The impact of aortic endografts on renal function

OBJECTIVE: To determine the impact on late postoperative renal function of suprarenal and infrarenal fixation of endografts used to treat infrarenal abdominal aortic aneurysm (AAA). METHODS: Retrospective analysis of 277 patients treated from 2000 to 2003 with three different endografts at two clinical centers. Five patients on dialysis for preoperative chronic renal failure were excluded. Group IF of 135 patients treated with an infrarenal device (Medtronic AneuRx) was compared with group SF of 137 patients treated with a suprarenal device (106 Cook Zenith and 31 Medtronic Talent). Renal function was evaluated by calculating preoperative and latest postoperative creatinine clearance (CrCl) using the Cockcroft formula. Patients who developed a >20% decrease in CrCl were considered to have significantly impaired renal function. RESULTS: There were no significant differences in patient age, sex, aneurysm size, preoperative risk factors, dose of intra- and postoperative contrast, or baseline CrCl (IF: 69.3 mL/min, SF: 71.7 mL/min, P = .4). Follow-up time of 12.2 months was the same in both groups. CrCl decreased significantly during the follow-up period in both groups (IF: 69.3 mL/min to 61.7 mL/min, P < .01; SF: 71.7 mL/min to 64.9 mL/min, P < .03). Postoperative CrCl (IF: 61.7 mL/min, SF: 64.9 mL/min, P = .3), and the rate of CrCl decrease during the follow-up period (IF: -10.9%, SF: -9.5%, P = .2) was not different between the two groups. The number of patients with a >20% decrease in CrCl was not different between the two groups (IF: n = 35 [25.9%], SF: n = 41 [29.9%], P = .46). However, the magnitude of decrease in CrCl in patients with renal impairment was greater in patients treated with suprarenal fixation endografts (SF: -39%) compared with those treated with infrarenal endografts (IF: -31%, P = .005). This greater degree of renal impairment was not due to identifiable differences in preoperative risk factors, age, or baseline CrCl. No patients in these series required dialysis. CONCLUSIONS: Regardless the type of endograft used, there is a 10% decrease in CrCl in the first year after endovascular aneurysm repair. Suprarenal fixation does not seem to increase the likelihood of postoperative renal impairment. Decline in renal function over time after endovascular aortic repair is probably due to multiple factors, and measures known to be effective in protecting kidneys should be considered for these patients. Long-term follow-up with measurement of CrCl, along with renal imaging and regular blood pressure measurements, should be performed to detect possible late renal dysfunction. Prospective studies comparing suprarenal versus infrarenal fixation are needed to confirm those results.     

Cyclosporine challenge test revisited: does it predict outcome after solitary pancreas transplantation?

BACKGROUND: The selection of patients for solitary pancreas transplantation (PTA) requires identification of individuals who will not develop acute renal dysfunction in response to immunosuppressants. A cyclosporine challenge test (CCT) was developed to predict post-PTA kidney dysfunction secondary to calcineurin inhibitor immunosuppressants. We now report on the long-term follow-up of patients who received a PTA after undergoing a CCT. METHODS: Twelve potential PTA recipients were administered cyclosporine A (CsA) for 6 wk. Creatinine clearance (CrCl) was measured at 2, 4, and 6 wk. Those who did not fail the CCT received PTA. Baseline and post-transplant CrCl were retrospectively evaluated in the original cohort and in a group of matched patients who received PTA without a CCT. RESULTS: Of the original 12 recipients evaluated with the CCT, 6 received PTA. CrCl was followed for a mean of 45.8 months. Of the 4 who remained alive, 2 went on to develop renal failure (CrCl < 30 mL/min) at 18 and 65 months post-transplant. The baseline CrCl was higher in PTA recipients who had not been selected to be studied with CCT than those that were (117 +/- 32 vs 78 +/- 13 mL/min). By 12 months post-PTA, the CrCl was no longer different between the groups selected to be screened with CCT and those that were not. CONCLUSIONS: CCT may help predict risk for short-term changes in renal function (< 18 months) in response to CsA. CCT may be most helpful in candidates for PTA with borderline renal insufficiency (60-80 mL/min).     

Risk analysis for deterioration of renal function after pancreas alone transplant

The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m(2). This is a retrospective, single-center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (> 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥ 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤ 45 and ≤ 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured.     

