Living donor kidney transplant in Italy: is the underutilization justified?

Living donor transplants (LDtx) represent an underutilized resource in Italy. It is, however, a therapeutic option that deserves greater consideration not only due to the increasing gap between the number of uremic patients on waiting lists (6956) and the number (1464) of cadaveric transplants (CADtx), as evidenced in 2002, but also due to the advantages of LDtx over CADtx. The superiority of LDtx include better graft survival, independent of the donor/recipient relationship, less need for dialytic treatment with preemptive transplants and reduced immunogenicity of the graft due to the brain death-related "cytokine storm." Moreover, some emerging procedures namely laparoscopic nephrectomy instead of open surgery and spiral CT instead of renal angiography namely, reduce the physical and socioeconomic burden of the donor. In the light of these considerations, LDtx should be reconsidered in the Italian scenario of kidney transplantation.     

Does donor brain death influence acute vascular rejection in the kidney transplant?

BACKGROUND: There is increasing experimental evidence to suggest that donor brain death enhances susceptibility to early inflammatory responses such as acute rejection in the kidney transplant. The aim of the present study was to establish whether the injury induced or aggravated by donor brain death could exert an effect on recipient immunologic tolerance by comparing data from patients receiving a kidney from non-heart-beating donors (NHBD) or from brain-dead donors (BDD). METHODS: We reviewed data corresponding to 372 renal transplants performed from January 1996 to May 2002. The data were stratified according to donor type as 197 (53%) brain-dead and 175 (47%) non-heart-beating donors, and the two groups were compared in terms of acute vascular rejection by Cox's regression analysis. RESULTS: The rate of vascular rejection was 28% in the BDD group and 21.7% in the NHBD (P=0.10). The following predictive variables for acute vascular rejection were established: brain death [RR 1.77 (95% CI 1.06-3.18)], presence of delayed graft function [RR 3.33 (1.99-5.55)], previous transplant [RR 2.35 (1.34-4.13)], recipient age under 60 years [RR 1.86 (0.99-2.28)], female recipient [RR 1.50 (0.99-2.28)], cerebrovascular disease as cause of donor death [RR 1.72 (1.02-2.91)], and triple therapy as immunosuppressive treatment. CONCLUSION: Donor brain death could be a risk factor for the development of vascular rejection in kidney recipients. This process could affect the quality of the graft and host alloresponsiveness. Delayed graft function in transplants from dead brain donors could be a reflection of severe autonomic storm, leading to a higher incidence of vascular rejection in these patients.     

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor–recipient combination

The impact of donor quality on post–kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post‐KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5‐year post‐KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5‐year waitlist survival was 47.6%, and 5‐year post‐KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool ( www.transplantmodels.com/kdpi-epts ) can support individualized decision‐making on kidney offers in clinical practice.     

Can a living kidney donor become a kidney recipient?

The living kidney donor represents a good resource for kidney transplantation. These grafts display better function and long-term graft survival at 5 and 10 years of follow-up. Furthermore, living donors prefer the possibility to increase kidney donation for a large waiting list of patients with end-stage renal disease (ESRD). However, kidney donation is a major surgical procedure associated with benefits and risks. The risks of donation have been studied in large series of living donors to focus on morbidity and mortality rates associated with the surgical procedure. New surgical laparoscopic techniques promote living kidney donation. While the benefits to the recipient are obvious, those for the donor are subjective and not quantifiable. However, donors describe donation as a great experience in life. The risk of kidney donation may be divided into the perioperative and the long-term risks. The evaluate the long-term risks for kidney donors requires a long follow-up. The main source of kidney donors in our transplant center has been living-related and -unrelated donors, with a minor percentage of cadaveric donors. In this report we present four kidney donors who developed ESRD thereafter, three becoming kidney recipients.     

Preoperative evaluation of living related kidney donor: which kidney to donate?

