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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.

Patients with biochemical evidence of chronic kidney disease (CKD) without a diagnostic code (uncoded CKD) in primary care are at increased risk of death, acute kidney injury (AKI), and unplanned hospital care. Uncoded CKD is highly prevalent and there is no data to evaluate whether patients with uncoded CKD were at an increased risk of COVID-19 death. Aim: to assess whether patients with uncoded CKD stages 3-5 were at increased risk of death and COVID-19 deaths. Descriptive and inferential analyses to measure adjusted hazard of death, and COVID-19 death in patients with CKD stages 3-5 from 2.85 million primary care patients in Greater Manchester, England. Sensitivity analyses using propensity score matching and competing risk regression. Coded CKD stages 3 and 4 (versus uncoded) were associated with significantly lower adjusted hazards of death (HR 0.81, CIs 0.77-0.86, p=<0.0001; HR 0.45, CIs 0.34-0.60, p=<0.0001, respectively), and COVID-19 death (HR 0.74, CIs 0.55-0.99, p = 0.03; HR 0.55, CIs 0.30-0.99, p = 0.045, respectively). Descriptive analyses were conducted for patients with CKD stage 5 due to low numbers of patients with uncoded CKD stage 5, precluding survival analyses. Our retrospective cohort study suggests that clinical coding is a digital intervention associated with a lower adjusted hazard of death and COVID-19 death in patients with CKD stages 3 and 4, and should be considered a key element in the organisation and delivery of care for people with CKD.

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.

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.

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.

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.

Chronic kidney disease (CKD) is a global public health problem with major human and economic consequences. Despite advances in clinical guidelines, classification systems and evidence-based treatments, CKD remains underdiagnosed and undertreated and is predicted to be the fifth leading cause of death globally by 2040. This review aims to identify barriers and enablers to the effective detection, diagnosis, disclosure and management of CKD since the introduction of the Kidney Disease Outcomes Quality Initiative (KDOQI) classification in 2002, advocating for a renewed approach in response to updated Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical guidelines. The last two decades of improvements in CKD care in the UK are underpinned by international adoption of the KDIGO classification system, mixed adoption of evidence-based treatments and research informed clinical guidelines and policy. Interpretation of evidence within clinical and academic communities has stimulated significant debate of how best to implement such evidence which has frequently fuelled and frustratingly forestalled progress in CKD care. Key enablers of effective CKD care include clinical classification systems (KDIGO), evidence-based treatments, electronic health record tools, financially incentivised care, medical education and policy changes. Barriers to effective CKD care are extensive; key barriers include clinician concerns regarding overdiagnosis, a lack of financially incentivised care in primary care, complex clinical guidelines, managing CKD in the context of multimorbidity, bureaucratic burden in primary care, underutilisation of sodium-glucose co-transporter-2 inhibitor (SGLT2i) medications, insufficient medical education in CKD, and most recently – a sustained disruption to routine CKD care during and after the COVID-19 pandemic. Future CKD care in UK primary care must be informed by lessons of the last two decades. Making step change, over incremental improvements in CKD care at scale requires a renewed approach that addresses key barriers to detection, diagnosis, disclosure and management across traditional boundaries of healthcare, social care, and public health. Improved coding accuracy in primary care, increased use of SGLT2i medications, and risk-based care offer promising, cost-effective avenues to improve patient and population-level kidney health. Financial incentives generally improve achievement of care quality indicators – a review of financial and non-financial incentives in CKD care is urgently needed.

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.

In a multicenter, blinded end-point, open-label trial, adults undergoing maintenance hemodialysis were assigned to receive high-dose iron proactively or low-dose iron reactively. High-dose iron therapy was noninferior and led to lower doses of erythropoiesis-stimulating agent.

Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90[mu]mol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.