Biomedical subjects

Chris E Freise

Publications and source records attributed to Chris E Freise.

At least 19 recordsLinked to original sources

PubMed2007

Predicting biliary complications in right lobe liver transplant recipients according to distance between donor's bile duct and corresponding hepatic artery.

PURPOSE: To retrospectively determine whether biliary complications in recipients of living-donor right lobe liver grafts can be predicted at pretransplantation donor computed tomography (CT). MATERIALS AND METHODS: The human research committee approved this study. The requirement for informed consent was waived. Multi-detector row CT cholangiography and CT angiography were performed in 44 consecutive right lobe liver donors (25 men, 19 women; mean age, 37 years). When CT cholangiography in the donor demonstrated the right biliary anatomy (conventional or variant), the shortest distance between the right main (or second-order) hepatic artery and the corresponding right main (or second-order) bile duct was measured and compared with posttransplantation biliary complications in the transplant recipient by using generalized estimating equations. RESULTS: In 22 transplant recipients with one right main duct-to-common duct anastomosis (ie, conventional donor anatomy), the distance between the donor's right main bile duct and hepatic artery generally was small (mean distance, 3.8 mm; range, 1-14 mm) and unrelated (P=.46) to biliary complications (n=6). In 22 recipients who required two second-order right duct anastomoses (ie, with variant donor anatomy), the distance between the donor's second-order duct and corresponding hepatic artery was more variable (mean distance, 6.6 mm; range, 1-32.5 mm), and biliary complications were significantly more common when this distance was 10 mm or greater (in eight of 13 ducts with conventional anatomy and four of 31 ducts with variant anatomy, P<.05). CONCLUSION: Right lobe liver graft recipients who have variant right biliary anatomy and a second-order bile duct 10 mm or farther from the corresponding hepatic artery are at high risk for biliary complications, possibly because of a predisposition to ischemic injury.

Adult↗

PubMed2005

More than 500 consecutive laparoscopic donor nephrectomies without conversion or repeated surgery.

HYPOTHESIS: Concern exists as to the safety of laparoscopic donor nephrectomy (LDN) compared with open donor nephrectomy. Reported complications of LDN include emergent conversion to an open procedure, repeated surgery for postoperative bleeding, and even death. We hypothesize that LDNs can be performed safely, with a complication rate comparable with that of open donor nephrectomies. DESIGN: Case series and review of the literature. SETTING: Tertiary care university hospital. PATIENTS: Five hundred thirty kidney donors. INTERVENTION: An LDN performed without hand assistance, with the kidney extracted through a low transverse incision. MAIN OUTCOME MEASURES: Mean operative time, requirement for transfusion, intraoperative complications, and postoperative complications. RESULTS: This series includes 84 right-sided donor nephrectomies, 86 donors with a body mass index greater than 30 (calculated as weight in kilograms divided by the square of height in meters), and 91 donors with complex vascular anatomy. Mean donor age was 40 years (range, 18-73 years), and mean +/- SD operative time was 196 +/- 43 minutes. The only conversion occurred early in the series, and there have been 525 subsequent cases without the need for conversion or repeated surgery. There were no donor deaths. Five donors (0.9%) required perioperative blood transfusions. Overall complication rate was 6.4%, including 14 minor wound infections, 2 bowel injuries, 1 case of prolonged ileus, 3 splenic injuries, 2 bladder infections, 1 bladder injury, 1 case of rhabdomyolysis, 1 case of pneumonia, and 2 thromboembolic events. CONCLUSION: This series demonstrates that LDN can be performed at least as safely as open donor nephrectomy, with minimal bleeding and few postoperative complications.

Adolescent↗

PubMed2005

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation.

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and < or =8 cm, 2 or 3 lesions at least 1 >3 cm but < or =5 cm with total tumor diameter of < or =8 cm, or 4 or 5 nodules all < or =3 cm with total tumor diameter < or =8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT.

Aged↗

PubMed2005

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation.

PURPOSE: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32 patients were retrospectively reviewed using the electronic database at our institution. RESULTS: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively. CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.

Adult↗

PubMed2005

Outcomes of 385 adult-to-adult living donor liver transplant recipients: a report from the A2ALL Consortium.