OBJECTIVES: As the number of cadaveric donor is far beyond the demand of the waiting list, living related kidney transplantation is important for the worldwide organ shortage. Besides, living related transplantation has advantages compared with cadaveric transplantation in terms of graft function and survival. However, the remaining kidney function of the living donor needs to be evaluated. METHODS: We collected 28 paired living kidney donations from March 2003 to March 2005. All patients underwent laparoscopic donor nephrectomy. The preoperative kidney evaluation included renal echography, renal nuclear scan, computed tomography angiography (CTA), and creatinine clearance (CCr). The renal function of the donor kidney was expressed as (donor kidney/both kidneys)%. The percentage renal function from renal echography, renal nuclear scan, and CTA were correlated with CCr. RESULTS: The mean percentage of donor kidney function according to renal echo, nuclear scan, and CTA were 49.77%, 51.83%, and 50.70%, respectively. The correlation coefficients for renal echography, nuclear scan, and CTA to CCr were -0.316, -0.201, and 0.123, respectively. The correlation coefficients for renal echography, nuclear scan, and CTA to postoperative serum creatinine of donor were 0.426, 0.036, and -0.119, respectively. CONCLUSION: From the viewpoint of donor postoperative residual renal function, preoperative renal sonography offered a better predictive value than nuclear scan or CTA.     

Does pre‐emptive kidney transplantation with a deceased donor improve outcomes? Results from a French transplant network

Large analyses have demonstrated that pre‐emptive kidney transplantation (PKT) leads to significant improvements in patient and graft survival when compared with transplantation performed after a period of dialysis. We analysed 1585 patients who received a first renal transplantation from a deceased donor between 2000 and 2004 in four French transplantation centres. The objective was to compare the characteristics of the deceased donor transplantations with or without previous dialysis and to evaluate the impact of PKT and length of dialysis on patient and graft outcomes. Mean age of recipients was 48.1 ± 13.4 years, 62% were men, and 118 (7.4%) of them received a pre‐emptive transplantation. For the nonpre‐emptive patients, mean time on pretransplant dialysis was 3.4 ± 3.2 years. Pretransplant factors independently related to pre‐emptive transplantation were year of transplantation, centre and recipients characteristics: gender, diabetes history, blood group and donor age. Patients with pretransplant dialysis were three times more likely to have delayed graft function than pre‐emptive transplant patients, and were 10 times more likely to receive post‐transplant dialysis. Five‐year patient survival was 92.9%. Five‐year graft survival was 89.0%. Neither pre‐emptive transplantation nor time on dialysis was significantly associated with patient and/or graft survival.     

Bilirubin,a new therapeutic for kidney transplant?

In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival rates. However, over 20% of kidney transplants result in rejection within five years. Rejection is primarily due to a hypersensitive immune system and ischemia/reperfusion injury. Bilirubin has been shown to be a potent antioxidant that is capable of potentially reversing or preventing damage from reactive oxygen species generated from ischemia and reperfusion. Additionally, bilirubin has several immunomodulatory effects that can dampen the immune system to promote organ acceptance. Increased bilirubin has also been shown to have a positive impact on renal hemodynamics, which is critical post-transplantation. Lastly, bilirubin levels have been correlated with biomarkers of successful transplantation. In this review, we discuss a multitude of potentially beneficial effects that bilirubin has on kidney acceptance of transplantation based on numerous clinical trials and animal models. Exogenous bilirubin delivery or increasing endogenous levels pre- or post-transplantation may have therapeutic benefits.     

Living donor kidney transplantation: chance for the recipient--financial risk for the donor?

BACKGROUND: With living donation, in addition to the medical risk, the financial risk for the donor is essential, especially in case of complications that potentially can led to disability and loss of work. We report the experiences of those who have donated a kidney in our transplant center. METHODS: We contacted 80 donors who donated a kidney at least 6 months prior to evaluation: 72% answered 33 questions. [mean age: 54 +/- 10 (33-75) years; 69% living related, 31% unrelated]. RESULTS: Of the 80 donors contacted, 91% (53) reported to have no financial expenses due to donation; 9% (5) had expenses, but only few of them clarified exact amount. One donor had to borrow money to cover the lack when he was unable to perform his job. Another claimed the disparity between normal salary and payment from insurance company as a financial expense. Evaluation procedure prior to donation was organized variously: some donors were on holiday while evaluated, some officially were ill, others had to take off some days without payment. None of the donors lost his or her job due to donation. CONCLUSION: The financial risk of living donation is theoretically well covered by different insurances. However, some of the donors had to cover some expenses by themselves. Fortunately, so far in our center no major complications occurred and all donors went home in good health after donation. If costs are covered when a healthy donor loses his or her ability to work due to donation remains unclear since no donor has experienced this problem.     

Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients?

