Examining post-donation outcomes in Hispanic/Latinx living kidney donors in the United States: A systematic review.

We conducted a systematic review to assess outcomes in Hispanic donors and explore how Hispanic ethnicity was characterized. We searched PubMed, EMBASE, and Scopus through October 2021. Two reviewers independently screened study titles, abstracts, and full texts; they also qualitatively synthesized results and independently assessed quality of included studies. Eighteen studies met our inclusion criteria. Study sample sizes ranged from 4007 to 143,750 donors and mean age ranged from 37 to 54 years. Maximum follow-up time of studies varied from a perioperative donor nephrectomy period to 30 years post-donation. Hispanic donors ranged between 6% and 21% of the donor populations across studies. Most studies reported Hispanic ethnicity under race or a combined race and ethnicity category. Compared to non-Hispanic White donors, Hispanic donors were not at increased risk for post-donation mortality, end-stage kidney disease, cardiovascular disease, non-pregnancy-related hospitalizations, or overall perioperative surgical complications. Compared to non-Hispanic White donors, most studies showed Hispanic donors were at higher risk for diabetes mellitus following nephrectomy; however, mixed findings were seen regarding the risk for post-donation chronic kidney disease and hypertension. Future studies should evaluate cultural, socioeconomic, and geographic differences within the heterogeneous Hispanic donor population, which may further explain variation in health outcomes.

Donor-reported barriers to living kidney donor follow-up.

BACKGROUND: Despite regulations mandating follow-up laboratory testing for living kidney donors, less than half of transplant centers are in compliance. We sought to understand barriers to follow-up testing from the donors' perspective. METHODS: We surveyed our center's living kidney donors. Binary logistic regression was used to assess factors associated with follow-up testing completion. RESULTS: Of 185 living kidney donors, 110 (59.4%) participated. Among them, 82 (74.5%) completed 6-month laboratory testing, 76 (69.1%) completed 12-month testing, 68 (61.8%) completed both, and 21 (19.0%) completed neither. Six-month testing completion was strongly associated with 12-month testing completion (OR 9.74, 95%CI: 2.23-42.50; p = .002). Those who disagreed with the statements, "Getting labs checked wasn't a priority for me," (OR for completing 6-month testing: 15.05, 95%CI: 3.70-61.18; p < .001; OR for completing 12-month testing: 5.85, 95%CI: 1.94-17.63; p = .002); and, "I forgot to get labs drawn [until I was reminded]" (OR for completing 6-month testing: 6.93, 95%CI: 1.59-30.08; p = .01; OR for completing 12-month testing: 6.55, 95%CI: 1.98-21.63; p = .002) were more likely to complete testing. CONCLUSIONS: To our knowledge, this is the only study providing perspective on donor insights regarding the need for follow-up testing post donation. Interventions to influence living donor attitudes toward follow-up testing may improve follow-up.

Uninephrectomy and class II PI3K-C2ß inactivation synergistically protect against obesity, insulin resistance and liver steatosis in mice.

Uninephrectomy (UNx) in living kidney donors for transplantation is now routine clinical practice. While chronic kidney disease, due to bilateral kidney dysfunction, is associated with insulin resistance, liver steatosis, and type 2 diabetes, the metabolic impact of UNx remains unclear. To better understand the crosstalk between the kidney and insulin target tissues, we studied the metabolic consequences of UNx and the potential involvement of class II PI3K-C2ß, the inactivation of which has been reported to result in insulin sensitization. Mice underwent UNx or sham operation followed by either normal chow or high-fat diet (HFD). Seventeen weeks post-UNx, mice showed improved glucose tolerance, insulin sensitivity, and decreased HFD-induced liver steatosis. This was associated with an enhanced serum FGF21 and insulin-stimulated Akt signaling in the liver and muscle of both lean and obese mice. Remarkably, the combination of UNx and PI3K-C2ß inactivation protected against HFD-induced obesity and further potentiated the metabolic improvement observed in WT UNx mice correlating with a synergistic increase in metabolic tissues of (1) insulin-stimulated Akt signaling (2) FGFR1 and ßKlotho expression. We demonstrated a potential beneficial effect of kidney donation and more effectively with PI3K-C2ß inactivation to protect against metabolic disorders through a mutual insulin/FGF21 sensitization.

Epigenetic-based therapy in allogenic hematopoietic stem cell transplantation: Novel opportunities for personalized treatment.

Current management of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) lacks immunosuppressant drugs able to block the host immune response toward the graft antigens. Novel treatments may include epigenetic compounds (epidrugs) some of which have been yet approved by the Food and Drugs Administration for the treatment of specific blood malignancies. The most investigated in clinical trials for allo-HSCT are DNA demethylating agents (DNMTi), such as azacitidine (Vidaza) and decitabine (Dacogen) as well as histone deacetylases inhibitors (HDACi), such as vorinostat (Zolinza) and panobinostat (Farydak). Indeed, azacitidine monotherapy before allo-HSCT may reduce the conventional chemotherapy-related complications, whereas it may reduce relapse risk and death after allo-HSCT. Besides, a decitabine-containing conditioning regimen could protect against graft versus host disease (GVHD) and respiratory infections after allo-HSCT. Regarding HDACi, the addition of vorinostat and panobinostat to the conditioning regimen after allo-HSCT seems to reduce the incidence of acute GVHD. Furthermore, panobinostat alone or in combination with low-dose decitabine may reduce the relapse rate in high-risk patients with acute myeloid leukemia patients after allo-HSCT. We discuss the phase 1 and 2 clinical trials evaluating the possible beneficial effects of repurposing specific epidrugs which may guide personalized therapy in the setting of allo-HSCT.

Molecular diagnosis of kidney transplant failure based on urine.

In light of the organ shortage, there is a great responsibility to assess postmortal organs for which procurement has been consented and to increase the life span of transplanted organs. The former responsibility has moved many centers to accept extended criteria organs. The latter responsibility requires an exact diagnosis and, if possible, omission of the harmful influence on the transplant. We report the course of a kidney transplant that showed a steady decline of function over a decade, displaying numerous cysts of different sizes. Clinical workup excluded the most frequent causes of chronic transplant failure. The filed allocation documents mentioned the donor's disease of oral-facial-digital syndrome, a rare ciliopathy, which can also affect the kidney. Molecular diagnosis was performed by culturing donor tubular cells from the recipient´s urine more than 10 years after transplantation. Next-generation panel sequencing with DNA from tubular urinary cells revealed a novel truncating mutation in OFD1, which sufficiently explains the features of the kidney transplants, also found in the second kidney allograft. Despite this severe donor disease, lifesaving transplantation with good long-term outcome was enabled for 5 recipients.

Long-term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study.

This study aimed to evaluate postoperative long-term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.

Patterns and predictors of fatigue following living donor nephrectomy: Findings from the KDOC Study.

This study sought to identify the prevalence, pattern, and predictors of clinical fatigue in 193 living kidney donors (LKDs) and 20 healthy controls (HCs) assessed at predonation and 1, 6, 12, and 24 months postdonation. Relative to HCs, LKDs had significantly higher fatigue severity (P = .01), interference (P = .03), frequency (P = .002), and intensity (P = .01), and lower vitality (P < .001), at 1-month postdonation. Using published criteria, significantly more LKDs experienced clinical fatigue at 1 month postdonation, compared to HCs, on both the Fatigue Symptom Inventory (60% vs. 37%, P < .001) and SF-36 Vitality scale (67% vs. 16%, P < .001). No differences in fatigue scores or clinical prevalence were observed at other time points. Nearly half (47%) reported persistent clinical fatigue from 1 to 6 months postdonation. Multivariable analyses demonstrated that LKDs presenting for evaluation with a history of affective disorder and low vitality, those with clinical mood disturbance and anxiety about future kidney failure after donation, and those with less physical activity engagement were at highest risk for persistent clinical fatigue 6 months postdonation. Findings confirm inclusion of fatigue risk in existing OPTN informed consent requirements, have important clinical implications in the care of LKDs, and underscore the need for further scientific examination in this population.

Pain expectancy, prevalence, severity, and patterns following donor nephrectomy: Findings from the KDOC Study.

Postoperative pain is an outcome of importance to potential living kidney donors (LKDs). We prospectively characterized the prevalence, severity, and patterns of acute or chronic postoperative pain in 193 LKDs at six transplant programs. Three pain measurements were obtained from donors on postoperative Day (POD) 1, 3, 7, 14, 21, 28, 35, 41, 49, and 56. The median pain rating total was highest on POD1 and declined from each assessment to the next until reaching a median pain-free score of 0 on POD49. In generalized linear mixed-model analysis, the mean pain score decreased at each pain assessment compared to the POD3 assessment. Pre-donation history of mood disorder (adjusted ratio of means [95% confidence interval (CI)]: 1.40 [0.99, 1.98]), reporting "severe" on any POD1 pain descriptors (adjusted ratio of means [95% CI]: 1.47 [1.12, 1.93]) and open nephrectomy (adjusted ratio of means [95% CI]: 2.61 [1.03, 6.62]) were associated with higher pain scores across time. Of the 179 LKDs who completed the final pain assessment, 74 (41%) met criteria for chronic postsurgical pain (CPSP), that is, any donation-related pain on POD56. Study findings have potential implications for LKD education, surgical consent, postdonation care, and outcome measurements.

The landscape of international living kidney donation in the United States.

