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Background: Posttransplant bone disease is a well recognized and undertreated problem. The use of protocols within other populations has been shown to improve recognition and treatment of common disease states, but outcome studies involving the use of protocols within transplant patients are lacking., Objective: To compare the appropriate screening for and the prevention and treatment of osteopenia and osteoporosis in transplant patients before and after a bone health protocol was implemented., Methods: A retrospective analysis in a single institution was designed to determine whether the development and implementation of a comprehensive bone health protocol impacted disease outcomes in posttransplant kidney and simultaneous kidney-pancreas patients., Results: There were 132 patients in the historical control group and 76 in the treatment group. The groups were well matched, with no statistically significant differences noted for any of the baseline characteristics that were compared, including the modifiable and nonmodifiable risk factors known to put a patient at increased risk for osteopenia or osteoporosis. Significantly more patients in the treatment group received proper screening and prevention compared with the historical control group (p < 0.001). Although more patients in the treatment group received proper bone disease treatment, this did not reach statistical significance (81% vs 66%; p < 0.22). Additionally, the dual energy X-ray absorptiometry scans were performed, on average, 19 days earlier in the treatment group, although this also did not achieve statistical significance (p = 0.149)., Conclusions: The multidisciplinary development and implementation of a comprehensive bone health protocol improves the screening and prevention of osteopenia and osteoporosis within kidney and pancreas transplant recipients.

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.

Desmopressin (DDAVP) is commonly used in cadaveric organ donors to treat diabetes insipidus. The thrombogenic potential of DDAVP is well known. Recent animal data have demonstrated that DDAVP impairs pancreas graft (PG) microcirculation and perfusion. The aim of this study was too evaluate the effect of DDAVP on the incidence of PG thrombosis in clinical pancreas transplantation. A retrospective review of simultaneous kidney-pancreas transplant (SKPT) entered in the Scientific Registry of Transplant Recipients (SRTR) between 10/5/87 and 9/27/02 was performed. Patients were included for analysis if there was definitive documentation as to whether DDAVP was (DDAVP-Y) or was not (DDAVP-N) administered to the donor. Both dose and duration of DDAVP treatment were not recorded by SRTR. A total of 2804 SKPTs were available for analysis. Mean follow-up was 1.75 years (range, 1 month to 8.4 years). A total of 1287 SKPT patients (46%) received a PG from a DDAVP-Y donor. Graft ischemia times, donor and recipient ages, recipient gender distribution, surgical techniques, and immunosuppressive regimens were similar in both groups. The overall incidence of PG thrombosis was 4.3%. The incidence of PG thrombosis in recipients of grafts from DDAVP-Y donors was 5.1% compared to 3.5% in recipients of grafts from DDAVP-N donors (P =.04). Fifty-eight percent of thrombosed PG came from DDAVP-Y donors compared to 42% from DDAVP-N donors (P =.04). We conclude that there appears to be a relationship between donor treatment with DDAVP and PG thrombosis. A prospective study is needed to verify these findings and to determine their clinical significance.

The aim of this study was to evaluate long-term outcome of sirolimus (SRL) rescue in kidney-pancreas transplantation (KPTx). We reviewed 112 KPTx performed at our institution from 12/3/95 to 6/27/02. All patients received antibody (Ab) induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-five patients (31%) had SRL substituted for MMF for the following indications: (1) acute rejection (AR) of kidney or pancreas despite adequate TAC levels; (2) intolerance of full-dose MMF; (3) rising creatinine; and (4) TAC-induced hyperglycemia. Target SRL and TAC levels were 10 ng/mL and 5 ng/mL, respectively. Mean follow-up was 3 +/- 2 years overall and 1.2 +/- 0.5 years after SRL rescue. No patients died. One- and 3-year actuarial kidney and pancreas graft survival was 97%, 97%, and 95%, 90%, respectively. Of 10 patients switched to SRL for AR, 1 kidney failed from Ab-resistant AR, 1 kidney developed borderline AR, and the other 8 remain AR-free. Seven other patients developed AR despite therapeutic SRL levels; of these, 6 (86%) had mean TAC levels of <4.5 in the month preceding AR. Mean creatinine overall and for the rising creatinine group remained stable. All patients switched to SRL for TAC-induced hyperglycemia or MMF intolerance demonstrated biochemical or clinical improvement. Sirolimus-related infection or other serious adverse events (SAE) were uncommon. In conclusion, KPTx recipients can be safely switched to SRL with long-term stabilization of renal function, excellent graft and patient survival, and no increase in SAE. A minimum TAC level of 4.5 ng/mL may be necessary to prevent late AR.

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.

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.

Reports on renal graft outcome after kidney-alone (KA) and simultaneous pancreas-kidney (SPK) transplants have focused on graft survival instead of function. The aim of this study is to compare renal graft outcome after KA and SPK using graft function and survival as the measures of outcome. The records of 102 transplants performed in type I diabetics from 10/90 to 9/96 were reviewed (SPK 42, KA 60). Serum creatinine (Cr) and calculated glomerular filtration rate (GFR) were used as estimates of graft function. Cr were similar in SPK and KA on day 3 (4.8 +/- 2.9 vs. 4.8 +/- 2.8 mg/dl, P = 0.9) and day 7 (2.5 +/- 1.8 vs. 3.0 +/- 2.5 mg/dl, P = 0.3). GFR was higher KA at 6 months (57 +/- 18 vs. 51 +/- 12 ml/min, P = 0.08), 1 yr (55 +/- 23 vs. 51 +/- 11 ml/min, P = 0.4) and 3 yr (60 +/- 22 vs. 42 +/- 16 ml/min, P = 0.03). Kidney graft survival was similar in KA and SPK at 1 and 5 yr (87% vs. 89% and 44% vs. 47%, P = 0.8). Immunologic failure of the renal graft occurred more frequently in SPK (58% vs. 48%, P = 0.04) whereas death with function was more common in KA (33% vs. 17%, P = 0.04). In KA, risk factors for failure of the renal graft included acute rejection (P = 0.008, relative risk or rr = 3.4) and African American recipient (P = 0.06, rr = 2.8). In SPK, risk factors included donor age > 40 yr (P = 0.05, rr = 5.3) and African American donor (P = 0.03, rr = 4.5). Logistic regression analysis revealed the following risk factors for GFR < 50 ml/min at 1 yr: acute rejection (P = 0.03, rr = 2.2) and Cr > 3 mg/dl on day 7 (P = 0.06, rr = 2.3). In conclusion, although renal graft survival was similar after KA and SPK, better graft function was observed in KA at 3 yr. Assessment of renal graft function allows us to evaluate outcome from a different perspective than graft survival, and these two measures of outcome complement each other.