Basil Alnasrallah

BACKGROUND: Post transplantation diabetes mellitus (PTDM) is a common and serious complication after renal transplantation with significant morbidity and mortality. Metformin has proven benefits in the general population and might be advantageous in the prevention and management of PTDM. METHODS: Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants had an oral glucose tolerance test (OGTT) in the 4-12 weeks post-transplantation; those with IGT were randomised to standard care or standard care and metformin 500 mg twice daily and followed up for 12 months. RESULTS: Seventy eight patients had an OGTT over 24 months, 25 of them had IGT, of those, 19 patients were randomised, giving a feasibility of recruitment of 24.4%. Ten patients were randomised to metformin and 9 patients to standard care. Tolerability and efficacy was similar between the 2 groups with no serious adverse events. There was no difference in secondary outcomes relating to the metabolic profile. CONCLUSIONS: The use of metformin post renal transplantation appeared feasible and safe. Larger randomised controlled trials (RCTs) are needed to establish and confirm the efficacy and safety of metformin post renal transplantation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001171606 . Date of registration 7/11/2014.

Introduction Post-transplant diabetes mellitus (PTDM) is a common complication of kidney transplantation and is associated with significant morbidity and mortality. In the general population, metformin has been used for diabetes prevention in high-risk individuals. Improving insulin sensitivity is one of many proven favourable effects of metformin. Despite the high incidence of PTDM in kidney transplant recipients, there is a lack of evidence for the role of metformin in the prevention of diabetes in this setting. Methods and analysis Trans plantation and Diab etes (Transdiab ) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants will undergo an oral glucose tolerance test in the 4–12 weeks post-transplantation; those with IGT will be randomised to standard care or standard care and metformin 500 mg twice daily, and followed up for 12 months. The primary outcomes of the study will be the feasibility of recruitment, the tolerability of metformin assessed using the Gastrointestinal Symptom Rating Scale at 3 and 12 months, and the efficacy of metformin assessed by morning glucose and glycated haemoglobin at 3, 6, 9 and 12 months. Ethics and dissemination Despite the significant morbidity and mortality of PTDM, there are currently no randomised clinical trials assessing pharmacological interventions for its prevention after kidney transplantation. The Transdiab trial will thus provide important data on the feasibility, safety, tolerability and efficacy of metformin after renal transplantation in patients with IGT; this will facilitate undertaking larger multicentre trials of interventions to reduce the incidence or severity of diabetes after kidney transplantation. This study has been approved by the Northern B Health and Disability Ethics Committee of the Ministry of Health in New Zealand. On study completion, results are expected to be published in a peer-reviewed journal. Trial registration number Australian New Zealand Clinical Trials Registry Number: ACTRN12614001171606.

Background . Membranous nephropathy (MN) can be associated with malignancy. However, the relative risk for malignancy remains unclear. It has been reported that higher numbers of inflammatory cells seen in the glomeruli at biopsy correlate with the occurrence of malignancy in patients with MN and might be used to direct screening. Methods . We examined the occurrence of malignancy in 201 MN patients in Auckland, New Zealand. We also examined the pathology of renal biopsies from 17 MN patients with malignancies and compared the number of inflammatory cells per glomerulus with matched control patients with MN but no malignancy. Results . 40 malignancies were identified in 37 patients, 28 of which occurred after the MN diagnosis. The standardized incidence ratio (SIR) was 2.1 (95% CI, 1.3–2.85) which was similar between patients ≥ 60 years and those <60 years. The median number of inflammatory cells per glomerulus did not differ between MN patients with and without malignancy at 1.86 (IQR, 1.17–2.7) and 2.07 (IQR, 1.17–3.65), respectively ( p value 0.56). Conclusions . The relative risk of malignancy in MN patients was similar across different age groups. The number of inflammatory cells per glomerulus did not differentiate between MN patients with and without malignancies.

Kidney injury in the context of cholestatic liver dysfunction is not uncommon; this has been historically referred to as cholemic nephrosis implying a direct deleterious renal effect of cholemia. However, scepticism about the exact role that bile and its constituents play in this injury has led to the disappearance of the term. We describe a case of severe AKI due to bile nephropathy with bile casts in flucloxacillin-induced liver dysfunction. We also discuss the recent literature reviving the concept of bile nephropathy.

BACKGROUND: Venous thromboembolism is a well established risk in patients with primary membranous nephropathy (MN) due to deficiency in natural anti-coagulants. Recent studies suggested a higher risk of arterial thrombotic events as well in this group. AIM: To identify that risk in our cohort. METHODS: We reviewed the data of all patients who had biopsy proven primary MN at our institute between 2003 and 2013. Clinical data were retrospectively reviewed until November 2016. The cardiovascular (CV) events, including acute coronary syndromes and strokes were determined and included only if occurred after the diagnosis of the nephropathy. RESULTS: A total of 204 patients had biopsy proven MN. Follow up information was available for 166 patients. Thirty-one patients (18.6%) developed CV events during follow up. Thirty-eight per cent of total events occurred within 1 year of MN diagnosis. Forty-two per cent of those who developed CV events were not on anti-thrombotic medications and 60% were not on statin therapy. Male gender, age, diabetes and absence of statins therapy were associated with higher rates of CV events in this group. CONCLUSION: There is an increased risk of arterial events in patients with primary MN. This risk is greatest in the first year of diagnosis. The risk should be highlighted in this group of patients and anti-platelets and statin therapy should be considered especially during the initial phase of the disease.