Paul E. Stevens

Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline.

DESCRIPTION The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy. METHODS The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders. RECOMMENDATIONS The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.

Summary of KDIGO 2012 CKD Guideline: behind the scenes, need for guidance, and a framework for moving forward

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.

Accuracy of the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (CKD Epidemiology Collaboration) Equations for Estimation of GFR in the Elderly

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< 0.001], 1.7 [P < 0.001], and 0.8 [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.

Early identification and management of chronic kidney disease: summary of NICE guidance

Chronic kidney disease is associated with substantial comorbidity including hypertension, cardiovascular disease, anaemia, and renal bone disease. People with chronic kidney disease have a far greater likelihood of cardiovascular death than progression to established renal failure (requiring dialysis or kidney transplantation).1 2 3 4 Chronic kidney disease has been highlighted as a public health problem through the international adoption of the US National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative staging system and because the prevalence of the disease as defined by the staging system has risen from 10% (in 1988-94) to 13% (in 1999-2004) of the non-institutionalised adult US population.5 6 7 The staging system (which comprises five stages, 1-5) defines chronic kidney disease on the basis of either evidence of kidney damage (proteinuria, haematuria, or anatomical abnormality) or an impaired glomerular filtration rate <60 ml/min/1.73 m2, present on at least two occasions over three months or longer. The use of a threshold of estimated glomerular filtration rate, uncorrected for age or sex, to define disease has been rightly criticised.8 Nevertheless, based on this definition, the age standardised prevalence of stages 3-5 of chronic kidney disease was 8.5% in a representative UK population.9 This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) for identifying and managing chronic kidney disease. NICE recommendations are based on systematic reviews of the best available evidence. When minimal evidence is available, recommendations are based on the Guideline Development Group’s opinion of what constitutes good practice. Evidence levels for the recommendations are given in italics in square brackets. ### Classification of chronic kidney disease Because of evidence about differences in risk of adverse outcomes (particularly cardiovascular disease) with declining glomerular filtration rate, stage 3 should be split into two subcategories defined by glomerular filtration rate (table 1 …

How should proteinuria be detected and measured

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.

Assessment of quality of life in a single centre dialysis population using the KDQOL-SFTm questionnaire

Health-related quality of life (HRQOL) is a valid marker of outcome for chronic dialysis therapy. A wide range of questionnaires are now available which assess different aspects of an individuals health. Appreciation of those factors that contribute to explaining HRQOL items remains poorly defined. The development of disease-specific questionnaires such as KDQOL-SFTm, should allow for such questions to be better answered. A cross-sectional analysis of our chronic dialysis population was made using the KDQOL-SFTm questionnaire. By multiple linear regression analysis demographic, clinical and dialysis-related factors were assessed for their contribution to the HRQOL in this population. The HRQOL of these patients was also compared against a general population sample. From a total of 190 chronic dialysis patients, 146 completed the KDQOL-SFTm questionnaire. The haemodialysis (HD) and peritoneal dialysis (PD) patients were similar with respect to most demographic, clinical and dialysis variables except for haemoglobin and albumin which were significantly (p < 0.05) greater in the peritoneal and haemodialysis populations respectively. Compared to the general population, the HRQOL of dialysis patients was impaired for all SF-36 subscales. Use of the disease-specific components of KDQOL-SFTm discriminated between dialysis modality for our dialysis population. Multiple linear regression analysis demonstrated that 27.5 to 42.7% of the variance in the SF-36 subscales could be explained. Satisfactory sleep, dialysis related symptoms, effect of kidney disease on lifestyle and burden of kidney disease were found to be the most important determinants of HRQOL for this population.

Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice.

Aims  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.

