IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, with an incidence of 2.5 per 100,000 population per year. The 10-year risk of progression to end stage kidney disease (ESKD) or ...halving of eGFR is 26%. Here we aimed to collect a comprehensive dataset of IgAN patients at our centre over 2 decades to provide real world data, describe outcomes and determine the effects of immunosuppression use. All patients diagnosed with biopsy-proven IgAN at our centre over 2 decades were identified. After exclusions, the total cohort size was 401. Data relating to (i) baseline demographics, (ii) laboratory and urine results, (iii) histological data, and (iv) outcomes of initiation of renal replacement therapy (RRT) and mortality were collected. The median age was 45.0 years, with 69.6% male and 57.6% hypertensive; 20.4% received immunosuppression, 29.7% progressed to RRT and 19.7% died, over a median follow up period of 51 months. Baseline eGFR was 46.7ml/min/1.73m.sup.2 and baseline uPCR was 183mg/mmol. Median rate of eGFR decline was -1.31ml/min/1.73m.sup.2 /year. Those with a higher MEST-C score had worse outcomes. Immunosuppression use was associated with an increased rate of improvement in proteinuria, but not with a reduction in RRT or mortality. Factors favouring improved outcomes with immunosuppression use included female gender; lower age, blood pressure and T-score; higher eGFR; and ACEi/ARB use. A variety of clinical and histological factors are important in determining risk of progression in IgAN. Therapeutic interventions, particularly use of immunosuppression, should be individualised and guided by these factors.
It has been suggested that sudden cardiac death (SCD) contributes around 50% of cardiovascular and 27% of all-cause mortality in hemodialysis patients. The true burden of arrhythmias and arrhythmic ...deaths in this population, however, remains poorly characterised. Cardio Renal Arrhythmia Study in Hemodialysis (CRASH-ILR) is a prospective, implantable loop recorder single centre study of 30 established hemodialysis patients and one of the first to provide long-term ambulatory ECG monitoring.
30 patients (60% male) aged 68±12 years receiving hemodialysis for 45±40 months with varied etiology (diabetes 37%, hypertension 23%) and left ventricular ejection fraction (LVEF) 55±8% received a Reveal XT implantable loop recorder (Medtronic, USA) between August 2011 and October 2014. ECG data from loop recorders were transmitted at each hemodialysis session using a remote monitoring system. Primary outcome was SCD or implantation of a (tachy or bradyarrhythmia controlling) device and secondary outcome, the development of arrhythmia necessitating medical intervention.
During 379,512 hours of continuous ECG monitoring (mean 12,648±9,024 hours/patient), there were 8 deaths-2 SCD and 6 due to generalised deterioration/sepsis. 5 (20%) patients had a primary outcome event (2 SCD, 3 pacemaker implantations for bradyarrhythmia). 10 (33%) patients reached an arrhythmic primary or secondary end point. Median event free survival for any arrhythmia was 2.6 years (95% confidence intervals 1.6-3.6 years).
The findings confirm the high mortality rate seen in hemodialysis populations and contrary to initial expectations, bradyarrhythmias emerged as a common and potentially significant arrhythmic event.
Background Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly ...declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. Study Design Single-center prospective cohort study; retrospectively analyzed. Setting & Participants 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. Predictors Presentation with flash pulmonary edema (n = 37 7.8%), refractory hypertension (n = 116 24.3%), or rapidly declining kidney function (n = 46 9.7%) compared to low-risk presentation with none of these phenotypes (n = 230 49%). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. Outcomes Death, cardiovascular (CV) event, end-stage kidney disease. Results During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P = 0.02). Limitations Observational study; retrospective analysis; potential treatment bias. Conclusions This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.
Randomized controlled trials (RCT) have shown no overall benefit of renal revascularization in atherosclerotic renovascular disease (ARVD). However, 25% of patients demonstrate improvement in renal ...function. We used the ratio of magnetic resonance parenchymal volume (PV) to isotopic single kidney glomerular filtration rate (isoSKGFR) ratio as our method to prospectively identify "improvers" before revascularization.
