Tesis

Korelasi Perubahan Kadar Neutrophil Gelatinase - Associated Lipocalin (NGAL) Urin terhadap Perubahan Estimasi Laju Filtrasi Glomerulus dan Perubahan Kadar Albuminuria dalam Satu Tahun pasca Corona Virus Disease-19 (COVID-19) = Correlation of Changes in Urinary Neutrophil Gelatinase- Associated Lipocalin (uNGAL) Levels with Changes in Estimated Glomerular Filtration Rates and Changes in Albuminuria Levels in One Year after Corona Virus Disease-19 (COVID-19).

Latar Belakang: Corona Virus Disease 2019 (COVID-19) dapat menyebabkan kerusakan ginjal pada fase akut dan jangka panjang. Keterlibatan ginjal jangka panjang berupa perubahan estimasi laju filtrasi glomerulus (eLFG) dan albuminuria. Neutrophil Gelatinase-Associated Lipocalin (NGAL) urin sebagai penanda kerusakan tubulus meningkat pada fase akut COVID-19 dan juga penyakit ginjal kronik non-COVID. Belum diketahui korelasi jangka panjang kerusakan tubulus dengan kerusakan glomerulus pasca COVID-19. Tujuan : Mengetahui korelasi perubahan kadar NGAL urin dengan perubahan eLFG dan kadar albuminuria serta untuk mengetahui hubungan tren kadar NGAL urin dengan eLFG dan albuminuria, dalam satu tahun pasca COVID-19. Metode : Studi kohort retrospektif terhadap 73 pasien COVID-19 yang dirawat di rumah sakit Cipto Mangunkusumo (RSCM). Sampel darah dan urin diperiksa untuk eLFG, NGAL urin dan albuminuria, pada fase akut, tiga bulan dan satu tahun pasca COVID-19. Analisis korelasi perubahan kadar NGAL urin terhadap perubahan eLFG dan kadar albuminuria dilakuan dengan uji Spearman. Analisis regresi linier dilakukan untuk menilai variabel perancu terhadap hubungan tersebut. Analisis general linear model digunakan untuk menilai hubungan tren kadar NGAL urin dengan eLFG dan albuminuria dalam satu tahun pasca COVID-19. Hasil: Subjek yang direkrut pada fase akut mayoritas berusia muda, fungsi ginjal baik dan derajat ringan-sedang. Kadar NGAL urin menurun dan eLFG meningkat dari fase akut sampai satu tahun pasca COVID-19, sedangkan kadar albuminuria menurun pada tiga bulan pertama dan kemudian meningkat. Tidak didapatkan korelasi perubahan NGAL urin dengan perubahan eLFG dan albuminuria dalam satu tahun pasca COVID-19. Pada analisis subgrup korelasi perubahan kadar NGAL urin dengan perubahan eLFG didapatkan korelasi positif sedang pada periode T0-T3 pada subgrup diabetes, dan korelasi negatif lemah pada periode T3-T12 pada tiga subgrup yakni kategori usia < 60 tahun, tanpa diabetes, dan derajat keparahan sedang. Terdapat korelasi negatif sedang yang bermakna antara perubahan kadar NGAL urin dengan perubahan kadar albuminuria pada T3-T12 pada kelompok subgrup usia ≥ 60 tahun (r = -0,731; p = 0,005). Tidak ada hubungan tren kadar NGAL urin dengan eLFG dan albuminuria. Simpulan Tidak didapatkan korelasi perubahan NGAL urin dengan perubahan eLFG dan albuminuria dalam 1 tahun pasca COVID-19. Tidak didapatkan hubungan tren kadar NGAL urin dengan eLFG dan albuminuria antara saat rawat inap sampai satu tahun pasca COVID-19.
Kata kunci: albuminuria, Corona Virus Disease 2019, estimasi laju filtrasi glomerulus, Neutrophil Gelatinase-Associated Lipocalin urin


Background: Coronavirus disease 2019 (COVID-19) may cause kidney damage in both the acute and long-term phases. Long-term kidney involvement includes changes in estimated glomerular filtration rate (eGFR) and albuminuria. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a marker of tubular damage is increased in the acute phase of COVID-19 and in chronic kidney disease due to non-COVID etiologies. The long-term correlation between tubular damage and glomerular damage after COVID-19 is still unknown. Objective: To determine the correlation of the changes in uNGAL levels with the changes in eGFR and albuminuria levels and to determine the relationship between trends in uNGAL levels with eGFR and albuminuria in one year after COVID-19. Methods: A retrospective cohort study of 73 COVID-19 patients hospitalized in Cipto Mangunkusumo referral hospital was performed. Blood and urine samples were tested for eGFR, uNGAL, and albuminuria levels in the acute phase, three months and one year after COVID-19. The correlation of the changes in uNGAL levels with the changes in eGFR and albuminuria were analyzed with Spearman correlation test. A linear regression test was performed to assess the confounding variables in these relationships. General linear model analysis was used to assess the relationships between trends in uNGAL levels with eGFR and albuminuria. Results: Subjects’ recruited in the acute phase were mostly young, with good kidney function and mild to moderate severity of COVID-19. The uNGAL levels decreased and eGFR increased from the acute phase to one year after COVID-19, while the albuminuria levels decreased in the first three months and then increased. There were no correlation between the changes in uNGAL with changes in eGFR and albuminuria within one year after COVID-19. In the subgroup analysis, correlations of changes in uNGAL levels with changes in eGFR were found in the T0-T3 period in the diabetes subgroup; and in the T3-T12 period in three subgroups: age< 60 years, subjects without diabetes, and subjects with moderate severity. There was a significant moderate negative correlation between changes in uNGAL levels and changes in albuminuria levels at T3-T12 period in the subgroup aged ≥60 years (r = -0.731; p = 0.005). There were no relationships between trends in uNGAL levels with eGFR and albuminuria. Conclusions There were no correlation between changes in uNGAL levels with changes in eGFR and albuminuria within 1 year after COVID-19. There were no correlation between trends in u NGAL levels with eGFR and albuminuria between acute phase and 1 year after COVID-19.
Key words: albuminuria, Coronavirus disease 2019, estimated glomerular filtration rate, urinary neutrophil gelatinase-associated lipocalin