Worsening membranous nephropathy in a patient with GIST treated with sunitinib.

Tyrosine kinase inhibitors (TKI) are anticancer agents widely used for a variety of malignancies including gastrointestinal stromal tumours (GIST). Although generally well-tolerated, TKIs have been associated with a number of adverse events including hypertension, proteinuria and nephrotic syndrome. We present the case of a 70-year-old patient with metastatic GIST on long-standing sunitinib who developed hypertension, oedema and hypoalbuminemia with a rising serum creatinine and was found to have nephrotic syndrome. Workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titres and a kidney biopsy confirmed PLA2R-positive membranous nephropathy without findings of thrombotic microangiopathy. Cessation of sunitinib led to reduction in anti-PLA2R antibody IgG titres while resumption, due to concern for cancer progression, led to worsening symptoms. Treatment with rituximab led to undetectable anti-PLA2R IgG titres. We highlight the importance of maintaining a systematic approach for evaluating nephrotic syndrome and provide a case showing that TKIs can exacerbate underlying nephrotic syndrome.

Chronic kidney disease, cardiovascular risk markers and total mortality in older men: cystatin C versus creatinine.

BACKGROUND: It remains uncertain whether cystatin C is a superior marker of renal function than creatinine in older adults. We have investigated the association between estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine (CKD-EPIcr) and cystatin C (CKD-EPIcys), and cardiovascular risk markers and mortality in older adults. METHODS: This is a cross-sectional and prospective study of 1639 British men aged 71-92 years followed up for an average of 5 years for mortality. Cox survival model and receiving operating characteristic analysis were used to assess the associations. RESULTS: The prevalence of chronic kidney disease (CKD) was similar using the two CKD-EPI equations, although cystatin C reclassified 43.9% of those with stage 3a CKD (eGFR 45-59 mL/min/1.732, moderate damage) to no CKD. However, CKD stages assessed using both CKD-EPIcr and CKD-EPIcys were significantly associated with vascular risk markers and with all-cause and cardiovascular disease mortality. In all men with CKD (eGFR <60 mL/min/1.732), the HRs (95% CI) for all-cause mortality after adjustment for cardiovascular risk factors compared with those with no CKD were 1.53 (1.20 to 1.96) and 1.74 (1.35 to 2.23) using CKD-EPIcr and CKD-EPIcys, respectively. Comparisons of the two CKD equations showed no significant difference in their predictive ability for mortality (difference in area under the curve p=0.46). CONCLUSION: Despite reclassification of CKD stages, assessment of CKD using CKD-EPIcys did not improve prediction of mortality in older British men >70 years. Our data do not support the routine use of CKD-EPIcys for identifying CKD in the elderly British male population.

Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men.

STUDYOBJECTIVES: Daytime sleep has been associated with increased risk of cardiovascular disease and heart failure (HF), but the mechanisms remain unclear. We have investigated the association between daytime and night-time sleep patterns and cardiovascular risk markers in older adults including cardiac markers and subclinical markers of atherosclerosis (arterial stiffness and carotid intima-media thickness (CIMT)). METHODS: Cross-sectional study of 1722 surviving men aged 71-92 examined in 2010-2012 across 24 British towns from a prospective study initiated in 1978-1980. Participants completed a questionnaire and were invited for a physical examination. Men with a history of heart attack or HF (n=251) were excluded from the analysis. RESULTS: Self-reported daytime sleep duration was associated with higher fasting glucose and insulin levels (p=0.02 and p=0.01, respectively) even after adjustment for age, body mass index, physical activity and social class. Compared with those with no daytime sleep, men with daytime sleep >1 hour, defined as excessive daytime sleepiness (EDS), had a higher risk of raised N-terminal pro-brain natriuretic peptide of ≥400 pg/mL, the diagnostic threshold for HF (OR (95% CI)=1.88 (1.15 to 3.1)), higher mean troponin, reduced lung function (forced expiratory volume in 1 s) and elevated von Willebrand factor, a marker of endothelial dysfunction. However, EDS was unrelated to CIMT and arterial stiffness. By contrast, night-time sleep was only associated with HbA1c (short or long sleep) and arterial stiffness (short sleep). CONCLUSIONS: Daytime sleep duration of >1 hour may be an early indicator of HF.

Effectiveness and Safety of Sitagliptin in Patients with Beta-thalassaemia Major and Diabetes Mellitus: A Case Series.

Sitagliptin, a modern antidiabetic agent which is weight neutral and associated with low rate of hypoglycaemias, is being increasingly used in type 2 diabetes mellitus (DM). However, there is a paucity of data about its efficacy and safety in beta-thalassaemia major (ß-TM). This retrospective case series of five patients (mean age of 45 years) is the first study evaluating the use of sitagliptin in patients with ß-TM and DM. Four patients responded well to sitagliptin, as evidenced by a decrease in fructosamine by 77 and 96µmol/L (equivalent reduction in HbA1c of 1.5% and 1.9%) observed in two patients and reduction in the frequency of hypoglycaemia without worsening glycaemic control in two others. One patient did not respond to sitagliptin. No patients reported significant side effects. This study provides evidence that sitagliptin may be considered, with caution, for use in patients with ß-TM and DM, under the close monitoring of a Diabetologist.

Vascular hamartoma of the parotid gland.

Hamartomas of the parotid gland are highly unusual. We present a case of a vascular hamartoma of the parotid gland arising as a 1.5 cm mass in a 5-year-old girl. As far as we are aware, no other case with the same features has been reported. We present this case to generate greater consideration of hamartomas as part of the differential diagnosis of parotid lesions, and to reflect over the criteria used to identify a hamartoma from other parotid lesions, as there appears to be some confusion in the literature.