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P R Rajagopalan

Publications and source records attributed to P R Rajagopalan.

At least 19 recordsLinked to original sources
PubMed2006

Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation.

BACKGROUND: Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. METHODS: This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. RESULTS: FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. CONCLUSIONS: While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

Adult↗
PubMed2006

Parenchymal transection of the kidney inflicted by endocatch bag entrapment during a laparoscopic donor nephrectomy.

We present a case of inadvertent decapsulation and grade IV renal parenchyma laceration during laparoscopic donor nephrectomy. The kidney was repaired, used and functioned immediately. There were no complications in the donor. To our knowledge, this type of injury has not been reported previously and the purpose of this report is to focus attention on the potential for this unusual injury, which can occur during delivery of the kidney using the endocatch bag.

Adult↗
PubMed2005

Does bioequivalence between modified cyclosporine formulations translate into equal outcomes?

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Biopsy↗
PubMed2005

Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study.

BACKGROUND: This 36-month, randomized, parallel-group study compared safety and efficacy of two doses of everolimus with mycophenolate mofetil (MMF) in de novo renal-transplant recipients. METHODS: Renal-allograft recipients received 1.5 mg/day or 3 mg/day of everolimus or 2 g/day of MMF, plus full-dose cyclosporine (CsA) and corticosteroids after randomization. For at least their first year, patients received study medication according to a double-blinded, double-dummy design. Concerns over nephrotoxicity led to a protocol amendment to an open-label design with reduced CsA troughs. RESULTS: Incidences of primary efficacy failure at 36 months (biopsy-proven acute rejection, graft loss, death, or loss to follow-up) were everolimus 1.5 mg/day, 33.7% (65/193); everolimus 3 mg/day, 34.0% (66/194); and MMF, 31.1% (61/196) (P=0.810). Antibody-treated acute rejection at 36 months was significantly lower with everolimus 1.5 mg (9.8%) than MMF (18.4%, P=0.014). Discontinuation for adverse events was more frequent with everolimus and hemolytic uremic syndrome, lymphoproliferative disease, and proteinuria, and higher serum creatinine occurred at increased frequency relative to the MMF arm. Creatinine levels in the everolimus arms were stable in follow-up: the mean rise in creatinine over the first 6 months of the open-label phase was 3 micromol/L or greater with everolimus and 7 micromol/L with MMF. However, serum creatinine levels were lower in the MMF group throughout. Death and graft loss were higher in the everolimus arms (not significant). CONCLUSIONS: As part of triple-drug immunosuppression, everolimus (1.5 or 3 mg/day) was as efficacious as MMF, although the side-effect profile featured increased adverse events. Nephrotoxicity/calcineurin-inhibitor-related adverse events will require judicious lowering of CsA exposure with monitoring of everolimus troughs.

Adolescent↗
PubMed2004

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.

Child↗
PubMed2004

Thrombosed dialysis access grafts: randomized comparison of the Amplatz thrombectomy device and surgical thromboembolectomy.

We report the final results of the trial comparing the Amplatz thrombectomy device (ATD) with surgical thromboembolectomy (ST) to declot thrombosed dialysis access grafts (DAG). The study population consisted of 174 DAG, 109 of which were randomized to mechanical thrombectomy using the ATD and 65 of which were randomized to conventional surgical thromboembolectomy. Forty grafts were re-enrolled in the trial when they failed beyond the 90 days follow-up after the initial treatment. Thirty-one were re-enrolled for mechanical thrombectomy and nine were re-enrolled for surgical thrombectomy, resulting in a total of 140 ATD procedures and 74 surgical thromboembolectomy. Immediate thrombectomy success was defined as greater than 90% thrombus removal followed by the ability to dialyze after treatment, and analysis of long term success based on graft patency at 30 and 90 days, with successful dialysis. Immediate thrombectomy success with the ATD procedure was achieved in 79.2% and with ST in 73.4%. Patency of the graft, with successful dialysis, at 30 days with the ATD procedure was 79.2% and with ST was 73.4%. Patency of the graft, with successful dialysis, at 90 days with the ATD procedure was 75.2% and with ST was 67.8%. The data collected in this study provided a prospective comparison of mechanical thrombectomy with the ATD and ST performance in thrombosed DAG. The results of the performance of both methods were comparable. No statistically significant differences were seen.

Catheterization↗
PubMed2004

Does treatment of cadaveric organ donors with desmopressin increase the likelihood of pancreas graft thrombosis? Results of a preliminary study.

