Study of the renal function in nonrenal organ transplantation.

Kidney disease after transplantation of a nonrenal organ has been described to be the result of the nephrotoxicity from the commonly used calcineurin-inhibitors as well as other factors. The aim of this study was to evaluate renal function and potential risk factors for the development of chronic renal failure among nonrenal organ recipients. We designed a single-center retrospective study including all 165 of our cardiac and liver recipients between February 1998 and October 2003, collecting clinical, analytic, and therapeutic data. We excluded double transplants and patients with survival less than 6 months. Creatinine clearance was calculated according to the Cockcroft-Gault and the Levey Modification of Diet in Renal Disease (MDRD)-5 equations. Although 165 patients received a cardiac or liver transplantation, 17 died in the first 6 months and three were double transplants; therefore we analyzed 145 patients: 107 (74%) cardiac transplantations and 38 (26%) liver transplantations. There were 106 male and 39 female recipients. The mean age (+/-SD) at the time of transplantation was 54 +/- 10 years and the mean follow-up was 2.9 +/- 1.7 years. Urinalysis before transplantation was only performed in 33 patients (22.8%) including three (2.1%) who had proteinuria. Serum creatinine increased until 12 months after transplantation (P < .001), then it recovered its average level. Creatinine clearance calculated using the aforementioned equations showed a similar pattern, with a progressive decline to 12 months (P < .05), with eventual stabilization or even improvement. The factors that we observed to increase the risk of renal damage were age, female sex, obesity, and the presence of proteinuria prior to transplantation. There was a good correlation (r = 0.96) between cyclosporine but not tacrolimus trough levels and serum creatinine at 48 hours after transplantation.

Risk factors for cardiovascular disease during the first 2 years after renal transplantation.

The aim of the present study was to assess the role of cardiovascular risk factors in the occurrence of cardiovascular events among 100 consecutive renal transplant recipients during the first 2 years after transplantation. The following parameters were analyzed: (1) demographic data (gender, age, dialysis duration, preexistent diabetes, and pretransplantation events) as well as (2) basal 1-year, and 2-year posttransplantation data for events, body mass index, arterial hypertension, number of drugs for hypertension control, use of ACE or ARA II inhibitors, treatment with lipid- lowering drugs, de novo diabetes, anemia, immunosuppression with cyclosporine versus tacrolimus, and homocysteine, folic acid, serum creatinine, uric acid, PTH-i, and cholesterol total, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels. At the end of the second posttransplantation year, 14 patients versus 86 who did not experience a new cardiovascular event. Patients in the event group had more events pretransplantation and during the first posttransplantation year than those in the non event group (57.1% vs 17.4%; P = .003 and 78.6% vs 2.3%; P = .000, respectively). Furthermore, the former cohort of patients were older, had greater ventricular hypertrophy and had higher triglyceride and serum creatinine concentrations during the 2 years after transplantation. A multiple logistic regression analysis confirmed the relationship between events within 1 year of transplantation and serum creatinine level at the end of 2 years as well as the development of cardiovascular disease within 2 years. In conclusion, our data suggest the need for aggressive intervention during the first year to prevent the development of new cardiovascular events. Renoprotective strategies may also contribute to reduce the cardiovascular risk of renal transplant recipients.

Posttransplantation diabetes mellitus: prevalence and risk factors.

BACKGROUND: Prevalence of diabetes mellitus (DM) type 2 in Asturias is 10%. The associations between age, family history of diabetes, hypertension, obesity, hypertriglyceridemia, and development of type 2 diabetes are well established. The aim of this study was to evaluate the prevalence of and risk factors for posttransplantation diabetes mellitus (PTDM). METHODS: We retrospectively studied 500 patients who had received a cadaveric renal transplant. Subjects with pretransplantation diabetes (5.6% type 1 and 7% type 2) and nondiabetics (78.2%) were excluded. We only evaluated 46 (9.2%) patients with PTDM. The follow-up period was 6 months to 15 years. We reviewed gender, age, family history of diabetes, body weight, hypertension, cardiovascular events, serum creatinine, hepatitis C virus infection, triglycerides, hyperuricemia, high-density lipoprotein and low-density lipoprotein cholesterol, and immunosuppressive therapies. RESULTS: The median time to diagnosis of PTDM was 3 months (range 1-56 months) after transplantation, a period in which 47% patients developed this complication. Compared with nondiabetics, PTDM patients were significantly older (P = .000), more obese (P = .002), received tacrolimus (P = .027), and had hypertension (P = .014) or cardiovascular events (P = .000). Serum creatinine and hepatitis C virus infection rated were similar in both groups. On multivariate analyses, the risk factors significantly associated with the development of PTDM were greater age (P = .0024), obesity (P = .0032), and hypertension (P = .0516). CONCLUSIONS: Half of the patients with PTDM developed new-onset diabetes within the first 3 months. Age, obesity, and hypertension were among the risk factors for diabetes posttransplantation. After the transplantation, the modifiable risk factors are control of body weight and control of hypertension.

