Publications by authors named "Fawaz Al Ammary"

25 Publications

  • Page 1 of 1

Long-term kidney function and survival in recipients of allografts from living kidney donors with hypertension: a national cohort study.

Transpl Int 2021 Jun 15. Epub 2021 Jun 15.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Allografts from living kidney donors with hypertension may carry subclinical kidney disease from the donor to the recipient and, thus, lead to adverse recipient outcomes. We examined eGFR trajectories and all-cause allograft failure in recipients from donors with versus without hypertension, using mixed-linear and Cox regression models stratified by donor age. We studied a US cohort from 1/1/2005 to 6/30/2017; 49 990 recipients of allografts from younger (<50 years old) donors including 597 with donor hypertension and 21 130 recipients of allografts from older (≥50 years old) donors including 1441 with donor hypertension. Donor hypertension was defined as documented predonation use of antihypertensive therapy. Among recipients from younger donors with versus without hypertension, the annual eGFR decline was -1.03 versus -0.53 ml/min/m (P = 0.002); 13-year allograft survival was 49.7% vs. 59.0% (adjusted allograft failure hazard ratio [aHR] 1.23; 95% CI 1.05-1.43; P = 0.009). Among recipients from older donors with versus without hypertension, the annual eGFR decline was -0.67 versus -0.66 ml/min/m (P = 0.9); 13-year allograft survival was 48.6% versus 52.6% (aHR 1.05; 95% CI 0.94-1.17; P = 0.4). In secondary analyses, our inferences remained similar for risk of death-censored allograft failure and mortality. Hypertension in younger, but not older, living kidney donors is associated with worse recipient outcomes.
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http://dx.doi.org/10.1111/tri.13947DOI Listing
June 2021

The Tangible Benefits of Living Donation: Results of a Qualitative Study of Living Kidney Donors.

Transplant Direct 2020 Dec 10;6(12):e626. Epub 2020 Nov 10.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

The framework currently used for living kidney donor selection is based on estimation of acceptable donor risk, under the premise that benefits are only experienced by the recipient. However, some interdependent donors might experience tangible benefits from donation that cannot be considered in the current framework (ie, benefits experienced directly by the donor that improve their daily life, well-being, or livelihood).

Methods: We conducted semistructured interviews with 56 living kidney donors regarding benefits experienced from donation. Using a qualitative descriptive and constant comparative approach, themes were derived inductively from interview transcripts by 2 independent coders; differences in coding were reconciled by consensus.

Results: Of 56 participants, 30 were in interdependent relationships with their recipients (shared household and/or significant caregiving responsibilities). Tangible benefits identified by participants fell into 3 major categories: health and wellness benefits, time and financial benefits, and interpersonal benefits. Participants described motivations to donate a kidney based on a more nuanced understanding of the benefits of donation than accounted for by the current "acceptable risk" paradigm.

Discussion: Tangible benefits for interdependent donors may shift the "acceptable risk" paradigm (where no benefit is assumed) of kidney donor evaluation to a risk/benefit paradigm more consistent with other surgical decision-making.
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http://dx.doi.org/10.1097/TXD.0000000000001068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665258PMC
December 2020

Health Care Policy and Regulatory Challenges for Adoption of Telemedicine in Kidney Transplantation.

Am J Kidney Dis 2021 05 7;77(5):773-776. Epub 2020 Nov 7.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Acute and Chronic Care, Johns Hopkins School of Nursing, Baltimore, MD.

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http://dx.doi.org/10.1053/j.ajkd.2020.09.013DOI Listing
May 2021

Financial incentives versus standard of care to improve patient compliance with live kidney donor follow-up: protocol for a multi-center, parallel-group randomized controlled trial.

BMC Nephrol 2020 11 9;21(1):465. Epub 2020 Nov 9.

Department of Surgery, Division of Transplantation, Johns Hopkins University School of Medicine, 2000 E. Monument Street, Baltimore, MD, 21205, USA.

Background: Live kidney donors (LKDs) account for nearly a third of kidney transplants in the United States. While donor nephrectomy poses minimal post-surgical risk, LKDs face an elevated adjusted risk of developing chronic diseases such as hypertension, diabetes, and end-stage renal disease. Routine screening presents an opportunity for the early detection and management of chronic conditions. Transplant hospital reporting requirements mandate the submission of laboratory and clinical data at 6-months, 1-year, and 2-years after kidney donation, but less than 50% of hospitals are able to comply. Strategies to increase patient engagement in follow-up efforts while minimizing administrative burden are needed. We seek to evaluate the effectiveness of using small financial incentives to promote patient compliance with LKD follow-up.

Methods/design: We are conducting a two-arm randomized controlled trial (RCT) of patients who undergo live donor nephrectomy at The Johns Hopkins Hospital Comprehensive Transplant Center (MDJH) and the University of Maryland Medical Center Transplant Center (MDUM). Eligible donors will be recruited in-person at their first post-surgical clinic visit or over the phone. We will use block randomization to assign LKDs to the intervention ($25 gift card at each follow-up visit) or control arm (current standard of care). Follow-up compliance will be tracked over time. The primary outcome will be complete (all components addressed) and timely (60 days before or after expected visit date), submission of LKD follow-up data at required 6-month, 1-year, and 2-year time points. The secondary outcome will be transplant hospital-level compliance with federal reporting requirements at each visit. Rates will be compared between the two arms following the intention-to-treat principle.

Discussion: Small financial incentivization might increase patient compliance in the context of LKD follow-up, without placing undue administrative burden on transplant providers. The findings of this RCT will inform potential center- and national-level initiatives to provide all LKDs with small financial incentives to promote engagement with post-donation monitoring efforts.

Trial Registration: ClinicalTrials.gov number: NCT03090646 Date of registration: March 2, 2017 Sponsors: Johns Hopkins University, University of Maryland Medical Center Funding: The Living Legacy Foundation of Maryland.
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http://dx.doi.org/10.1186/s12882-020-02117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654057PMC
November 2020

Evolving Impact of COVID-19 on Transplant Center Practices and Policies in the United States.

Clin Transplant 2020 12 28;34(12):e14086. Epub 2020 Sep 28.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.
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http://dx.doi.org/10.1111/ctr.14086DOI Listing
December 2020

Care of international living kidney donor candidates in the United States: A survey of contemporary experience, practice, and challenges.

Clin Transplant 2020 11 19;34(11):e14064. Epub 2020 Oct 19.

Cedars-Sinai Comprehensive Transplant Center, Los Angeles, California, USA.

The evaluation and care of non-US citizen, non-US residents who wish to come to the United States to serve as international living kidney donors (ILKDs) can pose unique challenges. We surveyed US transplant programs to better understand practices related to ILKD care. We distributed the survey by email and professional society list-servs (Fall 2018, assessing 2017 experience). Eighty-five programs responded (36.8% program response rate), of which 80 considered ILKD candidates. Only 18 programs had written protocols for ILKD evaluation. Programs had a median of 3 (range: 0,75) ILKD candidates who initiated contact during the year, from origin countries spanning 6 continents. Fewer (median: 1, range: 0,25) were approved for donation. Program-reported reasons for not completing ILKD evaluations included visa barriers (58.6%), inability to complete evaluation (34.3%), concerns regarding follow-up (31.4%) or other healthcare access (28.6%), and financial impacts (21.4%). Programs that did not evaluate ILKDs reported similar concerns. Staff time required to evaluate ILKDs was estimated as 1.5-to-3-times (47.9%) or >3-times (32.9%) that needed for domestic candidates. Among programs accepting ILKDs, on average 55% reported successful completion of 1-year follow-up. ILKD evaluation is a resource-intensive process with variable outcomes. Planning and commitment are necessary to care for this unique candidate group.
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http://dx.doi.org/10.1111/ctr.14064DOI Listing
November 2020

Telemedicine in the Care of Kidney Transplant Recipients With Coronavirus Disease 2019: Case Reports.

Transplant Proc 2020 Nov 16;52(9):2620-2625. Epub 2020 Jul 16.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

Kidney transplant recipients who develop symptoms consistent with coronavirus disease 2019 (COVID-19) are bringing unique challenges to health care professionals. Telemedicine has surged dramatically since the pandemic in effort to maintain patient care and reduce the risk of COVID-19 exposure to patients, health care workers, and the public. Herein we present reports of 3 kidney transplant recipients with COVID-19 who were managed using telemedicine via synchronous video visits integrated with an electronic medical record system, from home to inpatient settings. We demonstrate how telemedicine helped assess, diagnose, triage, and treat patients with COVID-19 while avoiding a visit to an emergency department or outpatient clinic. While there is limited information about the duration of viral shedding for immunosuppressed patients, our findings underscore the importance of using telemedicine in the follow-up care for kidney transplant recipients with COVID-19 who have recovered from symptoms but might have persistently positive nucleic acid tests. Our experience emphasizes the opportunities of telemedicine in the management of kidney transplant recipients with COVID-19 and in the maintenance of uninterrupted follow-up care for such immunosuppressed patients with prolonged viral shedding. Telemedicine may help increase access to care for kidney transplant recipients during and beyond the pandemic as it offers a prompt, safe, and convenient platform in the delivery of care for these patients. Yet, to advance the practice of telemedicine in the field of kidney transplantation, barriers to increasing the widespread implementation of telemedicine should be removed, and research studies are needed to assess the effectiveness of telemedicine in the care of kidney transplant recipients.
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http://dx.doi.org/10.1016/j.transproceed.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365092PMC
November 2020

Kidney Dyads: Caregiver Burden and Relationship Strain Among Partners of Dialysis and Transplant Patients.

Transplant Direct 2020 Jul 8;6(7):e566. Epub 2020 Jun 8.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Caring for dialysis patients is difficult, and this burden often falls on a spouse or cohabiting partner (henceforth referred to as caregiver-partners). At the same time, these caregiver-partners often come forward as potential living kidney donors for their loved ones who are on dialysis (henceforth referred to as patient-partners). Caregiver-partners may experience tangible benefits to their well-being when their patient-partner undergoes transplantation, yet this is seldom formally considered when evaluating caregiver-partners as potential donors.

Methods: To quantify these potential benefits, we surveyed caregiver-partners of dialysis patients and kidney transplant (KT) recipients (N = 99) at KT evaluation or post-KT. Using validated tools, we assessed relationship satisfaction and caregiver burden before or after their patient-partner's dialysis initiation and before or after their patient-partner's KT.

Results: Caregiver-partners reported increases in specific measures of caregiver burden ( = 0.03) and stress ( = 0.01) and decreases in social life ( = 0.02) and sexual relations ( < 0.01) after their patient-partner initiated dialysis. However, after their patient-partner underwent KT, caregiver-partners reported improvements in specific measures of caregiver burden ( = 0.03), personal time ( < 0.01), social life ( = 0.01), stress ( = 0.02), sexual relations ( < 0.01), and overall quality of life ( = 0.03). These improvements were of sufficient impact that caregiver-partners reported similar levels of caregiver burden after their patient-partner's KT as before their patient-partner initiated dialysis ( = 0.3).

Conclusions: These benefits in caregiver burden and relationship quality support special consideration for spouses and partners in risk-assessment of potential kidney donors, particularly those with risk profiles slightly exceeding center thresholds.
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http://dx.doi.org/10.1097/TXD.0000000000000998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339348PMC
July 2020

Early steroid withdrawal in HIV-infected kidney transplant recipients: Utilization and outcomes.

Am J Transplant 2021 02 13;21(2):717-726. Epub 2020 Aug 13.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR: 1.61 , P = .04) and over the study period (aHR: 1.39 , P = .03), without difference in death-censored graft failure (aHR 0.91 , P = .33) or mortality (aHR: 1.15 , P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable.
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http://dx.doi.org/10.1111/ajt.16195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927911PMC
February 2021

The first increase in live kidney donation in the United States in 15 years.

Am J Transplant 2020 12 17;20(12):3590-3598. Epub 2020 Jul 17.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The first sustained increase in live kidney donation in the United States in 15 years was observed from 2017 to 2019. To help sustain this surge, we studied 35 900 donors (70.3% white, 14.5% Hispanic, 9.3% black, 4.4% Asian) to understand the increase in 2017-2019 vs 2014-2016 using Poisson regression. Among biologically related donors aged <35, 35-49, and ≥50 years, the number of donors did not change across race/ethnicity but increased by 38% and 29% for Hispanic and black ≥50. Among unrelated donors <35, 35-49, and ≥50, white donors increased by 18%, 14%, and 27%; Hispanic donors <35 did not change but increased by 22% and 35% for 35-49 and ≥50; black donors <35 declined by 23% and did not change for 35-49 and ≥50; Asian donors did not change. Among kidney paired donors <35, 35-49, and ≥50, white donors increased by 42%, 50%, and 68%; Hispanic donors <35 and 35-49 increased by 36% and 55% and did not change for ≥50; black donors did not change; Asian donors <35 did not change but increased by 107% and 82% for 35-49 and ≥50. The increase in donation was driven predominantly by unrelated and paired white donors. Donation among unrelated black individuals should be promoted.
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http://dx.doi.org/10.1111/ajt.16136DOI Listing
December 2020

Antithymocyte Globulin Versus Interleukin-2 Receptor Antagonist in Kidney Transplant Recipients With Hepatitis C Virus.

Transplantation 2020 06;104(6):1294-1303

Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD.

Background: Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that antithymocyte globulin (ATG) might increase HCV-related complications.

Methods: Using Scientific Registry of Transplant Recipients and Medicare claims data, we studied 6780 HCV+ and 139 681 HCV- KT recipients in 1999-2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (versus IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (versus IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression.

Results: HCV+ recipients were less likely to receive ATG than HCV- recipients (living donor, adjusted odds ratio [aOR] = 0.640.770.91; deceased donor, aOR = 0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-y crude incidence = 11.6% versus 12.6%; aOR = 0.680.820.99). There was no significant difference in the risks of graft failure (adjusted hazard ratio [aHR] = 0.861.001.17), death (aHR = 0.850.951.07), liver transplant registration (aHR = 0.580.971.61), and cirrhosis (aHR = 0.730.921.16).

Conclusions: Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.
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http://dx.doi.org/10.1097/TP.0000000000002959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534413PMC
June 2020

Long-term renal function in living kidney donors with simple renal cysts: A retrospective cohort study.

Clin Transplant 2020 09 13;34(9):e13905. Epub 2020 Aug 13.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Simple (Bosniak I) renal cysts are considered acceptable in living kidney donor selection in terms of cancer risk. However, they tend to increase in number and size over time and might compromise renal function in donors. To clarify their implications for long-term renal function, we characterized the prevalence of renal cysts in 454 individuals who donated at our center from 2000 to 2007. We estimated the association between the presence of cysts in the kidney remaining after nephrectomy (ie, retained cysts) and postdonation eGFR trajectory using mixed-effects linear regression. Donors with retained cysts (N = 86) were older (P < .001) and had slightly lower predonation eGFR (median 94 vs 98 mL/min/1.73 m , P < .01) than those without cysts. Over a median 7.8 years, donors with retained cysts had lower baseline eGFR ( -5.6  mL/min/1.73 m , P < .01) but similar yearly change in eGFR ( 0.02  mL/min/1.73 m , P = .2) compared to those without retained cysts. Adjusting for predonation characteristics, there was no difference in baseline eGFR (P = .6) or yearly change in eGFR (P > .9). There continued to be no evidence of an association when we considered retained cyst(s) ≥10 mm or multiple retained cysts (all P > .05). These findings reaffirm current practices of accepting candidates with simple renal cysts for donor nephrectomy.
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http://dx.doi.org/10.1111/ctr.13905DOI Listing
September 2020

Association Between Living Kidney Donor Postdonation Hypertension and Recipient Graft Failure.

Transplantation 2020 03;104(3):583-590

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Recipients of kidneys from living donors who subsequently develop end-stage renal disease (ESRD) also have higher graft failure, suggesting the 2 donor kidneys share risk factors that could inform recipient outcomes. Given that donor ESRD is rare, an earlier and more common postdonation outcome could serve as a surrogate to individualize counseling and management for recipients. Hypertension is a frequent event before donor ESRD; thus, early postdonation hypertension might indicate higher risk of graft failure.

Methods: We studied Scientific Registry of Transplant Recipients data to quantify the association between early postdonation hypertension and recipient graft failure using propensity score-weighted Cox proportional hazards regression. We also examined the association between postdonation systolic blood pressure and graft failure.

Results: Of 37 901 recipients, 2.4% had a donor who developed hypertension within 2 years postdonation. Controlling for donor and recipient characteristics, recipients whose donors developed hypertension had no higher risk for graft failure (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.85-1.25, P = 0.72). This was consistent among subgroups of recipients at higher risk for adverse outcomes due to hyperfiltration: African American recipients (aHR 1.10, 95% CI 0.70-1.73, P = 0.68) and those with ESRD caused by hypertension (aHR 1.10, 95% CI 0.65-1.85, P = 0.73) or diabetes (aHR 0.80, 95% CI 0.56-1.13, P = 0.20). However, graft failure was associated with postdonation systolic blood pressure (per 10 mm Hg, aHR 1.05, 95% CI 1.03-1.08, P < 0.001).

Conclusions: Although postdonation systolic blood pressure is associated with graft failure, the reported diagnosis of hypertension as determined by the requirement for blood pressure treatment early postdonation did not portend a higher risk of recipient graft failure in the same way as eventual postdonation ESRD.
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http://dx.doi.org/10.1097/TP.0000000000002832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960370PMC
March 2020

Evaluation and care of international living kidney donor candidates: Strategies for addressing common considerations and challenges.

Clin Transplant 2020 03 29;34(3):e13792. Epub 2020 Feb 29.

Saint Louis University Center for Abdominal Transplantation, St. Louis, Missouri.

End-stage kidney disease patients in the United States may have family members or friends who are not US citizens or residents but are willing to serve as their living kidney donor in the United States ("international donors"). In July 2017, the American Society for Transplantation (AST) Live Donor Community of Practice (LDCOP) convened a multidisciplinary workgroup of experts in living donation care, including coordinators, social workers, donor advocates, administrators, and physicians, to evaluate educational gaps related to the evaluation and care of international donors. The evaluation of international living donor candidates is a resource-intensive process that raises key considerations for assessing risk of exploitation/inducement and addressing communication barriers, logistics barriers, and access to care in their home country. Through consensus-building discussions, we developed recommendations related to: (a) establishing program guidelines for international donor candidate evaluation and selection; (b) initial screening; (c) logistics planning; (d) comprehensive evaluation; and (e) postdonation care and follow-up. These recommendations are not intended to direct formal policy, but rather as guidance to help programs more efficiently and effectively structure and execute evaluations and care coordination. We also offer recommendations for research and advocacy to optimize the care of this unique group of living donors.
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http://dx.doi.org/10.1111/ctr.13792DOI Listing
March 2020

Association of Early Postdonation Renal Function With Subsequent Risk of End-Stage Renal Disease in Living Kidney Donors.

JAMA Surg 2020 03 18;155(3):e195472. Epub 2020 Mar 18.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Living kidney donation is associated with increased long-term risk of end-stage renal disease (ESRD). An early postdonation marker of ESRD risk could improve postdonation risk assessment and counseling for kidney donors and allow early intervention for donors at increased risk.

Objective: To determine the association between renal function in the first 6 months postdonation and subsequent risk of ESRD in kidney donors.

Design, Setting, And Participants: This secondary analysis of a prospective national cohort uses a population-based registry of all living kidney donors in the United States between October 26, 1999, and January 1, 2018, with follow-up through December 31, 2018. All kidney donors who had donated in the date range and had serum creatinine measured at 6 months (±3 months) postdonation were included.

Exposures: Renal function as measured by estimated glomerular filtration rate 6 months after donation (eGFR6).

Main Outcomes And Measures: End-stage renal disease, ascertained via linkage to Centers for Medicare & Medicaid Services data.

Results: A total of 71 468 living kidney donors were included (of 109 065 total donors over this period). Their median (interquartile range) eGFR6 was 63 (54-74) mL/min/1.73 m2. Cumulative incidence of ESRD at 15 years postdonation ranged from 11.7 donors per 10 000 donors with eGFR6 values greater than 70 mL/min/1.73 m2 to 33.1 donors per 10 000 donors with eGFR6 values of 50 mL/min/1.73 m2 or less. Adjusting for age, race, sex, body mass index, and biological relationship, every 10 mL/min/1.73 m2 reduction in eGFR6 was associated with a 28% increased risk of ESRD (adjusted hazard ratio, 1.28 [95% CI, 1.06-1.54]; P = .009). The association between predonation eGFR and ESRD was not significant and was fully mediated by eGFR6 (adjusted hazard ratio, 1.00 [95% CI, 0.86-1.17]; P = .97). The postdonation eGFR value was a better marker of ESRD than eGFR decline after donation or the ratio of eGFR6 to predonation eGFR, as determined by the Akaike information criterion (in which a lower value indicates a better model fit; eGFR6, 1495.61; predonation eGFR - eGFR6, 1503.58; eGFR6 / predonation eGFR, 1502.30).

Conclusions And Relevance: In this study, there was an independent association of eGFR6 with subsequent ESRD risk in living kidney donors, even after adjusting for predonation characteristics. The findings support measurement of early postdonation serum creatinine monitoring in living kidney donors, and the use of these data to help identify donors who might need more careful surveillance and early intervention.
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http://dx.doi.org/10.1001/jamasurg.2019.5472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990748PMC
March 2020

Donor-Recipient Relationship and Risk of ESKD in Live Kidney Donors of Varied Racial Groups.

Am J Kidney Dis 2020 03 12;75(3):333-341. Epub 2019 Nov 12.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD; Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN.

Rationale & Objective: Risk factors for kidney failure are the basis of live kidney donor candidate evaluation. We quantified risk for end-stage kidney disease (ESKD) by the biological relationship of the donor to the recipient, a risk factor that is not addressed by current clinical practice guidelines.

Study Design: Retrospective cohort study.

Setting & Participants: A cohort of 143,750 US kidney donors between 1987 and 2017.

Exposure: Biological relationship of donor and recipient.

Outcome: ESKD. Donors' records were linked to national dialysis and transplantation registries to ascertain development of the outcome.

Analytic Approach: Donors were observed over a median of 12 (interquartile range, 6-18; maximum, 30) years. Survival analysis methods that account for the competing risk for death were used.

Results: Risk for ESKD varied by orders of magnitude across donor-recipient relationship categories. For Asian donors, risks compared with unrelated donors were 259.4-fold greater for identical twins (95% CI, 19.5-3445.6), 4.7-fold greater for full siblings (95% CI, 0.5-41.0), 3.5-fold greater for offspring (95% CI, 0.6-39.5), 1.0 for parents, and 1.0 for half-sibling or other biological relatives. For black donors, risks were 22.5-fold greater for identical twin donors (95% CI, 4.7-107.0), 4.1-fold for full siblings (95% CI, 2.1-7.8), 2.7-fold for offspring (95% CI, 1.4-5.4), 3.1-fold for parents (95% CI, 1.4-6.8), and 1.3-fold for half-sibling or other biological relatives (95% CI, 0.5-3.3). For white donors, risks were 3.5-fold greater for identical twin donors (95% CI, 0.5-25.3), 2.0-fold for full siblings (95% CI, 1.4-2.8), 1.4-fold for offspring (95% CI, 0.9-2.3), 2.9-fold for parents (95% CI, 2.0-4.1), and 0.8-fold for half-sibling or other biological relatives (95% CI, 0.3-1.6).

Limitations: Insufficient sample size in some race and relationship groups. Absence of data for family history of kidney disease for donors biologically unrelated to their recipients.

Conclusions: Marked differences in risk for ESKD across types of donor-recipient relationship were observed for Asian, black, and white donors. These findings warrant further validation with more robust data to better inform clinical practice guidelines.
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http://dx.doi.org/10.1053/j.ajkd.2019.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042071PMC
March 2020

Risk of ESKD in Older Live Kidney Donors with Hypertension.

Clin J Am Soc Nephrol 2019 07 25;14(7):1048-1055. Epub 2019 Jun 25.

Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background And Objectives: Hypertension in older kidney donor candidates is viewed as safe. However, hypertension guidelines have evolved and long-term outcomes have not been explored. We sought to quantify the 15-year risk of ESKD and mortality in older donors (≥50 years old) with versus those without hypertension.

Design, Setting, Participants, & Measurements: A United States cohort of 24,533 older donors from 1999 to 2016, including 2265 with predonation hypertension, were linked to Centers for Medicare and Medicaid Services data and the Social Security Death Master File to ascertain ESKD development and mortality. The exposure of interest was predonation hypertension. From 2004 to 2016, hypertension was defined as documented predonation use of antihypertensive therapy, regardless of systolic BP or diastolic BP; from 1999 to 2003, when there was no documentation of antihypertensive therapy, hypertension was defined as predonation systolic BP ≥140 or diastolic BP ≥90 mm Hg.

Results: Older donors were 82% white, 6% black, 7% Hispanic, and 3% Asian. The median follow-up was 7.1 years (interquartile range, 3.4-11.1; maximum, 18). There were 24 ESKD and 252 death events during the study period. The 15-year risk of ESKD was 0.8% (95% confidence interval [95% CI], 0.4 to 1.6) for donors with hypertension (mean systolic BP, 138 mm Hg) versus 0.2% (95% CI, 0.1 to 0.4) for donors without hypertension (mean systolic BP, 123 mm Hg; adjusted hazard ratio, 3.04; 95% CI, 1.28 to 7.22; =0.01). When predonation antihypertensive therapy was available, the risk of ESKD was 6.21-fold higher (95% CI, 1.20 to 32.17; =0.03) for donors using antihypertensive therapy (mean systolic BP, 132 mm Hg) versus those not using antihypertensive therapy (mean systolic BP, 124 mm Hg). There was no significant association between donor hypertension and 15-year mortality (hazard ratio, 1.18; 95% CI, 0.84 to 1.66; =0.34).

Conclusions: Compared with older donors without hypertension, older donors with hypertension had higher risk of ESKD, but not mortality, for 15 years postdonation. However, the absolute risk of ESKD was small.
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http://dx.doi.org/10.2215/CJN.14031118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625624PMC
July 2019

The changing landscape of live kidney donation in the United States from 2005 to 2017.

Am J Transplant 2019 09 3;19(9):2614-2621. Epub 2019 May 3.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

The number of live kidney donors has declined since 2005. This decline parallels the evolving knowledge of risk for biologically related, black, and younger donors. To responsibly promote donation, we sought to identify declining low-risk donor subgroups that might serve as targets for future interventions. We analyzed a national registry of 77 427 donors and quantified the change in number of donors per 5-year increment from 2005 to 2017 using Poisson regression stratified by donor-recipient relationship and race/ethnicity. Among related donors aged <35, 35 to 49, and ≥50 years, white donors declined by 21%, 29%, and 3%; black donors declined by 30%, 31%, and 12%; Hispanic donors aged <35 and 35 to 49 years declined by 18% and 15%, and those aged ≥50 increased by 10%. Conversely, among unrelated donors aged <35, 35 to 49, and ≥50 years, white donors increased by 12%, 4%, and 24%; black donors aged <35 and 35 to 49 years did not change but those aged ≥50 years increased by 34%; Hispanic donors increased by 16%, 21%, and 46%. Unlike unrelated donors, related donors were less likely to donate in recent years across race/ethnicity. Although this decline might be understandable for related younger donors, it is less understandable for lower-risk related older donors (≥50 years). Biologically related older individuals are potential targets for interventions to promote donation.
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http://dx.doi.org/10.1111/ajt.15368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711793PMC
September 2019

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

Am J Transplant 2019 07 8;19(7):2009-2019. Epub 2019 Feb 8.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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 =  0.36 , P < .001) and biologically related (aOR =  0.59 , 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 =  0.89 , P = .1) but lower mortality (aHR =  0.62 , 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.
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http://dx.doi.org/10.1111/ajt.15256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591087PMC
July 2019

Better graft outcomes from offspring donor kidneys among living donor kidney transplant recipients in the United States.