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.

Cadaver↗
PubMed2004

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

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.

Creatinine↗
PubMed2004

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.

Humans↗
PubMed2004

Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease.

BACKGROUND: Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the L-valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high-risk renal and pancreas transplant recipients. METHODS: Patients at high risk for development of CMV disease were defined as either those who had donor positive, recipient-negative serostatus (D+/R-), or those who received antilymphocyte antibody (ALA) therapy for either rejection treatment or induction. A retrospective review was conducted of all kidney and pancreas transplants performed between August 2001 and December 2003. A total of 341 transplants were performed, of which 109 received VGC, and 88 were included in this analysis. RESULTS: The overall incidence of CMV disease was 5.7% (5/88). All of the CMV episodes were in patients who were D+/R- (17.2% [5/29] versus 0% [0/59], P<0.001). Of these patients, all the episodes of CMV were in patients who received VGC prophylaxis for<100 days post transplant (29% [5/17] versus 0% [0/12], P=0.06). The overall incidence of leukopenia was 11% and thrombocytopenia was 7%, with the incidence between the D+/R- group and the ALA group being similar. CONCLUSION: VGC is an effective agent in preventing CMV disease in kidney and pancreas transplant recipients who are at high risk for developing the disease. The optimal length of prophylaxis in D+/R- patients is still undefined, while 3 months of prophylaxis appears to be sufficient in patients who received ALA therapy.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

Thromboembolic risk factors in patients undergoing kidney transplant: implication of abnormally short activated partial thromboplastin time.

This study was designed to examine the relationship of short activated partial thromboplastin time (aPTT) and prothrombin time (PT) to the incidence of thromboembolic events, hereditary and acquired coagulation defects associated with an increased risk of thrombosis, or cardiovascular diseases in patients undergoing renal transplantation. The prevalence of these conditions in our patients (n = 436) was 55%. Forty-two percent of the patients had short aPTT or PT. Multivariate analysis revealed that patients with short aPTT have an odds ratio (OR) = 2.15, 95% Confidence Interval (CI) (1.27-3.64) (p = 0.0042), and for patients with short PT, an OR = 2.01, 95% CI (0.99-4.08) (p = 0.052). Our study also suggests that other risk factors, including non-white ethnicity (98% blacks), OR = 1.64, 95% CI (1.01-2.67) (p = 0.047), diabetes mellitus, OR = 2.62, 95% CI (1.11-6.18) (P = 0.028), and autosomal dominant polycystic kidney disease (ADPKD) (p < 0.0001). Short aPTT results, or probably short PT results, pre- or post-transplantation may be associated with increased risks for thromboembolism.

Adult↗
PubMed2001

Further improvements in laparoscopic donor nephrectomy: decreased pain and accelerated recovery.

Fear of postoperative pain is a disincentive to living donor kidney transplantation. Laparoscopic donor nephrectomy (LDN) was developed in part to dispel this disincentive. The dramatic increase in the number of laparoscopic donor nephrectomies performed at our institution has been in part due to the reduction in postoperative pain as compared to traditional, open donor nephrectomy. We sought to further diminish the pain associated with this surgical technique. The purpose of this study was to compare the efficacy of three different postoperative pain management regimens after LDN. All living kidney donors performed laparoscopically (n=43) between September 1998 and April 2000 were included for analysis. Primary endpoints included postoperative narcotic requirements and length of stay. Narcotic usage was converted to morphine equivalents (ME) for comparison purposes. Patients received one of three pain control regimens (group 1: oral and intravenous narcotics; group II: oral and intravenous narcotics and the On-Q pump delivering a continuous infusion of subfascial bupivicaine 0.5%; and group III: oral and intravenous narcotics and subfascial bupivicaine 0.5% injection). Postoperative intravenous and oral narcotic use as measured in morphine equivalents was significantly less in group III versus groups I and II (group III: 28.7 ME versus group I: 40.2 ME, group II: 44.8 ME; P<0.05). Postoperative length of stay was also shorter for group III (1.8 days) versus group I (2.5 days) and group II (2.9 days). LDN has been shown to be a viable alternative to traditional open donor nephrectomy for living kidney donation. We observed that the use of combined oral and intravenous narcotics alone is associated with greater postoperative narcotic use and increased length of stay compared to either a combined oral and intravenous narcotics plus continuous or single injection subfascial administration of bupivicaine. The progressive modification of our analgesic regimen has resulted in decreased postoperative oral and intravenous narcotic use and a reduction in the length of stay. We recommend subfascial infiltration with bupivicaine to the three laparoscopic sites and the pfannenstiel incision at the conclusion of the procedure to reduce postoperative pain. We believe this improvement in postoperative pain management will continue to make LDN even more appealing to the potential living kidney donor.

