Prevalence of chronic kidney disease stages 3 5 among acute medical admissions: another opportunity for screening

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1 Q J Med 2008; 101:91 97 doi: /qjmed/hcm130 Advance Access published on 9 January 2008 Prevalence of chronic kidney disease stages 3 5 among acute medical admissions: another opportunity for screening N.M.P. ANNEAR 1, D. BANERJEE 1, J. JOSEPH 1, T.H. HARRIES 1, S. RAHMAN 2 and J.B. EASTWOOD 1 From the 1 Department of Renal Medicine and Transplantation and 2 Department of Information and Computing, St Georges Hospital, London, SW17 0QT, UK Received 17 July 2007 and in revised form 20 August 2007 Summary Background: Early identification of chronic kidney disease (CKD) can help delay or prevent its progression, but the opportunities for systematic screening of patients are not well defined. Aim: To define the prevalence of CKD Stages 3 5 and related anaemia among acute medical admissions. Design: Retrospective analysis. Methods: We studied all acute medical admissions to a major London teaching hospital during one year. The lowest creatinine, highest haemoglobin (Hb) and average mean corpuscular volume (MCV) were determined for 3 months before and after admission. Patients were categorized as CKD Stages 3 5 if the highest estimated GFR (egfr) was <60 ml/min/1.73 m 2. CKD-related anaemia was diagnosed if these patients had Hb <11 g/dl with normal MCV. Results: A total of 6073 patients were studied: male 49.0%, age years (mean SD), Introduction The spectrum of acute medical emergencies, the admission process and length of stay has changed considerably in recent years. Specialty-led care in many acute hospitals in the UK has meant the separation of neurology, cardiology, haematology, infectious diseases and oncology from general medicine, removing acute myocardial infarcts and cerebro-vascular accidents in particular from the acute medical intake. Thus, the acute medical creatinine mmol/l, egfr ml/ min/1.73 m 2, Hb g/dl, MCV fl. There was an inverse correlation between egfr and age (r 2 ¼ 0.5; P < 0.001). Males were younger than females ( years vs ) and had higher egfr ( vs ml/ min/1.73 m 2 ; P < 0.001). A total of 743 patients (12.2%) had raised creatinine4110 mmol/l, however using egfr <60 ml/min/1.73 m 2, 1075 patients (17.7%) were identified. The patients were categorized as follows: Stage 3: 950 (15.6%), Stage 4: 100 (1.7%), Stage 5: 25 (0.4%). Ninety-nine (9.2%) of the 1075 patients had normocytic anaemia. Conclusions: We have found a high prevalence of CKD Stages 3 5 (17.7%) among acute medical admissions, of whom 9.2% had a related anaemia. Our findings highlight an important opportunity (amongst the 1.9 million acute medical admissions annually in England) for detecting patients with CKD. intake is now dominated by patients in the disciplines of chest medicine, gastro-enterology and diabetes/endocrinology. Surprisingly little has been published on the prevalence of chronic kidney disease (CKD) among acute medical admissions. CKD is now recognized as a growing worldwide health epidemic that brings with it considerable morbidity even before the patient reaches end stage renal failure (ESRF). The UK incidence of new Address correspondence to Dr Debasish Banerjee, Department of Renal Medicine and Transplantation, St Georges Hospital, London SW17 0QT, UK. debasish.banerjee@stgeorges.nhs.uk! The Author Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

2 92 N.M.P. Annear et al. patients requiring renal replacement therapy has doubled over the past decade, to 101/million/year, and is projected to rise by 5 8% annually. 1 Early diagnosis in CKD presents an opportunity to delay, if not prevent, progression to ESRF. The aim of the study reported here is to draw the attention of consultant physicians and their teams to the hidden burden of renal disease. It is hoped that acute medical admitting teams will: be aware that egfr (estimated Glomerular Filtration Rate) is now reported by most laboratories in the UK know that staging the degree of a patient s renal impairment can influence management make control of blood pressure in such patients a priority look for the cardiovascular complications in patients with decreased GFR remember to adjust as necessary the dose of all drugs used look for any possible remediable factors for the decreased GFR be aware of complications such as anaemia and renal bone disease In this report, we present data on all acute medical admissions for one year in a teaching hospital with a catchment population of around Methods A retrospective search was performed using the hospital Patient Administration System to obtain details of all attendances and admissions via the Accident and Emergency