"Suboptimal" kidney donors: The experience with tacrolimus-based immunosuppression

Female, pediatric, and older donors have been associated with inferior graft survival after renal transplantation. We analyzed these three subgroups in 397 patients receiving tacrolimus-based immunosuppression. There were no differences in recipient age, incidence of retransplantation, or percentage of sensitized patients. Female donors, compared with male donors, were associated with comparable 1- and 3-year patient survival rates (96% and 93% vs. 95% and 92%, respectively) and comparable 1- and 3-year graft survival rates (90% and 80% vs. 88% and 81%, respectively). Renal function was also similar. Recipients of pediatric en bloc kidneys, when compared with recipients of other cadaveric kidneys, also had comparable 1- and 3-year patient survival rates (94% and 94% vs. 95% and 91%, respectively) and comparable 1- and 3-year graft survival rates (84% and 84% vs. 89% and 79%, respectively). Renal function was better in recipients of en bloc kidneys, with a mean serum creatinine level of 1.4±1.8 mg/dl vs. 2.0±1.5 mg/dl (P=0.01). In contrast to the first two subgroups, donors over 60 years of age, when compared with donors under 60 years of age, were associated with worse 1- and 3-year patient survival rates (88% and 80% vs. 96% and 94%, respectively; P<0.03) and worse 1- and 3-year graft survival rates (74% and 62% vs. 91% and 83%, respectively; P<0.0001). Renal function was worse in the older donor group, with a serum creatinine level of 2.7±1.2 mg/ml vs. 1.9±1.5 mg/dl (P=0.01). We conclude that, under tacrolimus-based immunosuppression, kidneys from female or very young pediatric donors are not associated with adverse outcomes, whereas kidneys from donors over 60 years of age are associated with inferior outcomes

Ethical Issues in the Use of Suboptimal Kidneys for Transplants: an Italian Point of View

The shortage of organs leads to the need for utilizing suboptimal kidneys for transplantation. The distinction between optimal, marginal, and suboptimal kidneys leads surgeons to face not only technical problems but also ethical and legal issues related to clinical advantages offered by the transplant of a nonstandard kidney and the acquisition of consent. Between 1999 and 2015, we performed 658 transplants, 49 (7.5%) using suboptimal kidneys. All patients were alive and with vital graft throughout follow-up. We did not encounter any major surgical complications. From a technical point of view, our experience and literature review confirm that transplant of suboptimal kidney leads to good clinical results but exposes patients to a increased risks of surgical complications. Therefore, these interventions must take place in hospitals fully prepared for this type of surgery and performed by experienced transplant surgeons with proper matching between organ and recipient. Considering the insufficient resources available, from an ethical and legal point of view, doctors play an essential role in optimizing the use of these kidneys by avoiding wastage of organs, ensuring that transplants are done in suitable patients, and that patients are fully informed and aware of the risks and benefits associated with the specific suboptimal kidney being transplanted. We believe that, in highly specialized centers, the number of suboptimal kidney transplants should be increased, as their use has shown good clinical results and carries fewer ethical issues compared with marginal kidneys. Further, suboptimal kidneys may also be proposed for use in young patients with end-stage renal disease

