Uremic toxin development in living kidney donors: a longitudinal study.

BACKGROUND: Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known. METHODS: Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques. RESULTS: Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03). CONCLUSION: This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.

The role of novel biomarkers of cardiovascular disease in chronic kidney disease: focus on adiponectin and leptin.

Cardiovascular disease (CVD) remains a major cause of premature death in patients with chronic kidney disease (CKD), including renal transplant recipients. Both interplay of traditional cardiovascular and renal specific risk factors have been shown to be associated with an increased risk of cardiovascular death in patients with CKD. Recently, there has been great interest in the role of novel biomarkers, in particular adiponectin and leptin, and its association with CVD in the CKD population. Adiponectin is a multifunctional adipocyte-derived protein with anti-inflammatory, antiatherogenic and insulin sensitizing activity. Recent observational studies have shown adiponectin to be a novel risk marker of CVD in patients with stages 1 to 5 CKD. Leptin is an adipocyte-derived hormone that promotes weight loss by decreasing food intake. Similarly, there are observational studies to support an association between leptin and CVD, including patients with CKD. In the CKD population, leptin may be associated with uremic cachexia and subsequent increased mortality. This review aims to summarize the pathophysiological and potential clinical roles of these cardiovascular biomarkers in patients with CKD.

'Iron lung': distinctive bronchoscopic features of acute iron tablet aspiration.

Three confirmed cases of acute iron tablet-induced necrosis due to a fulminant chemical burn injury to the tracheobronchial tree as a result of accidental inhalation and/or aspiration of iron tablets are described. Although histological confirmation has been relied upon for diagnosis, the distinctive bronchoscopic features may allow prompt recognition and treatment by bronchoscopists to prevent this potentially fatal condition.