Patrick P. Luke

Use of a Pelvic Kidney for Living Transplantation: Case Report and Review of the Literature

Pelvic kidneys have anomalous vascular supplies and collecting systems. Therefore, careful radiologic and functional evaluation of these kidneys must be performed prior to procurement for transplantation. We report the successful use of a pelvic kidney for living‐related transplantation.

The prognostic value of time needed on dialysis in patients with delayed graft function

INTRODUCTIONnWe hypothesize that in patients with delayed graft function (DGF), the need for a longer time needed on dialysis (TND) post-kidney transplant is associated with poorer long-term function and an increase in complications.nnnMETHODSnThis was a retrospective chart review involving collaboration between Western University (WU) Renal Transplant Program of London, Ontario and the Saskatchewan renal transplant program (SRTP). A total of 774 patients (567 WU and 207 SRTP) received kidney transplants between 2004 and 2011, of which 83 patients with deceased donor transplants (59 WU and 24 SRTP) developed DGF, defined as the need for dialysis in the first week posttransplant.nnnRESULTSnPatients with DGF were divided into three groups depending on TND [group 1: <7 days (n = 52), group 2: 7-14 days (n = 13) and group 3 (n = 18): >14 days]. The creatinine clearance (CrCl) at 30 days (42.5, 33.8, 20.0 cc/min; P < 0.001) and 1 year (56.7, 49.2, 37.3 cc/min, P = 0.031) were significantly different between the three groups. Multivariate regression analysis identified length of TND posttransplant (β = -0.5, P < 0.001) and donation after cardiac death (DCD) donor (β = 19.5, P < 0.001) as the most significant predictors of CrCl at 1 year in these patients with DGF. DCD kidneys with DGF had a higher CrCl at 1 year and fewer readmissions in the first year compared with non-DCD kidneys with DGF.nnnDISCUSSIONnOur study suggests that increased TND is associated with worse CrCl at 1 year. The data also support the hypothesis of a different mechanism for DGF in DCD and non-DCD kidneys.

Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

Background Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion. Methods Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD). Results Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers. Conclusions Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.

Five-year experience with donation after cardiac death kidney transplantation in a Canadian transplant program: Factors affecting outcomes.

BACKGROUNDn: Donation after cardiac death (DCD) has led to an increase of up to 40% in the number of kidney transplants in some programs. Unfortunately, the increase in warm ischemic time results in higher rates of delayed graft function (DGF). The purpose of our study was to examine our initial 5-year experience with DCD kidney transplantation and to determine the factors involved in early postoperative function and function at 1 year.nnnMETHODSn: This retrospective study included a review of the recipient and donor charts of 63 DCD kidneys retrieved and transplanted by the London Multi-Organ Transplant Program between July 2006 and October 2011. Comparisons were carried out between our early (n=31, July 2006 to January 2009) and our recent experience (n=32, March 2009 to October 2011). DGF and creatinine clearance at 3, 7 and 365 days were examined with regression analyses.nnnRESULTSn: DGF was seen in 65% of transplanted kidneys. Mean creatinine clearance (CrCl) at 1 year was 66.7 mL/min. Low pre-transplant recipient daily urine output was the most statistically significant predictor of DGF in multivariate analysis (p < 0.001). In comparisons between our early and more recent results, improvements were noted in time from asystole to flush (16.0 vs. 12.0 minutes, p = 0.003), while cold ischemic time increased (464 vs. 725 minutes, p = 0.006). Experience contributed to a significant reduction in hospital length of stay (16 vs. 13 days, p = 0.035) and improved early renal function (CrCl at 3 days 7.8 vs. 11.9 mL/min, p = 0.027). The use of machine cold perfusion and higher recipient preoperative daily urine output predicted improved early renal function, while increasing donor age predicted poorer function at 1 year.nnnDISCUSSIONn: Despite early DGF, our results justify the continued transplantation of kidneys from DCD donors.

Donation after Circulatory Death Renal Allografts—Does Donor Age Greater than 50 Years Affect Recipient Outcomes?

PURPOSEnDonation after circulatory death renal allografts are associated with excellent outcomes. We performed a retrospective chart review to investigate the impact of donor age on postoperative and intermediate term outcomes.nnnMATERIALS AND METHODSnWe compared recipient outcomes of donation after circulatory death allografts from donors older vs younger than 50 years. A total of 118 single donations after circulatory death renal transplants were performed at our institution between July 2006 and September 2013. Outcome variables (creatinine clearance, readmission rate, length of hospital stay, delayed graft function, graft loss and rejection) were compared between the 2 age categories using the Student t-test and the Pearson chi-square test. Independent prognosticators of creatinine clearance at 12 months were assessed with multivariate linear regression modeling.nnnRESULTSnMean ± SD recipient age was 53.8 ± 14.7 years and 45.8% of donation after circulatory death donors were older than 50 years. Median followup was 21 months (range 1 to 87). Recipients of kidney transplants from donation after circulatory death donors older than 50 years demonstrated lower creatinine clearance at 1 month (mean 50.3 ± 25.3 vs 72.7 ± 31.7 ml per minute, p <0.001), 3 months (62.5 ± 22.9 vs 87.9 ± 36.4, p <0.001) and 1 year (66.2 ± 26.8 vs 87.8 ± 38.7, p = 0.013). However, the 2 groups did not differ with regard to delayed graft function, graft loss, hospital readmissions or length of hospital stay. Multivariate linear regression demonstrated that donor age, recipient age, recipient gender and cold ischemia time were independent predictors of creatinine clearance at 12 months.nnnCONCLUSIONSnRecipients of allografts from donors older than 50 years showed inferior renal function at 1 year but the 2 groups had similar graft survival and short-term outcomes. Longer followup is required to determine long-term allograft survival.

