Search

Background Quality of life (QoL) is an important measure of disease burden and general health perception. The relationship between early chronic kidney disease (CKD) and QoL remains poorly understood. The Oxford Renal Study (OxRen) cohort comprises 1063 adults aged ≥60 years from UK primary care practices screened for early CKD, grouped according to existing or screen-detected CKD diagnoses, or biochemistry results indicative of reduced renal function (referred to as transient estimated glomerular filtration rate (eGFR) reduction). Objectives This study aimed to compare QoL in participants known to have CKD at recruitment to those identified as having CKD through a screening programme. Methods Health profile data and multi-attribute utility scores were reported for two generic questionnaires: 5-level EuroQol-5 Dimension (EQ-5D-5L) and ICEpop CAPability measure for Adults (ICECAP-A). QoL was compared between patients with existing and screen-detected CKD; those with transient eGFR reduction served as the reference group in univariable and multivariable linear regression. Results Mean and standard deviation utility scores were not significantly different between the subgroups for EQ-5D-5L (screen-detected:0.785±0.156, n = 480, transient:0.779±0.157, n = 261, existing CKD:0.763±0.171, n = 322, p = 0.216) or ICECAP-A (screen-detected:0.909±0.094, transient:0.904±0.110, existing CKD:0.894±0.115, p = 0.200). Age, smoking status, and number of comorbidities were identified as independent predictors of QoL in this cohort. Conclusion QoL of participants with existing CKD diagnoses was not significantly different from those with screen-detected CKD or transient eGFR reduction and was similar to UK mean scores for the same age, suggesting that patient burden of early CKD is minor. Moreover, CKD-related comorbidities contribute more significantly to disease burden in earlier stages of CKD than renal function per se. Larger prospective studies are required to define the relationship between QoL and CKD progression more precisely. These data also confirm the essentially asymptomatic nature of CKD, implying that routine screening or case finding are required to diagnose it.

Background In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD). Methods and findings Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739). Participants were excluded if they had multiple myeloma or any other B cell lymphoproliferative disorder with end-organ damage. Median age was 71.0 years, 50.6% were male, median estimated glomerular filtration rate was 42.3 ml/min/1.73 m2, and median urine albumin-to-creatinine ratio was 3.4 mg/mmol. All non-malignant MG was identified in the baseline serum of participants of RIISC. Further, light chain MG (LC-MG) was identified and studied in participants of RIISC, SKS, and RRID. Participants were followed up for kidney failure (defined as the initiation of dialysis or kidney transplantation) and death. Associations with the risk of kidney failure were estimated by competing-risks regression (handling death as a competing risk), and associations with death were estimated by Cox proportional hazards regression. In total, 102 (11.6%) of the 878 RIISC participants had an MG. During a median follow-up time of 74.0 months, there were 327 kidney failure events and 202 deaths. The presence of MG was not associated with risk of kidney failure (univariable subhazard ratio [SHR] 0.97 [95% CI 0.68 to 1.38], P = 0.85; multivariable SHR 1.16 [95% CI 0.80 to 1.69], P = 0.43), and although there was a higher risk of death in univariable analysis (hazard ratio [HR] 2.13 [95% CI 1.49 to 3.02], P < 0.001), this was not significant in multivariable analysis (HR 1.37 [95% CI 0.93 to 2.00], P = 0.11). Fifty-five (1.6%) of the 3,478 participants from all 3 studies had LC-MG. During a median follow-up time of 62.5 months, 564 of the 3,478 participants progressed to kidney failure, and 803 died. LC-MG was not associated with risk of kidney failure (univariable SHR 1.07 [95% CI 0.58 to 1.96], P = 0.82; multivariable SHR 1.42 [95% CI 0.78 to 2.57], P = 0.26). There was a higher risk of death in those with LC-MG in the univariable model (HR 2.51 [95% CI 1.59 to 3.96], P < 0.001), but not in the multivariable model (HR 1.49 [95% CI 0.93 to 2.39], P = 0.10). An important limitation of this work was that only LC-MG, rather than any MG, could be identified in participants from SKS and RRID. Conclusions The prevalence of MG was higher in this CKD cohort than that reported in the general population. However, the presence of an MG was not independently associated with a significantly higher risk of kidney failure or, unlike in the general population, risk of death., Anthony Fenton et al describe the association of monoclonal gammopathy with kidney failure and mortality in patients with Chronic Kidney Disease., Author summary Why was this study done? Non-malignant monoclonal gammopathy (MG) is a common pre-malignant condition that can be associated with kidney damage and a higher risk of death. Chronic kidney disease (CKD) is also common, affecting approximately 10% of adults, and people with CKD may be more likely to have an MG. It is unknown whether having an MG is associated with higher risk of kidney failure or death in people with CKD. What did the researchers do and find? We examined how common an MG is in patients with CKD, and also examined the associations between MG and kidney failure and death using data from 3 cohort studies of patients with CKD in the UK. An MG was present in 11.6% of patients with CKD. Patients with an MG did not have a higher risk of kidney failure or death. What do these findings mean? Our results are consistent with a previous study that suggested that MG is more common in patients with CKD. However, the presence of an MG was not associated with a higher risk of kidney failure or death. Although this is reassuring for patients with CKD and their healthcare providers, we did not examine whether having an MG is associated with the risk of other adverse outcomes.