[Parvovirus B9 infection in a renal transplant recipient. Diagnosis by detection of viral genome in peripheral blood]. / Infección por parvovirus B19 en trasplante renal. Diagnóstico por detección del genoma viral en sangre periférica.

Parvovirus B19 can produce a picture known as pure red blood aplasia in recipients of solid organ. Occasionally the viruses cause decrease of the other blood cells, and various extra-hematologic manifestations. Common diagnosis is realised by bone marrow examination. The diagnostic value of the viral genome in the blood stream is not well defined. We reported the case of a male of 17 years of age, whose diagnosis was done by repeated determinations of the viral parvovirus B19 genome in peripheral blood. It was confirmed by a biopsy of the iliac crest. The patient was treated with unspecific IgG immunoglobulins, with complete recovery from the symptoms and signs. It did not have any recurrence of the disease. This case suggests that the realisation of PCR of Parvovirus B19 in renal transplant patients with pure red cell aplasia could be of greater interest in the diagnosis and monitoring of the disease. The detection of the viral genome could avoid the administration of unnecessary blood transfusions, and possibly the realization of bone marrow biopsy.

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Influence of anticalcineurinic therapy in plasma homocysteine levels of renal transplant recipients: a prospective study.

Hyperhomocysteinemia is an independent factor for cardiovascular disease. Renal function and folate level are important determinants of total plasma homocysteine levels. The influence of anticalcineurin drugs on homocysteine levels is controversial. The aims of the study were: (1) to analyze changes in homocysteine levels after the first year of 73 renal transplants and (2) to determine the influence of immunosuppressive anticalcineurin drug therapy on fasting homocysteine concentrations. We examined homocysteine, serum creatinine, folate, and vitamin B12 concentrations immediately after transplant, at 6 months, and after 12 months from renal transplant. Also, MTHFRC677T polymorphism was investigated. Tacrolimus was administered in 28 patients and cyclosporine in 45. Homocysteine levels decreased from 28.41+/-13.71 micromol/L to 18.59+/-8.31 micromol/L after 6 months and to 17.13+/-7.06 micromol/L after 1 year. No relationship was found between homocysteine and folate levels. When anticalcineurin drugs were considered, the homocysteine levels in patients treated with tacrolimus was lower than that in patients treated with cyclosporine at month 6 after transplant (16+/-7.4 micromol/L vs 20.1+/-8.5 micromol/L, P=.03) and after 1 year (15+/-7.6 micromol/L vs 18.4+/-6.4 micromol/L, P=.04). Serum creatinine levels followed the same evolution: they were lower in patients treated with tacrolimus at 6 months (1.35+/-0.36 mg/dL vs 1.57+/-0.45 mg/dL, P=.03) and to a lesser extent at 1 year after renal transplant (1.38+/-0.35 mg/dL vs 1.54+/-0.45 mg/dL, P=.09). The homocysteine value closely related with serum creatinine in both groups. In conclusion, 1 year posttransplant, the homocysteine level was lower among patients treated with tacrolimus, the cohort that also showed the lower serum creatinine concentrations.

[Changes in health-related quality of life in the first year of kidney transplantation]. / Cambios en la calidad de vida relacionada con la salud durante el primer año del trasplante renal.

OBJECTIVE: To study the changes in the health related quality of life (HRQOL) during the first year following renal transplant (RT), comparing azathioprine vs mycophenolate mofetil (MMF) in triple immunosuppressant therapy with prednisone and cyclosporine. METHODS: Prospective, open and random study with 26 patients who received a primary cadaveric renal transplant consecutively. Analysis of clinical variables: delayed graft function (DGF), acute rejection (AR), infections and comorbidity; analytical: haemogram, albumin and serum creatinine, hepatic function, cyclosporin levels; instruments for assessing the HRQOL: Psychological General Well-being Index (PGWBI) and Euroqol-5d (EQ-5d) health questionnaire, which includes a self-assessment scale of the state of health, Visual Analogical Scale (VAS). Controlled collection of data upon discharge following renal transplant, and subsequently 1, 3, 6, and 12 months following the first questionnaire. RESULTS: There were no differences between patients on azathioprine or MMF, except that AR occurred less frequently with MMF (7% vs 42%, p = 0.065). Global AR: 23%, cytomegalovirus infection/illness: 81%/8%, readmissions: 42%. There was an improvement in HRQOL measured by the progressive increase in the scores on the PGWBI, EQ-5d and VAS during the first three months following RT. By the sixth month, in comparison to the third, a decrease in the score was observed (PGWBI, p = 0.011). Later the HRQOL improved, but without reaching the maximum scores achieved. CONCLUSIONS: Patients on MMF showed less frequent incidence of AR. The HRQOL decreases during the third and the sixth month, but with less intensity in patients on MMF, probably related to the lower rate of AR, and excluding the over 60s.

