Contraceptive Choices and Counseling in Norwegian Female Renal Transplant Recipients.

BACKGROUND: There are major gaps in the understanding of sexual and reproductive health in female renal transplant recipients. METHODS: In this Norwegian multicenter retrospective observational study, 118 female renal transplant recipients aged 22 to 49 years responded to a questionnaire on fertility, contraceptive use, and pregnancy. RESULTS: More than one-third (37%) of patients reported that they did not receive advice on contraceptive methods from health care personnel in the early post-transplant phase. These women used effective contraceptive methods less often. Nearly half of the patients (45%) reported that they had not received any advice on timing of conception after transplant. From 95 pregnancies after renal transplant, 52 (55%) resulted in live births. CONCLUSION: Counseling on contraceptive methods should be part of standard care in conjunction with transplantation. More than one-third of young female renal transplant recipients of reproductive age could not recall having received advice from health care personnel about contraceptive use, and nearly half of the patients did not receive preconceptional advice after transplant. Although the current study does not discriminate between lack of advice and recall bias, the findings signal the need for improved counseling on female sexual and reproductive health after renal transplant.

Pancreas transplant rejection episodes are not revealed by biopsies of the donor duodenum in a prospective study with paired biopsies.

The surgical technique with duodeno-duodenal enteroanastomosis of pancreas transplants allows for representative endoscopic ultrasound-guided needle biopsies of the donor duodenum and the pancreas graft. We assessed whether histological findings in transplanted donor duodenal biopsies can indicate rejection in the transplanted pancreas. Since September 2012, a duodeno-duodenal enteroanastomosis has been the default technique for pancreas transplantations at our center. In 67 recipients we prospectively examined 113 endoscopic ultrasound-guided procedures with representative biopsies from the duodenum grafts and the pancreas grafts (97 per protocol and 16 on indication). All graft biopsies were evaluated according to established rejection criteria. A total of 22 biopsy-proven pancreas rejections were detected, with 2 matching duodenal biopsies showing rejection. This gives a sensitivity of 9% for detection of a pancreas rejection by duodenal biopsies. The other matching duodenal biopsies were either normal (n = 13) or indeterminate (n = 7). Rejection of the donor duodenum was found in only 6/113 biopsies, with 2 concurrent pancreas rejections. In conclusion, the donor duodenum is not a useful reporter organ for rejection in the pancreas graft.

European perspective on human polyomavirus infection, replication and disease in solid organ transplantation.

Human polyomaviruses (HPyVs) are a growing challenge in immunocompromised patients in view of the increasing number of now 12 HPyV species and their diverse disease potential. Currently, histological evidence of disease is available for BKPyV causing nephropathy and haemorrhagic cystitis, JCPyV causing progressive multifocal leukoencephalopathy and occasionally nephropathy, MCPyV causing Merkel cell carcinoma and TSPyV causing trichodysplasia spinulosa, the last two being proliferative skin diseases. Here, the current role of HPyV in solid organ transplantation (SOT) was reviewed and recommendations regarding screening, monitoring and intervention were made. Pre-transplant screening of SOT donor or recipient for serostatus or active replication is currently not recommended for any HPyV. Post-transplant, however, regular clinical search for skin lesions, including those associated with MCPyV or TSPyV, is recommended in all SOT recipients. Also, regular screening for BKPyV replication (e.g. by plasma viral load) is recommended in kidney transplant recipients. For SOT patients with probable or proven HPyV disease, reducing immunosuppression should be considered to permit regaining of immune control. Antivirals would be desirable for treating proven HPyV disease, but are solely considered as adjunct local treatment of trichodysplasia spinulosa, whereas surgical resection and chemotherapy are key in Merkel cell carcinoma. Overall, the quality of the clinical evidence and the strength of most recommendations are presently limited, but are expected to improve in the coming years.

Improved patient survival with simultaneous pancreas and kidney transplantation in recipients with diabetic end-stage renal disease.

