The Trending Current Renal function tests

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1. . College of Medicine and Health Sciences School of Medicine and Pharmacy Department of Physiology Master of Science in Medical Physiology Topic: Current Trends in Renal Function Tests and Emerging Biomarkers in Kidney Diseases Module: ADVANCED RENAL PHYSIOLOGY Prepared by 1. Stella Matutina ISINGIZWE 2. Aime Patrick NIYOMUGABO 3. Joel Museveni URIMUBENSHI 8/27/2025 1

2. TABLE OF CONTENT INTRODUCTION CURRENT TRENDS IN RENAL FUNCTION TESTS TECHNOLOGICAL ADVANCEMENTS EMERGING AND NOVEL BIOMARKERS CONCLUSION REFERENCES 2

3. INTRODUCTION Renal function tests are a group of laboratory investigations designed to assess the health and efficiency of the kidneys by measuring various substances in the blood and urine(Peake et al., 2021). These tests play a crucial role in detecting kidney disease at an early stage, monitoring disease progression, and evaluating the effectiveness of treatment . Common renal function tests include measurement of serum creatinine, blood urea nitrogen (BUN), glomerular filtration rate (GFR), electrolytes such as sodium and potassium, and urinalysis to check for protein, blood, or glucose in the urine(Francis et al., 2024). Biomarkers also play a central role in kidney function assessment. 8/27/2025 3

4. specimen Collection 8/27/2025 4

5. 8/27/2025 5 Figure 1. Clinical continuum of acute kidney injury

6. CURRENT TRENDS IN RENAL FUNCTION TESTS Serum Creatinine and Blood Urea Nitrogen (BUN): Urea, or BUN, is an end product of protein metabolism and the urea cycle. About 85% of urea is eliminated through the kidneys. Glomerular Filtration Rate (GFR) Estimation : eGFR remains the gold standard for assessing renal function. GFR is the rate in milliliters per minute at which substances in plasma are filtered through the glomerulus; in other words, the clearance of a substance from the blood(Guzzi et al., 2019). 8/27/2025 6

7. Stage GFR (mL/min/1.73 m²) Description G1 ≥90 Normal or high kidney function† G2 60–89 Mildly decreased† G3a 45–59 Mild to moderately decreased G3b 30–44 Moderately to severely decreased G4 15–29 Severely decreased G5 <15 Kidney failure (end-stage renal disease) 8/27/2025 7 STAGES OF CHRONIC KIDNEY DISEASES

8. Albumin-to-Creatinine Ratio (ACR): A lso called urine albumin-to-creatinine ratio ( uACR ), is a urine test that measures the amount of albumin (a protein) compared to creatinine (a waste product) in the urine . Increasingly used for detecting early kidney damage, especially in diabetic patients(Albert et al., 2020). 8/27/2025 8

9. Normal: Less than 30 mg/g albumin in urine Moderate: 30–300 mg/g may indicate mild to moderate kidney disease. High: Over 300 mg/g suggests significant kidney damage or advanced chronic kidney disease Cystatin C: Less affected by muscle mass; better GFR estimate Normal range: 0.6-1 mg/L It's freely filtered by the kidneys and then reabsorbed and broken down in the proximal tubule. When kidney function is impaired, the levels of cystatin C in the blood increase because the kidneys are not filtering it efficiently 8/27/2025 9

10. Technological Advancements: Point-of-Care Testing (POCT): The development of POCT devices for kidney function (e.g., for creatinine, UACR) allows for rapid results in various settings, including primary care, emergency departments, and remote areas (Mishra et al., 2021; Nichols, 2020). This facilitates earlier detection and more timely management decisions. Recent acquisitions and developments in this area aim to bring quantitative, home-based kidney testing to the forefront, improving accessibility and adherence(Morris and Richards, 2023) 8/27/2025 10

11. Point-of-Care Testing (POCT) Rapid tests: Portable analyzers such as: Afinion ™ AS100 Analyzer (Abbott) Siemens DCA Vantage Analyzer Nova StatSensor Creatinine Meter Samples: Urine for albumin and finger prick for creatinine 8/27/2025 11

12. Advanced Imaging Techniques: While not strictly "renal function tests," advanced imaging modalities like functional MRI and contrast-enhanced ultrasound can provide valuable information on renal perfusion, oxygenation, and microstructure, complementing traditional function tests. 3D microscopy and AI-based image analysis of kidney biopsies are also emerging as tools for more precise diagnostics (Hermsen et al., 2019; Kuppe et al., 2022) . 8/27/2025 12

13. Emerging and Novel Biomarkers: Beyond creatinine and albumin, research is actively identifying and validating new biomarkers to enable earlier and more specific detection of kidney injury and dysfunction. These include: Kidney Injury Molecule-1 (KIM-1): A protein shed by injured proximal tubule cells, KIM-1 is a promising biomarker for acute kidney injury (AKI) and may also have a role in monitoring CKD(Zhang et al., 2023). Neutrophil Gelatinase-Associated Lipocalin (NGAL): Released from damaged kidney tubules, NGAL can be detected in urine and plasma and is an early indicator of AKI(Patel et al., 2024). Liver-Type Fatty Acid-Binding Protein (L-FABP): Produced in the proximal tubules, urinary L-FABP reflects tubular stress and injury(Lee & Nakamura, 2023). Interleukin -18(IL-18): pro-inflammatory cytokine primarily produced by macrophages and renal tubular epithelial cells(Proximal epithelial cells). Produced in response to ischemia or nephrotoxic insults. 8/27/2025 13

