Cystatin C dan NGAL Sebagai Biomarker pada Gagal Ginjal

By: M Farid Rakhman Advicer: dr. M Rudiansyah, M.Kes, Sp.PD

Department of Internist, Ulin Hospital/ UNLAM School of Medicine Banjarmasin, Indonesia September 2012

Acute kidney injury (AKI)

Acute

kidney injury (AKI) is characterized by the sudden impairment of kidney function resulting in the retention of nitrogenous and other waste products normally cleared by the kidneys (1).

1.

Fauci, Braunwald, Kasper et all. 2012. Harrison's Principles of Internal Medicine Eightteenth Edition. United States. Mc Graw Hill.

Pathogenesis of AKI (1)

1.

Fauci, Braunwald, Kasper et all. 2012. Harrison's Principles of Internal Medicine Eightteenth Edition. United States. Mc Graw Hill.

Chronic kidney disease (CKD)

Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate (GFR) (1). The term chronic renal failure applies to the process of continuing significant irreversible reduction in nephron number and typically corresponds to CKD stages 35.

1.

Fauci, Braunwald, Kasper et all. 2012. Harrison's Principles of Internal Medicine Eightteenth Edition. United States. Mc Graw Hill.

CKD Stage

1.

Fauci, Braunwald, Kasper et all. 2012. Harrison's Principles of Internal Medicine Eightteenth Edition. United States. Mc Graw Hill.

What is NGAL

NGAL (Neutrophil gelatinaseassociated lipocalin) is a 25 kDa protein that consists of a polypeptide chain of 178 amino acids (1). NGAL is secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states(2). NGAL have bacteriostatic effects, which are explained by its ability to capture siderophores that are synthesized by certain bacteria (2).

1. 2.

Soni SS et all. 2010. NGAL: a Biomarker of Acute Kidney Injury and another systemic conditions. Int Urol Nephrol. Vol 42; 141-150 Schmitt-Ott KM et al. 2007. Dual Action of Neutrophil Gelatinase-Associated Lipocalin. J ant Soc Nephrol. Vol 18; 407 413.

NGAL and Kidney Injury

NGAL acts as a growth and differentiation factor in mature renal epithelia (1). NGAL is massively upregulated (up until 1000 fold) after renal tubular injury and may participate in limiting kidney damage (1,2).

1. 2.

Schmitt-Ott KM et al. 2007. Dual Action of Neutrophil Gelatinase-Associated Lipocalin. J ant Soc Nephrol. Vol 18; 407 413. Soni SS et all. 2010. NGAL: a Biomarker of Acute Kidney Injury and another systemic conditions. Int Urol Nephrol. Vol 42; 141-150

NGAL and Kidney Injury

Mishra et al (2003) first proposed NGAL as a novel early biomarker (1). In mouse models of renal ischemia-reperfusion injury subjected to 30 min of bilateral renal arteryocclusion, NGAL was easily detected in the urine within 2 h following ischemia (2).

1. 2.

Soni SS et all. 2010. NGAL: a Biomarker of Acute Kidney Injury and another systemic conditions. Int Urol Nephrol. Vol 42; 141-150 Mishra J, Ma Q, Prada A et al. 2003. Identification of Neutrophil Gelatinase-Associated Lipocalin as a Novel Early Urinary Biomarker for Ischemic Renal Injury. J Am Soc Nephrol 14: 2534 2543

NGAL and Kidney Injury

In the same study, separate sets of mice were subjected to 5, 10, and 20 min of ischemia. Importantly, uNGAL was detected even in these mice, appearing after 6 h in mice with 5 min ischemia and after 4 h in mice with 10 and 20 min of ischemia (1). Thus, uNGAL was found to be a very sensitive marker of ischemic AKI and its levels correlated to the dose and duration of renal ischemia (1).

1.

Soni SS et all. 2010. NGAL: a Biomarker of Acute Kidney Injury and another systemic conditions. Int Urol Nephrol. Vol 42; 141-150

What is Cystatin C.

Cystatin C (cys-C) is a low molecular mass protein (1). Cys-C seems to be produced by all human nucleated cells (1). Cys-C has a molecular mass of 13,343 Da, but about 50% of cys-C carries a hydroxylated proline and the molecular mass of hydroxylated cys-C is thus 13,359 Da (1).

1.

Filler G, Bokenkamp, Hofmann et all. 2005. Cystatin C as a Marker of GFR History, Indication and Future Research. Elsevier Clinical Biochemistry vol 38; 1-8

What is Cystatin C.

The serum concentration of cys-C remains constant from around 1 to 50 years of age and independence from height, age and gender (1). Only few circumstances have been identified that have an impact on the production of cys-C (1). Very large doses of glucocorticoids have been described to increase the production of cys-C (1). Thyroid dysfunction also has a major impact on cysC levels. Cys-C levels are lower in the hypothyroid and higher in the hyperthyroid state (1).

1.

Filler G, Bokenkamp, Hofmann et all. 2005. Cystatin C as a Marker of GFR History, Indication and Future Research. Elsevier Clinical Biochemistry vol 38; 1-8

Cystatin C and GFR

Small molecular weight proteins have long been proposed as markers of GFR as they are normally almost freely filtered through the normal glomerular membrane(1). The serum concentration of cys-C remains constant from around 1 to 50 years of age and independence from height, age and gender (2).

1. 2.

Jung K. 1987, Low-Molecular-Mass Proteins in Serum and Their Relationship to the Glomerular Filtration Rate. Nephron ;47:160 168. Filler G, Bokenkamp, Hofmann et all. 2005. Cystatin C as a Marker of GFR History, Indication and Future Research. Elsevier Clinical Biochemistry vol 38; 1-8

Cystatin C and GFR

The renal function being the main determinant of cys-C serum concentration, makes cys-C an interesting candidate surrogate marker of GFR (1).

1.

Filler G, Bokenkamp, Hofmann et all. 2005. Cystatin C as a Marker of GFR History, Indication and Future Research. Elsevier Clinical Biochemistry vol 38; 1-8

Conclusion
NGAL

is a good biomarker to detect the renal Injury Cystatin C is a good biomarker to estimating the GFR.

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