Renal effects of amlodipine in normotensive renal transplant recipients.

Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA.     

Renal artery stenosis in hypertensive renal transplant recipients.

Reconstruction of a stenotic renal artery was done on 5 hypertensive renal transplant recipients, all of whom had deterioration of renal function when the stenosis was detected. After reconstruction renal function improved in 4 of the patients. The blood pressure was easier to control in all 5 patients, with 3 becoming normotensive. A high preoperative plasma renin activity returned to normal postoperatively in 4 patients. No recurrences were observed after a followup of more than a year.     

Comparative effects of enalapril and nifedipine on renal hemodynamics in hypertensive renal allograft recipients.

The comparative effects of enalapril (E) and nifedipine (N) on renal hemodynamics were assessed in twenty-two moderately hypertensive, cadaveric renal transplant patients who were maintaining stable renal function. Fourteen patients were on cyclosporin (CSA) and eight were receiving azathioprine with prednisolone (AZA). In each patient effective renal plasma flow (ERPF) was determined four times, first baseline, second with E, third as another baseline after a washout period, and fourth with N; and renal vascular resistance (RVR) was derived in each. ERPF and RVR were significantly compromised in the CSA group (202 +/- 55 ml/min and 65 +/- 18 mmHg/ml/min) compared to the AZA group (302 +/- 99 and 43 +/- 15 respectively). During E therapy, RVR further increased in the CSA group to 82 +/- 37 while it decreased in the AZA group to 31 +/- 7 (both changes were significant when compared to their respective baseline values). N, on the other hand, only significantly lowered RVR in the AZA group. Furthermore, two patients, one from each group, developed acute reversible renal failure shortly after E therapy. However, both agents were effective in lowering blood pressure to a comparable degree in both groups. In conclusion, our data showed a somewhat less favourable renal hemodynamic response to short-term enalapril therapy in hypertensive renal transplant patients maintained on CSA. However, the significance of such hemodynamic changes for long-term renal function remains uncertain.     

Use of atorvastatin in hyperlipidemic hypertensive renal transplant recipients

The aim of the present short-term study was to evaluate the use of a new HMG-CoA reductase inhibitor, atorvastatin, in the treatment of hyperlipidemia and the effect on blood pressure in a group of hypertensive stable renal transplant recipients with hypercholesterolemia who received kidney grafts before 18 years of age. Eight patients (aged 10.8-30.1 years) with inadequately controlled total cholesterol (TC) levels by a lipid-lowering diet (8 weeks) were treated daily for 12 weeks with atorvastatin at an initial dose of 2.5 mg. The dose was increased monthly by 2.5 mg in order to lower TC levels to less than 200 mg/dl. Serum lipoprotein profile, cyclosporin A (CsA), serum creatinine (SCr), and liver and muscle enzyme levels were measured before starting the lipid-lowering diet, at the start of treatment (baseline), and during treatment. Ambulatory blood pressure monitoring (ABPM) (24-h) was carried out in each patient at both baseline and the end of the follow-up. During the lipid-lowering diet, no significant changes in lipoprotein parameters were observed. Atorvastatin was tolerated well and no clinical side effects were noted during the follow-up. The final dose of atorvastatin ranged from 2.5 to 7.5 mg/day. At the end of the study, TC was reduced by 32.2% ( P<0.05), low-density lipoprotein cholesterol (LDL-C) by 41.8% ( P<0.05), and apo B by 29.5% ( P<0.05). No significant changes in HDL-C, VLDL-C, apolipoprotein AI, and lipoprotein(a) were observed. SCr and CsA levels were unaffected. Overall, no significant changes in mean 24-h, daytime, and nighttime ABPM values between the first and the second recordings were observed. However, both daytime and nighttime systolic and diastolic ABPM values dropped in four patients. In conclusion, low-dose atorvastatin appears to be safe, well tolerated, and effective in the treatment of post-transplant hyperlipidemia. In addition, the capacity of atorvastatin to reduce blood pressure, whether or not related to its lipid-lowering action, deserves further investigation.     

