Brain MR imaging abnormalities in kidney transplant recipients.

BACKGROUND AND PURPOSE: On the basis of limited available data, brain MR imaging abnormalities in kidney transplant recipients (KTRs) have been predominantly attributed to calcineurin inhibitors (CIs), characteristically presenting as posterior reversible encephalopathy syndrome (PRES). The goal of this study was to evaluate whether CIs play an important role in the incidence, nature, and location of MR imaging brain lesions in adult KTRs by comparing them with dialysis-dependent patients. METHODS: We retrospectively analyzed 98 brain MR imaging examinations in 77 consecutive KTRs presenting with neurologic symptoms from 1990 to 2003. The data were separated into 3 groups according to duration after transplantation of MR imaging: group 1, 0-3 months; group 2, 3-12 months; and group 3, >12 months. Twenty-six MR imaging examinations from 24 additional dialysis-dependent adults were used as controls and comprised group 0. RESULTS: Acute changes (infarcts, infections, PRES) comprised 24% and 19% of lesions in KTRs and group 0 patients, respectively, with infarcts being the most common in all groups. Chronic lesions were responsible for 76% of changes in KTR and 81% in group 0 and were predominantly vascular in etiology. No statistically significant differences in incidence of PRES or other acute changes were found between dialysis-dependent patients and either individual KTR groups or all KTR patients combined. The deep gray matter lesions were more common in KTR, whereas frontal white matter was more frequently affected in patients on dialysis. CONCLUSION: Our study does not support suggestion that MR imaging brain abnormalities in KTR are predominantly due to direct CI toxicity.

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation.

Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well described. We reviewed 112 KPTxs performed at our institution between December 3, 1995 and June 27, 2002. All patients received antibody induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was substituted for MMF for the following reasons: acute rejection (AR) of kidney or pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL because of AR, one kidney failed because of antibody-resistant AR, and one kidney developed borderline AR; the other eight patients remain AR-free. AR developed in seven other patients despite therapeutic SRL levels; six had TAC levels less than 4.5 ng/mL. The mean creatinine levels overall and for the group with increasing creatinine remained stable. All patients who were switched to SRL for TAC-induced hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients can be safely switched to SRL with excellent graft and patient survival.

Respiratory syncytial virus pneumonia in an adult renal transplant patient: an unexpected nosocomial infection.

This article describes a case of respiratory syncytial virus pneumonia believed to have been acquired nosocomially in an adult renal transplant recipient. The mode of transmission, diagnosis, and prevention of infection due to this virus in the immunocompromised patient are discussed.

Influence of mild obesity on outcome of simultaneous pancreas and kidney transplantation.

The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney transplantation (SPK) has not been well described. We retrospectively reviewed 88 consecutive primary SPKs performed at our institution between March 15, 1995 and August 28, 2001. All patients received antibody induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemic-enteric implantation was performed in all patients. Primary end points were patient, pancreas, and kidney survival. Secondary end points were rates of anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat laparotomy, and length of hospital stay. Values are shown as mean+/-standard deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a BMI < or =24.9 (mean 21.7+/-2.2, range 15.4 to 24.9). Thirty-six patients were mild to moderately obese with a BMI > or =25 (mean 27.7+/-2.2, range 25 to 35.1). Distribution of recipient age, sex, and ethnicity was similar between groups. Kidney and pancreas preservation times were similar between nonobese and obese patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95% vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%, 91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%) survival were comparable between nonobese and obese (P=NS). The mean rates of pancreas thrombosis, major infection, pancreas rejection, kidney rejection, relaparotomy, and length of hospital stay were similar in the two groups. The overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17% incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese patients (P=0.012). Six of seven leaks occurred in obese patients. Mean BMI in the seven patients with a leak (27+/-1.9) was significantly higher than in patients who did not develop a leak (24+/-3.7; P=0.05). Although obesity had no effect on patient or graft survival, it was associated with a significantly higher leakage rate. There should therefore be a higher degree of suspicion for the presence of duodenojejunal anastomotic leaks in obese SPK recipients.

Can a pharmacokinetic approach to immunosuppression eliminate ethnic disparities in renal allograft outcome?

