Effect of a soy protein diet on serum lipids of renal transplant patients.

OBJECTIVE: The aim of the present study was to evaluate the effect of a soy-protein diet on plasma lipid levels of renal transplant recipients with moderate hypercholesterolemia. DESIGN: Dietary intervention case-control observational study. SETTING: Renal transplantation outpatient clinic. PATIENTS: Fifteen stable patients who had renal transplantation (serum creatinine < 2 mg/dL) with moderate hypercholesterolemia (low-density lipoprotein [LDL] cholesterol > 140 mg/dL). INTERVENTION: After a baseline dietary interview, dietary counseling was given individually with the goal of substituting 25 g of animal protein with 25 g of soy protein for a 5-week period, using commercially available soy foods, according to each patient's own preference.Main outcome measures Before and after the soy-diet period, plasma lipid profiles including total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 and B were determined. Protein catabolic rate was assumed as a measure of dietary protein intake. RESULTS: Two patients dropped out. After the soy diet, total cholesterol (254 +/- 22 to 231 +/- 31 mg/dL, P <.05) and LDL cholesterol (165 +/- 20 versus 143 +/- 20 mg/dL, P <.01) decreased significantly. No significant changes were observed regarding HDL cholesterol and triglycerides. Dietary protein intake did not differ at baseline (73.2 +/- 22.9 g/day) and during the soy diet (72.6 +/- 15.6 g/day), when the reported actual soy protein intake resulted 26 +/- 8 g/day. CONCLUSIONS: This study shows that soy proteins given as part of the daily protein intake have beneficial effects on serum LDL cholesterol levels of renal transplant recipients with moderate hypercholesterolemia. Soy proteins could be of use in the nutritional management of renal transplant recipients.     

The renal safety profile of fluvastatin: results of a pooled analysis

A pooled analysis was designed to evaluate the effects of fluvastatin on the kidney, in terms of renal adverse events, laboratory abnormalities, and renal function over time. An analysis of adverse events was performed on data from 30 completed clinical trials of fluvastatin in 11,815 patients. An analysis of renal function was also performed on data from patients who participated in long-term studies >6 months in treatment duration. Creatinine clearance was calculated using the Cockcroft-Gault formula. Mean creatinine clearance values were in the normal to near-normal range at baseline. Changes in creatinine clearance and serum creatinine from baseline were similar in fluvastatin-treated patients and placebo-treated patients. In the all-fluvastatin group, mean creatinine clearance (+/-standard deviation) increased from 87.8 (+/-42.8) mL/min at baseline to 89.4 (+/-41.2) mL/min at endpoint. In the placebo group, mean creatinine clearance (+/- standard deviation) increased from 87.7 (+/- 43.9) mL/min at baseline to 88.7 (+/-41.4) mL/min at endpoint. In the all-fluvastatin group, mean serum creatinine (+/- standard deviation) decreased from 1.14 (+/-0.20) mg/dL at baseline to 1.11 (+/-0.20) mg/dL at endpoint. In the placebo group, mean serum creatinine (+/-standard deviation) decreased from 1.15 (+/-0.22) mg/dL at baseline to 1.12 (+/-0.22) mg/dL at endpoint. The incidence of renal adverse events was low and comparable between the fluvastatin and placebo treatment groups. This pooled analysis demonstrates that fluvastatin treatment across the approved daily dose range of 20 mg to 80 mg does not adversely affect creatinine or creatinine clearance over time in dyslipidemic patients.     

The Renal Safety Profile of Fluvastatin: Results of a Pooled Analysis

A pooled analysis was designed to evaluate the effects of fluvastatin on the kidney, in terms of renal adverse events, laboratory abnormalities, and renal function over time. An analysis of adverse events was performed on data from 30 completed clinical trials of fluvastatin in 11,815 patients. An analysis of renal function was also performed on data from patients who participated in long-term studies >6 months in treatment duration. Creatinine clearance was calculated using the Cockcroft-Gault formula. Mean creatinine clearance values were in the normal to near-normal range at baseline. Changes in creatinine clearance and serum creatinine from baseline were similar in fluvastatin-treated patients and placebo-treated patients. In the all-fluvastatin group, mean creatinine clearance (±standard deviation) increased from 87.8 (±42.8) mL/min at baseline to 89.4 (±41.2) mL/min at endpoint. In the placebo group, mean creatinine clearance (± standard deviation) increased from 87.7 (± 43.9) mL/min at baseline to 88.7 (±41.4) mL/min at endpoint. In the all-fluvastatin group, mean serum creatinine (± standard deviation) decreased from 1.14 (±0.20) mg/dL at baseline to 1.11 (±0.20) mg/dL at endpoint. In the placebo group, mean serum creatinine (±standard deviation) decreased from 1.15 (±0.22) mg/dL at baseline to 1.12 (±0.22) mg/dL at endpoint. The incidence of renal adverse events was low and comparable between the fluvastatin and placebo treatment groups. This pooled analysis demonstrates that fluvastatin treatment across the approved daily dose range of 20 mg to 80 mg does not adversely affect creatinine or creatinine clearance over time in dyslipidemic patients.     

