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In the general population, decreases in glomerular filtration rate (GFR) are associated with subsequent development of chronic kidney disease (CKD), cardiovascular disease (CVD), and death. It is unknown if low estimated GFR (eGFR) before or early after kidney donation was also associated with these risks.One thousand six hundred ninety-nine living donors who had both predonation and early (4-10 weeks) postdonation eGFR were included. We studied the relationships between eGFR, age at donation, and the time to sustained eGFR<45 (CKD stage 3b) and <30 mL/min/1.73m2(CKD stage 4), hypertension, diabetes mellitus (DM), CVD, and death. Median follow-up was 12 (interquartile range, 6-21) years. Twenty-year event rates were 5.8% eGFR<45 mL/min/1.73m2; 1.2% eGFR<30 mL/min/1.73m2; 29.0% hypertension; 7.8% DM; 8.0% CVD; and 5.2% death. The median time to eGFR<45 mL/min/1.73m2(N = 79) was 17 years, and eGFR<30 mL/min/1.73m2(N = 22) was 25 years. Both low predonation and early postdonation eGFR were associated with eGFR<45 mL/min/1.73m2(P< .0001) and eGFR<30 mL/min/1.73m2(P< .006); however, the primary driver of risk for all ages was low postdonation (rather than predonation) eGFR. Predonation and postdonation eGFR were not associated with hypertension, DM, CVD, or death. Low predonation and early postdonation eGFR are risk factors for developing eGFR<45 mL/min/1.73m2(CKD stage 3b) and <30 mL/min/1.73m2(CKD stage 4), but not CVD, hypertension, DM, or death.

Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

Historically, to minimize risks, living kidney donors have been highly selected and healthy. Operative risks are well-defined, yet concern remains about long-term risks. In the general population, even a mild reduction in glomerular filtration rate (GFR) is associated with cardiovascular disease, chronic kidney disease, and end-stage kidney disease (ESKD). However, reduction in GFR in the general population is due to kidney or systemic disease. Retrospective studies comparing donors with matched general population controls have found no increased donor risk. Prospective studies comparing donors with controls (maximum follow-up, 9 years) have reported that donor GFR is stable or increases slightly, whereas GFR decreases in controls. However, these same studies identified metabolic and vascular donor abnormalities. There are a few retrospective studies comparing donors with controls. Each has limitations in selection of the control group, statistical analyses, and/or length of follow-up. One such study reported increased donor mortality; 2 reported a small increase in absolute risk of ESKD. Risk factors for donor ESKD are similar to those in the general population. Postdonation pregnancies are also associated with increased risk of hypertension and preeclampsia. There is a critical need for long-term follow-up studies comparing donors with controls from the same era, geographic area, and socioeconomic status who are healthy, with normal renal function on the date matching the date of donation, and are matched on demographic characteristics with the donors. These data are needed to optimize donor candidate counseling and informed consent.

The kidney shortage continues to be a crisis for our patients. Despite numerous attempts to increase living and deceased donation, annually in the United States, thousands of candidates are removed from the kidney transplant waiting list because of either death or becoming too sick to transplant. To increase living donation, trials of a regulated system of incentives for living donation have been proposed. Such trials may show: (1) a significant increase in donation, and (2) that informed, incentivized donors, making an autonomous decision to donate, have the same medical and psychosocial outcomes as our conventional donors. Given the stakes, the proposal warrants careful consideration. However, to date, much discussion of the proposal has been unproductive. Objections commonly leveled against it: fail to engage with it; conflate it with underground, unregulated markets; speculate without evidence; and reason fallaciously, favoring rhetorical impact over logic. The present paper is a corrective. It identifies these common errors so they are not repeated, thus allowing space for an assessment of the proposal on its merits.

The kidney shortage continues to be a crisis for our patients. Despite numerous attempts to increase living and deceased donation, annually in the United States, thousands of candidates are removed from the kidney transplant waiting list because of either death or becoming too sick to transplant. To increase living donation, trials of a regulated system of incentives for living donation have been proposed. Such trials may show: (1) a significant increase in donation, and (2) that informed, incentivized donors, making an autonomous decision to donate, have the same medical and psychosocial outcomes as our conventional donors. Given the stakes, the proposal warrants careful consideration. However, to date, much discussion of the proposal has been unproductive. Objections commonly leveled against it: fail to engage with it; conflate it with underground, unregulated markets; speculate without evidence; and reason fallaciously, favoring rhetorical impact over logic. The present paper is a corrective. It identifies these common errors so they are not repeated, thus allowing space for an assessment of the proposal on its merits. The authors discuss numerous arguments against trials of a regulated system of incentives to living kidney donation, point out common errors in these arguments, and suggest that an informed, meaningful discussion of the merits of trials of a regulated system should occur.

African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n= 58) and low (n= 60) TAC troughs (N= 515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12 mg, respectively. Of 34,542 identified variants across 99 genes, 1406 variants were suggestively associated with TAC troughs in univariate models (p-value < 0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Living donor kidney transplantation benefits the recipient. However, kidney failure can occur in a small fraction of donors — the risk is not uniform but varies according to donor characteristics. Studies to date have failed to match on important factors, such as era, environment or family history. Long-term studies with well-matched healthy controls are therefore needed.

Inflammation in areas of fibrosis (i-IFTA) in posttransplant biopsies is part of the diagnostic criteria for chronic active TCMR (CA TCMR -- i-IFTA ≥ 2, ti ≥ 2, t ≥ 2). We evaluated i-IFTA and CA TCMR in the DeKAF indication biopsy cohorts: prospective (n = 585, mean time to biopsy = 1.7 years); cross-sectional (n = 458, mean time to biopsy = 7.8 years). Grouped by i-IFTA scores, the 3-year postbiopsy DC-GS is similar across cohorts. Although a previous acute rejection episode (AR) was more common in those with i-IFTA on biopsy, the majority of those with i-IFTA had not had previous AR. There was no association between type of previous AR (AMR, TCMR) and presence of i-IFTA. In both cohorts, i-IFTA was associated with markers of both cellular (increased Banff i, t, ti) and humoral (increased g, ptc, C4d, DSA) activity. Biopsies with i-IFTA = 1 and i-IFTA ≥ 2 with concurrent t ≥ 2 and ti ≥ 2 had similar DC-GS. These results suggest that (a) i-IFTA≥1 should be considered a threshold for diagnoses incorporating i-IFTA, ti, and t; (b) given that i-IFTA ≥ 2,t ≥ 2, ti ≥ 2 can occur in the absence of preceding TCMR and that the component histologic scores (i-IFTA,t,ti) each indicate an acute change (albeit i-IFTA on the nonspecific background of IFTA), the diagnostic category “CA TCMR” should be reconsidered.

Inflammation in areas of fibrosis (i‐IFTA) in posttransplant biopsies is part of the diagnostic criteria for chronic active TCMR (CA TCMR ‐‐ i‐IFTA ≥ 2, ti ≥ 2, t ≥ 2). We evaluated i‐IFTA and CA TCMR in the DeKAF indication biopsy cohorts: prospective (n = 585, mean time to biopsy = 1.7 years); cross‐sectional (n = 458, mean time to biopsy = 7.8 years). Grouped by i‐IFTA scores, the 3‐year postbiopsy DC‐GS is similar across cohorts. Although a previous acute rejection episode (AR) was more common in those with i‐IFTA on biopsy, the majority of those with i‐IFTA had not had previous AR. There was no association between type of previous AR (AMR, TCMR) and presence of i‐IFTA. In both cohorts, i‐IFTA was associated with markers of both cellular (increased Banff i, t, ti) and humoral (increased g, ptc, C4d, DSA) activity. Biopsies with i‐IFTA = 1 and i‐IFTA ≥ 2 with concurrent t ≥ 2 and ti ≥ 2 had similar DC‐GS. These results suggest that (a) i‐IFTA≥1 should be considered a threshold for diagnoses incorporating i‐IFTA, ti, and t; (b) given that i‐IFTA ≥ 2,t ≥ 2, ti ≥ 2 can occur in the absence of preceding TCMR and that the component histologic scores (i‐IFTA,t,ti) each indicate an acute change (albeit i‐IFTA on the nonspecific background of IFTA), the diagnostic category “CA TCMR” should be reconsidered. This study of two indication‐biopsy cohorts questions the Banff diagnostic category of chronic active T cell–mediated rejection. Naesens et al. comment on page 1689.

