Metformin use in the first year after kidney transplant,correlates, and associated outcomes in diabetic transplant recipients: A retrospective analysis of integrated registry and pharmacy claims data

While guidelines support metformin as a therapeutic option for diabetic patients with mild‐to‐moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008‐2015). Associations (adjusted hazard ratio, _{95% LCL}aHR_{95% UCL}) of diabetes regimens (with and excluding metformin) in the first year post‐transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post‐transplant; most also received diabetes comedications. Compared to those who received insulin‐based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin‐based regimens were associated with significantly lower adjusted all‐cause (aHR _0.180.41_0.91), malignancy‐related (aHR _0.450.45_0.99), and infection‐related (aHR _0.120.32_0.85) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin‐based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.     

Hydroxychloroquine and maintenance immunosuppression use in kidney transplant recipients: Analysis of linked US registry and claims data

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008–2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,_1.121.96_3.42, p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,_1.001.81_3.29, p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,_1.021.54_2.31, p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,_1.031.31_1.68, p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.     

Readability,content analysis,and racial/ethnic diversity of online living kidney donation information

More than three‐fourths of adults in the USA use the Internet to access health‐related information. Adults exploring the possibility of living donation should have access to online content that is readable and comprehensive. We simulated a search of online information about living kidney donation and evaluated readability, topics covered, and racial/ethnic diversity of 21 websites meeting inclusion criteria (eg, hosted by a nonprofit or patient advocacy organization, English content, based in USA). Using standard readability metrics, 62% of sites were classified as “Difficult to read” and none achieved the recommended reading level of sixth grade. On average, websites covered 18.5 (62%) of 30 recommended information topics (range: 7 to 28) and only 2.1 (23%) of 9 racial/ethnic diversity items (range: 0 to 6). Overall, the most common nonprofit or patient advocacy organization websites do not meet the readability standards established by the National Institutes of Health and the American Medical Association, many lack fundamental information about living kidney donation, and most are not racially/ethnically diverse. We encourage the transplant community to consider playing a more active role in improving the overall quality of online information disseminated to the general public. Further, there is a need to more critically examine the accuracy of online living donation content in future investigations.     

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.     

Accidental transplantation of a kidney with a cystic renal cell carcinoma following living donation: management and 1 yr follow-up

Transmission of cancer is a fatal risk in organ transplantation. We present a case of incidental renal carcinoma in a kidney obtained from a living donor. A 56-yr-old father was evaluated for donation for his 28-yr-old daughter. An MRT scan revealed two cysts in the right kidney. Right-sided donor nephrectomy and subsequent transplantation was performed. The wall of the prominent cyst was partially excised prior to transplantation. Histology revealed a high-grade renal clear cell carcinoma 10 d after transplantation. Following careful evaluation the recipient underwent partial nephrectomy. Immunosuppression was switched to rapamune. The graft function remained stable. Donor and recipient are without evidence of tumor recurrence 1 yr after transplantation. Our policy to obtain the kidney presenting anatomical variations proved to be beneficial for the donor. In case of transmission of cancer partial resection preserving graft function might be justified.     

Antidepressant medication use before and after kidney transplant: implications for outcomes – a retrospective study

We examined a novel database wherein national US transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008–2015) to characterize antidepressant use before and after kidney transplantation, and associations [adjusted hazard ratio (aHR) 95% CI] with death and graft failure. Among 72 054 recipients, 12.6% filled antidepressant medications in the year before transplant, and use was more common among women and patients who were white, unemployed, and had limited functional status. Pre‐transplant antidepressant use was associated with 39% higher 1‐year mortality (aHR 1.39, 95% CI 1.18–1.64) and 15% higher all‐cause graft loss risk (aHR 1.15, 95% CI 1.02–1.30). More than 50% of patients who filled antidepressants pre‐transplant continued fill post‐transplant. Antidepressant use in the first year after transplant was associated with twofold higher risk of death (aHR 1.94, 95% CI 1.60–2.35), 38% higher risk of death‐censored graft failure, and 61% higher risk of all‐cause graft failure in the subsequent year. Pre‐listing antidepressant use was also associated with increased mortality, but transplantation conferred a survival benefit regardless of prelisting antidepressant use status. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.     

Weight gain after kidney donation: Association with increased risks of type 2 diabetes and hypertension

In the general population, obesity is associated with an increased risk of developing hypertension (HTN), type 2 diabetes mellitus (DM), and end‐stage renal disease (ESRD). Therefore, most transplant centers have a body mass index (BMI) threshold for accepting living kidney donors. But there have been no studies of postdonation weight gain trends and any associated risks. We tracked serial BMIs in 940 donors for a median (IQ range) follow‐up of 22.3 (15.4‐35.8) years. We studied the impact of postdonation weight gain in a model adjusted for family history of HTN or DM. Donor characteristics included age, sex, smoking, fasting blood glucose, eGFR, systolic and diastolic BP, and BMI at time of donation and time postdonation. Postdonation weight gain was associated with a significant increase in the relative risk of developing HTN RR 1.93 (95% CI 1.51‐2.46) (P < 0.001) and/or DM RR 4.18 (95% CI 2.05‐8.5) (P < 0.0001), but not (to date) cardiovascular disease (CVD), reduced eGFR or death. Like the general population, donors gained weight as they aged; a higher BMI was associated with higher incidence of DM and HTN. Postdonation care should include ongoing counseling on the risks of substantial weight gain.     

