Desmond Y H Yap1,2, Colin Tang1,2, Gary C W Chan1,2, Lorraine P Y Kwan1,2, Maggie K M Ma1,2, Maggie M Y Mok1,2, Tak Mao Chan3,4. 1. From the Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong. 2. D.Y. Yap, MD, FRCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; C. Tang, BSc, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; G.C. Chan, FHKCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; L.P. Kwan, FHKCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; M.K. Ma, FRCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; M.M. Mok, FHKCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; T.M. Chan, MD, FRCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong. 3. From the Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong. dtmchan@hku.hk. 4. D.Y. Yap, MD, FRCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; C. Tang, BSc, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; G.C. Chan, FHKCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; L.P. Kwan, FHKCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; M.K. Ma, FRCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; M.M. Mok, FHKCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong; T.M. Chan, MD, FRCP, Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong. dtmchan@hku.hk.
Abstract
OBJECTIVE: To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients. METHODS: We retrospectively reviewed 16 class III/IV/V patients with LN who have received prednisolone (PSL) and sirolimus either as initial or maintenance treatment. RESULTS: Sixteen patients received sirolimus treatment (9 because of intolerance to standard immunosuppressants and 7 because of a history of malignancy) for 45.3 ± 36.5 months. In 5 patients, sirolimus and PSL were given as induction for active nephritis, and they showed improvements in proteinuria (2.8 ± 1.9 g/day at baseline, 0.1 ± 0.1 g/day after 36 mos, p = 0.011), anti-dsDNA (107.7 ± 91.9 IU/ml and 37.0 ± 55.4 IU/ml, respectively, p = 0.178), and C3 (54.8 ± 26.1 mg/dl and 86.3 ± 18.6 mg/dl, respectively, p = 0.081). Eleven patients received sirolimus and low-dose PSL as longterm maintenance, and they showed continued improvement in C3 (90.4 ± 18.1 mg/dl and 117.7 ± 25.1 mg/dl at commencement and after 36 mos, respectively, p = 0.025), stable renal function (estimated glomerular filtration rate 58.6 ± 25.8 ml/min and 63.0 ± 29.6 ml/min, respectively, p = 0.239), and proteinuria (0.8 ± 0.7 g/day and 0.7 ± 0.7 g/day respectively, p = 0.252). Renal flare occurred in 1 patient, and another patient who had stage 4 chronic kidney disease when sirolimus was started developed endstage renal failure after 27 months. Sirolimus was discontinued in 5 patients, in 4 cases related to drug side effects. Deterioration of dyslipidemia occurred in 4 patients, but was adequately controlled with statin therapy. CONCLUSION: The preliminary evidence suggests that sirolimus may serve as an alternative treatment for patients with LN who do not tolerate standard treatment or who had a history of malignancy, and it has an acceptable longterm safety profile.
OBJECTIVE: To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients. METHODS: We retrospectively reviewed 16 class III/IV/V patients with LN who have received prednisolone (PSL) and sirolimus either as initial or maintenance treatment. RESULTS: Sixteen patients received sirolimus treatment (9 because of intolerance to standard immunosuppressants and 7 because of a history of malignancy) for 45.3 ± 36.5 months. In 5 patients, sirolimus and PSL were given as induction for active nephritis, and they showed improvements in proteinuria (2.8 ± 1.9 g/day at baseline, 0.1 ± 0.1 g/day after 36 mos, p = 0.011), anti-dsDNA (107.7 ± 91.9 IU/ml and 37.0 ± 55.4 IU/ml, respectively, p = 0.178), and C3 (54.8 ± 26.1 mg/dl and 86.3 ± 18.6 mg/dl, respectively, p = 0.081). Eleven patients received sirolimus and low-dose PSL as longterm maintenance, and they showed continued improvement in C3 (90.4 ± 18.1 mg/dl and 117.7 ± 25.1 mg/dl at commencement and after 36 mos, respectively, p = 0.025), stable renal function (estimated glomerular filtration rate 58.6 ± 25.8 ml/min and 63.0 ± 29.6 ml/min, respectively, p = 0.239), and proteinuria (0.8 ± 0.7 g/day and 0.7 ± 0.7 g/day respectively, p = 0.252). Renal flare occurred in 1 patient, and another patient who had stage 4 chronic kidney disease when sirolimus was started developed endstage renal failure after 27 months. Sirolimus was discontinued in 5 patients, in 4 cases related to drug side effects. Deterioration of dyslipidemia occurred in 4 patients, but was adequately controlled with statin therapy. CONCLUSION: The preliminary evidence suggests that sirolimus may serve as an alternative treatment for patients with LN who do not tolerate standard treatment or who had a history of malignancy, and it has an acceptable longterm safety profile.
Authors: Aleksandra Wilk; Dagmara Szypulska-Koziarska; Karolina Kędzierska-Kapuza; Jerzy Sieńko; Agnieszka Kolasa-Wołosiuk; Kazimierz Ciechanowski; Barbara Wiszniewska Journal: Med Sci Monit Date: 2019-11-02