A 63 year-old male with history of Diabetes Mellitus Type 2 (DMT2) presented with diffuse swelling and dyspnea on exertion for 1 month. Outpatient labs showed progression of CKD from Stage II to Stage IV over the last 4 months. Paradoxically, the patient also noted an unintentional weight loss preceding the new swelling. The patient’s DMT2 had been well managed on oral hypoglycemic medications and he had no evidence of retinopathy or neuropathy. Admission labs showed creatinine of 2.4 mg/dL, serum albumin of 1.1 g/dL, and proteinuria of 16g/dL. Following unrevealing serologic work-up for secondary causes of proteinuria, the patient underwent renal biopsy, showing membranous nephropathy (MN).
Admission chest x-ray demonstrated incidental 1.4 cm nodular opacity and pulmonary edema. While he underwent diuresis for anasarca, a CT-Thorax was performed showing 1.8 cm Right Middle Lobe lung nodule. A follow-up PET/CT again recognized the suspicious lung nodule, but lesion was absent FDG-avidity. Given high clinical suspicion for malignancy, the nodule underwent biopsy confirming Stage 1A Lung Adenocarcinoma. Currently, the patient is scheduled for lobectomy. Immunosuppressive therapy for MN has been held in favor of monitoring for recovery after tumor removal.
Discussion:
Nephrotic syndrome is defined by heavy proteinuria (>3.5 g/day), hypoalbuminemia (< 3 g/dL), and peripheral edema. MN is the 2nd most common cause of Primary Nephrotic Syndrome. Diagnosis is established by renal biopsy. Our patient’s concomitant DMT2 caused reluctance amongst providers for pursuing renal biopsy, as DMT2 is a common cause of proteinuria. Ultimately, renal biopsy was pursued as he met many characteristics of non-diabetic glomerular disease. These features include: absence of other end-organ damage from DMT2 and faster progression to overt proteinuria in weeks-to-months, rather than years.
Although recognized as a cause of primary nephrotic syndrome, MN can be primary (idiopathic) or secondary. Causes include: Drugs (NSAIDs, Anti-TNF Therapy), Hepatitis B or C infection, Systemic Lupus and Malignancy, specifically solid tumors. In one review of 240 patients with biopsy-proven MN, the prevalence of cancer was 10%. For this cohort, the diagnosis of cancer and MN was often made within 1 year of one another. Given this association and the reported weight loss before edema accumulation, an aggressive approach was taken for an incidental pulmonary nodule. In patients with cancer-associated MN, a strong relationship between cancer remission and reduction in proteinuria has been observed.
Conclusions:
Despite the high prevalence of diabetes in the US population, the general hospitalist should continue to recognize the existence of non-diabetic glomerular disease. An established association between MN and malignancy exists. Patients with MN warrant more aggressive evaluation of unexplained weight loss or anemia, particularly in the population > 65 years old. At the very least, as with all patients, age-appropriate cancer screenings should be kept up-to-date.