Tesis

Pengaruh Pemberian Sinbiotik Terhadap Kadar Indoxyl Sulfate, Konstipasi dan Kualitas Hidup Akibat Konstipasi Pada Pasien Hemodialisis Kronik = Effects of Synbiotics Supplementation on Level of Indoxyl Sulfate, Constipation and Quality of Life Related to Constipation of Hemodialysis Patients.

Latar Belakang : Disbiosis mikrobiota usus yang terjadi pada pasien PGK-HD ditandai dengan peningkatan bakteri proteolitik dan penurunan bakteri sakarolitik. Hal ini menyebabkan peningkatan kadar toksin uremikum seperti indoxyl sulfate (IS) yang merupakan hasil metabolisme asam amino tryptophan dan penurunan Short Chain Fatty Acid (SCFA). Selain itu disbiosis usus juga menyebabkan konstipasi yang sering dialami pasien PGK HD. Konstipasi yang berkepanjangan akan menurunkan kualitas hidup pasien. IS tidak bisa diekskresikan melalui proses hemodialisis karena 90% terikat dengan albumin. Akumulasi IS pada pasien PGKHD menjadi salah satu faktor risiko non-tradisional yang meningkatkan risiko kardiovaskular pada pasien PGK-HD. Salah satu cara memperbaiki disbiosis mikrobiota usus pada pasien PGK-HD melalui pemberian sinbiotik. Tujuan : Mengetahui peranan pemberian sinbiotik terhadap kadar IS, konstipasi dan kualitas hidup akibat konstipasi pada pasien hemodialisis kronik Metode : Penelitian ini merupakan uji klinis acak tersamar ganda dengan plasebo yang dilakukan di unit hemodialisis Rumah Sakit Cipto Mangunkusumo, Agustus Desember 2020. Subjek yang memenuhi kriteria inklusi lalu dirandom kedalam dua kelompok yaitu kelompok sinbiotik yang mendapatkan kapsul yang berisi Bifidobacterium longum, Lactobacillus acidophilus (5x10 9 CFU) dan Fructooligosaccharides (FOS) 60 mg sedangkan kelompok plasebo mendapatkan kapsul yang berisikan saccharum lactis. Kedua kelompok mendapatkan 2 kapsul/hari selama masa observasi 60 hari. Konstipasi dinilai menggunakan kuesioner PACSYM dan kualitas hidup akibat konstipasi menggunakan kuesioner PAC-QOL. Kadar toksin indoxyl sulfate, PAC-SYM dan PAC-QOL dinilai di awal dan akhir penelitian. Analisis gizi menggunakan food recall-24 hours juga dinilai diawal dan akhir penelitian. Hasil : Dari 100 pasien, 60 pasien memenuhi kriteria inklusi dan diacak ke kelompok sinbiotik (n=30) dan plasebo (n=30). Tidak ada perbedaan bermakna pada karakteristik awal kedua kelompok. Pada kelompok sinbiotik didapatkan medium kadar IS sebelum dan sesudah adalah 26,98 (22,78-34,77) mg/L dan 27,94 (23,2534,05) mg/L sedangkan pada kelompok plasebo adalah 20,95 (17,25-27,07) mg/L dan 22,88 (18,20-29,38) mg/L. Hasil analisis menggunakan uji analisis bivariat Mann Whitney menunjukan tidak ada perbedaan bermakna selisih penurunan kadar IS pada kedua kelompok pasca pemberian sinbiotik bila dibandingkan dengan plasebo (p=0,438). Studi ini juga mendapatkan adanya perbaikan pada gejala konstipasi (p=0,006) dan kualitas hidup akibat konstipasi (p=0,001) pada kelompok sinbiotik bila dibandingkan dengan kelompok plasebo. Simpulan Suplementasi sinbiotik dapat, memperbaiki gejala konstipasi dan kualitas hidup akibat konstipasi pada pasien hemodialisis kronik meskipun belum dapat membuktikan manfaatnya dalam menurunkan kadar toksin indoxyl sulfate
Kata Kunci indoxyl sulfate, konstipasi, kualitas hidup, sinbiotik, hemodialisis, penyakit ginjal kronik


Background Gut dysbiosis that occurs in hemodialysis patients is characterized by an increase in proteolytic bacteria and a decrease in saccharolytic bacteria. This condition causes an increase in uremic toxin levels such as indoxyl sulfate which is the result of tryptophan amino acid metabolism and decrease in Short Chain Fatty Acid (SCFA). In addition, gut dysbiosis can also aggravate the symptoms of constipation that are often experienced by hemodialysis patients. Prolonged constipation will reduce the patient’s quality of life. Indoxyl sulfate cannot be excreted through the hemodialysis because 90% is bound to albumin. The accumulation of indoxyl sulfate in hemodialysis patient is one of the non-traditional risk factors that increase the risk of cardiovascular events in CKD. One way to improve gut dysbiosis in hemodialysis patients is through the administration of synbiotics Objective Knowing the role of synbiotics administration on indoxyl sulfate level, constipation and quality of life due to constipation in chronic hemodialysis patients. Methods This was a randomized double blind placebo controlled trial conducted in Cipto Mangunkusumo Hospital from August 2020 to December 2020. Subjects with inclusion criteria and gave informed consent were randomized into two groups: synbiotics group which given Bifidobacterium longum, Lactobacillus acidophilus (5x10 9 CFU) and fructooligosaccharide (FOS) 60 mg meanwhile placebo group received capsule containing saccharum lactis. Both group received two capsules/day during 8 weeks observation. Constipation symptoms was assessed using the PACSYM questionnaire and quality of life due to constipation using the PAC-QOL questionnaire. Indoxyl sulfate, PAC-SYM and PAC-QOL were assessed at the start and end of the study. Food intake data during study were taken twice at the beginning and end of the study using 24-hours food recall. Results From 100 patients, 60 fulfilled inclusion criteria and randomized into synbiotics (n=30) and placebo groups (n=30). At baseline characteristics, there were no significant difference between synbiotics and placebo group. In the synbiotics groups, the median level of indoxyl sulfate before and after were 26,98 (22,78-34,77) mg/L and 27,94 (23,25-34,05) mg/L while in the placebo group were 20,95(17,2527,07) mg/L and 22,88 (18,20-29,38) mg/L.The result of the analysis using Mann Whitney test showed that there was no significant difference in the level of indoxyl sulfate in the two groups after giving synbiotics (p=0,438). This study also found improvement in constipation symptoms (p=0,006) and quality of life due to constipation (p=0,01) in the synbiotics groups when compared to placebo groups. Conclusion Synbiotics supplementation can not reduce level of indoxyl sulfate but can improve symptoms of constipation and quality of life due to constipation in chronic hemodialysis patients
Keywords indoxyl sulfate, constipation, quality of life, synbiotics, hemodialysis, chronic kidney disease