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Inflammation in areas of fibrosis (i‐IFTA) in posttransplant biopsy specimens has been associated with decreased death‐censored graft survival (DC‐GS). Additionally, an i‐IFTA score ≥ 2 is part of the diagnostic criteria for chronic active TCMR (CA TCMR). We examined the impact of i‐IFTA and t‐IFTA (tubulitis in areas of atrophy) in the first biopsy for cause after 90 days posttransplant (n = 598); mean (SD) 1.7 ± 1.4 years posttransplant. I‐IFTA, present in 196 biopsy specimens, was strongly correlated with t‐IFTA, and Banff i. Of the 196, 37 (18.9%) had a previous acute rejection episode; 96 (49%) had concurrent i score = 0. Unlike previous studies, i‐IFTA = 1 (vs 0) was associated with worse 3‐year DC‐GS: (i‐IFTA = 0, 81.7%, [95% CI 77.7 to 85.9%]); i‐IFTA = 1, 68.1%, [95% CI 59.7 to 77.6%]; i‐IFTA = 2, 56.1%, [95% CI 43.2 to 72.8%], i‐IFTA = 3, 48.5%, [95% CI 31.8 to 74.0%]). The association of i‐IFTA with decreased DC‐GS remained significant when adjusted for serum creatinine at the time of the biopsy, Banff i, ci and ct, C4d and DSA. T‐IFTA was similarly associated with decreased DC‐GS. Of these indication biopsies, those with i‐IFTA ≥ 2, without meeting other criteria for CA TCMR had similar postbiopsy DC‐GS as those with CA TCMR. Those with i‐IFTA = 1 and t ≥ 2, ti ≥ 2 had postbiopsy DC‐GS similar to CA TCMR. Biopsies with i‐IFTA = 1 had similar survival as CA TCMR when biopsy specimens also met Banff criteria for TCMR and/or AMR. Studies of i‐IFTA and t‐IFTA in additional cohorts, integrating analyses of Banff scores meeting criteria for other Banff diagnoses, are needed. This study of indication biopsies examines i‐IFTA scores and their association with subsequent graft outcomes.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Tacrolimus trough and dose requirements vary dramatically between individuals of European and African American ancestry. These differences are less well described in other populations. We conducted an observational, prospective, multicenter study from which 2595 kidney transplant recipients of European, African, Native American, and Asian ancestry were studied for tacrolimus trough, doses, and genetic determinants of metabolism. We studied the well-known variants and conducted a CYP3A4/5 gene-wide analysis to identify new variants. Daily doses, and dose-normalized troughs were significantly different between the four groups (P< .001). CYP3A5*3(rs776746) was associated with higher dose-normalized tacrolimus troughs in all groups but occurred at different allele frequencies and had differing effect sizes. The CYP3A5*6(rs10264272) and *7(rs413003343) variants were only present in African Americans. CYP3A4*22(rs35599367) was not found in any of the Asian ancestry samples. We identified seven suggestive variants in the CYP3A4/5 genes associated with dose-normalized troughs in Native Americans (P= 1.1 × 10−5-8.8 × 10−6) and one suggestive variant in Asian Americans (P= 5.6 × 10−6). Tacrolimus daily doses and dose-normalized troughs vary significantly among different ancestry groups. We identified potential new variants important in Asians and Native Americans. Studies with larger populations should be conducted to assess the importance of the identified suggestive variants.

