Predicting donor,recipient and graft survival in living donor kidney transplantation to inform pretransplant counselling: the donor and recipient linked iPREDICTLIVING tool – a retrospective study

Although separate prediction models for donors and recipients were previously published, we identified a need to predict outcomes of donor/recipient simultaneously, as they are clearly not independent of each other. We used characteristics from transplantations performed at the Oslo University Hospital from 1854 live donors and from 837 recipients of a live donor kidney transplant to derive Cox models for predicting donor mortality up to 20 years, and recipient death, and graft loss up to 10 years. The models were developed using the multivariable fractional polynomials algorithm optimizing Akaike’s information criterion, and optimism-corrected performance was assessed. Age, year of donation, smoking status, cholesterol and creatinine were selected to predict donor mortality (C-statistic of 0.81). Linear predictors for donor mortality served as summary of donor prognosis in recipient models. Age, sex, year of transplantation, dialysis vintage, primary renal disease, cerebrovascular disease, peripheral vascular disease and HLA mismatch were selected to predict recipient mortality (C-statistic of 0.77). Age, dialysis vintage, linear predictor of donor mortality, HLA mismatch, peripheral vascular disease and heart disease were selected to predict graft loss (C-statistic of 0.66). Our prediction models inform decision-making at the time of transplant counselling and are implemented as online calculators.     

Effect of donor–recipient age difference on long-term graft survival in living kidney transplantation

Purpose

We aimed to examine the influence of donor age on living-donor kidney transplantation (KTx), particularly with regard to long-term graft survival in young recipients with aged kidney grafts.

Methods

Between 1988 and 2012, 287 living-donor KTxs were performed in our center. The recipients were divided into 3 groups according to age in years: under 30 (young), 30–49 (middle-aged), and over 50 (old). The data regarding the influence of kidneys from donors aged over 50 years were retrospectively analyzed.

Results

Graft survival at 1, 5, 10, and 15 years was 94.7, 94.7, 90.2, and 75.2 %, respectively, in young recipients who received grafts from donors aged under 50 years, and 96.4, 91.9, 65.4, and 41.4 %, respectively, in young recipients who received grafts from donors aged over 50 years (P = 0.023). In contrast, there were no significant differences regarding graft survival and donor age in the middle-aged and old recipient groups. Multivariate analysis revealed that young recipient and rejection episode were significant predictors of graft loss in transplantation from older donors. Histological examination revealed significant age-related changes in the grafts before transplant and a significant higher rate of glomerular hypertrophy at the 1-month protocol biopsy in young recipients with aged kidney grafts.

Conclusions

Kidney grafts from older living donors affected long-term graft survival in young recipients. In addition to the damage from rejection, aged kidney grafts, which have less nephron mass, may have a limited capacity to appropriately respond to increases in physiological or metabolic demands of young recipients, leading to a greater reduction in renal function.     

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.     

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.     

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.     

Should a homeless person become a deceased organ donor?

Efforts to increase deceased donation have included the use of US Public Health Service (PHS) high‐risk donors. The homeless have high rates of medical and substance abuse issues that are often unrecognized. This study investigates whether the homeless should become suitable organ donors. We retrospectively reviewed 193 brain‐dead prospective donors from Hawaii's organ procurement organization (OPO; 2013‐2018) and compared two groups: homeless (n = 13) and non‐homeless (n = 180) prospective donors. The homeless prospective donors were older (48.0 vs 40.7 years, P = .009) and had more substance abuse (30.8% vs 10%, P = .046), methamphetamine use (53.8% vs 12.2%, P = .001), cocaine use (23.1% vs 3.9%, P = .022), and urine with amphetamines (54.5% vs 17.9%, P = .049). The homeless prospective donors trended toward more PHS high‐risk designation (50% vs 19%, P = .062). There was no difference in medical history, gender/race, hepatitis serologies, authorization for donation, and organs procured/transplanted between prospective donors. We have provided evidence that the homeless should become prospective organ donors; however, they have more high‐risk behaviors and often have limited information. Larger studies from OPOs are needed to better characterize organ donation and track disease transmission in this population.     

Which score system can best predict recipient outcomes after living donor liver transplantation?

Introduction

Many scoring systems have been suggested to predict the outcomes of deceased donor liver transplantations. The aims of this study were to compare the Model for End-Stage Liver Disease (MELD) score with respect to other scores among patients who underwent living donor liver transplantation (LDLT) seeking to evaluate the best system to correlate with postoperative outcomes after LDLT.

Methods

We analyzed retrospectively data from 202 adult patients who underwent LDLT from January 2008 to July 2010. We calculated preoperative MELD, MELD-sodium, MELD to serum sodium ratio (MESO), integrated MELD, United Kingdom MELD, Child-Turcotte-Pugh, Acute Physiology and Chronic Health evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores in all patients. We analyzed the correlation of each score with postoperative laboratory results, as well as survival at 1, 3, 6 and 12 months after LDLT.

Results

There was significant positive correlation between all scores and peak total bilirubin during the first 7 days after LDLT. The MELD score showed the greatest correlation with peak total bilirubin (r = 0.745). APACHE II and SOFA scores at 6 months and 1 year after LDLT and MESO score at 1 year after LDLT showed acceptable discrimination performance {area under the receiver operating characteristic curves (AUC) >0.7, while other scoring systems showed poor discrimination. However, the AUCs of each score were not significantly different from the MELD score AUC.

