What are the next steps in managing an adult or elderly patient with impaired renal function, indicated by high serum creatinine and high serum urea, and a potential history of kidney disease, diabetes, or hypertension?

Management of High Serum Creatinine and High Serea Urea

Calculate the estimated glomerular filtration rate (eGFR) using the CKD-EPI equation and obtain a spot urine albumin-to-creatinine ratio (UACR) immediately, as these two measurements together determine the stage of kidney disease, guide medication adjustments, and dictate the urgency of nephrology referral. 1

Immediate Diagnostic Steps

Calculate eGFR and Assess Albuminuria

• Use the CKD-EPI equation to calculate eGFR from serum creatinine (preferred over other formulas), as this is routinely reported by laboratories and available at nkdep.nih.gov 1
• Obtain a random spot urine collection for UACR (not a 24-hour collection, which is more burdensome and adds little accuracy) 1
• Confirm albuminuria with 2 of 3 specimens collected within 3-6 months before diagnosing persistent albuminuria, due to >20% biological variability 1

Determine if This is Acute or Chronic Kidney Disease

• Acute kidney injury (AKI) is defined as ≥50% sustained increase in serum creatinine over a short time period 1
• Review prior creatinine values to establish baseline kidney function 2
• Assess the BUN/creatinine ratio: A ratio >20:1 suggests prerenal azotemia from volume depletion, heart failure, or reduced renal perfusion rather than intrinsic kidney disease 2, 3

Identify Reversible Causes

Prerenal causes (BUN/creatinine ratio >20:1):

• Volume depletion/dehydration 2, 3
• Heart failure with reduced cardiac output 2, 3
• Medication-induced prerenal azotemia (diuretics, ACE inhibitors/ARBs causing excessive diuresis) 2, 3

Intrinsic renal causes:

• Diabetic nephropathy (most common cause of end-stage renal disease in the U.S.) 2
• Hypertensive nephrosclerosis 2
• Acute tubular necrosis 2
• Glomerulonephritis 2
• Multiple myeloma causing cast nephropathy 1, 2

Medication-related causes:

• NSAIDs should be discontinued immediately 2
• ACE inhibitors/ARBs can cause modest creatinine increases up to 30% through hemodynamic changes, which are acceptable and do not require discontinuation unless the rise exceeds 30% or hyperkalemia develops 1, 4

Clinical Assessment for Etiology

Look for Red Flags Suggesting Non-Diabetic Kidney Disease

Refer to nephrology promptly if any of the following are present: 1

• Active urinary sediment (red or white blood cells, cellular casts)
• Rapidly increasing albuminuria or nephrotic syndrome
• Rapidly decreasing eGFR
• Absence of diabetic retinopathy in type 1 diabetes (rare to have diabetic kidney disease without retinopathy)
• Gross hematuria

Assess Volume Status and Cardiac Function

• Check for orthostatic hypotension, decreased skin turgor, dry mucous membranes, and recent weight loss to assess dehydration 2
• Evaluate for heart failure (present in 36% of hospitalized patients with raised plasma urea) 3
• If dehydration is suspected, improvement should occur within 24-48 hours of adequate fluid repletion; if values remain elevated despite 2 days of adequate hydration, consider intrinsic kidney disease 2

Review Medications

• Temporarily discontinue NSAIDs 2
• Assess for diuretic-induced volume depletion (most common avoidable reason for creatinine elevation in patients on ACE inhibitors/ARBs) 2
• Do not discontinue ACE inhibitors or ARBs for creatinine increases <30% in the absence of volume depletion, as these medications provide renal protection 1, 4

Staging and Risk Stratification

CKD Staging Based on eGFR and Albuminuria

• Stage 1-2 CKD: eGFR ≥60 mL/min/1.73 m² with albuminuria ≥30 mg/g 1
• Stage 3 CKD: eGFR 30-59 mL/min/1.73 m² 1
• Stage 4 CKD: eGFR 15-29 mL/min/1.73 m² 1
• Stage 5 CKD: eGFR <15 mL/min/1.73 m² 1

Both eGFR and albuminuria must be quantified together, as the degree of albuminuria at any eGFR level is associated with cardiovascular disease risk, CKD progression, and mortality 1

Treatment Decisions Based on eGFR and Albuminuria

For Diabetic Patients with Hypertension

UACR 30-299 mg/g (moderately elevated):

• Initiate either an ACE inhibitor or ARB 1

UACR ≥300 mg/g and/or eGFR <60 mL/min/1.73 m²:

• Strongly recommend ACE inhibitor or ARB 1, 5
• Monitor serum creatinine and potassium periodically when using ACE inhibitors, ARBs, or diuretics 1

Normal UACR (<30 mg/g) with normal blood pressure and normal eGFR:

• Do not use ACE inhibitor or ARB for primary prevention 1

Medication Adjustments Based on eGFR

• eGFR levels are essential to modify drug dosages or restrict use of renally cleared medications 1
• Bortezomib/dexamethasone regimens do not require renal dose adjustment and can be used in severe renal impairment or dialysis 1

Nephrology Referral Criteria

Refer to nephrology immediately if: 1

• eGFR <30 mL/min/1.73 m² (mandatory referral)
• Uncertainty about the etiology of kidney disease
• Difficult management issues
• Rapidly progressing kidney disease
• Consideration for kidney biopsy

Monitoring Frequency

Based on eGFR and albuminuria stage: 1

• Green zone (low risk): Annual monitoring
• Yellow zone (moderate risk): At least once yearly
• Orange zone (high risk): Twice yearly
• Red zone (very high risk): Three times yearly
• Dark red zone (highest risk): Four times yearly

Common Pitfalls to Avoid

• Do not confuse modest creatinine increases (up to 30%) with ACE inhibitors/ARBs as AKI—these hemodynamic changes are acceptable and the medications should be continued 1, 4
• Do not rely on BUN/creatinine ratio >20:1 alone to classify AKI type in critically ill patients, as it is associated with increased mortality rather than better prognosis 3
• Do not use serum creatinine alone to assess kidney function, as it can be normal even when GFR has decreased by 40% 2
• Do not measure spot urine albumin without simultaneous creatinine measurement, as this is susceptible to false results due to hydration status 1
• In diabetic patients, consider that hyperglycemia-induced osmotic diuresis can cause prerenal azotemia; target glucose <180 mg/dL in hospitalized patients 3