Renal and systemic effects of atenolol and tertatolol in renal transplant recipients on cyclosporine A

Background. Hypertension and nephrotoxicity are well-known side-effects of cyclosporine A (CsA). CsA-induced vasoconstriction of the afferent glomerular arteriole probably plays a role in at least the nephrotoxicity. Frequently renal transplant recipients on CsA have to be treated with antihypertensive drugs and for this purpose also {beta}-blockers are used. Tertatolol is a new {beta}-blocker with specific vasodilatory properties, and thus might be particularly useful in CsA-treated transplant recipients. Methods. We studied the systemic and renal haemodynamic effects of atenolol and tertatolol in 12 hypertensive renal transplant recipients on cyclosporine A (CsA). In a cross-over way, all patients were treated with atenolol and tertatolol for 4 weeks each, separated by a wash-out period also of 4 weeks. At the end of each period, the mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. Results. The mean arterial pressure was lower (P<0.05) during atenolol (124±2 mm Hg) and tertatolol (125±2 mm Hg) treatment compared with wash out (132±4 mm Hg). Also the heart rate was lower (P<0.01) during atenolol and tertatolol (54±3 and 55±2 beats/min respectively) than in the wash-out period (65±3 beats/min). GFR and RPF were not changed by either {beta}-blocker. Conclusion. In CsA treated renal transplant recipients both atenolol and tertatolol effectively reduced blood pressure. In these patients we found no evidence of a specific vasodilatory effect of tertatolol. Both {beta}-blockers had no negative influence on renal function. Hence, these cardioprotective agents are an attractive and safe choice for the treatment of hypertension in such patients.     

Physical training effects in renal transplant recipients

Romano G, Simonella R, Falleti E, Bortolotti N, Deiuri E, Antonutto G, De Vita S, Ferraccioli GF, Montanaro D. Physical training effects in renal transplant recipients.
Clin Transplant 2010: 24: 510–514.
© 2009 John Wiley & Sons A/S. Abstract: Introduction: Several studies demonstrated the benefits of rehabilitation in uraemic patients. This study evaluates physical and psychosocial effects of exercise on renal transplant recipients (RTRs). Patients and methods: Eight RTRs were evaluated before and after an exercise training consisting of thirty 40‐minute sessions, three times a week, performed with the interval training technique. Results: Hospital Anxiety and Depression Scale (HADS) significantly decreased (p < 0.04 and <0.008, respectively). Quality of life mean scores (SF‐36 test) significantly increased (p < 0.000). No differences were recorded for muscle and fat mass, maximal explosive power of the lower limbs, alkaline and acid phosphatase, parathormone (PTH), myoglobin, lipoprotein‐A, glomerular filtration rate (GFR), at rest heart rate, and cardiac troponin. IL‐6 decreased from 2.8 ± 0.6 to 1.7 ± 0.5 pg/mL (p < 0.01). Resting MAP fell from 112 ± 4 to 99 ± 3 mmHg (p < 0.02). The metabolic threshold rose from 33 ± 4 to 43 ± 5% (p < 0.033). The blood lactate level at peak exercise increased from 5.2 ± 0.9 to 6.2 ± 0.7 mmol/L (p < 0.012). The maximum oxygen uptake increased from 1200 ± 210 to 1359 ± 202 mL/min (p < 0.05), iso‐load oxygen uptake decreased from 1110 ± 190 to 1007 ± 187 mL/min (p < 0.034). The maximum working capacity increased from 90 ± 14 to 115 ± 15 watts (p < 0.000). Conclusion: This study suggests that an appropriate dose of physical training is a useful, safe and non‐pharmacologic contribution to RTR treatment.     

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.     

Renal transplant recipients

Summary Decision making in renal transplantation is largely based on considerations concerning risk factors in the treatment of end-stage renal disease. The attempt to identify minimize individual risks has proven to be a key to success in renal 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.     

Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients.

BACKGROUND: Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5-10 mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension. METHODS: Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure. RESULTS: Amlodipine significantly decreased serum uric acid levels from 483 +/- 99 to 431 +/- 110 microM/l (P < 0.001), while tertatolol significantly increased uric acid from 450 +/- 98 to 476 +/-84 microM/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P = 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P = 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated. CONCLUSIONS: Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.     

