Contributed by J. Thomas Molina, M.D., Ph.D., and Sheldon Bastacky, M.D.
Published online in July 2002

The patient is a 58-year-old male with a history of coronary artery disease, presenting with proteinuria of approximately 2-years duration and hyperglycosuria (2-3+) with normoglycemia. The patient is not taking any medications. Pertinent laboratory data include:

Laboratory Data: Blood Tests
Test	Reference Range	Result
Creatinine	(0.2-1.1 mg/dl)	1.6 mg/dl
HCO3	(22-26 mm Hg)	24 mm Hg
Potassium	(3.5-5.1 mEq/L)	4.6 mEq/L

Serum Protein Electrophoresis
Total protein	6.8 gm/dL
albumin	4.4 gm/dL (65%)
alpha-1 globulins	0.2 gm/dL (3%)
alpha-2 globulins	0.6 gm/dL (9%)
beta globulins	0.7 gm/dL (10%)
gamma globulins	0.9 gm/dL (13%) with monoclonal IgG-kappa - 0.5 gm/dL (7%)

Urine Protein Electrophoresis
Total 24 hour protein excretion	4.0 gm
albumin	20%
alpha-1 globulins	13%
alpha-2 globulins	19%
beta globulins	15%
gamma globulins	25% (including monoclonal kappa light chain protein - 22%)

A random bone marrow biopsy revealed approximately 1% plasma cells without evidence of monoclonality. Urine sediment contained 18 RBCs/hpf. A percutaneous needle biopsy of the right kidney was performed.

H&E	H&E	H&E	H&E	H&E

Trichrome	PAS	Silver stain	Silver stain	Lambda / Kappa

Light microscopy
The tissue examined by light microscopy consists of renal cortex and medulla. The profiles of approximately 55 glomeruli are identified in the paraffin, frozen and plastic sections, which of six (9%) are globally sclerotic. The non-sclerotic glomeruli are normocellular, and focally congested by red blood cells. Some of the podocytes are prominent. The capillary walls are of a normal thickness. There are no segmental sclerosing lesions, necrotizing lesions, proliferative lesions, crescents, spikes nor tram-tracking (PAS and silver stains). The tubules show focal reactive epithelial changes and focal loss of brush border (PAS stain), and there are rare granular casts, suggesting acute tubular injury. There is minimal atrophy. Occasional tubules contain hyaline casts, and a rare tubule contains intraluminal red blood cells. Kappa and lambda light chain immunostains reveal droplet staining in some of the proximal tubular epithelial cells, with stonger (but not restricted) staining for kappa light chain protein. The interstitium contains a sparse lymphocytic infiltrate. There is a rare interstitial calcification. No fibrosis is seen (trichrome stain). The arteries show up to moderate fibroelastic intimal thickening. The arterioles show mild to moderate mural thickening, suggesting arteriolar sclerosis. There is no evidence of vasculitis or thromboemboli.

Lambda	Kappa	C3

Immunofluorescence
Immunofluorescence stains show non-specific findings. There is trace tubular staining with both lambda and kappa, and arteriolar staining for C3 suggesting chronic vascular change.

EM	EM	EM	EM	EM	EM

EM	EM	EM	EM	EM	EM

Electron microscopy
The ultrastructural findings are based on the examination of three normocellular, non-sclerotic glomeruli with no significant light microscopic abnormality and several tubules. The podocytes contain occasional lipoprotein resorption droplets. One podocyte contains peculiar, electron dense, tubular shaped inclusion within a cytoplasmic vesicle. The foot processes are discrete. The mesangial areas are unremarkable. The glomerular basement membrane is uniform and of a normal thickness. No mesangial nor glomerular basement membrane immune complex nor paraprotein deposits are identified. The capillary lumina are patent and the endothelial cells are unremarkable, without cytoplasmic tuboreticular inclusions. The proximal tubules are remarkable for numerous crystalline and paracrystalline cytoplasmic inclusions. Some of the inclusions are needle shaped with pointed ends and are electron dense without substructure. Other inclusions are more polygonal in shape with a paracrystalline substructure. Still, other inclusions are elongated/rectangular, and consists of parallel arrays of fibrillar structures with a crystalline substructure. In addition to these inclusions, there are many inclusions which appear to be within membrane bound structures (lysosomes). These inclusions have a substructure resembling microtubules cut in cross section. Many of these inclusions appear to be within proximal tubular epithelial cells. The microvillous apical borders of these cells are intact ultrastructurally. The mitochondria show no specific abnormality. The tubular basement membranes range from normal to thickened, but have no electron dense material suggestive of a monoclonal immunoglobulin deposition disorder. The intrarenal vessels are also unremarkable.