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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


Patho-physiological basis

Number of patients

Definition progression

Evidence to date

Cystatin C

Marker of kidney function [123]


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]


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]


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]


Doubling serum creatinine or arrival at ESKD


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]


Doubling serum creatinine or arrival at ESKD

Elevated BNP and pro BNP were associated with progression to end points [132]



Arrival at ESKD

BNP correlated strongly with risk of mortality but not progression of CKD [38]

Homocysteine (Hcy)

Marker of endothelial dysfunction [133]


Development of albuminuria from normoalbuminuria

Hyperhomocysteinaemia was a predicted the development is albuminuria [134]

C-reactive protein (CRP)

Marker of inflammation


Rate of change of eGFR

Neither serum CRP or leptin predicted renal progression [135]


Marker of metabolic disturbance [136]


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.