The selection of potential living donor may be determined on the basis of age by avoiding, if possible, elderly or minor volunteers. Age <18 years is considered an absolute contraindication and most programs consider age of 18–21 years as a relative contraindication [3]. This is because younger donors, even if without risk factors for kidney disease at the time of evaluation, may still develop diabetes, hypertension, and obesity and have more time for these risk factors to progress to CKD. Younger potential donors with presence of even borderline risk factors are likely at higher long-term risk, and it is recommended to use exclusion criteria more stringently in this population [6].

Old age (defined in various studies as age >60 or 65 years) is not an absolute contraindication to donation. However, in such cases, the medical workup of older donors must be particularly rigorous to ensure that they are suitable for donation [7]. Although older donors are more likely to have complex medical histories and lower glomerular filtration rate (GFR), studies have shown similar outcomes in selected older donors versus younger donors for perioperative outcomes such as operative time, blood loss, and length of hospital stay [8]. With regard to long-term risks, older donors with potential risk factors for kidney disease (such as hypertension) are less likely than younger donors to have enough time for such risk factors to generate kidney disease that would affect their life expectancy [9].

Donation for some hypertensive individuals may be acceptable if blood pressure is well controlled, the GFR for donation and age is as expected, and there are no features of end-organ involvement from hypertension [3, 4]. However, the overall risk for cardiovascular events in hypertensive patients is higher than in normotensive individuals with the same age, sex, and race. It is therefore important to perform cardiovascular evaluation and careful blood pressure (BP) measurement in potential living kidney donors with hypertension. The evaluation for hypertension should include BP measurements by experienced providers on three separate occasions; verification of elevated levels should be undertaken with ambulatory BP monitoring. If elevated BP are detected while the potential donor is still under consideration, a cardiovascular (electrocardiogram, echocardiogram, stress test, etc.) and ophthalmologic evaluation should be performed to assess the secondary consequences of hypertension. In addition, a 24–h urine collection for albumin excretion or a spot urine for albumin/creatinine ratio should be performed along with a urinalysis and a formal GFR measurement. Some patients with easily controlled hypertension who meet other defined criteria (e.g., >50 years of age, GFR >80 ml/min, urinary albumin excretion <30 mg/day) may be considered a low-risk group for development of kidney disease after donation and may be acceptable as kidney donors. Candidates with a blood pressure >140/90 mmHg are generally not accepted as donors. Mild to moderate hypertension that is controlled with single or double antihypertensive agents is not a contraindication to kidney donation providing significant end-organ damage is excluded. The presence of hypertensive end-organ damage, poorly controlled hypertension, and hypertension that requires more than two drugs to achieve adequate control are relative contraindications to living donation [3–5].

Among living kidney donors with normal renal function prior to donation, the risk of developing end-stage renal disease (ESRD) after unilateral nephrectomy is not higher than among individuals in the general population [10]. In general, individuals who are being evaluated for kidney donation should have “normal” renal function as determined by GFR. Renal function can be measured with various methods, and the multifactorial nature of the various tests may lead to either an overestimation or an underestimation of the true physiological function of the kidneys. However, in the case of living kidney donations, the accurate measure of renal function is of fundamental importance. GFR is either measured as endogenous creatinine clearance by 24-h urine collection or estimated based on serum creatinine measurement by various formulas such as Cockroft-Gault, modification of diet in renal disease (MDRD), and the chronic kidney disease epidemiology collaboration equation (CKD-EPI). The use of a 24-h urine collection to estimate GFR with creatinine clearance is the most common technique of donor evaluation; however, creatinine clearance has many deficiencies, including errors from urine collection. MDRD, CKD-EPI, and other equations based on serum creatinine have been compared with measured GFR, and it was proved that it is unreliable for evaluation of donors; hence, it should be avoided [11]. Likewise, KDIGO guidelines discuss the limitation of these methods especially for patients with normal renal function [12]. The direct measure of GFR using iodinated or radioactive isotopes is ideal for evaluating kidney function in donors. This is because the methods that measure renal function with a higher precision use radioisotopic markers for scintigraphy such as technetium-99m-labeled diethylenetriaminepentaacetate (DTPA), chrome-51m-labeled ethylenediaminetetraacetate (EDTA), and techenetium-99m-labeled mercaptoacetyltriglycine (MAG3). In addition to these functional tests, imaging techniques such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are used to determine the vasculature, kidney size, and volume [13].

Although various reports of normal kidney function stratified by age differ somewhat, due to the technique used and the proportion of patients with medical problems that are included, the importance to use different cutoffs depending on the age of the potential donor can be seen from any reports. Several studies recommend that living donors should have a GFR of ≥80 ml/min or, alternatively, a normal kidney function for age and gender [5, 7].

All donors should be evaluated with fasting blood glucose. Diabetes is associated with a higher risk of postsurgical complications and of future development of renal failure compared to the general population. The individuals at risk of developing type 2 diabetes include those with a familiar history, a body max index (BMI) >30 kg/m², woman with gestational diabetes, and excessive alcohol use. Individuals with a history of diabetes or fasting blood glucose ≥126 mg/dl (≥7 mmol/l) on at least two occasions should not donate [3]. Only one study, carried out in Japan, examined the effect of impaired glucose tolerance on living donor outcome. The results of this study suggest that individuals who have glucose intolerance without diabetic complication may be able to donate their kidney safely with little surgical complication and slightly higher morbidity if strict evaluation is performed before transplant [14]. Individuals often lose weight and change their lifestyle (exercise, diet), leading to an improvement of their results and increasing their eligibility as donors. It is therefore important that these modifications of lifestyle and risk factors be sustained after donation occurs.

Dyslipidemia should be included in donor risk assessment along with other risk factors although dyslipidemia alone does not exclude kidney donation. All potential donors should have a health-promoting dialogue with doctors (or another health professional) with the objective of promoting on alcohol and smoking cessation among other risk factors [3].

Patients with BMI >35 kg/m² should be discouraged from kidney donation, especially when other comorbid conditions are present. Obesity is associated with proteinuria and hypertension and may lead to ESRD. In the case of obese donors, the operative time and the length of hospital stay are longer, and the risk of peri- and postoperative complication is higher than in patients with BMI <30 kg/m². Overweight donors should be advised to lose weight before donation, and the potential risks of being overweight should be carefully discussed [3–6].

Proteinuria should be considered as an ordinary element of the donor evaluation process. The collection of urine should be repeated and its accuracy checked when the result is outside the normal values. Because proteinuria is potentially a sign of renal disease, a potential donor with significant and persistent proteinuria should not be considered. A 24-h urine protein higher than 300 mg/day and a urine albumin/creatinine ratio higher than 30 mg/mmol are contraindications to donation. The significance of microalbuminuria and of a 24-h urine protein of 150–300 mg has not been fully evaluated among living kidney donors. However, because the risk of both chronic kidney disease and cardiovascular morbidity increases progressively with increasing albuminuria, such donors require careful evaluation and counseling about the risks of donation [3, 7].