From the Guidelines
The most appropriate additional treatment for this patient is canagliflozin (option A). This 60-year-old woman with stage G3 chronic kidney disease (CKD) and significant proteinuria due to diabetic kidney disease would benefit from an SGLT2 inhibitor like canagliflozin. Her uncontrolled diabetes (HbA1c 8.3%) and high proteinuria (urine protein-creatinine ratio 3680 mg/g) indicate a need for therapy that addresses both glycemic control and kidney protection. Canagliflozin has demonstrated significant renoprotective effects in patients with diabetic kidney disease by reducing albuminuria, slowing GFR decline, and decreasing the risk of kidney failure, as supported by recent guidelines 1. It also provides cardiovascular benefits, which is important since patients with CKD have increased cardiovascular risk.
The use of SGLT2 inhibitors in patients with CKD is recommended by several guidelines, including the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report 1, and the European Society of Cardiology guidelines 1. According to these guidelines, SGLT2 inhibitors are recommended for patients with type 2 diabetes and CKD to reduce the risk of kidney disease progression and cardiovascular events.
The other options are less appropriate:
- Glyburide carries hypoglycemia risk in CKD, and its use is not recommended in patients with significant kidney disease 1.
- Losartan would be redundant with lisinopril (she's already on an ACE inhibitor), and there is no clear benefit to adding another renin-angiotensin-aldosterone system (RAAS) inhibitor in this case.
- Pioglitazone can cause fluid retention, which is problematic in CKD, and its use is not recommended in patients with significant kidney disease 1.
- Sitagliptin, while safe in CKD, lacks the kidney-protective benefits of SGLT2 inhibitors, and its use would not address the patient's significant proteinuria and kidney disease progression risk.
In summary, canagliflozin is the most appropriate additional treatment for this patient, given its proven benefits in reducing kidney disease progression and cardiovascular risk in patients with diabetic kidney disease, as supported by recent guidelines and studies 1.
From the FDA Drug Label
The CREDENCE trial was a multinational, randomized, double-blind, placebo-controlled trial comparing canagliflozin with placebo in adult patients with type 2 diabetes mellitus, an eGFR ≥ 30 to < 90 mL/min/1. 73 m 2and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g) who were receiving standard of care including a maximum-tolerated, labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)
The most appropriate additional treatment for this patient is Canagliflozin.
- The patient has type 2 diabetes mellitus with an eGFR of 45 mL/min/1.73 m2 and albuminuria (urine albumin/creatinine ratio of 3680 mg/g), which meets the criteria for the CREDENCE trial.
- The patient is already receiving an ACEi (lisinopril), which is part of the standard of care for patients with diabetic nephropathy.
- Canagliflozin has been shown to reduce the risk of renal and cardiovascular outcomes in patients with diabetic nephropathy and albuminuria, as demonstrated in the CREDENCE trial 2.
From the Research
Patient Profile
- 60-year-old woman with stage G3 proteinuric chronic kidney disease due to type 2 diabetes mellitus
- Current medications: lisinopril and metformin
- Laboratory studies:
- Hemoglobin A1c: 8.3%
- Creatinine: 1.3 mg/dL (114.9 µmol/L)
- Potassium: 4.3 mEq/L (4.3 mmol/L)
- Estimated glomerular filtration rate: 45 mL/min/1.73 m2
- Spot urine protein-creatinine ratio: 3680 mg/g
Treatment Options
- The patient's current treatment regimen includes lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, which is commonly used to manage proteinuric chronic kidney disease
- Considering the addition of another medication to improve glycemic control and reduce proteinuria
- Options include:
- A: Canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor
- B: Glyburide, a sulfonylurea
- C: Losartan, an angiotensin II receptor blocker (ARB)
- D: Pioglitazone, a thiazolidinedione
- E: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor
Recommended Treatment
- Based on the patient's profile and laboratory studies, the most appropriate additional treatment is canagliflozin (Option A) 3, 4, 5, 6, 7
- Canagliflozin has been shown to improve glycemic control, reduce proteinuria, and have beneficial effects on cardiovascular outcomes in patients with type 2 diabetes mellitus and chronic kidney disease 3, 4, 5, 7
- The patient's estimated glomerular filtration rate (eGFR) is 45 mL/min/1.73 m2, which is within the range where canagliflozin has been shown to be effective and safe 7