14. Kidney Injury Molecule-1 (KIM-1) Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane glycoprotein primarily expressed in renal proximal tubular cells. It is normally present at low levels in the kidney but is highly upregulated in response to acute kidney injury (AKI) and other forms of renal tubular damage(Caroli et al., 2018; Pohlmann et al., 2020). 8/27/2025 14

15. Biological Role and Expression KIM-1 expression increases significantly in damaged proximal tubular cells after ischemic or toxic injury. Its extracellular domain is shed into urine and blood, making it detectable as a soluble biomarker(Ahmed et al., 2024). It participates in renal repair processes, including phagocytosis of dead cells and modulation of inflammation. KIM-1 can activate signaling pathways such as ERK/MAPK and JAK/STAT, promoting tubular epithelial cell migration and proliferation during kidney repair(Torres et al., 2024). KIM-1 also interacts with G protein signaling (e.g., Gα12) to protect against ischemic damage by regulating downstream molecular events 8/27/2025 15

16. Kidney Injury Molecule-1 (KIM-1) 8/27/2025 16 Figure2: Kidney Injury Molecule-1 (KIM-1)

17. Clinical Utility as a Biomarker KIM-1 is a sensitive and specific early biomarker for acute tubular injury and acute kidney injury. Its urinary and blood levels correlate with the severity of tubular damage, including acute tubular necrosis (ATN) and tubulointerstitial fibrosis(Torres et al., 2024). In patients with acute renal failure, urinary KIM-1 levels are significantly elevated compared to other renal diseases or healthy controls, and higher levels are associated with increased risk and severity of ATN(Lin et al., 2023). Blood KIM-1 levels also correlate with kidney injury severity and the need for renal replacement therapy in diseases such as ANCA-associated vasculitis with glomerulonephritis (ANCA-GN) 8/27/2025 17

18. Neutrophil Gelatinase-Associated Lipocalin (NGAL) Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a small glycoprotein belonging to the lipocalin family, originally identified in activated neutrophils but also expressed in various tissues, including kidney tubular cells and cardiomyocytes(Lopez-Garcia et al., 2024). 8/27/2025 18

19. Biological Role and Expression NGAL is rapidly upregulated and released by renal tubular epithelial cells in response to acute kidney injury (AKI) caused by ischemic or nephrotoxic insults(Singh et al., 2023). It functions in innate immunity by binding iron-loaded siderophores , limiting bacterial growth, and also participates in kidney repair and regeneration processes following injury. NGAL is secreted into urine and plasma soon after tubular damage, making it a sensitive and early biomarker of intrinsic AKI, often detectable before rises in serum creatinine(Lopez-Garcia et al., 2024). Besides AKI, NGAL levels increase in chronic kidney disease and inflammatory states, reflecting ongoing kidney damage and systemic inflammation. 8/27/2025 19

20. Liver-Type Fatty Acid-Binding Protein (L-FABP). Liver-type Fatty Acid-Binding Protein (L-FABP) is a 14-kDa cytoplasmic protein predominantly expressed in the renal proximal tubular cells. It plays a key biological role in binding free fatty acids and their oxidation products, facilitating their transport to mitochondria and peroxisomes for beta-oxidation, thus contributing to cellular energy metabolism and homeostasis(Lee and Nakamura, 2023). 8/27/2025 20

21. Biological Role L-FABP acts as an endogenous antioxidant by binding long-chain fatty acid oxidation products, which are increased during oxidative stress and ischemic injury in the kidney(Tanaka et al., 2023). Its gene expression is upregulated in response to hypoxic stress, such as ischemia-reperfusion injury, reflecting proximal tubular cell stress and damage(Matsumoto et al., 2024). By binding toxic lipid peroxides generated during tubular injury, L-FABP may exert a renoprotective effect, attenuating renal damage. 8/27/2025 21

22. Conclusion Renal diagnostics is rapidly evolving from traditional function-based tests to early detection of subclinical injury, prognostication, and precision medicine. The integration of emerging biomarkers and AI tools will likely redefine the way kidney diseases are diagnosed and monitored shortly. 8/27/2025 22

23. References Peake PW, Egerton RE, Shen Q, et al. The severity of acute kidney injury is associated with increased urinary biomarkers. Clin Biochem Rev. 2018;39(3):91–103. Francis, A., Harhay, M.N., Ong, A.C.M. et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol 20, 473–485 (2024). Albert C, Haase M, Albert A, et al. Biomarker-guided risk assessment for acute kidney injury: time for clinical implementation? Ann Lab Med. 2020;40(5):393–400. 8/27/2025 23

24. Mishra, P., Chatterjee, P., & Sinha, S. (2021). Point-of-care testing in nephrology: An overview. Clinical Biochemistry, 90, 1–8. Pohlmann A, Seeliger E, Persson PB. Imaging renal blood flow and oxygenation in experimental models and humans. Am J Physiol Renal Physiol. 2020;319(5). Hermsen M, de Bel T, den Boer M, Steenbergen EJ, Kers J, Florquin S, et al. Deep learning-based histopathologic assessment of kidney tissue. J Am Soc Nephrol. 2019;30(10). 8/27/2025 24

25. Zhang Y, Chen L, Wang J, Huang X. Emerging roles of KIM-1 in acute and chronic kidney diseases. Front Nephrol. 2023;2:112–9. Patel R, Singh M, Gupta A. NGAL as an early biomarker in acute kidney injury: A clinical perspective. J Ren Med . 2024;15(1):33–41. Guzzi LM, Poussel M, Lautrette A, et al. Biomarkers in acute kidney injury: insights into the future. Ann Intensive Care. 2019;9(1):53 Lee H, Nakamura T. Urinary L-FABP and its utility in predicting renal tubular damage. Clin Kidney J . 2023;16(4):450–7. 8/27/2025 25

26. 8/27/2025 26 THANK YOU!