department of St George s Hospital, London, UK over the period 1 January to 31 December A total of patients were assessed in A&E. Of these, 8602 were admitted under the Acute medical teams. After excluding patients aged <16 years (6), and individuals on renal replacement therapy (50), as well as readmissions, there remained 6774 individuals. Data collection Data on age, gender and race were collected at the time of admission. Laboratory data were obtained for the 6774 individuals and matched using the APEX pathology management (ACT Medisys Ltd, Newbury, Berkshire, UK) and Electronic Patient Record systems. Values were obtained for the lowest creatinine for each hospital admission and, where available, for up to 3 months before and after the admission. Similarly, the highest haemoglobin (Hb) value and average mean corpuscular volume (MCV) were identified. The data were collated using a Microsoft Access database. In 546 patients the data were incomplete (no results for creatinine, Hb or Methods: The study population A&E attendances in Acute medical admissions 6774 Less readms/rrt 6073 Complete data Figure 1. Design of the study. 928 Readmissions RRT / <16y 546 incomplete Data 155 creat<40 MCV during the 1-year period). In 155 patients the lowest reported laboratory creatinine value was <40 mmol/l; these were considered to be unreliable. These 701 patients were excluded from further analysis. The resulting cohort for the study comprised 6073 patients (Figure 1). Identification of CKD Cockcroft Gault formula Body weight is one of the variables used to calculate this formula. As the patients were not routinely weighed on admission, we could not calculate the Cockroft Gault egfr. Current data show, however, that for individuals with an egfr of <60 ml/min/ 1.73 m 2 (CKD Stages 3 5) the MDRD formula correlates better with iothalamate-measured GFR than does the Cockroft Gault formula. 2 MDRD formula egfr was calculated for the cohort of 6073 patients using the 4-variable (MDRD-4) formula: 186 (Creatinine) (Age) (0.742 if female) (1.210 if black). 2 Patients were identified as having CKD if the highest egfr was <60 ml/min/1.73 m 2. Identification of CKD-related anaemia The World Health Organisation (WHO) criteria 3 defines a patient as anaemic if the haemoglobin is <13 g/dl in males (<12 g/dl in females). Patients with a normocytic anaemia, and therefore possible CKD-related anaemia were identified if their average MCV over the same period was fl. For the purposes of this article a significant normocytic anaemia was taken to be where the haemoglobin was <11 g/dl and MCV fl.

3 Chronic kidney disease amongst acute medical admissions 93 Table 1 The stages of chronic kidney disease p<0.001(pearson s rank correlation) CKD stage Statistical analysis Stage 3 CKD was defined as an egfr of ml/min/1.73 m 2, Stage 4 CKD as an egfr of ml/min/1.73 m 2 and Stage 5 as <15.0 ml/ min/1.73 m 2 (Table 1). Statistical Analysis was performed using Microsoft Access and Excel programs, and Statistix Version 7.0 (Analytical Software Ltd). Descriptive statistics were used to characterise variables. The relationship between age and egfr was evaluated using Pearson s Rank correlation coefficient. Mean ages and prevalence of CKD identified using egfr were each compared in male and female populations, and in race groups using the 2 test. Significance tests were also performed on the number of patients identified with CKD by a raised serum creatinine (4110 mmol/l) compared with those with an egfr <60.0 ml/min/1.73 m 2 using the binomial distribution test approximated to the normal distribution. The two sample t-test was used to compare mean age and egfr between racematched and gender-matched groups. Results Demographics GFR ml/min/ Description 1.73 m Kidney damage with normal or increased GFR Kidney damage with mild decreased GFR Moderately decreased GFR Severely decreased GFR 5 <15 (or dialysis) Kidney failure CKD is defined as kidney damage with or without decreased glomerular filtration rate (GFR), or a GFR <60 ml/min/1.73 m 2 for 3 months or more, irrespective of the cause. Kidney damage may be manifest by pathologic abnormalities or by markers such as haematuria, proteinuria or abnormal renal imaging. The 6073 patients [male 2976 (49.0%)] had a mean age of years (mean SD) 620 patients (10.2%) were black. The mean value for creatinine was mmol/l; egfr ml/min/ 1.73 m 2 ; haemoglobin g/dl; MCV fl. There was a highly significant inverse correlation between egfr and age (Figure 2, r 2 ¼ 0.5; P < 0.001). Males ( years) were Highest egfr in ml/min/1.73m Table 2 Estimated GFR grouped by gender, racial group and age. Overall Number of patients % of study population significantly younger than females ( years; P < 0.001). Black patients ( years) were significantly younger than non-black patients ( years; P < 0.001). They had a significantly higher egfr ( ml/min/ 1.73 m 2 ) than non-black patients ( ml/ min/1.73 m 2 ; P < 0.001), independent of age. Correspondingly, males had a significantly higher mean egfr ( ml/min/1.73 m 2 ) than females ( ml/min/1.73 m 2 ; P < 0.001), independent of age (Table 2). Prevalence of CKD Age in yrs Figure 2. Estimated GFR vs. age. Percentage prevalence of egfr category (ml/min/1.73 m 2 ) Total Gender Male Female Race Black Other Age (year) Out of the 6073 patients, 1075 (17.7%) were found to have CKD Stages 3 5 (egfr <60.0 ml/min/ 1.73 m 2 ). Mean age of CKD group years; mean age of egfr ml/min/1.73 m 2

4 94 N.M.P. Annear et al Table 3 group Prevalence of normocytic anaemia vs. egfr n (17.7%) egfr <60ml/min/1.7m 2 group (4998 patients) years (P < 0.001). There were fewer black patients in the CKD group (5.1%) than in the egfr ml/min/1.73 m 2 group (11.3%; P < 0.001). There was a greater proportion of females (59.4%) in the CKD Stages 3 5 group than in the group with egfr ml/min/1.73 m 2 (49.2%; P < 0.001). The prevalence of CKD Stages 3, 4 and 5 in our cohort was 15.6, 1.7 and 0.4%, respectively (Table 2). Forty-seven percent (504 patients) from our CKD group had no serum creatinine result from the 12 months preceding admission. Creatinine as an indicator of GFR If serum creatinine measurements (5110 mmol/l) alone had been used, only 743 of the 1075 patients identified as having CKD using the MDRD-4 egfr would have been detected (Figure 3). In other words, 31% of patients with CKD would have been missed. CKD-related anaemia 743 (12.2%) Creatinine <110 µmol/l Figure 3. egfr vs. serum creatinine in the identification of chronic kidney disease. Creatinine alone identifies significantly less patients with CKD. P < (binomial distribution test). Out of the 6073 individuals in the study, 1317 patients (21.7%) were anaemic according to WHO criteria (Hb < 13.0 g/dl males, <12.0 g/dl females 3 ), of whom 1020 (16.8%) had a normal MCV. The prevalence of normocytic anaemia in the CKD group (stages 3 5) was 29.6%, and 14.1% in the egfr 560 ml/min/1.73 m 2 group. The haemoglobin was <11 g/dl in 5.8% of the 6073 individuals, (of whom 3.9% had a normal MCV). The prevalence of normocytic anaemia with haemoglobin <11 g/dl, was higher in the CKD Stages 3 5 group (9.2%) than in the egfr 560 ml/min/1.73 m 2 group (2.7%). There was an increasing prevalence of normocytic anaemia associated with increasing severity of renal dysfunction (Table 3). EGFR ml/min/1.73 m 2 Patients n Patients with Hb <11 g/dl and normal MCV % < Stage 3: Stage 4: Stage 5: Discussion The prevalence of CKD (Stages 3 5) in this retrospective cohort study of acute medical admissions over one year was 17.7% (Stage 3, 15.6%; Stage 4, 1.7%; Stage 5, 0.4%). The overall prevalence of normocytic anaemia (Hb<11 g/dl with MCV fl) in the CKD group was 9.2%. The prevalence was progressively higher in CKD Stages 3 (8.2%), 4 (13.0%) and 5 (32.0%). These findings demonstrate a high prevalence of CKD and CKD-related anaemia among acute medical admissions that may be amenable to systematic screening. Strengths and limitations Serum creatinine measurements spread over 3 months before and after admissions were not available for all patients. Thus reliance on serum creatinine values obtained during an acute admission may have led to over-identification. On the other hand, we will undoubtedly have missed patients with renal disease among those with egfr 460 ml/min/1.73 m 2. Lack of standardization of creatinine assays leads to variability in measured creatinine values between centres. It should be noted that our biochemistry laboratories utilize the modified Jaffe creatinine assay, as was used in the original MDRD paper. 4 In establishing the diagnosis of chronic normocytic anaemia in patients with an egfr<60 ml/min/ 1.73 m 2, we could not wholly exclude other causes without more detailed perusal of the medical notes. Prevalence of CKD We have been unable to find comparable international data for the prevalence of CKD among acute medical admissions. On the other hand, there is prevalence data for renal dysfunction of the same degree from the general population in the USA (4.7% 5 ), Norway (4.4% 6 ) and China (5.2% 7 ). It is

