Araştırma Makalesi
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The Effects of Dipeptidyl Peptidase-4 Inhibitors on Kidney Function in Advanced CKD

Yıl 2023, Cilt: 7 Sayı: 3, 166 - 173, 25.10.2023
https://doi.org/10.34084/bshr.1347133

Öz

Objective: This study aimed to investigate the effects of DPP-4 inhibitors on kidney function in type 2 diabetes mellitus patients with stages 3-5 chronic kidney disease, focusing on estimated glomerular filtration rate and proteinuria.
Methods: This is a retrospective case-control design, and data were collected from a single hospital's software and the Turkish Ministry of Health's National Data Tracking System. Diabetic patients with T2DM and CKD stages 3-5 were included, with dipeptidyl peptidase-4 inhibitor users (n=118) and non-users (n=48) forming the intervention and control groups, respectively. Baseline demographics, clinical characteristics, and outcomes were compared between groups.
Results: At baseline, both groups demonstrated similar age, gender distribution, body mass index, and eGFR. Over a 12-month follow-up, while slight improvements in eGFR were observed in the intervention group and minor reductions in the control group, these changes did not reach statistical significance (p>0.05). Proteinuria showed a stable trend in the intervention group, whereas a significant increase was noted in the control group (p=0.035). Age significantly correlated with eGFR (p<0.001) but not proteinuria (p=0.156). The study found that DPP-4 inhibitor users experienced a statistically significant reduction in HbA1c levels (p=0.041) compared to minimal changes in the control group.
Conclusion: The study suggests potential renoprotective effects of DPP-4 inhibitors in T2DM patients with advanced CKD, as evidenced by trends in eGFR and proteinuria stabilization.

Teşekkür

The authors would like to thank Prof. Dr. Hamad Dheir for his ideas and suggestions for improving the manuscript. Warm thanks to Dr. Fevziye Türkoğlu Genç for her participation in the data collection and preparation of the spreadsheet.

