aHUS Leads to Kidney Failure in Infant with Cystic Fibrosis

A 6-month-old girl who was diagnosed with cystic fibrosis (CF) went into kidney failure due to atypical hemolytic uremic syndrome (aHUS), according to scientists who worked on her case report.

Her kidney function was completely restored following hemodialysis, plasma exchange therapy — a form of treatment that replaces the liquid portion of blood — and treatment with Soliris (eculizumab).

The case study, “Atypical haemolytic uraemic syndrome in a child with cystic fibrosis,” was published in the Journal of Paediatrics and Child Health.

aHUS is a rare disease characterized by the progressive destruction of red blood cells due to impaired function of the complement system — a set of more than 30 proteins that forms part of the body’s immune defenses — which increases the risk of permanent kidney damage.

CF is a progressive disease caused by mutations in the CFTR gene, which provides instructions to make a protein needed to transport water and other substances in and out of cells. The disease is characterized by the buildup of thick mucus in various organs, including the lungs, pancreas, liver, and intestines, gradually affecting their function.

Children with CF have been reported to be 100 times more likely to develop acute kidney injury.

Investigators in Australia described the case of a baby girl with CF who developed kidney failure due to aHUS.

The infant came to the hospital after having vomited for two days and urinating less than normal. Three days earlier, she had been vaccinated for hepatitis B, tetanus, polio, diphtheria, acellular pertussis, and influenza.

A physical exam revealed she was dehydrated and had tachycardia (a fast heart beat), with a heart rate of 156 beats per minute. She also showed signs of acute kidney injury, and her blood sodium levels were low.

She was given a combo of intravenous (into-the-vein) antibiotics — ampicillan and a lower dose of gentamicin — for a suspected urinary tract infection.

Despite her sodium levels slowly returning to normal within the next 48 hours, her kidneys ceased being able to produce urine — a condition called anuria. She became anemic, her platelet counts dropped, and her kidneys started to fail.

Within 24 hours, she underwent a procedure called continuous veno-venous hemofiltration (CVVH), a temporary treatment for patients with acute kidney failure who are unstable, together with plasma exchange therapy. In CVVH, blood flows out of the body into a machine to be “cleaned,” removing waste material and replacing important electrolytes like sodium. The blood is then infused back to the patient.

Her symptoms, along with subsequent tests that excluded other conditions as potential causes, suggested aHUS. This led physicians to start treating the infant with Soliris together with phenoxymethylpenicillin. At this point, she was also vaccinated against meningitis and received treatment to control her high blood pressure.

After starting treatment with Soliris, her levels of CH50, a complement protein, dropped by 50%. She did not have self-reactive antibodies against complement factor H, a key regulator of the complement system.

A genetic analysis then confirmed the presence of mutations, inherited from both parents, on complement genes. These mutations had been previously reported in other aHUS patients. She also inherited from both parents a mutation in the CFTR gene that is associated with CF.

Five months after starting Soliris, the girl remained relapse-free and showed normal kidney function. Nevertheless, researchers noted she remains at “an increased risk” of a relapse, and will have to continue treatment with Soliris indefinitely “due to the numerous risk factors for aHUS relapse,” while being closely monitored for any signs of disease recurrence.

They also added that she may later need lung, liver, and kidney transplants to manage both CF and aHUS.