Methods and compositions for diagnosis and prognosis of renal injury and renal failure

A method for predicting progression to AKI stage III in patients with AKI stage I or II, wherein AKI stage is defined by the AKIN criteria, comprising:

• (a) selecting a critically ill patient diagnosed with AKI stage I or II, wherein the subject is euvolemic;
• (b) obtaining a urine sample from the subject for measuring a biomarker in the urine and measuring urine output,
• wherein the biomarker comprises one or more of Metalloproteinase inhibitor 2, Thrombospondin-1, Antileukoproteinase, Insulin-like growth factor-binding protein 7, Metalloproteinase inhibitor 4, Metalloproteinase inhibitor 1, Hyaluronic acid, Transmembrane glycoprotein NMB, Follistatin, Hepatocyte growth factor, Tumor necrosis factor receptor superfamily member 6, Growth-regulated alpha protein, C-C motif chemokine 24, Metalloproteinase inhibitor 3, C-X-C motif chemokine 6, Tumor necrosis factor receptor superfamily member 11B, Cystatin-C, Beta-2-microglobulin, Serum albumin, Clusterin, Interleukin-8, Neutrophil gelatinase-associated lipocalin, Interleukin-2 receptor alpha chain, Hepatitis A virus cellular receptor 1, Chitinase-3-like protein 1, or Serum creatinine, and wherein the result of the biomarker assay indicates that the subject has stage I or stage II acute kidney injury progression;
• (c) performing a diuretic stress test comprising:
• 1. determining the baseline urine output for the subject,
• 2. administering a diuretic intravenously to the subject in an amount effective to cause diuresis;
• and
• 3. determining the diuretic-induced urine output for the first 2 hours after administering the diuretic intravenously;
• (d) identifying the subject at risk for progressing to AKI stage III in 14 days and in need of treatment, when the diuretic-induced urinary output is 200 mL or less for the first two hours after administering of the diuretic;
• (e) administering treatment to the identified patient of (d) wherein the treatment comprises one or more of initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, and modifying diuretic administration,
• wherein the diuretic is a loop diuretic selected from the group consisting of furosemide, bumetanide, ethacrynic acid, torsemide, mannitol, torsemidehydrochlorothiazide, bendroflumethiazide, hydroflumethiazide, chlorothiazide, polythiazide, trichlormethiazide, cyclopenthiazide, methyclothiazide, cyclothiazide, and mebutizide, and
• wherein the biomarker comprises one or more of Metalloproteinase inhibitor 2, Thrombospondin-1, Antileukoproteinase, Insulin-like growth factor-binding protein 7, Metalloproteinase inhibitor 4, Metalloproteinase inhibitor 1, Hyaluronic acid, Transmembrane glycoprotein NMB, Follistatin, Hepatocyte growth factor, Tumor necrosis factor receptor superfamily member 6, Growth-regulated alpha protein, C-C motif chemokine 24, Metalloproteinase inhibitor 3, C-X-C motif chemokine 6, Tumor necrosis factor receptor superfamily member 11B, Cystatin-C, Beta-2-microglobulin, Serum albumin, Clusterin, Interleukin-8, Neutrophil gelatinase-associated lipocalin, Interleukin-2 receptor alpha chain, Hepatitis A virus cellular receptor 1, Chitinase-3-like protein 1, and Serum creatinine.