Although renal allograft outcome correlates more closely with area under the concentration time curve (AUC) for cyclosporin (CsA) compared with the 12-h trough level (C0), few studies have prospectively evaluated pharmacokinetic monitoring in kidney transplantation. This paper describes a study designed to evaluate the impact of a novel approach to CsA-based immunosuppression on ethnic differences in renal allograft outcome. Sixty (32 African Americans and 28 Caucasians) renal transplant recipients were treated with cyclosporin-based triple therapy. Morning and evening doses were independently adjusted to reach an AUC0-12 of 6600-7200 ng h/mL and a C0 of 250-325 ng/mL, respectively. AUCs were measured within 48 h of starting CsA, and as often as necessary to maintain target levels. Only two patients experienced significant adverse events related to immunosuppression. One (Caucasian) developed haemolytic uremic syndrome and was converted to tacrolimus, while another (African American) developed acute vascular rejection. One graft was lost (Caucasian) due to death with a functioning graft. An average of 8 AUCs (range 5-13) were measured in the first 3 months. AUCs were significantly higher in African Americans compared with Caucasians only in the first and second month. C0 values were similar in both groups throughout the study period. A pharmacokinetic approach to immunosuppression allows individualization of CsA exposure, and appears to reduce ethnic disparities in renal allograft outcome.

Delayed graft function may not adversely affect short-term renal allograft outcome.

INTRODUCTION: Delayed graft function (DGF) is commonly believed to adversely impact both short- and long-term renal allograft function. Because immunosuppressive therapy is commonly altered after DGF is identified, retrospective analyses are difficult to interpret. We therefore prospectively sought to examine the natural history of DGF in a controlled patient population under identical immunosuppressive protocols. METHODS: Adult patients undergoing cadaveric renal transplantation were treated with sequential triple drug immunotherapy. High-dose steroids were administered in the operating room and rapidly tapered to 20 mg prednisone by post-operative day (POD) 6. Cyclosporine (CsA) microemulsion was begun on POD 1, and dosed asymmetrically at 12-h intervals to reach a daytime Cav of 650 ng/mL (utilizing 2-h and 6-h levels), while PM doses were adjusted to an AM trough of 300 ng/mL. Mycophenolate (1000 mg q12 h) was added on POD 3 in most patients and discontinued after 3 months. No induction agents were used. All patients were followed for at least 6 months. RESULTS: Sixty consecutive patients received 64 allografts (four double grafts). In all, 17 patients required dialysis and were considered to have DGF. Eight of these patients received marginal organs turned down by at least one other centre. Cold ischaemia time was significantly longer in patients with DGF (24 h vs. 19 h, P < 0.01) All patients were treated as planned and there were no major protocol violations. One patient had primary non-function and was excluded from analysis. CsA trough and Cav values were similar between groups. Mean serum creatinine levels (mg/mL) fell more slowly in patients with DGF but there was no significant difference by 3 months (1.7 vs. 1.5) and the creatinine clearance was not significantly different between the groups after 1 year (71 cm3/min in DGF vs. 61 cm3/min, P = 0.13). Our data demonstrate that alterations in routine immunosuppressive strategies may not be necessary to achieve equivalent outcomes in patients with DGF.

Effect of cyclosporin pharmacokinetics on renal allograft outcome in African-Americans.

African-Americans (A-As) experience inferior outcome after transplantation compared with other ethnic groups. Bioavailability of cyclosporin (CsA) has been implicated as a possible contributing factor. This paper describes the outcome of 32 A-A recipients of de novo renal allograft who received CsA-based triple immunotherapy according to individual pharmacokinetic profiles. Patients received CsA-microemulsion q 12 h, dosed initially at 3.5 mg/kg (8 am) and 3.0 mg/kg (8 pm). The am and pm doses were independently adjusted to achieve a 12-h area under the concentration-time curve (AUC0-12) of 6600-7200 nghr/mL and morning trough level (C0) of 250-325 ng/mL, respectively. Mean age was 43 +/- 12 yr, 37% (12) female. Mean AUC0-12 in 1 wk, 1, 3, 6, and 12 months were 7810 +/- 1880 nghr/mL, 9057 +/- 2097 nghr/mL, 7674 +/- 1912 nghr/mL, 7132 +/- 2040 nghr/mL, and 6503 +/- 1410 ngl/h with corresponding C0 of 301 +/- 79 ng/mL, 316 +/- 66 ng/mL, 275 +/- 59 ng/mL, 273 +/- 66 ng/mL, and 224 +/- 49 ng/mL, respectively. Acute rejection occurred in two patients (6%) 1 yr after transplantation. Prospective use of CsA pharmocokinetic profiles improves renal allograft outcome in A-As.

Living donor transplantation of a pelvic kidney.

Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living-donor transplantation using a pelvic kidney in a 17-month-old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment.

Effect of ethnicity on outcome of simultaneous pancreas and kidney transplantation.

The influence of ethnicity on outcome of simultaneous pancreas-kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African-Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One-, 3-, and 5-year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One-, 3-, and 5-year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One-, 3-, and 5-year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.