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Introduction Idiopathic focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and end-stage renal disease. In preclinical models and biopsies of human FSGS kidneys, p38 mitogen-activated protein kinase (MAPK) has demonstrated enhanced activity; and p38 MAPK inhibition has improved disease markers. This proof-of-concept trial aimed to assess efficacy, safety, tolerability, and pharmacokinetics of losmapimod, an oral p38 MAPK inhibitor, in humans with FSGS. Methods A single-arm, multicenter, open-label, Phase II trial (NCT02000440) was conducted in adults with FSGS; proteinuria ≥2.0 g/d; estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2; blood pressure 20% in 3 patients. One patient achieved a proteinuria response (≥50% reduction) at week 2 but subsequently relapsed. Losmapimod pharmacokinetics were consistent with prior studies. No serious adverse events (AEs) were reported. Conclusion p38 MAPK inhibition with losmapimod did not result in ≥50% reduction of proteinuria in patients with FSGS. However, study population heterogeneity may have contributed to our negative findings and therefore this does not eliminate the potential to demonstrate benefit in a population more sensitive to p38 MAPK inhibition if identifiable in the future by precision-medicine methods., Graphical abstract

Introduction The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Glomerulonephritis recommend that patients with membranous nephropathy (MN) at risk for progression receive immunosuppressive therapy (IST), usually after 6 months of observation. A cyclophosphamide (CYC) or calcineurin inhibitor (CNI)–based regimen is recommended as first-line IST. However, the extent to which KDIGO recommendations are adopted in practice remains largely unknown. Methods We evaluated prescribing practice among patients with primary MN (diagnosed 2010–2018) enrolled in the Cure Glomerulonephropathy Network (CureGN) cohort study. We also evaluated the availability of testing for phospholipase A2 receptor (PLA2R) in the contemporary era. Results Among 361 patients (324 adults and 37 children) with MN who were IST-naïve at biopsy and had at least 6 months of follow-up, 55% of adults and 58% of children initiated IST, Graphical abstract

Summary: Pregnancy associated with lupus, especially lupus nephritis, is often fraught with concern for both the mother and fetus. Thus, it is paramount that care begins preconception so that proper planning in terms of optimizing the medical regimen, discontinuation of fetotoxic agents, and treatment of active disease can occur. It is well known that active nephritis at the time of conception is associated with poor outcomes. Even with quiescent disease, recent data indicate that being lupus anticoagulant–positive, nonwhite or Hispanic, and using antihypertensive medications were all predictors of worse pregnancy outcomes. Further, prior lupus nephritis also predicts higher rates of preeclampsia and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. Differentiating lupus nephritis from preeclampsia often presents as a conundrum, but lupus nephritis can be confirmed by the presence of decreasing complement levels and increasing double-stranded DNA (dsDNA) antibody levels in addition to new onset hypertension and proteinuria. We hope that the more mechanistic approach of measuring angiogenic markers, which are diagnostic for preeclampsia, will be the standard of care in the future. Women with lupus and prior lupus nephritis can have successful pregnancies, but outcomes are dependent on “the art of planning” as well as close communication between the obstetrician, the nephrologist, and the rheumatologist.