In an 85‑year‑old woman with elevated blood urea nitrogen (BUN) and reduced estimated glomerular filtration rate (eGFR), what is the initial evaluation and management?

Initial Evaluation and Management of Elevated BUN and Reduced eGFR in an 85-Year-Old Woman

In an 85-year-old woman with elevated BUN and reduced eGFR, immediately measure urine albumin-to-creatinine ratio (UACR) and confirm chronicity by reviewing past laboratory values or repeating measurements in 2-4 weeks, while simultaneously assessing for reversible pre-renal causes such as dehydration and medication effects. 1, 2

Confirm Chronicity vs. Acute Kidney Injury

• Do not assume chronic kidney disease based on a single abnormal eGFR measurement, as this could represent acute kidney injury (AKI) or acute kidney disease (AKD) rather than CKD. 1
• Review historical eGFR and creatinine measurements to determine if kidney dysfunction has persisted >3 months, which is required to confirm CKD diagnosis. 2
• If no prior measurements exist or duration is unclear, repeat serum creatinine and eGFR within 2-4 weeks to distinguish CKD from AKI. 2
• CKD requires proof of chronicity through past eGFR measurements, past albuminuria measurements, imaging findings (reduced kidney size, cortical thinning), kidney pathology, medical history of conditions causing CKD, or repeat measurements beyond 3 months. 1, 3

Assess for Reversible Pre-Renal Causes

Evaluate Volume Status and Dehydration

• A BUN/creatinine ratio >20:1 strongly suggests pre-renal azotemia from dehydration or volume depletion, which is potentially reversible with fluid repletion. 4, 5
• Assess volume status clinically by checking for orthostatic hypotension (systolic BP drop ≥20 mmHg or diastolic drop ≥10 mmHg upon standing), decreased skin turgor, dry mucous membranes, and recent weight loss. 4
• Check serum osmolality as the gold standard for diagnosing dehydration, with values >300 mOsm/kg confirming dehydration. 4
• If dehydration is present, improvement in BUN and creatinine should occur within 24-48 hours of adequate fluid repletion; if values remain elevated despite adequate hydration for 2 days, intrinsic kidney disease should be considered. 4

Review Medications

• Immediately review all medications for nephrotoxic agents and drugs that affect renal hemodynamics, including NSAIDs, ACE inhibitors, ARBs, diuretics, trimethoprim, and cimetidine. 1, 4
• Diuretics can cause pre-renal azotemia through volume depletion, which is the most common avoidable cause of creatinine elevation in patients on RAAS-modulating drugs. 4
• NSAIDs should be discontinued when elevated BUN and creatinine are detected, as they impair renal perfusion. 1, 4
• ACE inhibitors and ARBs can cause modest creatinine increases (up to 30% or <266 μmol/L [3 mg/dL]) through hemodynamic changes; these are acceptable and do not require discontinuation unless the rise exceeds 30% or hyperkalemia develops. 1, 4
• Trimethoprim, cimetidine, and salicylates can raise serum creatinine without reducing true GFR by blocking tubular secretion. 4

Measure Urine Albumin-to-Creatinine Ratio (UACR)

• Measure UACR on a random spot urine sample immediately, as albuminuria classification is essential for risk stratification and treatment decisions independent of eGFR. 1, 2, 3
• UACR ≥30 mg/g indicates kidney damage and confirms CKD diagnosis when present for ≥3 months. 2, 3
• The combination of eGFR and UACR determines progression risk and monitoring intensity, with both providing independent prognostic information for cardiovascular events, CKD progression, and mortality. 2
• Do not rely on urine dipstick alone, as UACR measurement is more accurate and quantitative. 2

Determine Underlying Cause

Screen for Primary CKD Risk Factors

• Screen for diabetes immediately by measuring hemoglobin A1c or fasting glucose, as diabetes is the leading cause of CKD and end-stage kidney disease in the United States, accounting for 30-40% of cases. 2
• Measure blood pressure at every clinical encounter, as hypertension is present in 91% of CKD patients and is one of the most frequent causes of CKD in developed countries. 2
• Assess for cardiovascular disease history, as 46% of CKD patients have atherosclerotic heart disease and the combination dramatically accelerates kidney damage. 2

Obtain Urinalysis with Microscopy

• Perform urinalysis with microscopy to look for hematuria, pyuria, or casts that suggest glomerulonephritis or other primary kidney diseases. 2, 4
• Urine microscopy has excellent negative predictive value for ruling out clinically important intrinsic kidney injury. 4
• Active sediment (red blood cells or cellular casts) suggests non-diabetic kidney disease and may warrant nephrology referral for possible kidney biopsy. 4

