Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults

BackgroundTacrolimus is used as a steroid-sparing immunosuppressant in adults with minimal change nephrotic syndrome. However, combined treatment with tacrolimus and low-dose steroid has not been compared with high-dose steroid for induction of clinical remission in a large-scale randomized study.MethodsIn this 24-week open-label noninferiority study, we randomized 144 adults with minimal change nephrotic syndrome to receive 0.05 mg/kg twice-daily tacrolimus plus once-daily 0.5 mg/kg prednisolone, or once-daily 1 mg/kg prednisolone alone, for up to 8 weeks or until achieving complete remission. Two weeks after complete remission, we tapered the steroid to a maintenance dose of 5–7.5 mg/d in both groups until 24 weeks after study drug initiation. The primary end point was complete remission within 8 weeks (urine protein: creatinine ratio <0.2 g/g). Secondary end points included time until remission and relapse rates (proteinuria and urine protein: creatinine ratio >3.0 g/g) after complete remission to within 24 weeks of study drug initiation.ResultsComplete remission within 8 weeks occurred in 53 of 67 patients (79.1%) receiving tacrolimus and low-dose steroid and 53 of 69 patients (76.8%) receiving high-dose steroid; this difference demonstrated noninferiority, with an upper confidence limit below the predefined threshold (20%) in both intent-to-treat (11.6%) and per-protocol (17.0%) analyses. Groups did not significantly differ in time until remission. Significantly fewer patients relapsed on maintenance tacrolimus (3–8 ng/ml) plus tapered steroid versus tapered steroid alone (5.7% versus 22.6%, respectively; P=0.01). There were no clinically relevant safety differences.ConclusionsCombined tacrolimus and low-dose steroid was noninferior to high-dose steroid for complete remission induction in adults with minimal change nephrotic syndrome. Relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone. No clinically-relevant differences in safety findings were observed.

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Complete remission induced by tacrolimus and low-dose prednisolone in adult minimal change nephrotic syndrome: A pilot study

Kidney Research and Clinical Practice ◽

10.1016/j.krcp.2012.04.321 ◽

2012 ◽

Vol 31 (2) ◽

pp. 112-117 ◽

Cited By ~ 4

Author(s):

Yong Chul Kim ◽

Tae Woo Lee ◽

Hajeong Lee ◽

Ho Suk Koo ◽

Kook-Hwan Oh ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Pilot Study ◽

Complete Remission ◽

Low Dose ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change

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A Case of Frequently Relapsing Minimal-Change Nephrotic Syndrome with Steroid-Induced Psychiatric Syndrome Treated by Low-Dose, Short-Term Steroid Therapy in Combination with Cyclosporine

Case Reports in Nephrology and Dialysis ◽

10.1159/000505313 ◽

2020 ◽

Vol 10 (1) ◽

pp. 1-8

Author(s):

Isao Kondo ◽

Yohei Arai ◽

Akiyoshi Hamada ◽

Kota Yamada ◽

Shingo Shioji ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Steroid Therapy ◽

Clinical Remission ◽

Low Dose ◽

Initial Dosage ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

High Dose ◽

Short Term ◽

Psychiatric Syndrome

Adults with minimal-change nephrotic syndrome (MCNS) generally receive oral prednisolone (PSL) at an initial dosage of 1.0 mg/kg/day for a minimum of 4 weeks, with 80% of patients achieving clinical remission. However, relapses are frequent, necessitating repeated treatment with high-dose PSL. Long-term treatment with high-dose steroids increases the risk of steroid toxicities, such as diabetes mellitus, gastric complications, infections, osteoporosis, and steroid-induced psychiatric syndrome (SIPS), which may compromise the patient’s quality of life. Strategies are therefore needed to reduce the dosage and duration of steroid therapy for frequently relapsing MCNS (FRNS). Here, we suggest a new combination therapy of low-dose and short-term steroid with cyclosporine (CsA). We encountered an adult patient who developed recurrence of FRNS with depression arising from SIPS and was treated using low-dose, short-term PSL combined with CsA. He was successfully treated with PSL at an initial dosage of 0.3 mg/kg/day (20 mg/day) for just 2 weeks combined with CsA, allowing earlier induction of complete remission. We then promptly reduced the dose of PSL to below a physiological dosage (5 mg/day) over 3 weeks without relapse after episodes of SIPS and quickly resolved psychiatric symptoms. CsA in combination with PSL can reduce the initial dosage of PSL, shorten the time to remission, and easily maintain clinical remission. This protocol appears clinically useful and potentially applicable as a future treatment strategy for FRNS troubled by SIPS.

