Allows Detection of Acute Kidney Damage Days Before Creatinine Rises
Creatinine Do Not Detect Kidney Damage Until Nearly 50% Of Nephrons Are Nonfunctional(1)
Current diagnosis of AKI and CKD is limited by generally available clinical measures of kidney structure (renal ultrasound and biopsy) and function (serum creatinine concentration and urine albumin excretion). Reliance on the clearance of creatinine [or other markers of glomerular filtration rate (GFR)]as the mainstay of renal functional status is undermined by the well-established process of nephron loss accompanied by adaptive hypertrophy of remaining nephrons in CKD. A rise in serum creatinine concentration does not occur until nearly 50% of nephrons are nonfunctional(1).
Proximal Tubules Are More Sensitive To İnjury:
The proximal tubular mass constitutes over 50% of the volume of the normal kidney, and growth of the proximal tubule accounts for the increasing size of the kidney through early childhood. Its rate of growth outstrips that of the glomerulus. The kidneys constitutes 1% of body weight but utilize 10% of total body oxygen consumption, primarily devoted to proximal tubule sodium reabsorption(1).
Compared with distal tubules, proximal tubules are more susceptible to ischemic and toxic injury, largely a consequence of their lower capacity for anaerobic glycolytic ATP production and lack of antioxidant and antiapoptotic proteins. In addition, the proximal tubule is particularly vulnerable to mitochondrial toxicity, and production of reactive oxygen species is greater in proximal tubules. Proximal tubular injury alone can lead to the cascade of events. The dose dependent effect of repeated proximal tubular injury confirms that repeated episodes of AKI result in CKD. The proximal tubule is a primary source for biomarkers of AKI and CKD (2).
Patients with chronic kidney disease (CKD) are predisposed to develop acute kidney injury (AKI), because CKD is an independent risk factor for AKI::
The diagnosis of AKI in patients with CKD is difficult, because these patients have impaired kidney function and the percentage changes in serum creatinine level after AKI are in part confounded by baseline kidney function. Only larger absolute rises in creatinine levels indicate an independent association with mortality. However, AKI in patients with CKD conveys serious risks”(2).
New Diagnostic Criteria of AKI Require The Use of New Biomarkers:
A panel of 23 international experts in nephrology, critical care, and related specialties published a concensus statement: “Current evidence from clinical studies supports the use of new biomarkers in prevention and management of AKI” (3)
The panel decided to use new biomarkers for AKI stages 1S, 1B, 2B, 3B.
Acute Kidney Injury (AKI) and the Need for New Biomarkers(4)
Acute kidney injury (AKI) is defined as;
- an increase in serum creatinine of 0.3 mg/dL or more within 48 hours,
- an increase in serum creatinine of 1.5 times or more from baseline, known or estimated to occur within 7 days
- urine volume less than 0.5 mL/kg/hour for 6 hours or more
But, acute kidney disease (AKD) is defined as kidney disease that is thought to last less than 90 days.
AKI can occur for a variety of reasons. It most commonly occurs after exposure to hemodynamic damage (eg, high volumes of blood loss or surgeries) or administration of nephrotoxic pharmaceutical agents (eg, radiographic contrast agents, chemotherapeutics, or antibiotics).
It is difficult to predict acute kidney function loss from “estimated glomerular filtration rate” (“eGFR”) that is derived from the equations or from serum/plasma concentrations of creatinine or cystatin C, the endogenous filtration markers used for filtration of blood by the kidneys (glomerular filtration). Because, changes in serum concentrations fall behind the change in measured GFR. For example, after a sudden decrease in GFR, creatinine serum concentration returns to steady state only after 2-3 days. It is even more difficult to estimate GFR from serum creatinine or cystatin C concentrations when GFR is continuously changing (higher or lower). EGFR is important in the management of patients with AKI because of the need for appropriate drug dosing. Estimation of GFR requires an analysis from baseline.
New biomarkers are needed for early detection of kidney damage before kidney function declines to overcome the limitations of current markers.
AKI biomarkers are expected to;
- provide evidence for renal tubular function,
- make the differential diagnosis of AKI etiologies,
- differentiate prerenal disease from acute tubular necrosis, and
- detect subclinical AKI that does not decrease GFR but indicates a poor prognosis.
Argeron NephroTesT is a test that meets these expectations.