[Preeclampsia and peripartum cardiomyopathy: infrequent association]. / Pre-eclampsia y miocardiopatía periparto: una asociación infrecuente.

Peripartum cardiomyopathy (PPCM) is a rare form of congestive heart failure that affects women late in pregnancy or in the early puerperium. PPCM is a disorder of unknown etiology that can have potentially devastating consequences. Although the etiology of PPCM remains unclear, a number of risk factors for this disorder have been proposed. However, the disease can occurred in women without these risk factors. Preeclampsia is associated with PPCM. However, cardiomyopathy is an infrequent complication of preeclampsia. Treatment of PPCM is similar to that other types of congestive heart failure. The pregnancy outcome is uncertain. Probably it depends on whether ther heart size returns to normal. We present the case of a 38 years old woman, who developed in an 33rd week of gestation a PPCM. She had some risk factors (include preeclampsia) but had a favorable evolution with conventional treatment. The rarity of the syndrome, its potential consequences, and the probable association with preeclampsia, stimulated us to present this case.

[Remission of severe disease induced by CMV and lymphoproliferative post-transplant disease after changing the immunosuppressive regime]. / Remisión de enfermedad severa por citomegalovirus y enfermedad linfoproliferativa post-trasplante en un receptor de trasplante renal tras terapia con ganciclovir y cambio en la medicación inmunosupresora.

We describe a renal transplant recipient, with overimmunosuppression induced by the interaction of tacrolimus and fluconazole, who developed two severe diseases produced by two different viruses of the herpes group (cytomegalovirus [CMV] disease and posttransplant lymphoproliferative [PTLD] disease EBV-related). Detection of Epstein-Barr virus (EBV) DNA in the blood preceded the histological diagnosis of PTLD. Both diseases improved after changes in the immunosuppressive regime and treatment with ganciclovir. Because CMV infection is a risk factor in developing PTLD, and the clinical and endoscopic manifestations of both diseases could be become confused, PTLD should be excluded in EBV seronegative patients that develop CMV disease. The detection of the EBV genome in blood could help in the early diagnosis of PTLD in these patients.

Disseminated herpes simplex virus infection in a renal transplant patient as possible cause of repeated urinary extravasations.

Disseminated herpes simplex virus type 2 (HSV-2) infections are infrequent in patients receiving organ transplants, but usually have a poor outcome. We describe the case of a renal transplant patient who developed a disseminated HSV-2 infection with repeated urinary extravasations. The diagnosis was carried out using a multiplex polymerase chain reaction nested assay and it suggested HSV-2 as a possible cause of repeated urinary fistulas.

A prospective study of a rapid method for diagnosing cytomegalovirus infections in immunosuppressed patients.

A rapid assay is described for detection of cytomegalovirus in peripheral blood lymphocytes. It consists of an indirect immunofluorescence technique for detection of cytomegalovirus antigens by means of a monoclonal antibody directed against early viral coded proteins. This assay was compared with the conventional cell culture system. Patients transplanted between December 1986 and May 1988 were studied, and of 27 patients identified, two were excluded due to early graft failure. A total of 320 blood specimens obtained were studied, and from 12 patients cytomegalovirus was isolated in at least one specimen by conventional cell culture (in total 25 specimens). Results were available with the new technique within 6 h, whereas the cell culture took an average of 13 days to develop the typical cytopathic effects changes. Sensitivity and specificity compared with that of viral isolation in conventional cell culture was 92% and 95%, respectively. This technique provides an accurate and rapid diagnosis of cytomegalovirus infections, and allows specific antiviral therapy to be started earlier.

Cytomegaloviraemia and T cell subpopulations in renal transplant patients.

