The Effects of thiazides on eGFR changes in patients with advanced Chronic Kidney Disease

In patients with chronic kidney disease (CKD), thiazides diuretics (thiazides) not only provide a significant antihypertensive effect but also reduce the rate of estimated glomerular filtration rate（eGFR）decline and proteinuria, suggesting their potential glomerular protection effects through attenuating glomerular overload. However, the use of thiazides in patients with advanced CKD (stage G4 and G5), remains limited, and few studies have evaluated their impact on kidney function decline in advanced CKD. This study aimed to investigate the effects of thiazides on renal function decline in patients with advanced CKD.  

This was a single-center retrospective study of patients diagnosed with CKD G4 (eGFR 15–29 mL/min/1.73 m²) or G5 (eGFR <15 mL/min/1.73 m²) who initiated thiazides (trichloromethiazide, hydrochlorothiazide, or indapamide) from January 2014 to September 2024 in the Department of Nephrology, Kansai Electric Power Hospital in Japan. Patients who were on dialysis at initiation of thiazides or started dialysis within one year after thiazides initiation were excluded. Primary endpoint of this study was eGFR change during one year before (preΔeGFR) and after (postΔeGFR) initiating thiazides. Secondary endpoints were urinary protein, mean blood pressure (BP), and serum potassium levels at baseline (initiation of thiazides) and at one year after initiating thiazides. In a sub-analysis, preΔeGFR and postΔeGFR were evaluated separately for thiazide group (trichloromethiazide and hydrochlorothiazide) and indapamide group. Statistical analysis was performed using the Wilcoxon signed-rank test.

A total of 55 patients were included in the analysis, with CKD G4 (n=41), CKD G5 (n=14). Diabetes mellitus was present as a comorbidity in 33 patients (60%). Concomitant medications at the time of thiazides initiation included angiotensin receptor blocker (ARB)/ angiotensin-converting enzyme (ACE) inhibitors in 51 patients (92.7%), sodium-glucose cotransporter (SGLT2) inhibitors and mineralocorticoid receptor antagonist (MRA) in one patient (1.8%) for each. The primary renal diseases were diabetic kidney disease (47.2%), followed by nephrosclerosis (20.0%) and IgA nephropathy (7.3%). The median (IQR: interquartile range) preΔeGFR was 5.4 (2.4-8.3) mL/min/1.73 m² and the postΔeGFR was 2.7 (1.1-5.1) mL/min/1.73 m² (p <0.01). Urinary protein at baseline was 2.9 (0.7-3.7) g/gCr, after one year was 1.8 (0.6-3.9) g/gCr (p < 0.05). Mean BP at baseline was 104.7 (95.0-114.3) mmHg and after one year was 99.7 (89.3-105.7) mmHg (p < 0.01). Serum potassium level at baseline was 4.7 (4.3-5.1) mEq and after one year was 4.7 (4.2-5.0) mEq (p =0.71). In a sub-analysis, preΔeGFR and postΔeGFR reached statistical significance in both thiazide group (n=42) and indapamide group (n=13) (p <0.01 in both thiazide and indapamide group for each)

There are few studies examining the impact of thiazides on kidney function in patients with advanced CKD, particularly those with CKD G5. Although an initial dip in eGFR may occur after the initiation, this does not necessarily accelerate into long-term renal function decline. In this study, thiazides in patients with advanced CKD was associated with a slower decline in eGFR, suggesting their potential usefulness in managing advanced CKD. Furthermore, a reduction in proteinuria was observed in addition to antihypertensive effects, supporting the hypothesis that thiazides may have reno-protective effects by attenuating glomerular overload.