Kaynakça

  • Hansen L, Deacon CF, Orskov C, Holst JJ. Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology. 1999;140(11):5356-5363. doi:10.1210/endo.140.11.7143
  • Hocher B, Reichetzeder C, Alter ML. Renal and cardiac effects of DPP4 inhibitors--from preclinical development to clinical research. Kidney Blood Press Res. 2012;36(1):65-84. doi:10.1159/000339028
  • Hjøllund KR, Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs. Diabetologia. 2011;54(8):2206-2208. doi:10.1007/s00125-011-2168-7
  • Vergès B, Bonnard C, Renard E. Beyond glucose lowering: glucagon-like peptide-1 receptor agonists, body weight and the cardiovascular system. Diabetes Metab. 2011;37(6):477-488. doi:10.1016/j.diabet.2011.07.001
  • Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114(11):1788-1803. doi:10.1161/CIRCRESAHA.114.301958
  • Daza-Arnedo R, Rico-Fontalvo JE, Pájaro-Galvis N, Leal-Martínez V, Abuabara-Franco E, Raad-Sarabia M, et al. Dipeptidyl Peptidase-4 Inhibitors and Diabetic Kidney Disease: A Narrative Review. Kidney Med. 2021;3(6):1065-1073. doi:10.1016/j.xkme.2021.07.007
  • Kawanami D, Takashi Y, Takahashi H, Motonaga R, Tanabe M. Renoprotective Effects of DPP-4 Inhibitors. Antioxidants (Basel). 2021;10(2). doi:10.3390/antiox10020246
  • Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C. Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag. 2008;4(4):753-768. doi:10.2147/vhrm.s1707
  • Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis. 2013;226(2):305-314. doi:10.1016/j.atherosclerosis.2012.09.012
  • Kang SM, Park JH. Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control. Clin Med Insights Endocrinol Diabetes. 2021;14:11795514211051698. doi:10.1177/11795514211051698
  • Nistala R, Meuth AI, Smith C, An J, Habibi J, Hayden MR, et al. DPP4 inhibition mitigates ANG II-mediated kidney immune activation and injury in male mice. Am J Physiol Renal Physiol. 2021;320(3):F505-F517. doi:10.1152/ajprenal.00565.2020
  • Shi S, Koya D, Kanasaki K. Dipeptidyl peptidase-4 and kidney fibrosis in diabetes. Fibrogenesis Tissue Repair. 2016;9:1. doi:10.1186/s13069-016-0038-0
  • Relle M, Cash H, Brochhausen C, Strand D, Menke J, Galle PR, et al. New perspectives on the renal slit diaphragm protein podocin. Mod Pathol. 2011;24(8):1101-1110. doi:10.1038/modpathol.2011.58
  • Christensen EI, Birn H. Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol. 2002;3(4):256-266. doi:10.1038/nrm778
  • Benetti A, Martins FL, Sene LB, Shimizu MHM, Seguro AC, Luchi WM, et al. Urinary DPP4 correlates with renal dysfunction, and DPP4 inhibition protects against the reduction in megalin and podocin expression in experimental CKD. Am J Physiol Renal Physiol. 2021;320(3):F285-F296. doi:10.1152/ajprenal.00288.2020
  • Kanasaki K. The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin. Clin Sci . 2018;132(4):489-507. doi:10.1042/CS20180031
  • Groop PH, Cooper ME, Perkovic V, Emser A, Woerle HJ, von Eynatten M. Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction. Diabetes Care. 2013;36(11):3460-3468. doi:10.2337/dc13-0323
  • Smelcerovic A, Kocic G, Gajic M, Tomovic K, Djordjevic V, Stankovic-Djordjevic D, et al. DPP-4 Inhibitors in the Prevention/Treatment of Pulmonary Fibrosis, Heart and Kidney Injury Caused by COVID-19-A Therapeutic Approach of Choice in Type 2 Diabetic Patients? Front Pharmacol. 2020;11:1185. doi:10.3389/fphar.2020.01185
  • Hirakawa H, Zempo H, Ogawa M, Watanabe R, Suzuki JI, Akazawa H, et al. A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice. PLoS One. 2015;10(3):e0119360. doi:10.1371/journal.pone.0119360
  • Tomovic K, Lazarevic J, Kocic G, Deljanin-Ilic M, Anderluh M, Smelcerovic A. Mechanisms and pathways of anti-inflammatory activity of DPP-4 inhibitors in cardiovascular and renal protection. Med Res Rev. 2019;39(1):404-422. doi:10.1002/med.21513
  • Srivastava SP, Goodwin JE, Kanasaki K, Koya D. Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs. Genes . 2020;11(2). doi:10.3390/genes11020211
  • Zhang KW, Liu SY, Jia Y, Zou ML, Teng YY, Chen ZH, et al. Insight into the role of DPP-4 in fibrotic wound healing. Biomed Pharmacother. 2022;151:113143. doi:10.1016/j.biopha.2022.113143
  • Nitta K, Okada K, Yanai M, Takahashi S. Aging and chronic kidney disease. Kidney Blood Press Res. 2013;38(1):109-120. doi:10.1159/000355760
  • Denic A, Glassock RJ, Rule AD. Structural and Functional Changes With the Aging Kidney. Adv Chronic Kidney Dis. 2016;23(1):19-28. doi:10.1053/j.ackd.2015.08.004

İleri Evre Kronik Böbrek Hastalarında, Dipeptidl Peptidaz-4 İnhibitörlerinin Böbrek Fonksiyonu Üzerindeki Etkisi

Yıl 2023, Cilt: 7 Sayı: 3, 166 - 173, 25.10.2023
https://doi.org/10.34084/bshr.1347133

