What is the most likely cause of proteinuria in a 40‑year‑old obese (BMI 35) male weight lifter with hypertension (blood pressure 142/95 mm Hg), normal hemoglobin A1c (5.2 %), mildly elevated fasting glucose (101 mg/dL), dyslipidemia, and an albumin‑creatinine ratio of 304 mg/g?

Obesity-Related Glomerulopathy with Secondary Hypertension and Metabolic Syndrome

The most likely cause of proteinuria in this patient is obesity-related glomerulopathy (ORG), compounded by hypertension-induced glomerular injury and early metabolic dysfunction. 1

Primary Diagnosis: Obesity-Related Glomerulopathy

This 40-year-old male with BMI 35.28 and albumin-creatinine ratio of 304 mg/g meets the clinical profile for ORG, which is increasingly recognized as a distinct cause of proteinuria and progressive kidney disease in obese individuals. 1, 2

Key Supporting Features for ORG:

• Marked obesity (BMI 35.28) is the dominant risk factor, as obesity independently drives proteinuria through glomerular hyperfiltration, podocyte injury, and increased intraglomerular pressure. 1, 3

• The albumin-creatinine ratio of 304 mg/g indicates moderate-to-severe albuminuria, which correlates directly with BMI in obese patients—each 2 kg/m² increase in BMI is associated with a 5.6-9.4% increase in albuminuria. 4

• Relatively preserved serum albumin (5.3 g/dL) despite significant proteinuria is characteristic of secondary FSGS/ORG rather than primary nephrotic syndrome. 1

• Normal hemoglobin A1C (5.2%) effectively excludes diabetic nephropathy as the primary cause, though impaired fasting glucose (101 mg/dL) indicates early metabolic dysfunction. 5, 6

Contributing Pathophysiologic Mechanisms

Hypertension-Mediated Glomerular Injury

Blood pressure of 142/95 mmHg represents Stage 2 hypertension and independently contributes to proteinuria. 1

• Hypertension disrupts normal glomerular autoregulation, allowing systemic blood pressure to be transmitted directly to glomerular capillaries, causing barotrauma and podocyte injury. 1, 3

• 85% of individuals with chronic kidney disease have hypertension, and those with proteinuria demonstrate attenuated response to antihypertensive therapy. 1, 3

• The combination of obesity and hypertension creates synergistic glomerular injury through activation of the renin-angiotensin-aldosterone system, which causes efferent arteriolar vasoconstriction and further elevates intraglomerular pressure. 1, 3

Metabolic Syndrome Components

This patient meets criteria for metabolic syndrome (≥3 of: abdominal obesity, impaired fasting glucose 101 mg/dL, blood pressure 142/95 mmHg, triglycerides 218 mg/dL). 1, 6

• Dyslipidemia (cholesterol 246 mg/dL, triglycerides 218 mg/dL, LDL 159 mg/dL) independently worsens proteinuria and accelerates kidney disease progression. 1, 7

• Elevated triglycerides and triglyceride-rich lipoproteins are independently correlated with higher albuminuria in metabolic syndrome. 7

• Impaired fasting glucose (101 mg/dL) indicates early insulin resistance, which promotes sodium retention, glomerular hyperfiltration, and mesangial cell hypertrophy. 1, 6

Alternative Diagnoses to Exclude

Why NOT Diabetic Nephropathy:

• Hemoglobin A1C of 5.2% excludes diabetes mellitus (diagnostic threshold ≥6.5%). 5
• Diabetic nephropathy classically manifests 10-15 years after diabetes onset, not in prediabetic states. 3

Why NOT Primary Hypertensive Nephrosclerosis:

• Hypertensive nephrosclerosis typically presents with bland urinary sediment and minimal proteinuria (<300 mg/day), whereas this patient has significant albuminuria (304 mg/g). 5
• The degree of proteinuria is disproportionate to the blood pressure elevation, suggesting a primary glomerular process rather than pure vascular disease. 1

Why NOT Primary Glomerulonephritis:

• The clinical context (obesity, metabolic syndrome, hypertension) strongly favors secondary glomerulopathy over primary immune-mediated disease. 1
• Absence of systemic symptoms, hematuria, or rapidly declining renal function makes primary glomerulonephritis less likely. 1

Additional Considerations

Potential Confounding from Weight Training:

• Elevated hemoglobin (17.9 g/dL) and hematocrit (51.9%) may reflect relative polycythemia from anabolic steroid use, which is associated with hypertension and glomerular injury in bodybuilders. 1

• Elevated ALT (52 U/L) could indicate hepatic steatosis from obesity or exogenous anabolic steroid use, both of which worsen metabolic syndrome. 1

Measurement Considerations in Obesity:

The 30 mg/g albumin-creatinine ratio threshold may underestimate albuminuria severity in obese individuals with higher muscle mass, as increased urinary creatinine excretion artificially lowers the ratio. 8 However, this patient's ratio of 304 mg/g is well above diagnostic thresholds regardless of body composition.

Clinical Implications and Management Priorities

Weight loss is the single most effective intervention for ORG—a 9% reduction in BMI produces a 51% reduction in proteinuria over 24 months, an effect that cannot be replicated by pharmacotherapy alone. 2

Blood pressure must be aggressively controlled to <130/80 mmHg using renin-angiotensin system blockade (ACE inhibitor or ARB) to reduce intraglomerular pressure and slow nephropathy progression. 5, 1

Metabolic syndrome components require comprehensive management: statin therapy for dyslipidemia, lifestyle modification for impaired fasting glucose, and monitoring for progression to diabetes with repeat HbA1C every 3-6 months. 6, 1