Case Evaluation

Medical Case Studies: 60 Year-Old Woman With Rheumatoid Authritis

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.

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. 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.

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).

Non-specific immunofluorescence findings:

  • Weak granular mesangial staining for IgM and properdin.
  • Hyaline casts, without evidence of immunoglobulin light chain restriction.
  • Weak arteriolar staining for C3, suggesting chronic vascular injury.
  • 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. 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. 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:

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

FINAL DIAGNOSIS

  • Prominent intratublar and interstitial non-polarizable microcalcifications consistent with nephrocalcinosis.
  • Few clomeruli with partial clobal collapse associated with moderate podocyte injury (podoctye hypertrophy patchy foot process effacement, and few podocyte lipoprotein resorption droplets).
  • Parenchymal chronicity changes; focal global glomerulosclerosis involving 10/40 (25%) glomeruli, widespread probable subacute tubular atrophy, diffuse mild interstitial fibrosis with mild-moderate lymphocytic interstitial inflammation, and focal moderate aterial/arteriolar sclerosis.

DISCUSSION

The renal biopsy showed tubular injury and interstitial fibrosis with tubular and interstitial non-polarizable calcifications. Renal tubular / interstitial calcifications are most commonly either calcium phosphate or calcium oxalate. A key differential point is that calcium oxalate crystals, as often seen in other cases are polarizable whereas calcium phosphate is not. "Nephrocalcinosis" applies specifically to the damage caused by calcium phosphate and can occur as a result of numerous hypercalcemic states, such as hyperparathyroidism, vitamin D intoxication, milk-alkali syndrome, or hypercalcemia of malignancy (Markowitz 2007). Thus, both a thorough clinical history and clinical correlation are needed to confirm the etiology of the nephrocalcinosis.

As is the case with many patients undergoing renal biopsies, the history and medication list can be complicated, with numerous potential sources of renal injury that need to be evaluated individually. Remicade (Infliximab / anti-TNF-alpha monoclonal antibody) has been reported to be associated with a variety of proliferative / immune complex / necrotizing / crescentic glomerular disorders, but in this biopsy there was no evidence of such glomerular injury. What glomerular injury was observed (focal partial global glomerular collapse and podocyte injury) in the absence of significant proteinuria suggested the possibility of subacute glomerular injury, possibly ischemic. The underlying chronic vascular disease with 25% glomerular obsolescence was unlikely to account for the acute renal failure. The most likely relevant piece of history in this patient is the colonoscopy requiring bowel preparation with oral sodium phosphate solution (OSPS).

OSPS is the most widespread agent for colonoscopy bowel cleansing in the United States because it does not require large volumes of fluid ingestion and thus is more tolerable for the patient. However, several reports of renal failure following oral sodium phosphate bowel preparation have now been published (Desmeules et al., 2003; Markowitz et al., 2004; Markowitz et al., 2005; Gonlusen et al., 2006). The pathogenesis of renal tubular injury after OSPS ingestion appears to be the result of intestinal absorption and renal excretion of the sodium phosphate, during which some of the phosphate interacts with calcium and forms crystals within the tubular lumen. It has been calculated that up to 4 liters of water would have to be co-ingested to prevent such crystal formation (Patel et al., 2007), thereby eliminating one of the chief advantages to OSPS use.

Herein we have reported an additional case of renal failure following OSPS administration for colonoscopy. Although the overall rate of renal complications with OSPS is unknown, it is likely low given that this phenomenon has only recently been described. Still, it is important for clinicians and renal pathologists to be aware of this, and serves as an example of the importance of obtaining a thorough clinical history, including all prescription and non-prescription medications and substance use.

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