AIMS/HYPOTHESIS: We aimed to determine whether simultaneous pancreas and kidney (SPK) transplantation would improve patient and kidney graft survival in diabetic end-stage renal disease (ESRD) compared with kidney transplantation alone (KTA). METHODS: Follow-up data were retrieved for all 630 patients with diabetic ESRD who had received SPK or KTA at our centre from 1983 to the end of 2010. Recipients younger than 55 years of age received either an SPK (n = 222) or, if available, a single live donor kidney (LDK; n = 171). Older recipients and recipients with greater comorbidity received a single deceased donor kidney (DDK; n = 237). Survival was analysed by the Kaplan-Meier method and in multivariate Cox regression analysis adjusting for recipient and donor characteristics. RESULTS: Patient survival was superior in SPK compared with both LDK and DDK recipients in univariate analysis. Follow-up time (mean ± SD) after transplantation was 7.1 ± 5.7 years. Median actuarial patient survival was 14.0 years for SPK, 11.5 years for LDK and 6.7 years for DDK recipients. In multivariate analyses including recipient age, sex, treatment modality, time on dialysis and era, SPK transplantation was protective for all-cause mortality compared with both LDK (p = 0.02) and DDK (p = 0.029) transplantation. After the year 2000, overall patient survival improved compared with previous years (HR 0.40, 95% CI 0.30, 0.55; p < 0.001). Pancreas graft survival also improved after 2000, with a 5 year graft survival rate of 78% vs 61% in previous years (1988-1999). CONCLUSIONS/INTERPRETATION: Recipients of SPK transplants have superior patient survival compared with both LDK and DDK recipients, with improved results seen over the last decade.

A 1-year randomized, double-blind, placebo-controlled study of intravenous ibandronate on bone loss following renal transplantation.

The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated.

Single transplanted kidneys from a 90-year-old deceased donor perform acceptably at 1 year.

Most centers are reluctant to accept expanded criteria donors above 70 to 75 years of age. We accepted kidneys from a 90-year-old male and report the 1-year outcome. The kidneys were used as single transplants and both had immediate graft function. Recipient A was a 71-year-old male, with cold ischemia time of 4 hours 49 minutes. One rejection was successfully treated with intravenous methylprednisolone. At 1 year, serum creatinine was 146 µmol/L with estimated glomerular filtration rate (eGFR) 41 mL/min. Recipient B was a 79-year-old male with known panel-reactive antibody positivity prior to transplantation. Cold ischemia time was 10 hours 4 minutes. He experienced no rejections. At 1 year serum-creatinine was 99 µmol/L with eGFR 63 mL/min. Both recipients performed a surveillance biopsy at 1 year with identical findings: interstitial fibrosis and tubular atrophy grade 1 with moderate to severe arteriolosclerosis. We conclude that both kidneys performed acceptably 1 year after engraftment. The use of old kidneys in old recipients gives them a properly functioning kidney and improves quality of life. Longer observation is needed.

Quality of life in kidney donors.

Reports on quality of life of kidney donors include small populations with variable response rates. The aim was to evaluate quality of life in kidney donors in a large cross-sectional study. Through the Norwegian Renal Registry we contacted all 1984 kidney donors in the period 1963-2007 with a response rate of 76%. All received the Short-Form-36 (SF-36) survey form and a questionnaire specifically designed for kidney donors. SF-36 scores for a subgroup (n = 1414) of kidney donors were not inferior to a general population sample, adjusted for age, gender and education. When asked to reconsider, a majority stated that they still would have consented to donate. Risk factors for having doubts were graft loss in the recipient (OR 3.1, p < 0.001), medical problems after donation (OR 3.7, p < 0.001), unrelated donor (OR 2.2, p = 0.01) and less than 12 years since donation (OR 1.8, p = 0.04). Older age at donation was associated with lower risk (OR 0.98, p = 0.03). Compared with other donors, those expressing doubts had inferior SF-36 scores. Norwegian kidney donors are mostly first-degree relatives. They are fully reimbursed and offered life-long follow-up. All inhabitants are provided universal healthcare. This should be considered when extrapolating these results to other countries.

