Long-Term Kidney Outcomes in High BMI Living Kidney Donors: A Narrative Review

s excluded (n=200) Articles included: (n=9) Lack of LKD kidney-related outcomes PubMed Search All abstracts reviewed. (n=295) Abstracts selected for full-text reading (n=95)s selected for full-text reading (n=95) Articles excluded: (n=86) 1. Review articles (n=26) 2. No BMI breakdown (n=16) 3. Missing baseline and/or follow-up data (n=16) 4. Follow-up <5 years (n=16) 5. Not in English (n=5) 6. Not LKD specific (n=5) 7. Duplicate data (n=2) 46 The Open Urology & Nephrology Journal, 2017, Volume 10 Murthy et al. [23]. Two multivariate models were tested to evaluate the risk of CKD and the effect of hypertension. In each model, they evaluated the role of BMI on specific outcomes. The eGFR was calculated using the Cystatin-C based formula of Rule. The average BMI at follow-up was 26.65±5.04 kg/m [23]. In the prospective study by Ibrahim et al, hypertension, kidney function, general health status, and quality of life were evaluated in 255 LKDs [24]. GFR was measured by iohexol clearance and estimated by MDRD. LKDs were matched to controls from the National Health and Nutrition Examination Survey 2003-2004 and 2005-2006 [24]. Tavakol et al followed 98 LKDs with matched controls from the National Health and Nutrition Examination Survey 2005-2006 in a prospective study examining kidney-related outcomes [25]. The GFR was calculated using MDRD. They calculated total urine protein and albumin excretion (abnormal when values > 150 and 30 mg/d, respectively). Multivariate logistic regression and linear regression models helped determine the independent association between BMI at donation and kidney-related outcomes [25]. The prospective study of 46 LKDs by Taner et al evaluated the impact of older age, obesity, and hypertension on the compensatory response of the remaining kidney five years post donation [26]. The 11 obese LKDs and 9 hypertensive LKDs were compared to 16 standard LKDs. The mean BMI of obese LKDs was 38.1±2.2 kg/m compared to standard LKDs which 22.6±1.2 kg/m. GFR was measured by I-iothalamate clearance [26]. Kerkeni et al retrospectively evaluated 189 LKDs and assessed both post-operative and long-term consequences of nephrectomy based on BMI [27]. Outcomes for overweight and obese LKDs were compared to those with BMI <25 kg/m. The mean BMI at the time of donation was 26.5±4.8 kg/m, with 33% of LKDs being overweight and 21% obese. Kidney function was assessed by creatinine clearance [27]. The study by Gracida et al evaluated long-term kidney-related outcomes in 628 LKDs. There were 81 LKDs who were obese prior to donation and 16 with hypertension [28]. They compared outcomes with 422 LKDs without risk factors. Mean BMI was 32.8 kg/m in the obese group and 24.7 kg/m in the standard group. The kidney function was measured using creatinine clearance and the method of GFR calculation was not mentioned [28]. They did not report hypertension or proteinuria outcomes at follow-up. 3.1. Higher BMI and Kidney Function (CKD and ESRD) Having shown the data regarding increased risk of chronic kidney disease in the general higher BMI non-donor population, we will review the higher BMI LKD-specific data found in the studies selected for this narrative review. Five studies (range of follow-up, 7-20 years), noted significant decreases in kidney function for higher BMI LKDs. Ibrahim et al evaluated long-term outcomes and risk of ESRD for LKDs over the course of 12.2±9.2 years [24]. The mean GFR was 84±13.8 ml/min per 1.73 m at baseline and 63.7±11.9 ml/min per 1.73 m at follow-up. They noted that 29% of LKDs had BMI >30 kg/m at follow-up. These LKDs were found to carry significantly higher odds of having GFR< 60 ml/min per 1.73 m (OR 1.12, CI 1.02-1.23, p=0.02) compared to lower BMI LKDs [24]. In the study by Nogueira et al (2009), outcomes for 39 African American (AA) LKDs were reported [20]. Predonation eGFR was 102.5±20.3 ml/min per 1.73 m. They found a statistically significant greater absolute (40.1±7.3 vs. 28.3 ±17.1ml/min per 1.73m) and relative decrement (39.8% vs. 26.2%) in GFR at follow-up for those who were morbidly obese compared to those with BMI<35 kg/m. There were no BMI-stratified data available to compare outcomes for the normal, overweight, and obese LKDs within the BMI < 35 kg/m group [20]. Nogueira et al (2010) evaluated 36 obese LKDs (45.7% AA) [18]. The average eGFR was 91±20.3 ml/min per 1.73m at baseline and 63±15.3 ml/min per 1.73m at follow-up. They found a statistically significant overall drop in GFR from baseline to follow-up (29.2%) [21]. It is also important to note that the absolute decrement in GFR was similar for LKDs with BMI≥ 35 kg/m and obese LKDs with BMI< 35 kg/m (31.5±15.6 and 24.7±11.0 mL/min/1.73 m, P=NS). Nogueira et al also compared certain demographic and outcome data for the obese LKDs in this study and the LKD cohort from the study by Ibrahim et al. [24] They noted that higher percentages of the obese LKDs in this study had GFR values <60 mL/min compared to the Ibrahim cohort (47.2% vs. 39.3%). Additionally, AA obese LKDs had a statistically significant greater absolute drop in GFR compared to non-AA LKDs (33.3±9.6 and 22.7±12.7 mL/min/1.73m, respectively, p=0.016) [21]. The study by Locke et al reported long-term data examining outcomes and risk of ESRD for LKDs stratified by BMI ≥ 30 kg/m (n=20,588) and <30 kg/m (n=58,004) [22]. On multivariate analysis, obesity (HR 1.86, CI 1.05-3.30, Kidney Outcomes in High BMI LKD: Narrative Review The Open Urology & Nephrology Journal, 2017, Volume 10 47 p=0.04) and AA race (HR 4.62, CI 3.46-6.16, p<0.001) were the two risk factors that were significantly associated with the development of ESRD. The risk for ESRD post-donation increased 7% for every 1 unit increase in baseline BMI >27 kg/m [22]. In the study by Bello et al, renal outcomes and risk factors for 77 LKDs were evaluated. On multivariate analysis, higher BMI was found to have a statistically significant prevalence ratio for low GFR <60 mL/min at follow-up (PR 1.10, CI 1.05-1.15, p<0.0001) [23]. Four studies found no significant differences in kidney function between obese and non-obese LKDs at follow-up (range, 6-11 years) [25 28]. 3.2. Higher BMI and Blood Pressure The effects of higher BMI on the risk of hypertension in the general population have been reviewed. Hypertension data specific to higher BMI LKDs was available in eight studies in our review. BMI status was found to be associated with the presence of hypertension in six of these studies. Ibrahim et al reported that higher BMI significantly increased the risk of hypertension (OR 1.12, CI 1.04-1.21, p=0.003) [24]. In the two studies by Nogueira et al (2009, 2010), 41% of LKDs were found to be hypertensive at follow-up [20, 21]. In the 2009 study, mean blood pressures at follow-up were 120.8±14.5 mm Hg and 79.7±9.3 mm Hg for systolic and diastolic, respectively. In the 2010 study, mean blood pressures at follow-up were 122.0±13 mm and Hg 77.3±7.4mm Hg for systolic and diastolic, respectively. Nogueira et al (2010) also noted that, although mean blood pressures were similar at follow-up, a larger percentage of obese LKDs in their study had a diagnosis of hypertension than the LKDs from the Ibrahim study (30.6% vs. 24.7%) [21]. At follow-up, Tavakol et al noted that the mean systolic and diastolic blood pressures were higher for obese LKDs and non-obese LKDs who became obese during the study [25]. A greater number of obese LKDs carried a hypertension diagnosis at follow-up. On multivariate analysis, obesity at donation was found to be a risk factor for the development of hypertension during the study (OR 4.02; CI 1.2013.00, p=0.021) [25]. On multivariate analysis, Bello et al found that higher BMI carried a statistically significant prevalence ratio for hypertension at follow-up (PR 1.11, CI 1.04-1.17, p=.0003). At the time of follow-up, 20 LKDs had hypertension, with a mean BMI of 30.41±5.88 kg/m, compared to 57 without hypertension, with a mean BMI of 25.34±3.99 [23]. At baseline, in the study by Locke et al the mean systolic and diastolic blood pressures were higher for obese LKDs (124.1±13.1 mm Hg and 75.6±9.3 mm Hg, respectively) compared to non-obese LKDs (119.9±13.3 mm Hg and 72.9±9.4 mm Hg, respectively) [22]. Three studies either did not report comparison statistics [28] or did not find any differences in blood pressure relating to BMI status at follow-up [26, 27]. 3.3. Higher BMI and Proteinuria Risk of proteinuria has been discussed in the non-donor higher BMI population in the background section. Among the nine studies included in our current review, six studies presented data on proteinuria for higher BMI LKDs. The presence of proteinuria was noted to be significantly associated with higher BMI in three of these studies. Tavakol et al found that the 24-hour urine protein was 80±30 mg/d at baseline and 146 ± 62 mg/d at follow-up. A greater percentage of obese LKDs (44%) had abnormal proteinuria compared to non-obese LKDs (18%) (P=0.03). On multivariate analysis, obesity at donation was a significant predictor of abnormal proteinuria at follow-up (OR 8.9, CI 1.1-70.0, p=0.039) [25]. Nogueira et al (2009) found that 18% of the AA LKDs developed proteinuria at follow-up [20]. In the 2010 study by Nogueira et al, 19% of subjects developed microalbuminuria. They noted that development of microalbuminuria appeared to correlate with greater decrements in GFR [21]. The remaining three studies found no association between BMI and the presence of proteinuria [24, 26, 27]. 48 The Open Urology & Nephrology Journal, 2017, Volume 10 Murthy et al. 4. DISCUSSION In our current narrative review evaluating kidney-related outcomes for higher BMI LKDs, we noted significant heterogeneity in the reporting of data among the nine studies, ranging from the study design, follow-up period, control groups used, method of kidney function estimation, to the reporting of proteinuria and hypertension. The strengths of the included studies