Tacrolimus trough and dose requirements vary dramatically between individuals of European and African American ancestry. These differences are less well described in other populations. We conducted an observational, prospective, multicenter study from which 2595 kidney transplant recipients of European, African, Native American, and Asian ancestry were studied for tacrolimus trough, doses, and genetic determinants of metabolism. We studied the well‐known variants and conducted a CYP3A4/5 gene‐wide analysis to identify new variants. Daily doses, and dose‐normalized troughs were significantly different between the four groups (P< .001). CYP3A5*3(rs776746) was associated with higher dose‐normalized tacrolimus troughs in all groups but occurred at different allele frequencies and had differing effect sizes. The CYP3A5*6(rs10264272) and *7(rs413003343) variants were only present in African Americans. CYP3A4*22(rs35599367) was not found in any of the Asian ancestry samples. We identified seven suggestive variants in the CYP3A4/5 genes associated with dose‐normalized troughs in Native Americans (P= 1.1 × 10−5‐8.8 × 10−6) and one suggestive variant in Asian Americans (P= 5.6 × 10−6). Tacrolimus daily doses and dose‐normalized troughs vary significantly among different ancestry groups. We identified potential new variants important in Asians and Native Americans. Studies with larger populations should be conducted to assess the importance of the identified suggestive variants. Tacrolimus doses and troughs vary between kidney transplant recipients of different ancestries, which is possibly related to new variants identified in recipients of Native American and Asian ancestry.

Genetic variation across the human leukocyte antigen loci is known to influence renal-transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time-points, out to 5 years posttransplantation. We conducted GWAS meta-analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1-year posttransplant. Thirty-two percent of the variability in eGFR at 1-year posttransplant was explained by our model containing clinical covariates (including weights for death/graft-failure), principal components and combined donor-recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables.

Single-center studies have demonstrated regional organ procurement collaboration to reduce travel redundancy and improve procurement efficiency. We studied deceased donor kidney, liver, and pancreas transplants performed in the United States between 2002 and 2014 using the Scientific Registry of Transplant Recipients (SRTR). We compared graft failure (GF), death-censored graft failure (DCGF), and patient death (PD) between organs procured by surgeons from the recipient’s center (transplant procurement team [TPT]) versus surgeons from a different center (NTPT). Primary nonfunction (PNF) was assessed for liver and kidney and delayed graft function (DGF) for kidney using mixed-effects logistic modeling. There were 64 906 liver (61.6% TPT), 118 152 kidney (26.1% TPT), 10 832 simultaneous pancreas kidney (SPK; 56.6% TPT), and 4378 solitary pancreas (SP; 34.0% TPT) transplants. When compared to NTPT, DCGF for organs procured by TPT was significantly less for liver (adjusted HR: 0.93; 95% CI: 0.88-0.98) and marginally significant for kidney (0.97; 0.93-1.00) and SPK (0.90; 0.82-1.00), and not significant for SP (0.98; 0.86 -1.11). DGF for TPT kidney was significantly lower (adjusted OR 0.91; 0.87-0.95). Albeit modest, our findings demonstrate a difference between locally procured organs and those procured by the implanting team. Elucidating the etiology of these differences will enhance regional organ procurement collaboration.

Genetic variation across the human leukocyte antigen loci is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFRat different time‐points, out to 5 years posttransplantation. We conducted GWASmeta‐analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRScalculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFRat 1‐year posttransplant. Thirty‐two percent of the variability in eGFRat 1‐year posttransplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFRposttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRSbeing a significant predictor of eGFRposttransplant, the effect size of common genetic factors is limited compared to clinical variables. Polygenic risk score of nontransplant eGFR is a significant predictor of eGFR at 1 year posttransplant, but the effect size contributed by these common genetic variants is limited compared to that of clinical variables.

