From the Guidelines
For a patient with a GFR of 26, several medication adjustments are recommended to prioritize morbidity, mortality, and quality of life. Carbidopa/Levodopa should be increased from 1.5 tablets three times daily to 2 tablets three times daily. Dapagliflozin 10 mg, Fenofibrate 160 mg, Gliclazide 60 mg (2 tablets), Iron Plus Essentials (every 2 days), Pantoprazole 40 mg twice daily, Rosuvastatin 10 mg, and Tamsulosin 0.4 mg should all be continued at their current doses. Ramipril should be decreased from twice daily to once daily due to the reduced kidney function, as ACE inhibitors can accumulate and increase the risk of hyperkalemia and further kidney injury when GFR is low, as suggested by the 2014 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1. Semaglutide (Ozempic) should be increased according to the planned titration schedule while monitoring the patient's response, as no dose adjustment is required for eGFR 15 to 89 mL/min/1.73 m², according to the 2020 Endocrine Reviews article on glycemic monitoring and management in advanced chronic kidney disease 1. The patient is not taking Sitagliptin/Metformin, so adherence and necessity should be assessed, considering the recommendations for dose adjustments in patients with chronic kidney disease, as outlined in the 2022 Kidney International article on diabetes management in chronic kidney disease 1. With reduced kidney function (GFR 26), medication dosing requires careful adjustment to prevent adverse effects while maintaining therapeutic benefit, and regular monitoring of kidney function, blood pressure, and blood glucose is essential with these medication changes. Key considerations include the potential for reduced efficacy of certain medications, such as SGLT2 inhibitors, in advanced CKD, as well as the need for cautious use of medications that are primarily renally excreted, such as sulfonylureas, as noted in the 2014 KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD 1. Additionally, the 2007 KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease provide guidance on dosing adjustments for medications in patients with CKD, including the use of fenofibrate, which should be initiated at a dose of 54 mg daily and assessed for effects on kidney function and lipid concentrations 1.
From the FDA Drug Label
• DAPAGLIFLOZIN TABLETS are not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. • For Adults with Renal Impairment Receiving DAPAGLIFLOZIN TABLETS for Indications Other than Glycemic Control: • The recommended dosage of DAPAGLIFLOZIN TABLETS in patients with an eGFR greater than or equal to 25 mL/min/1.73 m2 is the same as the recommended dosage in patients with normal renal function. • Initiation with DAPAGLIFLOZIN TABLETS is not recommended in patients with an eGFR less than 25 mL/min/1.73 m2. • If the eGFR falls below 25 mL/min/1.73 m2 while receiving treatment with DAPAGLIFLOZIN TABLETS, patients may continue DAPAGLIFLOZIN TABLETS 10 mg orally once daily to reduce the risk of eGFR decline, ESKD, CV death and hHF.
The patient has a GFR of 26, which is greater than 25 mL/min/1.73 m2. Dapagliflozin dosage can be continued at the same level as for patients with normal renal function.
- The recommended dosage is 10 mg orally once daily.
- Since the patient's current dosage is 1 tablet QD, which is the same as the recommended dosage, no adjustment is needed 2.
From the Research
Medication Adjustments According to GFR 26
The provided medication adjustments are based on a patient's estimated glomerular filtration rate (GFR) of 26. The medications and their respective adjustments are as follows:
- Carbidopa/Levodopa 25 mg-100 mg Oral Tablet: Increase to 2 tablets TID (from 1.5 tablets TID)
- Dapagliflozin Propanediol 10 mg Oral Tablet: Continue 1 tablet QD
- Fenofibrate, Microcoated 160 mg Oral Tablet: Continue 1 tablet QD
- Gliclazide 60 mg Oral Tablet, Sustained Release 24hr: Continue 2 tablets QD
- Iron Plus Essentials 28 mg Capsule (28 mg-100 mg): Continue 1 capsule every 2 days (Q2D)
- Pantoprazole Sodium 40 mg Oral Tablet, Delayed Release: Continue 1 tablet BID
- Ramipril 5 mg Oral Capsule: Decrease to 1 capsule OD (from BID)
- Rosuvastatin Calcium 10 mg Oral Tablet: Continue 1 tablet QD
- Semaglutide (Ozempic): Increase as per planned titration schedule (monitor response)
- Sitagliptin Phosphate/Metformin HCL 50 mg-500 mg Oral Tablet: Patient is not taking; assess adherence and necessity
- Tamsulosin HCL 0.4 mg Oral Tablet, Sustained Release 24hr: Continue 1 tablet QD
Rationale for Medication Adjustments
The adjustments are likely based on the patient's kidney function, as indicated by the GFR of 26.
- Dapagliflozin has been shown to reduce the risk of kidney failure and heart failure in patients with chronic kidney disease, as demonstrated in the DAPA-CKD trial 3, 4.
- The effects of dapagliflozin on kidney and cardiovascular outcomes are consistent across patients with and without type 2 diabetes 3, 4.
- The DAPA-CKD trial also reported that dapagliflozin reduced the primary outcome of a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes by 39% in patients with chronic kidney disease 5.
- The estimation of GFR is crucial in clinical practice for diagnosing, staging, and managing chronic kidney disease, as well as determining drug dosages 6.
Key Considerations
- The patient's kidney function, as indicated by the GFR of 26, is a critical factor in determining the medication adjustments.
- The use of dapagliflozin in patients with chronic kidney disease has been shown to have renoprotective effects, regardless of the presence or absence of type 2 diabetes 3, 4, 5.
- The medication adjustments should be carefully monitored and adjusted as necessary to ensure optimal patient outcomes.