Evaluating Renal Disease in Pediatric-Onset Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Disease Course, Outcomes, and Predictors of Outcome

Abstract

Objective: We aimed to study the disease course, outcomes, and predictors of outcome in pediatric-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affecting the kidneys.

Methods: Patients eligible for this study had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or ANCA-positive pauci-immune glomerulonephritis, were 18 years or younger at diagnosis, had renal disease defined by biopsy or dialysis dependence, and had clinical data at diagnosis and at either 12 or 24 months. Ambispective data from A Registry for Children with Vasculitis/Pediatric Vasculitis Initiative Registry was used. The primary outcome was inactive renal disease (pediatric vasculitis activity score = 0 or 1) at 12 months. Secondary outcomes included rates of improved renal function and damage within 24 months. Renal function, defined by estimated glomerular filtration rate, was categorized into Kidney Disease Improving Global Outcomes (KDIGO) stages at diagnosis and tested as a predictor of outcome using a proportional-odds logistic regression model.

Results: A total of 145 patients were included: 68% were female, and 78% had GPA. At 12 months, 83% of patients achieved inactive renal disease; however, 42% had evidence of permanent renal damage. Compared with patients with normal renal function at diagnosis, patients with moderate to severely reduced renal function, or kidney failure at diagnosis, had an odds ratio of 8.62 (P = 0.002; 95% confidence interval [CI] 2.31-32.1) and 26.3 (P < 0.001; 95% CI 6.32-109), respectively, for being in a non-normal KDIGO category at 12 months.

Conclusion: The majority of patients with pediatric AAV achieve inactive renal disease by 12 months; however, almost half have evidence of damage. Renal function at diagnosis is a strong predictor of renal function at 12 months.

Figure 1

Extrarenal manifestations at diagnosis and renal disease activity in the first 24 months in pediatric AAV. (A) Percentage of pediatric‐onset AAV cases (y‐axis) with organ‐specific system involvement (x‐axis) at the time of diagnosis. (B) Renal PVAS (y‐axis) in patients at TOD (n = 145), 12‐month follow‐up (n = 143), and 24‐month follow‐up (n = 87). Each dot represents a single patient. The width of the line indicates the number of patients with the same value. Inactive renal disease indicated by renal PVAS = 0 or 1, regardless of glucocorticoid dosage. Active renal disease is indicated by PVAS ≥2. ***P < 0.001. AAV, antineutrophil cytoplasmic antibody–associated vasculitis; ENT, ear nose and throat; PVAS, pediatric vasculitis activity score; TOD, time of diagnosis.

Figure 2

eGFR at diagnosis, 12 months, and 24 months in pediatric AAV. Percentage of patients with pediatric‐onset AAV (%, y‐axis) with eGFR values corresponding to KDIGO category of renal function (see legend; eGFR values in brackets with units mL/min/1.73m²) at (x‐axis) diagnosis (n = 145), 12 months (n = 143), and 24 months (n = 79). AAV, antineutrophil cytoplasmic antibody–associated vasculitis; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes; KF, kidney failure; MildR, mildly reduced; Mild‐ModR, mild to moderately reduced; Mod‐SevR, moderately to severely reduced; SevR, severely reduced; TOD, time of diagnosis.

Figure 3

eGFR in pediatric AAV at diagnosis, 12‐month follow‐up, and 24‐month follow‐up for patients with “extreme” renal function (normal versus kidney failure) at diagnosis. (A–D) eGFR (y‐axis; mL/min/1.73m²) with (A–B) “normal” renal function (eGFR > 90) at diagnosis followed across (A) 12 months (n = 33) and (B) 24 months (n = 17) and (C–D) kidney failure (eGFR < 15) at diagnosis followed across (C) 12 months (n = 23, including renal transplant shown by dashed line; n = 6) and (D) 24 months (n = 9, including renal transplant shown by dashed line; n = 6). Upper dotted line represents the lower limit of normal eGFR (eGFR = 90); middle dotted line represents the lower limit of MildR eGFR (eGFR = 60); and lower dotted line represents the upper limit of kidney failure (eGFR = 15). AAV, antineutrophil cytoplasmic antibody–associated vasculitis; eGFR, estimated glomerular filtration rate; MildR, mildly reduced; TOD, time of diagnosis.

Figure 4

eGFR in pediatric ANCA‐associated vasculitis at diagnosis and 12 months. eGFR values at diagnosis (x‐axis; mL/min/1.73m²) against eGFR values at 12‐month follow‐up (y‐axis; mL/min/1.73 m²) in patients with pediatric ANCA‐associated vasculitis (n = 113). The vertical dotted line at the x‐axis represents the cut point eGFR value of 38. The horizontal line on the y‐axis represents the eGFR value of 44.0, the upper limit of the moderately reduced renal function (KDIGO category). ANCA, antineutrophil cytoplasmic antibody; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes.