Table 1 Individual proteins associated with the CKD progression primary outcome in both CRIC and ARIC studies

Twisted gastrulation protein homolog 1

4.95 (3.87, 6.32)

1.89e-37

2.8 (2.04, 3.84)

1.52e-10

Antagonist of bone morphogenetic proteins— such as BMP 7, which is protective against renal fibrosis⁶³

Alpha-1-microglobulin

4.55 (3.61, 5.74)

6.59e-38

1.41 (1.09, 1.83)

0.0083

Antioxidant, binds and degrades heme

Ephrin-A4

4.29 (3.43, 5.36)

1.85e-37

2.29 (1.76, 2.98)

5.18e-10

Protein-tyrosine kinase

CAR T-cell therapy

Follistatin-related protein 3

4.26 (3.38, 5.36)

6.31e-35

2.69 (2.06, 3.52)

4.68e-13

Antagonist of bone morphogenetic proteins⁶⁴ such as GDF11

Low-density lipoprotein receptor-related protein 11

4.15 (3.32, 5.18)

3.34e-36

2.05 (1.6, 2.61)

1.01e-08

Membrane protein related to lipid metabolism

Ephrin type-A receptor 2

3.98 (3.36, 4.72)

2.48e-57

1.98 (1.63, 2.40)

5.07e-12

Protein-tyrosine kinase; ongoing research to develop ephrins as therapeutic target⁶⁵

CAR T-cell therapy

Tumor necrosis factor receptor superfamily member 1 A

3.69 (3.06, 4.46)

3.85e-42

2.05 (1.66, 2.54)

4.40e-11

Inflammatory mediator; predicts ESRD¹² and incident CKD⁶⁶

VB-111

WAP four-disulfide core domain protein 2

3.54 (2.98, 4.22)

6.50e-46

2.35 (1.91, 2.90)

8.87e-16

Glycoprotein; protease inhibitor. Also called Human epididymis protein 4 or MMP2. Mediator of renal fibrosis^67,68,69

Matrix remodeling-associated protein 7

3.45 (2.93, 4.07)

2.46e-49

1.82 (1.51, 2.19)

1.93e-10

ECM protein involved in kidney fibrosis⁷⁰

Prinomastat

Erythropoietin receptor

3.24 (2.77, 3.77)

2.03e-50

1.73 (1.44, 2.07)

4.85e-09

Cytokine receptor. Active in a variety of tissues, including bone formation⁷¹

Tyrosine-protein kinase transmembrane receptor ROR2

3.2 (2.73, 3.75)

2.44e-46

1.83 (1.51, 2.22)

1.01e-09

Protein-tyrosine kinase

CCT301-38 (targeting ROR2)

Ephrin-A2

3.11 (2.53, 3.83)

8.41e-27

1.93 (1.53, 2.43)

3.38e-08

Protein-tyrosine kinase

CAR T-cell therapy

Brorin

3.04 (2.51, 3.69)

1.19e-29

1.61 (1.31, 1.98)

4.95e-06

Antagonist of bone morphogenetic proteins; antagonists of BMP modulate the ECM¹⁸

Netrin receptor UNC5B

3.0 (2.48, 3.63)

1.07e-29

1.75 (1.40, 2.17)

5.54e-07

Inhibits vascular branching during angiogenesis; active in diabetic kidney⁷²

Vesicular integral-membrane protein 36

2.92 (2.38, 3.58)

1.27e-24

1.53 (1.20, 1.95)

5.27e-04

Transport and secretion of glycoproteins

Ephrin type-B receptor 4

2.89 (2.42, 3.45)

8.054e-32

1.69 (1.38, 2.08)

4.27e-07

Protein-tyrosine kinase; stimulates angiogenesis after kidney injury to enhance recovery²⁷

KD019

Ephrin-B2

2.65 (2.23, 3.15)

4.41e-28

1.92 (1.56, 2.37)

6.69e-10

Protein-tyrosine kinase; stimulates angiogenesis after kidney injury to enhance recovery²⁷

BVD-523

Protein delta homolog 2

2.62 (2.27, 3.01)

3.66e-41

1.68 (1.41, 2.01)

1.27e-08

Soluble form inhibits adipogenesis; may antagonizes NOTCH pathway³²

Neuroblastoma suppressor of tumorigenicity 1

2.52 (2.24, 2.84)

6.68e-53

1.46 (1.27, 1.68)

5.89e-08

Antagonist of bone morphogenetic proteins, associated with progression to ESRD⁷³

Hepatitis A virus cellular receptor 1/KIM-1

2.31 (2.15, 2.48)

3.332e-116

1.55 (1.42, 1.7)

2.45e-22

Marker of acute kidney injury⁷⁴