We studied 54 consecutive recipients of renal transplants to evaluate their immunological responses to cytomegalovirus (CMV) infection. Forty-three (79.6%) patients developed CMV infection, and all of them subsequently recovered. Fourteen of these infected patients (32.6%) developed viraemia during the infectious process, four of whom then manifested the disease. The number of lymphocytes and their main subpopulations was normal before the appearance of CMV infection. During the infection there was a significant growth (P < 0.001) in the CD8+DR+ subset, corresponding to activated T suppressor/cytotoxic lymphocytes, whereas the natural killer measured subsets remained within normal limits during the whole infectious process. As all viraemic patients recovering from the infection developed CD8+DR+ activation, we conclude that this recovery is associated with the immunological activation.

Hyperthyroidism in a renal transplant recipient.

We report a case of toxic multinodular goiter with severe symptomatic hyperthyroidism in a female diagnosed 5 months after successful renal transplantation. To our knowledge, this is the first well-documented case of hyperthyroidism in a renal transplant recipient that responded well to methimazole. Special attention should be made to the use of methimazole and the possible interaction with immunosuppressive drugs.

Is the loss of health-related quality of life during renal replacement therapy lower in elderly patients than in younger patients?

BACKGROUND: Previous studies have reported that elderly (aged 65 years or over) end-stage renal disease (ESRD) patients have poorer health-related quality of life (HRQOL) than both younger patients and healthy subjects of the same age. The aim of present study was to evaluate the effect of ESRD and its treatment on the HRQOL, and to determine the effects of age and gender. METHODS: A cross-sectional multicentric study was carried out with 485 haemodialysis and renal-transplant patients, using the SF-36 Health Survey to evaluate their HRQOL. SF-36 scores were standardized by age and gender using Spanish normative data. Karnofsky scale score (KS), socio-demographic, and clinical data were also collected. RESULTS: In renal-replacement therapy (RRT), chronic haemodialysis, and renal-transplant patients, SF-36 standardized scores of elderly patients were higher than in younger patients. Therefore the reduction in HRQOL of elderly patients, in relationship with that of the general population of the same age and gender, was lower than in younger patients. In the case of renal-transplant patients, standardized scores in elderly patients were higher than in the general population for all parameters. CONCLUSIONS: Using standardized scores, elderly patients on renal replacement therapy (haemodialysis and kidney transplant) had relatively better HRQOL than younger patients, and in the case of transplant patients, they had even better HRQOL than in the general population of the same age and gender.

Control of cytomegalovirus disease in renal transplant patients treated with prednisone, azathioprine and cyclosporine using intensive monitoring and decreased immunosuppression.

BACKGROUND: The aim of this trial was to study the effectiveness of intensive monitoring, together with an early decrease in immunosuppression, in reducing the prevalence of CMV disease in renal transplant recipients treated with prednisone, azathioprine and cyclosporine. METHODS: From 1/95 to 11/97 a prospective, longitudinal study was conducted among 146 consecutive, unselected, renal transplant patients in our unit. Only 96 patients whose immunosuppressive regimens consisted of prednisone, azathioprine and cyclosporine and whose follow-up period was greater than 4 months were included in the study. Preemptive therapy was administered to 27 high-risk patients. CMV antigenemia (CMV-AG) and other virological tests were performed weekly for the first 4 posttransplant months. The immunosuppression was decreased when the first positive CMV-AG was detected. Azathioprine was completely withdrawn when the CMV-AG count was greater than 10 cells per 10(5) PBLs. The cyclosporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient. The prednisone dose was modified according to the immunosuppressive protocol. RESULTS: 53% (51/96) of the patients had positive CMV-AG on at least one occasion. The dose of azathioprine was decreased after CMV-AG detection in 41/51 (80.4%) patients and it was completely withdrawn in 23 of these (45%). The mean decrease in the dose of azathioprine was 73 +/- 31 (25-175) mg, a mean percentage decrease of 76 +/- 27% (25-100%). The dose of cyclosporine was progressively decreased during the 4 weeks after detection of the first CMV-AG (mean cyclosporine levels: 210 +/- 66, 196 +/- 54 and 164 +/- 36 ng/ml at the time of first CMV-AG detection, 2 and 4 weeks respectively, p < 0.0001, repeated measures analysis of variance). None of the 45 patients without CMV-AG and only 2 of 51 (3.9%) patients with CMV-AG developed symptomatic CMV disease (2% of the total). CMV disease was of moderate intensity in both patients. Only 3/51 (5.8%) patients developed acute rejection after the first CMV-AG detection in the 4 posttransplant months. CONCLUSION: The results of this study suggest that intensive monitoring and an early reduction of immunosuppression, together with preemptive therapy in high-risk patients, is effective in diminishing the prevalence and severity of CMV disease.