What causes a decrease in estimated Glomerular Filtration Rate (EGFR) with stable Blood Urea Nitrogen (BUN) and creatinine levels in an older adult with a history of hypertension and diabetes?

Decreased eGFR with Stable BUN and Creatinine in Older Adults

In older adults with hypertension and diabetes, a decreased eGFR while BUN and creatinine remain at baseline most commonly reflects age-related physiological decline in kidney function combined with reduced muscle mass that masks true creatinine elevation, rather than acute kidney injury or progressive chronic kidney disease.

Primary Mechanism: Age-Related GFR Decline with Muscle Mass Loss

The discordance between declining eGFR and stable creatinine occurs because serum creatinine does not accurately reflect age-related decline in GFR due to concomitant age-related decline in muscle mass that reduces creatinine generation 1, 2.

• In older adults, serum creatinine levels may remain within reference limits while renal function is actually reduced 1
• A serum creatinine of 1.2 mg/dL may correspond to a creatinine clearance of 110 mL/min in a young athlete but only 40 mL/min in an elderly woman 2
• Creatinine-based equations can misclassify kidney disease by one stage in >30% of older participants due to reduced muscle mass, exercise, and meat intake 1

Physiological Kidney Aging

Normal aging produces predictable reductions in kidney function that explain isolated eGFR decreases 1, 3, 2:

• GFR declines by 1-2 mL/min per year beginning in the sixth decade as a normal aging process 3
• Mean GFR loss is approximately 16.6 mL/min/1.73 m² per decade in elderly women, with acceleration after age 80 4
• Aging causes 30-35% reduction in renal mass and renal blood flow 1
• Approximately 17% of persons older than 60 years have an eGFR less than 60 mL/min/1.73 m² 2

Comorbidity-Related Mechanisms in Hypertension and Diabetes

Hypertension and diabetes cause progressive reductions in renal blood flow through vascular glomerulosclerosis and interstitial fibrosis, which decrease GFR independent of acute tubular injury 1:

• Hypertension causes vascular glomerulosclerosis that reduces glomerular filtration 1
• Diabetes produces interstitial fibrosis and reduces renal blood flow 1
• These chronic processes decrease GFR gradually without necessarily causing acute elevations in BUN or creatinine 1

Medication-Induced Hemodynamic Changes

Antihypertensive medications commonly used in this population can reduce GFR through hemodynamic effects without causing true kidney injury 1, 5:

• ACE inhibitors and ARBs reduce intraglomerular pressure and can cause up to 30% elevation in serum creatinine from baseline without representing acute kidney injury 1
• Diuretics reduce intravascular volume and renal blood flow, decreasing GFR hemodynamically 1
• These medication effects represent functional rather than structural kidney changes and do not indicate progressive kidney disease when creatinine increases remain under 30% 1

Why BUN and Creatinine Remain Stable

Several factors explain stable BUN and creatinine despite declining eGFR 1, 2:

• Reduced muscle mass in older adults decreases creatinine generation, keeping serum levels artificially stable 1, 2
• BUN is influenced by protein intake, hydration status, and catabolism—factors that may remain constant even as GFR declines 1
• The relationship between creatinine and GFR is not linear; small changes in creatinine can reflect larger changes in GFR at lower baseline kidney function 2

Clinical Implications and Monitoring Strategy

Serial eGFR measurements over time are more informative than single values for distinguishing physiological aging from pathological kidney disease 3:

• Monitor for rate of eGFR decline: If declining >4-8 mL/min per year, this suggests accelerated kidney disease requiring intervention 3
• Measure urinary albumin-to-creatinine ratio (UACR), as albuminuria ≥30 mg/g indicates kidney damage and dramatically increases cardiovascular risk even with preserved eGFR 1, 3
• Consider using CKD-EPI cystatin C equations, which are more accurate than creatinine-based equations in older adults 1

Key Pitfalls to Avoid

• Do not assume stable creatinine means stable kidney function in older adults—always calculate eGFR using validated equations that incorporate age 1, 2
• Do not discontinue ACE inhibitors or ARBs for creatinine increases up to 30% from baseline, as this does not represent acute kidney injury and these medications provide cardiovascular and renal protection 1
• Screen for retinopathy in diabetic patients, as its absence with kidney disease suggests alternative causes requiring nephrology referral 1