Patient: Mr. Niu; gender: male; age: 70 years old; occupation: retired medical staff. The chief complaint was intermittent facial and bilateral lower extremity edema. The patient developed facial and bilateral lower limb edema without any known cause one year ago. Increased nocturia was reported, although there was no hematuria, no fever, no malaise, no skin rash, and no photosensitivity. The patient was found to be positive for proteinuria several times. The patient was administered "Bailing Capsules and Shenyankangfu Tablets" orally, but the edema varied between mild and (at times) severe. The outpatient examination results were as follows (2021-10-13): urine protein quantification 5.54 g/24 h/2300 ml, blood glucose (BG) 7.5 mmol/L, glycosylated albumin 21.3%. The patient had a previous history of DM for 26 years with a maximum BG of 16 mmol/L. The patient was treated with Novolin 16 U bid and glargine insulin 12 U qn, together with oral administration of "Metformin". Fasting BG (FBG) was within the range of 10-15 mmol/L with basically normal postprandial blood glucose (PBG). The patient had a 20-year history of hypertension with maximum blood pressure (BP) of 160/90mmHg. He was medicated with oral administration of Norvasc 5 mg QD and BP was maintained at around 140/80 mmHg. He had a 20-year history of coronary heart disease (CHD) with long-term oral administration of Atorvastatin. A pacemaker had been implanted for eight months due to bradycardia. Patient had undergone cataract surgery in the right eye six months earlier, and suffered from blurred vision in both eyes at time of examination. Personal history: reported no history of smoking and drinking. Marital history: patient married at 29 years of age; spouse had hypertension and DM. Patient had one son, who was healthy. Family history: patient's father died of unknown cause; mother died of cerebral hemorrhage. Patient's two brothers died of renal failure and esophageal cancer, respectively. Patient's two sisters had DM and hypertension respectively before death. Results of physical examination at admission: T 36.5C, P 66/min, R 18 times/min, BP 153/92 mmHg. The patient was conscious and communicated fluently. The bilateral breath sound was clear without dry and moist rales. The pacemaker rate was 66 times/min. The abdomen was flat, and the liver and spleen were impalpable. Mild pit edema of both lower extremities was observed. Ultrasonography results: normal size of both kidneys, sclerosis plaque formation in the bilateral carotid artery. Chest computed tomography (CT) results: multiple micronodules in both lungs with partial calcification, which were considered to be benign. Post cardiac surgery, aortic and coronary artery sclerosis. No significant changes compared to the examination results on 3 Mar 2021. Electrocardiography (ECG) results: dual-chamber pacing rhythm with normal electrical axis. Routine blood test results: white blood cell (WBC) 5.78x109, red blood cell (RBC) 4.62x1012, platelet (PLT) 154x109, Neutrophil (N) 65%. Routine urine test results: urine protein 3+, occult blood, RBC 0.61/Hp, glucose (GLU)2+. Renal function test results: blood urea nitrogen (BUN) 7.63 mmol/L, creatinine (Cr) 57 mumol/L, uric acid (UA) 336 mumol/L. Liver function test results: albumin (ALB) 30 g/L, lipid:total cholesterol (TCH) 5.60 mmol/L, triglyceride (TG) 2.13 mmol/L. The levels of serum albumin, serum creatinine, and urine protein of this patient on different dates are show in  Table 1 . Glycosylated hemoglobin (HBA1c) 7.2%; albumin creatinine ratio (ACR) 5871.94 mg/g. No abnormalities in the following: four items of coagulation, three items of cardiac enzymes, eight items of infection, antineutrophil cytoplasmic antibody (ANCA), anti-phospholipase A2 antibody (PLA2R), antinuclear antibody profile, autoantibodies, blood and urine immunofixation electrophoresis, immunoglobulins, and complements. Impressions at admission: 1. nephrotic syndrome (NS); 2. hypertension, grade 2 with very high risk; 3. DM; 4. CHD; 5. post-pacemaker implantation; 6. post-operation of right cataract surgery. The treatments administered were as follows: 1. monitoring of BP and BG, with a low-salt, low-fat diabetic diet; 2. Atorvastatin for lipid-lowering, Novolin + glargine insulin + Metformin for BG lowering and amlodipine besylate for BP lowering; 3. plan to conduct a renal biopsy to confirm the pathological diagnosis. On 10 Nov 2021, following the completion of relevant examinations, a renal biopsy was conducted. On 12 Nov 2021, the T cell results for tuberculosis were found to be positive, and the department of tuberculosis was consulted. The suggestions were as follows: taking into account the calcific density nodule in the right middle lobe in lung CT and TB-IGRA (+), the status of tuberculosis infection should be considered, and old tuberculosis of the right lung could not be excluded; prophylactic anti-tuberculosis therapy should be conducted through the administration of hormones or immunosuppressants. Results following consultation with the department of ophthalmology were as follows: macular degeneration in both eyes, cataract in the left eye, post-operation of cataract surgery in the right eye. Calcium hydroxybenzene sulfonate was recommended along with regular review. Immunofluorescence (IF): IgA+ IgG+- IgM- C3+ C1q- FRA- Alb+- kappa+- lambda+- IgG1- IgG2- IgG3- IgG4-; Light microscopy showed moderate to severe diffuse proliferation of mesangial cells and stroma. The periodic acid-Schiff staining showed moderate to diffuse proliferation of mesangial cells and stroma ( Figure 1A ), and the periodic acid silver methenamine staining and Masson's staining showed severe diffuse proliferation of mesangial cells and stroma ( Figure 1B ). It was accompanied by diffuse thickening of the basement membrane, small eosinophilic deposits in the subendothelial segment, and microangioma-like expansion of segmental capillary loops. There were vacuoles and granular degeneration of renal tubular epithelial cells, focal atrophy, and a few protein casts were observed in the lumen. Renal interstitial focal lymphocyte and monocyte infiltration with fibrosis, wall thickening of small arteries, intimal fibrosis and sclerosis, and lumen stenosis were also observed.
Electron microscopy examination showed mild to moderate proliferation of glomerular mesangial cells, mostly homogeneous thickening of the glomerular basement membrane (GBM), occasional small deposits of electron-dense material in the mesangial region, and segmental fusion of epithelial foot processes. The renal tubular epithelial cells exhibited vacuolar degeneration with increased lysosomes and partial atrophy. The renal interstitium was infiltrated by a small number of lymphoid mononuclear cells with collagen fiber proliferation. These results were consistent with mild to moderate mesangial proliferative IgAN (Type IIa), as shown in  Figure 2 . Hormones (methylprednisolone: 32 mg, q.d.) and prophylactic (isoniazide: 0.3 g, q.d.) anti-tuberculosis therapy were conducted for three months, after which NS was found to be partially relieved. The patient is currently undergoing treatment.