Conversion from calcineurin inhibitors to sirolimus in patients with chronic renal allograft dysfunction

BACKGROUND: Chronic renal transplant dysfunction in part may be due to the nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of significant nephrotoxicity, might therefore exhibit beneficial effects when used in renal transplant recipients with graft dysfunction. METHODS: Twelve renal transplant recipients included in this study had all been receiving calcineurin inhibitors for more than 12 months, and were free of rejection for more than 12 months. However, they demonstrated moderate renal dysfunction with serum creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was withheld. RESULTS: One month after initiation of sirolimus therapy, all patients were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4 mg. No acute rejection episode and no graft failure was observed. No patient required hemodialysis or admission to the hospital. Calculated creatinine clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/-0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L, P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs 134+/-16.8/83+/-9.7). CONCLUSION: Conversion from calcineurin inhibitor therapy to sirolimus in patients more than 1 year after transplantation with impaired organ function is feasible, safe, and associated with a trend toward improved renal function.     

Cyclosporine versus tacrolimus in kidney transplantation: are there differences in nephrotoxicity?

Cyclosporine and tacrolimus, two calcineurin inhibitors, show different side effects and toxicities. The data concerning their nephrotoxicity are few and conflicting. A retrospective study was performed in 2 groups of renal transplant recipients treated with cyclosporine or tacrolimus to evaluate graft function and side effects. All patients had completed at least 6 months of follow-up before inclusion in the study. Group I included 10 patients who were converted from cyclosporine to tacrolimus, due to cosmetic problems or due to chronic graft dysfunction with creatinine values <3 mg/dL. After conversion, there was a significant reduction in creatinine values (from 2.43 +/- 1.21 to 1.86 +/- 0.72 mg/dL; P =.023) and an improvement in creatinine clearance (from 47.5 +/- 19.2 to 56.1 +/- 18.9 mL/min; P =.047). The lipid profile did not change, but there was a trend to better blood pressure control with less antihypertensive drugs. Group II compared 2 subgroups of patients receiving kidneys from the same donor, one treated with cyclosporine and the other with tacrolimus. Tacrolimus patients showed better renal function; namely, creatinine was 1.15 +/- 0.27 versus 1.44 +/- 0.33 mg/dL (P =.029) and creatinine clearance was 87.7 +/- 27.1 versus 60.3 +/- 25.9 mL/min (P =.043). Lipid and blood pressure values were not different between the 2 subgroups, but tacrolimus patients tended to need a lower number of antihypertensive medications. The incidence of de novo diabetes mellitus was approximately 20% among patients using tacrolimus. We concluded that tacrolimus may be less nephrotoxic than cyclosporine. Tacrolimus patients showed better graft function and easier blood pressure control, but a high incidence of posttransplantation diabetes mellitus.     

Meta-analysis of the effect of sevelamer on phosphorus,calcium, PTH,and serum lipids in dialysis patients

