TREATMENT OF KIDNEY DISEASE IN SUBJECTS WITH KIDNEY AND/OR URINARY TRACT ANOMALIES

1 . A method of treating kidney disease in a subject who has chronic kidney disease (CKD), the method comprising administering to the subject an effective amount of a composition comprising:

(i) a bioactive renal cell population;

(ii) vesicles secreted by the renal cell population; and/or

(iii) spheroids comprising the renal cell population and at least one non-renal cell population,

wherein the subject has an anomaly of a kidney and/or urinary tract.

2 . The method of claim 1 , wherein the subject has CKD from congenital anomalies of the kidney and urinary tract (CAKUT).

3 . The method of claim 1 or 2 , wherein the subject has anomolies in kidney development

4 . The method of any one of claims 1 to 3 , wherein the subject has or has had primary or secondary vesicoureteral reflux, reflux nephropathy, renal scaring, or renal hypodysplasia with or without infection and/or inflammation.

5 . The method of any one of claims 1 to 4 , wherein the subject is predisposed to urinary tract infections.

6 . The method of any of any one of claims 1 to 5 , wherein the subject has hypertension or proteinuria.

7 . The method of any one of claims 1 to 6 , wherein the subject has had post-antireflux surgery.

8 . The method of any one of claims 1 to 7 , wherein the subject has a glomerular filtration rate (GFR) of less than 90 mL/min/1.73 m 2 , microalbuminuria, or macroalbuminuria.

9 . The method of any one of claims 1 to 8 , wherein the subject is less than 18 years old.

10 . The method of any one of claims 1 to 9 , wherein the subject has a Renal Parenchymal Malformation.

11 . The method of any one of claims 1 to 10 , wherein the subject has a ureteral duplication, a ureteropelvic junction obstruction, renal agenesis, vesicoureteral reflux, renal dysplasia, renal hypoplasia, renal hypodysplasia, congenital hydronephrosis, a horseshoe kidney, posterior urethral valve and prune belly syndrome, obstructive renal dysplasia, or a nonmotile ciliopathy.

12 . The method of any one of claims 2 to 11 , wherein the CAKUT has been caused by or has been correlated with a genetic factor.

13 . The method of any one of claims 2 to 11 , wherein the CAKUT has been caused by or has been correlated with a non-genetic factor.

14 . The method of claim 13 , wherein the non-genetic factor is an environmental factor.

15 . The method of any one of claims 1 to 14 , wherein the anomaly comprises Alagille syndrome, Apert syndrome, Bardet-Biedl syndrome, Beckwith-Wiedemann syndrome, Branchio-Oto-Renal syndrome (BOR), Campomelic dysplasia, Cenani-Lenz syndrome, DiGeorge syndrome, Fraser syndrome, hypoparathyroidism sensorineural deafness and renal anomalies (HDR), Kallmann syndrome, Mammary-Ulnar syndrome, Meckel Gruber syndrome, nephronophthisis, Okihiro syndrome, Pallister-Hall syndrome, Renal coloboma syndrome, hypoplasia, dysplasia, renal dysplasia, cystic dysplasia, non-cystic dysplasia, VUR Cystic dysplasia, renal hypoplasia, isolated cystic renal hypoplasia, isolated non-cystic renal hypoplasia, isolated renal tubular dysgenesis, Rubinstein-Taybi syndrome, Simpson-Golabi Behmel syndrome, Townes-Brock syndrome, Zellweger syndrome, Smith-Lemli-Opitz syndrome, hydronephrosis, medullary dysplasia, unilateral/bilateral agenesis/dysplasia, collecting system anomalies, agenesis, ureteropelvic junction obstruction (UPJO) agenesis, dysplasia agenesis, unilateral agenesis, VUR, malrotation, cross-fused ectopia, VUR Dysplasia, a dual Serine/Threonine And Tyrosine Protein Kinase (DSTYK) mutation, a DSTYK mutation associated with UPJO, tubular dysgenesis, cysts, and/or aplasia.

16 . The method of any one of claims 1 to 15 , wherein the subject has end-stage kidney disease.

17 . The method of any one of claims 1 to 16 , wherein the chronic kidney disease is Stage I, II, III, IV, or V kidney disease.

18 . The method of any one of claims 1 to 17 , wherein the subject is receiving dialysis at least 1, 2, or 3 times per week.

19 . The method of any one of claims 1 to 18 , wherein at least greater than 80% of the cells in the bioactive renal cell population express GGT-1.

