Pre-donation Assessment of Cystatin C to Improve Prediction of Pre- and Post-Donation GFR in Potential Living Kidney Donors.

BACKGROUND AND HYPOTHESIS: Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most eGFR equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (CysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR. METHODS: We assessed the performance of CKD-EPI equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cystatin C (eGFRCysC-2012), or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation measured GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex-stratified and height-indexed). RESULTS: Pre-donation eGFRcombined 2012 and eGFRcombined 2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined 2021 was most accurate for estimating both pre-donation (bias 0.01±11.9 mL/min/1.73m2) and post-donation mGFR (bias 1.3±8.5 mL/min/1.73 m2). In donors with high/low muscle mass, CysC-based equations (with or without creatinine) performed better compared to equations based on only creatinine. CONCLUSIONS: In conclusion, combined eGFR equations yielded a better estimate of pre- and post-donation mGFR, compared to estimates based on creatinine or CysC only. The added value of CysC seems particularly pronounced in donors with high or low muscle mass.

Central Body Fat Distribution and Kidney Function after Living Kidney Donation.

BACKGROUND: In most screening guidelines, high body mass index (BMI) is considered a contraindication for kidney donation. New insights suggest that central body fat distribution might provide greater power in assessing kidney risk. This study aimed to determine whether BMI and central body fat distribution measures are associated with long-term kidney function after donor nephrectomy. We hypothesized that higher BMI, waist circumference (WC), and waist-to-height ratio (WHtR) were associated with lower kidney function long term after donation. METHODS: The study population consisted of living kidney donors. BMI, WC, and WHtR were measured during donor screening. The outcome postdonation kidney function was assessed using measured GFR (mGFR) (mGFR, 125 I-iothalamate infusion) at 3 months ( n =1042), 5 years ( n =556), and 10 years ( n =210) of follow-up. Primary multivariable linear regression analyses were performed with BMI and WC and secondary analyses with WHtR. Linear mixed models were performed to investigate change in postdonation eGFR. RESULTS: The donor age was 52±11 years, and 48% were male. The mean BMI was 26.1±3.6 kg/m 2 , and WC was 91±11 cm. Higher predonation BMI was associated with lower mGFR throughout follow-up: -1.35 (95% confidence interval [CI], -1.95 to -0.80), -1.55 (95% CI, -2.50 to -0.65), and -2.35 (95% CI, -4.10 to -0.60) ml/min per m 2 per 5 kg/m 2 higher BMI at 3 months, 5, and 10 years after donation, respectively, adjusted for sex, age, and predonation GFR. For WC, differences in mGFR were -1.30 (95% CI, -1.70 to -0.90), -1.50 (95% CI, -2.20 to -0.80), and -1.70 (95% CI, -3.00 to -0.50) ml/min per m 2 per 10 cm higher WC at 3 months, 5, and 10 years after donation, respectively. In male donors, BMI and WC were significantly associated with a negative postdonation change in eGFR. CONCLUSIONS: Higher BMI and WC were independently associated with lower GFR (long term) after living kidney donation.

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 < 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.

Validity of computed tomography defined body composition as a prognostic factor for functional outcome after kidney transplantation.

BACKGROUND: The prevalence of sarcopenia is markedly higher in kidney transplant candidates than in the general population. It is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which increases the risk of adverse postoperative outcomes. METHODS: We studied the impact of computed tomography defined preoperative sarcopenia, defined as a skeletal muscle index below age and gender specific cut-off values, on postoperative physical functional outcomes (grip strength, 4-m walking test, timed up and go, and sit to stand) at 6 months follow up. RESULTS: A total of 107 patients transplanted between 2015 and 2019 were included in this single-centre study. Mean age was 60.3 (±13.1), and 68.2% of patients were male. Ten patients (9.4%) were identified as sarcopenic. Sarcopenic patients were younger (55.6 (±15.1) vs. 60.8 (±12.9) years), more likely to be female (60.0% vs. 28.9%), and had an increased dialysis vintage (19 [2.5-32.8] vs. 9 [0.0-21.0] months) in comparison with their non-sarcopenic counterparts. In univariate analysis, they had a significantly lower body mass index and skeletal muscle area (P ≤ 0.001). In multivariate regression analysis, skeletal muscle index was significantly associated with grip strength (ß = 0.690, R2  = 0.232) and timed up and go performance (ß = -0.070, R2  = 0.154). CONCLUSIONS: We identified a significant association between sarcopenia existing pre-transplantation and poorer 6 months post-transplantation physical functioning with respect to hand grip strength and timed up and go tests in kidney transplant recipients. These results could be used to preoperatively identify patients with an increased risk of poor postoperative physical functional outcome, allowing for preoperative interventions to mitigate these risks.

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/m2. 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.