Therapy for kidney disease and/or heart failure

Abstract

Medical systems and methods for treating kidney disease alone, heart failure alone, chronic kidney disease with concomitant heart failure, or cardiorenal syndrome are described. The systems and methods are based on delivery of a natriuretic peptide such as Vessel Dilator to a subject. Methods for increasing and maintaining peptide levels at a certain concentration include direct peptide delivery via either an external or implantable programmable pump.

1 . A medical system, comprising:
 a drug provisioning component to administer a therapeutically effective amount of a natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, or with concomitant kidney disease and heart failure or cardiorenal syndrome, said drug provisioning component maintaining a plasma concentration of the natriuretic peptide within a specified range wherein the drug provisioning component administers the natriuretic peptide subcutaneously or intramuscularly.   
     
     
         2 . The medical system of  claim 1 , wherein the natriuretic peptide is selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), atrial natriuretic peptide (ANP), vessel dilator (VD) and brain natriuretic peptide (BNP). 
     
     
         3 . The medical system of  claim 1 , wherein the specified range is not greater than a plasma concentration of the natriuretic peptide reached during either a subcutaneous bolus of the natriuretic peptide at 6000 ng/kg or a 1 hour intravenous infusion of the natriuretic peptide at 100 ng/kg·min in the subject. 
     
     
         4 . The medical system of  claim 1 , wherein the drug provisioning component delivers a therapeutically effective amount of the natriuretic peptide at a rate (ng/kg of body weight) from any one of about 10 to about 300 ng/kg·min, about 10 to about 150 ng/kg·min, about 25 to about 145 ng/kg·min, about 30 to about 140 ng/kg·min, about 35 to about 125 ng/kg·min, about 50 to about 120 ng/kg·min, about 65 to about 115 ng/kg·min, and about 85 to about 110 ng/kg·min of the subject's body weight. 
     
     
         5 . The medical system of  claim 1 , wherein the drug provisioning component delivers a therapeutically effective amount of the natriuretic peptide to maintain a plasma level of the natriuretic peptide at a steady state concentration from any one of about 0.5 to about 60 ng/mL, about 0.5 to about 40 ng/mL, about 10 to about 60 ng/mL, about 20 to about 40 ng/mL, about 30 to about 60 ng/mL, about 15 to about 55 ng/mL, about 25 to about 55 ng/mL about 35 to about 55 ng/mL about 23 to about 42 ng/mL about 19 to about 43 ng/mL about 10 to about 50 ng/mL 10 to about 20 ng/mL, about 20 to about 30 ng/mL, about 20 to about 35 ng/mL, about 25 to about 40 ng/mL, and about 30 to about 40 ng/mL. 
     
     
         6 . The medical system of  claim 1 , wherein the specified range is in addition to an endogenous concentration of the natriuretic peptide. 
     
     
         7 . The medical system of  claim 1 , wherein the drug provisioning component delivers the natriuretic peptide at a fixed, pulsed, continuous or variable rate. 
     
     
         8 . The medical system of  claim 1 , wherein the dosing schedule is based on the subject's body weight. 
     
     
         9 . The medical system of  claim 1 , wherein the dosing schedule is adjusted to meet pharmacokinetic variables calculated from the subject parameters, wherein the pharmacokinetic variables are based on any one of area under the curve, clearance, volume of distribution, half-life, elimination rates, minimum inhibitory concentrations, route of administration, endogenous concentrations of the natriuretic peptides, diurnal variation, and rate of drug delivery. 
     
     
         10 . The medical system of  claim 1 , wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease. 
     
     
         11 . The medical system of  claim 1 , wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V. 
     
     
         12 . The medical system of  claim 1 , wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure 
     
     
         13 . A method, comprising the steps of:
 administering a natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, or with concomitant kidney disease and heart failure or cardiorenal syndrome using a drug provisioning component, and   maintaining a plasma concentration of the natriuretic peptide within a specified range, wherein the drug provisioning component delivers the natriuretic peptide subcutaneously or intramuscularly.   
     
     
         14 . The method of  claim 13 , wherein the natriuretic peptide is selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), atrial natriuretic peptide (ANP), vessel dilator (VD) and brain natriuretic peptide (BNP). 
     
     
         15 . The method of  claim 13 , wherein the drug provisioning component is selected from an external or implantable drug delivery pump, an implanted or percutaneous vascular access port, a direct delivery catheter system, and a local drug-release device, and the drug provisioning component delivers the natriuretic peptide at a fixed, pulsed, continuous or variable rate. 
     
     
         16 . The method of  claim 13 , wherein the specified range is not greater than a plasma concentration of the natriuretic peptide reached during either a subcutaneous bolus of the natriuretic peptide at 6000 ng/kg or a 1 hour intravenous infusion of the natriuretic peptide at 100 ng/kg·min in the subject. 
     
     
         17 . The method of  claim 13 , wherein the drug provisioning component subcutaneously delivers a therapeutically effective amount of the natriuretic peptide at a continuous rate (ng/kg of body weight) matching the area under the curve of a subcutaneous bolus at 6000 ng/kg of the subject. 
     
     
         18 . The method of  claim 13 , further comprising the step of calculating a dosing schedule based on the subject's body weight. 
     
     
         19 . The method of  claim 18 , further comprising the step of adjusting the dosing schedule to meet pharmacokinetic variables calculated from one or more subject parameters, wherein the pharmacokinetic variables are selected from any one of area under the curve, clearance, volume of distribution, half-life, elimination rates, minimum inhibitory concentrations, route of administration, endogenous concentrations of the natriuretic peptides, diurnal variation, and rate of drug delivery. 
     
     
         20 . A method for administering a natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, or with concomitant kidney disease and heart failure or cardiorenal syndrome, comprising:
 administering the natriuretic peptide to the subject using a drug provisioning component to maintain a plasma level of the natriuretic peptide at a steady state concentration at a specified range, wherein   the specified range is from about 0.5 to about 60 ng/mL and the drug provisioning component administers the natriuretic peptide subcutaneously or intramuscularly,   the natriuretic peptide is selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), atrial natriuretic peptide (ANP), vessel dilator (VD) and brain natriuretic peptide (BNP), and   the administration of the natriuretic peptide has one or more renal protective, cardiovascular protective or renal or cardiovascular protective effects.   
     
     
         21 . The method of  claim 20 , wherein the natriuretic peptide is administered at a rate (ng/kg of body weight) from any one of about 10 to about 300 ng/kg·min, about 10 to about 150 ng/kg·min, about 25 to about 145 ng/kg·min, about 30 to about 140 ng/kg·min, about 35 to about 125 ng/kg·min, about 50 to about 120 ng/kg·min, about 65 to about 115 ng/kg·min, and about 85 to about 110 ng/kg·min of the subject's body weight. 
     
     
         22 . The method of  claim 20 , wherein the one or more renal protective, cardiovascular protective or renal or cardiovascular protective effects includes one or more selected from the group consisting of lowering blood pressure; lowering right atrial pressure; slowing, preventing or reversing a change in the glomerular filtration rate of the subject; increasing urine flow rate or sodium excretion rate; lowering the presence of albumin in urine or lowering the presence of protein in urine; reducing renal tissue damage; and increasing renal cortical blood flow. 
     
     
         23 . The method of  claim 20 , wherein the natriuretic peptide is vessel dilator (VD). 
     
     
         24 . The method of  claim 20 , wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4 kidney disease, Stage 5 kidney disease, and end-stage renal disease. 
     
     
         25 . The method of  claim 20 , wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V. 
     
     
         26 . The method of  claim 20 , wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.