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.

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.

New-onset diabetes after kidney transplantation: risk factors.

New-onset diabetes after transplantation (NODAT) contributes to the risk for cardiovascular disease and infection, reducing graft and patient survival. For improvement of the outcome of kidney transplant recipients, it is of great interest to know precisely the risk factors that contribute to NODAT development. Nonmodifiable risk factors for development of NODAT are age, race, genetic background, family history of diabetes, and previous glucose intolerance. Modifiable risk factors are obesity and overweight, hepatitis C virus and cytomegalovirus infections, and immunosuppressive drugs. Both steroids and calcineurin inhibitors influence the appearance of NODAT, whereas the role of sirolimus in glucose metabolism currently is controversial.

Non-immunologic intervention in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy is the main cause of late graft loss. It has been suggested that both alloantigen-dependent and alloantigen-independent factors influence the development of progressive transplant failure. The present study analyzed the importance of non-immunologic factors in the progression of kidney disease in transplant patients, with the emphasis on well-established risk factors for progression in native kidneys. METHODS: A retrospective analysis was performed on 485 renal transplant patients who had functioning kidneys for at least 1 year. We investigated whether the initial presence and subsequent maintenance of proteinuria, hypertension, anemia, hyperlipidemia, and hyperparathyroidism influenced the progression of transplant failure. To analyze the relative effects of these factors, patients were categorized into two groups: group A had a baseline serum creatinine concentration of less than 1.5 mg/dL, and group B had a baseline serum creatinine concentration of 1.5 to 3 mg/dL. RESULTS: High urine protein excretion was a significant independent risk factor for progression of renal failure (group A: relative risk, 3.73; 95% confidence interval [CI], 2.24-6.21; group B: relative risk, 4.01; 95% CI, 2.51-6.39). Hypertension was also a significant independent risk factor for progression, but the risk was lower than for proteinuria (group A: relative risk, 1.2; 95% CI, 1.04-1.75; group B: relative risk, 1.20; 95% CI, 1.02-2.1). Anemia, hyperlipidemia, and hyperparathyroidism had no influence on the progression of renal failure. CONCLUSION: Our results show strong independent relationships between high blood pressure, urine protein excretion, and the relative risk of chronic progression of renal failure, as described for native kidney disease. These factors are potentially modifiable and are therefore attractive targets for therapeutic targets.

Evolution of tacrolimus blood levels and concentration-dose ratios in patients who develop new onset diabetes mellitus after kidney transplantation.

New onset diabetes mellitus (NODM) affects kidney transplantation outcome. Several risk factors, including immunosuppressive drug levels, are related with NODM development. This analysis evaluates the incidence and risk factors of NODM in kidney transplant patients receiving tacrolimus, taking into account 6-month blood levels and concentration-dose ratios (CDRs). Seventy-six patients under tacrolimus therapy who received a cadaveric renal transplant in our centre and with graft survival higher than 1 year were included in the study. NODM was defined as two fasting plasma glucose values > or =126 mg/dl or symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dl throughout the first year. We examined previously reported variables related with NODM development. The incidence of NODM at 12 months was 27.6%. Risk factors for NODM included older age, higher first tacrolimus level, higher body mass index and lower first year weight gain. In multivariate analysis, the first year occurrence of NODM was significantly determined by the first tacrolimus blood level >20 ng/ml and age older than 50 years. CDR remains significantly higher in NODM throughout the 6 months. Older age and a high first tacrolimus blood level are associated with the development of NODM during the first year after kidney transplantation. NODM patients show higher CDR during the first 6 months.

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.

Relationship of donor-specific class-I anti-HLA antibodies detected by ELISA after kidney transplantation on the development of acute rejection and graft survival.

BACKGROUND: The objective of this study was to evaluate the role of post-transplant donor-specific anti-HLA antibodies (DS-HLA Abs) detected by an ELISA method on long-term graft survival. METHODS: The serum pre-/post-transplant profile of anti-HLA Abs was analysed in 71 renal transplant patients by ELISA. The HLA specificity of positive sera was analysed by a different ELISA method. According to the results, patients were classified into two different groups: those who either developed DS-HLA Abs or significantly increased their panel-reactive antibody (PRA) (group A) and those who did not (group B). RESULTS: Thirteen out of 71 patients showed post-transplant DS-HLA Abs and were included in group A, whereas the remaining 58 were placed in group B. The incidence of acute rejection (AR) was significantly higher in group A than in group B (77 vs 10%). In addition, seven out of eight patients from group A had graft loss secondary to AR, whereas one of nine grafts lost in group B was due to AR. When analysing the clinical outcome according to HLA class specificity, only patients with HLA-I Abs lost their grafts due to vascular AR. The remaining patients with HLA-II Abs who lost their grafts also had HLA-I Abs. In four of the eight patients who lost their grafts, DS HLA-I Abs were detected several days before AR. CONCLUSIONS: The detection of DS HLA-I Abs in the post-transplant period may provide a good marker for AR and graft loss due to immunological origin. Monitorization of these Abs by ELISA may be a useful tool for tailoring immunosuppression after kidney transplantation.

Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation.

Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24-73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients.