TACROLIMUS IN THE TREATMENT OF MYH9-RELATED DISORDERS: CASE REPORT

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

TACROLIMUS IN THE TREATMENT OF MYH9-RELATED DISORDERS: CASE REPORT

Popis výsledku v původním jazyce

MYH9-related disorders (MYH9RD) belong to a group of inherited diseases caused by mutations of MYH9 gene, which encodes non-muscle myosin heavy chain IIA. The aim of the study is to report a patient with MYH9RD with progressive proteinuria (PU) treated with combination therapy of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and Tacrolimus (TAC). We report a girl with macrothrombocytopenia, Döhle like bodies in leukocytes, deafness, cataracts, hypertension, hematuria and continually increasing PU since 4 years of age reaching nephrotic level with generalized edemas at the age of 15 years. DNA analysis showed 7 known MYH9RD polymorphisms. Despite therapy with ACEi (Ramipril 0.1 mg/kg/d) and ARB (Losartan 1.0 mg/kg/d) since the age of 10 years, PU has been worsening to nephrotic range (5.4 g/24 h). The therapy with TAC has been started (TAC through level 2.8–4.0 μg/l) and has led to partial remission. After 3 month of combination therapy with TAC, ACEi and ARB, the ACEi was reduced (0.05 mg/kg/d) due to hypotension. This has led to a relapse of PU (6 g/24 h), which prompted re-increase of ACEi to the initial dosing (0.1 mg/kg/d); this combination therapy has then improved PU to 2.1 ± 0.59 g/24 h. The slopes of PU were significantly different when analyzed before TAC, on TAC + ACEi + ARB before PU relapse and on TAC + ACEi + ARB after PU relapse (+0.03,-0.74, −0.54 g/24 h/month; respectively, p = 0.019) suggesting a favorable effect of combination therapy with TAC and higher dose of ACEi and ARB. At the same time periods, the slopes of eGFR were not significantly different (−0.001, 0.037, 0.026 ml/s/1.73 m2/month; respectively, p = 0.75). The combination therapy with ACEi, ARB and TAC may lead to a significant improvement of proteinuria while preserving renal function in children with MYH9RD. We hypothesize that the therapy is effective not only via its hemodynamic changes, but also due to the TAC interaction with synaptopodin.

Název v anglickém jazyce

TACROLIMUS IN THE TREATMENT OF MYH9-RELATED DISORDERS: CASE REPORT

Popis výsledku anglicky

MYH9-related disorders (MYH9RD) belong to a group of inherited diseases caused by mutations of MYH9 gene, which encodes non-muscle myosin heavy chain IIA. The aim of the study is to report a patient with MYH9RD with progressive proteinuria (PU) treated with combination therapy of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and Tacrolimus (TAC). We report a girl with macrothrombocytopenia, Döhle like bodies in leukocytes, deafness, cataracts, hypertension, hematuria and continually increasing PU since 4 years of age reaching nephrotic level with generalized edemas at the age of 15 years. DNA analysis showed 7 known MYH9RD polymorphisms. Despite therapy with ACEi (Ramipril 0.1 mg/kg/d) and ARB (Losartan 1.0 mg/kg/d) since the age of 10 years, PU has been worsening to nephrotic range (5.4 g/24 h). The therapy with TAC has been started (TAC through level 2.8–4.0 μg/l) and has led to partial remission. After 3 month of combination therapy with TAC, ACEi and ARB, the ACEi was reduced (0.05 mg/kg/d) due to hypotension. This has led to a relapse of PU (6 g/24 h), which prompted re-increase of ACEi to the initial dosing (0.1 mg/kg/d); this combination therapy has then improved PU to 2.1 ± 0.59 g/24 h. The slopes of PU were significantly different when analyzed before TAC, on TAC + ACEi + ARB before PU relapse and on TAC + ACEi + ARB after PU relapse (+0.03,-0.74, −0.54 g/24 h/month; respectively, p = 0.019) suggesting a favorable effect of combination therapy with TAC and higher dose of ACEi and ARB. At the same time periods, the slopes of eGFR were not significantly different (−0.001, 0.037, 0.026 ml/s/1.73 m2/month; respectively, p = 0.75). The combination therapy with ACEi, ARB and TAC may lead to a significant improvement of proteinuria while preserving renal function in children with MYH9RD. We hypothesize that the therapy is effective not only via its hemodynamic changes, but also due to the TAC interaction with synaptopodin.

Druh

D - Stať ve sborníku

CEP obor

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OECD FORD obor

30217 - Urology and nephrology

Projekt

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Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

PEDIATRIC NEPHROLOGY

ISBN

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ISSN

0931-041X

e-ISSN

1432-198X

Počet stran výsledku

1

Strana od-do

1775-1775

Název nakladatele

SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA

Místo vydání

NEW YORK, NY 10013 USA

Místo konání akce

New York

Datum konání akce

1. 1. 2017

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

000408418900408