ABSTRACT
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.
ABSTRACT
Management of patients with relapsed or refractory (R/R) AL amyloidosis is complex. Some initial reports have shown positive results with daratumumab in heavily pre-treated AL amyloidosis patients. In this retrospective multicentric study, 38 patients (mean age 64 ± 9 years) with R/R AL amyloidosis treated with daratumumab were included. Cardiac and renal involvement was present in 76 and 74% of patients, and 42% had ≥3 organs involved. Median number of previous lines of therapy was 2 (range 1-8). Overall hematological response was 72%, including 28% complete responses. The median time to first hematological response was 2 weeks. A high-quality response (≥very good partial response) was obtained in 65% of patients who had never achieved such depth of response previously. Hematological responses were more frequent among patients receiving daratumumab as second-line therapy compared to subsequent therapies (92 vs. 61%). Cardiac and renal organ response rates were 37 and 59%. At 12 months, overall and progression-free survival were 59% (95%CI: 0.36-0.77) and 52% (95%CI: 0.29-0.70), respectively. Daratumumab is a safe and effective drug in the treatment of R/R AL amyloidosis and should be considered early in the course of the disease.