Multiple Renal Cystic Lesions and Acute Renal Failure in Non-Hodgkin's Testicular Lymphoma—A Case Report

To evaluate renal function after the use of a low-osmolality radiological contrast medium (CM), we prospectively analyzed 39 patients submitted to the following examinations: arteriography (n = 32), phlebography (n = 3), computed tomography (n = 3), angioplasty (n = 1), and retrograde pyelography (n = 1). The patients were divided into three groups: group 1, control, formed by renal donors (CT, n = 11 and 11 exams); group 2, hypertensive patients (HYPT, n = 15 and 16 exams): and group 3, patients with diseases of multiple etiologies (MIX, n = 13 patients and 13 exams). Additionally, the patients were divided according to their renal function into: group 4, with a moderate deficit of renal function, creatinine clearance (CrCl) 25 to 60 mL/min (n = 15 patients and 15 exams); and group 5, with a mild deficit of renal function, CrCl ≥ 60 mL/min (n = 14 patients and 14 exams). The CM utilized was ioxaglic acid (Hexabrix) the incidence of acute renal failure (ARF) among the patients studied was 12.5% (5/40), and CrCl was the best parameter to monitor the alterations in renal function, which occurred in 35% of the patients, although the changes were mild, reversible, and did not need any therapeutic interventions. The triggering of ARF in these patients may have been due to multiple factors presented at time of CM examination. Thus, it is not possible to identify a single risk factor. However, it is probable that previous important impairment of renal function was the most expressive risk factor.     

Chronic kidney disease,mortality, and treatment strategies among patients with clinically significant coronary artery disease

Cardiovascular disease is an important cause of mortality among patients with chronic kidney disease (CKD). This study describes associations between CKD, cardiac revascularization strategies, and mortality among patients with CKD and cardiovascular disease. All patients undergoing cardiac catheterization at Duke University Medical Center (1995 to 2000) with documented stenosis > or =75% of at least one coronary artery and available creatinine data were included. CKD was staged using creatinine clearance (CrCl) derived from the Cockcroft-Gault formula (normal, > or = 90 ml/min; mild, 60 to 89 ml/min; moderate, 30 to 59 ml/min; severe, 15 to 29 ml/min). Cox proportional-hazard regression estimated the relationship between clinical variables, including CrCl and percutaneous coronary artery intervention (PCI), coronary artery bypass grafting (CABG), medical management, and patient survival. There were 4584 patients included, and 24% had CrCl <60 ml/min. Each 10-ml/min decrement in CrCl was associated with an increase in mortality (hazard ratio, 1.14; P < 0.0001). CABG was associated with a survival benefit among patients with both normal renal function and patients with CKD compared with medical management. In patients with normal renal function, CABG was not associated with survival benefit over PCI. However, in patients with CKD, CABG was associated with improved survival. PCI was associated with a survival benefit compared with medical management among patients with normal, mildly, and moderately impaired renal function. Among patients with severe CKD, PCI was not associated with improved survival. CABG is associated with greater mortality reduction than PCI in severe CKD.     

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.     

Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n =34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n =12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n =10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n =12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78±0.23 mL/min; mean±SD) and day 5 (G: 0.91±0.36 mL/min) as compared with C (1.22±0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482±208 mg/day vs C: 716±233; P =0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84±0.40 mL/min) was similar to C (0.84±0.58 mL/min), whereas in G it remained stable (1.27±0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5±13.4%; GS: 10.3±12.3%) was no different to C (RIV: 24.5±12.5%; GS: 20.9±20.0%), whereas both parameters were reduced in G (RIV: 14.1±8.1%; GS: 4.0±4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. The mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function

Dietary protein restriction has been reported to delay the need for renal replacement therapy in clinical trials and meta-analyses. However, less clear is what effect dietary protein has on the rate of decline in renal function. We pooled the results of 13 randomized controlled trials (n = 1,919 patients) and found that dietary protein restriction reduced the rate of decline in estimated glomerular filtration rate by only 0.53 mL/min/yr (95% confidence interval [CI], 0.08 to 0.98 mL/min/yr). We also used weighted regression analysis to determine the reasons for the differences in the results of these 13 randomized trials along with 11 other nonrandomized controlled trials (n = 2,248 patients). The effect of dietary protein restriction (glomerular filtration rate decline in treatment minus control) was substantially less in randomized versus nonrandomized trials (regression coefficient, -5.2 mL/min/yr; 95% CI, -7.8 to -2.5 mL/min/yr; P < 0.05) and relatively greater among diabetic versus nondiabetic patients (5.4 mL/min/yr; 95% CI, 0.3 to 10.5 mL/min/yr; P < 0.05), while there was a trend toward a greater effect with each additional year of follow-up (2.1 mL/min/yr; 95% CI, -0.05 to 4.2 mL/min/yr; P = NS). However, the number of diabetic patients studied was small and the duration of follow-up was short in most trials. No other patient or study characteristics altered the effect of dietary protein restriction on the rate of decline in renal function. Thus, although dietary protein restriction retards the rate of renal function decline, the relatively weak magnitude of this effect suggests that better therapies are needed to slow the rate of renal disease progression.     

