Comparison of two strategies based on mammalian target of rapamycin inhibitors in secondary prevention of non-melanoma skin cancer after kidney transplantation, a pilot study.

After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non-melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post-transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen.

Heparin-Free Prolonged Intermittent Hemodialysis Using Calcium-Free Citrate Dialysate in Critically Ill Patients.

OBJECTIVES: Critically ill patients who have a high risk of bleeding but require prolonged intermittent dialysis need a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit. We assessed the safety and efficiency of heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance. DESIGN: Prospective cohort study. SETTING: Critical care units. PATIENTS: Critically ill patients who required renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 101 dialysis sessions were performed in 35 patients (mechanical ventilation n = 78; norepinephrine n = 13). Median duration of dialysis was 294 minutes (interquartile range, 240-300), and median ultrafiltration volume was 2.3 L (1-2.8). Urea and ß2-microglobulin reduction rates were 64.5% ± 0.4% and 48% ± 0.13%, respectively. Postfilter ionized calcium was 0.35 ± 0.17 and 0.38 ± 0.14 mmol/L at 1 and 3 hours, respectively, within the extracorporeal circuit. A major clotting event that led to premature termination of the session occurred in only three of 101 sessions. In these three cases, major catheter dysfunction occurred before clotting within the circuit. Prefilter ionized calcium remained within narrow ranges (before/after change +0.07 ± 0.006 mmol/L), and total-to-ionized calcium ratio, a surrogate marker for citratemia, was unchanged. CONCLUSIONS: Dialysis anticoagulation with calcium-free citrate-containing dialysate and calcium reinjection according to ionic dialysance is an easy-to-use, efficient, and inexpensive form of heparin-free regional anticoagulation. It allows prolonged hemodialysis sessions in critically ill patients without the need to systemically monitor ionized calcium. Furthermore, sessions can be safely extended according to the hemodynamic tolerance to ensure an adequate dose of dialysis and a negative water balance, a major point in patients with severe acute kidney disease.

Chronic tubulointerstitial nephropathy induced by glucosamine: a case report and literature review.

Glucosamine is a glycosylated amine and a slow-acting symptomatic treatment for osteoarthritis. Some experimental animal studies have shown that glucosamine can cause apoptosis in kidney tubular and mesangial cells as well as overexpression of transforming growth factor ß1 (TGF-ß1) and connective-tissue growth factor (CTGF), which are potent inducers of mesangial and interstitial tubulointerstitial fibrosis. We report the case of a 67-year-old patient who presented with non-proteinuric renal insufficiency and a reduction of the glomerularfiltration rate (GFR) from 86 to 46 mL/min within 3 months. A kidney biopsy showed noninflammatory 40 - 50% fibrosis of the renal cortex associated with acute tubular necrosis. The etiological investigation was negative apart from taking 1,200 mg of glucosamine daily for 3 years to treat osteoarthritic knee pain. Three weeks after stopping glucosamine, GFR increased from 47.5 to 60 mL/min. Reintroduction of glucosamine resulted in loss of kidney function after 3 weeks, with GFR reduced from 60 to 53 mL/ min. Thus, glucosamine was shown to cause renal toxicity. Referring to other reported cases, we conclude that toxicity is rare but may also be underreported.