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Disseminated Strongyloidiasis in Association with Nephrotic Syndrome

Case Reports in Nephrology and Dialysis ◽

10.1159/000491632 ◽

2018 ◽

Vol 8 (2) ◽

pp. 155-160 ◽

Cited By ~ 3

Author(s):

Amirahwaty Abdullah ◽

Lydia Winnicka ◽

Charumathi Raghu ◽

Violeta Zeykan ◽

Jagmeet Singh

Keyword(s):

Nephrotic Syndrome ◽

Causal Relationship ◽

Parasitic Infection ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

High Dose ◽

The World ◽

Disseminated Strongyloidiasis

Strongyloidiasis is a well-known parasitic infection endemic in tropical and subtropical areas of the world. While most infected individuals are asymptomatic, strongyloidiasis-related glomerulopathy has not been well documented. We present a case of disseminated strongyloidiasis in a patient with minimal change nephrotic syndrome treated with high-dose corticosteroids. The remission of nephrotic syndrome after treatment of strongyloidiasis suggests a possible causal relationship between Strongyloides and nephrotic syndrome.

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A Patient with IgA Nephropathy: 5 Years after Complete Remission of Minimal Change Nephrotic Syndrome

The Ewha Medical Journal ◽

10.12771/emj.2016.39.4.118 ◽

2016 ◽

Vol 39 (4) ◽

pp. 118 ◽

Cited By ~ 1

Author(s):

Ji Won Kim ◽

Jun Hyung Park ◽

Da Hee Kim ◽

Hyung Young Kim ◽

Sang Hyun Kim ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Complete Remission ◽

Iga Nephropathy ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change

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Favorable Outcome of Low-dose Cyclosporine after Pulse Methylprednisolone in Japanese Adult Minimal-change Nephrotic Syndrome

Internal Medicine ◽

10.2169/internalmedicine.43.668 ◽

2004 ◽

Vol 43 (8) ◽

pp. 668-673 ◽

Cited By ~ 15

Author(s):

Hiroshi MATSUMOTO ◽

Toshiyuki NAKAO ◽

Tomonari OKADA ◽

Yume NAGAOKA ◽

Fumihiro TAKEGUCHI ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Low Dose ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Favorable Outcome ◽

Japanese Adult ◽

Pulse Methylprednisolone

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Minimal change nephrotic syndrome showing complete remission after resection of a neurofibroma in a type I neurofibromatosis patient

The Korean Journal of Internal Medicine ◽

10.3904/kjim.2015.016 ◽

2017 ◽

Vol 32 (1) ◽

pp. 186-189 ◽

Cited By ~ 1

Author(s):

Ji In Hyun ◽

Ji Won Min ◽

Hye Min Lee ◽

Yong Kyun Kim ◽

Eu Jin Choi ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Complete Remission ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Type I

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MON-034 A case of frequent relapse minimal change nephrotic syndrome with steroid-induced psychiatric syndromes treated by a low-dose and short-term steroid therapy in combination with cyclosporine

Kidney International Reports ◽

10.1016/j.ekir.2019.05.821 ◽

2019 ◽

Vol 4 (7) ◽

pp. S317-S318 ◽

Cited By ~ 1

Author(s):

I. Kondo ◽

Y. Arai ◽

S. Shioji ◽

H. Beppu ◽

S. Emi ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Steroid Therapy ◽

Low Dose ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Short Term ◽

Frequent Relapse

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Controlled trial of methylprednisolone pulses and low dose oral prednisone for the minimal change nephrotic syndrome.

BMJ ◽

10.1136/bmj.291.6505.1305 ◽

1985 ◽

Vol 291 (6505) ◽

pp. 1305-1308 ◽

Cited By ~ 52

Author(s):

E Imbasciati ◽

R Gusmano ◽

A Edefonti ◽

P Zucchelli ◽

C Pozzi ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Low Dose ◽

Controlled Trial ◽

Oral Prednisone ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Dose Oral

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Efficacy of Semiannual Single Fixed Low-Dose Rituximab Therapy in Steroid-Dependent Minimal Change Nephrotic Syndrome: A Case Series

Case Reports in Nephrology and Dialysis ◽

10.1159/000493189 ◽

2018 ◽

Vol 8 (3) ◽

pp. 230-237 ◽

Cited By ~ 1

Author(s):

Ryosuke Usui ◽

Yohei Tsuchiya ◽

Kosaku Nitta ◽

Minako Koike

Keyword(s):

Nephrotic Syndrome ◽

Low Dose ◽

Chemotherapy Regimen ◽

Case Series ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Cell Hyperplasia ◽

Conventional Dose ◽

Steroid Dependent ◽

Refractory Nephrotic Syndrome

The frequency of using rituximab to treat refractory nephrotic syndrome has recently been increasing, and the conventional dose of rituximab used to treat it, 375 mg/m2 body surface area once weekly for 4 weeks, has been modelled on the chemotherapy regimen for B-cell non-Hodgkin’s lymphoma. The dose and intervals of rituximab in refractory nephrotic syndrome remain controversial. Clear lymphoma cell hyperplasia is seen in lymphoma patients, but not in nephrotic syndrome patients. Since we thought that it might be possible to reduce the dose of rituximab if only used for the purpose of depleting CD20-positive B cells in nephrotic patients’ peripheral blood, we tried semiannually with a single fixed rituximab dose of 100 mg/body, and a complete remission was attained in 3 cases without treatment with prednisolone or cyclosporine. Our report strongly suggests considering appropriate dose and interval of rituximab therapy in the treatment of steroid-dependent nephrotic syndrome.

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