Methods of treating ischemic tissue injury or kidney disease, e.g., delayed graft function, that include administering a Nicotinamide adenine dinucleotide (NAD)/niacinamide (NAM) pathway agonist.
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1. (canceled) 2. A method of treating, or reducing risk of developing, ischemic tissue injury or a chronic condition of the brain, kidney, or heart, in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a Nicotinamide adenine dinucleotid
1. (canceled) 2. A method of treating, or reducing risk of developing, ischemic tissue injury or a chronic condition of the brain, kidney, or heart, in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a Nicotinamide adenine dinucleotide (NAD)/niacinamide (NAM) pathway agonist. 3. The method of claim 2, wherein the ischemic tissue injury is acute kidney injury (AKI); ischemic stroke; or myocardial infarction; the chronic condition of the kidney is diabetic kidney disease, hypertensive nephropathy, FSGS, or ischemic nephropathy; the chronic heart disease is left ventricular hypertrophy, ischemic cardiomyopathy, or non-ischemic cardiomyopathy; or the chronic cerebral disease is multi-infarct dementia, Alzheimer's disease, or Parkinson's Lewy body dementia. 4. The method of claim 3, wherein the AKI is delayed graft function. 5. A method of treating, or reducing risk of developing, delayed graft function, in a subject, the method comprising administering to a donor subject or donor organ, and/or to the preservation solutions a therapeutically effective amount of a Nicotinamide adenine dinucleotide (NAD)/niacinamide (NAM) pathway agonist. 6. The method of claim 4, wherein the organ-graft is a metabolically active transplanted organ, comprising kidney, heart, liver, and lungs. 7. The method of claim 2, wherein the NAD/NAM pathway agonist is Nicotinamide adenine dinucleotide (NAD); niacinamide (NAM) itself; nicotinamide mononucleotide (NMN); Nicotinamide riboside (NR); and P7C3 and analogs thereof, optionally P7C3-A20. 8. The method of claim 2, wherein the NAD/NAM pathway agonist is a N′-Nicotinamide Methyltransferase (NNMT) inhibitor. 9. The method of claim 8, wherein the NNMT inhibitor is an inhibitory nucleic acid that specifically targets an NNMT nucleic acid, or 1-me-Nam or an analog thereof. 10. The method of claim 9, wherein the inhibitory nucleic acid is an antisense oligonucleotide or small interfering siRNA specifically targeting NNMT. 11. The method of claim 9, wherein the inhibitory nucleic acid is modified. 12. The method of claim 9, wherein the inhibitory nucleic acid includes one or more locked nucleotides. 13. The method claim 2, wherein the subject does not yet have AKI, but has been or will be hospitalized. 14. The method claim 2, wherein the subject has had or is at risk of developing an ischemic renal injury. 15. The method claim 2, wherein the subject has had or is at risk of developing delayed graft function. 16. The method of claim 2, wherein the subject has been or will be administered or exposed to a renal toxin, optionally a therapeutic agent with renal toxicity, optionally cisplatin. 17. A method of diagnosing kidney disease, or determining risk of developing risk of kidney disease, in a subject, the method comprising: obtaining a sample comprising urine from the subject;evaluating a level of one, two, or all three of Kyn, Kyu, and/or Quin, and/or a Nam metabolite selected from the group consisting of Nam, methyl-Nam, Anthranilate, hydroxy-anthranilate, Xanthurenate, and Picolinate, in the sample;optionally normalizing the level of Kyn, Kyu, and/or Quin and/or the Nam metabolite to another metabolite present in the urine sample, optionally Trp;comparing the level of Kyn, Kyu, and/or Quin or the Nam metabolite with one or more references; anddetermining that a subject who has a level of Kyn, Kyu, and/or Quin or a Nam metabolite above the reference level has or is at risk of developing kidney disease. 18. The method of claim 17, wherein the reference is a control reference that represents a normal level of one, two, or all three of Kyn, Kyu, and/or Quin, or a level of a Nam metabolite, optionally a level in an unaffected subject who does not have and is not at risk of developing kidney disease, and/or a disease reference that represents a level of the proteins associated with kidney disease, optionally a level in a subject having or at risk of developing kidney disease, optionally AKI or CKD. 19. The method of claim 17, further comprising administering to the subject a NAD/NAM pathway agonist. 20. The method of claim 5, further comprising diagnosing delayed graft function in a subject who has received an organ transplant, the method comprising: obtaining a sample, optionally a sample comprising a tissue biopsy from the transplanted organ in the subject, or a non-invasive surrogate thereof;determining a level of PGC1α in the sample, optionally using immunostaining;comparing the PGC1α level in the sample with one or more reference levels; anddetermining that a subject who has a PGC1α level below the reference level is at risk of developing delayed graft function and experiencing delayed recovery. 21. The method of claim 20, wherein the reference is a control reference that represents a normal PGC1α immunostaining score or a disease reference that represents PGC1α immunostaining score associated with delayed graft function. 22.-27. (canceled)
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