Accepting Living Kidney Donors with Preexisting Diabetes Mellitus

A Perspective on the Recent OPTN Policy Change—July 2022

Introduction

Diabetes mellitus is a leading cause of kidney disease. Accepting living kidney donors with diabetes mellitus remains a debatable issue. The necessity of this article's proposal resulted from recent Organ Procurement and Transplantation Network (OPTN) policy amendments regarding the acceptance of living kidney donors with diabetes mellitus (¹).

For a frame of reference, the European Best Practices Guidelines qualify living kidney donors with preexisting diabetes mellitus only under “exceptional circumstances” (²). The British Transplantation Society offers the opinion-based recommendation that “diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of cardiovascular and progressive kidney disease in the presence of a single kidney” (³). According to European guidelines, impaired glucose tolerance is not an absolute contraindication to donation (recommendation 2C) (²). As per Kidney Disease Improving Global Outcomes (KDIGO), the decision to accept potential living kidney donors with prediabetes should be “individualized based on demographic and health profile in relation to the transplant program's acceptable risk threshold, including projected risk of kidney failure estimated from consideration of all baseline factors” (⁴). On the basis of systematic evidence review and the guideline framework, KDIGO includes another similar recommendation for individualization to allow for the consideration of very low–risk (generally older) individuals with type 2 diabetes mellitus for kidney donation (⁴).

Historically, OPTN and many other international practice guidelines prohibited living individuals with preexisting diabetes mellitus from kidney donation. However, on July 27, 2022, OPTN guidelines were loosened. Patients with type 2 diabetes mellitus are now being considered for donation “unless assessment of donor demographics or comorbidities reveals either evidence of end organ damage or unacceptable lifetime risk of complications” (¹).

A significant challenge for clinicians with the evolving OPTN changes is the lack of a clear approach for assessing and accepting living kidney donors with preexisting diabetes mellitus. In this brief report, we intend to discuss the significant hurdles that clinicians face when evaluating living kidney donors with diabetes mellitus and propose an approach while evaluating potential living kidney donor candidates with preexisting diabetes mellitus.

Discussion

The metabolic syndrome, a cluster of risk factors, has a clear and multifaceted detrimental effect on the progression of kidney disease. Because of the lack of robust evidence on long-term outcomes of living kidney donors with multiple risk factors for diabetes mellitus, exclusion criteria on the basis of prediabetic status or diabetes mellitus risk factors vary across transplant centers. In most guidelines, prediabetes and a history of gestational diabetes mellitus are not considered absolute contraindications to living kidney donation. For context, over a mean follow-up of 15.7 years, a study of 8280 donors, including 1826 with impaired fasting glucose at the time of donation and 6204 without, found similar survival and rates of kidney failure among donors with and without impaired fasting glucose (⁵).

Because diabetes mellitus is a major cause of kidney failure, accepting diabetic living kidney donors with additional risk factors raises substantial clinical concerns and should be approached with caution. Uncontrolled hypertension (HTN) is a significant and independent risk factor for the development of CKD, kidney failure, and graft failure in transplant recipients. Living kidney donors with preexisting HTN have a higher long-term risk of developing kidney failure compared with nonhypertensives (⁶). Obesity, another risk factor, has been linked in multiple studies to the development and progression of CKD. A higher body mass index was found to be directly associated with the development and progression of proteinuria in people without kidney disease, and obesity has been proven to be an independent risk factor for the development of kidney failure (⁷). In a broader sense, it has been shown that obesity and HTN have an additive effect on decreasing GFR compensation after kidney donation (⁸). Smoking has been shown to increase the risk of CKD, notably hypertensive nephropathy and diabetic nephropathy. Furthermore, numerous animal and human studies have shown that hyperlipidemia accelerates the rate of kidney disease progression (⁹).

In the absence of clear literature to assist in the selection of living kidney donors with diabetes mellitus, it has been essential to carefully construct a thoughtful approach that takes into account the risk considerations and the global risk posed by these. Our proposed eligibility criteria for living kidney donors with preexisting diabetes mellitus are illustrated in Figure 1. The American Diabetes Association (ADA) recommends annual diabetes screenings after the age of 45, which is the average onset age for type 2 diabetes mellitus (¹⁰). From a safety perspective, in the absence of supporting literature, we arbitrarily suggest that eligible living kidney donors be at least 55 years old, have had diabetes mellitus for at least 3 years, and have demonstrated a hemoglobin A1C of ≤7% on at least three occasions in the last 2 years in order to verify adequate control and adherence. We rule out candidates who are insulin dependent or take more than two oral antidiabetic medications. We advocate adhering to ADA's treatment guidelines, which still identify metformin as the most often used first-line oral antidiabetic medication. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, with or without metformin, are acceptable first-line alternatives with proven cardiovascular and nephroprotective benefits, particularly in individuals with or at high risk of atherosclerotic cardiovascular disease, heart failure, and/or CKD (¹⁰).

Figure 1: Eligibility criteria for living kidney donors with preexisting type 2 diabetes mellitus (DM). HbA1C, hemoglobin A1C; HTN, hypertension.

Prior to donation, candidates must have a body mass index of <30 kg/m², be nonsmokers, and have well-controlled hyperlipidemia with recommended values as established by the ADA guidelines (LDL cholesterol of <100 mg/dl, HDL cholesterol of >40 mg/dl in men and >50 mg/dl in women, and triglyceride levels of <150 mg/dl) as demonstrated by lipid profile testing within the past year (¹⁰). The surgeon will assess the donor's body habitus during the evaluation to determine its suitability for surgery.

Candidates with diabetes mellitus and HTN are strongly discouraged from kidney donation. Acceptance of diabetic living kidney donors on a single antihypertensive medication or who demonstrate slight deviations from our proposed criteria but otherwise are deemed suitable by the selection committee for donation will be considered on a case-by-case basis. Some data suggest that diabetic retinopathy may precede or predict diabetic nephropathy (¹¹). We require donors to have a fundus examination to rule out diabetic retinopathy, which we use as a surrogate marker for diabetic microvascular damage. Eligible candidates must have a urine albumin-creatinine ratio of <30 mg/g or a urine protein-creatinine ratio of <200 mg/g. In addition to rigorous counseling, the donor’s and the program’s conjoint willingness to accept the high risk, and informed consent, we strongly recommend that living kidney donors maintain close follow-up with their primary care provider throughout their lifetime. Although we strive to help patients with kidney failure, we believe that a stringent approach to potential living kidney donors with diabetes mellitus should be taken to minimize harm and ensure their safety. Even though prior living kidney donors who develop kidney failure receive high priority on the OPTN kidney waiting list, granting donors with preexisting diabetes mellitus the highest priority merits serious consideration.

Because diabetes mellitus was formerly regarded as an absolute contraindication for kidney donation, there are currently no data comparing the lifetime risk of developing kidney failure in a diabetic donor with that of a diabetic nondonor and a nondiabetic donor. If kidney donation by patients with diabetes who meet specific criteria is implemented, both prospective and retrospective studies will be necessary to fill in these knowledge gaps. An evidence-based guideline developed through additional robust data to provide further guidance in selecting living kidney donors is desperately needed. Meanwhile, we are proposing a practical protocol to aid in the careful selection process of living kidney donors in order to protect the health and future welfare of prospective donors.