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Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.

BackgroundIngestion of cooked meat increases circulating blood creatinine concentration due to conversion of creatine during cooking. This may cause falsely low estimated glomerular filtration rate. National Institute for Health and Care Excellence chronic kidney disease guidelines recommend meat avoidance prior to blood testing for estimated glomerular filtration rate. Fish muscle also contains creatine, but the influence of fish consumption on blood creatinine concentration has not been studied.MethodFour blood samples were collected from each of 20 healthy volunteers: one before and three (at 2, 4 and 20 h) after consuming cooked fish (200 g/person cod, approximately 35 g/person protein). Apart from this meal, for the study duration, subjects were asked to avoid eating meat or fish. Creatinine and cystatin C were measured and estimated glomerular filtration rate (CKD-EPI equations) was calculated.ResultsSerum creatinine concentration (mean) was increased relative to the preprandial concentration (71.8 μmol/L) in all subjects at 2 h (77.3 μmol/L) and in 17/20 subjects at 4 h (75.5 μmol/L) ( P 0.05). Estimated glomerular filtration rate calculated using the CKD-EPI (creatinine) and CKD-EPI (creatinine and cystatin C) equations demonstrated significant declines at 2 and 4 h ( P 0.05).ConclusionCooked fish consumption transiently increases blood creatinine concentration and consequently lowers the estimates of glomerular filtration rate derived from creatinine-based equations. Consideration should be given to avoidance of cooked fish consumption before glomerular filtration rate estimation.

Background Patients with chronic kidney disease often have increased plasma cardiac troponin concentration in the absence of myocardial infarction. Incidence of myocardial infarction is high in this population, and diagnosis, particularly of non ST-segment elevation myocardial infarction (NSTEMI), is challenging. Knowledge of biological variation aids understanding of serial cardiac troponin measurements and could improve interpretation in clinical practice. The National Academy of Clinical Biochemistry (NACB) recommended the use of a 20% reference change value in patients with kidney failure. The aim of this study was to calculate the biological variation of cardiac troponin I and cardiac troponin T in patients with moderate chronic kidney disease (glomerular filtration rate [GFR] 30–59 mL/min/1.73 m2). Methods and results Plasma samples were obtained from 20 patients (median GFR 43.0 mL/min/1.73 m2) once a week for four consecutive weeks. Cardiac troponin I (Abbott ARCHITECT® i2000SR, median 4.3 ng/L, upper 99th percentile of reference population 26.2 ng/L) and cardiac troponin T (Roche Cobas® e601, median 11.8 ng/L, upper 99th percentile of reference population 14 ng/L) were measured in duplicate using high-sensitivity assays. After outlier removal and log transformation, 18 patients’ data were subject to ANOVA, and within-subject (CVI), between-subject (CVG) and analytical (CVA) variation calculated. Variation for cardiac troponin I was 15.0%, 105.6%, 8.3%, respectively, and for cardiac troponin T 7.4%, 78.4%, 3.1%, respectively. Reference change values for increasing and decreasing troponin concentrations were +60%/–38% for cardiac troponin I and +25%/–20% for cardiac troponin T. Conclusions The observed reference change value for cardiac troponin T is broadly compatible with the NACB recommendation, but for cardiac troponin I, larger changes are required to define significant change. The incorporation of separate RCVs for cardiac troponin I and cardiac troponin T, and separate RCVs for rising and falling concentrations of cardiac troponin, should be considered when developing guidance for interpretation of sequential cardiac troponin measurements.

The bidirectional relationship between cancer and chronic kidney disease (CKD) is complex. Patients with cancer, particularly those with hematological malignancies such as multiple myeloma and lymphoma, are at increased risk of developing acute kidney injury and CKD. On the other hand, emerging evidence from large observational registry analyses have consistently shown that cancer risk is increased by at least 2- to 3-fold in kidney transplant recipients, and the observed increased risk occurs not only in those who have received kidney transplants but also in those on dialysis and with mild- to moderate-stage CKD. The interactions between cancer and CKD have raised major therapeutic and clinical challenges in the management of these patients. Given the magnitude of the problem and uncertainties, and current controversies within the existing evidence, Kidney Disease: Improving Global Outcomes (KDIGO) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology to identify key management issues in nephrology relevant to patients with malignancy. This report covers the discussed controversies in kidney disease in hematological malignancies, as well as cancer after kidney transplantation. An overview of future research priorities is also discussed.

Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.

© 2020 Kidney Disease:Improving Global Outcomes (KDIGO)The association between kidney disease and cancer is multifaceted and complex. Persons with chronic kidney disease (CKD) have an increased incidence of cancer, and both cancer and cancer treatments can cause impaired kidney function. Renal issues in the setting of malignancy can worsen patient outcomes and diminish the adequacy of anticancer treatments. In addition, the oncology treatment landscape is changing rapidly, and data on tolerability of novel therapies in patients with CKD are often lacking. Caring for oncology patients has become more specialized and interdisciplinary, currently requiring collaboration among specialists in nephrology, medical oncology, critical care, clinical pharmacology/pharmacy, and palliative care, in addition to surgeons and urologists. To identify key management issues in nephrology relevant to patients with malignancy, KDIGO (Kidney Disease: Improving Global Outcomes) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology in December 2018. This report covers issues related to kidney impairment and solid organ malignancies as well as management and treatment of kidney cancer. Knowledge gaps, areas of controversy, and research priorities are described.

