Soliris, hemodialysis improved function of transplanted kidney in aHUS patient
Monitoring, testing key to preventing transplant failure, case study says
Soliris (eculizumab) and hemodialysis improved kidney function in a man with end-stage kidney disease who was diagnosed with atypical hemolytic uremic syndrome (aHUS) after a kidney transplant, according to a case study from South Korea.
The report “emphasizes the importance of primary kidney disease evaluation and careful monitoring” for aHUS and similar conditions, particularly in patients with end-stage kidney disease of uncertain origin, researchers wrote. “Prompt initiation of eculizumab can prevent [transplant] failure.”
The study, “Successful diagnosis and treatment of recurrent atypical hemolytic uremic syndrome posttransplantation caused by the heterozygous deletion of CFH in a patient with end-stage kidney disease of uncertain etiology,” was published in the journal Kidney Research and Clinical Practice.
aHUS belongs to a group of disorders called thrombotic microangiopathies (TMAs). TMAs are characterized by red blood cell destruction (hemolysis), low platelet counts, and the formation of blood clots inside small blood vessels that can damage internal organs, especially the kidneys. About half of aHUS patients develop end-stage kidney disease, which may require kidney transplant.
aHUS is also typically associated with mutations in genes that regulate the activity of the complement system, a part of the immune system, causing it to be overactive.
Expanded genetic testing leads to aHUS diagnoses after transplants
“Genetic testing is crucial for the diagnosis of aHUS, as variants in complement regulatory protein gene significantly increase disease risk,” the researchers wrote. “Advances in genetic testing and its widespread use have revealed cases of aHUS recurring after kidney transplantation.”
The report focuses on a 45-year-old man with end-stage kidney disease from an unknown cause who was diagnosed with aHUS after undergoing a kidney transplant.
His transplanted kidney started showing signs of dysfunction after one month, even though he was on a triple combination of immunosuppressive therapies including tacrolimus (sold as Prograf, among other brand names).
Lab tests confirmed abnormally elevated levels of creatinine, a sign of kidney dysfunction, along with hemolytic anemia (low red blood cell counts driven by hemolysis) and low platelet counts. Complement levels also were reduced.
Tests also revealed the presence of schistocytes, or red blood cell fragments, indicative of TMA. A biopsy of the transplanted kidney showed focally proliferative glomerulonephritis, or inflammation in the kidney’s tiny filtering units (glomeruli), but without signs of TMA.
The man underwent seven sessions of plasma exchange therapy, a blood-cleaning procedure, but the transplanted kidney did not recover, and he had to start hemodialysis.
Genetic testing revealed a mutation in the CFI gene, which had not been previously reported, and a partial deletion in the CFH gene. Mutations in both these genes have been implicated in aHUS.
Doctors diagnosed him with aHUS, which was considered to be the cause of his end-stage kidney disease as well as transplanted kidney dysfunction.
The patient completed four weeks of hemodialysis before undergoing a four-week induction with Soliris. After that, he no longer required hemodialysis, but continued receiving maintenance treatment with Soliris. Eventually, his hemolysis resolved and the function of his transplanted kidney began to improve.
The man’s aHUS was “overlooked” until after his transplant, indicating “genetic testing is crucial for aHUS diagnosis, regardless of typical TMA features,” the researchers wrote.
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