Adult↗
PubMed2001

Cadaveric renal transplantation in African-Americans in South Carolina.

The renal transplant program at the MUSC was established in 1968 and is the only transplant center in South Carolina. It serves a large population of African American patients who constitute nearly two-thirds of the waiting list and more than half of all renal transplants. Between 1968-2000, 969 transplants were performed in 906 AA patients. Most received organs from cadaveric donors, while only 99 (10%) of AA patients received living donor transplants. The acceptance of living unrelated donors and the use of laparoscopic nephrectomy have had a negligible impact on living donations in this racial group. Primary disease had little effect on outcome except in diabetics whose mortality was higher. The one-year graft survival rates improved dramatically with the aggressive use of CsA without the use of antibody induction. The overall one- and 5-year graft survival rates improved from 53% and 32%, respectively, in the 1978-1983 era to 87% and 59%, respectively, in the 1993-2001 era. At MUSC, the emphasis has been on reducing mortality due to sepsis by limiting the number of rejections treated particularly in recipients of cadaveric organs. While this has resulted in reduced overall early mortality, it has not adversely affected graft survival. Our experience suggests that while short-term graft survival has improved significantly over the years for AA patients, the long-term outcome still remains relatively unchanged.

Black or African American↗
PubMed2000

Acute renal artery and vein thrombosis after renal transplant, associated with a short partial thromboplastin time and factor V Leiden mutation.

Renal graft thrombosis is a rare but devastating complication of renal transplantation. It accounts for one-third to one-half of early graft losses. We report a patient with acute renal artery and vein thrombosis associated with abnormally short activated partial thromboplastin time (aPTT) and factor V Leiden mutation. Vascular thrombosis developed on the ninth post-transplant day and led to a graft loss. Before transplantation, the patient had three episodes of thrombosis of arteriovenous access for hemodialysis. Our case illustrates the importance of investigating pretransplant patients for hypercoagulable states, particularly those with short aPTT.

Acute Disease↗
PubMed1999

Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. The U.S. Simulect Renal Transplant Study Group.

BACKGROUND: Basiliximab is an interleukin-2 receptor (CD25) chimeric monoclonal antibody used for acute rejection prophylaxis in renal transplants. In the context of a randomized, double-blind efficacy trial, its population pharmacokinetics and potential exposure-response relationships were explored in de novo kidney allograft recipients receiving 40 mg basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppressive therapy with cyclosporine microemulsion and corticosteroids. METHODS: Serial blood samples (8.2+/-1.3 per patient) were collected over 12 weeks after transplant from 169 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. The duration of CD25 saturation was estimated as the time over which serum basiliximab concentrations exceeded 0.2 microg/ml. The relationships between pharmacokinetic parameters and demographic-clinical covariates were explored by regression methods and unpaired t-tests. RESULTS: Basiliximab clearance was 36.7+/-15.2 ml/hr, distribution volume 8.0+/-2.4 L, and half life 7.4+/-3.0 days. Patient weight (range, 44-131 kg) and age (range, 20-69 yrs) each contributed < or =6% to the variability in clearance and volume. Gender, ethnic group, and the presence of proteinuria had no clinically relevant influences on basiliximab disposition. Receptor-saturating basiliximab concentrations were maintained for 36+/-14 days (range, 12-91). There was no apparent relationship between the incidence or day of onset of acute rejection episodes during CD25 saturation and basiliximab concentration (range, 0.2-5.0 microg/ml). In patients who experienced a rejection episode after basiliximab was eliminated from serum (n=33), basiliximab had not been cleared faster than in their rejection-free peers (P=0.322) nor had CD25 been saturated for a shorter period of time (33+/-13 days vs. 37+/-14 days for rejection-free patients, P=0.162). CONCLUSIONS: There were no demographic or clinical subpopulations not adequately treated with the standard basiliximab dosing regimen. Over the range of CD25 suppression durations observed in this study, extended periods of receptor blockade did not seem to confer an immunoprophylactic advantage compared with shorter periods of receptor suppression.

Adult↗