Approach to Early Detection and Management of Kidney Disease

Serum urea (sU) is synthesized in liver and serum creatinine (sCr) is a degradation product of muscle cells, both represents for the efficacy of glomerular filtration. Both sU and sCr have poor predictive accuracy for renal injury, particularly in the early stages of kidney diseases because they are evaluated when 60-70% nephrons were already damaged and then kidney diseases changed to irreversible required only dialysis or kidney transplantation. Therefore, patients undergo into multi disorder health problems towards death. So, it is now most urgent required for early diagnosis of kidney injury by analysis of direct kidney injury markers, renal tubule injury markers and proteomic genomic markers of kidney disorders from both urine and serum and alternative treatment strategies for management of kidney diseases using medicinal plants. There are four major classes of markers viz., tubular injury markers e.g, KIM-1, proteomic and genomic marker from proximal nephron is IL-18, kidney functional marker-cystatin C and oxidation stress marker- Malon di aldehyde (MDA), alpha Glutathione S Transferase (alpha GST). IL-18, KIM-1, cystatin C and GST are important mediators appear in urine when renal tubules are stressed and injured. The medicinal plant like Terminellia arjuna (TA) has been a part of ayurvedic medicinal system contains phytoconstituents like triterpenoids, tannins, flavonoids and others they have proved anti cardiovascular properties, anticancer, antimicrobial properties, and neproprotective. Aqueous bark extract of TA possess antiuremic properties was already established in our laboratory on dehydration induced uremic rats. Therefore, the manuscript was designed to investigate the kidney injury proteomic and genomic biomarkers from both serum and urine on acetaminophen induced kidney disorder rats and analysis of therapeutic efficacy of phytocompounds from the bark of Terminalia arjuna (TA).

Objective: There were main two objectives, first was the identification of best biomarkers for early screening of kidney diseases whether plasma urea and creatinine or novel urinary low molecular weight protein biomarkers Interlukin-18 (IL-18), Kidney injury molecule-1(KIM-1), cystatin –C. Second, the therapeutic efficacy of methanol fraction of Terminalia arjuna (MFTA) on urinary novel biomarkers.

Methods: A total of 35 adult male rats were divided into three groups (n = 5), group 1 was fed normal food, group 2, normal food with administration of acetaminophen (APAP) for 5 days, 10 days and 15 days and group 3, normal food with administration of APAP and co-administration of MFTA for 5 days, 10 days and 15 days. All rats were sacrificed at 15th day of experiment.

Results: Results showed 5 day, 10 day, 15 day administration of APAP increased novel urinary biomarkers as IL-18, KIM-1 near two folds and cystatin-C near six folds increased than old biomarkers plasma urea and plasma creatinine. Administration of APAP with co-administration of MFTA represented the protective effect by decreasing old and new novel biomarkers with Superoxide dismutase (SOD) and catalase but Malondialdehyde (MDA) level increased. SDS-PAGE showed new low molecular weight urinary protein bands in APAP administration rats, protective effect of MFTA present no band in this molecular level as normal rats.

Conclusion: MFTA is the most potent nephroprotective agent and urinary low molecular proteins are the best diagnostic tools for early detection of kidney disease over common plasma urea and creatinine.