Senescence in Chronic Kidney Disease

The proposed studies will examine cellular senescence and the effect of senolytic therapy on
senescent cell burden, frailty, and adipose-derived mesenchymal stem cell function in
individuals with diabetic chronic kidney disease.

Inclusion Criteria:

1. Age 40-80 years

2. Chronic kidney disease estimated glomerular filtration rate (eGFR) 15-45 ml/min/1.73m2

3. Diabetes mellitus and taking diabetes medications

Exclusion Criteria:

1. Concomitant glomerulonephritis,

2. Nephrotic syndrome,

3. Solid organ transplantation,

4. Autosomal dominant or recessive polycystic kidney disease,

5. Known renovascular disease,

6. Pregnancy,

7. Active immunosuppression therapy,

8. Hemoglobin A1c≥11% at screening,

9. History of active substance abuse (including alcohol) within the past 2 years,

10. Current alcohol abuse (>3 alcoholic beverages/day or >21 per week),

11. Body weight >150 kg or body mass index>50

12. Human immunodeficiency virus infection

13. Active hepatitis B or C infection

14. Tyrosine kinase inhibitor therapy

15. Known hypersensitivity or allergy to dasatinib or quercetin

16. Inability to give informed consent

17. Uncontrolled systemic lupus erythematosus

18. Uncontrolled pleural/pericardial effusions or ascites

19. New invasive cancer except non-melanoma skin cancers

20. Invasive fungal or viral infection

21. Inability to tolerate oral medications

22. Total bilirubin>2x upper limit of normal

23. Subjects taking medications that are sensitive to substrates or substrates with a
narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or
inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are
absolutely necessary from an infectious disease perspective, then they will be allowed
only if the levels are therapeutic.

24. Subjects on strong inhibitors of CYP3A4.

25. Subjects on therapeutic doses of anticoagulants (e.g. warfarin, heparin, low molecular
weight heparin, factor Xa inhibitors, etc).

26. Subjects on antiplatelet agents (e.g. full dose aspirin which is deemed mandatory for
treatment, clopidogrel, etc.). Baby aspirin, if necessary for cardioprotection, will
be allowed.

27. Subjects on quinolone antibiotic therapy for treatment or for prevention of infections
within 10 days

28. Subjects taking H2-antagonists or proton pump inhibitors and unwilling to discontinue
therapy 1 week prior and 2 weeks following enrollment.

29. Corrected QT interval (QTc)>450 msec