltransplantation in 56 diabetic patients, 31Type I and 25 Type II diabetics (we excludedany who had combined kidney-pancreastransplants). We compared them with 51non-diabetic patients who were transplantedbecause of end-stage renal failure due tonephrosclerosis and age-matched to type IIdiabetic patients. We assessed the one- andthree-year patient and graft survival, thequality of renal function, the maincomplications and causes of mortality.Results: The overall one- and three-yearpatient survival was 69% and 60% in Type IIpatients; 73% and 69% in Type I diabetespatients and 88% and 80% in patients withnephrosclerosis. The overall one- andthree-year actuarial graft survival was 50%and 38% in patients with Type II disease and58% and 50% in Type I diabetes, and 76% and64% in nephrosclerosis. The main cause ofgraft loss in all groups was death (withfunctioning kidney) due to infections andcardiovascular complications.Conclusions: Diabetes itself is the mostimportant variable in patients who have poorresults after kidney transplantation.Increasing age increases slightly the risk forpoor graft and patient survival. Both groups ofdiabetic patients have poorer results thancontrols but in this comparison age was anindependent factor.

Pulse pressure is an independent risk factor of cardiovascular disease in renal transplant patients

Elevated pulse pressure in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effects that a wide pulse pressure has on cardiovascular disease after renal transplantation in a cohort of 532 transplant patients with functioning grafts for more than one year. Patients were classified into two groups depending on whether the one-year pulse pressure was less than or greater than 65 mm Hg. We analyzed patient survival, posttransplant cardiovascular disease and principle causes of death. Five- and ten-year patient survival were lower among the group with higher pulse pressures. The main cause of death was vascular disease in both groups. The presence of posttransplant cardiovascular disease was higher among the group with higher pulse pressures (RR=1.73). In addition, the incidence of an elevated pulse pressure was directly associated with recipient age and posttransplant diabetes mellitus. In conclusion, pulse pressure represents an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.