Associations of perceived information adequacy and knowledge with pursuit of live donor kidney transplants and living donor inquiries among African American transplant candidates

We studied associations between perceived adequacy of live donor kidney transplant (LDKT) information or knowledge with pursuit of LDKT or receipt of live donor inquiries among 300 African American kidney transplant candidates. Participants reported via questionnaire how informed or knowledgeable they felt regarding LDKT. Participants also reported their pursuit of LDKT, categorized as “low” (no discussion with family or friends about LDKT and no identified donor), “intermediate” (discussed LDKT with family but no identified donor) or “high” (discussed LDKT with family and identified a potential donor). We reviewed participants' electronic health records to identify potential donors' transplant center inquiries on participants' behalves. A minority of participants reported they felt “very” or “extremely” well informed about LDKT (39%) or had “a great deal” of LDKT knowledge (38%). Participants perceiving themselves as “very” or “extremely” (vs “not” or “slightly”) well informed about LDKT had statistically significantly greater odds of intermediate or high (vs low) pursuit of LDKT (odds ratio [95% confidence interval] 2.71 [1.02-7.17]). Perceived LDKT knowledge was not associated with pursuit of LDKT. Neither perceived information adequacy nor knowledge was associated with living donor inquiries. Efforts to better understand the role of education in the pursuit of LDKT among African American transplant candidates are needed.     

Death of recipients after kidney living donation triples donors’ risk of dropping out from follow‐up: a retrospective study

Although kidney transplantation from the donation of a living donor is a safe treatment for end‐stage renal disease, inferences about safety of living kidney donors might be biased by an informative censoring caused by the noninclusion of a substantial percentage of donors lost to follow‐up. With the aim of assessing the presence of a potential informative censoring in living kidney donation outcomes of Catalan donors for a period of 12 years, 573 donors followed and lost to follow‐up were compared. Losses of follow‐up over time were also assessed by univariate and multivariate survival analysis, along with Cox regression. Younger and older ages, and the death of their recipient differentiated those donors who were lost to follow‐up over time. The risk of dropping out from follow‐up was more than twofold for the youngest and oldest donors, and almost threefold for those donors whose recipient died. Results of studies on postdonation outcomes of Catalan living kidney donors might have overlooked older and younger cases, and, remarkably, a percentage of donors whose recipient died. If these donors showed a higher incidence of psychological problems, conclusions about living donors’ safety might be compromised thus emphasizing the necessity of sustained surveillance of donors and prompt identification of these cases.     

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.     

The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m²) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.     

Causes and timing of end‐stage renal disease after living kidney donation

End‐stage renal disease (ESRD) is a risk after kidney donation. We sought, in a large cohort of kidney donors, to determine the causes of donor ESRD, the interval from donation to ESRD, the role of the donor/recipient relationship, and the trajectory of the estimated GFR (eGFR) from donation to ESRD. From 1/1/1963 thru 12/31/2015, 4030 individuals underwent living donor nephrectomy at our center, as well as ascertainment of ESRD status. Of these, 39 developed ESRD (mean age ± standard deviation [SD] at ESRD, 62.4 ± 14.1 years; mean interval between donation and ESRD, 27.1 ± 9.8 years). Donors developing ESRD were more likely to be male, as well as smokers, and younger at donation, and to have donated to a first‐degree relative. Of donors with a known cause of ESRD (n = 25), 48% was due to diabetes and/or hypertension; only 2 from a disease that would have affected 1 kidney (cancer). Of those 25 with an ascertainable ESRD cause, 4 shared a similar etiology of ESRD with their recipient. Almost universally, thechange of eGFR over time was stable, until new‐onset disease (kidney or systemic). Knowledge of factors contributing to ESRD after living kidney donation can improve donor selection and counseling, as well as long‐term postdonation care.     

Pre‐ and postdonation kidney function in donors of a kidney paired donation with unique criteria for donor glomerular filtration rate – a longitudinal cohort analysis

Baseline predonation estimated GFR (eGFR) appears to predict the risk of postdonation chronic kidney disease in live donors. New KIDGO guidelines recommend an eGFR ≥90 ml/min/1.73 m² as an acceptable level of glomerular filtration rate (GFR) for kidney donation. In the Australian Paired Kidney Exchange (AKX) program, all donors with a raw measured GFR (mGFR) ≥80 ml/min are deemed suitable for donation, but the significance of this selection indicator is unclear. We analysed the first 129 live donors in the AKX program with at least 1‐year follow‐up linking records in the AKX database and ANZDATA. There were 73 male and 56 female donors; mean (±SD) age was 53 ± 11 years. Predonation eGFR was 94 ± 13 ml/min/1.73 m², mGFR 99 ± 17 ml/min/1.73 m² and raw mGFR 108 ± 18 ml/min. Baseline eGFR was <80 ml/min/1.73 m² in 19 donors, and <90 ml/min/1.73 m² in 42 donors. At 1 year postdonation eGFR was 68 ± 15 ml/min/1.73 m² and the predicted eGFR at 30 years postdonation was on average 50 (29–83) ml/min/1.73 m². The hypothetical mean age at end‐stage kidney disease was estimated to be 145 (95% CI 120–263) years. Over 30% of AKX live donors would have been excluded from donation using KDIGO guidelines. Using AKX donor guidelines, the majority of donors with predicted eGFR <30 ml/min/1.73 m² 30‐year postdonation were aged ≥50 years. Long‐term outcome data on AKX donors with low eGFR will need careful monitoring.     

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7–14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.