John Preston

Kidneys from patients with small renal tumours: a novel source of kidneys for transplantation.

To report the use of a novel donor source as a further option to increase the number of patients who might be able to receive a renal transplant.

Frequency and severity of acute rejection in live-versus cadaveric-donor renal transplants

Background. Live donors are an increasingly important source of kidneys for transplantation in Australia. The aim of this study was to compare the rate and severity of rejection between patients receiving kidney transplants from live versus cadaveric donors. Methods. A retrospective analysis was undertaken of all patients receiving live-donor (n=109) and cadaveric-donor (n=389) renal transplants at our institution between April 1, 1994, and March 31, 2000. Follow-up was completed on all patients until graft loss, death, or May 31, 2001. Results. The baseline characteristics of the live-donor and cadaveric groups were similar, except for recipient age (mean±SD, 36.3±15.6 vs. 44.5±14.4 years, respectively; P <0.001); donor age (46.1±11.3 vs. 36.1±16.4 years, P <0.001); pretransplant dialysis duration (1.36±2.1 vs. 3.4±4.4 years, P <0.001); and the proportions of patients receiving first allografts (95% vs. 88%, respectively; P <0.05), antibody induction (8% vs. 20%, P <0.01), and mycophenolate mofetil (MMF) (60% vs. 37%, P <0.001). Acute rejection was observed in 48 (44%) live-donor and 108 (28%) cadaveric transplants (P =0.001). Cadaveric donor type was independently predictive of less acute rejection both on logistic regression (adjusted odds ratio [AOR], 0.47; 95% confidence interval [CI], 0.30–0.73; P =0.001) and multivariate Cox proportional hazards model analysis (hazard ratio, 0.49; 95% CI, 0.34–0.69; P <0.001). Patients receiving cadaveric-donor transplants were also significantly less likely to receive antibody therapy for rejection (univariate, 18% vs. 9%; P =0.006; multivariate AOR, 0.45; 95% CI, −0.25–0.82; P <0.01), independent of recipient age, gender, race, transplant number, human leukocyte antigen mismatch, sensitization, induction therapy, delayed graft function, MMF use, tacrolimus or cyclosporine A use, sirolimus-everolimus use, year of transplant, donor age, or dialysis duration. However, donor type did not independently influence graft survival, immunologic graft survival, or patient survival. Conclusions. Live-donor kidney transplant recipients had a higher rate and severity of rejection and a shorter rejection-free period than cadaveric renal transplant recipients. Further consideration of the reasons for this difference and the use of alternative immunosuppressive strategies for live-donor transplants are recommended.

Association of micropapillary urothelial carcinoma of the bladder and BK viruria in kidney transplant recipients.

BK virus (BKV) is an ubiquitous human polyomavirus that establishes latency in urothelium. BKV is known to re‐activate in immunosuppressed individuals, and is an increasingly important cause of nephropathy and graft loss in kidney transplant recipients. Animal studies have demonstrated BKV has a potential role as a tumor virus. However, its role in precipitating or facilitating oncogenesis in humans is still debated.

Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients

Background. Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has been shown to be superior to azathioprine in preventing early acute rejection in the general renal transplant population. However, it is uncertain whether these benefits also apply to older renal transplant recipients, who are known to be more susceptible to infectious complications and have considerably lower rates of rejection and immunological graft loss. Methods. A retrospective analysis was undertaken of all elderly (≥55 years old) renal transplant recipients who underwent renal transplantation at the Princess Alexandra Hospital (1994–2000) and received either MMF (n=60) or azathioprine (n=55) in combination with prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis using a multivariate Cox proportional hazards model. Results. The azathioprine- and MMF-treated groups were well matched at baseline with respect to demographic characteristics, end-stage renal failure causes and transplant characteristics. Compared with the MMF cohort, azathioprine-treated patients experienced a shorter time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53–13.1, P <0.01]. However, azathioprine-treated patients were also less likely to develop opportunistic infections (HR 0.11, 95% CI 0.03–0.41, P =0.001). No differences were observed between the two groups with respect to hospitalization rates, intensive care admissions, hematological complications, or posttransplant malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF-treated patients were 100 and 87%, respectively (P <0.001). The principal cause of death in the MMF cohort was infection. Using a multivariate Cox regression analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001–0.08, P =0.001) was calculated in favor of azathioprine. Overall graft survival also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06–1.33, P =0.11), Conclusions. In elderly renal transplant recipients, the combination of MMF, cyclosporin, and prednisolone appears to result in a worse outcome compared with the less potent combination of azathioprine, cyclosporin, and prednisolone. Future prospective studies need to specifically evaluate the risk/benefit ratios of newer, more potent immunosuppressive protocols, such as MMF-based regimens, in this important and sizeable patient subgroup.