When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with moderate CKD (GFR 30-59 ml/min per 1.73 m2). Patients underwent weekly GFR measurement by iohexol clearance over four consecutive weeks. Simultaneously, GFR was estimated using the MDRD, CKD-EPIcreatinine, CKD-EPIcystatinC and CKD-EPIcreatinine+cystatinC equations. Within-subject biological variation expressed as a percentage [95% confidence interval] for the MDRD (5.0% [4.3-6.1]), CKD-EPIcreatinine (5.3% [4.5-6.4]), CKD-EPIcystatinC (5.3% [4.5-6.5]), and CKD-EPIcreatinine+cystatinC (5.0% [4.3-6.2]) equations were broadly equivalent. The within-subject biological variation for MDRD and CKD- EPIcreatinine+cystatinC estimated GFR were each significantly lower than that of the measured GFR (6.7% [5.6-8.2]). Reference change values, the point at which a true change in a biomarker in an individual can be inferred to have occurred with 95% probability were calculated. By the MDRD equation, positive and negative reference change values were 15.1% and 13.1% respectively. If an individual's baseline MDRD estimated GFR (ml/min per 1.73 m2) was 59, significant increases or decreases would be to values over 68 or under 51 respectively. Within-subject variability of estimated GFR was lower than measured GFR. Reference change values can be used to understand GFR changes in clinical practice. Thus, estimates of GFR are at least as reliable as measured GFR for monitoring patients over time.

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.

Surveillance of chronic kidney disease (CKD) prevalence over time and information on how changing risk factors influence this trend are needed to evaluate the effects of general practice and public health interventions. Because very few studies addressed this, we studied the total adult population of a demographically stable county representative of Norway using cross-sectional studies 10 years apart (Nord-Trøndelag Health Study (HUNT)2 and Nord-Trøndelag Health Study (HUNT)3, 65,237 and 50,586 participants, respectively). Thorough quality-control procedures and comparisons of methods over time excluded analytical drift, and multiple imputations of missing data combined with nonattendance weights contributed to unbiased estimates. CKD prevalence remained stable in Norway from 1995 through 1997 (11.3%) to 2006 through 2008 (11.1%). The association of survey period with CKD prevalence was modified by a strong decrease in blood pressure, more physical activity, and lower cholesterol levels. Without these improvements, a 2.8, 0.7, and 0.6 percentage points higher CKD prevalence could have been expected, respectively. In contrast, the prevalence of diabetes and obesity increased moderately, but the proportion of diabetic patients with CKD decreased significantly (from 33.4% to 28.6%). A CKD prevalence of 1 percentage point lower would have been expected without these changes. Thus, CKD prevalence remained stable in Norway for more than a decade in association with marked improvements in blood pressure, lipid levels, and physical activity and despite modest increases in diabetes and obesity.

Clinical practice guidelines provide guidance in decision making relating to diagnosis, management, and treatment in specific areas of health care. They play an essential role in the evaluation and synthesis of an ever-expanding evidence base and are of increasing importance in aging societies with a high prevalence of overlapping disease comorbid conditions. Integration of chronic disease guidance is essential, particularly in older people, in order to understand critical disease interactions and the potential adverse effects that individual guideline statements may engender in different disease areas. This requires a need for flexibility that not only recognizes the differences in patients' characteristics, but also their preferences for medical interventions and health outcomes. The question is how this can be achieved. In this article, we look at the standardization of clinical practice guidelines from the chronic kidney disease standpoint and consider how tools for integrating guidelines, such as the ADAPTE process and the knowledge-to-action cycle, can be used to guide appropriate decision making and take account of patient choice in older adults with multimorbidity.

Chronic kidney disease prevalence increases markedly with age1 and accurate estimation of GFR is an important issue in older people. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPIcr)2 and variations including cystatin C (CKD-EPIcys) or both creatinine and cystatin C (CKD-EPIcr-cys)3 have been recommended for estimating GFR.4 Recently, the Berlin Initiative Study (BIS) reported 2 GFR equations specifically developed in older people: BIS1, which uses creatinine, and BIS2, which uses both creatinine and cystatin C.5 Here, we compare how the BIS and CKD-EPI equations perform in a large cohort of older people.

The 2012 KDIGO Guideline for CKD evaluation, classification, and management has updated the original 2002 KDOQI Guidelines, using newer data and addressing issues raised over the last decade concerning definitions and assessment. This review highlights the key aspects of the CKD guideline, and describes the rationale for specific wording and the scope of the document. A précis of key concepts in each of the five sections of the guideline is presented. The guideline document is intended for general practitioners and nephrologists, and covers CKD evaluation, classification, and management for both adults and children. Throughout the guideline, we have attempted to overtly address areas of controversy or non-consensus, international relevance, and impact on practice and public policy.

Background: There is debate as to whether using the urinary albumin- or protein-to-creatinine ratio (ACR or PCR) should be the primary test for proteinuria. Whilst albuminuria (increased ACR) in the absence of proteinuria (increased PCR) may be expected in some patients, the converse (i.e., proteinuria in the absence of albuminuria) is more unusual and its cause and significance are unclear. We investigated the nature of such apparent non-albuminuric proteinuria in a primary care population of patients. Methods: ACR and PCR were measured in 569 urine samples from patients who either had chronic kidney disease or were at increased risk of the condition. Samples with apparent proteinuria (PCR ≥23 mg/mmol/≥200 mg/g) but no albuminuria (ACR Results: Electrophoresis did not identify significant proteinuria in the discrepant samples. The only evidence of tubular proteinuria following measurement of three urinary markers of the condition was a mildly increased α1-microglobulin-to-creatinine ratio in 10 of the 27 discrepant samples analysed, four of which also had a raised β-trace protein-to-creatinine ratio. Use of an alternative urinary total protein method resulted in significantly lower PCRs and 17 of the 27 samples were no longer classified as proteinuric. Conclusions: We were unable to confirm the cause of a raised PCR without albuminuria in these patients and suspect that in most cases it is artefactual.

In 2002, the US National Kidney Foundation published their seminal Kidney Disease Outcome Quality Initiative (KDOQI)4 guideline on chronic kidney disease (CKD) (1). This guideline led to a revolution in the detection and management of CKD. Two of the cornerstones of kidney disease diagnosis and management—proteinuria and decreased glomerular filtration rate (GFR)—had always relied heavily on laboratory support. Inevitably, the guideline was avidly read by laboratory scientists and clinicians, with dramatic changes in practice ensuing. Implementation of the guideline was facilitated by the fact that a simple equation, the Modification of Diet in Renal Disease (MDRD) Study equation, had been published several years previously. This equation enabled estimation of GFR from the serum creatinine concentration, in addition to basic demographic details routinely supplied to laboratories. For the first time, a kidney disease definition and staging system were in use and linked directly to detection and management, and there was a simple and practical laboratory test available for the objective categorization of patients. Publication of the guideline contributed to an explosion in research, clinical evidence, and debate, in addition to the publication of other guidelines in other countries. There were also problems. The influence of creatinine method bias on the estimated GFR (eGFR) was perhaps the paramount problem, together with concerns of overdetection among some clinicians as the scale of the CKD “epidemic” came to be appreciated. Through joint efforts of the laboratory and nephrology community, the problems of standardization have largely been resolved. Some observers still have concerns about so-called disease labeling, but there is general agreement that a low GFR is associated with increased risk, regardless of age, sex, ethnicity, or underlying disease. The evidence generated in the last decade has driven an increased recognition of the need to revise the guideline and for increased sophistication. The work …

Background Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine–based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI cr ) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m 2 . Newer equations have been reported using cystatin C concentration either alone (CKD-EPI cys ) or in combination with creatinine concentration (CKD-EPI cr-cys ). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. Study Design Diagnostic test evaluation in a prospective cohort. Setting & Participants Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. Index Test GFR estimated using the MDRD Study, CKD-EPI cr , CKD-EPI cys and CKD-EPI cr-cys equations. Reference Test GFR measured using an iohexol clearance method. Results Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m 2 . MDRD Study–, CKD-EPI cr –, and CKD-EPI cr-cys –estimated GFRs overestimated GFR (median differences of 3.5 [ P P P = 0.02] mL/min/1.73 m 2 , respectively); the CKD-EPI cys equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P 30 ]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI cr , CKD-EPI cys , and CKD-EPI cr-cys equations, respectively. Accuracy of the MDRD Study equation was inferior ( P = 0.004) to the CKD-EPI cr equation at GFR >60 mL/min/1.73 m 2 . Limitations Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. Conclusions The CKD-EPI cr equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P 30 in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.

BackgroundAcute kidney injury (AKI) is a common clinical problem with significant morbidity and mortality. All hospitalised patients are at risk. AKI is often preventable and reversible; however, the 2009 National Confidential Enquiry into Patient Outcome and Death highlighted systematic failings of identification and management, and recommended risk assessment of all emergency admissions.ObjectivesTo develop three predictive models to stratify the risk of (1) AKI on arrival in hospital; (2) developing AKI during admission; and (3) worsening AKI if already present; and also to (4) develop a clinical algorithm for patients admitted to hospital and explore effective methods of delivery of this information at the point of care.Study designQuantitative methodology (1) to formulate predictive risk models and (2) to validate the models in both our population and a second population. Qualitative methodology to plan clinical decision support system (CDSS) development and effective integration into clinical care.Settings and participantsQuantitative analysis – the study population comprised hospital admissions to three acute hospitals of East Kent Hospitals University NHS Foundation Trust in 2011, excluding maternity and elective admissions. For validation in a second population the study included hospital admissions to Medway NHS Foundation Trust. Qualitative analysis – the sample consisted of six renal consultants (interviews) and six outreach nurses (focus group), with representation from all sites.Data collectionData (comprising age, sex, comorbidities, hospital admission and outpatient history, relevant pathology tests, drug history, baseline creatinine and chronic kidney disease stage, proteinuria, operative procedures and microbiology) were collected from the hospital data warehouse and the pathology and surgical procedure databases.Data analysisQuantitative – both traditional and Bayesian regression methods were used. Traditional methods were performed using ordinal logistic regression with univariable analyses to inform the development of multivariable analyses. Backwards selection was used to retain only statistically significant variables in the final models. The models were validated using actual and predicted probabilities, an area under the receiver operating characteristic (AUROC) curve analysis and the Hosmer–Lemeshow test. Qualitative – content analysis was employed.Main outcome measures(1) A clinical pratice algorithm to guide clinical alerting and risk modeling for AKI in emergency hospital admissions; (2) identification of the key variables that are associated with the risk of AKI; (3) validated risk models for AKI in acute hospital admissions; and (4) a qualitative analysis providing guidance as to the best approach to the implementation of clinical alerting to highlight patients at risk of AKI in hospitals.FindingsQuantitative – we have defined a clinical practice algorithm for risk assessment within the first 24 hours of hospital admission. Bayesian methodology enabled prediction of low risk but could not reliably identify high-risk patients. Traditional methods identified key variables, which predict AKI both on admission and at 72 hours post admission. Validation demonstrated an AUROC curve of 0.75 and 0.68, respectively. Predicting worsening AKI during admission was unsuccessful. Qualitative – analysis of AKI alerting gave valuable insights in terms of user friendliness, information availability, clinical communication and clinical responsibility, and has informed CDSS development.ConclusionsThis study provides valuable evidence of relationships between key variables and AKI. We have developed a clinical algorithm and risk models for risk assessment within the first 24 hours of hospital admission. However, the study has its limitations, and further analysis and testing, including continuous modelling, non-linear modelling and interaction exploration, may further refine the models. The qualitative study has highlighted the complexity regarding the implementation and delivery of alerting systems in clinical practice.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Over the last decade, since the introduction of an international classification of chronic kidney disease (CKD) and the development of simple tools to detect people with CKD, primary care has had to adapt to a new paradigm of disease. Significantly, improved identification of CKD, and increased awareness and understanding of the potential associated adverse outcomes, has in turn required the development, implementation and integration of new policies, models and pathways of care. The UK health care system, including primary care, is uniquely positioned to respond to new initiatives. Despite early reservations, CKD has gone from an unheard of condition in primary care prior to 2006 to one where people with this condition are recorded in disease registers and increasingly managed in accordance with evidence-based guidance. National and local initiatives implemented together have contributed to the improved understanding and management of CKD in primary care in the UK and are showing signs of having made significant health gains in CKD.

Anaemia is a common finding in people with diabetes and chronic kidney disease and failure of the kidney to produce erythro-poietin in response to a falling haemoglobin concentration is a key component, correlating with the degree of albuminuria, renal dysfunction and iron deficiency. Anaemia in diabetes is associated with a number of adverse outcomes, including increased risk of all cause and cardiovascular mortality. Whether or not anaemia is a marker or mediator of adverse outcome still remains to be completely resolved. Treatment of anaemia in diabetes has quality of life benefits and reduces transfusion requirements. Correction of anaemia to normal haemoglobin concentrations is associated with significant adverse cardiovascular outcomes and is not recommended, escalating doses of erythropoiesis-stimulating agents should be avoided. The treatment of anaemia in people with diabetes and chronic kidney disease should begin with optimisation of iron stores. An aspirational haemoglobin concentration range of 10-12 g/dl with anaemia management, balances proven benefits of anaemia treatment with potential cardiovascular risk.

SUMMARY Aim: To examine whether there is an independent association between body mass index (BMI) and estimated glomerular filtration rate (GFR) in a large primary care population. Methods: Anonymous data were sequentially extracted from primary care records between 2006 and 2009 in a primary care population of approximately 220 000 people in Kent, South East UK. Using GFR, BMI, age, gender and comorbidities we examined the association between BMI and GFR. Univariate and multivariate analysis was performed using SPSS® (SPSS Inc., Chicago). Results: Sixty-one thousand six-hundred thirty seven people fulfilled the inclusion criteria. There was no correlation between BMI and GFR on univariate analysis. When stratified by BMI, ANOVA demonstrated a statistically significant difference in GFR across BMI strata (p < 0.001). However the absolute differences in BMI between groups were very small. There was a small association between BMI and GFR on multivariate analysis, much of which was lost on adjustment for confounding variables. Conclusion: These findings suggest that elevated BMI is not a biologically significant predictor of diminished GFR and therefore may be an insufficiently accurate measure of risk for the metabolic syndrome and CKD.

The past decade has seen an increasing focus on chronic kidney disease (CKD) and its attendant complications, which has resulted in improved understanding of their impact on health-care resources. The early detection of CKD has been facilitated by the implementation of routine reporting of estimated glomerular filtration rates (eGFRs) and by education of primary care physicians on the implications of detecting a decreased eGFR with respect to patient safety as well as to cardiovascular and renal outcomes. The goals of early CKD detection are to prevent CKD progression and associated complications, thus improving patient outcomes and reducing the impact of CKD on health-care resources. This Review examines the benefits of the early detection of CKD, and describes the limitations of current knowledge with respect to screening, early detection and treatment, as well as the unintended consequences of detection. In addition, this article highlights what is currently known about cardiovascular and renal outcomes and the effects of intervention in patients with CKD.

