Clinical evolution of post-transplant diabetes mellitus.

BACKGROUND: The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS: We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS: Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS: PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.

Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?

UNLABELLED: The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). METHODS: We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. RESULTS: Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) µg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. CONCLUSIONS: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

Prediabetes in patients receiving tacrolimus in the first year after kidney transplantation: a prospective and multicenter study.

BACKGROUND: Tacrolimus-based immunosuppression, the most widely used regimen in kidney transplantation, increases the risk of new onset diabetes after transplantation (NODAT). However, the prevalence, evolution and risk factors of different prediabetic alterations: impaired fasting glucose, impaired glucose tolerance, and provisional diabetes, have not been established. METHODS: In this multicenter and prospective study we evaluated 154 nondiabetic kidney transplant recipients receiving tacrolimus, mycophenolate mofetil and low dose steroids. An oral glucose tolerance test was performed 3 and 12 months after transplantation and prediabetes was defined by American Diabetes Association criteria. RESULTS: Prediabetes was highly prevalent and showed little variation between 3 and 12 months (36% and 33%, respectively). Impaired glucose tolerance was the most frequent abnormality observed (23% and 25%, respectively) observed. In addition, 20% of recipients showed NODAT by 1 year. Multivariate analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.004-1.14), pretransplant body mass index (OR: 1.3, CI: 1.09-1.6) and triglyceride/high density lipoprotein-cholesterol ratio, a marker of insulin resistance, (OR: 1.4, CI: 1.05-1.9) were independent risk factors for prediabetes. CONCLUSION: One in two recipients with tacrolimus-based immunosuppresion showed prediabetes or NODAT by 1 year posttransplantation when properly investigated. Older age and high pretransplant body mass index and triglyceride/high density lipoprotein-cholesterol ratio were risk factors for prediabetes. These findings may help applying early interventions to prevent the disorder.

Role of prostacyclin (epoprostenol) as anticoagulant in continuous renal replacement therapies: efficacy, security and cost analysis.

BACKGROUND: Heparin remains the drug most commonly used for anticoagulation in continuous renal replacement therapies (CRRTs). However, in patients with hypercoagulability, heparin is insufficient or, in cases with an increased risk of bleeding or thrombocytopenia, it may be contraindicated. Epoprostenol, a potent vasodilator, antithrombotic and antiplatelet agent, could be an alternative. PATIENTS AND METHODS: We studied the records of patients treated under continuous venovenous hemodiafiltration in an academic tertiary hospital of 900 beds, between January 2000 and June 2003. Epoprostenol was prescribed to patients with (i) filter hypercoagulability, defined as consumption of 2 or more filters in the last 24 hours; (ii) low platelet count; or (iii) recent severe hemorrhage. RESULTS: Thirty-eight out of 248 (15%) patients who were under CRRT received epoprostenol for more than 72 hours. Epoprostenol was indicated due to filter hypercoagulability in 48%, thrombocytopenia in 68% (7 patients both) and hemorrhage in 3% of cases. The overall time for epoprostenol therapy was 9,749 hours. The mean filter duration previous to epoprostenol was 23 +/- 12 hours and after administering this drug 38.2 +/- 11.9 hours (p = 0.0001). In 6 patients, heparin and epoprostenol were simultaneously administered. The adverse effects were hemorrhage, which presented in 7 patients (18%) and a fall in blood pressure in another 7 (18%), which recovered in the next 24 hour after starting treatment. Cost analysis demonstrates some advantage with epoprostenol in patients with increased tendency to clotting. CONCLUSIONS: Epoprostenol may be safely used to prevent clotting of the extracorporeal circuits, either alone in patients with thrombocytopenia and/or increased risk of bleeding, or in combination with heparin in states of hypercoagulability.

Late evolution of kidney transplants in elderly donors and recipients receiving initial immunosuppressant treatment with daclizumab, mycophenolate mofetil, and delayed introduction of tacrolimus.

