Continued monitoring of acute kidney injury survivors might not be necessary in those regaining an estimated glomerular filtration rate > 60 mL/min at 1 year

Background. Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function. Methods. All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently <60 mL/min/1.73 m2) from first dialysis for AKI. Results. Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8–12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8–8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively]. Conclusions. Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR >60 mL/min/1.73 m2 by 12 months after an episode of AKI

Association between urinary sodium, creatinine, albumin, and long term survival in chronic kidney disease

Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium excretion and urinary sodium:creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adults attending a renal clinic who had at least one 24-hour urinary sodium measurement were identified. 24-hour urinary sodium measures were collected and urinary sodium:creatinine ratio calculated. Time to renal replacement therapy or death was recorded. 423 patients were identified with mean estimated glomerular filtration rate of 48ml/min/1.73m<sup>2</sup>. 90 patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was -2.8ml/min/1.73m<sup>2</sup>/year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher urinary sodium excretion and urinary sodium:creatinine but the association with these parameters and poor outcome was not independent of renal function, age and albuminuria. When stratified by albuminuria, urinary sodium:creatinine was a significant cumulative additional risk for mortality, even in patients with low level albuminuria. There was no association between low urinary sodium and risk, as observed in some studies. This study demonstrates an association between urinary sodium excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease but further study is required to determine the target sodium intake

Renal replacement modality and stroke risk in end-stage renal disease—a national registry study

Background: The risk of stroke in end-stage renal disease (ESRD) on renal replacement therapy (RRT) is up to 10-fold greater than the general population. However, whether this increased risk differs by RRT modality is unclear. Methods: We used data contained in the Scottish Renal Registry and the Scottish Stroke Care Audit to identify stroke in all adult patients who commenced RRT for ESRD from 2005 to 2013. Incidence rate was calculated and regression analyses were performed to identify variables associated with stroke. We explored the effect of RRT modality at initiation and cumulative dialysis exposure by time-dependent regression analysis, using transplant recipients as the reference group. Results: A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5% were female and 277 patients suffered a stroke (incidence rate was 18.6/1000 patient-years). Patients who had stroke were older, had higher blood pressure and were more likely to be female and have diabetes. On multivariable regression older age, female sex, diabetes and higher serum phosphate were associated with risk of stroke. RRT modality at initiation was not. On time-dependent analysis, haemodialysis (HD) exposure was independently associated with increased risk of stroke. Conclusions: In patients with ESRD who initiate RRT, HD use independently increases risk of stroke compared with transplantation. Use of peritoneal dialysis did not increase risk on adjusted analysis

The association of atrial fibrillation and ischaemic stroke in patients on haemodialysis: a competing risk analysis

Background: Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear. Objective: The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses. Design: A national record linkage cohort study. Setting: All renal and stroke units in Scotland, UK. Patients: All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015). Measurements: Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records. Methods: Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke. Results: Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death. Limitations: Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available. Conclusions: The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes

A national study of autogenous arteriovenous access use and patency in a contemporary hemodialysis population

Objective: The predicted outcomes of autogenous arteriovenous (AV) hemodialysis access creation are predominantly based on historical data; however, both the hemodialysis population and clinical practices have changed significantly during the last decade. This study examined contemporary AV access clinical use and patencies. Methods: A multicenter observational cohort study was performed of all new AV accesses created in Scotland in 2015. The primary end point was efficacy assessed by successful AV access use for a minimum of 30 days and primary, primary assisted, and secondary patency at 1 year. Data obtained included all interventions to maintain or to restore patency. Predictors of patency loss including demographics, comorbid conditions, dialysis status, AV access location, duplex ultrasound surveillance, procedures, prior access, and antiplatelets were assessed. Kaplan-Meier and competing risks analyses were performed to estimate the probability of AV access failure. All patients were followed up for at least 1 year or had a censoring event. Results: A total of 582 AV accesses were created in 537 patients (mean age, 60 [standard deviation, 14] years; 60% men; 42% with diabetes) in nine adult renal centers. Mean follow-up was 11.8 (standard deviation, 7.6) months. By the end of the follow-up, 322 (55.3%) AV accesses were successfully used for dialysis. At 1 year, 48% (95% confidence interval [CI], 44-52) of AV accesses had primary patency, (95% CI, 63-71) had primary assisted patency, and 69% (95% CI, 65-73) had secondary patency. The leading cause of primary patency loss was primary failure (30%). An average of 0.48 intervention per patient-year was required to maintain patency. On multivariable analysis, patency was better for an upper arm than for a forearm AV access (1-year secondary patency of upper arm vs forearm AV accesses, 74% vs 58%). The cumulative hazard and incident functions for AV access failure were 31% (95% CI, 27-35) and 23% (95% CI, 20-27) at 1 year, respectively. Conclusions: Despite advances in recent years with preoperative vessel assessment and surveillance, patency rates have not improved, with primary failure remaining the major obstacle. Competing events should be taken into consideration; otherwise, biases may occur with overestimation of the probability of AV access failure