Öz

Amaç: Bu çalışmada, tahmini glomerüler filtrasyon hızı ve proteinüriye odaklanarak, evre 3-5 kronik böbrek hastalığı olan tip 2 diabetes mellitus hastalarında Dipeptidl Peptidaz-4 nhibitörlerinin böbrek fonksiyonu üzerindeki etkilerini araştırmayı amaçladık.
Yöntemler: Çalışma retrospektif vaka kontrol olarak tasarlandı. Veriler tek bir hastanenin yazılımından ve T.C. Sağlık Bakanlığı Ulusal Veri Takip Sisteminden toplanmıştır. Hastalar, vildaglatin kullanan (Müdahele; n=118) ve kullanmayanlar (kontrol; n=48) tip 2 diyabet ve aynı zamanda evre 3-5 kronik böbrek hstalarında oluşturuldu. Temel demografik özellikler, klinik özellikler ve sonuçlar gruplar arasında karşılaştırıldı.
Bulgular: Başlangıçta, her iki grup da benzer yaş, cinsiyet dağılımı, vücut kitle indeksi ve tGFH gösterdi. 12 aylık takipte, müdahale grubunda tGFH'da hafif iyileşmeler ve kontrol grubunda hafif azalmalar gözlenirken, bu değişiklikler istatistiksel olarak anlamlı bulunmadı (p>0,05). Proteinüri müdahale grubunda istikrarlı bir eğilim gösterirken, kontrol grubunda anlamlı bir artış kaydedildi (p=0,035). Yaş, tGFH ile anlamlı korelasyon gösterirken (p<0.001) proteinüri ile korelasyon göstermedi (p=0.156). Çalışma da, vildagliptin kullanıcılarının, kontrol grubundaki minimum değişikliklerle karşılaştırıldığında HbA1c düzeylerinde istatistiksel olarak anlamlı bir düşüş (p=0,041) yaşadığını saptandı.
Sonuç: Çalışma, tGFH ve proteinüri stabilizasyonundaki eğilimlerin kanıtladığı gibi, ilerlemiş kronik böbrek yetmezliği olan T2DM hastalarında DPP-4 inhibitörlerinin potansiyel renoprotektif etkilerini göstermektedir.

Kaynakça

  • Hansen L, Deacon CF, Orskov C, Holst JJ. Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology. 1999;140(11):5356-5363. doi:10.1210/endo.140.11.7143
  • Hocher B, Reichetzeder C, Alter ML. Renal and cardiac effects of DPP4 inhibitors--from preclinical development to clinical research. Kidney Blood Press Res. 2012;36(1):65-84. doi:10.1159/000339028
  • Hjøllund KR, Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs. Diabetologia. 2011;54(8):2206-2208. doi:10.1007/s00125-011-2168-7
  • Vergès B, Bonnard C, Renard E. Beyond glucose lowering: glucagon-like peptide-1 receptor agonists, body weight and the cardiovascular system. Diabetes Metab. 2011;37(6):477-488. doi:10.1016/j.diabet.2011.07.001
  • Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114(11):1788-1803. doi:10.1161/CIRCRESAHA.114.301958
  • Daza-Arnedo R, Rico-Fontalvo JE, Pájaro-Galvis N, Leal-Martínez V, Abuabara-Franco E, Raad-Sarabia M, et al. Dipeptidyl Peptidase-4 Inhibitors and Diabetic Kidney Disease: A Narrative Review. Kidney Med. 2021;3(6):1065-1073. doi:10.1016/j.xkme.2021.07.007
  • Kawanami D, Takashi Y, Takahashi H, Motonaga R, Tanabe M. Renoprotective Effects of DPP-4 Inhibitors. Antioxidants (Basel). 2021;10(2). doi:10.3390/antiox10020246
  • Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C. Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag. 2008;4(4):753-768. doi:10.2147/vhrm.s1707
  • Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. Atherosclerosis. 2013;226(2):305-314. doi:10.1016/j.atherosclerosis.2012.09.012
  • Kang SM, Park JH. Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control. Clin Med Insights Endocrinol Diabetes. 2021;14:11795514211051698. doi:10.1177/11795514211051698
  • Nistala R, Meuth AI, Smith C, An J, Habibi J, Hayden MR, et al. DPP4 inhibition mitigates ANG II-mediated kidney immune activation and injury in male mice. Am J Physiol Renal Physiol. 2021;320(3):F505-F517. doi:10.1152/ajprenal.00565.2020
  • Shi S, Koya D, Kanasaki K. Dipeptidyl peptidase-4 and kidney fibrosis in diabetes. Fibrogenesis Tissue Repair. 2016;9:1. doi:10.1186/s13069-016-0038-0
  • Relle M, Cash H, Brochhausen C, Strand D, Menke J, Galle PR, et al. New perspectives on the renal slit diaphragm protein podocin. Mod Pathol. 2011;24(8):1101-1110. doi:10.1038/modpathol.2011.58
  • Christensen EI, Birn H. Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol. 2002;3(4):256-266. doi:10.1038/nrm778
  • Benetti A, Martins FL, Sene LB, Shimizu MHM, Seguro AC, Luchi WM, et al. Urinary DPP4 correlates with renal dysfunction, and DPP4 inhibition protects against the reduction in megalin and podocin expression in experimental CKD. Am J Physiol Renal Physiol. 2021;320(3):F285-F296. doi:10.1152/ajprenal.00288.2020
  • Kanasaki K. The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin. Clin Sci . 2018;132(4):489-507. doi:10.1042/CS20180031
  • Groop PH, Cooper ME, Perkovic V, Emser A, Woerle HJ, von Eynatten M. Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction. Diabetes Care. 2013;36(11):3460-3468. doi:10.2337/dc13-0323
  • Smelcerovic A, Kocic G, Gajic M, Tomovic K, Djordjevic V, Stankovic-Djordjevic D, et al. DPP-4 Inhibitors in the Prevention/Treatment of Pulmonary Fibrosis, Heart and Kidney Injury Caused by COVID-19-A Therapeutic Approach of Choice in Type 2 Diabetic Patients? Front Pharmacol. 2020;11:1185. doi:10.3389/fphar.2020.01185
  • Hirakawa H, Zempo H, Ogawa M, Watanabe R, Suzuki JI, Akazawa H, et al. A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice. PLoS One. 2015;10(3):e0119360. doi:10.1371/journal.pone.0119360
  • Tomovic K, Lazarevic J, Kocic G, Deljanin-Ilic M, Anderluh M, Smelcerovic A. Mechanisms and pathways of anti-inflammatory activity of DPP-4 inhibitors in cardiovascular and renal protection. Med Res Rev. 2019;39(1):404-422. doi:10.1002/med.21513
  • Srivastava SP, Goodwin JE, Kanasaki K, Koya D. Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs. Genes . 2020;11(2). doi:10.3390/genes11020211
  • Zhang KW, Liu SY, Jia Y, Zou ML, Teng YY, Chen ZH, et al. Insight into the role of DPP-4 in fibrotic wound healing. Biomed Pharmacother. 2022;151:113143. doi:10.1016/j.biopha.2022.113143
  • Nitta K, Okada K, Yanai M, Takahashi S. Aging and chronic kidney disease. Kidney Blood Press Res. 2013;38(1):109-120. doi:10.1159/000355760
  • Denic A, Glassock RJ, Rule AD. Structural and Functional Changes With the Aging Kidney. Adv Chronic Kidney Dis. 2016;23(1):19-28. doi:10.1053/j.ackd.2015.08.004
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Hizmetleri ve Sistemleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Mahmud İslam 0000-0003-1284-916X

Ahmed Cihad Genç 0000-0002-7725-707X

Erken Görünüm Tarihi 27 Ekim 2023
Yayımlanma Tarihi 25 Ekim 2023
Kabul Tarihi 12 Eylül 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 7 Sayı: 3

Kaynak Göster

AMA İslam M, Genç AC. The Effects of Dipeptidyl Peptidase-4 Inhibitors on Kidney Function in Advanced CKD. J Biotechnol and Strategic Health Res. Ekim 2023;7(3):166-173. doi:10.34084/bshr.1347133
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