Abstract Non‐melanoma skin cancer is frequent in organ transplant recipients. The risk of post‐transplant cutaneous squamous cell carcinoma in Norwegian heart transplant recipients (n = 148) and kidney transplant recipients (n = 1020) on triple immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone, transplanted between 1983 and 1992, were studied. After adjustment for age at transplantation in multivariable Cox models, heart transplant recipients had a significantly 2.8‐times higher risk of developing squamous cell carcinoma relative to kidney transplant recipients. The risk relative to the general population (standardized incidence ratio) was higher in heart transplant recipients than in kidney transplant recipients. The results indicate that heart transplant recipients are more likely to be diagnosed with skin cancer than kidney transplant recipients, probably due to the higher doses of cyclosporine and azathioprine after heart transplantation used at our center in the study period.     

Northern Australian kidney transplant unit: A viable option?

AIMS: Kidney transplant units in Australia are confined to large hospitals in major metropolitan areas, yet this may limit access and diminish outcomes in people who do not live in these large centres. The authors examined the viability of a kidney transplant unit located in northern Australia (NA), with particular emphasis on recipient outcomes and the number of donors. METHODS: 'Northern Australia' was arbitrarily defined as 'north of the tropic of Capricorn' for Queensland and Western Australia and included the entire Northern Territory. Data on donors and transplant recipients were provided by ANZDATA and ANZOD registries, identified by postcode. RESULTS: Between 1998 and 2004 in NA there were 163 deceased donor kidneys and 97.5% of available organs were transplanted. There were no Aboriginal/Torres Strait Islander (ATSI) donors from NA. Recipients from NA in this time included 55 patients receiving living grafts and 156 receiving deceased donor grafts, of whom 36% were ATSI, making up half of the total ATSI transplanted in Australia during this time period. Compared with the rest of Australia, NA recipients were older, waited longer on dialysis, had longer ischaemic times and a greater number of human leucocyte antigen mismatches, and were more likely to be diabetic and obese. Despite the longer cold ischaemic time in NA recipients, no difference in immediate graft function was seen. ATSI recipients in NA, when compared with their southern Australian counterparts, had poorer patient survival (HR=3.19, 95% CI 1.44-7.08, P<0.001), but equivalent graft survival (HR=1.67, 95% CI 0.95-2.95, P=not significant) on multivariate analysis. Key factors that would influence feasibility of a Northern Australian transplant unit include adequate staffing, and support services in addition to currently available resources. CONCLUSION: Current donor numbers in NA are adequate for past recipients of kidney transplant, but may not cover future needs without a significant increase in donor rate. A transplant unit situated in northern Australian would require significant resources to ensure long-term viability and its effect on outcomes is uncertain.     

Prehabilitation for kidney transplant candidates: Is it time?

Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and healthcare utilization after kidney transplantation. Efforts to intervene with post‐transplant physical therapy have been met with limited success, in large part due to high study dropout. We reviewed the literature on chronic kidney disease and exercise to propose a clinical framework for physical therapy interventions to improve fitness, scheduled for before the transplant. This framework may lead to better patient retention and compliance, and thus demonstrate better efficacy in mitigating the effects of frailty and poor fitness after kidney transplantation.     

Does graft mass impact on pediatric kidney transplant outcomes?

Background

The aim of this study is to assess the evolution of renal size and function in pediatric transplant patients according to the graft mass/recipient size ratio.

Methods

Fifty pediatric renal transplant recipients were followed over 2 years. Grafts were weighed, and three different graft mass/m² ratios were determined: (1) low graft mass (58 g/m², range?31–57 g/m²), (2) median (142 g/m², range?59–141 g/m²) and high (267 g/m², range?143–353 g/m²). Patients underwent repeated ultrasound Doppler scans and repeated measurements of estimated glomerular filtration rate (eGFR; 1 week and 1, 6, 12 and 24 months), urinary retinol-binding protein (RBP) and proteinuria (1 week and 6, 12 and 24 months).

Results

The volume of renal tissue increased by 12?±?5.6 cm³ at 24 months (p?=?0.035) in the low graft mass and decreased by ?14?±?7 cm³ (p?=?0.046) in the high graft mass. The eGFR increased when either low (30?±?5 ml/min/1.73 m², p?<?0.001) or median (19?±?4 ml/min/1.73 m², p?<?0.001) graft mass was transplanted but remained stable when high graft mass was transplanted. The resistive index (RI) presented a significant decrease throughout early follow-up in the transplants involving low and median graft mass, whereas a slight rise was observed in those involving high graft mass. A significant difference was apparent 6 months post-transplant. Transplants of low and median graft mass were associated with an initial higher urinary RBP. No significant differences in proteinuria were detected.

