Estimating the Contribution of Renal Function to Endothelial Dysfunction and Subclinical Inflammation with a Two-Cohort Study: Living Kidney Donors and Their Transplant Recipients
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Renal Function at One Year
2.3. Endothelial Dysfunction and Inflammation Biomarkers
2.4. Relationship Between Renal Function and Biomarkers
2.5. Blood Pressure and Atherosclerotic Burden in the Donor Cohort
2.6. Follow-Up at 5 Years
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Patients
4.3. Study Procedures
- Glomerular filtration rate before nephrectomy in donors and at one year in donors and recipients was measured by iohexol clearance (mGFR). The protocol for the study was guided by Instituto de Tecnologías Biomédicas, University of La Laguna (Tenerife, Spain) [41]. Iohexol levels in plasma samples obtained at each center were sent to this validated lab for their determination by HPLC [29]. Results of mGFR were not available to clinicians at the time of kidney donation. Additionally, the estimated glomerular filtration rate by CKD-EPI (eGFR-CKD-EPI) and MDRD-4 (eGFR-MDRD-4) using standard formulas was employed to estimate renal function in both cohorts.
- Urinary albumin to creatinine ratio (UACR) in an early-morning spot sample was determined locally by an immunoturbidimetric assay.
- An oral glucose tolerance test (OGTT) was performed at baseline and at 1 year in the donors. Insulin levels were also determined locally at both time periods to calculate the HOMA-IR.
- Serum samples for the measurement of endothelial dysfunction and low-grade inflammation markers were obtained and stored at each center. At the end of the study, all samples were sent to Hospital Universitari Vall d’Hebron laboratories (Barcelona) for their determination.
- In the donor cohort the following procedures were also performed:
- Ambulatory blood pressure monitoring (ABPM) with an overnight-automated monitor (Spacelab 90207; Spacelabs Healthcare, Snoqualmie, WA, USA) with appropriate cuff sizes for each patient was performed at baseline and at one year.
- Baseline atherosclerotic burden:A carotid ultrasound to determine the number of plaques and intima-media thickness (IMT) was performed in both carotid arteries with a high-frequency (8–12 MHz) linear transducer (ESAOTE, 7300, Florence, Italy). The numbers of carotid plaques in both arteries were added and the mean intima-media thickness (IMT) of both arteries was calculated.Carotid–femoral pulse wave velocity (PWV, m/s) was measured by pulse tonometry (Sphingmocor Atcor, EM3, Sidney, Australia).The ankle–brachial index (ABI) was determined by an automated blood pressure monitor with appropriate cuff sizes (Omron, Kyoto, Japan).
4.4. Treatments
4.5. Biomarkers of Endothelial Dysfunction and Chronic Inflammation
- Endothelial dysfunction: Circulating levels of soluble VCAM (vascular cell adhesion molecule), soluble ICAM (intercellular adhesion molecule), soluble E-selectin and PTX-3 (pentraxin) were determined by the microfluidics-based quantitative immunoassay, ELLA® (Protein Simple, CA, USA) [42]. The serum concentration of PECAM (platelet/endothelial cell adhesion molecule) was determined by ELISA (Novus Biologicals, CO, USA). Determination of vWF (antigen of von Willebrand factor) serum levels was performed on an AcuStar instrument (Instrumentation Laboratories, Bedford, MA, USA), by using the HemosIL AcuStar VWF:Ag chemiluminescent cartridge reagent kit [43].
- Chronic inflammation: usPCR (ultrasensitive C-reactive protein) was determined by nephelometry. Circulating levels of IL-6 (interleukin 6), sTNFR1 and sTNFR2 (soluble tumor necrosis factor receptors 1 and 2) were determined using the microfluidics-based quantitative immunoassay, ELLA® (Protein Simple, CA, USA) [42]. The serum concentration of sTWEAK (soluble TNF-like weak inducer of apoptosis) was determined by ELISA (DuoSet, Minneapolis, MN, USA) [44].
