Contributed by Chris Gilbert, MD and Sheldon Bastacky, MD.
The patient is a 68 year-old Caucasian woman with a history of chronic intermittent diarrhea, acroparesthesias, inflammatory polyarthritis, tinnitus, asthma, osteoarthritis, hypothyroidism, Raynaud' s phenomenon, anemia with thrombocytosis, and atypical mycobacterial lung disease. She is status post Nissen fundoplication and right hip arthroplasty. She presents with complaints of polyuria and increased thirst. Physical exam reveals ankle edema.
Laboratory findings include:
Urine protein electrophoresis and immunofixation - Mixed glomerular and tubular pattern with no monoclonal immunoglobulin.
Lower extremity Doppler scans show no deep venous thrombosis.
Renal ultrasound: The right kidney measures 9.9 x 3.8 cm, with mild fullness of the collecting system, increased renal parenchymal echogenicity, and right-sided renal cysts. The left kidney measures 9.7 x 5.5 cm, with mild fullness of the collecting system, increased renal parenchymal echogenicity, and one left-sided renal cyst.
A renal biopsy was performed.
The tissue examined by light microscopy consists predominantly of renal cortex (Figure 1). Many glomeruli are identified in the paraffin, frozen, and plastic sections, of which 20% are globally sclerotic. Approximately 50% of the podocytes exhibit variably prominent, PAS-negative, cytoplasmic vacuolization (Figures 2, 3, 4, 5). Toluidine blue-stained plastic sections demonstrate the presence of zebra bodies in the vacuolated podocytes (Figure 6).
There are no proliferative, necrotizing or crescentic glomerular lesions, segmental glomerulosclerosis, increased circulating white blood cells, hyaline thrombi, hyalinosis lesions, mesangial matrix expansion, glomerular capillary wall thickening, spikes, tram tracking, or glomerular basement membrane breaks. The tubules are mostly back-to-back, with minimal chronic atrophy (Figure 7). There are rare granular and hyaline casts. Some of the tubules are dilated with attenuation of the epithelial cells, but no overt coagulation necrosis. A few tubular cells contain lipofuscin pigment. Silver stain reveals the presence of protein resorption droplets in some of the proximal tubular epithelial cells (Figure 8).
There are sparse lymphocytes within the interstitium, most concentrated around a sclerotic glomerulus (Figure 9). Trichrome stain reveals minimal interstitial fibrosis (Figure 10). There are three or four small arteries with mild-to-moderate fibroelastic intimal thickening present in the paraffin section. There is no arteriolar hyaline sclerosis. There is no evidence of vasculitis, thromboemboli, or thrombotic microangiopathy in the small number of blood vessels examined in the biopsy.
Immunofluorescence studies show weak, non-specific mesangial staining for IgM, C3, and Properdin and a few hyaline casts. Vascular staining for C3 and Focal C1q is also identified suggesting early chronic vascular injury.
Electron microscopy demonstrates patchy podocyte zebra body inclusions and mild podocyte foot process effacement (Figures 11, 12 13, 14, 15). No ultrastructural evidence of an immune complex disorder or protein deposition disorder with organized substructure is identified.