Estimating glomerular filtration rate: comparison of the CKD-EPI and MDRD equations in a large UK cohort with particular emphasis on the effect of age

BACKGROUND The chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation was developed to address the underestimation of measured glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) equation at levels >60 mL/min/1.73 m(2). AIM To assess the impact of the CKD-EPI equation on the estimation of GFR in a large adult UK population (n = 561,400), particularly looking at the effect of age. DESIGN Serum creatinine results (ID-MS-aligned enzymatic assay) were extracted from the pathology database during 1 year on adult (≥ 18 years) patients from primary care. METHODS The first available creatinine result from 174,448 people was used to estimate GFR using both equations and agreement assessed. RESULTS Median CKD-EPI GFR was significantly higher than median MDRD GFR (82 vs. 76 mL/min/1.73 m(2), P < 0.0001). Overall mean bias between CKD-EPI and MDRD GFR was 5.0%, ranging from 13.0% in the 18-29 years age group down to -7.5% in those aged ≥ 90 years. Although statistically significant at all age groups the difference diminished with age and the agreement in GFR category assignment increased. Age-adjusted population prevalence of CKD Stages 3-5 was lower by CKD-EPI than by MDRD (4.4% vs. 4.9%). CONCLUSION CKD-EPI produces higher GFR and lower CKD estimates, particularly among 18-59 year age groups with MDRD estimated GFRs of 45-59 mL/min/1.73 m(2) (Stage 3A). However, at ages >70 years there is very little difference between the equations, and among the very elderly CKD-EPI may actually increase CKD prevalence estimates.

Variability of Parathyroid Hormone and Other Markers of Bone Mineral Metabolism in Patients Receiving Hemodialysis

BACKGROUND AND OBJECTIVES Clinical management of mineral bone disorder in patients with kidney failure is guided by biochemical targets, in particular parathyroid hormone (PTH) concentration. The biologic variation of PTH and other bone mineral markers was measured in hemodialysis patients to better define their role in management. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Intact PTH, biointact (whole-molecule) PTH, calcium, albumin-adjusted calcium, phosphate, and alkaline phosphatase (ALP) were measured in nonfasting samples obtained twice a week (both short-dialysis interval) over a 6-week period in 22 stable hemodialysis patients. Concurrently, samples were obtained from 12 healthy volunteers. Intraindividual coefficients of variance (CVI) were calculated and used to derive the reference change value (RCV) required to be 95% certain that a change has occurred. RESULTS CVI of all markers was significantly (P<0.05) greater in patients than in healthy volunteers. For phosphate, ALP, and PTH this implies that an increased number of samples is required to estimate an individuals homeostatic set point. CVI of intact PTH was 25.6% in hemodialysis patients and 19.2% in healthy volunteers. A greater RCV should be used for patients (72%) compared with healthy volunteers (54%). Ideally 26 specimens should be measured to estimate a patients intact PTH homeostatic set point (within +/-10%) with 95% probability. The CVI of biointact PTH was at least as high as that for intact PTH. CONCLUSIONS The uncertainty of PTH estimation in an individual significantly undermines its value as a tool in the management of chronic kidney disease-mineral bone disorder using current management approaches.

Change in the estimated glomerular filtration rate over time and risk of all-cause mortality

Using a community-based cohort we studied the association between changes in the estimated glomerular filtration rate (eGFR) over time and the risk of all-cause mortality. We identified 529,312 adults who had at least three outpatient eGFR measurements over a 4-year period from a provincial laboratory repository in Alberta, Canada. Two indices of change in eGFR were evaluated: the absolute annual rate of change (in ml/min per 1.73 m(2) per year) and the annual percentage change (percent/year). The adjusted mortality risk associated with each category of change in eGFR was assessed, using stable eGFR (no change) as the reference. Over a median follow-up of 2.5 years there were 32,372 deaths. Compared to the reference participants, those with the greatest absolute annual decline less than or equal to 5 ml/min per 1.73 m(2) per year had significantly increased mortality (hazard ratio of 1.52) adjusted for covariates and kidney function at baseline (last eGFR measurement). Participants with the greatest increase in eGFR of 5 ml/min per 1.73 m(2) per year or more also had significantly increased mortality (adjusted hazard ratio of 2.20). A similar pattern was found when change in eGFR was quantified as an annual percentage change. Thus, both declining and increasing eGFR were independently associated with mortality and underscore the importance of identifying change in eGFR over time to improve mortality risk prediction.