Conclusion

The MELD score most correlated with total bilirubin after LDLT, while the APACHE II and SOFA scores seemed to correlate with mortality after LDLT.     

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–recipient age difference matter in outcome of kidney transplantation? Implications for kidney paired donation

Background: Kidney paired donation (KPD) is a rapidly growing modality for facilitating living donor kidney transplantation (LDKTx) for patients who are incompatible with their healthy, willing and living donor. The impact of donor–recipient age difference on long and short-term graft and patient survivals in LDKTx is still uncertain. Methods: A total of 1502 LDKTx recipients who received regular follow-up in our center from 1999 to 2012 were studied. Donor–recipient age difference was divided into subgroups (donor–recipient 0?10, 11–20, 0–20, 21–30, 31–40, and 21–40 years). Outcome measures included death censored graft, patient survival and acute rejection rate. Results: The 1-, 5-, 10-year patient survival of the donor–recipient age difference ≤20 years group showed no difference compared with the age difference >20 years group (94.5%, 83.2%, 71.9% and 95.2%, 86%, 77.8%, p?=?0.053). The 1-, 5-, 10-year graft survival of the donor–recipient age difference ≤20 years group showed no difference compared with the age difference >20 years group (94.6%, 81.6%, 72.1% and 94%, 80%, 72.2%, p?=?0.989). The rejection were also similar (17.5% vs. 16.5%, p?>?0.05). There was no statistically significant difference in graft survival and acute rejection rate in all subgroups. Conclusions: Older donors (usually within families) are not associated with worse outcome is reassuring. KPD should not be prohibited due to high donor–recipient age difference, when size of donor pool is small as in single center KPD program.     

Is there a role for living donor intestine transplants?

The use of living donors with intestinal transplantation is controversial because it may not significantly improve candidate access to organs when intestine-only grafts are needed, and may involve excessive donor risk when combined liver-intestine grafts are required. Although limited data are available for comparison at this time, graft and patient survival rates for intestinal transplantations using living donors are no different than for deceased donor transplantations. Potential benefits that may be provided to the intestine transplant recipient through the use of living donors include better HLA matching, shorter ischemia times, better bowel preparation, and better opportunities for introducing immunomodulatory strategies. Conversely, living intestine donors are at risk for mortality, significant morbidity, financial loss, and psychologic trauma. The long-term outcomes of living intestine donors have not yet been reported. Ultimately, these data are essential before the wider use of living donors can be advocated for intestinal transplantation.     

Can current technology be integrated to facilitate laparoscopic living donor hepatectomy?

Background: Living donor hepatectomy (LDH) is a technically demanding procedure that is an alternative for providing livers for transplantation. Unlike liver resections for other pathology, LDH requires preservation of the major vessels and biliary tree. This study was performed to determine if current technology can be integrated to perform laparoscopic LDH. Methods: Six adult sheep underwent laparoscopic LDH of the left lateral segment under general anesthesia. Instruments utilized included standard dissecting instruments, ultrasound, ultrasonic dissectors, CUSA, the TissueLink Floating Ball, and endoscopic staplers. Results: LDH-harvested liver grafts were 44% of whole liver weight. Estimated blood loss was 300 cc. Warm ischemia time was 5–7 min. Grafts were delivered through 18-cm abdominal wounds. Major vessels and biliary anatomy were positively identified in the grafts. Conclusions: Laparoscopic LDH can be performed with available technology. Theoretical advantages include reduced liver manipulation and smaller wound size. Paper presented at the eighth World Congress of Endoscopic Surgery, New York, NY, USA     

Preemptive living donor kidney transplantation: do the benefits extend to all recipients?

BACKGROUND: Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients. METHODS: We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months). RESULTS: Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37). CONCLUSION: With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.     

Use of stenting in living donor kidney transplantation: does it reduce vesicoureteral complications?

The risk of urologic complications after kidney transplantation is 0% to 30%. We studied the impact of prophylactic stent placement during transplantation by assessing the necessity for a percutaneous nephrostomy (PCN) after living kidney transplantation. From January 2003 to December 2007, 342 living donor kidney transplantations were performed. Intra- and postoperative data were collected retrospectively from 285 patients with stent and 57 without. Baseline characteristics were not significantly different between groups, except for the number of previous transplantations: 31 (11%) patients with versus 16 (28%) without stent had a history of >1 transplantation (P < .001). From patients with PCN, 55 (87%) patients in the stented group received a PCN <3 months versus 11 (100%) in the nonstented group (P = .71). The reoperation rate for urologic complications was similar in both groups (3% (stented) versus 5% (nonstented; P = .43). In multivariate analysis, risk for PCN was similar in both groups (odds ratio 1.21, 95% confidence interval 0.5-2.5). Recipient survival was not significantly different. One- and 3-year death-censored graft survival was not significantly different between stented (89% and 84%) and nonstented group (90% and 85%, P = .71 and P = .96). Ureteral stent insertion is not associated with a reduced rate of PCN placement in living donor kidney transplantation.