BACKGROUND: Organ transplants in elderly recipients have increased over the past few years. This situation poses specific problems both in terms of organs and recipients; therefore, immunosuppressant regimens must be adapted accordingly. A previous study demonstrated good initial results in kidney transplant cases in which older donors and recipients (average ages of 64.4 years and 61.3 years) had received initial immunosuppressant therapy with daclizumab and mycophenolate mofetil as well as delayed introduction of reduced-dose tacrolimus. In this study we reviewed the long-term results in the same group of patients. METHODS: An observational, retrospective multi-centre study carried out at a national level to determine survival rates and renal function in 126 patients included in the initial study (127 patients who survived the first year with a functioning graft, 123 treated according to protocol). We gathered data from the 2nd to the 6th year for 120, 118, 113, 102 and 62 patients, respectively. The evolution of renal function, relevant clinical data, and safety profiles were also analysed. RESULTS: After five years, most patients continued with the initial immunosuppressant regimen: 92% tacrolimus and 80% mycophenolate mofetil; 48% had abandoned steroids and proliferation signal inhibitors had been introduced in 3%. Patient and graft survival (adjusted for patient death) after five years was 93.1% and 93.8%, respectively. The main cause of death was neoplasia (in 7 out of 10 cases) whilst graft loss was mainly due to death with a functioning graft. The other causes of death were 2 acute myocardial infarctions and a gastrointestinal haemorrhage. Renal function was moderately but significantly reduced with the passing of time (P<.001): average creatinine levels in the overall group of patients rose from 1.60 ± 0.50mg/dl after the 1st year to 1.63 ± 0.70 mg/dl at the end of study. MDRD dropped from 46.28 ± 15.64 ml/min after the 1st year to 45.69 ± 15.44 ml/min at the end of study (P<.01). Only two acute rejections were observed after the 1st year. There were 19 cardiovascular events registered in 12 patients. CONCLUSIONS: The regimen used in our study was useful and appropriate for elderly donor-recipient pairs as demonstrated by the good long-term survival results, continued optimum renal function, and acceptable safety profile.

Pre-transplant weight but not weight gain is associated with new-onset diabetes after transplantation: a multi-centre cohort Spanish study.

Background. New-onset diabetes after transplantation (NODAT) is associated with poorer outcomes in kidney transplantation (KT). Thus, identification of modifiable risk factors may be crucial for ameliorating the impact of this entity on transplant outcomes. We assessed the relationships between the weight, body mass index (BMI) and weight gain with NODAT.Methods. We retrospectively analysed 2168 KT performed in Spain during 1990, 1994, 1998 and 2002, with a functioning graft after the first year. At 1 year after KT, three groups were considered: (i) NODAT group (n = 215); (ii) impaired fasting glucose (IFG) group (n = 389); (iii) control group (n = 1564).Results. The incidence of NODAT was 10.8%, 9.9% and 10.0% at 3, 12 and 24 months post-transplantation, respectively. Older recipient age (P < 0.0001) and greater use of tacrolimus (P < 0.0001) were observed in NODAT group. Obesity was more frequent in NODAT group (P < 0.0001), but patients with NODAT had a lower weight gain during the first year after KT (P = 0.038). On multivariate analysis, independent risk factors associated with the development of NODAT were: recipient age [odds ratio (OR): 1.060, P = 0.0001], tacrolimus (OR: 1.611, P = 0.005), triglycerides (OR: 1.511, P = 0.018), positive hepatitis C virus (HCV) status (OR: 1.969, P = 0.001) and pre-transplant body mass index (BMI) (OR: 1.135, P = 0.0001), but not the weight gain.Conclusions. BMI, but not the weight gain at 1 year after transplant, is an independent risk factor for NODAT. Tailoring clinical strategies may minimize the impact of this complication.

Hyperinsulinemia and hyperfiltration in renal transplantation.

