New Combination Therapy Potentially Protects Kidneys from the Impact of Methanol Intoxication

New Combination Therapy Potentially Protects Kidneys from the Impact of Methanol Intoxication


Located in the Postgraduate Hall, 3rd Floor of the Postgraduate Building, Udayana University, the Doctoral Study Program in Medical Science, Faculty of Medicine, Udayana University held an open Doctoral Promotion examination with the candidate promovendus, dr. Prayuda, M.Biomed, Sp.PD., with the dissertation title "Hydroxychloroquine, Folinic Acid, and the Combination of Hydroxychloroquine and Folinic Acid Affect Low Expression of Endothelin-1, Nucleotide-Binding Domain Leucine-Rich Containing Family Pyrin Domain-Containing-3, and Tubular Injury Score in Rabbits with Acute Kidney Injury Due to Methanol". (5/15/2025)


Methanol intoxication has a fairly high case fatality rate and experiences a very significant increase if acute kidney injury due to methanol occurs. The pathophysiology of acute kidney injury due to methanol can be mediated by ET-1 and NLRP 3. Research is needed to determine the role of folinic acid therapy which is a standard therapy and hydroxychloroquine through the mechanism of inhibition of ET-1 and NLRP3 expression in conditions of acute kidney injury due to methanol.


The design of this study was a pure experimental study randomized posttest only control group design comparing 4 treatment groups, namely a rabbit model of acute kidney injury due to methanol that received aquabides (control), hydroxychloroquine, folinic acid, and a combination of hydroxychloroquine and folinic acid. The results evaluated: histopathology of tubular injury scores, immunohistochemistry of NLRP3 and ET-1 expression. Analysis of the difference test using the Anova statistical test, and post hoc with LSD.


There was a significant difference (p < 0.001) in the percentage of ET-1 expression between controls with hydroxychloroquine, folinic acid and a combination of hydroxychloroquine and folinic acid. There was a significant difference (p< 0.001) in the percentage of NLRP3 expression between controls with hydroxychloroquine, folinic acid and a combination of hydroxychloroquine and folinic acid. There was a significant difference (p< 0.001) in the percentage of Tubular Injury Score between controls with the hydroxychloroquine, folinic acid, and hydroxychloroquine + folinic acid groups, as well as between folinic acid and the combination of hydroxychloroquine + folinic acid and between hydroxychloroquine and the combination of hydroxychloroquine + folinic acid. Both therapies have a synergistic effect in repairing kidney damage through complementary mechanisms.


Administration of hydroxychloroquine and/or folinic acid causes lower expression of ET-1, NLRP3 and renal tubular injury scores compared to controls in a rabbit model of acute kidney injury due to methanol. Further research is needed on patients with acute kidney injury due to methanol intoxication to assess the effectiveness of therapy.


This examination was led by the Coordinator of the Doctoral Study Program in Medical Sciences, Faculty of Medicine, Udayana University, Prof. Dr. dr. I Made Jawi, M.Kes., with the examining team:

1. Prof. Dr. Dr. I Gde Raka Widiana, Sp.PD-KGH (Promoter)

2. Prof. Dr. Dr. Ketut Suega, Sp.PDKHOM (Copromotor I)

3.Dr. Dr. Yenny Kandarini, Sp.PDKGH (Copromotor II)

4. Prof. Dr. Dr. I Made Jawi, M. Kes

5. Prof. Dr. Dr. I Wayan Putu Sutirta Yasa, M.Sc

6. Prof. Dr. Dr. HM. Bambang Purwanto, Sp.PD-KGH, FINASIM

7. Prof. Dr. Dr. Putu Anda Tusta Adiputra, Sp.B.Subsp.Onk(K)

8.Dr. Dr. Luh Putu Ratna Sundari, M. Biomed

9.Dr. drh. Ida Bagus Oka Winaya, M.Kes

10.Dr. Dr. Ni Wayan Winarti, S.Ked., Sp.PA., Subsp.U.R.L(K)


With academic invitation:

1. Dr. dr. I Gusti Putu Hendra Sanjaya, Sp.B., Sp.BP-RE

2. Dr. dr. I Gde Ardika Nuaba, Sp.THT-KL(K)., FICS

3. Dr. dr. Luh Oliva Saraswati Suastika, Sp.JP Eko.(K), FIHA

4. Dr. dr. I Wayan Subawa, Sp.OT.Subsp,KP(K)

5. Dr. dr. I Gde Sastra Winata, M.Biomed., Sp.OG., Subsp.Onk


In this exam, Dr. dr. Prayuda, M.Biomed, Sp.PD., was declared to have passed as the 458th Graduate Doctor of the Doctoral Degree Program in Medical Sciences, Faculty of Medicine, Udayana University with the predicate Very Satisfactory