Estimated donor glomerular filtration rate is the most important donor characteristic predicting graft function in recipients of kidneys from live donors

We hypothesized that predictors of outcome in live donor transplants were likely to differ significantly from deceased donor transplants, in which cold ischaemia time, cause of donor death and other donor factors are the most important predictors. The primary aim was to explore the independent predictors of graft function in recipients of live donor kidneys (LDK). Our secondary aim was to determine which donor characteristics are the most useful predictors. A retrospective analysis was undertaken of all patients receiving live donor (n = 206) renal transplants at our institution between 31 May 1994 and 15 October 2002. Twelve patients were excluded from the analysis. Follow‐up was completed on all patients until graft loss, death or 22 November 2003. We explored predictors of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear regression. In the 194 patients studied, the mean recipient 6‐month Nankivell GFR was 59 ± 15 ml/min/1.73 m2. Independent predictors of recipient GFR in at 6 months were donor Cockcroft‐Gault GFR (CrCl; β 0.16; CI 0.13 to 0.29; P < 0.0001), steroid resistant rejection (β–6.07; CI −12.05 to −0.09; P = 0.006) and delayed graft function (DGF) (β–10.0; CI −19.52 to −0.49; P = 0.039). Renal function in an LDK transplant recipients is predicted by donor GFR, episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft‐Gault GFR is the most important characteristic for predicting the recipient renal function.

Laparoscopic vs open living donor nephrectomy: a contemporary series from one centre.

Laparoscopic versus open living‐donor nephrectomy has become a frequent debate amongst urologists involved in this area of expertise, with the laparoscopic argument being most popular at present. Authors from Australia describe a prospective comparative trial using both techniques, finding that the laparoscopic approach could be introduced without compromising results.

Change in live donor characteristics over the last 25 years: A single centre experience

Aim:  While deceased donor kidney transplantation rates have remained stagnant, live donor kidney transplantation (LDKT) rates have increased significantly over the last decade, and are now a major component of renal transplantation programmes worldwide. Additionally, there has been an increased utilization of more marginal donors, including donors who are obese, older and subjects with well‐controlled hypertension.

Clear cell renal cell carcinoma: validation of World Health Organization/ International Society of Urological Pathology grading

In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma. This system is incorporated into the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading. This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC.

Use of mycophenolate mofetil in immunosuppressive protocols in elderly renal transplant recipients

We welcome Dr. Sureshkamur’s reported experience with azathioprineand mycophenolate mofetil (MMF)-based immunosuppression protocols in elderly renal transplant recipients at the Allegheny General Hospital. In contrast with the results of our study (1) and those of Meier-Kriesche et al. (2), azathioprine-treated patients at the Allegheny General Hospital demonstrated significantly worse graft and patient survival rates than MMF-treated patients. Infectious complications were not reported by Dr. Sureshkamur, but it is noteworthy that the 1-year graft survival rate for azathioprine-treated patients at the Allegheny General Hospital was particularly poor (1-year survival of 79% vs. 96% for our unit). This indicates the possibility of under-immunosuppression in this cohort, which is supported to some extent by the relatively low dose of azathioprine used (1.5 mg/kg/day). The generalizability of Dr. Sureshkamur’s data is therefore questionable. Dr. Sureshkamur’s report is also limited by the presentation of univariate outcome analyses, the possibility of cointervention bias, and the lack of information about important confounding variables (e.g., live renal donor transplants), which may have been more prevalent in the MMF era. In contrast, our study attempted to overcome these potential pitfalls by statistically adjusting outcome results for all known potentially confounding factors, including immunosuppressive drugs, age, gender, racial status, body mass index, donor status, initial graft function, total ischemic time, episodes of acute rejection, exposure to antilymphocyte antibody preparations, diabetes mellitus, smoking status, and previous ischemic heart disease. Dr. Sureshkamur’s contention (3) that the observed differences in outcomes between the two studies could be explained by our use of intravenous methylprednisolone for the treatment of acute rejection is unlikely, because this occurrence was less frequent in the MMF group in our study and was adjusted for in the multivariate Cox proportional hazards model analysis. Finally, we agree with Dr. Sureshkamur’s concluding remarks that although the overall benefits of MMF-based protocols seem to be significant, their risk and benefit ratios need further evaluation in elderly patients. Only a prospective controlled clinical trial comparing azathioprineand MMF-based immunosuppression protocols in elderly renal transplant recipients will be able to definitively resolve this important issue.

Life-threatening adenovirus infection in a kidney transplant recipient

Adenovirus causes 5–10% of all childhood febrile illnesses [1]. In the immunocompetent host, infection is usually associated with mild, self-limiting upper respiratory tract syndromes. Most individuals have serologic evidence of prior adenoviral infection by age 10 [1]. Following initial infection, adenovirus establishes lifelong latent infection in lympho-epithelial tissues [2]. In immunocompromised hosts, the spectrum of adenovirus infection can range from asymptomatic shedding to fatal disseminated disease [2]. It may represent primary infection, usually the case in paediatric transplant recipients, or reactivation of latent disease. Latent viruses may be of donor or recipient origin [2]. Adenovirus infection has been documented in solid organ transplantation, but is relatively rare and therefore a paucity of epidemiologic data exists. This case of adenovirus infection in a kidney transplant recipient is unusual for the severity of allograft dysfunction and the life-threatening nature of disease. It highlights the need for consideration of adenovirus as a cause of fever of unknown origin in the post-transplant setting. Potential therapeutic options are discussed, including use of cidofovir in a dialysis-dependent patient.