Climate change is now considered to be a major global public health concern. However, the very provision of health care itself has a significant impact upon the environment. Action must be taken to reduce this impact. Water is a precious and finite natural resource. Vast quantities of high-grade water are required to provide haemodialysis. The reverse osmosis systems used in the purification process reject approximately two-thirds of the water presented to them. Therefore, around 250 litres of 'reject water' result from the production of the dialysate required for one treatment. This good quality reject water is lost-to-drain in the vast majority of centres worldwide. Simple methodologies exist to recycle this water for alternative purposes. We describe here a case study of the only UK renal service we know to have implemented such water-saving methodologies. We outline the benefits in terms of financial and environmental savings.

The main sources of guidelines in kidney disease in the United Kingdom are the National Institute of Health and Clinical Excellence (NICE), the UK Renal Association, and the Scottish Intercollegiate Guideline Network (SIGN). These groups now all adopt similar methods of guideline development, but implementation methods differ and also vary in their effectiveness. The structure of UK health care lends itself to an integrated implementation strategy, and the United Kingdom is almost unique in being able to introduce simultaneously related changes that aid implementation nationally, thereby enabling implementation locally. Use of these strategies is variable with possibly too much reliance on existing systems that deliver predictable suboptimal results and a failure to embed implementation strategies into routine organizational structure. The next steps for us in the United Kingdom are to use service improvement methods to improve and sustain consistently implementation of evidence-based practice.

Summary The British National Health Service is a closed managed care system. This single health care system for the United Kingdom is funded by the government and paid for by general taxation. All UK citizens are registered with primary care physicians who control access to secondary care services. As a managed care system it should be able to offer integrated care across the whole patient pathway. In reality there are professional, organizational, and institutional barriers to coordination and delivery of care in the NHS. Historically, the United Kingdom has been among the lowest health care spenders of organizations for economic cooperation in developed countries, in absolute terms as well as proportion of the gross domestic product. However, since a Government pledge to place quality at the heart of the NHS and a commitment in 2000 to increase spending on the NHS, the NHS budget has more than doubled—an unprecedented rate of growth, roughly by 7.5% annually in real terms. A quality and outcomes framework has been introduced into primary care to systematically incentivize process measures such as computerization and chronic disease management by establishing practice-based disease registers. The strategic planning for kidney services in England has been developed in this national environment complemented by local research findings and the wider international consensus that has emerged since the publication of the classification of chronic kidney disease in 2002. This program of work has resulted in a paradigm shift from kidney disease being viewed as a secondary care condition to being a primary care priority as part of vascular disease control and management. In the first 2 years of the initiative more than 40% of the expected chronic kidney disease stage 3 to 5 population have been registered in primary care. Kidney disease now is recognized as a public health problem in the United Kingdom, preventative strategies are being integrated into comprehensive vascular risk assessment and management programs, and kidney disease has become an NHS priority area.

Background and objectives: Anemia and hemoglobin (Hb) variability are associated with mortality in hemodialysis patients who are on erythropoiesis-stimulating agents (ESA). Our aim was to describe the degree of Hb variability present in nondialysis patients with chronic kidney disease (CKD), including those who were not receiving ESA, and to investigate the association between Hb variability and mortality. Design, setting, participants, & measurements: Hb variability was determined using 6 mo of “baseline” data between January 1, 2003, and October 31, 2005. A variety of definitions for Hb variability were examined to ensure consistency and robustness. Results: A total of 6165 patients from 22 centers in seven countries were followed for a mean of 34.0 ± 15.8 mo; 49% were prescribed an ESA. There was increased Hb variability with ESA use; the residual SD of Hb was 4.9 ± 4.4 g/L in patients who were not receiving an ESA, compared with 6.8 ± 4.8 g/L. Hb variability was associated with a small but significantly increased risk for death per g/L residual SD, irrespective of ESA use. Multivariate linear regression model explained only 11% of the total variance of Hb variability. Conclusions: Hb variability is increased in patients who have CKD and are receiving ESA and is associated with an increased risk for death (even in those who are not receiving ESAs). This analysis cannot determine whether Hb variability causally affects mortality. Thus, the concept of targeting Hb variability with specific agents needs to be examined within the context of factors that affect both Hb variability and mortality.

Background. Awareness of chronic kidney disease (CKD) has been prompted by the publication of several large epidemiological studies since 2002. This has led to various initiatives for the early identification and management of CKD, including the introduction of automated glomerular filtration rate (GFR) reporting and renal indicators in the primary care quality and outcomes framework (QOF) since April 2006. These initiatives were intended to promote identification of CKD and have had an impact on referral patterns to renal services. The aim of this study was to understand the nature of this impact in a catchment population of 1.2 million people. Methods. Data were collected and recorded from all written referrals from primary care between 1 April 2004 and 31 March 2008. Referral patterns for each postcode sector were mapped using Microsoft MapPoint 2004. The effect of chance on referral patterns was modelled by using small area analysis techniques. The association between the CKD prevalence reported from QOF data and the estimated CKD prevalence was examined at post-code district level. Results. There were 1461 referrals in 2 years prior to the introduction of the initiatives and 2890 referrals in the 2 years post-introduction. The main reason for referral in both groups was impaired renal function or previously established renal disease. Reported comorbidity was similar between the groups. Mapping showed that there was wide heterogeneity in referral behaviour in the first 2 years of the study, which was less in the second period. Small area analysis suggested that the variation that led to the extremal quotients observed in both of the study periods was not due to random variation in referral pattern alone. There was no correlation between the reported CKD prevalence and the referral rates. Conclusion. Referral patterns have changed between 1 April 2004 and 31 March 2008. The main findings were an increase in referral rate and in the age at referral without a significant change in reported comorbidity of the people referred. The main increase in referral rates was seen in more advanced CKD suggesting more targeted referral of patients with CKD to renal services.