Intrahepatic extension of renal cell carcinoma tumor thrombus causing Budd-Chiari syndrome

A 66-year-old woman presented with a 10-day history of progressive shortness of breath, epigastric pain and 10-pound weight loss. Physical examination revealed a palpable mass involving the right upper quadrant. Computed tomography (CT) of the abdomen demonstrated a 6.8 × 8.8 × 7.5 cm right renal mass with tumour thrombus extending into the inferior vena cava and right atrium (Fig 1). In addition, the tumour extended retrograde into the right hepatic vein, associated with abnormal attenuation in the right lobe of the liver on the CT scan of the abdomen (Fig 2). This obstruction caused Budd-Chiari syndrome, associated with abnormal liver function tests and ascites. Alanine transferase, aspartate trasnferrase, alkaline phosphatase and gamma-glutamyl transpeptidase levels were 946, 1047, 396 and 203 U/L, respectively. The bilirubin level was 76 umol/L and the international normalized ratio was 1.5. n n n nFig. 1. n nA: Coronal computed tomography image of thorax/abdomen/pelvis with intravenous contrast demonstrating a large tumour thrombus extending into the right hepatic vein (double arrows) and just below the right atrium (single arrow). B: Sagittal view showing ... n n n n n nFig. 2. n nA: Axial computed tomography image of tumour thrombus extending into the right hepatic vein. Arterial phase scan demonstrates enhancement of the tumour in the inferior vena cava and of the tumour extension into the right hepatic vein (red arrow). B: Portal ... n n n nThe patient underwent right radical nephrectomy, cardiopulmonary bypass and caval thrombectomy with right hepatic venotomy. Notably, the thrombus slid out of the hepatic vein without evidence of hepatic attachment or infiltration (Fig. 3). n n n nFig. 3. n nTumour thrombus with extension into the right hepatic vein (blue arrow) and associated bland thrombus (red arrow). The thrombus slid out of the vein without evidence of hepatic attachment or infiltration. n n n nFinal pathology revealed Fuhrman 3 clear cell renal cell carcinoma with negative margins (T3cN0M0). She was re-imaged with thoracic and abdominal CT scanning and is free of disease 4 months postoperatively. Liver function tests have also normalized.

Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation

Abstract:u2002 Bioavailability and exposure of cyclosporine microemulsion and tacrolimus in renal transplantation are governed by many complex factors. Failure to achieve therapeutic two‐h post‐dose (C2) levels despite adequate doses of cyclosporine (“low absorbers”) may merit conversion to tacrolimus. We compared tacrolimus dose requirements in “low absorbers” (nu2003=u200315) with a random control group of de novo tacrolimus patients (nu2003=u200314). Low absorbers failed to reach target C2 despite increasing dose from 10.1 to 16.2u2003mg/kg/d. At conversion the mean C2 was 969u2003ng/mL (95% CI: 684–1255; target 1700u2003ng/mL). Low absorbers tended to be younger, heavier, and diabetic. Despite a similar initial tacrolimus dose (0.17–0.18u2003mg/kg/d), low absorbers required a much higher daily dose to achieve target; 0.25 vs. 0.16u2003mg/kg/d (pu2003=u20030.016). Furthermore, daily maintenance tacrolimus remained much higher in low absorbers at three wk (0.22 vs. 0.13u2003mg/kg/d, pu2003=u20030.012). Although not statistically significant, this group experienced an acute rejection rate of 33%, compared with 21% in the control group. Patients treated with cyclosporine as initial immunosuppression who fail to reach target C2 levels in a timely fashion are at risk for impaired bioavailability of tacrolimus. Based on our data, a starting dose of 0.25u2003mg/kg/d in divided doses may be warranted for low absorbers converting to tacrolimus; however, we encourage larger studies with formal pharmacokinetic analysis in this population.

Organ trafficking in Canada: Is it relevant to the urologist?

Organ transplant commercialism has been condemned by the World Health Organization for decades. In 2008, the Istanbul Declaration proclaimed that the poor who sell their organs are being exploited, while unregulated and illegal transplantation place physical harm to both organ donor and recipient. n nIn addition to the ethical issues that underlie the practice of transplant tourism, there is mounting evidence that transplant outcomes are poor. The authors have unequivocally shown that recipient mortality and morbidity rates are unacceptably high, likely as a result of cost-cutting and limited expertise in the practice of commercial transplantation.1 The fact that a sister renal transplant group in Ontario has published similar data indicate that this phenomenon is highly relevant to Canadian transplant centres.2 Accordingly, the Canadian Society of Transplantation has provided a policy statement to summarize the Canadian Healthcare Providers’ fiduciary and legal obligations to patients who participate in transplant tourism both before and after transplantation.3 All Canadian surgeons and physicians who provide care to renal transplant recipients should have a working knowledge of this policy statement.