Background The clinical significance of renal vascular lesions remains unknown in childhood-onset lupus nephritis (LN) and is not currently factored into WHO and ISN/RPS classification.
Objectives The aim of this study is to determine the incidence and outcomes of childhood-onset LN in the presence of these lesions.
Methods We conducted a retrospective review at the tertiary paediatric nephrology centre in Hong Kong of children with LN who presented before 18 years with active follow-ups for 12 or more months by July 2020. Estimated glomerular filtration rate (eGFR) was calculated by modified Schwartz and CKD-EPI formula as appropriate.
Results Among 90 children with childhood-onset systemic lupus erythematosus, 61 patients (68%; mean age of 13.2 ±3.4 years; 85% girls) diagnosed to have biopsy-proven LN. The predominant presentation was nephritic-nephrotic syndrome (n=30, 50%), with 4 patients required acute dialysis. One (4%), 17 (28%), 29 (48%), 9 (15%), 4 (7%) and 1 (2%) patients had class II (lupus podocytopathy), III, IV, III/IV + V, V and VI LN, respectively.
Of the 61 patients with LN, renal vascular lesions were observed in 9 children (15%) at a mean age of 14.1 ±4.3 years, including lupus vasculopathy (LV; n=4, 7%), thrombotic microangiopathy (TMA; n=4, 7%) and true vasculitis (n=1, 2%). Eight patients had co-existing proliferative LN (Class III [n=3]; IV [n=3]; mixed III/IV and V [n=2]) and one patient had pure membranous LN. All children except two developed nephritic-nephrotic syndrome and AKI, and acute dialysis were initiated in 2 patients with TMA. At presentation, patients with renal vascular lesions had a significantly lower median eGFR (21.0, IQR 14.0–51.0 versus 88, IQR 48.5–107.5 ml/1.73 m2/min; p=0.011) but similar degree of proteinuria (3.1, IQR 2.4–8.04 versus 2.5, IQR 1.3–5.1 mg/mg) than those without such lesions.
Treatments were heterogeneous due to variable disease severity. In addition to pulse methylprednisolone, 6 and 3 patients received induction therapies with intravenous cyclophosphamide and mycophenolate mofetil, respectively. Three patients with severe AKI (LV n=2; TMA n=1; mean GFR 18.6 ml/1.73 m2/min) responded to rituximab as add-on rescue therapies and eventually did not require acute dialysis. Therapeutic plasma exchange was performed in three patients with TMA as adjunctive therapies. Following induction, 6 patients attained complete remission and had normal GFR and no proteinuria at last follow-up. Three patients failed to respond and developed chronic kidney disease (CKD). One LV patient had poor adherence and repeated relapses leading to end stage kidney disease (ESKD) and received a kidney transplant. One patient with TMA and another with LV developed CKD II (GFR 74 ml/1.73 m2/min) and CKD IV (28 ml/1.73 m2/min), respectively. At the end of the study, more children with LN and renal vascular lesions developed either CKD or ESKD (3/6 [33.3%] versus 4/48 [7.7%], p=0.06), although it did not reach statistical significance.
Conclusions Childhood-onset LN with renal vascular lesions had more severe presentation and may be associated with worse kidney outcomes. Identifying these lesions may have prognostic value and guide clinical management. Further large-scale studies are required to define its role in the future LN classification.
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