IntroductionMetformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease.MethodsIn this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring.ResultsThere was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts.DiscussionIn our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing.

Hypertension is common following renal transplantation and has adverse effects on cardiovascular and graft health. Ambulatory blood pressure monitoring (ABPM) is better at overall blood pressure (BP) assessment and is necessary to diagnose nocturnal hypertension, which is also implicated in poor outcomes. The authors performed a retrospective analysis of 98 renal transplant recipients (RTRs) and compared office BP and ambulatory BP recordings. ABPM revealed discordance between office BP and ambulatory BP in 61% of patients, with 3% caused by white-coat and 58% caused by masked hypertension (of which 33% were caused by isolated nocturnal hypertension). Overall, mean systolic BP was 3.6 mm Hg (0.5-6.5) and diastolic BP was 7.5 mm Hg (5.7-9.3) higher via ambulatory BP than office BP. This was independent of estimated glomerular filtration rate, proteinuria, transplant time/type, and comorbidities. A total of 42% of patients had their management changed after results from ABPM. ABPM should be routinely offered as part of hypertension management in RTRs. J Clin Hypertens (Greenwich).

We describe a case of successful removal of an adherent dialysis catheter after an unsuccessful attempt with surgical cut down on the internal jugular vein. A 57-year-old female on maintenance haemodialysis via a left internal jugular tunnelled catheter (Hemoglide, BARD) had an attempted removal of her 17-month-old line after a leak was noted at the catheter hub. By this stage, she had just commenced full cannulation of a left brachiobasilic fistula which had been slow to mature. She had coincidentally been admitted to hospital 2 days prior for treatment of a urinary tract infection from which she was recovering.Under sterile conditions and local anaesthetic, an incision was made in the tract, and the cuff was easily mobilised. The line was transected at the cuff, and the distal segment discarded. The clamped proximal segment was then withdrawn 3 to 4 cm. At this stage, despite moderate traction, the line appeared adherent at the clavicle. After surgical consultation, a CT venogram was requested that appeared to show scarring around the internal jugular vein. With the line clamped (but exposed), she proceeded to theatre the