Solitary renal allografts from pediatric cadaver donors less than 2 years of age transplanted into adult recipients

BACKGROUND: Transplantation of solitary pediatric renal allografts from donors 2 years of age or younger into adult recipients is controversial. METHODS: Between 1998 and 2001, 15 solitary renal allografts from pediatric donors 2 years of age or younger were transplanted into adult recipients. Thirty-three en bloc renal allografts transplanted between 1994 and 2001 were used for comparison. En bloc kidneys were considered for separation if they measured greater than or equal to 6 cm in length. Renal function (creatinine clearance [CrCl]) was estimated using the Cockroft-Gault formula. RESULTS: Two-year graft survival for the solitary and en bloc groups were 93% and 77%, respectively (P =0.405). Five grafts were lost because of arterial thrombosis (four en bloc and one solitary). Ureteral complications occurred in three grafts in the en bloc group. One-year postoperative CrCl of the surviving solitary (n=14) and en bloc (n=26) grafts were 51.4+/-26.2 mL/min and 55.1+/-27.5 mL/min (P >0.05), respectively. Donor weight and kidney length were greater in the solitary group (14.3+/-3.5 kg and 6.3+/-0.4 cm, respectively) compared with the en bloc group (10.8+/-2.6 kg and 5.9+/-0.3 cm, respectively) (P =0.001 and P <0.001). CONCLUSIONS: Separation of en bloc pairs into solitary allografts can be considered when the graft measures greater than or equal to 6 cm in length and donor weight is greater than or equal to 14 kg. The transplantation of solitary pediatric kidneys into adult recipients is successful, and the majority of pediatric en bloc allografts can be separated before transplantation.     

Prospective study on renal outcome of IgA nephropathy superimposed on diabetic glomerulosclerosis in type 2 diabetic patients.

BACKGROUND AND METHODS: In order to examine the clinical outcome of IgA nephropathy (IgAN) superimposed on diabetic glomerulosclerosis in type 2 patients we studied 36 Chinese patients (26 men, 10 women), who were recruited for renal biopsy when they had proteinuria of more than 1 g/day. Twenty-seven had isolated diabetic glomerulosclerosis and nine had IgAN superimposed on diabetic glomerulosclerosis (combined). Renal function was assessed by serial serum creatinine, 24-h urine protein and creatinine measurements. Patient survival rate, incidence of end-stage renal disease (ESRD), blood pressure, and glycaemic control status were determined. RESULTS: The age at the time of renal biopsy was younger for the combined group when compared with the diabetic glomerulosclerosis group (44+/-3.6 vs 58+/-2.1 years, P=0.006). The duration of diabetes was, however, similar for the two groups (8.0+/-2.3 vs 6.7+/-1.2 years, P=NS). After a mean follow-up of 31.6+/-15.3 months, 15 patients (one in the combined group and 14 in the diabetic glomerulosclerosis group) developed ESRD. Nine patients (all in the diabetic glomerulosclerosis group) died during follow-up. With similar glycaemic and blood pressure control, the two groups had comparable rate of decline of creatinine clearance (CrCl) (-0.73+/-0.26 vs -0.73+/- 0.18 ml/min/1.73 m(2)/month, P=NS), final serum creatinine (363+/-134 vs 426+/-52 micromol/l, P=NS) and proteinuria levels (4.3+/-0.9 vs 4.4+/-0.6 g/day, P=NS), as well as CrCl (44.1+/-19.0 vs 33.4+/-6.9 ml/min/ 1.73 m(2), P=NS). CONCLUSION: It is concluded that the superimposed IgAN does not significantly alter the medium-term clinical outcome of patients with diabetic glomerulosclerosis.     

