Boy’s kidney issues resolve after Soliris treatment: Case report
4-year-old had PIGN, aHUS; achieved remission after treatment
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A 4-year-old boy developed post-infectious glomerulonephritis (PIGN) and later atypical hemolytic uremic syndrome (aHUS), both of which affect the kidneys, but once doctors started treatment with the complement inhibitor Soliris (eculizumab), his blood problems resolved, his kidney function recovered, and he achieved long-term remission.
“This case shows that PIGN may trigger aHUS in genetically predisposed children and underscores the need for early recognition and prompt complement inhibition,” researchers wrote in a report on the boy’s case, “From post-infectious glomerulonephritis to complement-mediated aHUS: a diagnostic challenge,” published in Pediatric Nephrology.
Both PIGN — an inflammatory response to infection that affects the filtering units of the kidneys — and aHUS occur due to problems with the complement system, a part of the immune system that helps the body fight infection. Sometimes the alternative complement system, a branch of the complement system, becomes overactive and damages the kidneys.
The boy in the report from Saudi Arabia first developed PIGN and later developed aHUS due to genetic mutations affecting the alternative complement system. The child arrived at the hospital with tea-colored urine and reduced urine output. These symptoms suggested that his kidneys were not filtering blood normally.
Doctors examined him and also found high blood pressure and widespread swelling called anasarca, which is characterized by severe buildup of fluid in the tissues of several parts of the body. Initial blood tests showed poor kidney function. Creatinine and urea, waste products normally removed by the kidneys, were elevated. Albumin, a protein that normally helps keep fluid inside blood vessels, was low.
Tests and treatment
Urine tests revealed hematuria (blood in the urine) and proteinuria (protein in the urine). Further tests pointed to a recent infection. The antistreptolysin-O titer (ASOT), a blood test that indicates a recent infection by certain streptococcal bacteria, was high. Complement proteins C3 and C4 were low, meaning the complement system had been activated. These findings suggested PIGN.
Because kidney function continued to worsen and swelling remained severe, doctors performed a kidney biopsy, removing a small sample of tissue and examining it under a microscope. The tissue showed inflammation inside the glomeruli, the filtering units of the kidneys. Electron microscopy revealed subepithelial humps, immune deposits typically observed in PIGN. These findings helped confirm the diagnosis.
Treatment started with high-dose corticosteroids to reduce immune activity. After treatment, urine output improved and creatinine decreased, suggesting partial recovery of kidney function. However, the boy still had proteinuria and low albumin in the blood. Because of this, doctors added mycophenolate mofetil, an immunosuppressive medication.
Ten weeks later, his symptoms worsened again. The doctors considered repeating the kidney biopsy, but the situation changed when the child suddenly developed seizures and required intensive care. New blood tests showed low hemoglobin (the protein that carries oxygen in red blood cells) and platelets, suggesting thrombotic microangiopathy, in which blood clots form in small blood vessels and damage organs.
Additional tests supported this diagnosis. Lactate dehydrogenase, which is released when red blood cells are damaged, was high, and a blood smear showed schistocytes, which are fragmented red blood cells caused by mechanical damage in blood clots. Complement testing showed low levels of factor H, a protein that normally controls complement activation. This suggested that uncontrolled complement activity was damaging the blood vessels.
The boy started Soliris, an antibody that inhibits complement protein C5, preventing further damage to blood vessels. His condition improved within three weeks. Blood pressure normalized, swelling disappeared, and laboratory values returned to normal. Genetic testing later showed mutations in CD46 and deletions in CFHR1 and CFHR3. These genes normally help regulate the complement system, and mutations can predispose to aHUS.
Six years after stopping Soliris, the boy remained in remission.
The case shows that PIGN can act as a trigger for aHUS in children who are already genetically predisposed. However, “while PIGN may serve as a trigger, complement gene abnormalities suggest that aHUS development is more likely due to underlying genetic susceptibility than PIGN alone,” the researchers concluded.
Doctors should carefully monitor children with PIGN who do not recover as expected, the researchers said. If signs of thrombotic microangiopathy appear, early treatment with complement-blocking therapy such as eculizumab can stop the disease process, protect the kidneys, and lead to long-term recovery.
