Living kidney donor evaluation and safety assessment

To be able to safely accept potential living kidney donors, more insight is needed in the effect of nephrectomy on a living donor. In this thesis, we aimed to investigate the role of both established and novel glomerular, tubular, and other donor outcome predictors in donor screening and follow-up. We performed renal function measurements in living kidney donor candidates both before and after living kidney donation. We found that estimated Glomerular Filtration Rate (eGFR) can be used in living kidney donation, but that a proportion of living donors will still require measured GFR (mGFR), both in donor screening and in follow-up, to minimize failure of detection of declining renal function. We also demonstrated that the renal functional reserve capacity is a predictor of short-term renal hemodynamics after donation, but not of long-term GFR. Furthermore, we demonstrated that living donor tubular phosphate handling is a predictor of recipient renal function and that post-transplant hypophosphatemia is associated with beneficial outcomes. Finally, we found that pain after nephrectomy is an important donor outcome parameter. These results show that more insight into living kidney donation may lead to better donor outcomes. Therefore, we call for a study involving all aspects of organ donation and transplantation

The Association between Body Composition Measurements and Surgical Complications after Living Kidney Donation

Obesity is considered a risk factor for peri- and postoperative complications. Little is known about this risk in overweight living kidney donors. The aim of this study was to assess if anthropometric body measures and/or surgical determinants are associated with an increased incidence of peri- and postoperative complications after nephrectomy. We included 776 living kidney donors who donated between 2008 and 2018 at the University Medical Center Groningen. Prenephrectomy measures of body composition were body mass index (BMI), body surface area (BSA), waist circumference, weight, and waist-hip ratio. Incidence and severity of peri- and postoperative complications were assessed using the Comprehensive Complication Index. Mean donor age was 53 +/- 11 years; 382 (49%) were male, and mean BMI at donor screening was 26.2 +/- 3.41 kg/m(2). In total, 77 donors (10%) experienced peri- and postoperative complications following donor nephrectomy. Male sex was significantly associated with fewer surgical complications (OR 0.59, 0.37-0.96 95%CI, p = 0.03) in binomial logistic regression analyses. Older age (OR: 1.03, 1.01-1.05 95%CI, p = 0.02) and a longer duration of surgery (OR: 1.01, 1.00-1.01 95%CI, p = 0.02) were significantly associated with more surgical complications in binomial logistic regression analyses. Multinomial logistic regression analyses did not identify any prenephrectomy measure of body composition associated with a higher risk of surgical complications. This study shows that higher prenephrectomy BMI and other anthropometric measures of body composition are not significantly associated with peri- and postoperative complications following living donor nephrectomy

Reference values for low muscle mass and myosteatosis using tomographic muscle measurements in living kidney donors

Low muscle mass and myosteatosis are associated with poor clinical outcomes. Computed tomography (CT) imaging is an objective method for muscle mass and quality assessment; however consensus on cut-off values is lacking. This study assessed age-, sex-, and body mass index (BMI)-specific reference values of skeletal muscle parameters and correlated muscle mass with 24-h urinary creatinine excretion (24-h UCE). In total, 960 healthy subjects were included in this study. Muscle mass and quality were determined using axial CT slices at the vertebral level L3. The muscle area was indexed for height (skeletal muscle index [SMI]). The mean age was 53 ± 11 years, and 50% were male. The SMI reference values for low muscle mass in males were 38.8 cm2/m2 (20–29 years), 39.2 (30–39 years), 39.9 (40–49 years), 39.0 (50–59 years), 37.0 (60–69 years), and 36.8 (70–79 years). For females, these reference values were 37.5 cm2/m2 (20–29 years), 35.5 (30–39 years), 32.8 (40–49 years), 33.2 (50–59 years), 31.2 (60–69 years), and 31.5 (70–79 years). 24-h UCE and SMI were significantly correlated (r = 0.54, p &lt; 0.001) without bias between the two methods of assessing muscle mass. This study provides age-, sex-, and BMI-specific reference values for skeletal muscle parameters that will support clinical decision making.</p

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients - a prospective cohort study

Hydrogen sulfide (H2S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-four-hour urinary sulfate excretion (USE) may reflect H2S bioavailability. We aimed to investigate the association of USE with graft failure in a large prospective cohort of renal transplant recipients (RTR). We included 704 stable RTR, recruited at least 1 year after transplantation. We applied log-rank testing and Cox regression analyses to study association of USE, measured from baseline 24 h urine samples, with graft failure. Median age was 55 [45–63] years (57% male, eGFR was 45 ± 19 ml/min/1.73 m2). Median USE was 17.1 [13.1–21.1] mmol/24 h. Over median follow-up of 5.3 [4.5–6.0] years, 84 RTR experienced graft failure. RTR in the lowest sex-specific tertile of USE experienced a higher rate of graft failure during follow-up than RTR in the middle and highest sex-specific tertiles (18%, 13%, and 5%, respectively, log-rank P < 0.001). In Cox regression analyses, USE was inversely associated with graft failure [HR per 10 mmol/24 h: 0.37 (0.24–0.55), P < 0.001]. The association remained independent of adjustment for potential confounders, including age, sex, eGFR, proteinuria, time between transplantation and baseline, BMI, smoking, and high sensitivity C-reactive protein [HR per 10 mmol/24 h: 0.51 (0.31–0.82), P = 0.01]. In conclusion, this study demonstrates a significant inverse association of USE with graft failure in RTR, suggesting high H2S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR

Impact of measured versus estimated glomerular filtration rate-based screening on living kidney donor characteristics:A study of multiple cohorts

Background Most transplant centers in the Netherlands use estimated glomerular filtration rate (eGFR) for evaluation of potential living kidney donors. Whereas eGFR often underestimates GFR, especially in healthy donors, measured GFR (mGFR) allows more precise kidney function assessment, and therefore holds potential to increase the living donor pool. We hypothesized that mGFR-based donor screening leads to acceptance of donors with lower predonation eGFR than eGFR-based screening. Methods In this longitudinal cohort study, we compared eGFR (CKD-EPI) before donation in one center using mGFR-based screening (mGFR-cohort, n = 250) with two centers using eGFR-based screening (eGFR-cohort1, n = 466 and eGFR-cohort2, n = 160). We also compared differences in eGFR at five years after donation. Results Donor age was similar among the cohorts (mean±standard deviation (SD) mGFR-cohort 53 ±10 years, eGFR-cohort1 52±13 years, P = 0.16 vs. mGFR-cohort, and eGFR-cohort2 53±9 years, P = 0.61 vs. mGFR-cohort). Estimated GFR underestimated mGFR by 10±12 mL/ min/1.73m2 (mean±SD), with more underestimation in younger donors. In the overall cohorts, mean±SD pre-donation eGFR was lower in the mGFR-cohort (91±13 mL/min/ 1.73m2) than in eGFR-cohort1 (93±15 mL/min/1.73m2, P<0.05) and eGFR-cohort2 (94±12 mL/min/1.73m2, P<0.05). However, these differences disappeared when focusing on more recent years, which can be explained by acceptance of more older donors with lower predonation eGFR over time in both eGFR-cohorts. Five years post-donation, mean±SD eGFR was similar among the centers (mGFR-cohort 62±12 mL/min/1.73m2, eGFR-cohort1 61±14 mL/min/1.73m2, eGFR-cohort2 62±11 mL/min/1.73m2, P = 0.76 and 0.95 vs. mGFR-cohort respectively). In the mGFR-cohort, 38 (22%) donors were excluded from donation due to insufficient mGFR with mean±SD mGFR of 71±9 mL/min/1.73m2. Conclusions Despite the known underestimation of mGFR by eGFR, we did not show that the routine use of mGFR in donor screening leads to inclusion of donors with a lower pre-donation eGFR. Therefore eGFR-based screening will be sufficient for the majority of the donors. Future studies should investigate whether there is a group (e.g. young donors with insufficient eGFR) that might benefit from confirmatory mGFR testing