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With the increasing F1 peptide concentrations, from 0.8 to 3.2 M, the V max value decreased from 0.833 mol/mg/min to 0.645 mol/mg/min, K i value increased from 4.0 M to 5.82 M, and [I]/K i value increased from 0.2 to 0.55

4 INCREASED PRODUCTION (muscle related) Rhabdomyolysis Very high muscle mass Intense exercise Trauma Burns 5 DRUG-INDUCED Drugs that reduce filtration or secretion: NSAIDs ACE inhibitors (initial rise) Aminoglycosides Cisplatin Radiocontrast agents PATHOPHYSIOLOGY (STEPWISE) Kidney injury or low blood flow Reduced glomerular filtration Creatinine not filtered Creatinine retained in blood Serum creatinine rises CELLULAR LEVEL (WHY IT ACCUMULATES) Creatinine: Freely filtered at glomerulus Not reabsorbed Slightly secreted in tubules So when nephrons are damaged: filtration falls blood level rises SIMPLE MEDICAL FIGURE (Educational) [ Muscle ] produces [ Creatinine ] normally filtered by [ Kidney (Glomerulus) ] excreted in urine If kidney damaged: [ Creatinine ] in blood ABOUT "CREATININE UNDER MICROSCOPE" Creatinine: Cannot be seen as a structure in blood smear It is a small molecule (113 Da) measured by: Biochemical assay (Jaffe / enzymatic method) Not by light microscopy Lab view: Blood sample analyzer numeric value (mg/dL) NORMAL VALUES (approx) Adult female: 0.5 1.1 mg/dL Adult male: 0.7 1.3 mg/dL But interpretation depends on: Age Sex Muscle mass GFR (eGFR is better than creatinine alone) IMPORTANT CLINICAL MEANING Rising creatinine = loss of kidney filtration capacity marker of kidney injury predictor of mortality & ESRD AUTHENTIC REFERENCES 1

Peptide therapies should only be initiated under the care of a licensed medical provider following an appropriate evaluation