Slideshow
-
Slide
-
Slide
A 31-year-old woman with a history of renal failure of unknown origin presents for transplant waitlist work-up after a failed kidney transplant one year previously. She had been on hemodialysis from 2000 to 2005. She had undergone cadaver kidney transplantation in 2005 and the graft worked very well until 2010. No rejection, delayed graft function or any surgical complications were detected during the transplant period. Her graft function diminished suddenly with elevated lactate dehydrogenase, serum bilirubin, and low hemoglobin and haptoglobin level. No abnormal neurological symptoms were detected. Treatment was unsuccessful and graft biopsy was taken (see images). She had returned to regular hemodialysis.
The patient has excellent performance status and has minimal significant comorbidities. Physical examination revealed a blood pressure of 140/85 mm Hg and mild cachexia, without other significant findings. In addition to a creatinine level of 5.9, laboratory results showed BUN 40, K 5.0, Na 133, Hgb 11.9, and hct 35. She had no rest diuresis. Liver function tests were normal, HIV serology was pending, and the following serologic studies were done:
Anti-HF IgG autoantibody: negative
Anti-BF IgG autoantibody: negative
Anti-Properdin IgG autoantibody: negative
Total-complement (hemolytic test): 54 CH50/mL (reference range: 48-103 CH50/mL)
Alternative complement activity (Wielisa ALT): 1 % (reference range: 70%-105 %)
Complement C3: 0.4 g/L (reference range: 0.7-1.8 g/L)
Complement C4: 0.49 g/L (reference range: 0.15-1.55)
H-factor antigen: 124 mg/L (reference range: 127-447)
I-factor antigen: 65 % (reference range: 70%-130%)
B-factor antigen: 51% (reference range: 70%-130%)
ADAMTS13 metalloprotease activity: 56% (reference range: 67%-151%)
Submit your diagnosis to see full explanation.
The clinical history and laboratory results (decreased alternative complement activity, decreased C3, B-, I- and H factor antigen level) confirmed the diagnosis of atypical hemolytic uremic syndrome (HUS). Atypical HUS is often associated with mutations in genes encoding complement regulatory proteins and secondary disorders of complement regulation. Progression to kidney failure and recurrence with graft loss after kidney transplantation are frequent. The most common mutation is in the gene encoding complement factor H. In our case we identified Val609Asn mutation (heterozygote) in H factor (see image). We also identified the heterozygote type of the MCPggaac aHUS risk haplotype.
The treatment of atypical HUS is unclear. A consensus conference to establish treatment guidelines for atypical hemolytic uremic syndrome was held in Bergamo in December 2007. If the genetic mutation is confirmed, as in our case, single kidney transplantation by itself is contraindicated. Combined liver-kidney transplantation may correct this complement abnormality and prevent recurrence when the defect involves genes encoding circulating proteins that are synthesized in the liver, such as factor H or I. Case reports have suggested that eculizumab, a monoclonal antibody that blocks complement activity by cleavage of C5, is effective in the treatment of atypical HUS or preventing relapse after transplantation. However, the long-term results are not available.
The case was prepared by Miklos Z Molnar, MD, PhD, Research Associate, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif.
QUESTION