Patients with renal artery stenosis who were due revascularization were recruited alongside non-ARVD hypertensive CKD controls. Using the controls, 95% CI were calculated for expected PV:isoSK-GFR at given renal volumes. For ARVD patients, "improvers" were defined as having both >15% and >1ml/min increase in isoSK-GFR at 4 months after revascularization. Sensitivity and specificity of PV:isoSK-GFR for predicting improvers was calculated.
30 patients (mean age 68 ±8 years), underwent revascularization, of whom 10 patients had intervention for bilateral RAS. Stented kidneys which manifested >15% improvement in function had larger PV:isoSK-GFR compared to controls (19±16 vs. 6±4ml/ml/min, p = 0.002). The sensitivity and specificity of this equation in predicting a positive renal functional outcome were 64% and 88% respectively. Use of PV:isoSK-GFR increased prediction of functional improvement (area under curve 0.93). Of note, non-RAS contralateral kidneys which improved (n = 5) also demonstrated larger PV:isoSK-GFR (15.2±16.2 ml/ml/min, p = 0.006).
This study offers early indicators that the ratio of PV:isoSK-GFR may help identify patients with kidneys suitable for renal revascularization which could improve patient selection for a procedure associated with risks. Calculation of the PV:isoSK-GFR ratio is easy, does not require MRI contrast agent.
Acute Kidney Injury (AKI) is common and associated with increased morbidity and mortality. This retrospective analysis quantified and compared the association between AKI and the risk of death and ...admission to critical care in acute admissions of different aetiology.
Data were extracted anonymously from the Trust 'data warehouse' for admissions between 2011and 2017. We applied KDIGO AKI criteria to establish AKI stage. Odds ratios (OR) for death and critical care admission were calculated for patients with AKI stage 3 (compared to all other patients), and patients with any stage AKI (compared to non-AKI admissions). Analyses were performed using logistic regression, adjusted for age, pre-existing CKD, co-morbid index, and gender.
There were 26,052 medical and 12,560 surgical patient episodes within sixteen common diagnoses with 3823 medical and 1520 surgical patients with AKI events. The likelihood of AKI was highest in sepsis (31.8%), and the likelihood of death in AKI 3 highest in femoral neck fracture (54.5%). AKI 3 has a OR for death for acute coronary syndrome of 12.8 and a OR of 24.6 in femoral neck fracture. Admission to critical care for any AKI in medical patients has a OR of 9.6, but increases to OR 37.2 for heart failure.
The clinical impact of AKI differs across medical and surgical diagnoses, but is a significant contributor to the risk for death and critical care admission. This body of work may indicate a benefit to a more diagnosis-specific stratified approach to AKI care.
Abstract
Background
The optimal intravenous (IV) iron would allow safe correction of iron deficiency at a single infusion over a short time. The FERWON-NEPHRO trial evaluated the safety and efficacy ...of iron isomaltoside 1000/ferric derisomaltose (IIM) in patients with non-dialysis-dependent chronic kidney disease and iron deficiency anaemia.
Methods
In this randomized, open-label and multi-centre trial conducted in the USA, patients were randomized 2:1 to a single dose of 1000 mg IIM or iron sucrose (IS) administered as 200 mg IV injections up to five times within a 2-week period. The co-primary endpoints were serious or severe hypersensitivity reactions and change in haemoglobin (Hb) from baseline to Week 8. Secondary endpoints included incidence of composite cardiovascular adverse events (AEs).
Results
A total of 1538 patients were enrolled (mean estimated glomerular filtration rate 35.5 mL/min/1.73 m2). The co-primary safety objective was met based on no significant difference in the incidence of serious or severe hypersensitivity reactions in the IIM and IS groups 0.3% versus 0%; risk difference: 0.29% (95% confidence interval: –0.19; 0.77; P > 0.05). Incidence of composite cardiovascular AEs was significantly lower in the IIM versus IS group (4.1% versus 6.9%; P = 0.025). Compared with IS, IIM led to a more pronounced increase in Hb during the first 4 weeks (P ≤ 0.021), and change in Hb to Week 8 showed non-inferiority, confirming that the co-primary efficacy objective was met.
