Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations

Abstract

ObjectivesTo analyse the current evidence for the management of lupus nephritis (LN) informing the 2019 update of the EULAR/European Renal Association-European Dialysis and Transplant Association recommendations.MethodsAccording to the EULAR standardised operating procedures, a PubMed systematic literature review was performed, from January 1, 2012 to December 31, 2018. Since this was an update of the 2012 recommendations, the final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including literature prior to 2012.ResultsWe identified 387 relevant articles. High-quality randomised evidence supports the use of immunosuppressive treatment for class III and class IV LN (LoE 1a), and moderate-level evidence supports the use of immunosuppressive treatment for pure class V LN with nephrotic-range proteinuria (LoE 2b). Treatment should aim for at least 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (<500–700 mg/day) at 12 months (LoE 2a-2b). High-quality evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) as initial treatment of active class III/IV LN (LoE 1a). Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a). There is low-quality level evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease, all methods of kidney replacement treatment can be used, with transplantation having the most favourable outcomes (LoE 2b).ConclusionsThere is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment, but low-to-moderate quality evidence to guide treatment of class V LN, monitoring and optimal duration of immunosuppression.

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis

“…26 As such, the anifrolumab IR was required to reach clinical efficacy, with clinically meaningful responses across renal endpoints, including proteinuria, multiple stringent CRR definitions (including requirements for UPCR ≤0.5 mg/ mg or inactive urinary sediment), sustained oral glucocorticoid dosage reductions, disease activity measures and lupus serologies. Reduction of proteinuria is associated with reduced risk of end-stage kidney disease [27][28][29] ; thus, it is an appropriate and objective surrogate endpoint for a proof-of-concept trial. Here, numerically greater improvements in 24-hour UPCR were observed early in the trial with both anifrolumab groups vs placebo; however, by week 52, all treatment groups had improvements in baseline 24-hour UPCR of approximately 70%.…”

Prognostic factors for chronic kidney disease and end-stage renal disease in patients with lupus nephritis: A retrospective cohort study

“…For hypertension, many studies have shown it as a risk factor for CKD [16,17,21,[35][36][37][38][39]53]. Presence of hypertension has also been found to be a predictor in Brazilian patients of African extraction [54].…”

Respiratory Manifestations in Systemic Lupus Erythematosus

“…A broad-spectrum antibiotic coverage should be started until an infection is ruled out, and then prophylaxis against opportunistic pathogens (e.g., Pneumocystis jirovecii) can be considered during immunosuppressive treatment [ 10 , 17 , 23 , 24 , 25 , 28 , 29 ]. Factors that seem to contribute to poor outcome include intercurrent infections, aspiration, diaphragmatic dysfunction, cardiac and renal failure, drug and oxygen toxicity [ 7 , 29 , 30 , 31 ]. Of those who recover from the acute episode, 50–100% may eventually develop chronic interstitial pneumonia so a thorough follow-up is advisable [ 10 , 31 ].…”

“…Recently, a new set of classification criteria was proposed by American College of Rheumatology/European League Against Rheumatism (ACR/EULAR), designed to increase classification sensitivity and specificity for inclusion in SLE research studies and trials [ 5 ]. Furthermore, recommendations on disease management from EULAR were recently updated [ 6 , 7 ].…”