One hundred six live kidney donors in a single German transplantation center: renal, physical, and psychological follow-up.

OBJECTIVE: The objective of this study was to analyze the psychological and physical status as well as renal outcomes of 106 live kidney donors between 1993 and 2003. METHODS: We performed general and nephrological examinations, including measurements of creatinine clearance (ClCr), proteinuria, and 24-hour blood pressure monitoring. We evaluated the psychological and general health situation using the standardized SF-36 questionnaire. RESULTS: We evaluated 69/106 (65%) live kidney donors at 5.3 ± 0.4 years after donation. The reason for the 37 drop-outs were unknown current address (n = 21), refusal of study participation (n = 14), and death due to accident and suicide (n = 2). In the 69 donors renal function was well preserved: serum creatinine 1.3 ± 0.0 mg/dL; ClCr 81 ± 2 mL/min; postdonation to predonation ClCr ratio 0.73 ± 0.02; and proteinuria 104 ± 11 mg/d. None of the donors experienced renal failure, although 36/69 (52%) patients have developed de novo hypertension. Compared with normotensive donors, the hypertensive subgroup was significantly older at the time of donation (50.7 ± 1.4 vs 46.4 ± 1.6 years; P = .010) and had a longer interval since donation (6.4 ± 0.2 vs 3.9 ± 0.1 years; P = .001). SF-36 questionnaire results in live kidney donors showed higher scores regarding physical (54.3 ± 0.8 vs 49.3 ± 0.1; P = .048) and psychological health (53.8 ± 0.6 vs 50.7 ± 0.1; P = .043) compared with the average German population. CONCLUSION: Our cohort of live kidney donors showed good renal outcomes and superior SF-36 scores in both physical and psychological health compared with the German population. The risk of de novo hypertension increased with age and time after donation. Blood pressure screening should be regularly performed especially in the long term after donation.

Immunoglobulin induction therapy in renal transplant recipients: Effects on immunoglobulin and regulatory antibody levels.

We have previously shown that high pretransplant regulatory autoantibodies are associated with better kidney graft outcome. To analyze the effect of intravenous immunoglobulin (IVIG) induction therapy on these regulatory antibodies, we performed a prospective randomized study in 50 renal transplant recipients who were randomly assigned to receive 7 x 10 g IVIG or 7 x 10 g IV albumin infusions. Basic immunosuppressive therapy consisted of tacrolimus/azathioprine (n = 24) and tacrolimus/mycophenolate mofetil (n = 26), respectively. ELISA was used to assess IgG-/IgA-anti-Fab, -anti-F(ab)2 and -anti-hinge regulatory antibodies. IVIG induction therapy resulted in upregulation of serum IgG and IgA levels within the first 20 days posttransplant (P = .001, IgG; P = .04, IgA), so that a significant IgG deficiency was found only in non-IVIG patients (day 10: IgG <6 g/L: 7/25 (28%) non-IVIG versus 0/25 IVIG patients; P = .005). As the IVIG charges contained all of the regulatory antibodies tested, intravenous administration of these antibodies explain the elevated IgG- and IgA-anti-F(ab)2 antibody levels found in IVIG compared to non-IVIG patients on day 10 (P = .005 and P = .04, respectively). Our data indicated that IVIG induction prevented severe IgG deficiency in the early posttransplant period but had no impact on severe infectious complications. IVIG induction enhanced immunoregulatory antibody levels early posttransplant, which might provide graft protective effects.

Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens.

Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin.

sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil.

High pretransplantation sCD30 levels have been shown to be associated with lower 5-year kidney graft survival in mainly Cyclosporine A (CsA)-treated recipients (Collaborative Transplant Study database). To analyze the effect of different immunosupressive regimens (CsA/Azathioprine [Aza], CsA/Mycophenolate Mofetil [MMF], Tacrolimus [Tacr]/Aza) on sCD30, we assessed serum sCD30 and neopterin together with in vitro cytokine responses in a prospective randomized study of 84 renal transplant recipients before, 4 months, and 1 year after transplantation. Panel-reactive antibody (PRA) formation, HLA matching, ATG induction therapy, and acute rejections had no impact on sCD30 levels, whereas cytomegalovirus (CMV) infections induced an up-regulation of sCD30 4 months posttransplantation (P = .003). Whereas MMF showed no effect on sCD30 compared with Aza therapy, we found a significant impact of Tacr versus CsA treatment (1-year sCD30 > or = 60 U/mL: 14/42 (33%), CsA; 1/38 (3%), Tacr; P < .0005). Chronic rejection 2 years posttransplantation was associated with elevated 1-year sCD30 (P = .001) and neopterin levels (P = .006). Our data indicate that the Th2 activation marker sCD30 provides a risk factor for chronic rejection independent of classical immunological risk factors and may be down-regulated using Tacr treatment.

Investigation on interaction between tacrolimus and sildenafil in kidney-transplanted patients with erectile dysfunction.

OBJECTIVE: Sildenafil may provide an effective treatment for erectile dysfunction, frequently observed in uremic patients and after kidney transplantation. Pharmacokinetic interactions between sildenafil and tacrolimus are to be expected due to a common elimination pathway via cytochrome P450 3A4. Therefore, the pharmacokinetics during combined use of these agents were studied over 9 days. MATERIAL AND METHODS: Nine male patients (age 29-52 years) were included, who had previously participated in a recent interaction study with sildenafil given as a single dose. Comedication remained unchanged in order to avoid introducing confounding factors. In the previous study in the patients, tacrolimus blood levels with and without sildenafil were measured for pharmacokinetic analysis. In the present study, 25 mg sildenafil were coadministered daily over 9 days and tacrolimus levels were assessed at sampling times optimized using simulation. In addition, laboratory parameters and blood pressure changes were measured and adverse effects monitored. RESULTS: Terminal half-lives of tacrolimus did not differ significantly and trough levels did not change when sildenafil was coadministered daily over 9 days. Mean arterial blood pressure was lower after sildenafil intake. Two patients had to reduce their antihypertensive treatment, 6 patients reported mild side effects. In 1 case, there was an asymptomatic, temporary increase in the serum concentration of gamma-GT. CONCLUSIONS: There was no evidence obtained for a change in elimination half-life or average concentration of tacrolimus during repeated coadministration of sildenafil. Since blood pressure decreased, a starting dose of 25 mg sildenafil and, if necessary, adjustment of the dose of antihypertensive drugs on days when sildenafil is given has to be considered. With respect to the observed blood pressure changes, pharmacokinetic/pharmacodynamic interaction studies with other antihypertensive drugs are of critical importance in these patients.