Am J Transplant 2019 01 16;19(1):269-276. Epub 2018 Oct 16.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

A recent study reported that kidney transplant recipients of offspring living donors had higher graft loss and mortality. This seemed counterintuitive, given the excellent HLA matching and younger age of offspring donors; we were concerned about residual confounding and other study design issues. We used Scientific Registry of Transplant Recipients data 2001-2016 to evaluate death-censored graft failure (DCGF) and mortality for recipients of offspring versus nonoffspring living donor kidneys, using Cox regression models with interaction terms. Recipients of offspring kidneys had lower DCGF than recipients of nonoffspring kidneys (15-year cumulative incidence 21.2% vs 26.1%, P < .001). This association remained after adjustment for recipient and transplant factors (adjusted hazard ratio [aHR] =  0.77 , P < .001), and was attenuated among African American donors (aHR 0.85 ; interaction: P = .01) and female recipients (aHR 0.84 , P < .001). Although offspring kidney recipients had higher mortality (15-year mortality 56.4% vs 37.2%, P < .001), this largely disappeared with adjustment for recipient age alone (aHR =  1.06 , P = .002) and was nonsignificant after further adjustment for other recipient characteristics (aHR =  0.97 , P = .1). Kidneys from offspring donors provided lower graft failure and comparable mortality. An otherwise eligible donor should not be dismissed because they are the offspring of the recipient, and we encourage continued individualized counseling for potential donors.
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http://dx.doi.org/10.1111/ajt.15126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310629PMC
January 2019

Living donor postnephrectomy kidney function and recipient graft loss: A dose-response relationship.

Am J Transplant 2018 11 31;18(11):2804-2810. Epub 2018 Aug 31.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Development of end-stage renal disease (ESRD) in living kidney donors is associated with increased graft loss in the recipients of their kidneys. Our goal was to investigate if this relationship was reflected at an earlier stage postdonation, possibly early enough for recipient risk prediction based on donor response to nephrectomy. Using national registry data, we studied 29 464 recipients and their donors from 2008-2016 to determine the association between donor 6-month postnephrectomy estimated GFR (eGFR) and recipient death-censored graft failure (DCGF). We explored donor BMI as an effect modifier, given the association between obesity and hyperfiltration. On average, risk of DCGF increased with each 10 mL/min decrement in postdonation eGFR (adjusted hazard ratio [aHR] 1.06, 95% confidence interval [CI] 1.02-1.10, P = .007). The association was attenuated with higher donor BMI (interaction P = .049): recipients from donors with BMI = 20 (aHR 1.12, 95% CI 1.04-1.19, P = .002) and BMI = 25 (aHR 1.07, 95% CI 1.03-1.12, P = .001) had a higher risk of DCGF with each 10 mL/min decrement in postdonation eGFR, whereas recipients from donors with BMI = 30 and BMI = 35 did not have a higher risk. The relationship between postdonation eGFR, donor BMI, and recipient graft loss can inform counseling and management of living donor kidney transplant recipients.
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http://dx.doi.org/10.1111/ajt.15061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219620PMC
November 2018

Racial differences in completion of the living kidney donor evaluation process.

Clin Transplant 2018 07 15;32(7):e13291. Epub 2018 Jun 15.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Racial disparities in living donor kidney transplantation (LDKT) persist but the most effective target to eliminate these disparities remains unknown. One potential target could be delays during completion of the live donor evaluation process. We studied racial differences in progression through the evaluation process for 247 African American (AA) and 664 non-AA living donor candidates at our center between January 2011 and March 2015. AA candidates were more likely to be obese (38% vs 22%: P < .001), biologically related (66% vs 44%: P < .001), and live ≤50 miles from the center (64% vs 37%: P < .001) than non-AAs. Even after adjusting for these differences, AAs were less likely to progress from referral to donation (aHR for AA vs non-AA: 0.47 P = .01). We then assessed racial differences in completion of each step of the evaluation process and found disparities in progression from medical screening to in-person evaluation (aHR: 0.62 P = .02) and from clearance to donation (aHR: 0.51 P = .02), compared with from referral to medical screening (aHR: 1.02 P = .95) and from in-person evaluation to clearance (aHR: 0.93 P = .54). Delays may be a manifestation of the transplant candidate's social network, thus, targeted efforts to optimize networks for identification of donor candidates may help address LDKT disparities.
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http://dx.doi.org/10.1111/ctr.13291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398948PMC
July 2018

Mortality and Graft Loss Attributable to Readmission After Kidney Transplantation: Immediate and Long-term Risk.

Transplantation 2017 10;101(10):2520-2526

1 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. 2 Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD. 3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: After kidney transplantation, early readmission is independently associated with graft loss and mortality. The mechanism of this association is poorly understood. Understanding the timeline of risk, that is, during the readmission hospitalization versus periods postreadmission, will provide additional insights.

Methods: We used national registry data to study 56 076 adult Medicare-primary first-time kidney transplant recipients from December 1999 to October 2011. Piecewise Cox proportional hazard models were used to estimate the association between graft loss, mortality, and readmission for 2 periods: readmission hospitalization and postreadmission.