Proteinuria is a classic sign of kidney disease and its presence carries powerful prognostic information. Although proteinuria testing is enshrined in clinical practice guidelines, there is surprising variation among such guidelines as to the definition of clinically significant proteinuria. There is also poor agreement as to whether proteinuria should be defined in terms of albumin or total protein loss, with a different approach being used to stratify diabetic and non-diabetic nephropathy. Further, the role of reagent strip devices in the detection and assessment of proteinuria is unclear. This review explores these issues in relation to recent national and international guidelines on chronic kidney disease (CKD) and epidemiological evidence linking proteinuria and clinical outcome. The authors argue that use of urinary albumin measurement as the front-line test for proteinuria detection offers the best chance of improving the sensitivity, quality and consistency of approach to the early detection and management of CKD.

Background Clinical management of peritoneal dialysis patients includes assessments of peritoneal and renal clearances of the low-molecular-weight endogenous solutes creatinine and urea. Cystatin C is a low-molecular-weight protein used as a glomerular filtration rate marker. We investigated whether serum cystatin C concentration is related to peritoneal and renal clearances of creatinine and urea. Study Design Cross-sectional study. Setting & Participants 119 patients undergoing peritoneal dialysis in a single dialysis unit. Predictor Peritoneal, renal, and total clearance of urea as Kt/V urea and creatinine as weekly creatinine clearance (C Cr ). Residual renal function (RRF) as the average of renal clearances of urea and creatinine. Outcomes & Measurements Serum concentrations of cystatin C measured by using a particle-enhanced nephelometric immunoassay. Results Serum cystatin C concentration was related inversely to RRF (Spearman rank correlation coefficient [ r s ] = −0.65; P Cr ( r s = −0.52; P urea ( r s = −0.23; P = 0.01). In a multiple regression model, weight, normalized protein catabolic rate, and RRF had independent effects on serum cystatin C concentrations. Additional multiple regression models showed that only the renal components of Kt/V urea and weekly C Cr contributed to serum cystatin C concentrations. Limitations Absence of reference GFR method. Conclusions Serum cystatin C concentrations reflect predominantly renal, not peritoneal, clearance. Serum cystatin C measurement may be a simple and practical alternative to measurement of RRF.

The last few years have seen new developments to understand and tackle the significant public health issue posed by chronic kidney disease (CKD). Established renal disease currently consumes 2% of the UK National Health Service budget and predictions are that this figure will increase significantly due to the rising number of people requiring renal replacement therapy fuelled by the ageing population and the diabetes mellitus epidemic. This paper reviews the scale of CKD and discusses the new developments such as staging, referral guidelines and new Department of Health incentives brought about to improve awareness. The importance of Information Technology in assisting the management of renal disease is also outlined. We identify various types of intervention which might be used to do this: feedback in an educational context, the establishment of computerized decision support and enhancement of the patient journey. Many principles may be extended to the management of any chronic disease. While new developments are necessary to improve care, wider implementation is required to be able to see if improved outcomes are achieved. © The Author 2007. Published by Oxford University Press. All rights reserved.

Acute renal failure (acute kidney injury) is a clinical syndrome characterized by a rapid reduction in renal excretory function underpinned by a variety of causes. Key aspects in the assessment of patients presenting with acute renal failure include assessment of volume status, assessment aimed at eliminating intrinsic renal disease as a cause and an assessment of renal morphology and presence or absence of obstruction.

Background. Chronic kidney disease (CKD) is a major public health problem. In the UK, guidelines have been developed to facilitate case identification and management. Our aim was to estimate the annualized cost of implementation of the guidelines on newly identified CKD cases.\ud Methods. We interrogated the New Opportunities for Early Renal Intervention by Computerised Assessment (NEOERICA) database using a Java program created to recompile the CKD guidelines into rule-based decision trees. This categorized all patients with a serum creatinine recorded over a 1-year period into those requiring more tests or referral. A 12-month cost analysis for following the guidelines was performed.\ud \ud Results. In the first year, a practice of 10 000 would identify 147.5 patients with stages 3-5 CKD over and above those already known. All stages 4-5 CKD cases would require nephrology referral. Of those with stage 3 CKD (143.85), 126.27 stable patients would require more tests. The following would require referral: 14.8 with estimated glomerular filtration rate decline >= 5 ml/min/ 1.73m(2)/year, 1.11 with haemoglobin < 11 g/dl and 1.67 with blood pressure > 150/90 on three anti-hypertensives. The projected cost per practice of investigating stable stage 3 CKD was is an element of 6111; and is an element of 7836 for nephrology referral. Total costs of is an element of 17 133 in the first year were increased to is an element of 29 790 through the effect of creatinine calibration.\ud \ud Conclusions. CKD guideline implementation results in significant increases in nephrology referral and additional investigation. These costs could be recouped by delaying dialysis requirement by 1 year in one individual per 10 000 patients managed according to guidelines