Hyperphosphatemia and dyslipidemia are common clinically significant conditions in end-stage renal disease (ESRD). Hyperphosphatemia management is essential; however, use of calcium-based phosphate binder has been associated with elevated risk of cardiac calcification in ESRD, increasing risks for cardiovascular disease and death. An alternative to calcium-based phosphate binders is sevelamer hydrochloride, a calcium-free, metal-free, nonabsorbed polymer that binds phosphate effectively. We conducted a meta-analysis on the effects of sevelamer hydrochloride on parameters of mineral metabolism (serum phosphorous, calcium, Ca x P, and iPTH) and the lipid profile (total, LDL, HDL, and non-HDL cholesterol, and triglycerides) in dialysis patients. After application of inclusion/exclusion criteria, 17 core studies were statistically analyzed to determine the sevelamer treatment effect on the study parameters as demonstrated by simple, n-weighted, and inverse variance-weighted mean changes. Analysis of inverse variance-weighted mean changes indicated that sevelamer treatment was associated with a 2.14 mg/dL drop in serum phosphorus (P <.001), no significant overall effect on calcium (0.09 mg/dL, P =.364), significant decline in Ca x P product (15.91 mg(2)/dL(2), P <.001), 35.99 pg/mL reduction in iPTH (P =.026), significant reduction in total cholesterol (30.58 mg/dL, P <.001), 31.38 mg/dL drop in LDL cholesterol (P <.001), significant increase in HDL cholesterol (4.09 mg/dL, P =.008), and a significant reduction in triglycerides (22.04 mg/dL, P x.001). This meta-analysis suggests that sevelamer offers a dual therapeutic benefit in dialysis patients-a population at high risk for cardiovascular disease-by improving phosphorus control and the lipid profile, without altering serum calcium.     

Effect of low doses of atorvastatin on adiponectin, glucose homeostasis, and clinical inflammatory markers in kidney transplant recipients

INTRODUCTION: Various studies describe the pleiotropic antiinflammatory and antioxidant effects of atorvastatin, in addition to its hypolipemic effects. It has been suggested that statins modify glucose homeostasis via their antiinflammatory effects. A further hypothesis suggests that the incidence of posttransplantation diabetes is lower in statin-treated patients. This study sought to ascertain whether atorvastatin modifies glucose homeostasis, adiponectin, and inflammatory markers in kidney transplant recipients. PATIENTS AND METHODS: Sixty-eight kidney transplant recipients (41 men, 27 women; mean age, 53 +/- 12 years) with stable renal function and dyslipidemia were treated with atorvastatin (10 mg/d) for 12 weeks. Glucose, insulin, homeostasis model assessment (HOMA-IR) index, adiponectin, tumor necrosis factor (TNF)-alpha, and serum C-reactive protein (CRP) concentrations were determined at baseline and at 3 months. The lipid profile, renal function parameters (creatinine, creatinine clearance, and proteinuria), as well as GOT, GPT, and CK were determined at baseline and at 3 months. RESULTS: Treatment with atorvastatin achieved a statistically significant decrease in lipid profile. After 3 months of treatment, 74.6% of patients had total cholesterol and 78.7% low-density lipoprotein (LDL) cholesterol concentrations within reference range (<5.2 and 3.3 mmol/L, respectively). Furthermore, 47.5% of patients attained an LDL concentration <2.59 mmol/L. A greater reduction in total cholesterol (P = .05) and LDL cholesterol (P = .04) was achieved in patients with creatinine clearance <60 mL/min. Atorvastatin did not modify glucose homeostasis parameters, adiponectin, TNF-alpha, or CRP. At baseline and after 3 months of treatment, an inverse correlation was found between adiponectin and glucose, insulin, HOMA- IR index, and creatinine clearance, and a positive correlation was found between adiponectin and high-density lipoprotein (HDL) cholesterol. CONCLUSION: Atorvastatin at a dose of 10 mg/d in kidney transplant recipients does not modify glucose homeostasis or alter inflammatory markers, despite its hypolipemic effects. Its efficacy to reduce total cholesterol and LDL cholesterol was greater in patients with worse renal function.     

Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease

BACKGROUND: There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin. METHODS: After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients. RESULTS: Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups. CONCLUSIONS: Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.     

mTOR inhibitors: do they help preserve renal function?

