Impaired renal function, the presence of ANCA antibodies against the MPO protein, and a score of 2 or higher in the five-factor score — which measures prognosis at diagnosis in ANCA-associated vasculitis (AAV) — are all potential predictors of poor renal outcomes in children with AAV, a study has found.
The study, “Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis,” was published in the journal Pediatric Nephrology.
AAV is a condition characterized by small vessel inflammation that affects mostly adults. The condition is rare during childhood, but children who develop AAV often have symptoms in their kidneys, which severely affects their quality of life and survival.
Because of its rarity, children with AVV are treated according to information collected in adult patients. However, the approaches that work for adult patients may not be adequate for pediatric patients.
Turkish researchers set out to evaluate the prognostic potential of some factors, including vasculitis type, type of ANCA antibodies, five-factor score (FFS), and the type of kidney alterations seen in microscopic analysis (histopathologic classification).
FFS is a tool that assesses prognosis at diagnosis in patients with systemic necrotizing vasculitides. It includes five measures, including levels of blood creatinine (a good indicator of renal insufficiency), levels of protein in urine, central nervous system involvement, cardiac involvement, and severe gastrointestinal involvement. Each item scores one point, and an increased score is related to increased risk of death.
The study included 39 patients, with a median age of 17.2 years, followed at 11 centers in Turkey between January 2016 and March 2018. Patients had been diagnosed with a median age of 12.8 years, and most (66.7%) had granulomatosis with polyangiitis (GPA).
The most common symptoms at diagnosis were a general feeling of discomfort (82.1%), dark urine (51.3%), muscle or joint pain (46.2%), fever (43.6%), weight loss (38.5%), and high blood pressure (33.3%). Also, 76.9% of the children had high levels of red blood cells and 64.1% had high levels of protein in urine.
The most common initial organ involvement was renal involvement, affecting 74.4% of the children, followed by ear-throat-nose symptoms, musculoskeletal and skin involvement.
Regarding the type of ANCA antibodies, 48.7% of patients were positive for antibodies against the proteinase 3 (PR3) protein, 30.8% had antibodies against myeloperoxidase (MPO), and the remaining were negative for ANCA antibodies.
Most patients (97.4%) were treated initially with corticosteroids for induction therapy, 64.1% also received intravenous cyclophosphamide, and 25.6% received Rituxan (rituximab) for induction or remission therapy. Approximately 66.7% of cases also were treated with azathioprine and 15.4% received mycophenolate mofetil for remission induction.
During follow-up more than half of the children experienced a decline of more than 25% in renal filtration function, and end-stage renal disease (ESRD) — when the kidneys no longer work properly — was detected in 28.2% of cases.
Patients with an FFS score of above 2 were found to have more gastrointestinal and renal involvement, high protein levels in the urine, to be MPO-ANCA positive, and to have 25% decline in annual renal function.
The analysis of kidney tissue samples revealed that patients with FFS higher than 2 had significantly more cell proliferation and scar tissue, indicative of more tissue damage.
Also, patients with MPO-ANCA antibodies had significantly higher creatinine levels and lower rates of renal filtration.
Further examinations showed that the initial level of creatinine was a good indicator of renal outcome in ESRD patients. Initial creatinine values above 1.44 mg/dl showed a high sensitivity and specificity at determining patients at risk of end-stage renal disease.
“Evaluation of the FFS, ANCA serology, and the creatinine levels may help to predict renal prognosis,” researchers wrote. “Early diagnostic and therapeutic approach is mandatory to improve outcome in AAV.”