Single‐center studies have demonstrated regional organ procurement collaboration to reduce travel redundancy and improve procurement efficiency. We studied deceased donor kidney, liver, and pancreas transplants performed in the United States between 2002 and 2014 using the Scientific Registry of Transplant Recipients (SRTR). We compared graft failure (GF), death‐censored graft failure (DCGF), and patient death (PD) between organs procured by surgeons from the recipient's center (transplant procurement team [TPT]) versus surgeons from a different center (NTPT). Primary nonfunction (PNF) was assessed for liver and kidney and delayed graft function (DGF) for kidney using mixed‐effects logistic modeling. There were 64 906 liver (61.6% TPT), 118 152 kidney (26.1% TPT), 10 832 simultaneous pancreas kidney (SPK; 56.6% TPT), and 4378 solitary pancreas (SP; 34.0% TPT) transplants. When compared to NTPT, DCGF for organs procured by TPT was significantly less for liver (adjusted HR: 0.93; 95% CI: 0.88‐0.98) and marginally significant for kidney (0.97; 0.93‐1.00) and SPK (0.90; 0.82‐1.00), and not significant for SP (0.98; 0.86 ‐1.11). DGF for TPT kidney was significantly lower (adjusted OR 0.91; 0.87‐0.95). Albeit modest, our findings demonstrate a difference between locally procured organs and those procured by the implanting team. Elucidating the etiology of these differences will enhance regional organ procurement collaboration. Organs procured by the implanting transplant team, as compared to those procured by a local surgeon, demonstrate superior outcomes for liver, kidney, and simultaneous pancreas–kidney transplants but not pancreas transplant alone, inciting questions about regional organ procurement collaboration.

An extreme phenotype sampling (EPS) model with targeted next-generation sequencing (NGS) identified genetic variants associated with tacrolimus (Tac) metabolism in subjects from the Deterioration of Kidney Allograft Function (DeKAF) Genomics cohort which included 1,442 European Americans (EA) and 345 African Americans (AA). This study included 48 subjects separated into 4 groups of 12 (AA high, AA low, EA high, EA low). Groups were selected by the extreme phenotype of dose-normalized Tac trough concentrations after adjusting for common genetic variants and clinical factors. NGS spanned > 3 Mb of 28 genes and identified 18,661 genetic variants (3961 previously unknown). A group of 125 deleterious variants, by SIFT analysis, were associated with Tac troughs in EAs (burden test, p= 0.008), CYB5R2was associated with Tac troughs in AAs (SKAT, p= 0.00079). In CYB5R2, rs61733057 (increased allele frequency in AAs) was predicted to disrupt protein function by SIFT and PolyPhen2 analysis. The variants merit further validation.

Supplemental Digital Content is available in the text.

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 CTand 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 m2in 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. Larger nephron size, low nephron number, and nephrosclerosis are each predictive of developing measured GFR, albuminuria, or hypertension after donation.

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 m2in 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.

Supplemental Digital Content is available in the text.

The DeKAF study was developed to better understand the causes of late allograft loss. Preliminary findings from the DeKAF cross-sectional cohort (with follow-up < 20 months) have been published. Herein, we present long-term outcomes in those recipients (mean follow-up ± SD, 6.6 ± 0.7 years). Eligibility included being transplanted prior to October 1, 2005; serum creatinine ≤ 2.0 mg/dL on January 1, 2006; and subsequently developing new-onset graft dysfunction leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Histologic findings and DSA were studied in relation to postbiopsy outcomes. Long-term follow-up confirms and expands the preliminary results of each of 3 studies: (1) increasing inflammation in area of atrophy (irrespective of inflammation in nonscarred areas [Banff i]) was associated with increasingly worse postbiopsy death-censored graft survival; (2) hierarchical analysis based on Banff scores defined clusters (entities) that differed in long-term death-censored graft survival; and (3) C4d−/DSA− recipients had significantly better (and C4d+/DSA+ worse) death-censored graft survival than other groups. C4d+/DSA- and C4d−/DSA+ had similar intermediate death-censored graft survival. Clinical and histologic findings at the time of new-onset graft dysfunction define high- vs low-risk groups for long-term death-censored graft survival, even years posttransplant. These findings can help differentiate groups for potential intervention studies.