Early, abrupt conversion of de novo renal transplant patients from cyclosporine to everolimus: results of a pilot study.

In a single-center study, 20 kidney transplant patients without prior rejection were abruptly converted from cyclosporine to everolimus at seven wk post-transplant. All patients received basiliximab induction with maintenance enteric-coated mycophenolate sodium and corticosteroids. Biopsy-proven acute rejection had occurred in three of 20 patients (15.0%) by the end of week seven post-conversion. All episodes were mild and reversible, with subsequent recovery of renal function. Calculated glomerular filtration rate (GFR) improved significantly (51 +/- 11 mL/min at time of conversion, 58 +/- 12 mL/min at week seven post-conversion, 57 +/- 17 mL/min at month six post-conversion; p = 0.001). No patient developed proteinuria in the nephrotic range. Twenty-two adverse events were reported in 10 patients, three of which had a suspected relationship to everolimus. Mean leukocyte and platelet count decreased significantly, and triglyceride level increased. This study suggests that kidney transplant patients without prior rejection can be converted abruptly from cyclosporine to everolimus at seven wk post-transplant, resulting in significantly improved renal function with no apparent increase, in risk of rejection and good tolerability.

ABO-incompatible deceased donor liver transplantation with the use of antigen-specific immunoadsorption and anti-CD20 monoclonal antibody.

In patients with fulminant liver failure requiring emergency liver transplantation, the only donor organ that becomes available may be ABO incompatible. The risk of graft failure because of antibody-mediated acute rejection is high, but can be reduced by various means. We reported a deceased donor ABO-incompatible liver allograft recipient who was treated with antigen-specific immunoadsorption in combination with anti-CD20 monoclonal antibody and conventional plasmapheresis and immunosuppression. The patient was a 33-yr-old male with blood group A who presented with subacute liver failure of unknown aetiology and received a blood group AB liver graft. Pretransplant he underwent plasmapheresis and received one dose of rituximab. The immunosuppressive regimen consisted of methylprednisolone, tacrolimus and mycophenolate mofetil. Despite regular post-operative plasmapheresis sessions, anti-B antibody titres increased. Antigen-specific immunoadsorption with depletion of anti-B antibodies was performed from day nine to day 17. Thereafter, anti-B IgM and IgG antibody titres remained low. After one month the patient was reoperated with hepaticojejunostomy because of bile duct necrosis and with reconstruction of a stenotic hepatic artery. A mild rejection was successfully treated with methylprednisolone four months post-transplant. At six months post-transplant there was a stricture of the biliary-enteric anastomosis, but the graft was well functioning. We conclude that antigen-specific immunoadsorption can be an important adjuvant therapy to control recipient anti-A/B antibody levels and prevent acute rejection in ABO-incompatible deceased donor liver transplantation.

Inosine monophosphate dehydrogenase activity in renal allograft recipients during mycophenolate treatment.