BACKGROUND: Insulin-resistance hyperinsulinemia is a novel risk factor for renal disease in the general population. Glomerular hyperfiltration has been proposed as an early consequence of hyperinsulinemia. METHODS: In this multicenter cohort study, we analyzed 202 patients without diabetes before or after renal transplantation during the first posttransplant year. Insulin was measured at 3 and 12 months. The majority of patients (91%) were on calcineurin inhibitors. Patients were classified as with persistent normo or hyperinsulinemia when situated below or above the median value of insulin (3 months: 9 muU/mL; 12 months: 8.74 muU/mL) at both periods. The 3 to 12 months percent change in calculated creatinine clearance (3-12 months DeltaCrCL) was calculated. RESULTS: Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12 months DeltaCrCL compared with those with persistent normoinsulinemia (12% [-20/40] vs. -0.03% [-12/18], P=0.035). We performed a multivariate linear regression analysis with the 3 to 12 months DeltaCrCL as the dependent variable and different factors that may induce hyperfiltration, including persistent hyperinsulinemia, as covariates. Persistent hyperinsulinemia was a risk factor for increased CrCL (beta 0.09, 95% CI 0.07/0.12, P=0.035). CONCLUSION: In nondiabetic recipients during the first posttransplant year, hyperinsulinemia induced increments in CrCL. As this may herald future renal dysfunction, hyperinsulinemia should not be ignored as a potential target in this population.

Kaposi's sarcoma in renal transplant patients: experience at the Cruces Hospital in Bilbao.

BACKGROUND: Kaposi's sarcoma (KS) in renal transplant recipients (RTRs) probably arises from a complex interplay of multiple factors. OBJECTIVE: In order to analyze the prevalence of KS in patients transplanted at the Cruces Hospital in Bilbao, together with their clinical features, treatment, and etiologic factors, we performed a study using the registry of RTRs in our center. METHODS: The records of 1,230 kidney transplant patients at the Cruces Hospital between 1979 and 1998 were reviewed. Immunosuppressive therapy was reduced once a diagnosis of KS was made. A nested polymerase chain reaction was used to detect human herpesvirus 8 (HHV-8) DNA in the biopsy tissue. The DNA was extracted from fresh tissue (n = 2) or from formalin-fixed, paraffin-embedded specimens (n = 5). RESULTS: Six cases of KS were diagnosed. All patients with cutaneous KS improved with a reduction in immunosuppressive drugs. HHV-8 was detected in 100% (2/2) of the frozen biopsies and 20% (1/5) of the formalin-fixed samples investigated. CONCLUSIONS: Our experience indicates that a continuous state of immunodeficiency is important for the development of KS in RTRs. The association, previously described between HHV-8 and transplant-associated KS, also exists in the studied population.

Early post-transplant renal allograft function between 1990 and 1998 in Spain.

BACKGROUND: The last decade has witnessed a sustained improvement of renal allograft survival that is partly explained by a better preservation of renal allograft function. This study describes time-dependent modifications of serum creatinine (SCr) during the first year after transplantation in the last decade in Spain and characterizes the predictive value of SCr on death-censored graft survival. METHODS: A total of 3365 adult patients transplanted in 1990 (n = 824), 1994 (n = 1075) and 1998 (n = 1466) with a functioning graft after the first year were included. Renal function deterioration during the first year was expressed as the difference between SCr at 1 year and SCr at 3 months. RESULTS: Despite the projected renal allograft half-life, estimation was significantly higher in 1998 than in 1990 (17.7 vs 15.4 years, P = 0.007), the SCr levels at 3 months were significantly lower in 1990 (1.59+/-0.64) than in 1998 (1.65+/-0.66). While SCr tended to worsen during the first year in 1990 (0.05+/-0.64) it improved in 1998 (-0.003+/-0.48), P = 0.0001. The following variables were significantly associated with SCr at 3 months: donor age and sex, cause of death, recipient sex, time on dialysis, cold ischaemia time, delayed graft function, acute rejection, cytomegalovirus infection and reintervention for any reason. Renal function deterioration during the first year was associated with the presence of acute rejection and hepatitis C virus antibodies in the recipient. CONCLUSIONS: Despite poorer renal function at 3 months in 1998 than in 1990, renal allograft survival has improved in Spain between 1990 and 1998. This result is partly explained by a slower deterioration of renal function during the first year of follow-up.