Chronic Kidney Disease – Where Next? : Predicting Outcomes And Planning Care Pathways

Peer reviewedPublisher PD

Long Term Prognosis after Acute Kidney Injury (AKI) - What is the Role of Baseline Kidney Function and Recovery? A Systematic Review

Peer reviewedPublisher PD

Thrombin-anti-thrombin levels and patency of arterio-venous fistula in patients undergoing haemodialysis compared to healthy volunteers : a prospective analysis

Peer reviewedPublisher PD

Platelet function in patients with end-stage renal failure undergoing haemodialysis

Background: The onset of thrombosis in the vascular access for dialysis has a significant impact on access survival, quality of life and health care cost. Controversy exists as to the role of platelet activation in vascular access thrombosis. We aimed to assess platelet activity in patients on haemodialysis (HD) compared with healthy volunteers. Methods: Venous blood samples were taken from 55 patients immediately before (baseline) and 30 min after HD and from 72 resting healthy volunteers. Platelet function was assessed by: (1) Ultegra rapid platelet function assay (RPFA), using the agonists thrombin receptor activating peptide (TRAP) and arachidonic acid (ASA), and (2) flow cytometric measurement of P-selectin expression and fibrinogen binding both with and without ex vivo 10 uM ADP stimulation. Results: At baseline, ASA-stimulated platelet aggregation was lower in patients on aspirin (n = 27) compared with volunteers (median (iqr) 471 (82) versus 650 (54), P 0·05). TRAP-stimulated platelet aggregation was not significantly different between patients and volunteers. P-selectin expression on unstimulated platelets was lower in patients than volunteers (% positive platelets 0·79 (1·0) versus 1·68 (1·43), P < 0·001). Fibrinogen binding on resting platelets was higher in patients than volunteers [median (IQR) 1·95 (0·99) versus 1·39 (0·75) P < 0·001] but ADP-stimulated fibrinogen binding was lower [40·9 (25·8) versus 50·6 (19·8]. Following HD, there were no significant changes in ASA aggregation, unstimulated P-selectin or fibrinogen binding. Changes in TRAP-aggregation, stimulated P-selectin and fibrinogen binding occurred post-dialysis. The effects of heparin could contribute to some of the post-HD changes. Conclusion: This study suggests a complex picture of platelet function, but no overall evidence of increased platelet activation in patients on haemodialysis. Although aspirin might be required for its cardioprotective role, it may not aid the prevention of access thrombosis. Other causes and preventative medical therapies for vascular access thrombosis require to be investigated.peer-reviewe

Activated platelets and coagulation in patients on haemodialysis

Objective: Patients on haemodialysis (HD) have an increased risk of cardiac events. Controversy exists as to whether these patients have a pro-thrombotic state. We aimed to determine markers of platelet activation and coagulation in patients on HD compared with healthy volunteers. Method: Platelet function was assessed in 78 patients pre-HD and 78 volunteers by: i) Ultegra rapid platelet function assay using the agonists thrombin receptor activating peptide (TRAP) and arachidonic acid (ASA); ii) flow cytometry of P-selectin expression and fibrinogen binding with/without ADP stimulation; and iii) measuring plasma soluble P-selectin. Coagulation and fibrinolysis were assessed by ELISA determination of thrombin-antithrombin (TAT) and D- dimer, respectively. Results: ASA-stimulated platelet aggregation was significantly reduced in HD patients, of whom 50 (64%) were on aspirin therapy (median [IQR] 555 [355–671] versus 649 [385–675], p < 0·001). TRAP-mediated aggregation was similar in both groups. Unstimulated fibrinogen binding was significantly increased in patients (2·02 [1·48–2·62] versus 1·46 [1·15–1·94], p < 0·001) but stimulated fibrinogen was decreased (40·75 [26·7–50·3] versus 50·05 [40·6–59·9], p < 0·001). Unstimulated P-selectin was significantly decreased in patients (0·82 [0·52–1·46] versus 1·62 [0·86–2·34], p < 0·001), yet soluble P-selectin was significantly increased (43·26 [13·88–86·7] versus 24·67 [13·41–43·32], p = 0·039). Stimulated P-selectin was similar in both groups. Markers of coagulation were significantly increased in patients on HD: TAT 4·59 (2·67–6·04) versus 2·84 (1·81–3·82), p < 0·001 and D-dimer 876·5 (434·2–1338·5) versus 265·5 (175·0–401·51), p < 0·001. Conclusion: Patients on HD have a pro-thrombotic state with chronically activated platelets and elevated markers of coagulation. Drug therapy to counteract this pro-thrombotic state should be considered with the aim of preventing both cardiac events and vascular access thrombosis.peer-reviewe

Acute kidney injury associated with COVID-19: A retrospective cohort study

BackgroundInitial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19–associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom.Methods and findingsWe extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19–negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p [less than] 0.001), had a greater proportion of men (56.6% versus 44.9%, p [less than] 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p [less than] 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19–positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19–negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p [less than] 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p [less than] 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p [less than] 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region.ConclusionsWe observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this

