Objective: To explore the clinical efficacy and mechanism of modified Ermiao Pills in improving refractory proteinuria of diabetic kidney disease(DKD) based on the ""Damp - Heat Damaging Kidney"" theory.Methods: A total of 126 patients with diabetic kidney disease were selected from the TCM department and nephrology department of Gulou Hospital affiliated to Nanjing University Medical School from January 2022 to January 2025. All patients were divided into the treatment group (Group A, n = 63) and the control group (Group B, n = 63) using a stratified randomization method with sealed envelopes. Group A received conventional basic treatment combined with modified Ermiao Pills, while Group B received only conventional basic treatment. Clinical assessments were conducted on enrollment day and at week 8 of treatment to evaluate TCM syndrome scores [including polydipsia, limb edema, sticky mouth, and epigastric distension], detect urinary protein profiles [24 - hour urine protein (24hUpro), urinary albumin (UAlb), urinary kidney injury molecule-1 (UKim - 1), urinary N - acetyl - β - D - glucosidase (UNAG)], analyze metabolomics parameters [palmitic acid, L - carnitine, phosphatidylcholine (PC), diacylglycerol (DG)], assess renal function[blood creatinine (Scr), blood urea nitrogen (BUN)], and evaluate safety indicators [red blood cells (RBC), alanine aminotransferase (ALT), albumin (Alb), glycated hemoglobin (HbA1c)]. The clinical efficacy of both groups was compared.Results: After treatment, compared with group B, the scores of polydipsia, limb edema, sticky mouth, epigastric and abdominal distension in group A, as well as the levels of 24hUpro, UAlb, UM - 1, UNAG, palmitic acid, Scr, BUN, were decreased (P < 0.05), while the levels of L - carnitine, PC and Dg were increased (P <0.05). Compared with group B, the total effective rate of group A increased (P <0.05).Conclusion: For the first time in a single - center randomized controlled trial, the combination of modified Ermiao pills and conventional treatment based on the ""damp - heat injuring kidney"" theory has been demonstrated to significantly improve refractory proteinuria in diabetic nephropathy, regulate metabolomic indicators, and protect renal function with high safety. Palmitic acid, L - carnitine, PC, and Dg may serve as potential therapeutic targets for modified Ermiao pills in treating refractory proteinuria of diabetic nephropathy.

"Damp - Heat Damaging Kidney" theory  /  Modified Ermiao Pills  /  Diabetic kidney disease  /  Refractory proteinuria