Case 514 -- A 60 year-old woman with elevated creatinine and BUN

Contributed by Craig Horbinski, MD, PhD and Sheldon Bastacky, MD
Published on line in June 2007


CLINICAL HISTORY:

The patient is a 60 year-old woman with a history of rheumatoid arthritis, 60 pack-year smoking, chronic obstructive pulmonary disease, and treated hypertension. She underwent a screening colonoscopy, then felt poorly for a week. Her creatinine and BUN 2 weeks after the screening were 4.6 and 46 mg/dl, respectively (baseline serum creatinine was 0.9 mg/dl). The bowel preparation for the colonoscopy procedure was Fleet' s Phospho-Soda and NuLytely.

Pertinent laboratory data:

creatinine 3.7 mg/dl (for women < 1.2 mg/dl), BUN 35 mg/dl (5-20 mg/dl), creatinine clearance 12.5 ml/min (75-115 ml/min/1.73 m2), urine protein/creatinine ratio 0.15, ANA negative, ANCA negative, C3 148 mg/dl (80-200 mg/dl), C4 (15-80 mg/dl), cryoglobulin screen negative, ESR 54 mm/hr (for women < 12mm/hr), calcium 9 mg/dl (8-10 mg/dl), phosphorous 4.5-5.4 mg/dl (2.5-4.5 mg/dl), serum albumin 3.6-4.1 g/dl (3.5-5.0 g/dl), uric acid 5.5-7.1 mg/dl (2.4-6.0 mg/dl), serum protein electrophoresis - polyclonal hypergammaglobulinemia with no monoclonal immunoglobulin spike identified, urine protein electrophoresis - protein 5.9 mg/dl with normal immunofixation electrophoresis, urine sediment - bland (no RBCs, 4-8 WBCs/hpf, granular and hyaline casts).

MICROSCOPIC DESCRIPTION:

LIGHT MICROSCOPY

The tissue examined by light microscopy consists of renal cortex and medulla. The profiles of approximately 40 glomeruli are identified in the paraffin, frozen, and plastic sections, of which 10 (25%) are globally sclerotic [image 1]. There are no proliferative lesions, segmental sclerosing lesions, necrotizing lesions, cellular crescents, increased circulating white blood cells, hyaline thrombi, hyalinosis lesions, glomerular capillary wall thickening, spikes, tram tracking, or glomerular basement membrane breaks (silver and PAS stains not shown). There is widespread cortical tubular atrophy characterized by loss of proximal tubular epithelial cell volume and luminal dilatation. There is no evidence of overt coagulative necrosis, cellular or granular casts, prominent reactive epithelial changes, or tubular epithelial mitotic activity. A number of the distal tubules contain luminal nonpolarizable calcifications [image 2, image 3, image 4, image 5]. A few calcifications are also present within the cortical interstitium. There is patchy, mild to moderate, lymphocytic interstitial inflammation. Trichrome stain reveals mild diffuse fibrosis within the cortical interstitium (not shown). Approximately seven or eight intrarenal arteries are present in the paraffin and frozen sections, showing mild through moderate fibroelastic intimal thickening. There is mild to moderate arteriolar sclerosis as well, with focal hyaline change. There is no evidence of vasculitis, thromboemboli, or thrombotic microangiopathy.

FLUORESCENT MICROSCOPY

The renal tissue examined by immunofluorescence microscopy contains 11 non-sclerotic glomeruli, 5 sclerotic glomeruli, 3 arteries and a few arterioles. Direct immunofluorescence was performed using a panel of 10 antisera (not shown).

FM Interpretation:

    Non-specific immunofluorescence findings:

  1. Weak granular mesangial staining for IgM and properdin.
  2. Hyaline casts, without evidence of immunoglobulin light chain restriction.
  3. Weak arteriolar staining for C3, suggesting chronic vascular injury.
  4. Focal global glomerulosclerosis involving 5/16 glomeruli

ELECTRON MICROSCOPY:

One glomerulus in plastic section a shows mild mesangial expansion, and both glomeruli in plastic section a show partial global glomerular collapse with hypertrophied podocytes [image 6]. The ultrastructural findings are based on the examination of two glomeruli with partial global glomerular collapse and podocyte hypertrophy. One of the glomeruli also exhibits mild mesangial matrix expansion. The podocytes show variable (up to moderate) foot process effacement and occasional podocytes contain lipoprotein resorption droplets [image 7]. The mesangium ranges from normal in size to mildly expanded by increased matrix. The glomerular basement membrane exhibits focal mild to moderate wrinkling secondary to partial global collapse. The glomerular capillaries are variably narrowed secondary to partial glomerular collapse. The endothelial cells are unremarkable, without cytoplasmic tubuloreticular inclusions. The tubular basement membranes are unremarkable. No electron dense immune complex type deposits or organized protein deposits are identified.

EM Interpretation:

  1. Partial global glomerular collapse with variable, widespread podocyte foot process effacement and variable glomerular basement membrane wrinkling; finding suggest subacute glomerular injury (possibly ischemic).
  2. No ultrastructural evidence of an immune complex / organized protein deposition disorder.

FINAL DIAGNOSIS


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