A new program of kidney transplantation from donors after cardiac death in Spain.

Despite the high rate of kidney transplantation in Spain, a disparity still exists between the numbers of donors and waiting-list patients. Donors after circulatory death (DCD) have been propagated as a promising approach to reduce the donor kidney shortage. In Europe most of the countries use controlled DCD, but in Spain, mainly uncontrolled DCD are harvested and until 2010 at only four institutions. In January 2010, we began a program of donation after uncontrolled DCD (Maastricht type II; unsuccessful resuscitation). The aim of this observational study was to describe our preliminary results. The numbers of recovered and transplanted organs per DCD were 27. There were no cases of primary nonfunction, but delayed graft function was present in 85% of recipients. Despite this impairment, about 75% of patients reached a serum creatinine below 2 mg/dL in the second month, with 1-year graft and patient survivals of 85% and 100%. Although, our preliminary results with a not very long follow-up and small number of patients suggested that utilization of DCD should be expanded because this type of donor increases the number of cases and opportunities of end-stage renal disease patients to reduce the waiting times for transplantation.

Evolution of left ventricular mass in renal transplant recipients: the influence of glucose homeostasis and oxidative stress.

BACKGROUND: Left ventricular hypertrophy, considered an independent factor for cardiovascular mortality, is frequent among renal transplant recipients (RTR), in whom we investigated changes in left ventricular mass (LVM) after grafting and associations with possible causal factors, especially glucose metabolism and oxidative stress. METHODS: We performed a prospective study of 37 RTR without prior diabetes mellitus who were evaluated at three times after transplantation (medians of 0.6, 16 and 28 months) by means of the LVM index (LVMI, echocardiographic measure of LVM related to body surface area, g/m(2)), oral glucose tolerance test and determinations of malondialdehyde and total glutathione (GSH), as well as glomerular filtration rate (GFR) estimate by the Modification of Diet in Renal Disease formula. We calculated the overall increment (DeltaLVMI) and percent change of LVMI. Patients were diagnosed to be prediabetic (PD) or new-onset diabetes after transplant (NODAT) according to ADA criteria. RESULTS: The mean LVMI decreased significantly over time among whole group baseline = 108.34 ± 27.71 g/m(2) versus middle: 100.03 ± 27.53 g/m(2) versus final: 90.62 ± 24.06 g/m(2) (P = .000). However, 13.5% of subjects showed an increased LVMI and 59.5%, a decrease less than 20%. Patients with NODAT at the end of the study showed a positive DeltaLVMI, which was negative in nondiabetics (0.24 ± 16.14 versus -19.86 ± 12.61 g/m(2), P = .018). Compared with DeltaLVMI(-) recipients, patients with DeltaLVMI(+) showed a greater proportion of PD and NODAT at baseline (60% and 40% versus 18.8% and 12.5%, P = .017), and significantly higher all-time fasting glycemia, lower estimated GFR, and greater increments of malondialdehyde and GSH over time. Those with a <20% LVMI decrease experienced progressive GFR impairment over time, as opposed to those with an LVMI decrease > 20%, who showed greater and improving GFR over the whole study. CONCLUSIONS: LVMI does not always improve in RTR; the evolution of ventricular mass after renal transplantation is influenced by glucose metabolism disorders, oxidative stress, and graft function.

Magnesemia in renal transplant recipients: relation with immunosuppression and posttransplant diabetes.

Hypomagnesemia, a frequent disorder in renal transplant patients related to the use of calcineurin inhibitors (CNIs), plays a causal role in insulin resistance and type 2 diabetes. Recently, hypomagnesemia has been identified as an independent predictor of new-onset diabetes after transplant (NODAT). The objective of this study was to investigate the influence of various immunosuppressive regimens on magnesemia in relation to the development of NODAT. We performed a retrospective study in 589 nondiabetic subjects who underwent serum magnesium measurements (mg/dL) on days 7 and 15 as well as at 1, 2, 3, 6, 9, and 12 months after transplantation. NODAT was diagnosed during the first year using American Diabetes Association criteria. The overall mean magnesemia was lower among CNI compared with non-CNI patients (1.73±0.25 vs 1.98±0.23; P=.000) and in patients on tacrolimus versus cyclosporine (1.72±0.24 vs 1.80±0.26; P=.007). It was higher in patients who received anti-CD25 antibodies with delayed CNI introduction (1.83±0.28 vs 1.71±0.23; P=.000). The use of CNIs and delayed CNI introduction were identified as independent factors related to magnesemia. No differences in magnesemia were observed among patients who developed NODAT versus the non-NODAT cohort. The incidence of NODAT was higher among patients on tacrolimus versus cyclosporine (26.8% vs 18.1%; P=.026), but no differences were found between the serum Mg tertiles at any time during the study or between mean magenesemia tertiles. In conclusion, despite the fact that CNI patients showed lower magnesemia and the group of tacrolimus, the lowest magnesemia and the highest incidence of NODAT, our study did not demonstrate a relationship between the Mg levels and the occurrence of NODAT. Patients treated with anti-CD25 antibodies and delayed CNI introduction maintained higher magnesemia during the first year after transplant.

