Molecular diagnosis of kidney transplant failure based on urine

Area of Science:

• Nephrology
• Genetics
• Transplantation

Background:

• Organ shortage necessitates using extended criteria donor organs.
• Increasing transplanted organ lifespan requires accurate diagnosis and management of detrimental influences.
• Chronic kidney transplant failure necessitates identifying underlying causes, including rare genetic disorders.

Purpose of the Study:

• To investigate the cause of chronic decline in kidney transplant function over a decade.
• To identify the genetic basis of oral-facial-digital syndrome in a donor and its impact on kidney allografts.
• To assess the long-term outcome of kidney transplantation from a donor with a rare genetic ciliopathy.

Main Methods:

• Clinical evaluation of kidney transplant recipients with declining function.
• Review of donor allocation documents mentioning oral-facial-digital syndrome.
• Molecular diagnosis via culturing donor tubular cells from recipient urine.
• Next-generation panel sequencing of donor DNA from urinary cells.

Main Results:

• A kidney transplant recipient experienced a decade-long decline in function with multiple cysts.
• Exclusion of common causes of chronic transplant failure.
• Identification of a novel truncating mutation in the OFD1 gene in donor tubular cells, confirming oral-facial-digital syndrome.
• The identified mutation explained the kidney transplant pathology and was present in a second kidney allograft.
• Successful transplantation in 5 recipients from this donor, despite the genetic condition.

Conclusions:

• Oral-facial-digital syndrome, caused by OFD1 mutations, can affect kidney allografts.
• Molecular diagnosis can be achieved years post-transplantation using recipient urine.
• Extended criteria donation from individuals with rare genetic diseases can lead to successful long-term transplant outcomes.
• Accurate diagnosis of donor conditions is crucial for managing transplanted organ health.