Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users:A GoDarts study

Aims: Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase the risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. Materials and Methods: We undertook a population‐based case‐control study of lactic acidosis in 1746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994 and 2014. AKI was stratified by severity according to “Kidney Disease: Improving Global Outcomes” guidelines. Mixed‐effects logistic and linear regression were used to analyse lactic acidosis risk and lactate concentrations, respectively. Results: Eighty‐two cases of lactic acidosis were identified. In Type 2 diabetes, those treated with metformin had a greater incidence of lactic acidosis [45.7 per 100 000 patient years; 95% confidence interval (CI) 35.9‐58.3] compared to those not exposed to this drug (11.8 per 100 000 patient years; 95% CI 4.9‐28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin‐exposed cohort (P < .001). The risk of lactic acidosis was higher in metformin users [odds ratio (OR) 2.3; P = .002] and increased with AKI severity (stage 1: OR 3.0, P = .002; stage 2: OR 9.4, P < .001; stage 3: OR 16.1, P < .001). Conclusions: A clear association was found between metformin, lactate accumulation and the development of lactic acidosis. This relationship is strongest in those with AKI. These results provide robust evidence to support current recommendations to omit metformin in any illness that may precipitate AKI

Radiotherapy after mastectomy for screen-detected ductal carcinoma in situ

Background. A role for radiotherapy after mastectomy for ductal carcinoma in situ (DCIS) is unclear. Using a prospective audit of DCIS detected through the NHS Breast Screening Programme we sought to determine a rationale for the use of postmastectomy radiotherapy for DCIS. Methods. Over a nine year period, from 9,972 patients with screen-detected DCIS and complete surgical, pathology, radiotherapy and follow up data, 2,944 women underwent mastectomy for DCIS of whom 33 (1.12%) received radiotherapy. Results. Use of post mastectomy radiotherapy was significantly associated with a close (<1mm) pathology margin, particularly (χ2(1) 95.81; p<0.00001), DCIS size (χ2 (3) 16.96; p<0.001) and the presence of microinvasion (χ2(1) 3.92; p<0.05). At median follow up 61 months, no woman who received radiotherapy had an ipsilateral further event, and only 1/33 women (3.0%) had a contralateral event. Of the women known not to have had radiotherapy post mastectomy, 45/2,894 (1.6%) had an ipsilateral further event and 83 (2.9%) had a contralateral event. Conclusion: For DCIS treated by mastectomy, a close (<1mm) margin, large tumour size and microinvasion, may merit radiotherapy to reduce ipsilateral recurrence