Membranous Nephropathy

Clinical History:  60 year old male with edema and nephrotic range proteinuria (>3.5 grams per 24 hours).Also found to have elevated lipids and decreased albumin.  Clinical diagnosis of nephrotic syndrome was made (proteinuria, hyperlipidemia, and hypoalbuminemia).  

Differential diagnosis includes membranous nephropathy, focal segmental glomerulopathy, minimal change disease, and other sytemic disease like diabetes.  

Renal biopsy shows the following on silver staining:

Notice the small eye-lash like projections form the glomerular basement membranes when cut perpendicular.  The mesangial regions are normal and there is no endocapillary proliferation.  By light microscopy these findings are consistent with membranous nephropathy.

IF studies confirm IgG, kappa, lambda,  and C3 in a glomerular basement membrane distribution.

EM shows dark electron dense deposits in the sub-epithelial space.  Note the severe overlaying foot process effacement.

Rare Productive Adenovirus Infection of a Renal Allograft

51 year old male 8 months status post kidney/pancreas transplant for type I diabetes.  Presents with a 2 week history of gross hematuria, fevers, and Cr increase to 2.8 (baseline 1.1).  Renal biopsy performed to rule out acute cellular rejection/infection.

Geographic necrotizing granulomatous tubulointerstitial nephritis.

High power shows prominent tubular destruction with a histiocyte and neutrophil rich infiltrate.  Rare irregular nuclear viral inclusions are noted in the right lower quadrant.

Immunohistochemistry for Adenovirus confirms the diagnosis.

Adenovirus infection in the renal allograft is very rare, but usually occurs early after transplant (first 3 months).  Clinically significant adenovirus infection typically involves the urothelium and causes hemorrhagic cystitis, primarily in immunosuppressed patients.  Hematuria is a common presenting symptom.  Serotype 11 is most often associated with clinical disease.

The histology is characterized by intranuclear viral inclusions in the tubular epithelial cells, severe tubular destruction with necrosis, marked interstitial granulomatous inflammation, and focal interstitial hemorrhage +/- RBC casts. 

Treatment for adenovirus nephritis is not well defined.  Different strategies have involved IVIG, decreased immunosuppression, and anti-viral agents.

Despite a lack of standardized treatment, the prognosis is good with graft loss rare. 

PubMed Reference

Early Chronic Rejection in a Liver allograft.

45 y/o status post liver transplant 1 year ago with increasing ALP over time

Early chronic rejection usually shows degenerative changes of the majority of the smaller bile ducts, ductopenia involving less than 50% of the portal tracts, and centrilobular hepatocyte dropout/fibrosis. The degenerative changes consists of eosinophilic transformation of the cytoplasm, nuclear hyperchromasia, uneven nuclear spacing, and sloughing of bile duct epithelial cells, as seen in this case.

The distinction between bile duct obstruction/stricturing and chronic rejection may be difficult. The presence of a marked ductular reaction and prominent periportal copper deposition favors bile duct obstruction/stricturing (primary or secondary) while the absence of a ductular reaction, absence of periportal copper deposition, and the presence of pericentral vein hepatocyte dropout/fibrosis favors chronic rejection.

Immunohistochemical staining for CK19 to highlight the bile ducts and ductular reaction as well as histochemical staining for peri-portal copper may be useful in the workup of liver allograft cases with biliary abnormalities.