Anasarca with normal glomerular filtration and renal imaging appearance: think nephrotic syndrome !

Clinical History

A young male Philippinian with unremarkable past medical history was referred with symptoms of diarrhoea, fever, dyspnoea and dorsal pain. Physical examination revealed peripheral oedema, diffusely tender abdomen without peritonism and decreased urinary output.
Laboratory tests revealed mild leukocytosis, hypoproteinaemia, and normal renal function (eGFR 95 ml/min).

Imaging Findings

On admission, chest X-rays (Fig. 1) showed bilateral pleural effusions. Abdominal ultrasound (Fig. 2) confirmed anechoic pleural fluid, and showed kidneys with normal size, morphology, parenchymal thickness and echogenicity; minimal perinephric fluid was present on the left side. In addition, the gallbladder showed mild, oedematous mural thickening, without stones.
Laboratory tests were consistent with the diagnosis of nephrotic syndrome.
Body CT (Fig. 3) confirmed bilateral water-attenuation pleural effusions consistent with transudate. The kidneys showed normal size, parenchymal thickness and nephrogram. Significant perinephric and fascial fluid was present, along with minimal ascites, gallbladder wall oedema, abundant subcutaneous and fascial fluid in the dorsum, consistent with anasarca state. Underlying tumours and venous thrombosis were excluded.
Renal biopsy diagnosed IgA nephropathy, and the patient recovered well on diuretics, high-dose steroids and later on cyclophosphamide.

Discussion

Adult-onset nephrotic syndrome (AONS) is a rare disease (incidence 3/100.000 cases/years) that includes peripheral oedema, severe proteinuria and hypoalbuminemia. The hypothesised mechanism involves an increased glomerular permeability to plasma proteins, which then leads to abnormal extravasation of fluid from the vascular space into the interstitium. The vast majority of AONS cases are primary (idiopathic), related to usual histological subtypes such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. The uncommon (10-15%) secondary AONS is associated with diabetes mellitus, systemic lupus erythematosus, acute viral illnesses, HIV infection, adverse effects of medications such as interferon, pamidronate and lithium. Furthermore, in patients over 50 years of age, AONS may occur paraneoplastic, related to primary lung, gastric and colon cancers or lymphoproliferative disorders. [1-4]
AONS typically is a clinical and laboratory diagnosis. The characteristic peripheral oedema typically involves the lower extremities and extends upwards to the genitalia and lower abdomen. Ascites, pleural effusions and fatigue are frequently associated, without signs of cardiac failure or liver disease. Diagnosis requires consistent proteinuria and hypoalbuminemia (<2.5g/dl). Renal biopsy is recommended for treatment and prognosis [1-3].
Abnormal imaging findings are inconsistently found in AONS: the usual unspecific appearance includes oedema in the subcutaneous fat and fasciae at the extremities, water-attenuation pleural, pericardial and peritoneal effusions consistent with transudates. Similarly to other hypoproteinaemic states, oedema may also involve the perinephric spaces, gallbladder and colon wall [5]. In most glomerular pathologies such as IgA nephropathy, membranous and minimal change glomerulonephritis, the renal cortical echogenicity is generally normal, since the glomerular component accounts only for <10% of the renal parenchyma. At later stages, the characteristic increased echogenicity of diffuse parenchymal diseases results from progressive histological changes (tubular atrophy, interstitial inflammation and fibrosis). As long as glomerular filtration is preserved, the CT-nephrogram is not significantly delayed nor decreased [6-8].
Radiologists interpreting studies of patients with anasarca should not dismiss the possibility of severe renal disease based on unremarkable or near-normal sonographic and CT-appearances. When a diagnosis of AONS is suspected or established, imaging studies are indicated to exclude the presence of malignancies and of venous thromboembolism: the latter occurs in 26.7% of patients and usually involves the renal veins. Other less common complications include infections (such as cellulitis), acute renal failure and hyperlipidaemia [9].
Treatment of AONS includes fluid and sodium restriction, loop diuretics, angiotensin converting enzyme inhibitors and corticosteroids, with immunosuppressive therapy reserved for refractory cases [1-3].

Differential Diagnosis List

Final Diagnosis

Primary adult-onset nephrotic syndrome (IgA nephropathy)

URL:	https://www.eurorad.org/case/15112
DOI:	10.1594/EURORAD/CASE.15112
ISSN:	1563-4086