Background Increased in-hospital mortality associated with weekend admission has been reported for many acute conditions, but no study has investigated “weekend effect” for acute kidney injury requiring dialysis (AKI-D). Methods In this large, propensity score matched cohort of AKI-D, we examined the impact of weekend admission and in-centre nephrology services in 53,170 AKI-D admissions between 1st April 2003 and 31st March 2015 using a hospital episode statistic dataset. Propensity score matching (PSM) was performed to match 4284 weekend admissions with AKI-D with 14,788 admissions on weekdays. Results Of the 53,170 admissions with AKI-D in the whole dataset, 12,357 (23%) were at weekends. The unadjusted mortality for weekend admissions was significantly higher compared to admissions on weekdays (40·6% versus 39·6%, p 0·046). However, in multivariable analysis of the PSM cohort, the odds of death for weekend admissions with AKI-D was 1·01 (95%CI 0·93,1·09). Mortality was higher for weekend admissions in West Midlands (odds ratio (OR) 1·32, 95% confidence interval (CI) 1·05, 1·66) and lower in East of England (OR 0·77, 95%CI 0·59, 1·00) but was not different to weekday admissions in all other regions. In 2003–04, weekend admissions had lower odds of death (OR 0·45, 95%CI 0·21, 0·96) and in 2010–11 higher odds of death (OR 1·28, 95%CI 1·00, 1·63) but in the other ten years observed, there was no significant difference in mortality between weekday and weekend admissions. Provision of in-centre nephrology services was associated with lower odds of death at 0·57 (95%CI 0·54, 0·62). Conclusions Weekend admissions in patients with AKI-D had no effect on mortality. Further research is warranted to elucidate the reasons for the lower mortality in hospitals with in-centre nephrology services.

Background To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45–59 ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed. Methods and findings A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to ‘no CKD’ or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFRcys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFRcys to confirm the diagnosis in people classified as CKD G3aA1 by eGFRcreat. Mean eGFRcys was significantly lower than mean eGFRcreat (45.1 ml/min/1.73 m2, 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m2, 95% CI 53.0 to 54.1, P < 0.001). eGFRcys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFRcreat to eGFR ≥ 60 ml/min/1.73 m2. However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFRcreat-cys, but lower proportions were reclassified. Change in eGFRcreat and eGFRcys over 5 years were weakly correlated (r = 0.33, P < 0.001), but eGFRcys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFRcreat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFRcys. Use of eGFRcys or eGFRcreat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFRcreat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1 increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort. Conclusions Implementation of current guidelines on eGFRcys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFRcreat. Use of eGFRcys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFRcys and eGFRcreat-cys., Adam Shardlow and colleagues investigate whether using cystatin C in addition to serum creatinine can improve diagnosis and risk prediction for progression of CKD among patients in primary care, and estimate the costs of additional testing and monitoring., Author summary Why was this study done? Estimation of kidney function (glomerular filtration rate) from serum creatinine concentration may be inaccurate in some people due to the impact of muscle mass, diet, and drugs on creatinine concentration. To reduce over-diagnosis of chronic kidney disease, international and UK guidelines recommend that the diagnosis of chronic kidney disease should be confirmed with an estimate of kidney function based on a different marker of glomerular filtration, cystatin C, in those people with only a mild reduction in glomerular filtration rate and no albuminuria. The clinical utility of this guidance has not been adequately evaluated in primary care, the setting in which most people with chronic kidney disease are cared for. What did the researchers do and find? We estimated glomerular filtration rate from serum creatinine and cystatin C in a cohort of 1,741 mainly older people diagnosed with chronic kidney disease in primary care. The use of cystatin C to confirm a diagnosis of chronic kidney disease resulted in reclassification of a small proportion (7.7%) of people as not having chronic kidney disease, but a much greater proportion were reclassified as having more advanced disease (59%). In this cohort, the use of cystatin C did not result in improved risk prediction for all-cause mortality or progression of chronic kidney disease. We estimate that the use of cystatin C as recommended in current guidelines would result in increased healthcare costs of £23 per person in the first year of implementation. What do these findings mean? Our data do not support the use of cystatin C to confirm a diagnosis of chronic kidney disease in primary care. Cystatin C may be useful for estimating glomerular filtration rate in other settings where creatinine is known to be unreliable, for example in people with extremes of body habitus.