In the United States, kidney donation from international (noncitizen/nonresident) living kidney donors (LKDs) is permitted; however, given the heterogeneity of healthcare systems, concerns remain regarding the international LKD practice and recipient outcomes. We studied a US cohort of 102 315 LKD transplants from 2000-2016, including 2088 international LKDs, as reported to the Organ Procurement and Transplantation Network. International LKDs were more tightly clustered among a small number of centers than domestic LKDs (Gini coefficient 0.76 vs 0.58, P < .001). Compared with domestic LKDs, international LKDs were more often young, male, Hispanic or Asian, and biologically related to their recipient (P < .001). Policy-compliant donor follow-up was substantially lower for international LKDs at 6, 12, and 24 months postnephrectomy (2015 cohort: 45%, 33%, 36% vs 76%, 71%, 70% for domestic LKDs, P < .001). Among international LKDs, Hispanic (aOR = 0.23 0.360.56 , P < .001) and biologically related (aOR = 0.39 0.590.89 , P < .01) donors were more compliant in donor follow-up than white and unrelated donors. Recipients of international living donor kidney transplant (LDKT) had similar graft failure (aHR = 0.78 0.891.02 , P = .1) but lower mortality (aHR = 0.53 0.620.72 , P < .001) compared with the recipients of domestic LDKT after adjusting for recipient, transplant, and donor factors. International LKDs may provide an alternative opportunity for living donation. However, efforts to improve international LKD follow-up and engagement are warranted.

Financial burden associated with time to return to work after living kidney donation.

Many living kidney donors undertake a significant financial burden in order to donate. We studied the association between time to return to work and reported financial burden. Kidney donors who donated from 2/2005 through 12/2015 (n = 1012) were surveyed 6 months after donation and asked about occupation, time to return to work, and financial burden (on a 10-point Likert scale). Of 856 donors working for pay, 629 (73%) responded. After adjusting for donor characteristics, increased length of time to return to work was a significant predictor of financial burden (P < .001). It is notable that those in manual/skilled trade occupations, compared with all other occupations, experienced greater financial burden for each week away from work (P = .003). Older age at donation and nondirected (vs directed) donation were associated with significantly decreased financial burden. These observations provide additional information to better inform donor candidates, and further emphasize the need to develop policies so that living kidney donation can be financially neutral.

Larger nephron size, low nephron number, and nephrosclerosis on biopsy as predictors of kidney function after donating a kidney.

It is unclear whether structural findings in the kidneys of living kidney donors predict postdonation kidney function. We studied living kidney donors who had a kidney biopsy during donation. Nephron size was measured by glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area. Age-specific thresholds were defined for low nephron number (calculated from CT and biopsy measures) and nephrosclerosis (global glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis). These structural measures were assessed as predictors of postdonation measured GFR, 24-hour urine albumin, and hypertension. Analyses were adjusted for baseline age, gender, body mass index, systolic and diastolic blood pressure, hypertension, measured GFR, urine albumin, living related donor status, and time since donation. Of 2673 donors, 1334 returned for a follow-up visit at a median 4.4 months after donation, with measured GFR <60 mL/min/1.73 m2 in 34%, urine albumin >5 mg/24 h in 13%, and hypertension in 5.3%. Larger glomerular volume and interstitial fibrosis/tubular atrophy predicted follow-up measured GFR <60 mL/min/1.73 m2 . Larger cortex volume per glomerulus and low nephron number predicted follow-up urine albumin >5 mg/24 h. Arteriosclerosis predicted hypertension. Microstructural findings predict GFR <60 mL/min/1.73 m2 , modest increases in urine albumin, and hypertension shortly after kidney donation.

Kidney donor outcomes ≥ 50 years after donation.

Many living kidney donors (LDs) are young at donation; yet there are little data on long-term LD follow-up. We report on 66 LDs who donated ≥50 years ago: 22 (33.3%) are still alive (current age, 78.5 ± 7.25 years); 39 (59%) died (mean age at death, 74.2 ± 12.3 years); and 5 are lost to follow-up (mean age at last contact, 68.7 ± 4.6 years). Those who died were older at donation (P < .001). Causes of death included 12 (30.8% of deaths) cardiovascular diseases, 9 (23.0%) respiratory failures, 5 (12.8%) malignancies and 4 (10.3%) infections, and 9 (23%) were unknown or miscellaneous. Forty-nine living donors (74%) developed hypertension at a mean age of 59.9 ± 14.0 years; 12 (18%) developed diabetes at a mean age of 62 ± 19.4 years; and 11 (16.7%) developed proteinuria at a mean age of 60.6 ± 18.2 years-each at a similar incidence as seen in the age-matched general population. At last follow-up, the eGFR by CKD-EPI (mean ± SD) for donors currently alive was 60.2 ± 13.4 mL/min/1.73 m2 ; for those that died, 54.0 ± 21.5 mL/min/1.73 m2 ; for those lost to follow-up, 55.6 ± 7.5 mL/min/1.73 m2 . ESRD developed in 2 (3.3%). SF-36 quality of life health survey scores (n = 21) were similar to the age-matched general population.