5 Chronic kidney disease amongst acute medical admissions 95 clear that the group we have studied here provide a better opportunity for screening than screening the whole population. In the past, a raised creatinine has been used in population studies as the marker for renal dysfunction. 8 We have shown here that, by using the MDRD-4 formula, 31% more patients were identified as CKD Stages 3 5 than were identified using a creatinine of 5110 mmol/l. When a creatinine 5180 mmol/l for males and 5135 mmol/l for females was used, 8 we found that over 80% of patients with CKD Stages 3 5 were missed. In addition, 36.7% of the CKD group had no serum creatinine result for the 2 years preceding admission, suggesting that their GPs were probably unaware of their CKD. It has always been important to be aware of any patient with renal dysfunction among acute medical admissions. The MDRD-4 formula, with its proven accuracy especially below a GFR of 60 ml/min, provides a quick way of identifying patients with renal dysfunction. Indeed, most laboratories in the UK, in response to the National Service Framework for Renal Disease, 9 now report egfr routinely; this is a vital resource in enabling primary care physicians to identify patients with renal dysfunction. In the hospital setting too, such patients can be quickly identified, and the admitting junior doctor can initiate relevant investigations for quantification of renal anaemia and cardiovascular risk. There would then be the opportunity of asking the opinion of a nephrologist or putting in place appropriate treatment oneself. Clearly, the patient s primary care physician will need to be notified too. In our study, there was roughly the same number of men as women. A higher proportion of the women had renal impairment (Stages 3 5), an effect that is probably a consequence of the women being older than the men [67.3 vs. 63.5(men) years]. The statistically significant trend of decreasing egfr with increasing age is certainly in keeping with other studies of CKD prevalence. 5,10,11 The proportion of black patients in the study was 10.2%, which reflects local demographics (London 10.9%, Tooting 10.9%). 12 The black patients were much younger than the Caucasians. This may simply reflect the young population of migrant blacks in south-west London, or perhaps there is a shorter life expectancy amongst the black population. If this were the case, blacks might be overrepresented among the acute medical intake which they are not. Given the evidence of higher prevalence of hypertension and diabetes in black populations, it is surprising that blacks in our cohort represent just 5.1% of the population with an egfr <60.0 ml/min/1.73 m 2, whereas they represent 11.3% of the population with an egfr 560 ml/min/ 1.73 m 2. Whilst we may postulate that there may have been inaccurate coding of those of mixed race, the lower prevalence of blacks in the CKD group is significant. Another interpretation could be that the significantly younger population of blacks with CKD is statistically overshadowed by the burgeoning population of older white patients with CKD. CKD-related anaemia The strong association between anaemia, CKD and cardiovascular disease through both direct and indirect effects on the heart, leading to impaired left ventricular (LV) function, LV dilatation, heart failure and death is well reported Evidence suggests too that even mild anaemia (Hb < 13.8 g/dl) is associated with an increased risk for progression to ESRF in patients with type II diabetes mellitus. 24 Despite the establishment of European Best Practice Guidelines and the National Kidney Foundation- Kidney Dialysis Outcomes Quality Initiative (NKF- KDOQI) guideline recommendations, surveys have shown that less than a quarter of pre-esrf patients in the USA (less than a third in Europe) receive active management of their anaemia in the form of iron replenishment and exogenous erythropoietin administration. 16 We have shown here that the prevalence of normocytic anaemia in the CKD group was 29.6%, using WHO criteria. 3 Evidence from a recent metaanalysis of nine randomized controlled trials has demonstrated that in patients with CKD-related anaemia, complete correction to a higher target haemoglobin (range g/dl) was associated with a higher risk of all cause mortality, arteriovenous access thrombosis and poorly controlled blood pressure, compared with that in the lower target haemoglobin group (range g/dl). There was no difference in the incidence of myocardial infarction between the two groups. 25 Furthermore, a higher target haemoglobin does not significantly reduce the rate of decline in egfr, and is associated with only mild improvement in general health and physical function. Patients with a greater degree of anaemia prior to commencement of treatment obtained more significant benefit in terms of general health and physical function. 26,27 The evidence therefore indicates that significant health benefit is derived only if treatment is started with anaemia well below the WHO limit. The cost-benefit implications of these studies are altering the emphasis for anaemia management, in the first instance by setting upper limits for target haemoglobin in treated CKD-related anaemia. 25 The trend we report of progressively higher prevalence of normocytic anaemia (Hb <11 g/dl),

