Researchers Study Unique Case of Alport Syndrome and Membranous Nephropathy

A rare case of combined Alport syndrome and rapidly progressing membranous nephropathy, another kidney disease that affects the kidneys’ filtering mechanism, has prompted researchers to further explore whether the two conditions are related.

Other factors, such as infectious disease, could also trigger additional kidney issues in Alport patients, researchers from the University of São Paulo School of Medicine in Brazil hypothesized.

The study, “Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?” appeared in the journal Nephron.

Doctors learned about the 37-year-old woman’s condition after she sought care for widespread swelling. She had foamy urine and had gained 22 pounds (10 kilograms) in the previous two months.

She had a family history of kidney disease, and four sons were diagnosed with Alport syndrome based on their symptoms. A physical examination of the woman showed no other abnormalities, but lab tests showed that she had nephrotic syndrome, with increased protein levels in the urine. The patient did not appear to have ongoing autoimmune processes, although she did test positive for syphilis.

While her kidneys looked normal when examined by ultrasound, a more thorough analysis using high-resolution microscopy of a tissue sample revealed changes consistent with Alport syndrome.

However, the patient also had kidney abnormalities not typical of Alport, including deposits of antibodies. Doctors said these symptoms were more typical of membranous nephropathy.

She tested positive for a mutation in the COL4A5 gene, which causes X-linked Alport.

The COL4A5 gene is located on the X chromosome. Since men have only one X chromosome, they always develop the disease with a mutated gene. Women, on the other hand, have two X chromosomes, but one of them is inactivated. Because this inactivation is random, some cells have a mutated gene copy, while others might have a normal COL4A5 gene. Because of this, X-linked Alport can range from mild to severe in women.

Earlier studies have described a few similar cases, but none had the exact same characteristics as this patient. Researchers said they could not exclude the possibility that the syphilis infection triggered membranous nephropathy, although the woman showed no symptoms of syphilis and had low levels of antibodies to the microbe.

They also said that abnormal kidney structure caused by Alport could have led to a nonspecific trapping of immune-complexes in the kidney, suggesting that Alport patients could be susceptible to developing this type of immune-related kidney disease.