OBJECTIVE: The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of perioperative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). SUMMARY BACKGROUND DATA: Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure. METHODS: Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure. RESULTS: Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors. CONCLUSIONS: This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience.

Adult↗

PubMed2005

H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants.

BACKGROUND: Severe ischemia/reperfusion (IR) injury is a risk factor for delayed graft function. Delayed graft function remains difficult to predict, and it currently relies primarily on serum creatinine (SCr), urine output, and occasionally on graft biopsy. (1)H-NMR (nuclear magnetic resonance spectroscopy) based metabolomics was used to establish IR-specific metabolic markers in both blood and kidney tissue. These markers were compared to SCr and graft histology. METHODS: Male Lewis rats were used for kidney transplantation. Two cold ischemia (CI) groups (24- and 42-hour) and two transplantation groups [after 24 (TX24) and after 42 hours (TX42) of CI] were compared to a control group. Whole blood and kidney tissue were collected for further analysis. RESULTS: SCr levels taken 24 hours after transplantation were 1.6 +/- 0.12 mg/dL (TX24) and 2.1 +/- 0.5 mg/dL (TX42), (P= n.s.). Histology samples revealed mild injury in the TX24 group and severe injury in the TX42 group. A significantly decreased level of polyunsaturated fatty acids (PUFA) and elevated levels of allantoin, a marker of oxidative stress, was found in the renal tissue. In the blood, both trimethylamine-N-oxide (TMAO), a marker of renal medullary injury, and allantoin were significantly increased. Allantoin levels were low in both the control and CI groups. Levels were significantly increased after reperfusion (control 0.02 +/- 0.03 micromol/mL, TX24 1.13 +/- 0.22, and TX42 1.89 +/- 0.38, P < 0.001), and correlated with cold ischemia time (r= 0.96) and TMAO (r= 0.94). CONCLUSION: The (1)H-NMR metabolic profiles of both the mild and severe IR groups revealed significant changes consistent with graft histology, while the SCr did not.

Allantoin↗

PubMed2005

BKV in simultaneous pancreas-kidney transplant recipients: a leading cause of renal graft loss in first 2 years post-transplant.

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.

Adult↗

PubMed2005

Laparoscopic procurement of kidneys with multiple renal arteries is associated with increased ureteral complications in the recipient.

This study investigates the effect of renal artery multiplicity on donor and recipient outcomes after laparoscopic donor nephrectomy. Three-hundred and sixty-one sequential procedures were performed over a 4-year period. Forty-nine involved accessory renal arteries; of these, 36 required revascularization and 13 were small polar vessels and ligated. The 312 remaining kidneys with single arteries served as controls. Study variables included operative times, blood loss, hospital stay, graft function and donor and recipient complications. Kidneys with multiple revascularized arteries had a longer mean warm ischemia time (35.3 vs. 29.2 min, p = 0.0003), and more ureteral complications (6/36 vs. 10/312, p = 0.0013) than single-artery controls. In contrast, ligation of a small superior accessory artery had no significant effect on donor operative time, blood loss, or complication rate while providing similar recipient graft function compared to single-artery controls. Renal artery number is important in selecting the appropriate kidney for laparoscopic procurement. Given the current excellent results with right-sided donor nephrectomy, kidneys with single arteries should be preferentially procured, irrespective of side.

Adult↗

PubMed2004

Laparoscopic right donor nephrectomy: a large single-center experience.

BACKGROUND: Laparoscopic procurement of right donor kidneys is frequently avoided or performed using hand-assist devices because of concerns regarding donor safety, adequate exposure, and vessel length. The present study describes the authors' large series of right donor nephrectomies performed laparoscopically without the use of hand ports or other manual assist devices. METHODS: The authors retrospectively analyzed all right laparoscopic donor nephrectomies performed at their center from November 1, 1999, to February 20, 2004. Study variables included operative times, blood loss, hospital stay, graft function, and donor and recipient complications. Left donor nephrectomies performed during the same period served as controls. RESULTS: Of 387 laparoscopic kidney procurements, 54 (14 %) were right nephrectomies. Blood loss, extraction times, length of stay, and overall complication rates were similar between right and left donor groups. The mean operative time in the right nephrectomy group was significantly shorter than in the left nephrectomy group (169 +/- 25 and 186 +/- 29 min, respectively; P = 0.003). Graft function 1 month after transplantation and the incidence of delayed graft function were similar in both groups. There was one graft loss caused by thrombosis in the left nephrectomy group; other graft-related complications in the recipients were similar in both groups. CONCLUSIONS: This large single-center experience demonstrates that laparoscopic right donor nephrectomy performed without hand-assist devices is safe and yields kidneys with excellent function. The authors conclude that selection of the appropriate kidney for donation using this approach can be based on the same criteria that have traditionally governed open donor nephrectomy.