Renal cell carcinoma of native kidney in renal transplant recipients

OBJECTIVE: To evaluate the prevalence, prognosis and possible risk factors of renal cell carcinoma (RCC) of the native kidney in renal transplant recipients. PATIENTS AND METHODS: We retrospectively re-examined the follow-up data of 373 consecutive renal transplant recipients at our institution between August 1993 and September 2004. We collected the data of all de novo RCC of the native kidney in the current analysis. RESULTS: Of the 373 patients examined, 12 tumours of the native kidney were diagnosed in 10 individuals. The mean ages at transplantation and diagnosis were 33 and 45.8 years, respectively. Thirteen malignancies were discovered fortuitously. Among the renal ultrasonograms there were two false-negative results. The mean tumour size was 21 mm. Nephrectomy was performed in all cases. Among the 12 kidney malignancies, there were five conventional RCCs and seven papillary RCCs. Half of all tumours were Furhman Grade 3 lesions, and pT1aN0M0 tumours also accounted for all malignancies in the current cohort. One of the 10 patients died, from progression of metastases 6 years after diagnosis. One patient had a local recurrence 2 years after diagnosis. The other eight patients were alive with no evidence of disease at the time of the current report. No significant relationship was detected between RCC occurrence and clinical patient characteristics. CONCLUSIONS: There appears to be a greater risk of RCC of the native kidney in patients with end-stage renal disease. The present results suggest that an annual examination of the native kidney before and after renal transplantation is essential.     

The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients — a randomised prospective study

The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P=0.0223) and 4-year (P=0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P<0.01). Group B also experienced fewer rejection episodes than groups A and C (P<0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.     

Increased vascular sensitivity to noradrenaline in hypertensive renal transplant recipients

We have studied several factors that may cause hypertension in renal transplant recipients. Cardiac output measurements suggest that hypertension is maintained by an increase in total peripheral resistance. Plasma noradrenaline concentration was significantly higher in both normotensive and hypertensive patients than in matched normal subjects. Plasma noradrenaline rose significantly in response to head-up tilt in normotensive, but not in hypertensive, patients. Resting plasma renin activity was significantly higher in both groups of patients than in normal subjects, but there was no relationship between plasma renin activity and blood pressure. Plasma renin activity did not change in response to head-up tilt or isoprenaline infusion in the patients. The rise in arterial pressure during noradrenaline infusion was significantly greater in hypertensive than in normotensive patients. Regression analysis showed a significant relationship between the combination of total exchangeable sodium and the rise in mean arterial pressure during noradrenaline infusion with resting mean arterial pressure.     

Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy

Background. The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non diabetic nephropathy. Methods. The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. Results. Mean arterial blood pressure decreased from 123±13 mmHg at baseline to 113±10 mmHg (P<0.01) on losartan and to 114±10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510±2586 mg/24 h at baseline to 2684±2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748±3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8±9.3% to 21.2±10.2% (P<0.05) on losartan and increased to 23.6±8.9 (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. Conclusion. Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.     

Angiotensin-II receptor antagonist losartan reduces microalbuminuria in hypertensive renal transplant recipients

In recent years, it has been demonstrated that losartan lowers macroproteinuria in diabetic or non-diabetic renal transplant recipients (RTx) similar to angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may reflect subclinical hyperfiltration damage of the glomerulus. It could be a marker of kidney dysfunction in renal transplantation. The aim of the study was to assess the efficacy of losartan in hypertensive RTx with MAU. This study was conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical treatment of the patients. All cases received 50 mg/day losartan therapy for 12 wk. Renal functions and MAU were determined 12 and 6 wk and just before the treatment as well as sixth and twelfth week of the treatment in all patients. Losartan satisfactorily lowered systemic blood pressure. A significant reduction in MAU was observed from 103 +/- 53 microg/min at the beginning to 59 +/- 25 microg/min in the sixth week and 47 +/- 24 microg/min in the twelfth week (p=0.0007 and 0.0005, respectively). From the sixth week of the treatment, the therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but did not change mean leukocyte and platelet counts, urea, creatinine levels and creatinine clearances. No serious side-effect was observed during the study. In conclusion, we found that losartan decreased MAU in hypertensive RTx. For that reason, it might be considered as the first choise antihypertensive agent for the renoprotection in selected patients.     

Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial

BACKGROUND: Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate. METHODS: A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability. RESULTS: At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group. CONCLUSION: Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine.     

Anemia due to losartan in hypertensive renal transplant recipients without posttransplant erythrocytosis

Losartan is a safe, effective long-term treatment for hypertension or posttransplant erythrocytosis (PTE) in renal transplant recipients. There were only a few studies in patients without PTE and their results were different. Starting from week 6 and continuing to the week 12 we observed a decrease in hemoglobin (Hb) and hematocrit (Hct) levels in patients without PTE. Anemia developed in 42.8% of the patients, and Hb levels increased after the withdrawal of losartan treatment. There was a significant decrease in Hct levels beginning from week 3 when compared with the control group. Our study suggests that losartan therapy can decrease Hb beyond its antihypertensive efficacy. Based on the capacity of losartan to decrease Hb and Hct, this drug should be carefully used in patients with preexistent anemia or low Hb levels.