To compare rates of chronic kidney disease (CKD) in patients with diabetes and management of risk factors compared with people without diabetes using general practice computer records, and to assess the utility of serum creatinine and albuminuria as markers of impaired renal function.The simplified Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR) and stage of CKD. Further data were extracted to assess how effectively impaired renal function was being identified and how well potentially modifiable risk factors were being managed. The setting was 17 practices in Surrey, Kent and Greater Manchester (2003-2004). Participants were all patients with serum creatinine (SCr) recorded.Of the total population of 162 113, 5072 were recorded as having a diagnosis of diabetes, giving a prevalence of 3.1%. Of patients with diabetes, 31% had clinically significant CKD (defined as eGFR60 ml/min per 1.73 m(2); CKD stages 3-5) compared with 6.9% of those without diabetes. Only 33% of patients with diabetes at CKD stage 3 had serum creatinine120 micromol/l. Of patients with diabetes with eGFR60 ml/min per 1.73 m(2), 63% had normoalbuminuria. Considering those with eGFR 30-60 ml/min per 1.73 m(2), 42% of people with diabetes were on an ACE inhibitor compared with 25% of those without diabetes; 32% of patients with diabetes who had any record of micro- or macroalbuminuria at CKD stage 3 were taking an ACE inhibitor. Of people with diabetes and hypertension (BP140/80 mmHg), 26% were not prescribed any hypertensive medication, regardless of level of CKD.CKD is common in people with diabetes living in the community in the UK. The study found a similar rate of stage 3-5 CKD to that found previously in the USA. Currently used measures of renal function fail to identify CKD as effectively as eGFR. Risk factors for CKD and its progression are suboptimally managed.

BACKGROUND Identification of acute kidney injury (AKI) is predominantly based on changes in plasma creatinine concentration, an insensitive marker. Alternative biomarkers have been proposed. The reference change value (RCV), the point at which biomarker change can be inferred to have occurred with statistical certainty, provides an objective assessment of change in serial tests results in an individual. METHODS In 80 patients with chronic kidney disease, weekly measurements of blood and urinary biomarker concentrations were undertaken over 6 weeks. Variability was determined and compared before and after adjustment for urinary creatinine and across subgroups stratified by level of kidney function, proteinuria, and presence or absence of diabetes. RESULTS RCVs were determined for whole blood, plasma, and urinary neutrophil gelatinase-associated lipocalin (111%, 59%, and 693%, respectively), plasma cystatin C (14%), creatinine (17%), and urinary kidney injury molecule 1 (497%), tissue inhibitor of metalloproteinases 2 (454%), N-acetyl-β-d-glucosaminidase (361%), interleukin-18 (819%), albumin (430%), and α1-microglobulin (216%). Blood biomarkers exhibited lower variability than urinary biomarkers. Generally, adjusting urinary biomarker concentrations for creatinine reduced (P < 0.05) within-subject biological variability (CVI). For some markers, variation differed (P < 0.05) between subgroups. CONCLUSIONS These data can form a basis for application of these tests in clinical practice and research studies and are applicable across different levels of kidney function and proteinuria and in the presence or absence of diabetes. Most of the studied biomarkers have relatively high CVI (noise) but also have reported large concentration changes in response to renal insult (signal); thus progressive change should be detectable (high signal-to-noise ratio) when baseline data are available.

Background: Subcutaneous administration of Eprex(®) (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex(®) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(®) (epoetin beta) and Aranesp(®) (darbepoetin alfa). Methods: PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(®), NeoRecormon(®) or Aranesp(®) for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. Results: Of the 15 333 patients enrolled, 5948 received Eprex(®) (8377 patient-years) and 9356 received NeoRecormon(®)/Aranesp(®) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(®), n = 3; NeoRecormon(®), n = 1; Aranesp(®), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(®) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(®)/Aranesp(®). The incidence of PRCA with Eprex(®) was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings. Conclusion: This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(®), or NeoRecormon(®) or Aranesp(®). This study was funded by Janssen, Pharmaceutical Companies of Johnson & Johnson.