6 96 N.M.P. Annear et al. normal MCV by stage of CKD is similar to that reported in the NHANES III study, which demonstrated the prevalence of renal anaemia in CKD Stages 3, 4 and 5 in the US general population to be: 1%, 9% and 33%, respectively. 16,28 A single UK study of significant anaemia (Hb <11 g/dl) among unreferred patients with chronic renal failure (Median egfr 28.5 ml/min/1.73 m 2 ), has suggested a prevalence of 27.5%. 8 Screening for CKD among acute medical admissions The evidence that early intervention can both delay progression and improve morbidity and mortality in the asymptomatic majority makes CKD an attractive proposition for screening. Moreover, the screening tools (egfr calculation and urinalysis) are cheap and readily available. At risk groups The benefits of screening at-risk populations, such as diabetics, hypertensives and patients with a family history of renal disease, are well established. 29 By contrast, the practicalities and cost effectiveness of whole population screening remain unclear. Studies have shown that screening people with hypertension, diabetes mellitus, and the over 55 s is an effective strategy in detecting patients with CKD, identifying 93.2% of all cases of CKD; on average 8.7 patients needed to be screened to identify one patient with CKD. The risk of progression to ESRF among those detected was low, at 1 2% for CKD Stage 3, and 20% for CKD Stage The higher prevalence of CKD among acute medical admissions compared with the general population makes the former group suitable for a systematic screening programme. Protocols could be established for initiating therapeutic interventions, including treatment of renal anaemia, avoidance of nephrotoxic drugs, optimizing control of blood pressure and blood glucose in diabetics, reduction of proteinuria using ACE inhibitors or angiotensin receptor blocking drugs, managing cardiovascular risk and arranging referral to a nephrologist. At present most patients with CKD patients die before they reach end-stage. Strategies that prevent progression may increase the numbers able to benefit from renal replacement therapy. 31 Conclusions The data presented in this article show that the proportion of patients with CKD Stages 3 5 admitted under the acute medical team is higher than in the general population. This is not surprising but presents an opportunity for identifying new patients with renal dysfunction. If the renal dysfunction is overlooked the next opportunity might be when the patient is admitted acutely again in the future, or the patient might present end-stage. Opportunities for formal and systematic screening for CKD are being evaluated, and indeed well established in some diabetic renal services. The higher prevalence of CKD among acute medical admissions compared with that of the general population suggests that such patients would be suitable for systematic screening. It should be remembered that the benefits of early identification of CKD must be set alongside the possible psychological and social harm resulting from the screening process itself, especially in a patient whose level of dysfunction is stable. 32 Nevertheless, we believe the benefits outweigh the risks and that screening of this at-risk population is worthwhile. Conflict of interest: None declared. References 1. El Nahas AM, Bello AK. Chronic kidney disease: the global challenge. Lancet 2005; 365: Levey AS, Greene T, Kusek JW, Beck GL, MDRD Study Group. A simplified equation to predict glomerular filtration rate from serum creatinine (abstract). J Am Soc Nephrol 2000; 11:155A. 3. Nutritional anemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser 1968;405: Levey AS, Bosch JP, Breyer Lewis J, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999; 130: Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41: Hallan SI, Coresh J, Astor BC, Asberg A, Powe NR, Romundstad S, et al. International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. J Am Soc Nephrol 2006; 17: Zhang L, Zuo L, Xu G, Wang F, Wang M, Wang S, Lv J, Liu L, Wang H. Community-based screening for chronic kidney disease among populations older than 40 years in Beijing. Nephrol Dial Transplant 2007; 22: John R, Webb M, Young A, Stevens PE. Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis 2004; 43: Department of Health. National service framework for renal services part two: chronic kidney disease, acute renal failure and end of life care. In: Health Do, ed. Crown Copyright, 2005.

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