The DeKAFstudy was developed to better understand the causes of late allograft loss. Preliminary findings from the DeKAFcross‐sectional cohort (with follow‐up < 20 months) have been published. Herein, we present long‐term outcomes in those recipients (mean follow‐up ± SD, 6.6 ± 0.7 years). Eligibility included being transplanted prior to October 1, 2005; serum creatinine ≤ 2.0 mg/dLon January 1, 2006; and subsequently developing new‐onset graft dysfunction leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Histologic findings and DSAwere studied in relation to postbiopsy outcomes. Long‐term follow‐up confirms and expands the preliminary results of each of 3 studies: (1) increasing inflammation in area of atrophy (irrespective of inflammation in nonscarred areas [Banff i]) was associated with increasingly worse postbiopsy death‐censored graft survival; (2) hierarchical analysis based on Banff scores defined clusters (entities) that differed in long‐term death‐censored graft survival; and (3) C4d−/DSA− recipients had significantly better (and C4d+/DSA+ worse) death‐censored graft survival than other groups. C4d+/DSA‐ and C4d−/DSA+ had similar intermediate death‐censored graft survival. Clinical and histologic findings at the time of new‐onset graft dysfunction define high‐ vs low‐risk groups for long‐term death‐censored graft survival, even years posttransplant. These findings can help differentiate groups for potential intervention studies. A long‐term follow‐up of previously reported findings from the DeKAF cross‐sectional cohort, in which allograft biopsies were done for graft dysfunction, continues to show that inflammation in areas of atrophy is associated with increased post–allograft biopsy graft loss, hierarchical cluster analysis based on Banff scores defines clusters that differ in graft survival, and C4d+/ DSA+ biopsies are associated with increased graft loss than C4d‐/DSA‐ biopsies.

Short‐term studies have demonstrated that nondirected donors (NDDs) have psychosocial outcomes that are similar to donors who donate directly, but long‐term studies have not been done. NDDs at our center were surveyed regarding motivation; support during donation; stress related to donation; regret; financial resources used for donation; preferences about communication with the recipient; and cost reimbursement. Of 100 NDDs who donated at our center in the last 20 years, 95 remain in contact with us, and 77 responded to our survey (mean ± standard deviation [SD] 6.7 ± 4 years postdonation). The most common motivation for donation was the desire to help another (99%). Many NDDs received support from family, friends, and employers. NDDs voiced stress about the possibility of recipient kidney rejection, physical consequences to themselves, and financial burden. Only one donor expressed regret. Almost half wanted some recipient information at donation; 61% preferred routine recipient status updates; 56% believed meeting the recipient should occur at any mutually agreeable time; and 55% endorsed reimbursement for expenses. Stressors for NDDs are analogous to those of directed donors; NDDs prefer having some information about the recipient and prefer to be given a choice regarding the timing for communication with the recipient. NDDs supported donation being financially neutral. Long‐term psychosocial outcomes after nondirected donation: A single‐center experience

Short-term studies have demonstrated that nondirected donors (NDDs) have psychosocial outcomes that are similar to donors who donate directly, but long-term studies have not been done. NDDs at our center were surveyed regarding motivation; support during donation; stress related to donation; regret; financial resources used for donation; preferences about communication with the recipient; and cost reimbursement. Of 100 NDDs who donated at our center in the last 20 years, 95 remain in contact with us, and 77 responded to our survey (mean ± standard deviation [SD] 6.7 ± 4 years postdonation). The most common motivation for donation was the desire to help another (99%). Many NDDs received support from family, friends, and employers. NDDs voiced stress about the possibility of recipient kidney rejection, physical consequences to themselves, and financial burden. Only one donor expressed regret. Almost half wanted some recipient information at donation; 61% preferred routine recipient status updates; 56% believed meeting the recipient should occur at any mutually agreeable time; and 55% endorsed reimbursement for expenses. Stressors for NDDs are analogous to those of directed donors; NDDs prefer having some information about the recipient and prefer to be given a choice regarding the timing for communication with the recipient. NDDs supported donation being financially neutral.

To determine long-term trends in the incidence of hypertension.

In the authors' multivariable models, the recent changes in the kidney allocation system is associated with increased cold ischemia time, delayed graft function rates, length of stay, and transplant related costs.

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. Increased length of time to return to work is a significant predictor of financial burden, with those in manual/skilled trade occupations, compared with all other occupations, experiencing greater financial burden for each week away from work.

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.

Nearly 2 decades after living kidney donation, postdonation GFR declines at a rate similar to that seen in the general population and in one-third GFR continues to increase.

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.