Single-Center Denial Reasons for Potential Living Kidney Donors

Because of the benefits of preemptive living donor (LD) transplant, the desire for LD is rising. However, in the last decade, there has been no increase in LD in the U.S, possibility due to older donor candidate population leading to increased denial rates. We previously studied denial rates and cause for denial for donor candidates between 2009 and 2011. We herein present for comparison causes for denial for donor candidates between 8/2012 and 6/2015. During the interval, our acceptance criteria have not changed. Results: Between August 2012 and June 2015, we evaluated 644 potential living donors: 2012=88, 2013=222, 2014=220, 2015 (Jan-June) =114. Of these, 31% of candidates were denied: 26% for medical reasons, 5% for psychosocial reasons. Mean age of approved candidates = 41 (range: 18-75); average denied = 43 (range, 18-72). To compare, between 2009-2011, 36% candidates were denied (32% medical, 4% psychosocial). The mean age for approved candidates = 40, while denied candidates mean age = 47 (range, 18-64). Current candidates most common medical denials reasons were obesity and suboptimal kidney anatomy, although the distribution of reasons varies by age cohort. Historical group (2009-2011): most common medical denials were hypertension and poor kidney function. Psychosocial denial reasons included: mental illness, lack of support and substance abuse. Conclusion: Over an interval of 6.5 years, the rate of donor candidate denial at our center has not changed. Overall, there has been a change in major reasons for denial; importantly, reasons for denial vary by donor age

Fetal kidney volume and its association with growth and blood flow in fetal life: The Generation R Study

An adverse fetal environment may lead to smaller kidneys and subsequent hypertension with renal disease in adult life. The aim of our study was to examine whether maternal characteristics, fetal growth, fetal blood flow redistribution, or inadequate placental perfusion in different periods of fetal life affect kidney volume in late fetal life. We also determined if fetal kidney volume was linked to the amount of amniotic fluid. In a population-based prospective study from early fetal life, fetal growth characteristics and fetal blood flow parameters were assessed by ultrasound and Doppler examinations in 1215 women in mid- and late-pregnancy. Kidney volume was measured in late pregnancy. Maternal height and pre-pregnancy weight were associated with kidney volume. After adjustment for the same characteristics in late pregnancy, fetal growth and blood flow in mid-pregnancy were not associated with kidney volume in late pregnancy. In late pregnancy, however, all fetal growth parameters were positively linked with kidney volume. The largest effect on kidney volume was found for abdominal circumference. Signs of fetal blood flow redistribution and increased placental resistance were associated with decreased kidney volume in late pregnancy. Amniotic fluid volume was positively associated with kidney volume. Our study shows that maternal anthropometrics, fetal growth, fetal blood flow redistribution, and raised placental resistance all correlate with kidney volume

Physical activity in elderly kidney transplant patients with multiple renal arteries

Introduction: Kidney transplantation (KT) is the gold standard for treatment of patients with end- stage-renal disease. To expand the donor reserve, it is necessary to use marginal/suboptimal kidneys. Methods: We retrospectively evaluated the short/long-term outcome of 34 KT elderly patients who received allografts with vascular abnormalities (MRA group), in comparison with 34 KT patients who received a kidney with a single renal artery (SRA group) pair-matched by age, length of time on dialysis, comorbidity and donor age. Results: All participants completed the International Physical Activity Questionnaire at KT, and then 4, 8, and 12 weeks after transplantation. Our data indicate that kidney with vascular anatomical variants may be successfully transplanted, since the overall rate of surgical complications was 20.6% in the SRA group and 17.6% in the MRA group and that the 5-year survival rate after KT was 100% in both groups. Conclusions: The data also underline that individualized physical activity programs induced similar excellent results in both groups, improving physical capacities, arterial pressure, lipid metabolism, insulin sensitivity, quality of life and physical and mental status

Histological evaluation of nephroprotective effect of Solanum nigrum fruit extract against gentamicin induced nephrotoxicity in experimental rats

Background: Drug induced nephrotoxicity, one of the most common renal problem, is a challenge to deal with especially in patients with renal dysfunction. It is responsible for 20% cases of acute renal failure in the community. Modern medicines are costly and have minimal nephroprotection. Solanum nigrum fruit extract, a cheaper drug, have antioxidant property and may help in nephroprotection.Methods: Total 54 rats were randomised in 3 groups named G10, G20 and G30 according to 10, 20 and 30 days of treatment. In each groups, rats were randomly assigned to any of the three subgroups i.e., control C group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration], gentamicin treated (GT) group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days] and S. nigrum treated (SNT) group [received S. nigrum orally (200 mg/kg/day) for the test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days]. Rats were sacrificed 24 hours after the last dose of gentamicin injection (on 11th, 21st and 31st day). Excised kidneys were weighted and prepared for histological examination.Results: The mean weight of kidneys in GT group was significantly higher than the SNT group in all test durations suggestive of decrease in inflammation in SNT group. This was also reflected histologically as SNT group kidney showed less amount of tubular destruction as compared to GT group.Conclusions: S. nigrum extract provide nephroprotection against gentamicin induced nephrotoxicity

