KDIGO Guidelines on Living Kidney Donors: A Call for A Paradigm Shift

The much-anticipated KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors was recently published. It is available in two versions: a 10-page summary that lists all the recommendations that is a relatively easy read, and a 102-page version which contains the complete guideline including the rationale for each of the recommendations, research recommendations, and all the references. This guideline took almost four years to complete and our colleagues who devoted countless hours of their time to make this happen undoubtedly deserve recognition and appreciation.

The crux of the guideline is a call for a paradigm shift in the way we assess a donor candidate’s long-term risks, particularly for ESRD. Rather than focusing on individual risk factors and determining whether donor candidates meet certain criteria (e.g. GFR has to be >=80 mL/min), the guideline proposes using an individualized approach. This involves using a quantitative framework that evaluates a donor’s risks based on a combination of factors including demographic, clinical, and donation-related factors. The guideline recognizes that risks are not equal among different individuals and that multiple factors are at play. For example, a white, middle-aged donor candidate with well-controlled hypertension probably has a lower risk of ESRD than a young, black donor candidate with normal BP and low-grade albuminuria.

In formulating the guideline, the KDIGO workgroup collaborated with the Chronic Kidney Disease Prognosis Consortium (CKD-PC) to perform a meta-analysis to estimate the ESRD risk of donor candidates in the absence of donation. The product of this work is a publicly available online calculator. With admittedly significant limitations, this tool is meant to be a starting point for estimating risk. What we would of course ultimately want is a tool that can reliably and accurately estimate post-donation risk, specifically risk attributed to donation. In the guideline, Table 9 outlines an approach to implementing the quantitative framework, including how this calculator can be utilized.

The guideline recommends that each center set predetermined acceptance thresholds for important short- and long-term risks, and to apply these uniformly among donor candidates. If a donor candidate’s estimated risk surpasses a certain acceptance threshold, then the donor candidate would be excluded from donation. This concept is nicely depicted in Figure 4. It is important to remember that these risks are mere estimates and fraught with uncertainty, which should be emphasized when counseling donor candidates.

In line with the paradigm shift, the guideline recommends an individualized approach in deciding whether donor candidates should proceed with donation if they have what I would call “borderline” numbers or conditions. Rather than setting hard cutoffs or thresholds, the guideline recommends considering donors on a case-by-case basis, “based on demographic and health profile in relation to the transplant program’s acceptable risk threshold.” These “borderline” numbers or conditions are:

  • Glomerular filtration rate of 60-89 mL/min per 1.73 m2
  • Albumin excretion rate of 30-100 mg/day
  • Hypertension controlled on 1-2 agents without end organ damage
  • Glucose intolerance or type 2 diabetes
  • Body mass index >30 kg/m2
  • Active tobacco users

Only 6 recommendations were graded within the guideline. The ones that pertain to the counseling of donors regarding risks are:

  • On the risk of kidney failure: “We suggest that donor candidates should be informed that the risk of someday developing kidney disease necessitating treatment with dialysis or kidney transplantation is slightly higher because of donation but average absolute risk in the first 15 years following donation remains low.” (2C)
  • On the risk of developing hypertension: “We suggest that donor candidates should be informed that blood pressure may rise with aging, and donation can accelerate the rise in blood pressure and the need for antihypertensive treatment over that expected with normal aging.” (2D)
  • On the risk of pregnancy-related complications: “We suggest that women with childbearing potential be counseled about the effects donation may have on future pregnancies, including the possibility of greater likelihood of being diagnosed with gestational hypertension or preeclampsia.” (2C)
  • On the effect on quality of life: “We suggest that donor candidates be informed that donors usually have a good quality of life after donation.” (2D)

Other important counseling recommendations worth mentioning are:

  • On the risk of death:Donor candidates should be informed that the risk of dying within 90 days after donation surgery is approximately 0.03%, or 3 deaths in every 10,000 donors (although this estimate may vary based on donor characteristics).”
  • On APOL1: “APOL1 genotyping may be offered to donor candidates with sub-Saharan African ancestry. Donor candidates should be informed that having 2 APOL1 risk alleles increases the lifetime risk of kidney failure but precise kidney failure risk for an affected individual after donation cannot be currently quantified.”

The authors acknowledge the paucity of good evidence in formulating these recommendations. Only 5 systematic reviews and 40 observational studies met the workgroup’s inclusion criteria. Table 7 lists the reasons why many ungraded recommendations are issued in the guideline. The authors noted that there was a clamor from the community for experts to share “what they would do.” In light of this and to ensure the guideline remained comprehensive, they included and specified recommendations that are based solely on expert opinion.

Overall, I believe this guideline is an important resource for transplant center clinicians who evaluate donor candidates. It can impact and change current practice patterns. Transplant centers are often driven by protocols and criteria. These protocols and criteria can be inflexible despite the absence of evidence supporting them. The guideline provides an opportunity for clinicians to use an individualized approach in living donor evaluation and care that can replace the current “one-size-fits-all” model. Within this new evaluation framework, I would expect to see an increase in the number of older living donor candidates with medical issues who would qualify for donation. At the same time, I assume greater caution would be applied in accepting young black donors with GFRs at the lower end of “normal.”

This guideline provides us with a comprehensive, practical, and rational approach in evaluating and counseling potential donors. It allows us to share information with donor candidates regarding post-donation risks that represent a combination of the best available data and expert opinion. It redefines risk assessment for clinicians through individualized evaluation of donor candidates. It also serves as a new baseline from which further research in donor evaluation and care can proceed.

– Post prepared by Beatrice Concepcion, AJKD Social Media Advisory Board member. Follow her @KidneyBea_n.

 

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