Background. We conducted a search of 12 practices' routinely collected computer data in three localities across the UK and found that 4.9% of the registered population had an estimated glomerular filtration rate (GFR) of

Chronic kidney disease (CKD) is a major health problem. A better understanding of the epidemiological characteristics of the different stages of CKD and the associated adverse outcomes is needed to establish and implement appropriate management strategies.A serum creatinine (SCr) level of 2.03 mg/dL or greater (or =180 micromol/L) in men and 1.53 mg/dL or greater (or =135 micromol/L) in women was used to identify patients with moderate to severe CKD in a predominantly Caucasian area of the United Kingdom. Patients who were unknown to renal services were identified and followed up to establish survival, rate of referral, and change in glomerular filtration rate (GFR).The prevalence of CKD defined by SCr cutoff values was 5,554 per million population (pmp). Median calculated GFR of the cohort was 28.5 mL/min/1.73 m2 (range, 4.1 to 42.8 mL/min/1.73 m2), and median age was 83 years (range, 18 to 103 years). A total of 84.8% of patients were unknown to renal services. During a mean follow-up of 31.3 months, 8.1% of patients were referred. Median survival of the unreferred population was 28.1 months. Cardiovascular disease, cancer, and infection were the most common causes of death. Male sex, low GFR, and nonreferral were associated with poor outcome. The majority of unreferred patients had stable renal function. The incidence of new unreferred CKD during the first year of follow-up was 2,435 pmp, such that the prevalence remained stable at 4,910 pmp. Significant anemia (hemoglobin11 g/dL [110 g/L]) was seen in 27.5% of the unreferred cohort.Referral of all patients with CKD is unrealistic and inappropriate. Management strategies aimed at improving adverse outcomes need to take account of this and be developed and implemented through collaboration between primary care and secondary care.

The incidence of renal stone disease in patients receiving topiramate (TopamaxTM) is 2-4 times that expected in the background population. This has been attributed to a weak carbonic anhydrase inhibitor effect, but published data are scant. Following three cases of renal stones in patients receiving topiramate, we evaluated biochemical risk for nephrolithiasis in eight further unselected patients. Most patients demonstrated inadequate urinary acidification and hypocitraturia; in some cases citrate was undetectable. Several patients also had other risk factors for nephrolithiasis, including increased urinary sodium, calcium and oxalate excretion. The biochemical changes induced by topiramate appear highly penetrant. Experience with this drug is relatively short-lived and it is being prescribed for long-term use in (often) relatively young patients. This report highlights the significantly increased metabolic risk of stone formation in patients receiving topiramate.

Diabetes mellitus is one of the two most common causes of end-stage renal disease and significant proportions of patients with diabetes mellitus develop renal complications. Anaemia is a key indicator of renal disease yet most patients with diabetes are rarely tested for anaemia and are unaware of the link between anaemia and kidney disease.A pan-European study was undertaken to assess patients' level of awareness and understanding of anaemia and of the complications of diabetes mellitus, and to determine the impact of anaemia on quality of life. The study comprised a questionnaire-based interview with 1,054 respondents from six countries (Belgium, France, Germany, Greece, Italy and the UK). Ages ranged from 18 to 85, the average duration of diabetes was 15 years and 69% of respondents had type 2 diabetes mellitus.Only 32% of respondents had been given information about anaemia, although 83% had heard of anaemia. Less than half were aware of being tested for anaemia and only 14% attributed anaemia to diabetes. Of 1,054 respondents, 132 were known to be anaemic, one-fifth had received no treatment, 12 had received blood transfusions, five were receiving erythropoietin therapy and the remainder had been given iron and/or vitamin supplementation. Perceived state of health was worse in those with anaemia, 47% had either experienced periods of ill health or were feeling in poor health generally compared with only 28% of those without anaemia. Tiredness and lethargy were more marked in those with anaemia, 74% feeling tired and lethargic considerably more often or somewhat more often than others compared with only 52% of those without anaemia. With respect to complications of diabetes, respondents were most concerned about retinopathy (40%) but 23% were concerned about developing nephropathy. Only 46% had received information about renal complications.Anaemia has a significant impact on the quality of life of patients with diabetes. Although patients are aware of anaemia, their awareness of being tested for anaemia is low. A significant number of those in whom anaemia was detected received no treatment. It is likely that anaemia in patients with diabetes is unrecognised, undetected and untreated.

♦ BackgroundSmall solute clearance, especially that derived from residual renal function (RRF), is an independent risk factor for death in peritoneal dialysis (PD) patients. Assessment of solute clearance is time-consuming and prone to multiple errors. Cystatin C is a small protein which has been used as a glomerular filtration rate (GFR) marker. We investigated whether serum cystatin C concentrations are related to mortality in patients receiving PD.♦ MethodsNew and prevalent PD patients ( n = 235) underwent assessment of Kt/Vurea, RRF, weekly creatinine clearance (CCr), normalized protein catabolic rate (nPCR) and a peritoneal equilibration test (PET) at intervals. Blood was collected simultaneously for cystatin C measurement. Patients were followed for a median of 1,429 days (range 12 to 2,964 days) until death or study closure. Cause of death was recorded where given. Cox regression was performed to determine whether cystatin C had prognostic value either independently or with adjustment for other factors (age, sex, dialysis modality, diabetic status, cardiovascular comorbidity, Kt/V, CCr, RRF, nPCR or 4 h dialysate to plasma creatinine ratio (4 h D/Pcr) during the PET). The primary outcomes were all-cause mortality and treatment failure.♦ResultsThere were 93 deaths. Increasing age and 4 h D/Pcrratio, decreased RRF and presence of diabetes were significantly [ p < 0.05] negatively associated with survival and treatment failure. Serum cystatin C was not related to either outcome.♦ ConclusionsSerum cystatin C concentration does not predict mortality or treatment failure in patients receiving PD.