Professor Dr. Abdullah Olgun Explains Argeron NephroTest...
Urine Trehalase Activity
Urine trehalase enzyme activity is an indicator of kidney damage. Argeron NephroTesT is suitable to measure urine trehalase enzyme activity by using all kits (including urine strip tests) used for urine glucose measurement in the field of in vitro diagnostics (biochemical medical diagnosis).
Trehalase is a glycoprotein enzyme with a molecular weight of 75kDa, found in the renal proximal tubules. Urine trehalase measurement can be used for screening, diagnosis and follow-up for kidney damage(5,6). For example, it has been reported that trehalase activity is higher than the control group in the early stages of diabetes, even when proteinuria and glucosuria are negative (7). It can show early kidney damage due to some environmental toxins such as lead and cadmium and drugs such as ampicillin and tobramycin (8-11). In addition, increased urinary trehalase activity has been reported in chronic glomerular disease and especially in nephrotic syndrome (12).
Diabetes and AKI(13)
AKI in Diabetes: (13)
Although albuminuria development is considered the natural course of diabetic kidney disease (DKD), increasing evidence indicate that the disease can present as non-albuminuric DKD (NA-DKD), characterized by prominent tubulointerstitial injury and fibrosis without obvious glomerulopathy. Diabetic patients are more susceptible to acute kidney injury (AKI), and the maladaptive repair of kidney tubules following AKI occurs more frequently in diabetic than non-diabetic patients. The enhanced AKI-to-CKD transition may be a significant contributor of NA-DKD (Lee 2022).
Tubular Damage in Kidneys Can Occur in Normal Pregnancy, Pregnancy-Associated Edema, and Toxemia of Pregnancy, and This Can Be Detected by Urinary Trehalase Activity Measurement:
It has been reported that even normal pregnancy leads to tubular dysfunction. It was shown that urinary trehalase activity increased significantly in the first, second and third trimesters of pregnancy compared with controls (p<0.01). Urinary trehalase activity was decreased to the first trimester level on the 5th postpartum day, and returned to normal values on the 30th pastpartum day. (14)
It was reported that tubular damage occurs in pregnancy associated edema and toxemia of pregnancy. Tubular damage can occur even when there is no obvious glomerular damage at the edema stage. In mild toxemia (edema: body weight gain more than 0.5 kg per week) urinary trehalase activity was significantly increased compared with normal pregnancy (less than 0.5 kg body weight gain per week) (p<0.02); however, the urinary albumin level did not change significantly with edema. Significantly higher urinary trehalase activity was measured in toxemia of pregnancy compared with the third trimester of pregnancy. Urinary trehalase activity was found to be significantly higher in severe toxemia than in mild toxemia. Significantly lower trehalase activity was detected on the 5th and 30th days after birth compared to the 3rd trimester; although urinary trehalase activity was decreased on the 5th day postpartum, it was still reported to be significantly higher.(15)
The primary purpose of the test is to ensure that the kits used for glucose measurement in urine (including urine strips) are also used for measurement of urine trehalase activity. Unlike urine trehalase measurement, urine glucose measurement is a routine measurement performed in almost all medical diagnostic laboratories around the world. This allows the very commonly used urine glucose measurements to be used for urine trehalase activity measurement as well.Screening, diagnosis and follow-up
Screening of kidney damage helps in early, rapid, widespread and economical diagnosis and follow-up.Provides the opportunity to take precautions thanks to early diagnosis
Thanks to the early diagnosis of kidney damage, the elimination of the factor(s) causing the damage or early treatment can prevent the progression of the damage.
EARLY DETECTION OF KIDNEY INJURY IS VERY IMPORTANT
Argeron NephroTesT trehalase test can meet the need for a much-needed widespread test that enables the early diagnosis of acute kidney damage. Early diagnosis also contributes greatly to reducing health expenditures.Kidney injury is a common problem
Kidney injury is a very common problem in both outpatients and inpatients. Kidney damage can occur as an adverse effect of many drugs or as a complication of many diseases. Existing tests for damage detection have many limitations.Early Detection for Timely Intervention
Many risk factors leading to kidney injury are known. However, it is difficult to predict exactly when the damage will occur. Therefore, there is a great need for common test methods that can be used for early diagnosis.
- Nephrotoxic drug use
- Heart disease
- Exposure to toxins
- Excessive fluid loss