Pediatric lupus nephritis: more options, more chances?

Abstract

Lupus nephritis (LN) is more common and severe in childhood-onset systemic lupus erythematosus (SLE) than in adults. It is one of the major causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in children. Steroid therapy has been used as the first-line treatment for SLE since 1970, and has improved the survival of SLE patients from ∼ 50% to >80%. Over the years many immunosuppressive drugs, including pulse methylprednisolone, oral cyclophosphamide, pulse intravenous cyclophosphamide, mycophenolate mofitil, rituximab, and tacrolimus, have been combined with prednisolone, further improving survival rates to 90%-95%. However, the effectiveness of these drugs is still uncertain, as most seem very good in the beginning, but in studies examining longer-term follow-up the remission of disease does not remain. Fatal infection is still a major complication of aggressive chemotherapy, and the potential benefits as well as adverse events from each drug need to be considered. Induction of remission is the major aim of therapy, with safe and effective maintenance therapy for long-term remission. The survival rates of many published studies vary widely because of differences in patients and treatment modalities, severity of disease, renal histopathology, racial factors, and duration of follow-up. Finding the optimal treatment for SLE and related co-morbidities is highly challenging, and will likely involve a complex combination of different drugs for different patients in the search for giving them an opportunity to be free from this debilitating disease.

The association between initial manifestations of childhood‐onset systemic lupus erythematosus and the survival

“…For instance, LN was associated with higher morbidity and mortality . About 50–80% of cSLE patients showed evidence of renal involvement, up to 90% within the first year of disease onset . Approximately 45% of our cases had hematuria at baseline, which included 60% of those who died versus less than 40% of those who had not.…”

“…Some clinical findings such as renal, neurologic and hematologic manifestations are more common in cSLE than in aSLE . Moreover, cSLE has a more rapid onset, more aggressive course and a higher tendency to organ involvement and damage, especially renal disease . Besides these characteristics, longer living time with active disease and subsequently, more treatment‐related adverse effects have been associated with more prolonged complications in cSLE .…”

“…[4][5][6] Moreover, cSLE has a more rapid onset, more aggressive course and a higher tendency to organ involvement and damage, especially renal disease. 7 Besides these characteristics, longer living time with active disease and subsequently, more treatment-related adverse effects have been associated with more prolonged complications in cSLE. 8,9 Although survival of children with SLE has increased significantly during the past three decades, 10 the above-mentioned characteristics need more attention to prevent later organ damage.…”

Off‐label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics

“…55 The major characteristic feature of paediatric-onset LN is acute inflammatory renal damage, which suggests that the use of immunosuppressants in the early stages of childhood LN may improve the prognosis of later stages. [56][57][58] Glucocorticoids in combination with CTX are currently a classic treatment for LN. 59 However, severe adverse reactions have also increased, such as amenorrhea, atypical hyperplasia of the cervix, leukocyte decline, infection and alopecia caused by CTX, and especially the obviously toxic effects of gonads.…”

Systemic Lupus Erythematosus

“…233,244,572 The utility of CSA is limited by its need for careful monitoring of drug levels and its potential toxicities, including hypertension, renal impairment, effects on lipid profile, tremor, hirsutism, and gum hyperplasia. 232,579,580 Regarding nonrenal SLE, a recent multicenter, randomized, controlled trial by BILAG concluded that low-dose CSA was as effective as AZA as a steroid-sparing agent in patients with severe SLE with a similar rate of adverse drug effects. Similarly, a number of small trials have shown efficacy of TAC in LN.…”