Hypertension after kidney donation: Incidence, predictors, and correlates.

Incidence of postdonation hypertension, risk factors associated with its development, and impact of type of treatment received on renal outcomes were determined in 3700 kidney donors. Using Cox proportional hazard model, adjusted hazard ratios (HRs) for cardiovascular disease (CVD); estimated glomerular filtration rate (eGFR) <60, <45, <30 mL/min/1.73m2 ; end stage renal disease (ESRD); and death in hypertensive donors were determined. After a mean (standard deviation [SD]) of 16.6 (11.9) years of follow-up, 1126 (26.8%) donors developed hypertension and 894 with known antihypertensive medications. Hypertension developed in 4%, 10%, and 51% at 5, 10, and 40 years, respectively, and was associated with proteinuria, eGFR < 30, 45, and 60 mL/min/1.73m2 , CVD, and death. Blood pressure was <140/90 mm Hg at last follow-up in 75% of hypertensive donors. Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (compared to other antihypertensive agents) was associated with a lower risk for eGFR <45 mL/min/1.73m², HR 0.64 (95% confidence interval [CI] 0.45-0.9), P = .01, and also less ESRD; HR 0.03 (95% CI 0.001-0.20), P = .004. In this predominantly Caucasian cohort, hypertension is common after donation, well controlled in most donors, and factors associated with its development are similar to those in the general population.

Mood, body image, fear of kidney failure, life satisfaction, and decisional stability following living kidney donation: Findings from the KDOC study.

Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.

Renal Consequences of Diabetes After Kidney Donation.

Whether diabetes after kidney donation is associated with an accelerated GFR decay in the remaining kidney has not been studied. We determined the incidence of diabetes in kidney donors, and compared GFR change over time in diabetic to nondiabetic donors, in addition to the effect of diabetes mellitus (DM) on the development of proteinuria, hypertension, and end-stage renal disease (ESRD). Of the 4014 donors, 309 (7.7%) developed diabetes at a median age of 56.0 years and after a median of 18 years after donation. The difference in annual estimated GFR (eGFR) change between diabetic and nondiabetic donors in the 7 years before the development of DM was -0.08 mL/min/year; p = 0.51. After DM development, the difference was -1.10 mL/min/year for diabetic donors with hypertension and proteinuria, p < 0.001; -0.19 for diabetic donors with hypertension but no proteinuria, p = 0.29; -0.75 mL/min/year for diabetic donors with proteinuria but no hypertension, p = 0.19; and -0.09 mL/min/year for diabetic donors without proteinuria or hypertension, p = 0.63. When DM was considered as a time-dependent covariate, it was associated with the development of proteinuria (hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.89-3.70; p < 0.001) and hypertension (HR 2.19, 95% CI 1.74-2.75; p < 0.001). It was not, however, associated with ESRD. eGFR decline after DM development exceeds that of nondiabetic donors only in diabetic donors with concomitant proteinuria and hypertension.

The Living Donor Collective: A Scientific Registry for Living Donors.

In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

Psychological Outcomes of Living Liver Donors From a Multicenter Prospective Study: Results From the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2).

Although single-center and cross-sectional studies have suggested a modest impact of liver donation on donor psychological well-being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0-3%), alcohol abuse (2-5%), and anxiety syndromes (2-3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well-being at various time points. We identified significant predictors for donors' perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data-driven follow-up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.

Long-Term Medical and Psychosocial Outcomes in Living Liver Donors.

Due to the enduring organ shortage, living donor liver transplantation has been a valuable treatment strategy for advanced liver disease patients for over 20 years. A variety of reviews have summarized the extensive data now available on medical and psychosocial risks to living donors in the aftermath of donation. However, evidence on donor medical and psychosocial outcomes beyond the first year postdonation has not been synthesized in any previous review. The evidence base on such "long-term" outcomes has been growing in recent years. A review of this evidence would therefore be timely and could serve as an important resource to assist transplant centers in their efforts to fully educate prospective donors and gain informed consent, as well as develop appropriate postdonation clinical care and surveillance plans. We reviewed recent literature on long-term donor outcomes, considering (a) medical outcomes, including mortality risk, rates of complications, abnormalities detected in laboratory testing, and the progress of liver regeneration; and (b) donor-reported psychosocial outcomes reflecting physical, emotional, and interpersonal/socioeconomic well-being, as well as overall health-related quality of life. We summarize limitations and gaps in available evidence, and we provide recommendations for future research and clinical care activities focused on long-term outcomes in liver donors.

Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2).

Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.

Long-Term Non-End-Stage Renal Disease Risks After Living Kidney Donation.

Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non-end-stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non-ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less-than-ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.