Pregnancy in Advanced Kidney Disease:Clinical Practice Considerations on a Challenging Combination

Background:Thanks to the advances in care, pregnancy is now attainable for the majority of young female CKD patients, although it is still a high-risk endeavor. Clinical decision-making in these cases is impacted by a myriad of factors, making (pre)pregnancy counseling a complex process. The complexities, further impacted by limited data and unknown risks regarding outcome, can cause discussions when deciding on the best care for a specific patient. Objectives:In this article, we provide an overview of the considerations and dilemmas we encounter in preconception counseling and offer our perspective on how to deal with them in daily clinical practice. Methods:The main topics we discuss in our counseling are (1) the high risk of pregnancy complications, (2) the risk of permanent CKD deterioration due to pregnancy and subsequent decreased life expectancy, (3) appropriate changes in renal medication, and (4) assisted reproduction, genetic testing, and prenatal or preimplantation genetic diagnostics. Results and Conclusions:In our clinic, we openly address moral dilemmas arising in clinical practice in pregnancy and CKD, both within the physician team and with the patient. We do this by ensuring an interpretive physician-patient interaction and shared decision-making, deliberating in a multidisciplinary setting and, if needed, with input from an expert committee

Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ± 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ± 13 months. Nine patients (the group I) had early postransplant conversion after 4 ± 3 months and 15 patients (the group II) late conversion after 46 ± 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ± 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ± 12.7 to 69 ± 15 mL/min), while the increase in proteinuria (from 265 ± 239 to 530.6 ± 416.7 mg/day) and lipidemia (cholesterol from 4.71 ± 0.98 to 5.61 ± 1.6 mmol/L and triglycerides from 2.04 ± 1.18 to 2.1 ± 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ± 232 to 1639 ± 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ± 28.09 to 47 ± 21 mL/min) and significantly improved proteinuria (from 1639 ± 1641 to 529 ± 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ± 88 to 202 ± 91 mmol/L), decrease in GFR (from 56.10 ± 28.09 to 47 ± 21 mL/day) and increased proteinuria (from 528.9 ± 688 to 850 ± 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications

Nephroprotection of Withania somnifera root extract against gentamicin induced nephrotoxicity: a histological evaluation in experimental Wistar rats

Background: Gentamicin, an aminoglycoside group of drug, used against aerobic gram negative bacteria, is known for nephrotoxicity. Herbal products have a special place in the world of pharmaceuticals with their safety, efficacy and cost effectiveness. Withania somnifera (Ashwagandha) roots had known since long for its antioxidant status and free radical scavenging property. So W. somnifera can be used as nephroprotective agent because of free radical scavenging property.Methods: Total 54 rats were randomised in 3 groups named G10, G20 and G30 according to 10, 20 and 30 days of treatment. In each groups, rats were randomly assigned to any of the three subgroups i.e., control C group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration], gentamicin treated GT group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days] and W. somnifera treated WST group [received W. somnifera orally (500 mg/kg/day) for the test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days]. Rats were sacrificed 24 hours after the last dose of gentamicin injection. Excised kidneys were weighted and prepared for histological examination.Results: The mean weight of kidneys in GT group was significantly higher than the WST group in all test durations indicating the antioxidant and free radical scavenging property. This was also reflected histologically as WST group kidney showed less amount inflammation as compared to GT group.Conclusions: W. somnifera root extract provide nephroprotection against gentamicin induced nephrotoxicity.

Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation

With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor