A Systematic Review of Renal Functional Reserve in Adult Living Kidney Donors
KI Reports. 2020;5(4):448-458
Introduction: The kidney's capacity to increase its glomerular filtration rate (GFR) in response to a higher functional demand is known as the renal functional reserve (RFR). Good short-term outcomes after living kidney donation have led to more acceptance of borderline donors (with hypertension, obesity, older age) due the ongoing shortage of donor organs. Given recent concerns about increased long-term risk in some donor subgroups, better donor stratification is needed. Measurement of RFR could inform assessment of donor risk. Methods: A systematic literature review of studies that assessed RFR in donors pre- and/or post-donation was performed. Given study heterogeneity, descriptive analysis and narrative synthesis was conducted. Results: Sixteen of 3250 identified studies published between 1956 and 2019 met inclusion criteria. Most studies were cross-sectional and conducted before (n = 8) and/or after (n = 16) kidney donation. Methods for measurement of GFR, effective renal plasma flow (ERPF) and RFR were not standardized. Changes in filtration fraction (FF) and ERPF relative to GFR observed after donation varied depending on stimulus used to induce RFR. Overall, RFR fell after donation; however, over the shorter term, RFR was largely preserved in young healthy donors. RFR was more significantly reduced in donors with hypertension, obesity, or older age. Conclusion: Existing data suggest possible blunting of RFR post-donation in older, obese, and hypertensive donors, which may represent increased single-nephron GFR at baseline. The long-term implications of these changes deserve further study to determine utility in informing selection of borderline kidney donors.
Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical Practice
Clinical Journal of The American Society of Nephrology: CJASN. 2020;[record in progress]:10
The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 "Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors" was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a "proof-of-concept" risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate's profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.
Effects of low versus standard pressure pneumoperitoneum on renal syndecan-1 shedding and VEGF receptor-2 expression in living-donor nephrectomy: a randomized controlled study
BMC Anesthesiology. 2020;20(1):37
The aim of this study was to examine the effect of low pressure pneumoperitoneum on renal tubular cells and vascular endothelium in patients undergoing transperitoneal laparoscopic living donor nephrectomy
Patients were randomized to either the standard (12mmHg) group or the low pressure (8 mmHg) group.
44 patients undergoing transperitoneal laparoscopic donor nephrectomy
The primary endpoint was the assessment of serum plasma levels and tubule syndecan-1 expression. The secondary endpoints were expression of VEGFR-2 and sVEGFR-2 (soluble VEGFR-2) in renal tubuloendothelial cells, and levels of urinary KIM-1 and plasma interleukin-6 (IL-6).
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
The small single-center study investigated the impact of low-pressure pneumoperitoneum (8 vs. 12 mmHg) during laparoscopic donor nephrectomy. The authors demonstrate significantly lower markers of inflammation and renal tubular injury with lower pressures. The clinical significance of these findings are uncertain – there were no differences in operative or other patient outcomes despite the changes in molecular markers. However, lower pressures did not seem to lead to an increase in operative complications or time, suggesting that the majority of procedures could be managed using lower pressures.
BACKGROUND Laparoscopic nephrectomy is a preferred technique for living kidney donation. However, positive-pressure pneumoperitoneum may have an unfavorable effect on the remaining kidney and other distant organs due to inflamed vascular endothelium and renal tubular cell injury in response to increased systemic inflammation. Early detection of vascular endothelial and renal tubular response is needed to prevent further kidney injury due to increased intraabdominal pressure induced by pneumoperitoneum. Transperitoneal laparoscopic living donor nephrectomy represented a human model of mild increasing intraabdominal pressure. This study aimed to assess the effect of increased intraabdominal pressure on vascular endothelium and renal tubular cells by comparing the effects of low and standard pressure pneumoperitoneum on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and the shedding of syndecan-1 as the early markers to a systemic inflammation. METHODS We conducted a prospective randomized study on 44 patients undergoing laparoscopic donor nephrectomy. Subjects were assigned to standard (12 mmHg) or low pressure (8 mmHg) groups. Baseline, intraoperative, and postoperative plasma interleukin-6, syndecan-1, and sVEGFR-2 were quantified by ELISA. Syndecan-1 and VEGFR-2 expression were assessed immunohistochemically in renal cortex tissue. Renal tubule and peritubular capillary ultrastructures were examined using electron microscopy. Perioperative hemodynamic changes, end-tidal CO2, serum creatinine, blood urea nitrogen, and urinary KIM-1 were recorded. RESULTS The low pressure group showed lower intra- and postoperative heart rate, intraoperative plasma IL-6, sVEGFR-2 levels and plasma syndecan-1 than standard pressure group. Proximal tubule syndecan-1 expression was higher in the low pressure group. Proximal-distal tubules and peritubular capillary endothelium VEGFR-2 expression were lower in low pressure group. The low pressure group showed renal tubule and peritubular capillary ultrastructure with intact cell membranes, clear cell boundaries, and intact brush borders, while standard pressure group showed swollen nuclei, tenuous cell membrane, distant boundaries, vacuolizations, and detached brush borders. CONCLUSION The low pressure pneumoperitoneum attenuated the inflammatory response and resulted in reduction of syndecan-1 shedding and VEGFR-2 expression as the renal tubular and vascular endothelial proinflammatory markers to injury due to a systemic inflammation in laparoscopic nephrectomy. TRIAL REGISTRATION ClinicalTrials.gov NCT:03219398, prospectively registered on July 17th, 2017.
Evaluation and Care of International Living Kidney Donor Candidates: Strategies for Addressing Common Considerations & Challenges
Clinical Transplantation. 2020;34(3):e13792
End-stage kidney disease patients in the United States may have family members or friends who are not U.S. citizens or residents but are willing to serve as their living kidney donors 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 the 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: 1) establishing program guidelines for international donor candidate evaluation and selection; 2) initial screening; 3) logistics planning; 4) comprehensive evaluation; and 5) 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 efforts to help optimize the care of this unique group of living donors.
The experience of donating and receiving a kidney: A systematic review of qualitative studies
Journal of Renal Care. 2019;[record in progress]:23
BACKGROUND The experiences described by people who have undergone kidney transplant are complex. Understanding how donors and recipients experience kidney transplantation can help us to design strategies that provide a more person-centred health care. OBJECTIVES To review articles that report the experiences of donors and recipients in the living-donor kidney transplantation process. METHOD A systematic review of qualitative studies was carried out. PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases were used to search for articles published in English, French and Spanish between 2005 and 2018. RESULTS Twenty-nine articles were included in this review. For recipients, receiving a kidney is a positive experience (positive feelings and significant experience) that also involves certain difficulties and stressors (making a difficult decision, fears and worries). The experience of the donors is positive as they are motivated to improve the life of the recipient. They are committed to donating and use coping strategies as well as experiencing personal growth. On the contrary, being a donor involves certain difficulties and stressors (personal investment, mental, physical and economic impact and overcoming opposition) and a perception of deficiency in the health system (lack of information and attentiveness). CONCLUSION Donating and receiving a kidney is a positive experience that involves certain difficulties and a variety of stressors for both the donors and recipients. Moreover, the donors note deficiencies in the health system.
Billing for living kidney donor care: Balancing cost recovery, regulatory compliance, and minimized donor burden
Current Transplantation Reports. 2019;6(2):155-166
Purpose: To provide standardized guidance for transplant programs to maximize financial reimbursement related to living donor care, and to minimize financial consequences of evaluation, surgical and follow-up care to living donor candidates and donors. Recent Findings: In 2014, the American Society for Transplantation (AST) Live Donor Community of Practice (LDCOP) "Consensus Conference on Best Practices in Live Kidney Donation" identified inconsistencies in billing practices as a barrier to living donor financial neutrality, and issued a strong recommendation that the transplant community actively pursue strategies and policies to make living donation a financially neutral act, within the framework of federal law. The LDCOP convened a multidisciplinary group of experts to review and synthesize current Medicare regulations and commercial payer practices related to billing for living donor care, and the implications for transplant programs and patients. We developed guidance for transplant program staff related to strategies to consistently and appropriately obtain reimbursement via the Medicare Cost Report by utilizing organ acquisition; coordinate available coverage for donor pretesting, evaluation, hospitalization, follow-up care, and complications; coordinate charges in kidney paired donation; and maximize coverage through private insurance contracting. We also offer recommendations to protect donor confidentiality in the context of billing, and to educate and prepare donor candidates and donors about any remaining gaps in coverage related to donation. Summary: Best practices in billing for living donation-related care should focus on balancing cost recovery, regulatory compliance, and minimized donor burden. Herein we offer 9 recommendations for best practice. We also offer a platform of 7 recommendations for research & advocacy efforts to better understand the climate of living donor medical costs, and to optimize billing practices that support provision of living donor transplant services to all patients who can benefit and to achieve financial neutrality for living donors.
Can Split Renal Volume Assessment by Computed Tomography Replace Nuclear Split Renal Function in Living Kidney Donor Evaluations? A Systematic Review and Meta-Analysis
Canadian Journal of Kidney Health & Disease. 2019;[record in progress]:2054358119875459
Background: As part of their living kidney donor assessment, all living donor candidates complete a computed tomography (CT) angiogram, but some also receive a nuclear renogram for split renal function (SRF%). Objective: We considered whether split renal volume (SRV%) assessed by CT can predict SRF%. Design: Systematic review and meta-analysis. Setting: Living donor candidates undergoing evaluation as potential living kidney donors. Patients: Living donor candidates who received both a nuclear renogram for split function and CT for SRV as part of their living donor work-up. Measurements: Split renal volume from CT scans and SRF from nuclear renography. Methods: We performed a systematic review and meta-analysis of the literature, abstracting data and digitizing plots where possible. We searched Medline, EMBASE, and the Cochrane Library. We added data from donor candidates assessed in London, Ontario from 2013 to 2016. We used fixed and random-effects models to pool Fisher's z-transformed Pearson's correlation coefficient (r). We conducted random-effects meta-regression on digitized and aggregate data. Studies were restricted to living kidney donors or living donor candidates. Results: After pooling 19 studies (n = 1479), we obtained a pooled correlation of r = 0.74 (95% confidence interval [CI] = 0.61-0.82). By linear regression using individual-level data, we observed a 0.76% (95% CI = 0.71-0.81) increase in SRF% for every 1% increase in SRV%. Split renal volume had a specificity of 88% for discriminating SRF at a threshold that could influence the decision of which kidney is to be removed (between-kidney difference >=10%). Predonation SRV and SRF both moderately predicted kidney function 6 to 12 months after donation: r = 0.75 for SRV and r = 0.73 for SRF; DELTAr = 0.05 (-0.02, 0.13). Limitations: Most studies were retrospective and measured SRV and SRF only on selected living donor candidates. Efficiency gains in removing the SRF from the evaluation will depend on the transplant program. Conclusion: Split renal volume has the potential to replace SRF for some candidates. However, it is uncertain whether it can do so reliably and routinely across different transplant centers. The impact on clinical decision-making needs to be assessed in well-designed prospective studies. Trial registration: The digitized data are registered with Mendeley Data (doi10.17632/dyn2bfgxxj.2).