OBJECTIVE: Mycophenolic acid (MPA) exerts its immunosuppression by inhibiting inosine 5'-monophosphate dehydrogenase (IMPDH), depleting activated lymphocytes of guanine nucleotides and retarding their proliferation. An optimal strategy for monitoring has not been established for mycophenolate mofetil (MMF) in renal transplantation, and clinical investigations of the pharmacokinetic-pharmacodynamic relationship are warranted. MATERIAL AND METHODS: Mycophenolic acid pharmacokinetics and whole blood cell IMPDH activity were investigated in two separate groups of renal allograft recipients. One group was studied within the 12-h dose interval, while the second group was examined by pre-dose samples pre-transplant and then repeatedly during 8 weeks post-transplant. RESULTS: An inverse relationship between plasma MPA and IMPDH activity within the dose interval was demonstrated. Minimum IMPDH activity was a median 8 % of values pre-MMF dose, coinciding with the MPA peak. Six hours post-dose, IMPDH activity had returned to pre-dose values. Patients receiving MMF had a 4.5-fold higher pre-dose enzyme activity than transplanted patients without MMF. During the 8 weeks post-transplant, the median MPA trough concentration was fairly stable. Following an initial decrease during the first 4 days post-transplant, IMPDH activity gradually increased during the 40 days post-transplant, reaching 5-fold the pre-transplant values. CONCLUSIONS: Provided that the changes in IMPDH activity in whole blood cells predict the clinical effect, these pharmacokinetic-pharmacodynamic findings may prove useful in the attempts to identify optimal timing and range for the monitoring of mycophenolate in renal transplantation. The question of whether MPA concentrations or measurements of IMPDH activity per se will be the optimal way of monitoring this immunosuppressant remains open and will only be answered by prospective clinical testing.

Calcineurin inhibitor-free immunosuppression in renal allograft recipients with thrombotic microangiopathy/hemolytic uremic syndrome.

Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent serious threats to kidney allograft recipients. During a 4-year period, among 850 kidney transplantations, seven recipients with primary HUS and seven recipients (eight transplants) with previous or de novo TMA/HUS were identified and given calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL), mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were successful in the long term; resulting in a mean creatinine of 101 mumol/L (16.4 months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS recurrences were observed. A high rate of acute rejections (53%) may indicate insufficient immunosuppressive power and/or a causative relationship between TMA/HUS and rejection. Wound-related complications were abundant (60%), and call for surgical/immunosuppressive countermeasures. Our experience supports the idea that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of TMA/HUS should be carefully explored in recurrent 'high responders'.

Therapeutic drug monitoring of cyclosporine.

Therapeutic drug monitoring of cyclosporine has been established as part of the routine clinical treatment for patients after organ transplantation. The inability to define optimal dose (maximize efficacy/minimize toxicity) has been a problem related to drug monitoring of cyclosporine. The original cyclosporine formula showed high intra-patient and inter-patient variability and low bioavailability. The microemulsion formulation of cyclosporine (Neoral) was introduced to address the absorption problems related to the original cyclosporine formulation. With the introduction of Neoral, renewed interest in methods of therapeutic drug monitoring brought us from trough monitoring (C0) to levels measured 2 hours after dosing (C2). The pharmacokinetic rationale for using C2 to monitor patients receiving Neoral has demonstrated a reduced incidence of rejection in de novo patients and improvements in safety profile in both renal and hepatic transplant recipients. Monitoring C2 levels is a more precise method for optimizing cyclosporine dosing and a better way to individualize therapy. Further data are required from prospective trials to evaluate the clinical benefits of adopting C2 monitoring in cardiac and lung transplant recipients as well as in long-term maintenance patients.

Efficacy of nifedipine or lisinopril in the treatment of hypertension after renal transplantation: a double-blind randomised comparative trial.

Calcium channel blockers and angiotensin converting enzyme-inhibitors are commonly used in the treatment of hypertensive renal transplant recipients. The purpose of this study was to investigate if the response rate to treatment differs with these drugs in this setting. A single centre, prospective, randomised, double-blinded, comparative study to address the efficacy of controlled release nifedipine or lisinopril in the treatment of hypertension (diastolic blood pressure > or =95 mmHg) in cyclosporin (CsA)-treated renal transplant recipients was performed. Recipients were randomised to receive either lisinopril (10 mg once daily) or controlled release nifedipine (30 mg once daily). The dose was doubled on indication. The number of responders (diastolic blood pressure <90 mmHg on monotherapy) were addressed during the early post-transplant phase (first 3 months) and during a late post-transplant phase (from 3 to 12 months after renal transplantation) in the same patient population. One hundred and fifty-four patients (nifedipine=78, lisinopril=76) with untreated hypertension (diastolic blood pressure> or =95 mmHg) were randomised within 3 wk after renal transplantation. One hundred and twenty-three patients (nifedipine=69, lisinopril=54) completed the study. Fourteen (20%) nifedipine-treated recipients responded during the early, and 26 (38%) during the late post-operative phase (months 4-12 after renal transplantation). Eleven (20%) lisinopril-treated recipients responded during the early, and 18 (33%) during the late post-transplant phase. Non-responders were, on average, 8.5+/-1.5 kg heavier both in the early phase and after 1 yr of treatment (p<0.01), and 6.1+/-0.9 yr older than responders (p<0.05). In conclusion, these results indicate that both controlled release nifedipine and lisinopril are equally efficient in the treatment of post-transplant hypertension. As monotherapy, both drugs show a "response rate" of 20-38%, depending on time interval after transplantation.

Sustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril.

BACKGROUND: Treatment of posttransplant hypertension is still a matter of debate. Calcium antagonists may ameliorate renal side effects of cyclosporin. Angiotensin converting enzyme- (ACE) inhibitors may be more effective in sustaining renal function in native chronic renal disease. We prospectively compared the effect of controlled release nifedipine and lisinopril on long-term renal function in hypertensive kidney transplant patients treated with cyclosporin. METHODS: A total of 154 renal transplant patients presenting with hypertension (diastolic blood pressure >or=95 mmHg) during the first 3 weeks after transplantation were randomised to receive double-blind nifedipine 30 mg or lisinopril 10 mg once daily. A total of 123 patients completed 1 year of treatment (69 nifedipine, 54 lisinopril) and 64 patients completed 2 years of double-blind treatment (39 nifedipine, 25 lisinopril). Baseline glomerular filtration rate was measured as 99 mTc-diethylene-triaminepentaacetate clearance in a stable phase 2 to 5 weeks after inclusion and repeated at 1 and 2 years. RESULTS: Baseline glomerular filtration rates were similar (46+/-16 ml/min with nifedipine, 43+/-14 ml/min with lisinopril). The changes in glomerular filtration rates from baseline were statistically significant between the groups after 1 year (9.6 ml/min mean treatment difference (95% confidence interval [CI]s 5.5-13.7 ml/min, P=0.0001) and remained statistically significant also after 2 years (10.3 ml/min mean difference (95% CIs 4.0-16.6], P=0.0017). After 1 year glomerular filtration rates averaged 56+/-19 ml/min in the nifedipine group and 44+/-14 ml/min in the lisinopril group. CONCLUSIONS: Both nifedipine and lisinopril were safe and effective in treatment of hypertension in renal transplant patients treated with cyclosporin. Patients receiving nifedipine but not lisinopril improved kidney transplant function over a period of 2 years.

Insulin resistance after renal transplantation: impact of immunosuppressive and antihypertensive therapy.

OBJECTIVE: The purpose of the present study was to validate various surrogate estimates of insulin sensitivity (IS) in a renal transplant population and to assess the influence of immunosuppressive and antihypertensive therapy on insulin resistance (IR) after renal transplantation. RESEARCH DESIGN AND METHODS: A total of 167 consecutive renal transplant recipients without previously known diabetes underwent a 75-g oral glucose tolerance test (OGTT) 3 months after renal transplantation. A total of 43 patients also underwent a euglycemic-hyperinsulinemic glucose clamp study. Six OGTT-derived IS indexes were validated against the euglycemic-hyperinsulinemic glucose clamp-derived IS index (ISI(CLAMP)). RESULTS: The OGTT-derived ISI(TX) correlated closely with the ISI(CLAMP) (r = 0.58, P < 0.001). The other surrogate estimates of IS were also significantly but less well correlated with the ISI(CLAMP) (Spearman's correlation; r = -0.45 to 0.41, P = 0.003-0.050). In the univariate model, BMI, daily prednisolone dose, creatinine clearance, hypertension, number of antihypertensive agents, and use of diuretics or beta-blockers were negatively associated with ISI(TX) (P < 0.05). After multiple regression analysis, BMI (P < 0.001), daily prednisolone dose (P < 0.001), cytomegalovirus infection (P = 0.030), and triglycerides (P = 0.034) were shown to be independent predictors of posttransplant IR. CONCLUSIONS: The OGTT-derived ISI(TX) may be a useful estimate of IS in Caucasian renal transplant recipients. Increasing daily prednisolone dose is an independent predictor of IR after renal transplantation. Hypertension and the use of beta-blockers and diuretics may also deteriorate IR in this group of patients.

