Effect of a multitarget therapy with prednisolone, mycophenolate mofetil, and tacrolimus in a patient with type B insulin resistance syndrome complicated by lupus nephritis

ABSTRACT Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease characterised by autoantibodies targeting insulin receptors. TBIR is often complicated by systemic lupus erythematosus (SLE). We describe the case of a 59-year-old Japanese man with TBIR complicated with lupus nephritis (LN), who presented with nephrotic syndrome and severe hypoglycaemia. Treatment with prednisolone (PSL), mycophenolate mofetil (MMF), and tacrolimus (TAC) resulted in improved SLE activity and glucose intolerance with the reduction of anti-insulin receptor autoantibodies. To the best of our knowledge, this is the first reported case of TBIR complicated with LN that was successfully treated using multitarget therapy with PSL, MMF, and TAC.

From hybrids to new scaffolds: the latest medicinal chemistry goals in multi-target directed ligands for Alzheimer’s disease

: Alzheimer’s disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of β amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous ADrelated targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted to be inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well stablished and incipient AD therapeutic targets, AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy.

SAT0177 MULTITARGET THERAPY WITH TACROLIMUS AND MYCOPHENOLATE MOFETIL FOR TREATMENT OF LUPUS NEPHRITIS PRESENTED WITH RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

Background:Although, most lupus nephritis patients present with chronic glomerulonephritis or nephrotic syndrome, some patients develop rapidly progressive glomerulonephritis (RPGN), which is a clinical syndrome characterized by rapid loss of renal function over a short period of time (days to months). Multitarget therapy using tacrolimus and mycophenolate mofetil (MMF) has been reported to be effective as induction therapy of Class III to Class V lupus nephritis1. However, its efficacy on lupus nephritis presented with RPGN has not been well reported.Objectives:We aimed to examine the efficacy of multitarget therapy on lupus nephritis presented with RPGN.Methods:We retrospectively analyzed patients with biopsy-proven lupus nephritis, who clinically showed RPGN, and were treated by multitarget therapy with tacrolimus and MMF in our department. Data were expressed as mean±SD.Results:Five lupus nephritis patients (3 female) with RPGN were treated by multitarget therapy as induction therapy. Mean age was 36.6±13.5 years old. Renal biopsy at treatment revealed Class IV(A) in 2, Class IV(A+C) in 1 and Class IV(A)+V in 2. The percentage of glomerular crescents was 23.1±25.4%. eGFR and proteinuria at the initiation of treatment were 46.8±11.5 mL/min/1.73m2and 7.7±3.4 g/gCr, respectively. Patients were initially treated with methylprednisolone pulse therapy followed by 0.8-1.0 mg/kg of prednisolone (PSL), 2-3 mg/day of tacrolimus and 1000 mg/day of MMF. At 6 months, eGFR and proteinuria improved to 72.9±11.3 mL/min/1.73m2and 0.19±0.13 g/gCr, respectively. At 12 months, eGFR and proteinuria further improved to 76.8±7.8 mL/min/1.73m2and 0.10±0.07 g/gCr, respectively and the dose of PSL was reduced to 6.6±1.5 mg/day. Three patients became positive for cytomegalovirus antigenemia and were successfully treated with antiviral therapy.Conclusion:Multitarget therapy is effective in lupus nephritis even in patients presented with RPGN.References:[1]Liu Z, Zhang H, Liu Z,et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial.Ann Int Med2015; 162: 18-26.Disclosure of Interests:Yoichi Imai: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc. b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.

The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis

The overall kidney survival among lupus nephritis patients has improved with currently used induction immunosuppression regimens of corticosteroids and either cyclophosphamide or mycophenolate mofetil; however, there still remains a significant number of lupus nephritis patients who do not achieve remission with these regimens. Investigators have looked at other immunosuppressive regimens for lupus nephritis, and there has been interest in the use of calcineurin inhibitors in this regard. Calcineurin inhibitors are potentially an attractive option because of their established ability to inhibit T cell function, attenuate proteinuria through non-immunologic means, and their safety in pregnancy and lactation. In this review, we discuss the findings and limitations of selected trials that evaluated the use of calcineurin inhibitors in the treatment of lupus nephritis, either with corticosteroids alone or as a component of multitarget therapy when combined with mycophenolate mofetil. There may be a role for calcineurin inhibitors among patients with heavy proteinuria, as well as younger patients with refractory lupus nephritis. The multitarget therapy trials reveal higher rates of remission compared with mycophenolate mofetil alone and cyclophosphamide; however, some trials highlight the possibility of more infectious adverse events. We discuss the need for further study of calcineurin inhibitors in more diverse patient populations and the need for trials with longer follow-up with “hard” endpoints beyond proteinuria reduction, such as worsening CKD or repeat protocol biopsies, given the calcineurin inhibitors ability to reduce proteinuria non-immunologically and thus increased rate of relapse when the drug is tapered. While there may indeed be a space for calcineurin inhibitors to help increase remission rates in lupus nephritis patients, more work is needed to help address the questions the studies available to date have yet to answer.

The Multicomponent, Multitarget Therapy SUC in Cats with Chronic Kidney Disease: A Multicenter, Prospective, Observational, Nonrandomized Cohort Study

Background: We compared the natural multicomponent, multitarget therapy SUC (Solidago compositum ad us. vet., Ubichinon compositum and Coenzyme compositum, Heel GmbH, Baden-Baden, Germany) to the well-known angiotensin-converting enzyme inhibitor benazepril in a prospective, observational, nonrandomized, two-arm cohort study of cats with chronic kidney disease (CKD). The objective was to assess the tolerability and the effectiveness of SUC in cats with CKD. Material and Methods: One hundred thirty-six cats were screened for CKD, and 70 cats were eligible for the study. Thirty-three cats were assigned to the SUC treatment, and 35 cats received benazepril. All cats were diagnosed with CKD. The follow-up period was 168 days. Response was assessed as an improved or stable serum creatinine from baseline to the end of the study. Additionally, a clinical summary score, as measure of quality of life, was evaluated. Results: Serum creatinine remained close to baseline in both study groups with slightly improved values in the SUC group. The clinical summary score improved significantly in the SUC group on days 3, 7, 28, 56 and 112, but not on day 168. Conclusions: Within the limitations of the study, the results carry implications for the usefulness of SUC as an interesting new treatment option for feline CKD. The results indicate that SUC might be more effective if given at least twice weekly.