Adult↗

PubMed2004

Increased rejection in living unrelated versus living related kidney transplants does not affect short-term function and survival.

BACKGROUND: At our institution, increased kidney donation from unrelated donors accounts for a steady rise in live donor kidney transplantation rates. We compared outcomes of living related (LRT) versus living unrelated kidney transplants (LURT) and analyzed the effect of early rejection upon graft survival. METHODS: A retrospective analysis on 428 adult living donor kidney transplants was performed. Graft function and survival were compared between LRT and LURT and risk factors for 1-year rejection were defined by multivariate analysis. RESULTS: Between 1/1/97 and 12/31/01, 308 LRT and 120 LURT were performed at the University of California San Francisco. Donor age and number of mismatches were significantly higher in the LURT group. Patient and graft survival were similar in both groups. After a median follow-up of 26 months, graft survival was 94.8% (LRT) versus 93.3% (LURT). Five-year serum creatinine levels were comparable in both populations. One-year rejection was higher in the LURT group (30% vs. 18.5%; P<0.01). Rejection was influenced by the number of human leukocyte antigen mismatches. Other independent risk factors for early rejection were poor initial graft function, donor age greater than 55 years, and recipient body mass index greater than 30. Patients with poor initial graft function and early rejection had a statistically greater incidence of subtherapeutic tacrolimus trough levels on postoperative day 7. CONCLUSIONS: Despite a higher incidence of early rejection, LURT show similar function and survival compared with LRT. In high-risk patients receiving living unrelated renal transplants, consideration should be given to intensify initial immunosuppression to prevent early rejection episodes.

Adult↗

PubMed2004

Laparoscopic donor nephrectomy for pediatric recipients: outcomes analysis.

OBJECTIVES: To present our outcomes of laparoscopic donor nephrectomy for pediatric recipients. Laparoscopic nephrectomy has become the technique of choice for live donor nephrectomy. However, limited data are available regarding the role of this technique for pediatric recipients, who may pose special challenges and considerations, and whose parents need additional information. METHODS: Since November 1999, we have performed laparoscopic nephrectomy in more than 300 consecutive patients for live donor transplantation. Of these, 20 cases were identified that involved a recipient younger than 18 years of age. The preoperative, intraoperative, and postoperative data were reviewed to analyze the outcomes of these specific cases. The data were compared with a similar group of pediatric recipients receiving kidneys procured using the traditional open technique. RESULTS: The mean donor and recipient age was 40 years (range 26 to 52) and 13 years (range 1.7 to 18), respectively, and 19 cases (95%) involved the left kidney. The mean donor and recipient operative time was 3.3 hours (range 2.5 to 5.2) and 3.9 hours (range 2.4 to 5.1), respectively. The warm and anastomotic time averaged 4 minutes (range 2 to 8) and 30 minutes (range 16 to 41), respectively. Nineteen of the grafts functioned immediately, with a mean creatinine at 24 hours of 2.0 mg/dL (range 0.3 to 6.0). At last follow-up (mean 13.6 months), the mean creatinine was 1.1 mg/dL. Ureteral stricture requiring stent placement occurred in 2 patients (10%). No statistically significant differences were noted in operative parameters, complications, or renal function compared with a contemporary cohort of 26 pediatric patients receiving organs obtained by open donor nephrectomy. CONCLUSIONS: Our early experience with laparoscopic donor nephrectomy for pediatric recipients confirmed that the technique provides quality organs with excellent function. The method yields outcomes comparable to those after traditional open donor nephrectomy and does not require modifications for the recipient operation.

Adult↗

PubMed2004

Laparoscopic-assisted upper pole ureterocalicostomy using renal inversion and autotransplantation.