Inequality in Care and Differences in Outcome Following Stroke in People With ESRD

Acknowledgments: MF is funded by a Kidney Research UK Training Fellowship and is supported by a grant from Darlinda’s Charity for Renal Research.Peer reviewedPublisher PD

Short- and long-term outcomes of intensive care patients with acute kidney disease

Background: Acute kidney disease (AKD) is a proposed definition for acute kidney injury (AKI) lasting 7 days or longer. Little has been reported regarding characteristics of patients with AKD and their short- and long-term outcomes. We describe the epidemiology and risk factors for AKD and outcomes following AKD. Methods: This retrospective observational cohort study identified patients aged 16 or older admitted to the Glasgow Royal Infirmary and Queen Elizabeth University Hospital intensive care units (ICUs) in Scotland between 1st July 2015 and 30th June 2018. Baseline serum creatinine and subsequent values were used to identify patients with de-novo kidney injury (DNKI). Patients with recovery prior to day 7 were classified as AKI; recovery at day 7 or beyond was classified as AKD. Outcomes were in-hospital and long-term mortality, and proportion of major adverse kidney events (MAKEs). Multivariable logistic regression was used to identify risk factors for AKD. A Cox proportional hazards model was used to identify factors associated with long-term outcomes. Findings: Of the 5,334 patients admitted to ICU who were assessed for DNKI, 1,620 (30·4%) suffered DNKI and of these, 403 (24·9%) met AKD criteria; 984 (60·7%) were male and the median age was 60·0 (IQR=48·0–72·0). Male sex, sepsis and lower baseline estimated glomerular filtration rate (eGFR) were associated with development of AKD. In-ICU (16·1%vs6·2%) and in-hospital (26·1%vs11·6%) mortality rates were significantly higher in AKD patients than AKI patients. Long-term survival was not different for AKD patients (HR=1·16; p-value=0·261) but AKD was associated with subsequent MAKEs (OR=1·25). Interpretation: One in four ICU patients with DNKI met AKD criteria. These patients had an increased risk of short-term mortality and long-term MAKEs. Whilst the trend for long-term survival was lower, this was not significantly different from shorter-term AKI patients. Patients with AKD during their ICU stay should be identified to initiate interventions to reduce risk of future MAKEs. Funding: No funding was associated with this study

Cold Atmospheric Plasma Induces Accumulation of Lysosomes and Caspase-independent Cell Death in U373MG Glioblastoma Multiforme Cells

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death

Interaction between socioeconomic deprivation and likelihood of pre‐emptive transplantation: influence of competing risks and referral characteristics – a retrospective study

Socioeconomic deprivation (SED) influences likelihood of pre‐emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end‐stage kidney disease (ESKD) and death. Of 7765 patients with follow‐up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were “less deprived” with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation

Proton pump inhibitor use and progression to major adverse renal events: a competing risk analysis

Background: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD). Aim: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD. Design: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 1 January 2006 until 31 December 2016. Methods: We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end-stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis. Results: There were 3824 patients with CKD included in the analyses of whom 1195 were prescribed a PPI. The PPI group was younger (64.8 vs. 67.0 years, P < 0.001), with lower estimated glomerular filtration rate (eGFR) (30 vs. 35 ml/min, P < 0.001) and more proteinuria (64 vs. 48 mg/mmol, P < 0.001). PPI use was associated with progression to MARE on multivariable adjustment (hazard ratio 1.13 [95% confidence interval 1.02–1.25], P = 0.021). Other factors significantly associated with progression to MARE were higher systolic blood pressure, lower eGFR, greater proteinuria, congestive cardiac failure and diabetes. Hypomagnesaemia was more common in the PPI group (39.5 vs. 18.9%, P < 0.001). Conclusion: PPI use was associated with progression to MARE, but not death in patients with CKD after adjusting for factors known to predict declining renal function, including lower eGFR, proteinuria and comorbidities. A prospective cohort study is required to validate these findings