Background The absence of effective interventions in presence of increasing national incidence and case-fatality in acute kidney injury requiring dialysis (AKI-D) warrants a study of regional variation to explore any potential for improvement. We therefore studied regional variation in the epidemiology of AKI-D in English National Health Service over a period of 15 years. Method We analysed Hospital Episode Statistics data for all patients with a diagnosis of AKI-D, using ICD-10-CM codes, in English regions between 2000 and 2015 to study temporal changes in regional incidence and case-fatality. Results Of 203,758,879 completed discharges between 1st April 2000 and 31st March 2015, we identified 54,252 patients who had AKI-D in the nine regions of England. The population incidence of AKI-D increased variably in all regions over 15 years; however, the regional variation decreased from 3·3-fold to 1·3-fold (p

• Acute Kidney Injury (AKI) is defined using widely accepted international criteria that are based on changes in serum creatinine concentration and degree of oliguria. • AKI, when defined in this way, has a strong association with poor patient outcomes, including high mortality rates and longer hospital admissions with increased resource utilisation and subsequent chronic kidney disease. • The detection of AKI using current criteria can assist with AKI diagnosis and stratification of individual patient risk. • The diagnosis of AKI requires clinical judgement to integrate the definition of AKI with the clinical situation, to determine underlying cause of AKI, and to take account of factors that may affect performance of current definitions.

A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P 43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P

Background: Early chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk but underlying mechanisms remain uncertain. Arterial stiffness (AS) is associated with increased CV risk in advanced CKD, but it is unclear whether AS is relevant to CV disease (CVD) in early CKD. Study Design: Cross-sectional. Setting and participants: 1717 patients with previous estimated glomerular filtration rate (eGFR) 59–30 mL/min/1.73 m2; mean age 7369y, were recruited from 32 general practices in primary care. Outcomes: Increased arterial stiffness. Measurements: Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Carotid to femoral pulse wave velocity (PWV) was determined as a measure of AS, using a VicorderTM device. Results: Univariate analysis revealed significant correlations between PWV and risk factors for CVD including age (r = 0.456; p,0.001), mean arterial pressure (MAP) (r = 0.228; p,0.001), body mass index (r = 20.122; p,0.001), log urinary albumin to creatinine ratio (r = 0.124; p,0.001), Waist to Hip ratio (r = 0.124, p,0.001), eGFR (r = 20.074; p = 0.002), log high sensitivity c-reactive protein (r = 0.066; p = 0.006), HDL (r = 20.062; p = 0.01) and total cholesterol (r = 20.057; p = 0.02). PWV was higher in males (9.6 m/sec vs.10.3 m/sec; p,0.001), diabetics (9.8 m/sec vs. 10.3 m/sec; p,0.001), and those with previous CV events (CVE) (9.8 m/s vs. 10.3 m/sec; p,0.001). Multivariable analysis identified age, MAP and diabetes as strongest independent determinants of higher PWV (adjusted R2 = 0.29). An interactive term indicated that PWV increased to a greater extent with age in males versus females. Albuminuria was a weaker determinant of PWV and eGFR did not enter the model. Limitations: Data derived from one study visit, with absence of normal controls. Conclusion: In this cohort, age and traditional CV risk factors were the strongest determinants of AS. Albuminuria was a relatively weak determinant of AS and eGFR was not an independent determinant. Long-term follow-up will investigate AS as an independent risk factor for CVE in this cohort.