Reduction of left ventricular mass by lisinopril and nifedipine in hypertensive renal transplant recipients: a prospective randomized double-blind study.

BACKGROUND: Cardiovascular disease is the dominant cause of death in renal transplant recipients. Left ventricular hypertrophy (LVH) is a known risk factor. After renal transplantation, persistent hypertension is an important determinant for the further evolution of LVH. The aim of the present study was to compare the effect of an angiotensin converting enzyme (ACE) inhibitor (lisinopril) with a calcium channel blocker (CCB) (controlled release nifedipine) in treatment of posttransplant hypertension focusing on changes in LVH. METHODS: One hundred fifty-four renal transplant recipients presenting with hypertension (diastolic BP> or =95 mmHg) during the first 3 weeks after transplantation were randomized to receive double-blind 30 mg nifedipine or 10 mg lisinopril once daily. RESULTS: One hundred twenty-three patients completed 1 year of treatment. Good quality echocardiographic data were available in 116 recipients (62 nifedipine/54 lisinopril) 2 and 12 months posttransplant. Blood pressure was equally well controlled in the two groups throughout the study (mean systolic/diastolic+/-SD after 1 year: 140+/-16/87+/-8 mmHg with nifedipine and 136+/-17/85+/-8 mmHg with lisinopril). Left ventricular mass index was reduced by 15% (P<0.001) in both groups (from 153+/-43 to 131+/-38 g/m2 with nifedipine and from 142+/-35 to 121+/-34 g/m2 with lisinopril). There were no statistically significant differences between the two treatment groups at baseline or at follow-up. CONCLUSIONS: In hypertensive renal transplant recipients with well-controlled blood pressure, there is a regression of left ventricular mass after renal transplantation. The regression of left ventricular mass index is observed to a similar extent in patients treated with lisinopril or nifedipine.

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.

BACKGROUND: The prevalence of hypertension in renal transplant recipients is high but the pathophysiology is poorly defined. Impaired endothelial function may be a factor of major importance. The present study addresses the effects of long-term treatment with either lisinopril or slow-release nifedipine on microvascular function and plasma endothelin in renal transplant recipients on cyclosporin A (CsA). METHODS: Seventy-five hypertensive renal transplant recipients were double-blind randomized to receive slow-release nifedipine (NIF, n=40) or lisinopril (LIS, n=35). Ten normotensive, age-matched recipients served as controls. All patients received CsA-based immunosuppressive therapy including prednisolone and azathioprine. Microvascular function was assessed in the forearm skin vasculature, using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia and endothelial-dependent function during local acetylcholine (ACh) stimulation. RESULTS: The analysis of microvascular function (AUC(rh)) showed that nifedipine-treated patients had significantly lower responses compared with lisinopril-treated patients (20+/-17 and 43+/-20 AU x min respectively, P=0.0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640+/-345 and 817+/-404 AU x min respectively, P=0.056). The responses in the LIS group were comparable with those in non-hypertensive controls (AUC(rh) was 37+/-16 and AUC(ACh) was 994+/-566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44+/-0.19 vs. 0.34+/-0.10 fmol/ml respectively, P=0.048), and were 0.29+/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.0053), while AUC(rh) was not (P=0.080). CONCLUSIONS: The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.