A 55-year-old woman comes to the office due to swelling around her ankles and face that has progressively worsened over the last 1-2 months. The patient has 2+ bilateral pitting edema in the lower extremities, trace edema in the upper extremities, and periorbital edema. Cardiopulmonary examination is normal. Laboratory evaluation shows a serum creatinine level of 2.0 mg/dL and an albumin level of 2.8 g/dL. Urinalysis shows 3+ proteinuria and no hematuria or casts. A kidney biopsy is performed; light microscopic findings following staining with hematoxylin and eosin are shown in the image below:
Show Explanatory Sources
Which of the following is the most likely explanation for this patient's biopsy findings?
Show Explanatory Sources
This patient's renal biopsy shows Kimmelstiel-Wilson (KW) nodules, characterized by:
KW nodules are diagnostic for nodular glomerulosclerosis, characterized by increased mesangial matrix deposition. Over time, mesangium expansion and KW nodule formation compress the glomerular capillaries, causing loss of glomerular function. Progressive proteinuria can lead to overt nephrotic syndrome (eg, peripheral edema, heavy proteinuria, fatty casts), hypertension, and renal failure. The urine sediment is typically bland (ie, no dysmorphic red cells or red cell casts).
Nodular glomerulosclerosis, most commonly caused by diabetic nephropathy (type 1 or 2 diabetes mellitus), indicates irreversible glomerular damage and predicts a rapid decline in kidney function. Additional features of diabetic nephropathy include glomerular basement membrane (GBM) thickening and hyaline arteriolosclerosis.
Other causes of nephrotic syndrome include the following:
(Choice A) Minimal change disease can occur as an immunologic reaction to pollen/dust, insect stings, infection, or immunization. Glomeruli appear normal on light microscopy (LM). Electron microscopy (EM) shows effacement of podocyte foot processes.
(Choice C) Membranoproliferative glomerulonephritis is often associated with hepatitis B or C. LM shows hypercellular glomeruli with thickening and splitting of the GBM due to subendothelial immune complex (IC) deposition.
(Choice D) Focal segmental glomerulosclerosis can be associated with HIV infection, heroin use, and severe obesity. LM shows sclerotic changes in some portions of some glomeruli (eg, consolidation of a portion of a glomerulus with capillary loops replaced by collagenous scar).
(Choice E) Solid tumors (eg, lung, breast, prostate) are associated with membranous nephropathy. LM shows capillary wall thickening and "membrane spikes" between subepithelial deposits on silver staining.
In contrast, a predominantly nephritic presentation (eg, hematuria, red cell casts, variable proteinuria) may be caused by the following:
(Choice F) In poststreptococcal glomerulonephritis, LM shows diffuse glomerular hypercellularity due to leukocyte infiltration and mesangial cell proliferation. Immunofluorescence shows IgG and C3 deposits, which can be visualized on EM as subepithelial humps.
(Choices G and H) Lupus nephritis most frequently manifests as diffuse proliferative glomerulonephritis. Drug-induced lupus (eg, procainamide, hydralazine, isoniazid) can rarely cause similar kidney involvement. LM frequently shows a variable pattern of mesangial proliferation and endocapillary hypercellularity. Wire loops (ie, thickened capillary walls due to subendothelial IC deposition) may also be seen.
Educational objective:
Nodular glomerulosclerosis is characterized by increased mesangial matrix deposition, forming Kimmelstiel-Wilson nodules. It is most commonly caused by diabetic nephropathy and indicates irreversible glomerular damage with a rapid decline in kidney function.