Methods and apparatus for kidney dialysis and extracorporeal detoxification

Abstract

The present disclosure relates to a dialysis apparatus comprising a membrane having at least one protein from the lipocalin family bound thereon. The disclosure further relates to methods of removing non-polar, hydrophobic and/or protein bound uremic toxins from a target subject utilizing the dialysis apparatus described herein as well as methods of extracorporeal detoxification.

What is claimed is: 
     
         1 . An apparatus for a dialysis procedure comprising a body having an inlet and an outlet and defining an interior, the interior including at least one membrane having at least one protein from the lipocalin family bound thereon, wherein the apparatus is arranged so that a fluid entering the apparatus contacts the at least one protein from the lipocalin family bound to the at least one membrane in the interior of the apparatus. 
     
     
         2 . The apparatus of  claim 1 , wherein the at least one protein from the lipocalin family is selected from the group consisting of alpha-1-microglobulin (protein HC), major urinary proteins, alpha-1-acid glycoprotein (orosomucoid), aphrodisin, apolipoprotein D, beta-lactoglobulin, complement component C8 gamma chain, crustacyanin, epididymal-retinoic acid binding protein (E-RABP), insectacyanin, odorant binding protein (OBP), human pregnancy-associated endometrial alpha-2 globulin (PAEP), probasin (PB), a prostatic protein, prostaglandin D synthase, purpurin, Von Ebner's gland protein (VEGP), and lizard epididymal secretory protein IV (LESP IV). 
     
     
         3 . The apparatus of  claim 1 , wherein the at least one protein from the lipocalin family is selected from the group consisting of FABP1, FABP2, FABP3, FABP4, FABP5, FABP6, FABP7, LCN1, LCN2, LCN8, LCN09, LCN10, LCN12, OBP2A, OBP2B, RBP1, RBP2, RBP4, RBP5, RBP7, PAEPPERF15, PMP2, PTGDSAMBP, APOD, C8G, CRABP1, CRABP2 UNX2541 ORM1 and ORM2. 
     
     
         4 . The apparatus of  claim 1 , wherein the at least one protein comprises a plurality of proteins wherein the proteins comprise the same type of protein selected from the lipocalin family. 
     
     
         5 . The apparatus of  claim 1 , wherein the at least one protein comprises a plurality of proteins wherein the proteins comprise a combination of different types of proteins selected from the lipocalin family. 
     
     
         6 . The apparatus of  claim 1 , wherein the membrane is at least one of polyamide, polysulfone, polyethersulfone, cellulose acetate, triacetate, polyacrylonitrile or polymethylmethacrylate. 
     
     
         7 . The apparatus of  claim 1 , wherein the at least one protein is covalently bound to the at least one membrane. 
     
     
         8 . The apparatus of  claim 1 , wherein the clearance of hydrophobic, protein bound uremic toxins is facilitated. 
     
     
         9 . The apparatus of  claim 8 , wherein the hydrophobic, protein bound uremic toxin is at least one of p-cresol, indoxyl sulfate or p-cresol sulfate. 
     
     
         10 . A method of dialysis comprising subjecting a bodily fluid from a subject to an apparatus comprising a body having an inlet and an outlet and defining an interior, the interior including at least one membrane having at least one protein from the lipocalin family bound thereon, wherein the apparatus is arranged so that the bodily fluid entering the apparatus contacts the at least one protein from the lipocalin family bound to the at least one membrane in the interior of the apparatus. 
     
     
         11 . The method of  claim 10 , wherein the at least one protein from the lipocalin family is selected from the group consisting of alpha-1-microglobulin (protein HC), major urinary proteins, alpha-1-acid glycoprotein (orosomucoid), aphrodisin, apolipoprotein D, beta-lactoglobulin, complement component C8 gamma chain, crustacyanin, epididymal-retinoic acid binding protein (E-RABP), insectacyanin, odorant binding protein (OBP), human pregnancy-associated endometrial alpha-2 globulin (PAEP), probasin (PB), a prostatic protein, prostaglandin D synthase, purpurin, Von Ebner's gland protein (VEGP), and lizard epididymal secretory protein IV (LESP IV). 
     
     
         12 . The method of  claim 10 , wherein the at least one protein from the lipocalin family is selected from the group consisting of FABP1, FABP2, FABP3, FABP4, FABP5, FABP6, FABP7, LCN1, LCN2, LCN8, LCN09, LCN10, LCN12, OBP2A, OBP2B, RBP1, RBP2, RBP4, RBP5, RBP7, PAEPPERF15, PMP2, PTGDSAMBP, APOD, C8G, CRABP1, CRABP2 UNX2541 ORM1 and ORM2. 
     
     
         13 . The method of  claim 10 , wherein the at least one protein comprises a plurality of proteins wherein the proteins comprise the same type of protein selected from the lipocalin family. 
     
     
         14 . The method of  claim 10 , wherein the at least one protein comprises a plurality of proteins wherein the proteins comprise a combination of different types of proteins selected from the lipocalin family. 
     
     
         15 . The method of  claim 10 , wherein the at least one membrane is at least one of polyamide, polysulfone, polyethersulfone, cellulose acetate, triacetate, polyacrylonitrile or polymethylmethacrylate. 
     
     
         16 . The method of  claim 10 , wherein the clearance of hydrophobic, protein bound uremic toxins is facilitated. 
     
     
         17 . The method of  claim 16 , wherein the hydrophobic, protein bound uremic toxin is at least one of p-cresol, indoxyl sulfate or p-cresol sulfate. 
     
