Kidney International

The ISN presents a selection of images, articles and abstracts from Kidney International – Volume 13, Issue 3, July 2015 – from our editorial office in Japan.

As the worldwide prevalence of end-stage renal disease increases it is important to evaluate the rate of living kidney donation in various countries; however there is no comprehensive global assessment of these rates. To measure this, we compiled data from representatives, renal registries, transplant networks, published reports in the literature, and national health ministries from 69 countries and made estimates from regional weighted averages for an additional 25 countries where data could not be obtained.

In 2006, about 27,000 related and unrelated legal living donor kidney transplants were performed worldwide, representing 39% of all kidney transplants. The number of living kidney donor transplants grew over the last decade, with 62% of countries reporting at least a 50% increase. The greatest numbers of living donor kidney transplants, on a yearly basis, were performed in the United States (6435), Brazil (1768), Iran (1615), Mexico (1459), and Japan (939). Saudi Arabia had the highest reported living kidney donor transplant rate at 32 procedures per million population (pmp), followed by Jordan (29), Iceland (26), Iran (23), and the United States (21). Our study shows that rates of living donor kidney transplant have steadily risen in most regions of the world, increasing its global significance as a treatment option for kidney failure.

The limitations of estimates of glomerular filtration rate (GFR) based only on serum creatinine measurements have spurred an interest in more sensitive markers of GFR. Beta-trace protein (BTP), a low-molecular-weight glycoprotein freely filtered through the glomerular basement membrane and with minimal non-renal elimination, may be such a marker. We have recently derived two GFR estimation equations based on BTP. To validate these equations, we measured BTP and the plasma clearance of 99mTc-DTPA in 92 adult kidney transplant recipients and 54 pediatric patients with impaired kidney function.

GFR was estimated using the serum creatinine–based Modification of Diet in Renal Disease (MDRD) Study equation for adults, the Schwartz and updated Schwartz equations in children, and 4 novel BTP-derived equations (our 2 equations and 2 proposed by Poge). In adults, our BTP-based equations had low median bias and high accuracy such that 89–90% of estimates were within 30% of measured GFR. In children, the median bias of our 2 equations was low and accuracy was high such that 78–83% of estimates were within 30% of measured GFR. These results were an improvement compared to the MDRD and Schwartz equations, both of which had high median bias and reduced accuracy. The updated Schwartz equation also performed well.

Despite the objections to transplant tourism raised by the transplant community, many patients continue travel to other countries to receive commercial transplants. To evaluate some long-term complications, we reviewed medical records of 215 Taiwanese patients (touring group) who received commercial cadaveric renal transplants in China and compared them with those of 321 transplant recipients receiving domestic cadaveric renal transplants (domestic group) over the same 20-year period.

Ten years after transplant, the graft and patient survival rates of the touring group were 55 and 81.5%, respectively, compared with 60 and 89.3%, respectively, of the domestic group. The difference between the two groups was not statistically significant. The 10-year cumulative cancer incidence of the touring group (21.5%) was significantly higher than that of the domestic group (6.8%). Univariate and multivariate stepwise regression analyses (excluding time on immunosuppression, an uncontrollable factor) indicated that transplant tourism was associated with significantly higher cancer incidence. Older age at transplantation was associated with a significantly increased cancer risk; however, the risk of de novo malignancy significantly decreased with longer graft survival. Thus, renal transplant tourism may be associated with a higher risk of post-transplant malignancy, especially in patients of older age at transplantation.

Participants in the International Summit on Transplant Tourism and Organ Trafficking convened by The Transplantation Society and International Society of Nephrology in Istanbul, Turkey, 30 April to 2 May 2008.*

*The Participants in the International Summit on Transplant Tourism and Organ Trafficking and the manner in which they were chosen and the meeting was organized were as given in the Appendix.

Organ shortage for transplantation remains a worldwide serious problem for kidney patients with end-stage renal failure, and several countries have tried different models to address this issue. Iran has 20 years of experience with one such model that involves the active role of the government and charity foundations. Patients with a desperate demand for a kidney have given rise to a black market of brokers and other forms of organ commercialism only accessible to those with sufficient financial resources.