Looking to the future: predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Background Chronic kidney disease (CKD) is common and important due to poor outcomes. An ability to stratify CKD care based on outcome risk should improve care for all. Our objective was to develop and validate 5-year outcome prediction tools in a large population-based CKD cohort. Model performance was compared with the recently reported ‘kidney failure risk equation’ (KFRE) models. Methods Those with CKD in the Grampian Laboratory Outcomes Mortality and Morbidity Study-I (3396) and -II (18 687) cohorts were used to develop and validate a renal replacement therapy (RRT) prediction tool. The discrimination, calibration and overall performance were assessed. The net reclassification index compared performance of the developed model and the 3- and 4-variable KFRE model to predict RRT in the validation cohort. Results The developed model (with measures of age, sex, excretory renal function and proteinuria) performed well with a C-statistic of 0.938 (0.918–0.957) and Hosmer–Lemeshow (HL) χ2 statistic 4.6. In the validation cohort (18 687), the developed model falsely identified fewer as high risk (414 versus 3278 individuals) compared with the KFRE 3-variable model (measures of age, sex and excretory renal function), but had more false negatives (58 versus 21 individuals). The KFRE 4-variable model could only be applied to 2274 individuals because of a lack of baseline urinary albumin creatinine ratio data, thus limiting its use in routine clinical practice. Conclusions CKD outcome prediction tools have been developed by ourselves and others. These tools could be used to stratify care, but identify both false positives and -negatives. Further refinement should optimize the balance between identifying those at increased risk with clinical utility for stratifying care

Late onset Pneumocystis jirovecii pneumonia (PJP) in patients with ANCA associated vasculitis

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Is routine hospital episode data sufficient for identifying individuals with chronic kidney disease?

Internationally, investment in the availability of routine health care data for improving health, health surveillance and health care is increasing. We assessed the validity of hospital episode data for identifying individuals with chronic kidney disease compared to biochemistry data in a large population-based cohort, the Grampian Laboratory Outcomes, Morbidity and Mortality Study-II (n = 70,435). Grampian Laboratory Outcomes, Morbidity and Mortality Study-II links hospital episode data to biochemistry data for all adults in a health region with impaired kidney function and random samples of individuals with normal and unmeasured kidney function in 2003. We compared identification of individuals with chronic kidney disease by hospital episode data (based on International Classification of Diseases-10 codes) to the reference standard of biochemistry data (at least two estimated glomerular filtration rates 97%). Using routine health care data from multiple sources offers the best opportunity to identify individuals with chronic kidney disease

Definitions of progression in chronic kidney disease-predictors and relationship to renal replacement therapy in a population cohort with a 6 year follow-up

Background. Chronic kidney disease (CKD) is common, important and associated with increased healthcare needs due to CKD progression. Definitions of renal disease progression are multiple, and not always comparable. A measure of 'progression' directly comparable with renal replacement therapy (RRT) initiation would identify 'progressors' in research and for healthcare planning.Methods. The Grampian Laboratory Outcomes Morbidity and Mortality Study (GLOMMS-I) is a community cohort with CKD from 2003, followed up to June 2009 for (i) RRT initiation and (ii) 'progression': sustained reduction in estimated glomerular filtration rate (eGFR) by 15 mL/min/1.73 m(2) (equivalent to CKD stage change), or to <10 mL/min/1.73 m(2), whichever occurs first. Predictors were baseline demographics and comorbidity. The use of the Kidney Disease: Improving Global Outcomes-2012 progression definition was also explored.Results. Two thousand two hundred and eighty-nine and 1044 had Stage 3 and 4 CKD, 44% were males. Overall, RRT initiation and progression rates were 0.97 and 3.50 per 100 patient-years (py). Females had significantly lower progression and RRT initiation rates. The progression rate was not dependent on CKD stage [incidence rate ratio (IRR) for Stage 4 (versus Stage 3) 0.9 (95% CI 0.8-1.2)], whereas the RRT initiation rate was [IRR 5.6 (95% CI 3.8-8.2)]. Increased proteinuria was associated with both greater RRT initiation and progression rates.Conclusions. Progression and RRT initiation rate ratios allow comparison of predictors of these outcomes. Higher rates of both in males suggest that greater RRT initiation rate is biological rather than due to preferential treatment. Similar progression but very different RRT initiation rates in Stage 3 and 4 CKD suggests that CKD stage effect on RRT initiation is a function of endpoint proximity rather than faster renal function deterioration.Background. Chronic kidney disease (CKD) is common, important and associated with increased healthcare needs due to CKD progression. Definitions of renal disease progression are multiple, and not always comparable. A measure of 'progression' directly comparable with renal replacement therapy (RRT) initiation would identify 'progressors' in research and for healthcare planning.Methods. The Grampian Laboratory Outcomes Morbidity and Mortality Study (GLOMMS-I) is a community cohort with CKD from 2003, followed up to June 2009 for (i) RRT initiation and (ii) 'progression': sustained reduction in estimated glomerular filtration rate (eGFR) by 15 mL/min/1.73 m(2) (equivalent to CKD stage change), or to <10 mL/min/1.73 m(2), whichever occurs first. Predictors were baseline demographics and comorbidity. The use of the Kidney Disease: Improving Global Outcomes-2012 progression definition was also explored.Results. Two thousand two hundred and eighty-nine and 1044 had Stage 3 and 4 CKD, 44% were males. Overall, RRT initiation and progression rates were 0.97 and 3.50 per 100 patient-years (py). Females had significantly lower progression and RRT initiation rates. The progression rate was not dependent on CKD stage [incidence rate ratio (IRR) for Stage 4 (versus Stage 3) 0.9 (95% CI 0.8-1.2)], whereas the RRT initiation rate was [IRR 5.6 (95% CI 3.8-8.2)]. Increased proteinuria was associated with both greater RRT initiation and progression rates.Conclusions. Progression and RRT initiation rate ratios allow comparison of predictors of these outcomes. Higher rates of both in males suggest that greater RRT initiation rate is biological rather than due to preferential treatment. Similar progression but very different RRT initiation rates in Stage 3 and 4 CKD suggests that CKD stage effect on RRT initiation is a function of endpoint proximity rather than faster renal function deterioration