Effect of preconditioning with triiodothyronine on renal ischemia/reperfusion injury and poly(ADP-ribose) polymerase expression in rats.

The ischemia/reperfusion (I/R) model in rats allows pharmacological investigation of protective renal effects of certain agents to thereby diminish the incidence of delayed graft function (DGF). The aim of this study was to determine the effects of preconditioning with triiodothyronine (T(3)) on renal function and oxidative status in renal I/R injury. Forty male Wistar rats were preconditioned with T(3) (100 microg/kg) or control (normal saline) at 24 hours prior to 45 minutes of renal ischemia, followed by a 4-hour (groups C-4h and T(3)-4h) or 24-hour (groups C-24h and T(3)-24h) reperfusion period. We determined renal function parameters (urea, creatinine, and proteinuria), oxidative stress biomarkers in plasma (malondialdehyde [MDA], glutathione [GSH], and superoxide dismutase [SOD]), urine (hydrogen peroxide [H(2)O(2)]), and renal tissue (GSH and MDA), and poly(ADP-ribose) polymerase (PARP-1) expression. Proteinuria was significantly lower in the T(3)-treated group (4.63 +/- 1.9 vs 9.27 +/- 0.72 mg/mL/100 g body weight). Pretreated rats showed lower levels of plasma and tissue MDA and urine H(2)O(2) (50.57 +/- 1.17 vs 71.16 +/- 1.14 micromol/100 g body weight). The T(3) treatment was associated with lower postischemia GSH concentrations (3.82 +/- 1.16 vs 4.89 +/- 0.68 nmol/mg protein) and higher SOD levels at 24 hours (11.27 +/- 0.86 vs 9.92 +/- 1.77 nmol/mg protein). Preconditioning with the hormone also reduced PARP-1 tissue expression by 18% (P

Prediabetic States, subclinical atheromatosis, and oxidative stress in renal transplant patients.

Prediabetic states are common among renal transplant patients, portending increased cardiovascular risk with associated carotid atheromatosis. Oxidative stress (OS) induces lipid peroxidation, a key factor in the development of atheromatosis. The aim of this study was to investigate the influence of OS and impaired glucose homeostasis status on carotid atheromatosis in nondiabetic recipients. Thirty-seven nondiabetic renal transplant patients were studied at baseline (<3 months) and at 1 and 2 years posttransplantation by ultrasound measurement of carotid intima-media thickness (CIMT), standard oral glucose tolerance test, and determination of blood markers of lipid peroxidation (8-isoprostanes [8-ISOP] and malondialdehyde [MDA]). Prediabetic state (impaired fasting glucose, impaired glucose tolerance, and provisional diagnosis of diabetes [provDM] and new-onset diabetes after transplantation [NODAT]) was classified following American Diabetes Association (ADA) criteria. Total CIMT index (TCIMT) was calculated as the sum of right and left CIMT and DeltaTCIMT as the difference in TCIMT values at 2 years (end of study) minus baseline. At baseline and 1 year, TCIMT was significantly related to 8-ISOP (r = .611; P = .002) and to recipient age (r = .654; P = .000). At 2 years, DeltaTCIMT was significantly correlated with MDA (r = .635; P = .001) with significant differences in TCIMT observed between prediabetic states and diabetes (P = .001). Multiple regression analysis identified 8-ISOP and age as factors independently associated with TCIMT and MDA with DeltaTCIMT. These results suggested that lipid peroxidation in renal transplant recipients contributed to increases in CIMT, which was more pronounced among older and diabetic (provDM or NODAT) patients.

Hepatitis C virus infection after renal transplantation.

Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.