Team:Brasil-SP/TheIssue

     Chronic kidney disease (CKD) is estimated to affect 10–14% of adult populations and is associated with outcomes such as end-stage kidney disease (ESKD), acute kidney injury and cardiovascular disease (CVD), leading to morbidity and mortality (TALL, 2014; TONELLI and RIELLA, 2014). Noticeably, March 13, 2014 marked the celebration of the 9th World Kidney Day (WKD), sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations, under the topic “CDK in older people”, highlighting the importance of kidney disease (TONELLI and RIELLA, 2014).

     A census conducted by the Brazilian Society of Nephrology, in 2012, shows that the number of patients on dialysis is approximately 97,500 per year (SESSO et al, 2014). This number generates a cost of 1.4 billion dollars annually to the Brazilian Federal Government, corresponding to 10% of public funds addressed to health in the country (SESSO et al, 2014). The earlier the diagnosis, the bigger the chances of success of kidney disease treatment. However, the commonly used methods that only diagnose renal dysfunction in late stages and the silent nature of some diseases, such as Chronic Kidney Disease, hampers an early diagnosis and the development of an appropriate treatment (SESSO et al, 2014; TONELLI and RIELLA, 2014).

References

SESSO RC, LOPES AA, THOMÉ FS, LUGON JR, WATANABE Y, SANTOS DR, et al. Relatório do Censo Brasileiro de Diálise Crônica 2012. Jornal Brasileiro de Nefrologia. 2014, 36(1):48-53.

TAAL MW. Progress in risk prediction for people with chronic kidney disease. Current Opinion in Nephrology and Hypertension. 2014, 23:000–000.

TONELLI M, RIELLA MC. Chronic kidney disease and the aging population. Kidney International, 2014, 85:487-491. doi:10.1038/ki.2013.467

     Kidney dysfunction has been diagnosed through the evaluation of glomerular filtration rate in the kidney (GFR, measured in mL/min), in which the determination of serum creatinine concentration is the predominant method (SAKAR et al, 2005; SHLIPAK and DAY, 2013). Changes in the levels of creatinine are detectable only at later stages of renal dysfunction, when the kidney has already lost about 30% of its filtration efficiency (SHLIPAK and DAY, 2013; WASUNG et al, 2014). Moreover, the serum creatinine concentration is extremely sensitive to several variables such as diet, gender, ethnicity, age, muscle mass, and others; impairing significantly its correlation rate with the GFR (SHLIPAK and DAY, 2013; WASUNG et al, 2014). Moreover, some renal complications are asymptomatic, such as Chronic Kidney Disease (CKD), not allowing the diagnosis of the disease in its early stage (WASUNG et al, 2014). Therefore, there is a lack of tools with the precision and sensitivity needed to measure GFR in early stages of kidney disease (SHLIPAK and DAY, 2013). The urea nitrogen is also a biomarker used in the diagnosis of kidney disease, but like creatinine, it is only capable of detecting advanced stages (WASUNG et al, 2014).

References

SARKAR PD, RAJESHWARI G, SHIVAPRAKASH TM. Cystatin C - a novel marker of glomerular filtration rate. Indian Journal of Clinical Biochemistry, 2005, 20(1):139-144. doi: 10.1007/BF02893060.

SHLIPAK MG, DAY, EC. Biomarkers for incident CKD: a new framework for interpreting the literature. Nature Review on Nephrology, 2013, 9(8):478-83. doi: 10.1038/nrneph.2013.108.

WASUNG ME, CHAWLA LS, MADERO M. Biomarkers of renal function, which and when? Clinica Chimica Acta, 2014, pii:S0009-8981(14):00391-X. doi: 10.1016/j.cca.2014.08.039.

     Several studies support Cystatin C as the best biomarker of renal dysfunction when compared to classical biomarkers (urea nitrogen and serum creatinine), because Cystatin C is very sensitive to changes in GFR (SHLIPAK and DAY, 2013). However, the available methods to evaluate the levels of Cystatin C are often very expensive and inefficient, such as the immunofluorescence method (SHLIPAK and DAY, 2013). Our solution to this problem is to develop a genetic circuit to detect different levels of Cystatin C in the blood. When the detectable levels of Cystatin C are higher than the normal, it will lead us to diagnose CKD and other renal dysfunctions in early stages. The genetic circuit is shown in the Figure below and the input information is based on Cystatin C inhibitory activity against cysteine proteases, in this case, cathepsin S.

Reference

SHLIPAK MG, DAY, EC. Biomarkers for incident CKD: a new framework for interpreting the literature. Nature Review on Nephrology, 2013, 9(8):478-83. doi: 10.1038/nrneph.2013.108.