What are the steps for nephrology clearance assessments and medication management in patients with impaired renal function?

Nephrology Clearance Assessments and Medication Management in Renal Impairment

Initial Assessment of Renal Function

Begin with creatinine-based estimated GFR (eGFRcr) as the initial test, which is routinely available as part of basic metabolic panels. 1

Baseline Testing Requirements

• Obtain baseline urinalysis and calculated creatinine clearance or estimated GFR before initiating care, especially in high-risk populations including Black patients, those with advanced disease, or patients with comorbidities. 1
• Measure serum creatinine to calculate eGFR using standardized equations 1
• Perform screening urinalysis for proteinuria at initiation of care and annually thereafter, particularly in patients at increased risk (Black patients, CD4 count <200 cells/µL, viral load >4000 copies/mL, diabetes, hypertension, or HCV coinfection) 1
• Patients with proteinuria ≥1+ by dipstick or reduced kidney function should be referred to nephrology for consultation and undergo additional studies including quantification of proteinuria. 1

When to Use More Accurate GFR Assessment

Use eGFRcr-cys (creatinine and cystatin C-based estimated GFR) when eGFRcr is expected to be inaccurate and GFR affects clinical decision-making, such as drug dosing or CKD staging. 1

Situations Requiring Enhanced Assessment

• Patients with altered muscle mass (very low or very high), where creatinine generation is affected 1
• Patients on medications affecting creatinine secretion (cobicistat, dolutegravir, trimethoprim), which elevate serum creatinine without affecting true renal function 1
• Patients with chronic illnesses including malnutrition, cancer, heart failure, cirrhosis, or muscle wasting diseases 1
• Patients with dietary extremes (low-protein, keto, vegetarian, or high-protein diets with creatine supplements) 1
• When even more accurate assessment is needed, measure GFR using plasma or urinary clearance of exogenous filtration markers (iothalamate, iohexol) 1

Medication Dosing Based on Renal Function

General Principles

Medications should be dosed based on renal function according to their package inserts, using the Cockcroft-Gault equation for creatinine clearance calculation, as this was used in most medication dosing studies. 1

Specific Medication Considerations

Before Initiating Nephrotoxic Drugs

• Perform urinalysis and calculated creatinine clearance before starting drugs with nephrotoxic potential such as tenofovir or indinavir. 1
• For denosumab therapy, assess renal function including serum creatinine and estimated creatinine clearance before initiation 2

Metformin Dosing Algorithm

Before initiating metformin, obtain an eGFR; metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m². 3

• Do not initiate metformin in patients with eGFR 30-45 mL/min/1.73 m². 3
• Obtain eGFR at least annually in all patients taking metformin. 3
• In patients at risk for developing renal impairment (elderly), assess renal function more frequently. 3
• In patients whose eGFR falls below 45 mL/min/1.73 m² while on metformin, assess benefit-risk of continuing therapy. 3
• Discontinue metformin at time of or prior to iodinated contrast imaging in patients with eGFR 30-60 mL/min/1.73 m², history of hepatic impairment, alcoholism, heart failure, or those receiving intra-arterial contrast; re-evaluate eGFR 48 hours after procedure. 3

Anticoagulant Management

For patients on NOACs (non-vitamin K antagonist oral anticoagulants), calculate creatinine clearance using Cockcroft-Gault method, as this was used in NOAC trials. 1

• Monitor renal function at least yearly in patients on NOACs. 1
• If CrCl <60 mL/min, evaluate more frequently (divide CrCl by 10 to obtain minimum frequency of testing in months). 1
• Dabigatran has 80% renal elimination, edoxaban 50%, rivaroxaban 35%, and apixaban 27% 1
• Rivaroxaban, apixaban, and edoxaban (but not dabigatran) are approved for use in severe CKD (Stage 4, CrCl 15-29 mL/min) with reduced dose regimens. 1

Monitoring Frequency

Standard Monitoring

• Annual eGFR measurement for all patients with or at risk for CKD 3
• More frequent monitoring (every 3-6 months) in patients with eGFR <60 mL/min/1.73 m² 3
• Quarterly or more frequent monitoring in elderly patients, those with multiple comorbidities, or those on nephrotoxic medications 1, 3

Trigger Points for Reassessment

• Any intercurrent acute illness (infections, acute heart failure) should trigger re-evaluation of renal function 1
• Before and after procedures involving iodinated contrast 3
• When initiating or adjusting doses of renally-cleared medications 1

Common Pitfalls to Avoid

• Do not rely solely on serum creatinine as it can be misleading in patients with altered muscle mass, extreme body weights, or those on medications affecting tubular secretion 1
• Do not use eGFRcr-cys in patients with very low muscle mass, high inflammation, high catabolic states, or exogenous steroid use, as these cause significant errors; instead measure GFR directly 1
• Do not assume renal function is stable in acute illness—calculated clearances may indicate normal function when it is severely impaired 1
• Do not forget that some medications (cobicistat, dolutegravir, trimethoprim) elevate creatinine without affecting true GFR, requiring alternative assessment methods 1
• Avoid using random spot urine collections for protein-creatinine ratio as there is significant variation; first morning collections are preferred 1