The Impact of the mKidney mHealth System on Live Donor Follow-Up Compliance: Protocol for a Randomized Controlled Trial
JMIR Research Protocols. 2019;8(1):e11000
BACKGROUND Every year, more than 5500 healthy people in the United States donate a kidney for the medical benefit of another person. The Organ Procurement and Transplantation Network (OPTN) requires transplant hospitals to monitor living kidney donors (LKDs) for 2 years postdonation. However, the majority (115/202, 57%) of transplant hospitals in the United States continue to fail to meet nationally mandated requirements for LKD follow-up. A novel method for collecting LKD follow-up is needed to ease both the transplant hospital-level and patient-level burden. We built mKidney-a mobile health (mHealth) system designed specifically to facilitate the collection and reporting of OPTN-required LKD follow-up data. The mKidney mobile app was developed on the basis of input elicited from LKDs, transplant providers, and thought leaders. OBJECTIVE The primary objective of this study is to evaluate the impact of the mKidney smartphone app on LKD follow-up rates. METHODS We will conduct a two-arm randomized controlled trial (RCT) with LKDs who undergo LKD transplantation at Methodist Specialty and Transplant Hospital in San Antonio, Texas. Eligible participants will be recruited in-person by a study team member at their 1-week postdonation clinical visit and randomly assigned to the intervention or control arm (1:1). Participants in the intervention arm will receive the mHealth intervention (mKidney), and participants in the control arm will receive the current standard of follow-up care. Our primary outcome will be policy-defined complete (all components addressed) and timely (60 days before or after the expected visit date) submission of LKD follow-up data at required 6-month, 1-year, and 2-year visits. Our secondary outcome will be hospital-level compliance with OPTN reporting requirements at each visit. Data analysis will follow the intention-to-treat principle. Additionally, we will collect quantitative and qualitative process data regarding the implementation of the mKidney system. RESULTS We began recruitment for this RCT in May 2018. We plan to enroll 400 LKDs over 2 years and follow participants for the 2-year mandated follow-up period. CONCLUSIONS This pilot RCT will evaluate the impact of the mKidney system on rates of LKD and hospital compliance with OPTN-mandated LKD follow-up at a large LKD transplant hospital. It will provide valuable information on strategies for implementing such a system in a clinical setting and inform effect sizes for future RCT sample size calculations. International registered report identifier (irrid): Derr1-10.2196/11000.
International Travel for Living Donor Kidney Donation: A Proposal for Focused Screening of Vulnerable Groups
As the gap between organ donors and patients on the recipient waiting list grows, residents of the US who are in need of kidney transplantation occasionally contract with living donors from outside the US. Those donors then travel to the US to undergo living donor kidney donation at US transplant centers. This practice is not limited to the US and occurs with some regularity around the world. However, there is very little written about this practice from the perspective of the US transplant system, and there is little in the way of guidance (either legal or ethical) to assist centers that accommodate it in distinguishing between ethically permissible travel for transplant and what could potentially be human trafficking for organ removal. This paper will present an ethical analysis of travel for organ donation with particular attention to lessons that can be drawn from living donor donation in other countries. This inquiry is particularly germane because OPTN has promulgated guidelines with respect to obligations owed to living donors, but those guidelines appear to assume that the donor is a US resident. The critical question then, is whether and/or to what extent those guidelines are applicable to the instant scenario in which the living donor is a non-resident. In addition, this paper addresses several critical ethical concerns implicated by the often vulnerable populations from which donors are drawn. Finally, this paper proposes that focused inquiry by transplant centers is necessary when donors are non-residents.
Solid organ transplantation following allogeneic haematopoietic cell transplantation: experience from a referral organ transplantation center and systematic review of literature
Bone Marrow Transplantation. 2019;54(2):190-203
Solid organ transplantation (SOT) following haematopoietic cell transplantation (HCT) is a rare event. Uncertainty exists whether such recipients are at higher risk of relapse of underlying haematological disease or at increased risk of developing infectious or immunological complications and malignancies following SOT. The experience at our referral organ transplantation center and the present literature of SOT (n = 198) in recipients following previous HCT was systematically reviewed. Outcome analysis of 206 SOT recipients following HCT challenges the validity of the frequently stated comparable outcome with recipients without prior HCT. SOT recipients after HCT are younger and have a higher mortality and morbidity in comparison with "standard" recipients. Rejection rates for SOT recipients following HCT appear to be lower for all organs, except for liver transplantation. In the setting of liver transplantation following HCT, mortality for recipients of deceased donor grafts appears to be exceptionally high, although experience with grafts of living donors are favourable. Morbidity was mostly associated with infectious and malignant complications. Of note some SOT recipients who received solid organ donation from the same HCT donor were able to achieve successful withdrawal of immune suppression. Despite limited follow-up, recipients with prior HCT show a different course after SOT, necessitating attention and closer follow-up.