Cytokine single nucleotide polymorphism. Role in acute renal failure.
Although the pathogenesis of ARF is heterogeneous and results from a combination of different environmental influences and host responses, there is overwhelming data to suggest a common pathway that involves pro- and anti-inflammatory molecules, which in turn, determines the extent of tissue injury. The number of recognized cytokine gene polymorphisms is growing daily. The development of cytokine gene mapping may help identify patients in whom an excessive systemic inflammatory response may follow a therapeutic intervention (e.g. CABG, contrast administration), and who may be at increased risk for developing acute organ dysfunction. Through these advances, tools may be developed to better understand, prevent and treat ARF. Genetic epidemiology studies may help characterize the importance of genetic markers in the development of ARF. This would require large prospective cohort studies aimed at examining associations between genetic markers, urinary (urine KIM-1 and NAG) and circulating (serum creatinine) markers of kidney injury. Once firmly established, the association of a particular genetic profile and outcome could be used to risk stratify patients for the development of ARF (fig. 4). Ultimately, cytokine-modulating therapies could be employed on the basis of genotypic risk stratification with the goal to prevent kidney injury or minimize its deleterious effects on patient outcome.
Liangos
Orfeas
O
Dialysis Research Laboratory, Division of Nephrology, Tufts-New England Medical Center, Boston, Mass., USA.
Balakrishnan
Vaidyanathapuram S
VS
Pereira
Brian J G
BJ
Jaber
Bertrand L
BL
D058186:Acute Kidney Injury / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002874:Chromosome Mapping; D002945:Cisplatin / Q000506:poisoning; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015894:Genome, Human; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002945:Cisplatin