Nephrotic Syndrome Without Nephrotic Range Proteinuria

Abstract

Nephrotic syndrome in adults is defined as nephrotic-range (≥3.5g/24h) proteinuria with low serum albumin, usually associated with edema, hyperlipidemia, and lipiduria. The 3.5g/24h threshold was selected arbitrarily and might not be reached in certain cases despite severe defects in glomerular permeability. We describe the case of a 57-year-old male who presented with progressively worsening swelling involving his limbs and abdomen. He also reported decreased urine output and fatigue. Physical examination was notable for severe pitting edema over legs, arms, and abdomen, in addition to peri-orbital puffiness. Labs revealed low serum albumin (1.3 g/dL), moderate proteinuria (2.3g/24h), and elevated total cholesterol (334 mg/dL). Renal biopsy showed amyloid light chain (AL) amyloidosis and bone marrow biopsy confirmed the presence of lambda-restricted plasma cells. Computed tomography, ultrasound, elastography, and laboratory findings were congruent with those seen in hepatic amyloidosis. A diagnosis of nephrotic syndrome caused by systemic AL amyloidosis was made despite the absence of nephrotic range proteinuria. The primary abnormality in nephrotic syndrome is increased glomerular permeability, leading to severe proteinuria causing low serum albumin, decreased oncotic pressure, and increased water retention by kidneys due to activation of the epithelial sodium channel (ENaC). The amount of albuminuria is influenced by both the extent of glomerular permeability and the rates of glomerular filtration and albumin synthesis. In cases where albumin synthesis is decreased secondary to concurrent liver disease, as in our case, a steady state of renal protein excretion may be reached at a lower threshold than 3.5g/24h despite severe defects in glomerular permeability.

Keywords: albumin clearance; hepatic amyloidosis; nephrotic syndrome; nephrotic-range proteinuria; systemic amyloidosis.

Figure 1. Ultrasound of the liver (sagittal) showing heterogeneous echogenicity (black arrow), ascites (white arrow), and hepatomegaly (cranio-caudal dimension 21.65 cm).

Figure 2. Non-contrast CT abdomen showing ascites (black arrow) and diffusely decreased hepatic attenuation (white arrow).

Abbreviations:  HU, Hounsfield unit.

Figure 3. Renal biopsy, hematoxylin and eosin: (a) The glomeruli show expansion of the mesangium and thickened glomerular capillary loops with deposition amorphous material (black arrow). (b) Protein reabsorption droplets are seen within tubular epithelial cells (white arrow). There is focal deposition of amorphous material in the interstitium.