An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study)

Rémy, Philippe; Audard, Vincent; Natella, Pierre-André; Pellé, Gaëlle; Dussol, Bertrand; Leray‐Moragues, Hélène; Vigneau, Cécile; Bouachi, Khedidja; Dantal, Jacques; Vrigneaud, Laurence; Karras, Alexandre; Pourcine, Frank; Gatault, Philippe; Grimbert, Philippe; Sahlia, Nawelle Aït; Moktefi, Anissa; Daugas, Éric; Rigothier, Claire; Bastuji‐Garin, Sylvie; Sahali, Dil; Aldigier, Jean-Claude; Bataille, Pierre; Canaud, Bernard; Chauveau, Dominique; Combe, Christian; Choukroun, Gabriel; Cornec-Legall, Emilie; Dahan, Karine; Delahousse, Michel; Desvaux, Dominique; Deteix, P; Dürrbach, Antoine; Esnault, Vincent; Essig, Marie; Fiévet, P.; Frouget, T.; Guerrot, Dominique; Godin, Michel; Gontiers-Picard, Annie; Gosselin, Morgane; Hanrotel-Saliou, Catherine; Heng, Anne-Élisabeth; Huart, Antoine; Humbert, Antoine; Kofman, Tomek; Hummel, Aurélie; Lang, Philippe; Laville, Maurice; Lemeur, Yannick; Malvezzi, Paolo; Matignon, Marie; Mesbah, Rafik; Moulin, Anne‐Marie; Muller, Sandrine; Olagne, Jérôme; Pardon, Agathe; François, Patrice; Queffeulou, Guillaume; Plaisier, Emmanuelle; Raimbourg, Quentin; Rieu, Philippe; Stehlé, Thomas; Vanhille, Philippe

doi:10.1016/j.kint.2018.07.021

Cited by 21 publications

(23 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Response to therapy is typically slower in adults than in children, justifying prolonged steroid courses before defining treatment failure. Mycophenolate mofetil (an immunosuppressant) combined with low-dose steroids may induce disease remission in adult podocytopathies at rates comparable with standard therapy 175,176 , possibly alleviating the risk of steroid-related adverse effects such as diabetes and hypertension in high-risk patients. Slow tapering of immunosuppressive drugs over 6 months is a widely accepted measure to reduce the risk of relapse 177 .…”

Section: New-onset Nephrotic Syndromementioning

confidence: 99%

Podocytopathies

Kopp

Anders

Suszták

et al. 2020

Nat Rev Dis Primers

269

270

View full text Add to dashboard Cite

Podocytopathies are kidney diseases in which direct or indirect podocyte injury drives proteinuria or nephrotic syndrome. In children and young adults, genetic variants in >50 podocyte-expressed genes, syndromal non-podocyte-specific genes and phenocopies with other underlying genetic abnormalities cause podocytopathies associated with steroid-resistant nephrotic syndrome or severe proteinuria. A variety of genetic variants likely contribute to disease development. Among genes with non-Mendelian inheritance, variants in APOL1 have the largest effect size. In addition to genetic variants, environmental triggers such as immune-related, infection-related, toxic and haemodynamic factors and obesity are also important causes of podocyte injury and frequently combine to cause various degrees of proteinuria in children and adults. Typical manifestations on kidney biopsy are minimal change lesions and focal segmental glomerulosclerosis lesions. Standard treatment for primary podocytopathies manifesting with focal segmental glomerulosclerosis lesions includes glucocorticoids and other immunosuppressive drugs; individuals not responding with a resolution of proteinuria have a poor renal prognosis. Renin-angiotensin system antagonists help to control proteinuria and slow the progression of fibrosis. Symptomatic management may include the use of diuretics, statins, infection prophylaxis and anticoagulation. This Primer discusses a shift in paradigm from patient stratification based on kidney biopsy findings towards personalized management based on clinical, morphological and genetic data as well as pathophysiological understanding.

show abstract

Section: New-onset Nephrotic Syndromementioning

confidence: 99%

Podocytopathies

Kopp

Anders

Suszták

et al. 2020

Nat Rev Dis Primers

269

270

View full text Add to dashboard Cite

show abstract

“…Steroids were withdrawn in 15/21 after a median time of 7.2 months. Renal relapse occurred in 7 patients after a median time of 13 months [10,11,12,13,14,15,16,17,18,19,20,21,22,23] following rituximab infusion. In the four patients with available data, CD19 + B-cells were detectable in the blood at the time of the relapse.…”

Section: Resultsmentioning

confidence: 99%

“…MCD is the main cause of nephrotic syndrome in children while it accounts for only 10%–15% of nephrotic syndrome in adulthood. Epidemiological and descriptive studies are scarce in adulthood or included mainly individuals less than 60 years of age [18,19,21,22,23,24,25]. Thus, incidence and outcomes of INS in older patients remains unknown, whereas these patients are at higher risk of treatment-related complications.…”

Section: Discussionmentioning

confidence: 99%

“…Management of older patients is also stressed by the frequent comorbidities (cardiovascular disease, diabetes mellitus, obesity) preceding INS and a higher risk of new-onset diabetes mellitus, hypertension, AKI or cancer while receiving steroids, CNI or alkylating agents. Alternative regimens to first-line oral steroid therapy have recently been proposed [18,19] but there is an unmet need to define the optimal immunosuppressive regimen in adult patients, especially in older patients (≥60 years old at the onset).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Outcomes of Older Patients (≥60 years) with New-Onset Idiopathic Nephrotic Syndrome Receiving Immunosuppressive Regimen: A Multicentre Study of 116 Patients

Colliou

Karras

Boffa

et al. 2019

JCM

Self Cite

View full text Add to dashboard Cite

Because of its rarity, renal presentation and outcomes of idiopathic nephrotic syndrome (INS; minimal changes disease or focal and segmental glomerulosclerosis) has poorly been described in elderly patients, precluding an individualized therapy procedure. Whether immunosuppressive regimens formerly designed in children and young adults are safe and efficient in elderly remains elusive. In a large multicentric retrospective study that included 116 patients with INS and onset ≥ 60 years of age, we showed that cumulative incidence of renal response was 95% after frontline therapy, with an age-dependent median time-to-response (60 days before 70 years of age at the onset vs. 120 days after; p = 0.03). Cumulative incidence of relapse was 90% at 7 years, with relapse occurring continuously over time. After a median follow-up of 34 months (IQR (12; 57)), 7 patients had died (6%) and 5 reached end-stage renal disease. Complications were highly prevalent: diabetes mellitus (23.3%), hypertension (24.1%), infection requiring hospitalization (21.6%) and acute kidney injury (9.5%). Thus, in older patients with INS and receiving steroids, renal response is delayed and relapse is the rule. Alternative immunosuppressive regimens, including B-cells depleting agents as frontline therapy, should be tested in this subset of patients to improve the mid- to long-term outcomes.

show abstract

“…A predicted slow response to corticosteroid treatment based on low nephron number may lead to a decision to consider alternative initial treatment with proven efficacy such as tacrolimus or mycophenolate. 14 , 15 The effect size of nephron number may potentially be even larger in European and American patients with MCD, who may manifest delayed proteinuria response to corticosteroid treatment as compared with Asians. 2 16 …”

mentioning

confidence: 99%