Despite various described methods of reconstruction after upper ureteral injury, many cases are complex and remain a surgical challenge. Careful preoperative evaluation and planning are crucial in the selection of the appropriate procedure, particularly in patients in whom preservation of the renal mass is imperative. We report a case of severe upper ureteral injury and subsequent fibrosis, with no usable renal pelvis and focal upper pole dilation, that was managed with renal inversion and upper pole ureterocalicostomy. The option of autotransplantation was provided by laparoscopic nephrectomy and ex vivo reconstruction, minimizing patient morbidity and maximizing a successful outcome. This case illustrates the expansion of laparoscopy from the mere extirpative to a role in complex reconstruction. To our knowledge, this reconstructive strategy has never been previously reported and may be applicable in a limited number of situations.

Anastomosis, Surgical↗

PubMed2004

Pure laparoscopic right donor nephrectomy: step-by-step approach.

BACKGROUND AND PURPOSE: Debate surrounds laparoscopic kidney procurement for right donor nephrectomy. We detail our pure laparoscopic technique of right kidney retrieval. TECHNIQUE: We use a four-port transperitoneal approach and extract the kidney through a low Pfannenstiel incision. Important elements include: (1) dividing the triangular ligament; (2) identifying the vena cava early; (3) minimizing ureteral dissection; (4) mobilizing the kidney within Gerota's fascia; (5) dissecting the renal artery behind the vena cava; (6) cutting the extraction incision to the peritoneum; (7) applying a Hem-o-Lok and single metal clip on the artery; (8) placing the Endo-TA stapler on the renal vein adjacent to the vena cava; (9) cutting the vessels without clips/staples on the kidney side; and (10) retrieving the kidney manually. RESULTS AND CONCLUSIONS: This is a reliable method of right pure laparoscopic donor nephrectomy that maximizes donor benefit and cost-effectiveness. Right laparoscopic nephrectomy is likely easier with this technique and should not be avoided if it is the preferred kidney for transplantation.

Humans↗

PubMed2004

Influence of donor pretreatment with N-acetylcysteine on ischemia/reperfusion injury in rat kidney grafts.

PURPOSE: N-acetylcysteine (NAC) has been shown to ameliorate ischemic acute renal failure. We determined the effect of donor pretreatment with NAC on ischemia reperfusion (I/R) injury in rat kidney grafts. MATERIALS AND METHODS: Lewis rats were divided into 3 groups (8 per group) and treated with saline, mannitol (1 gm/kg) or NAC (1 gm/kg intravenously) prior to donor nephrectomy. Cold stored kidneys (24 hours in UW solution) were transplanted into bilaterally nephrectomized recipients. Blood and graft tissue samples were taken 24 hours after transplantation for assessment of metabolic changes, histological damage and renal function. Metabolites associated with renal I/R injury were quantified in blood and renal tissue by magnetic resonance spectroscopy. RESULTS: The degree of histological damage was similar between the treatment groups. Of the counted tubules 60%were mildly damaged, whereas 40% showed moderate damage. Measurement of the metabolites allantoin and trimethylamine-N-oxide (TMAO) indicated a beneficial effect of NAC treatment. In graft tissue and recipient blood allantoin, a uric acid metabolite, was significantly lower in the NAC group vs the mannitol and saline groups (p <0.05). In recipient blood TMAO, an established marker of renal medullary injury, was significantly decreased in the NAC group vs mannitol and saline (p <0.05). Serum creatinine levels were not different between treatment groups. CONCLUSIONS: Donor pretreatment with NAC preserves renal metabolism and may improve outcomes of I/R injured kidney transplants. Allantoin and TMAO are sensitive metabolic markers of renal I/R injury that can be detected before the onset of functional and morphological changes.

Acetylcysteine↗

PubMed2004

Technique, indications and outcomes of pure laparoscopic right donor nephrectomy.

PURPOSE: Laparoscopic nephrectomy for living renal transplantation has emerged as the gold standard. Nevertheless, experience with this technique for procuring right kidneys is limited. We report our single institution results of pure laparoscopic right donor nephrectomy. MATERIALS AND METHODS: Laparoscopic donor nephrectomy was initiated at the our institution in November 1999. Patient selection was initially limited to the left kidney but right surgery was started 2 years later after 97 operations had been performed. We prospectively acquired data on the donor and recipient, and specifically analyzed outcomes of the right kidneys. RESULTS: In a 40-month period 300 laparoscopic donor operations were performed. Overall 44 procedures (15%) were on the right side with the fraction greater (22%) after removing exclusion of the right kidney from laparoscopic selection criteria. In this cohort mean operative time was 170 minutes, significantly less than the 190 minutes for 50 contemporaneous left kidneys (p = 0.001). No case of right donor nephrectomy required open conversion and vessels were of adequate length. Donor and recipient complications were similar in the 2 groups without technical graft loss in the entire series. CONCLUSIONS: Our method of laparoscopic right donor nephrectomy yields excellent graft quality with adequate vascular length and without the need for elaborate modifications or hand assistance. Moreover, the right operation is technically easier and it achieved comparable donor morbidity and recipient renal function. With sufficient experience the right kidney should be procured laparoscopically when indicated.

Adolescent↗

PubMed2004

Laparoscopic nephrectomy, ex vivo excision and autotransplantation for complex renal tumors.

PURPOSE: In many patients partial nephrectomy is the preferred alternative to radical nephrectomy for upper urinary tract cancers. We describe the use of laparoscopic nephrectomy, ex vivo excision and reconstruction, and autotransplantation to expand the realm of minimally invasive, nephron sparing surgery to the most complex renal tumors. MATERIALS AND METHODS: In our cohort undergoing renal surgery 2 patients had a solitary kidney with renal tumors not considered amenable to in situ partial nephrectomy. After transperitoneal laparoscopic nephrectomy ex vivo tumor excision and renorrhaphy were performed. The kidney was transplanted to the ipsilateral iliac vessels through the Gibson extraction incision. RESULTS: Indications for surgery were high grade urothelial carcinoma within a caliceal diverticulum and a central 5 cm renal cell carcinoma. Mean nephrectomy, cold ischemic and transplantation times were 4.5, 2 and 3.7 hours, respectively. No intraoperative or postoperative complications were noted. Hospitalization was 12 and 6 days, respectively. At 20 and 12 months of followup each patient remained off dialysis without evidence of recurrence. CONCLUSIONS: Despite experience with conventional nephron sparing surgery some cases may be more appropriate for ex vivo excision and reconstruction. In these situations the minimally invasive approach provides a kidney suitable for renal autotransplantation, while simultaneously decreasing patient morbidity. This novel approach to complex renal tumors is feasible when one applies principles of laparoscopic donor nephrectomy and possesses experience with renal transplantation.

Aged↗

PubMed2004

Early graft function after living donor kidney transplantation predicts rejection but not outcomes.

Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.

Diabetes Mellitus↗

PubMed2003

Sirolimus delays recovery of rat kidney transplants after ischemia-reperfusion injury.

BACKGROUND: Sirolimus (SRL) seems to impair renal recovery from ischemic injury in animal models and delayed graft function after clinical renal transplantation. This study determined the impact of SRL on renal recovery after ischemia-reperfusion injury in a rat kidney transplant model. METHODS: Syngeneic kidneys were preserved in University of Wisconsin solution before transplantation into bilaterally nephrectomized rats. Recipients received vehicle or SRL targeting for whole-blood trough levels of 10 to 20 ng/mL as measured by high-performance liquid chromatography. Renal function was assessed by animal survival or daily serum creatinine. Tissue samples were collected for histologic examination. RESULTS: Median SRL whole-blood concentrations were 16.6 +/- 1.6 ng/mL on postoperative day (POD) 1 and 12.0 +/- 0.9 ng/mL on POD 3. Transplantation of kidneys after 39 hr of cold storage resulted in 30% survival in the SRL-treated group compared with 100% survival in the control group (P=0.002). Transplantation of kidneys after 24 hr of cold storage resulted in no survival differences, but there were significant differences in renal function. Daily serum creatinine (PODs 1-4) was higher in the SRL-treated group compared with the control group (P<0.05 at all time points). Grafts from SRL-treated animals showed more severe tubular necrosis compared with control animals. CONCLUSIONS: When given at therapeutic immunosuppressive doses, SRL compromises renal function after ischemia-reperfusion injury in a rat kidney transplant model. The antiproliferative effect of SRL may translate into impairment of tubular repair and regeneration necessary for recovery after such injury.

Adenosine↗