β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus
Abstract
:1. Introduction
2. Results
2.1. Localization of β3-AR in Human Kidney Tubules
2.2. Study in OAB Patients
2.2.1. Study Design and Patients Demographics
2.2.2. Urine Output and Osmolality before and throughout Treatment with Betmiga®
2.2.3. Urine Electrolytes Excretion before and throughout Treatment with Betmiga®
2.2.4. Urine Excretion of AQP2 and NKCC2 before and throughout Treatment with Betmiga®
3. Discussion
4. Materials and Methods
4.1. Human Kidney Immunofluorescence
4.2. Participants and Study Design
4.3. Number of Subjects
4.4. Urine Collection and Analyses
4.5. ELISA Test for uAQP2 and uNKCC2 on Urine Sample
4.6. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cluster 1, N = 25 | Cluster 2, N = 20 | Cluster 3, N = 16 | |||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | T1 | T2 | T4 | Baseline | T8 | Baseline | T12 | ||
24 h Urine Output | L | 1.428 ± 0.161 | 1.314 ± 0.121 | 1.306 ± 0.109 | 1.220 ± 0.106 | 1.385 ± 0.162 | 1.130 ± 0.137 | 1.288 ± 0.183 | 1.419 ± 0.123 |
Urine Osmolality | mOsm/Kg | 601.2 ± 40.7 | 589.2 ± 40.5 | 620.6 ± 47.8 | 644 ± 46.2 | 638.2 ± 42.2 | 699.4 ± 49.1 | 658.4 ± 45.9 | 596.4 ± 43.3 * |
Urine Na+ | mEq/L | 115.3 ± 8.9 | 114.7 ± 10.5 | 118.8 ± 9.9 | 116.9 ± 10.5 | 122.4 ± 9.2 | 122 ± 12.5 | 122.1 ± 9.5 | 113.2 ± 8.8 |
mEq/24 h | 151.9 ± 17 | 139.7 ± 13 | 143.4 ± 10 | 132 ± 15 | 154.6 ± 18 | 137 ± 16 | 144.4 ± 19.3 | 157.1 ± 14 | |
mEq/mg Creatinine | 0.103 ± 0.006 | 0.111 ± 0.007 | 0.107 ± 0.006 | 0.098 ± 0.007 | 0.10 ± 0.005 | 0.092 ± 0.007 | 0.102 ± 0.006 | 0.101 ± 0.006 | |
Urine K+ | mEq/L | 44.3 ± 3.7 | 41.9 ± 4.2 | 45.2 ± 3.3 | 45.9 ± 3 | 45.01 ± 4.1 | 51.5 ± 4 | 47.5 ± 4.8 | 40.3 ± 3.3 |
mEq/24 h | 54.7 ± 5.7 | 48 ± 4.6 | 53.4 ± 4 | 50.1 ± 3.7 | 54.8 ± 6.1 | 54.5 ± 4.7 | 54.2 ± 7.7 | 54 ± 4.7 | |
mEq/mg Creatinine | 0.038 ± 0.003 | 0.039 ± 0.003 | 0.04 ± 0.002 | 0.038 ± 0.002 | 0.04 ± 0.003 | 0.039 ± 0.002 | 0.04 ± 0.003 | 0.036 ± 0.002 | |
Urine Cl− | mEq/L | 116.5 ± 8 | 115.8 ± 9 | 123.6 ± 9 | 127.8 ± 11 | 120 ± 8.6 | 135.5 ± 13 | 119.7 ± 8.5 | 115.4 ± 9 |
mEq/24 h | 149.7 ± 17 | 137.3 ± 12 | 143 ± 11 | 137.9 ± 15 | 153.3 ± 18.2 | 145.9 ± 15 | 140 ± 19.1 | 156.4 ± 14 | |
mEq/mg Creatinine | 0.101 ± 0.008 | 0.110 ± 0.007 | 0.109 ± 0.005 | 0.104 ± 0.006 | 0.1 ± 0.006 | 0.099 ± 0.006 | 0.1 ± 0.006 | 0.101 ± 0.006 | |
Urine Creatinine | mg/ml | 1.18 ± 0.09 | 1.15 ± 0.09 | 1.21 ± 0.09 | 1.22 ± 0.08 | 1.26 ± 0.10 | 1.29 ± 0.10 | 1.32 ± 0.12 | 1.18 ± 0.09 |
mg/24 h | 1450 ± 130 | 1240 ± 80 | 1350 ± 90 | 1350 ± 80 | 1470 ± 140 | 1400 ± 110 | 1490 ± 90 | 1570 ± 90 |
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Milano, S.; Maqoud, F.; Rutigliano, M.; Saponara, I.; Carmosino, M.; Gerbino, A.; Lucarelli, G.; Battaglia, M.; Svelto, M.; Procino, G. β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus. Int. J. Mol. Sci. 2023, 24, 1136. https://doi.org/10.3390/ijms24021136
Milano S, Maqoud F, Rutigliano M, Saponara I, Carmosino M, Gerbino A, Lucarelli G, Battaglia M, Svelto M, Procino G. β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus. International Journal of Molecular Sciences. 2023; 24(2):1136. https://doi.org/10.3390/ijms24021136
Chicago/Turabian StyleMilano, Serena, Fatima Maqoud, Monica Rutigliano, Ilenia Saponara, Monica Carmosino, Andrea Gerbino, Giuseppe Lucarelli, Michele Battaglia, Maria Svelto, and Giuseppe Procino. 2023. "β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus" International Journal of Molecular Sciences 24, no. 2: 1136. https://doi.org/10.3390/ijms24021136