What is the likely diagnosis and management for a patient with normal urine microalbumin, elevated creatinine, and decreased Glomerular Filtration Rate (GFR), indicating impaired renal function?

Likely Diagnosis: Non-Albuminuric Chronic Kidney Disease

The most likely diagnosis is non-albuminuric chronic kidney disease (CKD), an increasingly recognized phenotype where patients develop reduced eGFR without preceding or concurrent albuminuria, particularly common in type 2 diabetes and hypertensive nephropathy. 1

Understanding This Clinical Presentation

This pattern—elevated creatinine with decreased GFR but normal microalbumin—represents a departure from the traditional diabetic kidney disease progression model where albuminuria precedes GFR decline. 1

• Non-albuminuric CKD is becoming more common over time as diabetes prevalence increases in the U.S., and now accounts for a substantial proportion of CKD cases in both type 1 and type 2 diabetes 1
• There is no correlation between GFR and microalbuminuria because albuminuria primarily reflects glomerular damage, while GFR decline can result from tubular, interstitial, or vascular lesions 1
• This presentation suggests tubulointerstitial or vascular disease rather than classic glomerulosclerosis 1

Diagnostic Confirmation and Staging

Confirm CKD Diagnosis

• Repeat eGFR measurement in 3 months to document chronicity, as CKD requires persistent abnormalities for at least 3 months to distinguish from acute kidney injury 1, 2
• Repeat UACR testing on at least two occasions within 3-6 months, as biological variability exceeds 20% between measurements 1, 2
• Consider cystatin C-based eGFR if uncertainty exists, as creatinine-based calculations can be affected by muscle mass and diet 2

Determine CKD Stage and Risk

• Stage the patient using both eGFR and albuminuria categories according to KDIGO classification, as this determines prognosis, monitoring frequency, and referral timing 1
• Even with normal albuminuria (UACR <30 mg/g), reduced eGFR alone defines CKD if it persists for ≥3 months 1, 2
• Risk stratification depends on the specific eGFR value: Stage G3a (eGFR 45-59) requires monitoring 1-2 times yearly, Stage G3b (eGFR 30-44) requires 2-3 times yearly, and Stage G4 (eGFR 15-29) requires nephrology referral 1

Investigate Underlying Etiology

Essential Evaluation

• Review medication history for nephrotoxic exposures including NSAIDs, lithium, calcineurin inhibitors, and aminoglycosides 3
• Assess for diabetes and hypertension, the two leading causes of CKD, with diabetes accounting for 30-40% of cases and hypertension being present in approximately 70% of patients with elevated creatinine 3, 4
• Obtain family history of kidney disease, as this significantly increases CKD risk and prevalence of earlier-stage disease 3
• Examine for cardiovascular disease history, particularly cerebrovascular accident, which strongly suggests long-standing poorly controlled hypertension with end-organ damage 3

Consider Non-Diabetic Causes

Nephrology referral for possible kidney biopsy should be considered if any of the following atypical features are present 1:

• Absence of diabetic retinopathy in type 1 diabetes (rare to have kidney disease without retinopathy) 1
• Rapid GFR decline (>5 mL/min/1.73 m² per year) 1
• Active urinary sediment with hematuria, pyuria, or casts suggesting glomerulonephritis 3
• Systemic symptoms suggesting autoimmune disease or infiltrative disorders 3

Management Strategy

Blood Pressure Control

• Target blood pressure <130/80 mmHg for all CKD patients regardless of albuminuria status 1, 3
• Initiate ACE inhibitor or ARB if hypertension is present, even with normal albuminuria, as these agents provide renoprotection 1
• For patients with UACR ≥300 mg/g, ACE inhibitor or ARB is strongly recommended regardless of blood pressure 1
• Monitor serum creatinine and potassium within 2-4 weeks after initiating RAS blockade 1, 3
• Do not discontinue ACE inhibitor/ARB for creatinine increases ≤30% in the absence of volume depletion 1

Cardiovascular Risk Reduction

• Initiate statin therapy for cardiovascular risk reduction, as CKD patients have 5-10 times higher cardiovascular mortality risk than progression to end-stage kidney disease 3, 4
• Optimize glucose control if diabetic, targeting HbA1c <7% 1
• Consider SGLT2 inhibitor with demonstrated kidney and cardiovascular benefits if diabetic and eGFR ≥20 mL/min/1.73 m² 1, 3

Screen for CKD Complications

At eGFR <60 mL/min/1.73 m², systematically screen for complications 3:

• Complete metabolic panel for electrolyte abnormalities, metabolic acidosis, and hyperkalemia 3
• Hemoglobin for anemia 3
• Serum calcium, phosphate, intact PTH, and 25-hydroxyvitamin D for mineral bone disease (PTH begins rising when eGFR falls below 60) 3
• Blood pressure and volume status assessment 3

Monitoring Frequency

• For eGFR 45-59 with UACR <30 mg/g: Monitor 1-2 times per year 1
• For eGFR 30-44 with UACR <30 mg/g: Monitor 2-3 times per year 1
• For any eGFR with UACR 30-300 mg/g: Increase monitoring frequency by one level 1
• For any eGFR with UACR >300 mg/g: Monitor 3-4 times per year and refer to nephrology 1

Nephrology Referral Indications

Refer to nephrology if any of the following are present 1, 3:

• eGFR <30 mL/min/1.73 m² 1
• Uncertainty about etiology or atypical features 1, 3
• Continuously increasing albuminuria despite optimal management 3
• Continuously decreasing eGFR or rapid decline (>5 mL/min/1.73 m² per year) 1, 3
• Difficulty managing CKD complications (hyperkalemia, metabolic acidosis, anemia, mineral bone disease) 3
• Resistant hypertension 3

Common Pitfalls to Avoid

• Do not assume absence of kidney disease based on normal albuminuria alone—reduced eGFR without albuminuria is an increasingly common CKD phenotype 1
• Do not diagnose CKD based on a single eGFR measurement—chronicity must be confirmed with repeat testing at least 3 months apart 1, 2
• Do not rely on serum creatinine alone—always calculate eGFR using validated equations (CKD-EPI 2021) 3
• Do not skip albuminuria testing—eGFR and UACR provide independent prognostic information for cardiovascular events, CKD progression, and mortality 3
• Do not combine ACE inhibitors with ARBs—this increases adverse events without additional benefit 3
• Do not discontinue RAS blockade for minor creatinine increases (<30%)—this is expected and acceptable 1