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Table 6 Biomarkers measured as part of the RIISC protocol

From: The natural history of, and risk factors for, progressive Chronic Kidney Disease (CKD): the Renal Impairment in Secondary care (RIISC) study; rationale and protocol

Biomarker Patho-physiological basis Number of patients Definition progression Evidence to date
Cystatin C Marker of kidney function [123] 117 Doubling serum creatinine or ESKD Cystatin C predicted renal decline (doubling of Creatinine or arrival at ESKD) in the MMKD study [124]
Neutrophil Gelatinase-Associated Lipocalin (NGAL) Marker of tubulo-interstitial injury [125] 96 Doubling serum creatinine Serum and urine NGAL was associated with renal decline (doubling of serum creatinine) [126]
Asymmetric Dimethylarginine (ADMA) Marker of endothelial dysfunction [127] 225 Increased proteinuria, rate of change of eGFR A study of 225 diabetics found that ADMA was associated with renal progression (increase in proteinuria, rate of change of eGFR) [128]
227 Doubling serum creatinine or arrival at ESKD
131 Arrival at ESKD ADMA levels above the median were more likely to reach an endpoint [129]
ADMA was an independent risk factor for renal progression [130]
B-type Natriuretic protein (BNP) Marker of cardiovascular dysfunction [131] 227 Doubling serum creatinine or arrival at ESKD Elevated BNP and pro BNP were associated with progression to end points [132]
   382 Arrival at ESKD BNP correlated strongly with risk of mortality but not progression of CKD [38]
Homocysteine (Hcy) Marker of endothelial dysfunction [133] 316 Development of albuminuria from normoalbuminuria Hyperhomocysteinaemia was a predicted the development is albuminuria [134]
C-reactive protein (CRP) Marker of inflammation 804 Rate of change of eGFR Neither serum CRP or leptin predicted renal progression [135]
Adiponectin Marker of metabolic disturbance [136] 1330 Arrival at ESKD The group of patients with microalbuminuria who progressed to ESRF had higher adiponectin levels [137]
Free light chains (FLCs) Marker of renal function and possible inflammation [138] 282 healthy controls, 772 South Asian diabetics, 91 Caucasian diabetics Development of microalbuminuria Elevated serum FLCs were a risk factor for the development of microalbuminuria [138]
Fibroblast growth factor 23 (FGF 23) Marker of metabolic disturbance [139] 227 non-diabetics with normal renal function and CKD (GFR>60 = 121, GFR<60 =106 Doubling serum creatinine or arrival at ESKD Both c-terminal and intact FGF23 independently predicted progression of CKD after adjustment for age/gender/GFR and proteinuria [139]
Urinary MCP1 MCP-1/CCL2 is a chemokine which is upregulated in CKD [140, 141] 215 patients with CKD undergoing a renal biospy Doubling of serum creatinine or arrival at ESKD ACR, urinary MCP-1 and interstial macrophage numbes were interdependent. ACR, macrophage numbers chronic damage and creatinine predicted renal survival [142]
  1. MMKD- mild to moderate kidney disease study.