Decline in native renal function early after bladder-drained pancreas transplantation alone

BACKGROUND: Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). METHODS: Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. RESULTS: Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. CONCLUSIONS: Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.     

Prevalence and progression of chronic kidney disease after renal transplantation

Background

We studied the prevalence of chronic kidney disease (CKD) and its progression after kidney transplantation.

Methods

We retrospectively analyzed the evolution of renal graft function, as estimated by the Cockcroft-Gault equation in 567 patients. CKD was classified in accordance with the National Kidney Foundation/Kidney Disease Outcome Quality Initiative with progression estimated by calculating the slope over time.

Results

Creatinine clearance (CrCL) at 1 year after transplantation was 57.8 ± 15.5 mL/min with 61.9% patients presenting de novo chronic renal failure. The 1-year-CrCl provided the best correlation with the 3-year CrCl (R² = 0.58; P < .001). Medians of slope (MS) among all patients was −2.38 ± 5.7 mL/min/y (−11.9 mL/min over 5 years). Patients who reached a CrCl < 60 at 1 year after transplantation showed a MS of −3.92 ± 6.5, while the others, −2.03 ± 5.2 mL/min/y (P = .046). Similarly, patients who reached a CrCL < 60 at 3 years after transplantation displayed a MS of −1.49 ± 3.5 mL/min/y, while the others, 0.62 ± 3.0 mL/min/y (P < .001).

Conclusions

The majority of renal transplant patients present de novo chronic renal failure already at 1 year posttransplantation. The rate of graft functional deterioration was 2.38 mL/min/y. It was worse among patients who displayed a CrCL less than 60 mL/min both at 1 and at 3 years. One-year CrCL was a good marker for 3-year CrCL.     

The impact of renal dysfunction on aprotinin pharmacokinetics during cardiopulmonary bypass.

Aprotinin is a serine protease inhibitor that undergoes metabolism in the kidney. Because elimination is almost entirely renal, the clearance of aprotinin may be reduced in patients with renal insufficiency. Unfortunately, there are no data regarding aprotinin pharmacokinetics in cardiac surgical patients with renal insufficiency or end-stage renal disease (ESRD) undergoing cardiopulmonary bypass (CPB). We, therefore, determined the clearance (ApCl) and elimination half-life (T1/2) of aprotinin in 26 cardiac surgical patients with normal and abnormal renal function (creatinine clearance [CrCl] 0-122 mL/min) undergoing CPB. Subjects were given a 2 million kallikrein inhibiting unit (KIU) initial dose of aprotinin, followed by a 0.25 million KIU/h infusion. No aprotinin was added to the pump prime. Plasma aprotinin concentrations were sampled at 30 min after completion of the loading dose, 30 and 60 min after the onset of CPB, at the end of CPB, and at 8, 24, and 32 h after completion of the loading dose. ApCl was directly related and the elimination T1/2 inversely related to CrCl (r = 0.75 and 0.42, respectively). In patients with a CrCl >50 mL/min, the T1/2 and ApCl were 7.8 h and 53 mL/min, respectively, compared with 19.9 h and 25 mL/min (P < 0.05, P < 0.002, respectively) for patients with ESRD. In conclusion, ApCl is reduced, and T1/2 is prolonged in patients with renal insufficiency or ESRD undergoing CPB. Dosing modifications may be necessary for patients with abnormal renal function undergoing cardiac surgery. IMPLICATIONS: Because aprotinin is metabolized and eliminated in the kidney, its clearance may be reduced in patients with renal insufficiency. Our data suggest that aprotinin clearance is reduced, and aprotinin half-lives are prolonged in patients with renal insufficiency undergoing CPB. Dosing modification may therefore be indicated when aprotinin is administered to these patients for cardiac surgery.     

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.     