BACKGROUND: Renal function deterioration is one of the main problems facing heart transplant recipients. The mammalian target of rapamycin (mTOR) inhibitors, in combination with or replacing calcineurin inhibitors, may help preserve renal function. The aim of this study was to evaluate the progression of renal function after switching the immunosuppressive regimen. PATIENTS AND METHODS: We studied 23 heart transplant recipients (5.5 +/- 4.5 years since transplantation). An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Patient clinical characteristics and renal function were studied after switching. The statistical analysis used Student t test for paired data. RESULTS: The reason for the transplantation was ischemic cardiopathy (52%), dilated myocardiopathy (39%), or other causes (9%). Mean age at time of transplantation was 52 +/- 9 years. Comorbidities were as follows hypertension (43%), insulin-dependent diabetes (22%), hypercholesterolemia (39%), and ex-smokers (70%). The reason for the switch was increased creatinine (65%), appearance of tumors (26%), or others (8%). Previous creatinine level was 1.89 +/- 0.6 mg/dL with clearance of 61.7 +/- 23 mL/min and at the end of follow-up (mean follow-up, 11 +/- 6 months) creatinine level was 2.0 +/- 1.45 mg/dL with clearance of 68.3 +/- 35 mL/min, namely, no significant difference (P = .49 and P = .57, respectively). In the subgroup of patients who switched treatment due to renal dysfunction, initial creatinine level was 2.38 +/- 0.4 mg/dL with clearance of 42.3 +/- 10 mL/min and at the end of follow-up it was 2.28 +/- 0.2 mg/dL and 43.6 +/- 11 mL/min, respectively (P = .68 for creatinine and clearance). CONCLUSIONS: The introduction of mTOR inhibitors to the immunosuppressant regimen may be useful to delay renal functional deterioration caused by calcineurin inhibitors.     

Short-term effect of atorvastatin in hypercholesterolaemic renal-transplant patients unresponsive to other statins.

BACKGROUND: Atherosclerosis associated with hyperlipidaemia is a major cause of morbidity and mortality after renal transplantation. Atorvastatin is a new HMG-CoA reductase inhibitor that has shown a favourable profile of lipid reduction when compared with other statins. The aim of the study was to assess the efficacy and safety of atorvastatin in hypercholesterolaemic renal transplant patients who had previously been on statins with little or no effect. METHODS: Atorvastatin, 10 mg/day, was administered to 10 renal transplant recipients with persistent hypercholesterolaemia (total cholesterol >240 mg/dl) for a period of 3 months. All of them had already been on statins for at least 3 months. RESULTS: Atorvastatin exerted a satisfactory lipid-lowering effect in seven of 10 patients. On average, serum total cholesterol (311+/-36.2 vs 253+/-48.8 mg/dl; P:<0.05) and serum LDL cholesterol (184+/-30.9 vs 136+/-22.9 mg/dl; P:<0.05) significantly decreased after atorvastatin therapy, whereas serum HDL cholesterol (86+/-14.6 vs 84+/-22.1 mg/dl) remained unchanged. In five subjects with a baseline serum triglyceride level above 150 mg/dl, a marked reduction in triglycerides was also observed (261+/-80.3 vs 193+/-53.3 mg/dl; P:<0.05). Lp(a) did not significantly change (13+/-16.3 vs 15+/-23.9 mg/dl, P:=NS). Serum creatinine, transaminases, creatinine phosphokinase (55+/-21.3 vs 56+/-29.4 IU/l) and fasting cyclosporin A levels were unaffected. The drug was generally well tolerated and neither myositis nor rhabdomyolysis was reported. CONCLUSION: Short-term therapy with the new HMG-CoA reductase inhibitor, atorvastatin, appears to be effective in lowering atherogenic lipids in renal transplant patients who had had little or no response to other statins.     

Renal allograft protection with early angiotensin-converting enzyme inhibitors administration

Twenty renal transplant recipients (RTx) with a normal ultrasound pattern of renal artery who began angiotensin-converting enzyme inhibitor (ACEI) therapy within 14 months after surgery (ACEI(+)) were studied retrospectively to evaluate endogenous creatinine clearance/1.73 m(2) body surface area (CrCl), proteinuria (UP), UP/CrCl (FUP), mean arterial pressure (MBP), total cholesterol, LDL, HDL, and triglycerides. Before (T(0)) and every month for 2 years after initiation of ACEI. Twenty-four RTx who never received ACEI (ACEI(-)) were studied in the same fashion. No differences in the parameters were noted at T(0); all RTx had CrCl >60 mL/min, Up less than 0.5 g/d, and stable renal function for 3 months before the study. In the ACEI cohort CrCl was reduced after 2 years compared with T(0) (65.6 +/- 2.8 vs 76 +/- 3.2 mL/min, P <.004), UP and FUP were both increased (660 +/- 60 vs 130 +/- 20 mg/d, 8.9 +/- 1.3 vs 2.8 +/- 0.6 mg/mL x 10(3); P <.001 and.002, respectively). UP >0.5 g/d was present in three cases. After 2 years the ACEI(+) group showed a decrease in CrCl (68.2 +/- 3.1 vs 73 +/- 2.2 mL/min) and the increase in UP (181 +/- 21 vs 139 +/- 18 mg/d) and in FUP (3.1 +/- 0.7 vs 2.6 +/- 0.9 mg/mL x 10(3)), which were not significantly different from the values at T(0). No cases showed UP >0.5 g/d. Moreover UP (P <.04), FUP (P <.03) and the percent reduction of CrCl (11.2 +/- 2.5% vs 4.6 +/- 1.8%, P <.05) were greater among ACEI(-) than ACEI(+) patients at 2 years. ACEI(-) patients showed correlation between the percent reduction of CrCl and UP (r =.51, P <.04). The values of MBP and lipids did not reveal any significant difference between the two groups. In conclusion, this study suggests that ACEI have a renoprotective effect, when used early, and may also prevent chronic allograft nephropathy.     