     
         18 . A method of preventing or treating uremia comprising subjecting a bodily fluid from a subject to an apparatus comprising a body having an inlet and an outlet and defining an interior, the interior including at least one membrane having at least one protein from the lipocalin family bound thereon, wherein the apparatus is arranged so that the bodily fluid entering the apparatus contacts the at least one protein from the lipocalin family bound to the at least one membrane in the interior of the apparatus. 
     
     
         19 . The method of  claim 18 , wherein the at least one protein from the lipocalin family is selected from the group consisting of alpha-1-microglobulin (protein HC), major urinary proteins, alpha-1-acid glycoprotein (orosomucoid), aphrodisin, apolipoprotein D, beta-lactoglobulin, complement component C8 gamma chain, crustacyanin, epididymal-retinoic acid binding protein (E-RABP), insectacyanin, odorant binding protein (OBP), human pregnancy-associated endometrial alpha-2 globulin (PAEP), probasin (PB), a prostatic protein, prostaglandin D synthase, purpurin, Von Ebner's gland protein (VEGP), and lizard epididymal secretory protein IV (LESP IV). 
     
     
         20 . The method of  claim 18 , wherein the at least one protein from the lipocalin family is selected from the group consisting of FABP1, FABP2, FABP3, FABP4, FABP5, FABP6, FABP7, LCN1, LCN2, LCN8, LCN09, LCN10, LCN12, OBP2A, OBP2B, RBP1, RBP2, RBP4, RBP5, RBP7, PAEPPERF15, PMP2, PTGDSAMBP, APOD, C8G, CRABP1, CRABP2 UNX2541 ORM1 and ORM2. 
     
     
         21 . The method of  claim 18 , wherein the at least one membrane is at least one of polyamide, polysulfone, polyethersulfone, cellulose acetate, triacetate, polyacrylonitrile or polymethylmethacrylate. 
     
     
         22 . The method of  claim 18 , wherein the clearance of hydrophobic, protein bound uremic toxins is facilitated. 
     
     
         23 . The method of  claim 22 , wherein the hydrophobic, protein bound uremic toxin is at least one of p-cresol, indoxyl sulfate or p-cresol sulfate. 
     
     
         24 . The method of  claim 18 , wherein the uremia is characterized by at least one of fatigue, anemia, itching, peripheral neuropathy, a gastrointestinal disorder, nausea, vomiting, diarrhea, cardiovascular complications, coronary vascular disease, peripheral vascular disease, left ventricular hypertrophy, cardiac fibrosis and accelerated rates of arrhythmias. 
     
     
         25 . A method of dialysis comprising:
 (a) providing a solution comprising at least one protein from the lipocalin family to the interior of a dialysis apparatus; and   (b) subjecting a bodily fluid from a subject to the dialysis apparatus comprising a body having an inlet and an outlet and defining an interior, wherein the interior includes at least one membrane capable of binding the at least one protein from the lipocalin family and the dialysis apparatus is arranged so that the bodily fluid entering the dialysis apparatus contacts the at least one protein from the lipocalin family bound to the least one membrane in the interior of the apparatus.   
     
     
         26 . The method of  claim 25 , wherein the at least one protein from the lipocalin family is selected from the group consisting of alpha-1-microglobulin (protein HC), major urinary proteins, alpha-1-acid glycoprotein (orosomucoid), aphrodisin, apolipoprotein D, beta-lactoglobulin, complement component C8 gamma chain, crustacyanin, epididymal-retinoic acid binding protein (E-RABP), insectacyanin, odorant binding protein (OBP), human pregnancy-associated endometrial alpha-2 globulin (PAEP), probasin (PB), a prostatic protein, prostaglandin D synthase, purpurin, Von Ebner's gland protein (VEGP), and lizard epididymal secretory protein IV (LESP IV). 
     
     
         27 . The method of  claim 25 , wherein the at least one protein from the lipocalin family is selected from the group consisting of FABP1, FABP2, FABP3, FABP4, FABP5, FABP6, FABP7, LCN1, LCN2, LCN8, LCN09, LCN10, LCN12, OBP2A, OBP2B, RBP1, RBP2, RBP4, RBP5, RBP7, PAEPPERF15, PMP2, PTGDSAMBP, APOD, C8G, CRABP1, CRABP2 UNX2541 ORM1 and ORM2. 
     
     
         28 . A method of extracorporeal detoxification comprising subjecting a bodily fluid from a subject to an apparatus comprising a body having an inlet and an outlet and defining an interior, wherein the interior includes at least one membrane capable of binding the at least one protein from the lipocalin family and the apparatus is arranged so that the bodily fluid entering the apparatus contacts the at least one protein from the lipocalin family bound to the at least one membrane in the interior of the apparatus, wherein clearance of a drug is facilitated. 
     
     
         29 . The method of  claim 28 , wherein the at least one protein from the lipocalin family is selected from the group consisting of alpha-1-microglobulin (protein HC), major urinary proteins, alpha-1-acid glycoprotein (orosomucoid), aphrodisin, apolipoprotein D, beta-lactoglobulin, complement component C8 gamma chain, crustacyanin, epididymal-retinoic acid binding protein (E-RABP), insectacyanin, odorant binding protein (OBP), human pregnancy-associated endometrial alpha-2 globulin (PAEP), probasin (PB), a prostatic protein, prostaglandin D synthase, purpurin, Von Ebner's gland protein (VEGP), and lizard epididymal secretory protein IV (LESP IV). 
     
     
         30 . The method of  claim 28 , wherein the drug is a prescription or a non-prescription drug. 
     
     
         31 . The method of  claim 28 , wherein the detoxification concerns an accidental or intentional drug overdose.