Pharmacokinetics of mycophenolate mofetil in kidney transplant patients with renal insufficiency

Mycophenolate mofetil (MMF) is an immunosuppressant that is widely used for prophylaxis of rejection in solid organ transplantation. In this study, we examined the effect of renal insufficiency on the pharmacokinetics of MMF, particularly on the free fraction of drug in renal transplant patients. Our study was performed on 10 patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min), and 10 control patients with preserved renal function (CrCl >90 mL/min). All the patients had received a cadaveric donor graft at least 1 year prior and were clinically stable under treatment with MMF and cyclosporine. For each patient, we determined 12-hour areas under the curve (AUC(0-12 h)) for the metabolites: mycophenolic acid (MPA), 7-O-mycophenolic acid glucuronide (MPAG), and the free non-protein-bound fraction of MPA (f-MPA). The two groups were matched for age, sex, and MMF dose. Mean AUC(0-12 h) values for MPA were similar in both groups. The renal insufficiency group showed a significantly increased AUC(0-12 h) for MPAG (1550 +/- 392 vs 3527 +/- 1130 microg.h/mL, P < .001) and increased trough and AUC(0-12 h) values for f-MPA (0.023 +/- 0.02 vs 0.094 +/- 0.07 microg/mL, P = .003, and 0.87 +/- 0.3 vs 1.52 +/- 0.8 microg . h/mL, P = .016, respectively). We proposed that these differences should be taken into account when deciding upon the dose of this drug for the subset of patients with impaired transplant function.     

Sirolimus conversion in liver transplant recipients with renal dysfunction: a prospective, randomized, single-center trial

This pilot trial was designed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction. Forty patients with renal dysfunction (24-hr CrCl 40-80 mL/min) were randomized to be withdrawn from the calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control, P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection. Side effects of SRL were limited and included hyperlipidemia requiring treatment (15%), pruritis (5%), and mouth sores (25%). In this trial, SRL-based immunosuppression was a safe alternative to CNI. Although early improvements were observed, withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up.     

The management of renal artery atherosclerosis for renal salvage: does stenting help?

OBJECTIVE: The use of endovascular techniques to treat renal artery stenosis (RAS) has increased in recent years but remains controversial. The purpose of this study was to review the outcomes and durability of percutaneous transluminal angioplasty and stenting (PTA/S) for patients with RAS and decreasing renal function. METHODS: Between 1999 and 2004, 125 consecutive patients underwent angiography and intervention for renal salvage and formed the basis of this study. Inclusion criteria for this study included serum creatinine greater than 1.5 mg/dL, ischemic nephropathy, and high-grade RAS perfusing a single functioning kidney. Patients undergoing PTA/S for renovascular hypertension or fibromuscular dysplasia or in conjunction with endovascular stent grafting for aneurysm repair were excluded. The original angiographic imaging was evaluated for lesion grade and parenchymal kidney size. All medical records and noninvasive testing were reviewed. Preoperative and postoperative patient data were standardized and analyzed by using chi(2) tests for nominal values and t tests for continuous variables. The Modification of Diet in Renal Disease equation was used to estimate glomerular filtration rate (GFR), and univariate analysis was performed. RESULTS: Preoperative variables included the presence of coronary artery disease (93%), diabetes (44%), tobacco use (48%), and hypercholesterolemia (70%). RAS was suspected on the basis of preoperative duplex imaging or magnetic resonance angiography. Aortography and PTA/S were performed in 125 patients (mean age, 71 years; 59% male) with a mean baseline creatinine level of 2.2 mg/dL. There were two mortalities (1.6%) in the 30-day postoperative period, but there was no case of acute renal loss. Blood pressure decreased after PTA/S (151/79 mm Hg before vs 139/72 mm Hg after 1 month; P < .03). For all patients, the estimated GFR went from 33 +/- 12 mL . min(-1) . 1.73 m(-2) (mean +/- SD) to 37 +/- 19 mL . min(-1) . 1.73 m(-2) at 6 months (P = .10). Sixty-seven percent of treated patients had improvement (>10% increase in GFR) or stabilization of renal function. A rapid decline in GFR before intervention was correlated with improvement after PTA/S. Responders after PTA/S had a 27% decrease in GFR before intervention (44 +/- 13 mL . min(-1) . 1.73 m(-2) to 32 +/- 13 mL . min(-1) . 1.73 m(-2); P < .001) with a negative to positive slope change in GFR values. Ten patients underwent reintervention for in-stent restenosis. Cases without improvement in GFR after PTA/S were associated with eventual dialysis need (P = .01; mean follow-up, 19 months). Survival at 3 years was 76%, and dialysis-free survival was 63% as estimated by Kaplan-Meier analyses. CONCLUSIONS: Renal artery stenoses causing renal dysfunction can be safely treated via endovascular means. Rapidly decreasing renal function is associated with the response to renal artery angioplasty/stenting and helps identify patients for renal salvage.