Abstract
There is limited information on the efficacy of pioglitazone in diabetic kidney diseases (DKD). We evaluated whether pioglitazone exerts renal-protective effects in DKD patients. We designed a retrospective cohort study, which included 742 type 2 diabetes mellitus (T2DM) patients with DKD in Taiwan, with eGFR between 30 and 90 ml/min/1.73 m2 and UACR level 300–5000 mg/g. Patients not meeting the target range for HbA1c (above 7%) were given additional medication with pioglitazone (n = 111) or received standard care (non-pioglitazone group, n = 631). The primary endpoint was the occurrence of composite renal endpoints, which was defined as sustained eGFR<15 ml/min/1.73 m2 (confirmed by two measurements within 90 days); doubling of serum creatinine (compared to baseline); and the presence of hemodialysis or renal transplantation. The median follow-up duration was two years. At baseline, the mean HbA1C levels in the pioglitazone and non-pioglitazone groups were 8.8% and 8.1%, respectively; mean ages were 64.4 and 66.2 years old, respectively; diabetes durations were 14.3 and 12.3 years, respectively. Baseline eGFR showed no significant difference between the pioglitazone and non-pioglitazone groups (55.8 and 58.8 mL/min/1.73 m2, respectively). In terms of gender, 63% of patients were male in the pioglitazone group compared with 57% in the non-pioglitazone group. Pioglitazone use did not reduce the risk of composite renal endpoints in DKD patients (HR: 0.97, 95% CI = 0.53–1.77), including persistent eGFR<15 ml/min/1.73 m2 (HR = 1.07, 95% CI = 0.46–2.52), doubling of serum creatinine (HR = 0.97, 95% CI = 0.53–1.77), or ESRD (HR = 2.58, 95% CI = 0.29–23.04). The results were not changed after various adjustments. A non-significant albuminuria reduction was also noted after pioglitazone prescription in DKD patients. Further randomized controlled studies are needed to establish the effects of pioglitazone definitively.
Highlights
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and is characterized by progressive worsening of albuminuria and decline of kidney function
The CREDENCE trial is a groundbreaking study that tested the primary hypothesis that SGLT2 inhibitors (SGLT2i) confers a renal benefit in patients with DKD and the results proved its benefit
The mean HbA1C values were 8.8% ± 5.9 and 8.1% ± 2.5, respectively. Both HbA1C and renal function in the pioglitazone and non-pioglitazone groups were similar (Fig 2), which indicated there were no obvious differences in blood glucose between the two study groups
Summary
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and is characterized by progressive worsening of albuminuria and decline of kidney function. The current evidence shows that intensive glucose control, antidiabetic medication, and blood pressure control, especially Renin-Angiotensin-system (RAS) blockade, reduce the risk of kidney disease [3,4,5,6,7]. The role of glucose is still difficult to define in DKD. Still, it appears to involve pivotal intermediates, including oxidative stress and dicarbonyl stress, which promote fibrosis and inflammation in the kidney [8, 9]. Several landmark trials over the past few decades have already shown intensive glucose control in T2DM patients may reduce albuminuria without preventing loss of GFR or progression to ESRD [3, 10, 11]. There is growing interest in the efficacy of these antidiabetic agents in terms of hard renal outcomes
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