Related Experiment Video
Updated: Jun 17, 2025
Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats
Published on: March 11, 2016
Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats
Víctor Blanco-Gozalo1, Yaremi Quiros1, Laura Vicente-Vicente2
1Instituto de Investigación Biomédica de Salamanca (IBSAL) de la Fundación Instituto de Ciencias de la Salud de Castilla y León (ICSCYL), Salamanca, Spain; Universidad de Salamanca (USAL), Departamento de Fisiología y Farmacología, Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain.
Abstract:
Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.
Insights
Urinary ganglioside GM2 activator protein (GM2AP) shows promise as a novel biomarker for detecting specific patterns of kidney damage caused by cisplatin and gentamicin. This finding could lead to better patient stratification and prognosis for acute kidney injury (AKI).
Area of Science:
- Nephrology
- Biomarker Discovery
- Toxicology
Background:
- Nephrotoxicity from platinum-based chemotherapy, like cisplatin, limits drug dosage and effectiveness, causing acute kidney injury (AKI) and electrolyte imbalances.
- Current diagnostic methods for AKI, including plasma creatinine and existing biomarkers, lack the pathophysiological specificity needed for personalized patient management.
- Cisplatin-induced nephrotoxicity primarily affects the proximal tubule's medullary segments (S2, S3), with higher doses impacting the cortical S1 segment.
Purpose of the Study:
- To investigate the association between urinary ganglioside GM2 activator protein (GM2AP) and specific patterns of tubular damage induced by cisplatin in rats.
- To evaluate GM2AP as a potential diagnostic biomarker for stratifying AKI patients and monitoring treatment response and prognosis.
Main Methods:
- Rats were treated with varying doses of cisplatin (5 and 10 mg/kg) to induce nephrotoxicity.
- Urinary GM2AP levels were measured and correlated with the extent and location of tubular damage.
- Comparisons were made with urinary neutrophil gelatinase-associated lipocalin (NGAL) and the effects of gentamicin and renal ischemia on GM2AP excretion were assessed.
Main Results:
- Urinary GM2AP excretion was specifically detected following damage to the cortical segment of the proximal tubule.
- GM2AP provides distinct and complementary information to NGAL, indicating different aspects of renal injury.
- Gentamicin-induced cortical damage increased urinary GM2AP, while renal ischemia, which spares the cortex, did not affect GM2AP levels.
Conclusions:
- Urinary GM2AP serves as a sensitive indicator of cortical proximal tubule damage, a critical area for renal function.
- GM2AP holds potential as a diagnostic biomarker for stratifying AKI patients based on damage patterns, aiding in prognosis and patient management.
- Prospectively, urinary GM2AP could be integrated into non-invasive liquid biopsies to assess the severity of chemotherapy-induced nephrotoxicity.