4.6. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Donors | Recipients |
---|---|---|
Age (years) | 52 ± 12 | 48 ± 14 |
Sex (male/female) | 20/30 | 29/21 |
Race (Caucasian/Hispanic) | 46/4 | 47/3 |
Height (cm) | 165 ± 9 | 168 ± 10 |
Weight (kg) | 72 ± 13 | 74 ± 16 |
BMI (kg/m2) | 26.0 ± 3.8 | 26.2 ± 5.2 |
Hypertension (no/yes) | 42/8 | 7/43 |
Diabetes (no/yes) | 50/0 | 44/6 |
Smoker (never/past/current) | 32/8/10 | 30/14/6 |
Office systolic blood pressure (mm Hg) | 126.4 ± 14.8 | 137.6 ± 17.9 |
Office diastolic blood pressure (mm Hg) | 73.2 ± 9.4 | 83.1 ± 12.4 |
Mean office blood pressure (mm Hg) | 91.0 ± 10.0 | 101.3 ± 13.0 |
Serum glucose (mg/dL) | 91 ± 6 | 125 ± 42 |
Total cholesterol (mg/dL) | 219 ± 41 | 194 ± 38 |
LDL cholesterol (mg/dL) | 140 ± 36 | 125 ± 35 |
Triglycerides (mg/dL) | 113 ± 37 | 109 ± 68 |
Cause of ESRD | ||
GN/CTIN/ADPKD/DN/vascular/others | 12/9/7/3/5/14 | |
Pre-emptive/HD/PD | 30/15/5 | |
Time on RRT (mo.) | 11 ± 4 |
Donors | Recipients | |||
---|---|---|---|---|
Baseline | 1 Year | Baseline | 1 Year | |
Creatinine (mg/dL) | 0.75 ± 0.15 | 1.08 ± 0.22 | 6.01 ± 2.62 | 1.36 ± 0.41 |
eGFR CKD-EPI | 98 ± 13 | 66 ± 11 | 10 ± 4 | 64 ± 17 |
eGFR MDRD-4 | 95 ± 16 | 61 ± 10 | 10 ± 4 | 56 ± 15 |
mGFR | 93 ± 17 | 65 ± 12 | n.a. | 57 ± 13 |
Donors | Recipients | |||
---|---|---|---|---|
Baseline | 1 Year | Baseline | 1 Year | |
VCAM-1 [ng/mL] | 635 ± 197 | 718 ± 213 * | 1208 ± 417 | 943 ± 313 * |
ICAM-1 [ng/mL] | 382 ± 91 | 407 ± 101 | 430± 159 | 433 ± 109 |
E-selectin [ng/mL] | 29 ± 10 | 30 ± 11 | 37 ± 19 | 34 ± 14 ** |
PECAM-1 [ng/mL] | 73 ± 13 | 80 ± 14 | 79 ± 23 | 71 ±15 * |
vWF [%] | 96 ± 36 | 103 ± 35 | 181 ± 53 | 167 ± 57 |
PTX-3 [ng/mL] | 2.7 ± 1.8 | 3.4 ± 2.1 | 3.7 ± 3.1 | 3.0 ± 2.3 |
UACR [mg/g] | 5.9 ± 6.3 | 10.5 ± 24.0 | - | - |
IL-6 [pg/mL] | 4.6 ± 5.7 | 6.1 ± 10.8 | 7.7 ± 9.0 | 6.1 ± 3.6 |
TNFR1 [ng/mL] | 1.4 ± 0.9 | 1.9 ± 0.4 * | 10.2 ± 5.6 | 2.4 ± 0.8 * |
TNFR2 [ng/mL] | 2.8 ± 1.2 | 3.8 ± 0.7 * | 12.2 ± 4.0 | 4.8 ± 1.9 * |
TWEAK [pg/mL] | 544 ± 499 | 493 ± 100 | 437 ± 107 | 465 ± 122 |
hsCRP [mg/dL] | 0.36 ± 1.04 | 0.31 ± 0.39 | 0.41 ± 0.69 | 0.36 ± 0.41 |
Time Point | Office BP | ABPM-Day | ABPM-Night | ABPM-Pattern | |||
---|---|---|---|---|---|---|---|
SBP | DBP | SBP | DPB | SBP | DPB | Non-Dipper (%) | |
Baseline | 124 ± 15 | 76 ± 9 | 122 ± 13 | 76 ± 9 | 109 ± 11 | 66 ± 8 | 18% |
1 year | 129 ± 15 | 77 ± 10 | 120 ± 10 | 77 ± 8 | 108 ± 9 | 66 ± 8 | 34% |
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Torres, I.B.; Burballa, C.; González-Posada, J.M.; Hernández, D.; Porrini, E.; Perurena, J.; Cortina, V.; Perelló, M.; Redondo-Pachón, D.; González-Rine, A.; et al. Estimating the Contribution of Renal Function to Endothelial Dysfunction and Subclinical Inflammation with a Two-Cohort Study: Living Kidney Donors and Their Transplant Recipients. Int. J. Mol. Sci. 2025, 26, 9535. https://doi.org/10.3390/ijms26199535
Torres IB, Burballa C, González-Posada JM, Hernández D, Porrini E, Perurena J, Cortina V, Perelló M, Redondo-Pachón D, González-Rine A, et al. Estimating the Contribution of Renal Function to Endothelial Dysfunction and Subclinical Inflammation with a Two-Cohort Study: Living Kidney Donors and Their Transplant Recipients. International Journal of Molecular Sciences. 2025; 26(19):9535. https://doi.org/10.3390/ijms26199535
Chicago/Turabian StyleTorres, Irina B., Carla Burballa, José M. González-Posada, Domingo Hernández, Esteban Porrini, Janire Perurena, Vicente Cortina, Manel Perelló, Dolores Redondo-Pachón, Ana González-Rine, and et al. 2025. "Estimating the Contribution of Renal Function to Endothelial Dysfunction and Subclinical Inflammation with a Two-Cohort Study: Living Kidney Donors and Their Transplant Recipients" International Journal of Molecular Sciences 26, no. 19: 9535. https://doi.org/10.3390/ijms26199535
APA StyleTorres, I. B., Burballa, C., González-Posada, J. M., Hernández, D., Porrini, E., Perurena, J., Cortina, V., Perelló, M., Redondo-Pachón, D., González-Rine, A., Cabello, M., Pérez-Sáez, M. J., Crespo, M., Bestard, O., Serón, D., & Moreso, F. (2025). Estimating the Contribution of Renal Function to Endothelial Dysfunction and Subclinical Inflammation with a Two-Cohort Study: Living Kidney Donors and Their Transplant Recipients. International Journal of Molecular Sciences, 26(19), 9535. https://doi.org/10.3390/ijms26199535