Treatment of the hyperlipidemia of the nephrotic syndrome: a controlled trial

The hyperlipidemia of the nephrotic syndrome is often associated with elevated total and low-density lipoprotein (LDL) cholesterol levels and low or normal high-density lipoprotein (HDL) cholesterol levels. This pattern of hyperlipidemia has been associated with an increased risk of accelerated atherosclerosis in other populations. Despite extensive studies of diet and drug therapy in other populations, few such therapeutic studies exist in patients with the nephrotic syndrome. To investigate the effect of diet and lipid-lowering drugs on the lipoprotein-lipid profile of patients with unremitting nephrotic syndrome and marked hyperlipidemia, we conducted a controlled trial using two such drugs: colestipol and probucol. Colestipol lowered the mean total fasting plasma cholesterol of seven patients from 397 +/- 27 to 317 +/- 37 mg/dL, a 20.2% decrease, and lowered the LDL cholesterol from 398 +/- 28 to 203 +/- 18 mg/dL, a 31.9% decrease. It did not affect the HDL cholesterol level, and thus lowered the LDL-to-HDL cholesterol ratio. Probucol lowered the mean total cholesterol from 439 +/- 72 to 339 +/- 60 mg/dL, a 22.6% decrease, and the LDL cholesterol from 282 +/- 43 to 215 +/- 26 mg/dL, a 23.8% decrease. Although the HDL cholesterol was lowered from 49 +/- 9 to 43 +/- 7 mg/dL by probucol, a 12.2% decrease, the LDL-to-HDL cholesterol ratio still declined. Both drugs were well tolerated and proved safe in this short-term trial. Antihyperlipidemic therapy may well be indicated in certain patients with unremitting nephrotic syndrome.     

Effectiveness of diet in hyperlipidemia in renal transplant patients

In renal transplant patients dietary therapy alone does not always provide satisfactory results to control hyperlipidemia. To assess the effectiveness of diet, 151 renal transplant patients were selected for a prospective clinical study using pre- and posttest groups. During 8 weeks these patients received a diet with 25% energy intake from lipids, less than 10% from saturated fats, and less than 500 mg of cholesterol per day. Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured (pre- versus postdiet). The degree of compliance with the diet was measured by a 24-hour food recall record. Patients who had 90% compatibility between the questionnaire and the prescribed diet were considered compliant. The diet was considered effective in the patients who achieved a reduction of cholesterolemia to less than 200 mg/dL after 8 weeks of treatment. Ultimately 108 patients completed the study, with a significant reduction in total serum cholesterol from 262.37 mg/dL pretest to 252.85 mg/dL posttest (P =.010); LDL cholesterol from 174.29 mg/dL pretest to 166.60 mg/dL posttest (P =.036), of body weight from 68.98 kg pretest to 67.78 kg posttest (P =.01) and of body mass index from 25.86 kg/m(2) pretest to 25.41 kg/m(2) posttest (P =.01). Cholesterol variation was 3.63% as compared to prediet levels. Only 22 patients (20.4%) achieved cholesterol levels below 200 mg/dL. In conclusion, although diets decrease cholesterolemia, they alone are not effective to control hyperlipidemia in most renal transplant patients.     

