Renal · Year 2 · from Renal
Case 1: Diabetic Glucosuria and SGLT2 Inhibitor Therapy
Patient Presentation
A 58-year-old female with type 2 diabetes mellitus presents for diabetes management. Her hemoglobin A1c is 8.4% despite maximum dose metformin and a sulfonylurea. She also has stage 3 CKD with eGFR 45 mL/min/1.73m2 and albuminuria (UACR 180 mg/g).
History of Present Illness
- Type 2 diabetes for 12 years
- Hypertension controlled on lisinopril
- BMI 32 kg/m2
- Fasting glucose levels 160-200 mg/dL
- No symptoms of hypoglycemia
Physical Examination
- Blood pressure: 138/84 mmHg
- Weight: 89 kg
- No peripheral edema
- Monofilament sensation reduced in both feet
- Urine dipstick: 2+ glucose
Workup
Laboratory Studies:
- HbA1c: 8.4%
- Fasting glucose: 182 mg/dL
- Creatinine: 1.4 mg/dL (eGFR 45)
- UACR: 180 mg/g
- Urinalysis: 2+ glucose, trace protein
Diagnosis
Type 2 Diabetes with Diabetic Kidney Disease - Candidate for SGLT2 Inhibitor Therapy
Discussion
This case illustrates glucose handling in the proximal tubule:
- Normal Glucose Reabsorption: The lecture describes that SGLT2 (90%) and SGLT1 (10%) in the proximal tubule normally reabsorb all filtered glucose. The transport maximum (Tm) is approximately 375 mg/min.
- Renal Threshold: When plasma glucose exceeds ~180-200 mg/dL, the transport maximum is exceeded and glucose appears in urine. Her fasting glucose of 182 mg/dL is at the threshold.
- SGLT2 Inhibitor Mechanism: Dapagliflozin or empagliflozin block SGLT2, deliberately causing glucosuria to lower blood glucose. This also delivers more sodium to the macula densa, activating tubuloglomerular feedback and reducing intraglomerular pressure.
Treatment
- Add empagliflozin 10 mg daily
- Continue lisinopril for renal protection
- Counsel about increased urinary frequency and genital yeast infection risk
- Monitor creatinine (expect small initial rise of 3-5 mL/min which is hemodynamic and protective)
Clinical Pearl
SGLT2 inhibitors work by blocking proximal tubule glucose reabsorption, causing intentional glucosuria. The renal protective effects extend beyond glucose control to include reduced intraglomerular pressure through tubuloglomerular feedback.