Kidney international
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Kidney international · Feb 2019
The Fracture Risk Assessment Tool (FRAX®) predicts fracture risk in patients with chronic kidney disease.
The Fracture Risk Assessment Tool (FRAX®) was developed to predict fracture risk in the general population, but its applicability to patients with chronic kidney disease (CKD) is unknown. Using the Manitoba Bone Mineral Density (BMD) Database, we identified adults not receiving dialysis with available serum creatinine measurements and bone densitometry within 1 year. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. ⋯ FRAX predicted risk for major osteoporotic fracture and hip fracture in all eGFR strata. For every standard deviation increase in FRAX score derived with BMD, the hazard ratio (HR) for hip fracture was 4.54 (95% confidence interval [CI] 3.57-5.77) in individuals with eGFR ≥ 60 mL/min/1.73m2, 4.52 (95% CI 3.15-6.49) in individuals with eGFR 30-60 mL/min/1.73m2, and 3.10 (95% CI 1.80-5.33) in individuals with eGFR <30 mL/min/1.73m2. The relationship between FRAX and major osteoporotic fracture was stronger in those with CKD compared to those with preserved eGFR. These findings support the use of FRAX to risk stratify patients with non-dialysis CKD for major osteoporotic fractures and hip fractures.
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Kidney international · Feb 2019
mTOR inhibitors may benefit kidney transplant recipients with mitochondrial diseases.
Mitochondrial diseases represent a significant clinical challenge. Substantial efforts have been devoted to identifying therapeutic strategies for mitochondrial disorders, but effective interventions have remained elusive. Recently, we reported attenuation of disease in a mouse model of the human mitochondrial disease Leigh syndrome through pharmacological inhibition of the mechanistic target of rapamycin (mTOR). ⋯ Rapamycin rescued multiple deficits in cultured cells including mitochondrial morphology, mitochondrial membrane potential, and replicative capacity. Clinical measures of health and mitochondrial disease progression were improved in all four patients following the switch to an mTOR inhibitor. Metabolomic analysis was consistent with mitochondrial function improvement in all patients.
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Kidney international · Feb 2019
Kidney transplantation from donors after uncontrolled circulatory death: the Spanish experience.
Donation after uncontrolled circulatory death (uDCD) refers to donation from persons who have died following cardiac arrest and unsuccessful attempt at resuscitation. We report the Spanish experience of uDCD kidney transplantation, and identify factors related to short-term post-transplant outcomes. The Spanish CORE system compiles data on all donation and transplant procedures in the country. ⋯ In a Cox-Model, donor age ≥ 60 years (odds ratio [OR] 2.7; 95% confidence interval [CI] 1.2-6.1), in situ cooling of kidneys versus normothermic regional perfusion (OR 5.6; 95% CI 2.7-11.5) or hypothermic regional perfusion based on the use of extracorporeal membrane oxygenation devices (OR 4.3; 95% CI 2.1-8.6), and a recipient history of prior kidney transplant (OR 3.5; 95% CI 1.5-8.3) all significantly increased the risk of graft loss during the first year after transplantation. Kidney transplantation from uDCD donors provides acceptable 1-year outcomes, although there is room for improvement. Hypothermic and normothermic regional perfusion strategies are preferable to in situ cooling of kidneys from uDCD donors.
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Kidney international · Jan 2019
Randomized Controlled Trial Multicenter Study Comparative StudyA randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis.
Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. ⋯ The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.
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Suzuki et al. analyzed a mouse model of erythropoietin-deficient anemia to show that during iron overload renal interstitial fibroblasts accumulate iron, and this impairs the hypoxia-driven transcription of the erythropoietin gene. The authors show that excess iron decreases levels of hypoxia-inducible transcription factor 2α (HIF2α), the main driver of erythropoietin production in hypoxia and anemia. The work advances our understanding of the effect of iron on hypoxia signaling, but its implications for anemia treatment are less clear.