SGLT-2 İnhibitörlerinin GFR Üzerindeki İlk Etkisi: Hemodinamik Bir Bakış Açısı – Tek Merkez Deneyimi

Öz

Başlangıçta tip 2 diyabet tedavisi amacıyla geliştirilen sodyum-glukoz kotransporter-2 (SGLT-2) inhibitörleri, hemodinamik etkileri aracılığıyla renoprotektif özellikler göstermiştir. Bu çalışmada, SGLT-2 inhibitörü tedavisi başlanan hastalarda erken dönemde glomerüler filtrasyon hızı (GFR) ve proteinüri değişimlerinin gerçek yaşam verileriyle değerlendirilmesi amaçlanmıştır. Bu retrospektif gözlemsel çalışma, Ocak 2023 – Nisan 2025 tarihleri arasında Bursa Şehir Hastanesi Nefroloji Polikliniği’nde SGLT-2 inhibitörü tedavisine başlanan ≥18 yaş bireyleri içermektedir (n=100). Hastaların klinik ve laboratuvar verileri (kreatinin, eGFR, proteinüri, albüminüri) başlangıç ve 14–90 gün sonraki ilk kontrolde karşılaştırıldı. GFR düşüş düzeyine göre alt gruplar oluşturuldu. Eşzamanlı Finerenon kullanımı ve renal histopatolojik veriler de kaydedildi. Ortalama yaş 61,4±10,9 yıl olup, olguların %91’inde diyabet mevcuttu. Takipte hastaların %76’sında GFR düşüşü izlenirken, %24’ünde GFR korundu. Proteinüri ve albüminüride anlamlı düşüş izlendi (p<0,001). GFR düşüşü gözlenen hastalar anlamlı olarak daha genç, daha düşük beden kitle indeksine ve HbA1c düzeylerine sahipti (p<0,05). GFR düşüşü >30 mL/dk/1,73 m² olan grupta diüretik kullanımı daha fazlaydı. Lojistik regresyon analizine göre daha genç yaş, düşük HbA1c ve yüksek proteinüri düzeyleri GFR düşüşüyle ilişkili bulundu. Hastaların %10’unda SGLT-2 inhibitörüne ek olarak Finerenon başlanmıştı; ancak düşük örneklem sayısı ve eşzamanlı tedavi başlangıcı nedeniyle bu etkinin bağımsız değerlendirilmesi mümkün olmadı. SGLT-2 inhibitörü tedavisi sonrası erken dönemde GFR’de izlenen düşüşler sıklıkla fizyolojik hemodinamik adaptasyonla ilişkilidir. Proteinüri ve albüminürideki belirgin azalmalar, bu ajanların kısa dönem renoprotektif etkilerini desteklemektedir. Takip süresinin kısa olması ve çalışmanın kısıtlılıklarındandır. Bununla birlikte, diyabetik ve non-diyabetik bireyleri içermesi, kombinasyon tedavi verileri ve renal histopatolojik bulguların değerlendirilmesi klinik uygulamaya anlamlı katkılar sunmaktadır.

Anahtar Kelimeler

• SGLT-2 inhibitörleri
• glomerüler filtrasyon hızı
• proteinüri
• kronik böbrek hastalığı
• hemodinamik etki

The Initial Effect of SGLT 2 Inhibitors on GFR: A Hemodynamic Perspective – Single-Center Experience

Öz

Initially developed for glycemic control in type 2 diabetes, sodium-glucose cotransporter-2 (SGLT-2) inhibitors have emerged as renoprotective agents through their hemodynamic effects. This study aimed to evaluate early changes in glomerular filtration rate (GFR) and proteinuria following SGLT-2 inhibitor initiation in real-world nephrology outpatient practice. This retrospective observational study included adult patients (n=100) who were initiated on SGLT-2 inhibitors between January 2023 and April 2025 at the Bursa City Hospital Nephrology Outpatient Clinic. Clinical and laboratory parameters—including serum creatinine, estimated GFR, proteinuria, and albuminuria—were recorded at baseline and at follow-up (14–90 days). Subgroup analyses were performed based on the degree of GFR decline. The presence of concurrent Finerenone use and renal histopathological data were also documented. The mean age was 61.4±10.9 years, and 91% of patients had diabetes. During early follow-up, GFR decline was observed in 76% of patients, while 24% showed preservation. Significant reductions in proteinuria and albuminuria were noted (p<0.001). Patients with GFR decline were younger and had lower BMI and HbA1c levels (p<0.05). Diuretic use was significantly more frequent among those with >30 mL/min/1.73 m² GFR decline. In logistic regression, younger age, lower HbA1c, and higher proteinuria were associated with GFR decline. Concurrent Finerenone was used in 10% of cases; however, the limited sample and simultaneous treatment initiation precluded isolated evaluation of its effect. Our findings suggest that early GFR reductions after SGLT-2 inhibitor initiation are common and may reflect physiological hemodynamic adaptation rather than pathological injury. Concurrent improvements in proteinuria and albuminuria further support the short-term renoprotective effects. Although limited by short follow-up and the inclusion of non-diabetic patients, combination therapy, and renal histopathological findings provides meaningful insights for clinical decision-making.

Anahtar Kelimeler

• SGLT2 inhibitors
• glomerular filtration rate
• proteinuria
• chronic kidney disease
• hemodynamic effect

Kaynakça

1. 1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
2. 2. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
3. 3. Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med.2023;388(2):117-127.
4. 4. Cherney DZ, Perkins BA, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587-597.
5. 5. Sugiyama S, Yoshida A, Hieshima K, et al. Initial acute decline in estimated glomerular filtration rate after sodium-glucose cotransporter-2 inhibitor in patients with chronic kidney disease. J Clin Med Res. 2020;12(11):724-733.
6. 6. Bailey CJ, Gross JL, Pieters A, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet.2010;375(9733):2223-2233.
7. 7. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
8. 8. Almaimani M, Sridhar VS, Cherney DZI. Sodium-glucose cotransporter 2 inhibition in non-diabetic kidney disease. Curr Opin Nephrol Hypertens. 2021;30(5):474-481.

9. 9. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4S):S1-S276.
10. 10. Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60(2):215-225.
11. 11. Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306.
12. 12. Wanner C, Inzucchi SE, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323-334.
13. 13. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2022;102(5S):S1-S127.
14. 14. Levin A, Perkovic V, Wheeler DC, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and cardiovascular and kidney outcomes across KDIGO risk categories: post hoc analysis of a randomized, double-blind, placebo-controlled, multinational trial. Clin J Am Soc Nephrol. 2020;15(10):1433-1444.
15. 15. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219-2229.
16. 16. Agarwal R, Filippatos G, Pitt B, et al; FIDELIO-DKD and FIGARO-DKD Investigators. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484.