Conclusions
Compared with multiple doses of IS, a single dose of IIM induced a non-inferior 8-week haematological response, comparably low rates of hypersensitivity reactions, and a significantly lower incidence of composite cardiovascular AEs.
Graphical Abstract
Background Calcium-phosphate levels, linked to vascular dysfunction in chronic kidney disease, may represent novel risk factors for coronary heart disease, stroke, and death in community-dwelling ...adults. Methods We tested this hypothesis over 12.6 years of follow-up in the prospective, community-based Atherosclerosis Risk in Communities Study (n = 15,732). Results At baseline, mean (SD) values were 9.8 (0.4) mg/dL for serum calcium, 3.4 (0.5) mg/dL for serum phosphate, 33.6 (5.3) mg2 /dL2 for calcium-phosphate product, 54.2 (5.7) years for age, and 93.1 (21.5) mL/min per 1.73 m2 for glomerular filtration rate (GFR). Shared associations of calcium, phosphate, and calcium-phosphate product included older age, female sex, African American race, cigarette-years, current cigarette smoking, low body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, low serum albumin, low GFR, low caloric intake, and phosphorus intake. With adjustment for age, demographic characteristics, comorbid conditions, albumin, and GFR, calcium-associated hazards ratios for coronary heart disease, stroke, and death were, respectively, 1.01 (95% confidence interval 0.96-1.06), 1.16 (1.07-1.26, P = .0005), and 1.03 (0.98-1.08); phosphate-associated hazards ratios were 1.03 (0.98-1.08), 1.11 (1.02-1.21, P = .0219), and 1.14 (1.09-1.20, P < .0001); calcium-phosphate product-associated hazards ratios were 1.03 (0.98-1.08), 1.15 (1.05-1.26, P = .0017), and 1.15 (1.09-1.20, P < .0001). Conclusions Although calcium, phosphate, and calcium-phosphate product levels exhibit complex associations with traditional cardiovascular risk factors and outcomes, they may be potentially modifiable risk factors for stroke and death in community-dwelling adults.
Vascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for ...this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs.
We demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization. FTI-277 increases Akt signaling in VSMC in short-term serum-stimulation assays and in long-term mineralization assays. In contrast, manumycin A has no effect on Akt signaling or mineralization. Co-incubation of VSMC with FTI-277 and SH6 (an Akt inhibitor) significantly reduces the inhibitory effect of FTI-277 on mineralization, demonstrating that FTI-277 inhibits calcification by activating Akt signaling. Over-expression of the constitutively active p110 sub-unit of PI3K in VSMC using adenovirus activates Akt, inhibits mineralization, suppresses VSMC differentiation and significantly enhances MGP mRNA expression. FTI-277 also inhibits phosphate-induced activation of caspase 3 and apoptosis of VSMC, and these effects are negated by co-incubation with SH6. Finally, using an ex vivo model of vascular calcification, we demonstrate that FTI-277 inhibits high phosphate-induced mineralization in aortic rings derived from rats with end-stage renal failure.
Together, these results demonstrate that FTI-277 inhibits VSMC mineral deposition by up-regulating PI3K/Akt signaling and preventing apoptosis, suggesting that targeting farnesylation, or Akt specifically, may have therapeutic potential for the prevention of vascular calcification.
Estimates of glomerular filtration rate (eGFR) should provide accurate measure of an individual’s kidney function because important clinical decisions such as timing of renal replacement therapy and ...drug dosing may be dependent on eGFR. Formulae from which eGFR is derived are generally based on serum creatinine measurement, such as Cockcroft–Gault, MDRD and CKD-EPI. More recently, calculation of eGFR using other laboratory biomarkers such as cystatin C has emerged with apparent greater accuracy. In old people, there is age-related physiological change in the kidney, which could lead to reduced GFR. Likewise, physiological changes in body composition that occur with the ageing process impede the use of a single creatinine-based calculation of eGFR across all adult age groups. Studies have shown differences in the prevalence of CKD based on the type of equation used to estimate GFR. This review discusses the evolution of eGFR calculations and the relative accuracy of such equations in older population.
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