Disertasi

Efek Kalsitriol pada Pasien Penyakit Ginjal Diabetik: Kajian terhadap Nefrin, Podosin, Rasio Albumin Kreatinin, KIM-1, Interleukin-6 Urin dan Renin Plasma = The Effect of Calcitriol in Diabetic Kidney Disease: A Study on Urinary Nephrin, Podocin, Albumin Creatinine Ratio, Interleukin-6, KIM-1, and Plasma Renin.

Berbagai studi menunjukkan efek renoprotektif vitamin D pada progresivitas penyakit ginjal diabetik (PGD). Namun, studi efek renoprotektif kalsitriol pada pasien PGD tahap awal masih terbatas. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian kalsitriol terhadap kerusakan podosit, penanda tubular, inflamasi ginjal, sistem renin-angiotensin-aldosteron (SRAA) dan albuminuria pada pasien PGD tahap awal. Studi ini merupakan uji klinis acak tersamar ganda pada 120 pasien PGD dengan eLFG > 45 mL/min/1.73 m2 dan rasio albumin kreatinin urin (RAKU) > 30 mg/g di RSCM dan RS Pelni periode Juli 2022–Agustus 2023. Subjek dibagi menjadi 2 kelompok, dengan jumlah 60 subjek menerima kalsitriol 0,25 mcg/hari dan 60 subjek menerima plasebo, diamati selama 6 bulan. Kerusakan podosit diukur dengan nefrin dan podosin urin. Kerusakan tubular dan inflamasi dinilai dengan KIM-1 dan IL-6 urin. Efek terhadap aktivitas RAS dinilai dengan renin plasma. Setelah follow-up 6 bulan, dilakukan analisis terhadap 60 subjek kelompok kalsitriol dan 59 subjek kelompok plasebo. Terjadi penurunan nefrin lebih banyak pada kelompok kalsitriol - 326 (-1152–1063) ng/mL dibandingkan plasebo -152 (- 1505–1054) ng/mL, tetapi secara statistik tidak bermakna (p = 0,215). Tidak terjadi perbedaan perubahan podosin pada kelompok kalsitriol dan plasebo 0,03 (-0,07– 0,19) vs 0,01 (-0,08–0,11) ng/mL; p = 0,427. Diamati penurunan RAKU lebih tinggi pada kelompok kalsitriol -37,63 (-138,98–13,87) mg/g dibandingkan plasebo -22,17 (-74,77–380,49) mg/g yang secara statistik tidak bermakna; p = 0,225. Kadar KIM-1 bulan keenam kelompok kalsitriol 0,51 (0,2–1,56) ng/mL lebih rendah bermakna dibandingkan kelompok plasebo 0,99 (0,31–2,86) ng/mL; p = 0,020. Didapatkan pula peningkatan IL-6 lebih rendah pada kelompok kalsitriol 0,12 (- 0,72–1,33) pg/mL dibandingkan plasebo 1,60 (-0,05–4,99) pg/mL yang secara statistik bermakna (p = 0,030). Kalsitriol menurunkan plasma renin -9,42 (-458,98– 447,52) pg/mL sedangkan renin meningkat pada plasebo [166,08 (-148,04–473,37) pg/mL, tetapi secara statistik tidak bermakna (p = 0,919). Ditemukan korelasi kuat antara KIM-1 dan IL-6 kedua kelompok (r = 0,677, p = < 0,001) dan korelasi moderat perubahan IL-6 dengan nefrin (r = 0,342, p = 0,007) kelompok kalsitriol. Simpulan: Pemberian kalsitriol 0,25 mcg/hari selama 6 bulan menyebabkan penurunan bermakna kadar IL-6 dan KIM-1 urin. Studi ini mendapatkan perubahan IL-6 urin berhubungan kuat dengan perubahan KIM-1, dan berhubungan moderat dengan perubahan nefrin urin.
Kata kunci: albuminuria, IL-6 urin, kalsitriol, KIM-1 urin, nefrin, penyakit ginjal diabetik, podosin, renin plasma


Previous studies demonstrated the renoprotective effects of vitamin D in slowing the progression of diabetic kidney disease (DKD). However, limited evidence exists regarding the impact of calcitriol during the early stages of DKD. This study aims to investigate the effects of calcitriol on podocytopathy, tubulopathy, inflammatory markers, the renin-angiotensin-aldosterone system (RAAS), and albuminuria in the early stages of DKD. This double-blind, randomized clinical trial involved 120 DKD patients with eGFR > 45 mL/min/1.73m2 and urinary albumin creatinine ratio (UACR) > 30 mg/g at RSCM and Pelni Hospital from July 2022 to August 2023. Subjects were randomly assigned to receive either 0.25 mcg/day of calcitriol or a placebo for six months. Podocytopathy was assessed through urinary nephrin and podocyte measurements. Tubular injury and inflammation were represented by urinary KIM-1 and IL-6, respectively. The impact on RAAS was measured through plasma renin levels. After a six-month follow-up, an analysis was conducted on 60 subjects receiving calcitriol and 59 subjects on placebo. The calcitriol group exhibited a decrease in nephrin -326 (-1152–1063) ng/mL, whereas the placebo group showed a decrease of-152 (-1505–1054) ng/mL, but statisticaly not significant (p = 0.215). There was no significant difference in podocin changes between the calcitriol and placebo groups 0.03 (-0.07–0.19) vs. 0.01 (-0.08–0.11) ng/mL; p = 0.427. UACR showed a greater decrease in the calcitriol group -37.63 (-138.98–13.87) mg/g compared to the placebo group -22.17 (-74.77–380.49) mg/g; but was not significant (p = 0.225). KIM-1 level in the calcitriol group in the sixth month was 0.51 (0.2–1.56) ng/mL, significantly lower than that of placebo 0,99 (0,31–2.86) ng/mL; p = 0.020. The increase in IL-6 was significantly less pronounced in calcitriol 0.12 (-0.72–1.33) pg/mL compared to the placebo group 1.60 (-0.05–4.99) pg/mL; p = 0.030. Calcitriol lowered plasma renin -9.42 (-458.98–447.52) pg/mL, while those on placebo experienced renin increase 166.08 (-148.04–473.37) pg/mL; p = 0.919. A strong correlation was observed between change in urinary KIM-1 and change in urinary IL-6 in both groups (r = 0.677, p = < 0.001). Additionally, there was a moderate correlation between change in urinary IL-6 and change in urinary nephrin (r = 0.342, p = 0.007) in those receiving calcitriol. Conclusion: The administration of 0.25 mcg/day of calcitriol for 6 months resulted in a significant reduction in urinary IL-6 and KIM-1 levels. This study reported that changes in urinary IL-6 was strongly associated with changes in urinary KIM-1, and moderately associated with changes in urinary nephrin.
Keywords: albuminuria, calcitriol, diabetic kidney disease, nephrin, plasma renin, podocin, urinary IL-6, urinary KIM-1.