Results: During the readmission hospitalization, graft loss was substantially higher (deceased donor kidney transplant [DDKT] without delayed graft function [DGF] hazard ratio: 24.634.447.9, P < 0.001; with DGF: 10.815.221.4, P < 0.001; live donor kidney transplant [LDKT]: 18.136.774.2, P < 0.001) and mortality was substantially higher (DDKT without DGF: 14.120.830.7, P < 0.001; with DGF: 9.0312.818.0, P < 0.001; LDKT: 9.0018.241.3, P < 0.001). Immediately after readmission discharge, graft loss (DDKT without DGF: 2.082.402.77, P < 0.001; with DGF: 1.832.142.51, P < 0.001; LDKT: 2.002.503.13, P < 0.001), and mortality (DDKT without DGF: 2.162.432.73, P < 0.001; with DGF: 1.832.162.88, P < 0.001; LDKT: 1.902.342.88, P < 0.001) remained elevated, but much less so. After readmission, the hazard of graft loss remained, but decreased 19% per year for DDKT recipients (time varying coefficient 0.780.810.85, P < 0.001) and 14% per year for LDKT recipients (0.790.860.93, P < 0.001). The hazard of mortality remained, but decreased 14% per year for DDKT recipients (0.830.860.89, P < 0.001) and 9% per year for LDKT recipients (0.850.910.98, P < 0.001).

Conclusions: In conclusion, readmission is most strongly associated with graft loss and mortality during the readmission hospitalization, but also portends a lasting, albeit attenuated, risk postreadmission.
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http://dx.doi.org/10.1097/TP.0000000000001609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462864PMC
October 2017

Role of diuretics and ultrafiltration in congestive heart failure.

Pharmaceuticals (Basel) 2013 Jul 4;6(7):851-66. Epub 2013 Jul 4.

University of Colorado Division of Renal Diseases and Hypertension, 12700 East 19th Avenue, C281, Aurora, CO 80045, USA.

Volume overload in heart failure (HF) results from neurohumoral activation causing renal sodium and water retention secondary to arterial underfilling. Volume overload not only causes signs and symptoms of congestion, but can impact myocardial remodeling and HF progression. Thus, treating congestion is a cornerstone of HF management. Loop diuretics are the most commonly used drugs in this setting. However, up to 30% of the patients with decompensated HF present with loop-diuretic resistance. A universally accepted definition of loop diuretic resistance, however, is lacking. Several approaches to treat diuretic-resistant HF are available, including addition of distal acting thiazide diuretics, natriuretic doses of mineralocorticoid receptor antagonists (MRAs), or vasoactive drugs. Slow continuous veno-venous ultrafiltration is another option. Ultrafiltration, if it is started early in the course of HF decompensation, may result in prominent decongestion and a reduction in re-hospitalization. On the other hand, ultrafiltration in HF patients with worsening renal function and volume overload after aggressive treatment with loop diuretics, failed to show benefit compared to a stepwise pharmacological approach, including diuretics and vasoactive drugs. Early detection of congested HF patients for ultrafiltration treatment might improve decongestion and reduce readmission. However, the best patient characteristics and best timing of ultrafiltration requires further evaluation in randomized controlled studies.
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http://dx.doi.org/10.3390/ph6070851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816706PMC
July 2013

Angiotensin receptor blockade with candesartan attenuates atherosclerosis, plaque disruption, and macrophage accumulation within the plaque in a rabbit model.

Circulation 2004 Oct 27;110(14):2060-5. Epub 2004 Sep 27.

Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, RW-453, Boston, MA 02115, USA.

Background: Little is known about whether direct angiotensin receptor blockade can reduce atherosclerosis and plaque disruption. This study evaluated the effect of angiotensin receptor blockade on both the development of atherosclerosis and the disruption of plaque in a modified Constantinides animal model.

Methods And Results: Twenty-eight New Zealand White rabbits underwent aortic balloon injury followed by a 1% cholesterol diet for 8 weeks. Thirteen rabbits received candesartan at 0.5 mg x kg(-1) x d(-1) beginning 2 days before aortic balloon injury and continued for the total 8 weeks of the cholesterol diet. The rabbits were then pharmacologically triggered and humanely killed, and their aortas were analyzed. The degree of atherosclerosis was determined by intima-media ratio of the infrarenal portion of the aorta. The frequency of intra-aortic thrombosis, a measure of plaque disruption, and the percentages of macrophage area and collagen-staining area of the plaque were determined. Candesartan-treated rabbits had less atherosclerosis (intima-media infrarenal aorta ratio of 1.18+/-0.08 versus 1.57+/-0.08 [mean+/-SEM] for the placebo group, P<0.001); fewer thrombi (3 of 13 versus 11 of 15; P<0.05); lower percentage area of macrophages to total plaque (18.8+/-2.7% versus 27+/-2.5%, P<0.05); and higher collagen to total plaque area (45+/-3% versus 35+/-2%, P<0.01).

Conclusions: These results demonstrate that angiotensin receptor blockade attenuates the degree of atherosclerosis and reduces both plaque disruption and macrophage accumulation while increasing collagen deposition in the aortas of this animal model.
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http://dx.doi.org/10.1161/01.CIR.0000143627.55926.4CDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906248PMC
October 2004
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