What is the appropriate management for an adult patient with a history of kidney disease, diabetes, or hypertension and impaired renal function, as indicated by a low Glomerular Filtration Rate (GFR)?

Management of Low GFR in Adults with Kidney Disease Risk Factors

For adults with diabetes, hypertension, or kidney disease and low GFR, assess both serum creatinine-based eGFR and urine albumin excretion annually, stage the CKD appropriately, optimize glycemic and blood pressure control, and refer to nephrology when eGFR falls below specific thresholds or complications arise. 1

Initial Assessment and Staging

GFR Measurement and Staging

• Use creatinine-based eGFR (eGFRcr) as the primary assessment tool, with the CKD-EPI equation being the preferred calculation method over the older MDRD equation 1
• If cystatin C is available, combine it with creatinine (eGFRcr-cys) for more accurate GFR estimation 1
• Assess both eGFR and urine albumin-to-creatinine ratio (UACR) simultaneously, as screening with albumin excretion alone misses >20% of progressive disease in diabetic patients 1

CKD Staging Based on GFR

The staging system guides management intensity 1:

• Stage 1: GFR ≥90 mL/min/1.73 m² with kidney damage - Focus on CKD risk reduction and screening
• Stage 2: GFR 60-89 mL/min/1.73 m² with kidney damage - Diagnose, treat comorbidities, slow progression
• Stage 3: GFR 30-59 mL/min/1.73 m² - Estimate progression rate and evaluate/treat complications
• Stage 4: GFR 15-29 mL/min/1.73 m² - Prepare for renal replacement therapy
• Stage 5: GFR <15 mL/min/1.73 m² or dialysis - Kidney failure requiring replacement therapy

Confirming Chronicity

• Do not diagnose CKD based on a single abnormal eGFR or UACR value, as this could represent acute kidney injury or acute kidney disease 1
• Establish chronicity (≥3 months duration) through: review of past GFR measurements, past albuminuria measurements, imaging showing reduced kidney size/cortical thickness, kidney biopsy findings, medical history of CKD-causing conditions, or repeat measurements beyond 3 months 1
• Consider initiating CKD treatments at first presentation if CKD is deemed likely based on other clinical indicators, even before confirming 3-month chronicity 1

Monitoring Strategy

Frequency of Assessment

• Measure serum creatinine with eGFR and urinary albumin excretion at least annually in all adults with diabetes, regardless of baseline albumin excretion level 1
• When eGFR <60 mL/min/1.73 m², screen for CKD complications including anemia, bone disease, electrolyte disturbances, and hypertension 1

Albumin Monitoring

• Normal albumin excretion is defined as UACR <30 mg/g creatinine 1
• Increased urinary albumin excretion (historically "microalbuminuria") is UACR ≥30 mg/g 1
• Require two of three specimens within 3-6 months to show elevated levels before diagnosing persistent albuminuria, as spontaneous remission occurs in up to 40% of type 1 diabetic patients 1
• Exercise within 24 hours, infection, fever, heart failure, marked hyperglycemia, and marked hypertension can falsely elevate urinary albumin 1

Treatment Interventions

Blood Pressure and RAAS Blockade

• Optimize blood pressure control to reduce risk and slow progression of both nephropathy and retinopathy 1
• For patients with diabetes, hypertension, and any degree of albuminuria, use ACE inhibitors or ARBs as first-line therapy 1
• In type 1 diabetes with hypertension and any albuminuria, ACE inhibitors delay nephropathy progression 1
• In type 2 diabetes with hypertension and UACR 30-299 mg/g, both ACE inhibitors and ARBs delay progression to higher albuminuria levels 1
• In type 2 diabetes with hypertension, UACR ≥300 mg/g, and serum creatinine >1.5 mg/dL, ARBs delay progression to ESRD 1

Critical caveat regarding ACE inhibitors/ARBs: Small creatinine increases (up to 30% from baseline) during initiation are often transient and acceptable 2. However, discontinue if serum creatinine exceeds 3 mg/dL or doubles from baseline, or if potassium exceeds 5.5 mmol/L 2. Monitor renal function within the first few weeks of therapy, especially in patients with pre-existing renal impairment 2.

Glycemic Control

• Optimize glycemic control to reduce risk and slow progression of microvascular complications including nephropathy 1
• Consider SGLT2 inhibitors in appropriate patients, as evidence suggests screening for CKD in diabetic and hypertensive patients may now be cost-effective with these agents available 1

Additional Interventions

• When nephropathy is present, initiate protein restriction to 0.8 g/kg body weight/day (10% of daily calories) 1
• Monitor and manage complications that correlate with declining GFR: hypertension (prevalence approaches 80% at stage 4), anemia, malnutrition (declining albumin), and bone/mineral disorders 1

Nephrology Referral Criteria

Mandatory Referral Triggers

Refer to nephrology when stage 4 CKD develops (eGFR 15-29 mL/min/1.73 m²), as consultation at this stage reduces cost, improves quality of care, and delays dialysis 1

Additional Referral Indications

Consider nephrology referral for 1:

• Uncertainty about etiology (heavy proteinuria, active urine sediment, absence of retinopathy despite diabetes, rapid GFR decline)
• Difficult management issues: anemia, secondary hyperparathyroidism, metabolic bone disease, resistant hypertension, electrolyte disturbances
• eGFR <60 mL/min/1.73 m² with management difficulties 1
• eGFR 45-60 mL/min/1.73 m² if possibility of non-diabetic kidney disease exists 1

Important: Other providers should not delay patient education about progressive disease nature, kidney preservation benefits of blood pressure/glucose control, and potential need for renal transplant while awaiting nephrology consultation 1

Risk Stratification for Progression

High-Risk Features for Progressive Disease

Patients with the following are more likely to experience diabetic kidney disease progression 1:

• Increasing albumin levels over time
• Declining GFR trajectory
• Increasing blood pressure
• Presence of retinopathy
• Macrovascular disease
• Elevated lipids and/or uric acid concentrations
• Family history of CKD

Cardiovascular Risk

• Persistent albuminuria (UACR 30-299 mg/g) is a well-established marker of increased cardiovascular disease risk 1
• All patients with CKD have increased risk of hospitalizations, cardiovascular mortality, myocardial infarction, atrial fibrillation, stroke, and peripheral vascular disease 1

Common Pitfalls to Avoid

• Do not rely on clinical symptoms and signs alone to detect reduced renal function, as they are poorly predictive until very advanced disease (eGFR <15 mL/min/1.73 m²) 3
• Do not use age-adjusted definitions of CKD, as there are no age-adjusted definitions for diabetes or hypertension; rather, recognize that individual implications differ by age group 1
• Do not assume all diabetic kidney disease follows the classical albuminuria-first pattern, as substantial percentages of adults with type 2 diabetes develop decreased GFR without increased urine albumin excretion 1
• Do not discontinue ACE inhibitors/ARBs prematurely for modest creatinine increases during appropriate therapy, unless creatinine exceeds 2.5-3.0 mg/dL or potassium exceeds 5.5 mmol/L 2
• Do not delay nephrology referral until dialysis is imminent, as early referral at stage 4 CKD improves outcomes 1