In a 56‑year‑old woman with diabetes mellitus, hypertension, hyperuricemia, normal blood urea nitrogen and a serum creatinine of 23.7 µmol/L, what is the most likely diagnosis and recommended management?

Low Serum Creatinine in a Diabetic Patient with Hypertension and Hyperuricemia

A serum creatinine of 23.7 µmol/L (approximately 0.27 mg/dL) in this 56-year-old woman with diabetes, hypertension, and hyperuricemia most likely indicates reduced skeletal muscle mass or protein-energy malnutrition, not superior kidney function, and requires comprehensive evaluation to exclude masked chronic kidney disease.

Understanding the Laboratory Pattern

This extremely low creatinine value reflects decreased muscle mass rather than excellent renal function and may mask underlying diabetic kidney disease. 1

• Low serum creatinine (typically <0.8–1.0 mg/dL, and certainly at 0.27 mg/dL) in a hypertensive diabetic individual most often reflects decreased skeletal muscle mass and/or low dietary protein intake rather than superior renal function 1
• In dialysis recipients, serum creatinine <10 mg/dL triggers evaluation for protein-energy malnutrition and skeletal muscle wasting, making this value of 0.27 mg/dL particularly concerning 1
• Normal serum creatinine does not guarantee normal kidney function; up to 30–50% reduction in GFR can be present despite normal creatinine values 1
• Among hypertensive adults with normal serum creatinine, 18–38% may have unrecognized renal impairment (eGFR <60 mL/min/1.73 m²) 1

Diagnostic Work-Up

Immediate Laboratory Assessment

Calculate eGFR using the CKD-EPI equation adjusted for age, sex, and race, because normal serum creatinine does not guarantee normal kidney function. 1

• Obtain a first-morning spot urine albumin-to-creatinine ratio (ACR) to detect low-grade albuminuria, as standard dipsticks miss albumin levels <300 mg/g 1
• Repeat any abnormal ACR on a separate occasion before labeling the result abnormal, as exercise, infection, fever, marked hyperglycemia, or severe hypertension can cause transient elevations 2, 1
• Measure serum albumin and pre-albumin to assess protein-energy nutritional status 1
• Obtain serum electrolyte panel (sodium, potassium, chloride, bicarbonate) to detect accompanying metabolic disturbances 3

Diabetes-Specific Screening

All patients with type 2 diabetes should have eGFR and urine albumin-to-creatinine ratio measured at diagnosis and annually thereafter. 2

• Diabetic kidney disease is generally diagnosed as the presence of albuminuria or reduced eGFR in the absence of clinical indicators of other causes of kidney disease 2
• Screening includes measurement of both urine albumin and eGFR; abnormalities should be confirmed, and persistent abnormalities in either diagnose chronic kidney disease 2
• Two of three specimens of urine ACR collected within a 3- to 6-month period should be abnormal before considering a patient to have high or very high albuminuria 2

Assessment of Muscle Mass and Nutritional Status

Evaluate for causes of reduced muscle mass including advanced age, malnutrition, chronic illness, neuromuscular disorders, amputations, or cachexia. 1

• The creatinine index, which estimates fat-free body mass, can be used to confirm suspected muscle loss when serum creatinine is low or falling 1
• Low urinary creatinine excretion indicates reduced muscle mass or inadequate protein intake, supporting the interpretation that low serum creatinine is not renal-protective 1

Hyperuricemia Considerations

Hyperuricemia is frequently seen in untreated hypertensives and correlates with reduced renal blood flow and nephrosclerosis. 2

• Hyperuricemia is particularly common in patients with kidney disease, metabolic syndrome, and diabetes mellitus 4
• Elevated serum uric acid is associated with markers of pro-inflammatory state and may serve as a link between renal dysfunction and both pro-inflammatory and prothrombotic states in patients with metabolic syndrome 4
• Hyperuricemia is a specific risk factor for chronic renal failure and cardiovascular morbidity and mortality 5

Management Approach

Renal Function Monitoring

Re-measure serum creatinine and eGFR 7–14 days after initiating or changing antihypertensive therapy to detect any drug-related changes. 1

• Assess GFR and albuminuria at least annually; increase monitoring frequency if risk factors for progression emerge 1
• Measure BUN, creatinine, and electrolytes routinely in patients with volume overload 3
• Periodically monitor serum creatinine and potassium levels when ACE inhibitors, angiotensin receptor blockers, or diuretics are used 2

Antihypertensive Therapy

An ACE inhibitor or angiotensin receptor blocker is recommended for patients with type 2 diabetes who have hypertension and albuminuria, titrated to the maximum antihypertensive or highest tolerated dose. 2

• In nonpregnant patients with diabetes and hypertension, either an ACE inhibitor or angiotensin receptor blocker is recommended for those with modestly elevated urinary albumin-to-creatinine ratio (30–299 mg/g creatinine) 2
• An ACE inhibitor or angiotensin receptor blocker is strongly recommended for those with urinary albumin-to-creatinine ratio ≥300 mg/g creatinine and/or eGFR <60 mL/min/1.73 m² 2
• An ACE inhibitor or angiotensin receptor blocker is not recommended for primary prevention of chronic kidney disease in patients with diabetes who have normal blood pressure, normal urinary albumin-to-creatinine ratio (<30 mg/g creatinine), and normal eGFR 2

Diabetes Management

A sodium-glucose cotransporter-2 inhibitor with proven kidney or cardiovascular benefit is recommended for patients with type 2 diabetes, chronic kidney disease, and eGFR ≥20 mL/min/1.73 m². 2

• Metformin is recommended for patients with type 2 diabetes, chronic kidney disease, and eGFR ≥30 mL/min/1.73 m² 2
• A GLP-1 receptor agonist with proven cardiovascular benefit is recommended for patients with type 2 diabetes and chronic kidney disease who do not meet their individualized glycemic target with metformin and/or an SGLT2 inhibitor 2
• A statin is recommended for all patients with type 1 or type 2 diabetes and chronic kidney disease, moderate intensity for primary prevention of atherosclerotic cardiovascular disease 2

Nutritional Intervention

If protein-energy malnutrition is confirmed, prescribe dietary protein intake of approximately 0.8–1.0 g/kg/day. 1

• Refer the patient to a dietitian for comprehensive nutritional assessment and individualized meal planning 1
• Track response to nutritional therapy with serial measurements of serum creatinine, albumin, and body weight 1

Referral Criteria

Patients should be referred for evaluation by a nephrologist if they have an eGFR <30 mL/min/1.73 m². 2

• Promptly refer to a nephrologist for uncertainty about the etiology of kidney disease, difficult management issues, and rapidly progressing kidney disease 2
• Consider intrinsic kidney disease if elevation persists after 2 days of adequate rehydration, proteinuria, hematuria, or abnormal urinary sediment present, eGFR <30 mL/min/1.73 m², or rapidly progressive kidney disease 3

Critical Pitfalls to Avoid

Do not assume normal kidney function based solely on low serum creatinine; always calculate eGFR to uncover hidden renal impairment. 1

• Do not interpret low serum creatinine as "good" kidney function; in patients with reduced muscle mass it may mask underlying renal disease 1
• Normal blood urea nitrogen and serum creatinine values do not by themselves rule out significant reduction in glomerular filtration rate 6
• Any interpretation of blood levels of these substances must be done with awareness that a variety of extrarenal factors can affect them 6