20 . The method of any one of claims 1 to 19 , wherein 4.5% to 81.2% of the cells in the bioactive renal cell population express GGT-1, 3.0% to 53.7% of the cells within the bioactive renal cell population express AQP2, and 81.1% to 99.7% of the cells within the bioactive renal cell population express CK18.

21 . The method of any one of claims 1 to 20 , wherein the bioactive renal cell population is enriched for renal tubular cells compared to a primary culture of kidney cells from a kidney biopsy, and the tubular cells express higher molecular weight species of hyaluronic acid (HA) both in vitro and in vivo, through the actions of hyaluronic acid synthase-2 (HAS-2).

22 . The method of any one of claims 1 to 21 , wherein the bioactive renal cell population has a lesser proportion of distal tubular cells, collecting duct cells, endocrine cells, vascular cells, and/or progenitor-like cells compared to a primary culture of kidney cells from a kidney biopsy.

23 . The method of any one of claims 1 to 22 , wherein the vesicles comprise a paracrine factor.

24 . The method of any one of claims 1 to 23 , wherein the vesicles comprise an miRNA that inhibits Plasminogen Activation Inhibitor-1 (PAI-1) and/or TGFβ1.

25 . The method of any one of claims 1 to 24 , wherein the at least one non-renal cell population is an endothelial cell population or an endothelial progenitor cell population.

26 . The method of any one of claims 1 to 24 , wherein the at least one non-renal cell population is a mesenchymal stem cell population.

27 . The method of any one of claims 1 to 26 , wherein the administering is by injection into one or both kidneys of the subject.

28 . The method of any one of claims 1 to 27 , wherein the composition further comprises a temperature-sensitive cell-stabilizing biomaterial that maintains (i) a substantially solid state at 8° C. or below, and (ii) a substantially liquid state at ambient temperature or above, wherein the biomaterial comprises a hydrogel, wherein the biomaterial is in a solid-to-liquid transitional stage between 8° C. and ambient temperature or above.

29 . The method of claim 28 , wherein the bioactive renal cell population, the vesicles, and/or the spheroids are suspended in and dispersed throughout the cell-stabilizing biomaterial.

30 . The method of claim 28 or 29 , wherein the hydrogel comprises gelatin.

31 . The method of any one of claims 1 to 30 , wherein the bioactive renal cell population, the vesicles, and/or the spheroids are administered by injection through a 18 to 30 gauge needle.

32 . The method of claim 31 , wherein the needle has a diameter of about 27 gauge, about 26 gauge, about 25 gauge, about 24 gauge, about 23 gauge, about 22 gauge, about 21 gauge, or about 20 gauge.

33 . The method of any one of claims 1 - 17 , wherein the treating the kidney disease comprises improving renal function of the subject.

34 . The method of claim 33 , wherein the improving renal function comprises reducing albumin-to creatinine ratio (ACR) in the subject.

35 . The method of claim 34 , wherein the reducing ACR is by at least 50% relative to baseline ACR of the subject.

36 . The method of claim 35 , wherein the reducing ACR is by at least 60% relative to baseline ACR of the subject.

37 . The method of claim 34 , wherein the reducing the ACR is a reduction in ACR to between 30 mg/g and 300 mg/g, wherein subject comprises an ACR of greater than 300 mg/g prior to the administering a first dose of the composition.

38 . The method of claim 34 , wherein the reducing the ACR is a reduction in ACR to less than 30 mg/g, wherein the subject comprises an ACR of between 30 mg/g and 300 mg/g prior to the administering a first dose of the composition.

39 . The method of any of claims 34 - 36 , wherein the reducing ACR is achieved within 3-6 months following the administering a first dose of the composition.

40 . The method of any of claims 34 - 36 , wherein the reducing ACR is achieved within 2-3 months following the administering a first dose of the composition.

41 . The method of claim 33 , wherein the improving renal function comprises increasing eGFR of the subject.

42 . The method of 41 , wherein the increasing eGFR is achieved within two to four months following the administering a first dose of the composition.

43 . The method of claim 41 , wherein the increasing eGFR is achieved within two months following the administering a first dose of the composition.

44 . The method of any of claims 41 - 43 , wherein the increase in eGFR is at least 5% over baseline eGFR of the subject.

45 . The method of claim 44 , wherein the increase in eGFR is at least 10% over baseline eGFR of the subject.

46 . The method of any of claims 33 - 45 , wherein the anomaly of the kidney and/or urinary tract comprises a posterior urethral valve.

47 . The method of any of claims 1 - 46 , wherein the composition comprises the (i) bioactive renal cell population.

48 . The method of claim 47 , wherein the effective amount of the bioactive renal cell population comprises 3×10 6 cells/gram estimated kidney weight of the subject.