Abstract: PUB125
Considering Cholesterol: Apolipoprotein E Glomerulonephropathy
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Akahara, Ozioma A., Houston Methodist, Houston, Texas, United States
- Ahmed, Amina J., Houston Methodist, Houston, Texas, United States
- Adrogue, Horacio E., Houston Methodist, Houston, Texas, United States
- Truong, Luan D., Houston Methodist, Houston, Texas, United States
- Edwards, Angelina, Houston Methodist, Houston, Texas, United States
Group or Team Name
- Apo-E
Background
Apolipoprotein E is a protein that plays a crucial role in lipid metabolism through cholesterol transport and can lead to glomerulonephropathy, often mimicking other glomerular diseases associated with metabolic syndrome.
Methods
We present two cases that highlight key histopathologic findings which prompted genetic testing and targeted treatment.
Results
Case 1: A 61-year-old woman with hypertension and hyperlipidemia presented with bilateral lower extremity edema. She was non-diabetic and medications included lisinopril, amlodipine and furosemide. She was not on pharmacotherapy for hypercholesterolemia. On exam, she had bilateral lower extremity edema and labs revealed creatinine of 1.8 mg/dL (baseline 1.0mg/dL), 3+ protein on urinalysis, protein/creatinine ratio (UPCR) of 3668 mg/gram creatinine and albumin/creatinine ratio (UACR) of 2444 mcg/mg. Renal biopsy demonstrated dilated glomerular capillaries with extensive foamy cell deposition and vacuolated cytoplasm. Genetic testing identified homozygous ApoE2-mutation leading to dyslipidemia and lipoprotein glomerulopathy with type III hyperlipoproteinemia. With pharmacotherapy, diet and lifestyle modifications, lipid profile and renal parameters (UPCR of 70 mg/gm, UACR is 23 mcg/mg, creatinine 1.18, GFR 53 ml/min) showed improvement.
Case 2 : A 67-year-old man with obesity, hypertension, and diabetes, presented for evaluation of nephrotic range proteinuria. Laboratory data demonstrated creatinine of 1.84 mg/dL, urine microalbumin/creatinine ratio of 1052 mg/g, and severe dyslipidemia (total cholesterol 520 mg/dL, triglycerides 522 mg/dL). Renal biopsy displayed no evidence of diabetic nephropathy but rather diffuse foamy cell infiltration and lipid vacuoles with lamellated inclusions concerning for ApoE-related lipoprotein abnormality. Genetic evaluation and dyslipidemia interventions are ongoing, with the hope that treatment response will be seen.
Conclusion
These cases highlight the under-recognized entity of ApoE-related glomerulonephropathy as a major contributor to glomerular disease in cardio-kidney-metabolic syndrome. Pathogenesis reflects impaired ApoE-mediated lipoprotein clearance, resulting in progressive glomerular injury. Prompt recognition and early kidney biopsy aid in excluding diagnostic mimickers, avoiding misdiagnosis, refining genotype-phenotype correlations, and enabling targeted therapy, in the context of a multidisciplinary team.