Lercanidipine in patients with chronic renal failure: the ZAFRA study

OBJECTIVE: The objective was primary to evaluate the safe use of a new calcium channel blocker, lercanidipine, in patients with chronic renal failure (CRF). The secondary objective was to study the protective effect of calcium channel blocker on renal function in CRF patients previously treated with ACE inhibitors or angiotensin receptor blockers. DESIGN AND METHODS: The study recruited 203 CRF patients (creatinine >1.4 mg/dL for males, creatinine > 1.2 mg/dL for females, or creatinine clearance <70 mL/min). All patients were receiving ACE inhibitors (63.4%) or angiotensin II antagonist (36.6%) therapy, but they had higher blood pressure than recommended for CRF (130/85 mmHg). No patients were under diuretic treatment. Patients were clinically evaluated 1, 3, and 6 months after starting treatment with lercanidipine. Samples for urine and blood examination were taken during the examination. When needed, a third drug was added to the treatment, excluding diuretics. Creatinine clearance was measured using 24 h urine collection. RESULTS: 175 patients rendered valuable for the study (age 63.9+/-11.9 years, 52.9% males and 47.1% females). Blood pressure (BP) significantly decreased from 162+/-17/93+/-8.3 mmHg to 132+/-12/78+/-6 mmHg. 89.2% of patients showed a significant BP reduction, and 58.1% achieved optimal BP control (<130/85 mmHg). Seven patients (3.4%) showed untoward effects. Not one case of edema was detected, and the prevalence of adverse effects related to vasodilatation was extremely low (three patients, 1.48%). Plasmatic creatinine did not change (1.9+/-0.5 baseline versus 1.9+/-0.6 mg/dL), but creatinine clearance increased at the end visit (41.8+/-16.0 baseline versus 45.8+/-18.0 mL/min, p=0.019). Plasmatic cholesterol also decreased from 221+/-46 to 211+/-35 mg/dL (p=0.001). CONCLUSIONS: Lercanidipine showed a high antihypertensive effect in CRF patients. It has a good tolerability profile and showed an interesting effect on plasmatic lipids. An improvement in renal function, measured through creatine clearance, was detected.     

Living donor nephrectomy--no impact of genetic relationship

PURPOSE: A retrospective, single-center analysis was conducted to compare the results of living donor kidney transplantation between living unrelated (LURD) and living related (LRD) donors. PATIENTS AND METHODS: One hundred forty-seven consecutive living renal transplantations were performed at our institution, starting in 1983. Graft and patient survival were assessed as well as transplant function, including a subgroup analysis for the period of kidney transplantation. RESULTS: Mean follow up for the LRD group was 88.5 months and for the LURD cohort 34.4 months. One- and 3-year graft survival (censored for death with functioning graft) for LRD versus LURD was 97.5% versus 94.4% (P =.4) and 95.3% versus 88.8% (P =.35). Patient survival at 1 and 3 years was 95.1% versus 94.7% (P =.91) and 87.8% versus 90.0% (P =.79). Of the related recipients, 37% experienced at least one episode of rejection in the first year following renal transplantation, compared to 34% in the LURD group (P =.80). Mean serum creatinine for LRD versus LURD after 1, 3, and 12 months () was 1.52 +/- 0.81 versus 1.59 +/- 1.17 mg/dL (P =.98), 1.41 +/- 0.55 versus 1.30 +/- 0.40 mg/dL (P =.51), and 1.44 +/- 0.39 versus 1.40 +/- 0.40 mg/dL (P =.75). Mean creatinine clearance after 1 year was 82.2 versus 71.7 mL/min (P =.26). Subgroup analysis for the time between 1996 and 2002 revealed no difference between LURD and LRD. Multivariate analysis could exclude an impact of the significantly different recipient age and of first/second warm ischemic time on the endpoints described above. CONCLUSION: LURD is a good way to meet the growing organ shortage and should be encouraged.     

The clinical status of cadaveric renal transplant patients treated for 10 year with cyclosporine therapy

In this paper we assessed the clinical status of 150 cadaveric renal transplant patients who received cyclosporine without interruption for 10 yr. The mean creatinine clearance was 59.2 +/- 15.71 at 1 yr and 55.6 +/- 24.91 mL/min at 10 yr (p = 0.039). Patients were subdivided into four quartiles according to the mean creatinine clearance at 1 yr. The 14 patients with the lowest quartile showed a significant decrease of creatinine clearance from the 1st to 10th year (from 31.5 +/- 5.83 to 24.8 +/- 14.00 mL/min; p = 0.038) while no difference between the mean creatinine clearance at 1 and at 10 yr was found in the other three quartiles. At 10 yr, 84.6% patients needed antihypertensive therapy, a rate similar to that seen at 1 yr (81.4%). The mean plasma cholesterol (253 +/- 57.8 mg/dL) and triglyceride (197 +/- 113.1 mg/dL) at 10 yr were similar to those found at +/- yr (243 +/- 48.2 and 201 +/- 143.0 mg/dL, respectively). Most patients have a high degree of rehabilitation 10 yr after uninterrupted cyclosporine therapy and all patients but 3 were able to work.     

