Medicosnext
Kidney is the major retroperitoneal organ in the body. The function of kidney involves mainly filtration and excretion to get rid of metabolic waste, reabsorption or secretion of substances, and acid-base, electrolyte, and fluid balance. In addition, kidney also regulates endocrine functions, such as synthesis of vitamin D and erythropoietin, and controls blood pressure. Despite having varied functions, the measure of glomerular function rate (GFR) remains the most sensitive and specific indicator of renal function. GFR is defined as the rate of flow of plasma through the glomerulus. The average GFR in a healthy person is about 120 ml per minute.
Pathological conditions affecting kidney function is broadly categorized as either acute kidney injury, where there is sudden decline in kidney function over a time of a week, or chronic kidney disease, characterized by gradual loss of renal function over an extended period of time (at least three months). For a medical person involved in the management of kidney disease, irrespective of the etiology, it is imperative to assess the GFR to understand the extent of renal impairment and administer the effective treatment regime.
Because direct measurement of GFR is virtually impractical, a method that measures the renal clearance of exogenous substance, such as insulin, is considered gold standard or reference method to determine the GFR. Equally, renal clearance of 125 iothalamate, 51-labeled ethylenediaminetetraacetic acid (51 Cr-EDTA), and iohexol gives accurate GFR measurement. However, the downside of these techniques is that they are invasive, labor-intensive, expensive, and cumbersome to carry out routinely (Soveri, Berg, and Bjo 2014). Therefore, serum level of endogenously produced creatinine and its renal clearance continue to be only biomarker that has been used routinely in clinical practice as an index of renal function.
Although serum creatinine and creatinine clearance remain as the most widely used laboratory marker for assessment of renal function, its use comes with several caveats. Serum creatinine level is influenced by age, gender, race, muscle mass, diet, and also medications. Moreover, assays that quantify serum creatinine succumb to various interferences, as a consequence, gives inaccurate results. Most importantly, serum creatinine remains within normal limit even when there exists substantial decline in the kidney function, generating diagnostic dilemma.
Additionally, creatinine-based GFR measurement is known to overestimate GFR. For the purpose of convenience, various creatinine-based prediction equations to estimate GFR have been proposed. Cockcroft and Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas are two such equations in use that confer quick estimates of GFR without the necessity of collecting 24-hour urine. However, because both of these equations are based on serum level of creatinine, they tend to either overestimate or underestimate GFR. Consequently, the serum creatinine and its estimate of GFR as a marker of renal function has been a matter of debate.
Recently, a new biomarker of renal function has been recognized as a better marker than creatinine for the assessment of renal function. Cystatin C, also known as beta trace protein, was reported in 1981. Cystatin C is produced endogenously by all nucleated cells and embodies the characteristics of an ideal biomarker for renal function. Recent evidence suggests that serum cystatin C is better than creatinine in early diagnosis of deteriorating renal function. Moreover, cystatin C based equation to calculate the GFR has also superseded creatinine-based equation (Id et al. 2020). KDIGO guideline for the management kidney disease recommend the measurement of serum cystatin C and reporting of estimate GFR based on its CKD EPI equation, especially to confirm decline in renal function not revealed by creatinine measurements (Journal and Society 2013).
Despite the widespread evidences and recommendation by KDIGO, use of cystatin C is not well established in Nepal. It could be because of the preconceived notion that the newer tests are expensive, sophisticated, and scarcely feasible. However, in recent years, the number of laboratory service providers is increasing in Nepal, ensuring accessibility to the newer biomarkers. Fostering a two-way communication between clinicians and laboratory professionals could facilitate provision of the test within the hospital and private laboratories, and thus promote the judicious use of cystatin C in the effective management of kidney disease.
References:
Id, Joshua Z Willey, Yeseon Park Moon, S Ali Husain, Mitchell S V Elkind, L Sacco, Myles Wolf, Ken Cheung, Clinton B Wright, and Sumit Mohan Id. 2020. “Creatinine versus Cystatin C for Renal Function- Based Mortality Prediction in an Elderly Cohort : The Northern Manhattan Study,” 1–26.
Journal, Official, and International Society. 2013. “KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease” 3 (1).
Soveri, Inga, Ulla B Berg, and Jonas Bjo. 2014. “Original Investigation Measuring GFR: A Systematic Review, ¨ 411–24. https://doi.org/10.1053/j.ajkd.2014.04.010.
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