Consider Additional Causes in Elderly Women

• Evaluate for heart failure, as reduced cardiac output is a pre-renal cause of elevated BUN and creatinine with BUN/creatinine ratio >20:1. 4
• Consider multiple myeloma in patients with unexplained renal dysfunction, especially when accompanied by hypercalcemia, anemia, or bone pain. 4
• Assess for nephrotoxin exposure including heavy metals, agrochemicals, and contaminated drinking water. 2

Screen for CKD Complications

• At age 85 with reduced eGFR, systematically screen for CKD complications including serum electrolytes (sodium, potassium, chloride, bicarbonate), complete blood count (hemoglobin), serum calcium and phosphate, intact parathyroid hormone (PTH), and 25-hydroxyvitamin D. 2
• Monitor blood pressure and weight, and assess for edema, orthopnea, and signs of fluid retention. 2
• Check for metabolic acidosis (bicarbonate <22 mEq/L), hyperkalemia (potassium >5.0 mmol/L), and anemia (hemoglobin <12 g/dL in women). 1, 2

Risk Stratification and Monitoring Frequency

• Use the combination of eGFR and UACR to determine progression risk and monitoring intensity according to the KDIGO risk stratification grid. 2
• For eGFR 45-59 mL/min/1.73 m² (Stage 3a) with UACR <30 mg/g: monitor 2 times per year. 2
• For eGFR 45-59 mL/min/1.73 m² with UACR 30-300 mg/g: monitor 3 times per year. 2
• For eGFR 45-59 mL/min/1.73 m² with UACR >300 mg/g: monitor 4 times per year and refer to nephrology. 2
• For eGFR 30-44 mL/min/1.73 m² (Stage 3b): increase monitoring frequency and consider nephrology referral. 2
• For eGFR <30 mL/min/1.73 m² (Stage 4-5): immediate nephrology referral is required. 2, 4

Age-Specific Considerations

• In elderly women aged 75-85, eGFR typically ranges from 30-89 mL/min/1.73 m² (Stage 2-3), with an expected decline of approximately 16.6 mL/min/1.73 m² per decade that accelerates with age. 6
• Women with eGFR <45 mL/min/1.73 m² (CKD Stage 3B-5) demonstrate a 3.5-fold increased risk of death compared to Stage 1-2, confirming the clinical applicability of the KDIGO classification 3A and 3B in the elderly. 6
• Serum creatinine alone is unreliable for assessing kidney function in elderly women, as it can be normal even when GFR has decreased by 40%, and may underestimate kidney dysfunction if the patient has decreased muscle mass. 4

Nephrology Referral Indications

• Refer to nephrology immediately if eGFR <30 mL/min/1.73 m², continuously increasing urinary albumin levels despite optimal management, continuously decreasing eGFR, uncertainty about etiology or atypical features suggesting non-diabetic kidney disease, or difficulty managing CKD complications. 2, 4
• Consider nephrology referral for kidney biopsy when clinically appropriate to evaluate cause and guide treatment decisions, particularly when urine microscopy shows active sediment or when diagnosis is uncertain. 1, 4

Initiate Treatment if CKD is Likely

• Consider initiation of CKD treatments at first presentation of decreased eGFR if CKD is deemed likely due to presence of other clinical indicators, even before confirming 3-month chronicity. 1
• Target blood pressure <130/80 mmHg in all CKD patients, particularly those with albuminuria ≥300 mg/g. 2
• Initiate ACE inhibitor or ARB for patients with UACR ≥300 mg/g and/or eGFR <60 mL/min/1.73 m², unless contraindicated by significant hyperkalemia (K+ >5.0 mmol/L), significant renal dysfunction (creatinine >221 μmol/L [>2.5 mg/dL] or eGFR <30 mL/min/1.73 m²), or symptomatic hypotension (systolic BP <90 mmHg). 1, 2
• Initiate statin therapy for cardiovascular risk reduction in all CKD patients, as cardiovascular mortality risk is 5-10 times higher than progression to end-stage kidney disease. 2

Common Pitfalls to Avoid

• Do not rely on serum creatinine alone; always calculate eGFR using validated equations (CKD-EPI 2021) and measure UACR, as both provide independent prognostic information. 2, 4
• Do not assume chronicity based on a single abnormal eGFR level without confirming persistence for ≥3 months or reviewing historical values. 1, 3
• Do not discontinue ACE inhibitors or ARBs for minor increases in serum creatinine (<30%) in the absence of volume depletion or hyperkalemia. 2, 4
• Do not combine ACE inhibitors with ARBs, as this increases adverse events without additional benefit. 2
• Do not skip albuminuria testing, as eGFR and UACR provide independent prognostic information and guide treatment intensity. 2