Treatment of atherosclerotic ostial renal artery stenosis with the intravascular stent

Traditional approaches to revascularization for atherosclerotic ostial renal artery stenosis (RAS) have been suboptimal because of the invasiveness and relatively high perioperative morbidity and mortality of surgery and the low rates of success and long-term patency with percutaneous renal angioplasty (PTRA). We report our 5-year (1991 to 1996) experience with the intravascular stent (Palmaz stent; Johnson & Johnson, Miami Lakes, FL) for the treatment of ostial RAS in 129 patients (63 men, 66 women) and 148 arteries. The mean age of the patients was 71+/-10 years; 98% were hypertensive and 57% had renal dysfunction. Angiographic characteristics of RAS were unilateral in 78%, bilateral in 15%, and single kidney in 7%. The technical success rates were 98% for stent versus 11% for PTRA in the ostial location. The stent restenosis rate (angiographic) was 14% at 8+/-5 months. Systolic and diastolic blood pressures were as follows: baseline, 158+/-3 and 84+/-2 mm Hg; 6 months, 149+/-3 and 81+/-2 mm Hg; 12 months, 149+/-3 and 79+/-2 mm Hg; and 24 months, 135+/-3 and 79+/-2 mm Hg. Follow-up values were significantly lower than baseline (P < 0.05). The number of medications for hypertension initially decreased from 2.2+/-0.1 at baseline to 1.6+/-0.1 and 1.8+/-0.1 at 1 and 3 months, respectively (P < 0.05). By 6 months, however, the number of medications had increased and was not significantly different from before stent placement. Renal function was stable in the group as a whole: Cockroft-Gault creatinine clearance (C-G CrCl) at baseline was 40+/-2 mL/min; at 6 months, 36+/-3 mL/min; at 12 months, 39+/-3 mL/min; and at 24 months, 39+/-4 mL/min. When stratified by degree of renal function, values were similarly stable. Patients with a baseline serum creatinine level of 2 mg/dL or less had C-G CrCl values as follows: baseline, 53+/-3 mg/dL; 6 months, 43+/-4 mg/dL; 12 months, 46+/-4 mg/dL; and 24 months, 52+/-5 mg/dL. Those with a baseline serum creatinine level greater than 2 mg/dL had C-G CrCl values as follows: baseline, 26+/-2 mg/dL; 6 months, 31+/-4 mg/dL; 12 months, 32+/-6 mg/dL; and 24 months, 23+/-3 mg/dL. Of eight patients who were dialysis dependent, four (50%) recovered renal function with a mean serum creatinine level of 2.3+/-0.5 mg/dL at 15+/-6 months (range, 9 to 24 months). Stent placement for the treatment of atherosclerotic ostial RAS has a high success rate and a low rate of restenosis. Control of hypertension improves in most patients. Renal function stabilizes or improves in the majority of patients, even those with severe renal failure. These favorable outcomes are maintained long term.     

Does transrenal fixation of aortic endografts impair renal function?