The current Iranian model has enabled most of the Iranian kidney transplant candidates, irrespective of socioeconomic class, to have access to kidney transplantation. The Iranian government has committed a large budget through funding hospital and staff at the Ministry of Health and Medical Education by supporting the brain death donation (BDD) program or redirecting part of the budget of living unrelated renal donation (LURD) to the BDD program. It has been shown that it did not prevent the development and progression of a BDD program. However, the LURD program is characterized by several controversial procedures (e.g., confrontation of donor and recipient at the end of the evaluation procedure along with some financial interactions) that should be ethically reviewed. Operational weaknesses such as the lack of a registration system and long-term follow-up of the donors are identified as the ‘Achilles heel of the model’.

Pneumocystis jirovecii is a unicellular organism that in individuals with impaired immunity may cause pneumonia that can progress from minor illness to severe inflammatory pneumonia (PCP) with respiratory failure and death. Despite antimicrobial prophylaxis, which has reduced the incidence of PCP, clusters of late infections have been reported among kidney transplant recipients worldwide. A nosocomial PCP cluster was first recognized in 2010 at a Sydney hospital, but PCP clusters have since occurred in almost half of the renal transplant units on the eastern Australian seaboard, refocussing attention on optimal prophylaxis regimens and the likelihood of patient-to-patient transmission. A consensus meeting was conducted to derive the lessons from this experience for responding to PCP outbreaks.

These included: (1) acting quickly—clusters of PCP in kidney transplant recipients with patient-to-patient transmission required transplant programs to act quickly to institute prophylactic and treatment measures; (2) instituting universal prophylaxis for all patients seen in the affected unit; (3) reducing patient-to-patient transmission via airborne droplets in the outpatient waiting areas; (4) examining the P. jirovecii genotypes. The meeting also considered recommendations for the duration of prophylaxis following de novo transplant and, for the individuals in whom long term prophylaxis is required, separating units with and without clusters of PCP.

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls.

Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.

The prognosis of human immunodeficiency virus (HIV) infection has improved in recent years with the introduction of antiretroviral treatment. While the frequency of AIDS-defining events has decreased as a cause of death, mortality from non-AIDS-related events including end-stage renal diseases has increased. The etiology of chronic kidney disease is multifactorial: immune-mediated glomerulonephritis, HIV-associated nephropathy, thrombotic microangiopathies, and so on. HIV infection is no longer a contraindication to transplantation and is becoming standard therapy in most developed countries.

The HIV criteria used to select patients for renal transplantation are similar in Europe and North America. Current criteria state that prior opportunistic infections are not a strict exclusion criterion, but patients must have a CD4+ count above 200 cells/mm3 and a HIV-1 RNA viral load suppressible with treatment. In recent years, more than 200 renal transplants have been performed in HIV-infected patients worldwide, and mid-term patient and graft survival rates have been similar to that of HIV-negative patients. The main issues in post-transplant period are pharmacokinetic interactions between antiretrovirals and immunosuppressants, a high rate of acute rejection, the management of hepatitis C virus coinfection, and the high cardiovascular risk after transplantation. More studies are needed to determine the most appropriate antiretroviral and immunosuppressive regimens and the long-term outcome of HIV infection and kidney graft.

Chronic opioid usage (COU) for analgesia is common among patients with end-stage renal disease. In order to test whether a prior history of COU negatively affects post-kidney transplant outcomes, we retrospectively examined clinical outcomes in adult kidney transplant patients.

Among 1064 adult kidney transplant patients, 452 (42.5%) reported the presence of various body pains and 108 (10.2%) reported a prior history of COU. While the overall death or kidney graft loss was not statistically different between patients with and without a history of COU, the cumulative mortality rate at 1, 3, and 5 years after transplantation, and during the entire study period, appeared significantly higher for patients with than without a history of COU (6.5, 18.5, and 20.4 vs. 3.2, 7.5, and 12.7%, respectively). Multivariate Cox regression analysis adjusted for potential confounding factors in entire cohorts and Cox regression analysis in 1:3 propensity–score matched cohorts suggest that a positive history of COU was significantly associated with nearly a 1.6- to 2-fold increase in the risk of death (hazard ratio 1.65, 95% confidence interval 1.04–2.60, and hazard ratio 1.92, 95% confidence interval 1.08–3.42, respectively). Thus, a history of chronic opioid usage prior to transplantation appears to be associated with increased mortality risk. Additional studies are warranted to confirm the observed association and to understand the mechanisms.