Treatment of chronic kidney disease and other renal dysfunction using a gdf15 modulator

Abstract

The invention provides methods and compositions for treating a subject having a renal-related disorder, such as chronic kidney disease (CKD), end stage renal failure, diabetes, insulin resistance, kidney hypertrophy, kidney hypotrophy, polycystic kidney disease, proteinuria, hyperglycemia, hyperuricemia, gout, kidney stones, hypertension or hypertensive nephropathy, dyslipidemia, anemia and/or reduced erythropoietin production, iron deficiency or hyperfiltration. The methods and compositions use or contain a composition that reduces or inhibits GDF15 activity.

What is claimed is: 
     
         1 . A method of increasing renal function in a subject in need thereof, the method comprising administering an effective amount of a composition comprising a GDF15 modulator thereby to increase renal function in the subject. 
     
     
         2 . A method of treating a subject having a renal disorder or renal dysfunction in need thereof, the method comprising administering an effective amount of a composition comprising a GDF15 modulator thereby to ameliorate a symptom of the renal disorder or renal dysfunction. 
     
     
         3 . A method of reducing or reversing renal hypotrophy in a subject in need thereof wherein the subject has one or more symptoms of chronic kidney disease, the method comprising administering an effective amount of a composition comprising a GDF15 modulator thereby to reduce or reverse renal hypotrophy in the subject. 
     
     
         4 . A method of treating or preventing chronic kidney disease (CKD) in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a GDF15 modulator thereby to treat or prevent CKD in the subject. 
     
     
         5 . The method of any one of  claims 1 - 4 , wherein the subject has an elevated blood level of GDF15. 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the subject exhibits a glomerular filtration rate (GFR) below 90 ml creatinine/minute/1.73m 2  body-surface area. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the subject exhibits albuminuria. 
     
     
         8 . The method of  claim 7 , wherein the subject exhibits urinary excretion of albumin in excess of 30 mg per day, 30 mg per liter of urine, and/or 30 μg/mg of creatinine in urine. 
     
     
         9 . The method of any one of  claims 1 - 8 , wherein the subject exhibits hyperuricemia. 
     
     
         10 . The method of  claim 9 , wherein the subject exhibits a serum uric acid level of at least 6.3 mg/dL. 
     
     
         11 . The method of any one of  claims 1 - 10 , wherein the subject exhibits iron deficiency. 
     
     
         12 . The method of  claim 11 , wherein the subject exhibits transferrin saturation of below 25% and a low ferritin level. 
     
     
         13 . The method of any one of  claims 1 - 12 , wherein the subject has been diagnosed as having chronic kidney disease. 
     
     
         14 . The method of any one of  claims 1 - 13 , wherein GDF15 modulator decreases or inhibits GDF15 activity. 
     
     
         15 . The method of any one of  claims 1 - 14 , wherein the GDF15 modulator is an anti-GDF15 antibody. 
     
     
         16 . The method of  claim 15 , wherein the anti-GDF15 antibody is humanized or human.