Clinical History:

This 40-year-old woman has a long-standing history of diabetes mellitus, type I, which resulted in renal failure three years ago. Because of her renal failure, she was placed on dialysis awaiting renal transplantation. She received a cadaveric kidney transplant that was well-matched on HLA typing. She had done well for two and a half weeks, but then her creatinine began rising and her urine output decreased. A renal biopsy was performed.

Image 3.1:

The low power light microscopic appearance of the renal biopsy with H&E stain is shown here. What is wrong? There is inflammation involving primarily the tubules and interstitium.

Image 3.2:

This is a higher power view of the tubules and interstitium. What is the nature of the inflammatory infiltrate? The infiltrate is mostly lymphocytes of various sizes.

Image 3.3:

The immunofluorescence pattern (anti-IgG) shows extensive immune deposits in the tubulointerstitial region.

Further History:

She was treated for the above condition and did well for another two years, at which time renal function began to gradually decrease, with rising BUN and creatinine over the next 4 months. Another renal biopsy was performed.

Image 3.4:

The low power light microscopic appearance of the renal biopsy with H&E staining is shown here. What do you see? There is extensive interstitial fibrosis and tubular atrophy.

Image 3.5:

This is the high power light microscopic appearance of a renal cortical artery. There is marked intimal fibrosis.

Questions:

1. What is the significance of the pathologic findings? What do you suspect is happening?

The pathologic findings suggest that renal transplant rejection is occurring. The pattern is that of acute cellular rejection.

2. What immunologic mechanisms are operative here?

Acute cellular (tubulo-interstitial) rejection is predominantly mediated by type II hypersensitivity (antibody dependent cell mediated cytotoxicity - ADCC) and by type IV hypersensitivity (cell mediated). Both CD4 and CD8 lymphocytes can be found in the infiltrates.

3. What other problems can develop in this setting to produce a similar clincal picture?

The differential diagnosis includes acute tubular necrosis, cyclosporine nephrotoxicity, and acute vascular rejection. The difficulty in diagnosis lies in the fact that any or all of the above may be present in one patient. Acute vascular rejection (mediated by type III hypersensitivity - immune complexes) would be characterized on biopsy by necrotizing vasculitis with neutrophils.

4. What would be the mode of therapy and what would you predict as a response?

Immunosuppressive therapy generally leads to a good response with acute cellular rejection, but not acute vascular rejection.

5. What is the significance of the pathologic findings seen in the second biopsy? What do you suspect is happening?

The findings suggest chronic vascular rejection. This may occur months to years following transplantation.

6. What immunologic mechanisms are operative to explain the findings in the second renal biopsy?

Both cellular and humoral mechanisms (type II, III, and IV hypersensitivity reactions) are present, but many of the changes are secondary to ischemia as a result of the vascular changes.

7. What is the prognosis?

Not good. Go back on the list waiting for another kidney.