OBJECTIVES: Transrenal fixation (TFX) of aortic endografts is thought to increase the risk for renal infarction and impaired renal function. We studied the late effects of TFX on renal function and perfusion. METHODS: Of 189 patients with commercial aortic endografts, which we inserted between 1995 and 2002, we reviewed data for 130 patients (112 men, 18 women) with available creatinine (Cr) concentration and contrast enhanced computed tomography (CT) scans preoperatively and 1 to 97 months after the procedure. Of the 130 patients, 69 patients had TFX and 61 patients had infrarenal fixation (IFX). Both groups were physiologically comparable. Average age was 76 +/- 8 years for patients with TFX and 75 +/- 8 years for patients with IFX. Presence of renal infarct or renal artery occlusion was determined by nephrograms on serial contrast-enhanced CT scans. RESULTS: Mean follow-up was 17 +/- 16 months (range, 1-54 months) for TFX and 21 +/- 21 months (range, 1-97 months) for IFX. Mean serum Cr concentration increased significantly during long-term follow-up in both groups (TFX, 1.3 +/- 0.5 mg/dL to 1.5 +/- 0.8 mg/dL, P <.01; IFX, 1.3 +/- 0.7 mg/dL to 1.4 +/- 0.8 mg/dL, P <.03). Creatinine clearance (CrCl) similarly decreased over long-term follow-up in both groups (TFX, 53.3 +/- 17.7 mL/min/1.73 m(2) to 47.9 +/- 16.2 mL/min/1.73 m(2), P <.01; IFX, 58.1 +/- 22.7 mL/min/1.73 m(2) to 53.1 +/- 23.4 mL/min/1.73 m(2), P <.02). There were no significant differences in the increase in Cr concentration (P =.19) or decrease in CrCl (P =.68) between TFX and IFX groups. Small renal infarcts were noted in four patients (5.8%) in the TFX group and one patient (1.6%) in the IFX group. No increase in Cr concentration or decrease in CrCl was noted in any patient with a renal infarct. Postoperative renal dysfunction developed in 7 of 69 patients (10.1%) in the TFX group and 7 of 61 patients (11.5%) in the IFX group. There were no statistically significant differences between groups with respect to number of patients with new renal infarcts (P =.37) or postoperative renal dysfunction (P =.81). CONCLUSION: There is a slight increase in serum Cr concentration and decrease in CrCl after aortic endografting. However, there was no significant difference in these changes between patients with TFX and IFX. Although TFX may produce a higher incidence of small renal infarcts, these do not impair renal function. Thus our midterm results suggest that TFX can be performed safely, with no greater change in renal function than observed after IFX.     

Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency

BACKGROUND: Although cardiovascular disease and low high-density lipoprotein (HDL) cholesterol are common in people with renal insufficiency, data addressing the cardiovascular benefits of fibric acid derivatives in this population are sparse. We conducted a post hoc subgroup analysis of a randomized double-blind, placebo-controlled trial to determine whether gemfibrozil is effective and safe for secondary prevention of cardiovascular events in individuals with chronic renal insufficiency (CRI). METHODS: Using an analysis plan that was developed a priori, we analyzed data from the Veterans' Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) study; a randomized trial of gemfibrozil versus placebo in 2531 men with established coronary disease, an HDL cholesterol level of 40 mg/dL (1.0 mmol/L) or less, and a low-density lipoprotein (LDL) cholesterol level of 140 mg/dL (3.6 mmol/L) or less. Of these, 1046 men had CRI as defined by creatinine clearance 相似文献   

20-year experience with elderly donors in living renal transplantation

PURPOSE: This study evaluates the impact of living renal donors (LD) aged 60 years and older on graft performance and patient survival in an old-for-young constellation. PATIENTS AND METHODS: We analyzed 144 consecutive LDs between January 1983 and December 2002 (19 patients 60+/125 controls). RESULTS: Mean donor age in the 60+ group was 63.7 (+/- 2.6) years and 43.7 (+/- 9.0) years for the <60 group. Mean recipient age was 42.4 (+/- 15.2) years versus 32.6 (+/- 15.3) years HLA-A, -B, and DR-mismatches were 3.16 (+/- 1.3) for the 60+ group and 3.13 (+/- 1.7) for the controls (P = NS). Rejection episodes in the first year following LD did not differ (53% versus 33%, P =.25). Mean serum creatinine for 65+ versus <65 after 1, 3, and 12 months was 1.91 +/- 1.2 versus 1.48 +/- 0.85 mg/dL (P =.16), 1.82 +/- 0.89 versus 1.29 +/- 0.35 mg/dL (P <.05) and 1.80 +/- 0.31 versus 1.37 +/- 0.38 mg/dL (P <.05) and mean creatinine clearance at 12 months 62 versus 82 mL/min (P =.06). Censored 1-, 3-, and 5-year graft survival was 100% versus 95% (P = NS), 100% versus 93% (P = NS) and 100% versus 83% (P = NS) with no significant difference in the log-rank test for Kaplan Meier. CONCLUSION: No impact of donor age was found for graft survival but function of the 65+ kidneys at 3 and 12 months was reduced. Living renal donors 60+ are acceptable for carefully allocated recipients.