Conclusions

Small kidneys undergo increases in volume and function without escalation of either proteinuria or urinary RBP, characterizing an adequate adaptation to the recipient. Children receiving larger kidneys present a reduction in volume, stable GFR and higher RI at 6 months.     

Why do some diabetic patients on the kidney transplant waiting list not receive a transplant?

The waiting list (WL) history of 405 diabetic patients placed on the kidney transplantation WL for the years 1993–2000 was examined. By 31 December 2000, 295 (73 %) patients had received a transplant. Of the remaining 110 patients 53 (13 %) were still on the WL; 27 of these were temporarily withdrawn, i.e. non-active, 46 others (11 %) had died and 11 (3 %) had been permanently removed. Patient follow-up continued until the end of 2002. Although the mean total time on the WL of the non-transplanted was twice that of the transplanted patients there were no significant differences in the mean active times on the WL. The mean cumulative withdrawal time of the transplanted and those on the active WL was less than 10 % of their total time on the list, but for the patients who had died or were withdrawn on 31 December 2000 it exceeded 50 %, usually because of diabetic complications. The 5-year survival of the transplanted patients was greatly superior to that of the non-transplanted, as expected. However, the better survival of the transplanted patients is not necessarily proof of a better treatment modality but rather a consequence of the exclusion from transplantation of patients suffering from diabetic complications. It is not justified to compare the survival of transplantable and non-transplantable WL patients.     

Does preserved kidney volume predict 1 year donor renal function after laparoscopic living donor nephrectomy?

The aim of the present study was to evaluate whether preserved kidney volume predicts donor renal function at 1‐year post‐surgery. Data of patients who underwent laparoscopic living donor nephrectomy between October 2006 and September 2010 were retrospectively reviewed. All patients underwent computed tomography scan with an estimation of kidney volume by using an automated segmentation algorithm. We also calculated kidney volume adjusted for donor body surface area and donor preserved kidney volume ratio (split volume). Estimated glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Predictors of the estimated glomerular filtration rate at 1 year were assessed by multiple linear regression. The 1‐year estimated glomerular filtration rate was available in 140 patients. The median age was 40 years, and median adjusted preserved kidney volume was 160.5 cc/1.73 m² (interquartile range 143.7–177.9). Median estimated glomerular filtration rate was 92.4 (interquartile range 81.9–101.2) and 61.2 mL/min/1.73 m² (interquartile range 53.4–68.7), respectively, at baseline and at 1 year. Preserved kidney volume adjusted to body surface area (P = 0.02) with age (P = 0.002) and preoperative estimated glomerular filtration rate (P < 0.001) were independent predictors of estimated glomerular filtration rate at 1 year. However, split kidney volume was not statistically related to estimated glomerular filtration rate at 1 year (P = 0.47). In order to maximize preservation of donor renal function, the pre‐donation kidney volume adjusted to body surface area might be a useful parameter to consider when deciding on living kidney donation.     

Does donor kidney to recipient body weight ratio influence long-term outcomes of living-donor kidney transplantation?

This study evaluated the effect of the donor kidney to recipient body weight (Kw/Rw) ratio on long-term graft function and survival. We investigated retrospectively whether there was any association between Kw/Rw ratio and long-term graft survival and function after a follow-up of >10 years. We studied a consecutive series of 123 adult-to-adult living kidney transplants. According to the Kw/Rw ratio, patients were divided into 3 groups: “low” (Kw/Rw <2.85; n = 29), “medium” (2.85 ≤ Kw/Rw < 4.04; n = 63), and “high” (≥4.04; n = 31). Among the 3 groups, the mean serum creatinine levels at 1 and 6 months as well as 1 year after transplantation were significantly lower among patients with a high Kw/Rw ratio than in those with a medium or low ratio, but serum creatinine levels at 3 and 5 years did not differ significantly (P = .394 and 0.620, respectively). Graft survival rates at 5 and 10 years after transplantation were significantly lower in the “low” group. We observed a significant association between Kw/Rw ratio and graft survival (P = .018). The Kw/Rw ratio is an important factor for long-term graft survival and early graft function. However, it did not significantly affect subsequent renal function.