Older people remain on blood pressure agents despite being hypotensive resulting in increased mortality and hospital admission.

BACKGROUND: the use of antihypertensive medication in older people in order to prevent cardiovascular events is well established. The use of such agents has been encouraged by incentive schemes in the United Kingdom including the Quality and Outcomes Framework. In addition, many guidelines recommend good blood pressure (BP) control in the elderly. However, in older people antihypertensives can cause adverse effects related to hypotension. AIM: the aim of this study was to assess the prevalence of low BP and impact on outcomes, particularly in the presence of antihypertensive treatment, in a primary care population of older people. DESIGN: a retrospective observational cohort study in people over the age of 70 years registered with primary care providers in Kent. RESULTS: a total of 11,167 patients over 70 years old were analysed, 6,373 female (57%). Systolic blood pressure (SBP) was below 120 mmHg in 1,297 people (844 on antihypertensives), below 110 mmHg in 474 (313 on antihypertensives) and below 100 mmHg in 128 (89 on antihypertensives). Hypotension was independently associated with mortality, acute kidney injury and hospital admission. CONCLUSIONS: the results demonstrate that low SBP is associated with adverse events, it is possible that the pursuit of BP control at a population level may lead to over-treatment in certain groups of patients. This may result in an increased incidence of adverse events particularly in older people.

Acute kidney injury: an acceptable risk of treatment with renin-angiotensin system blockade in primary care?

BACKGROUND: Use of renin-angiotensin system (RAS) blockade has become increasingly widespread driven by evidence-based guidance. There is concern about the role of these agents in the genesis of avoidable acute kidney injury (AKI). OBJECTIVES: To investigate the association between AKI and use of RAS blockade. DESIGN: Multilevel hierarchical analysis of a large cohort of patients registered with UK general practitioners. SETTING: Primary care practices in East and West Kent, United Kingdom. PATIENTS: 244,715 patients from 27 practices. MEASUREMENTS: Demographic, clinical, biochemical and prescription data. METHODS: Analyses of data acquired between 02/3/2004 and 17/04/2012 using multilevel logistic regression to determine the relationship between AKI and use of RAS blockade; further analysed by indication for treatment with RAS blockade. RESULTS: Sufficient serum creatinine data were available to define AKI in 63,735 patients with 208,275 blood test instances. In 95,569 instances the patient was prescribed a RAS antagonist of which 5.4% fulfilled criteria for AKI. The unadjusted odds ratio (OR) for AKI in those prescribed RAS blockade was 1.93 (1.81-2.06, 95%CI) falling to 1.11 (1.02-1.20, 95%CI) when adjusted for age, gender, co-morbidity, GFR category, proteinuria, systolic blood pressure and diuretic therapy. In patients with an evidence-based indication there was no difference in absolute risk of AKI. However, prescription of RAS blockade in the absence of indication appeared to be associated with greater risk of AKI. When analysis was repeated with AKIN2/AKIN3 as the outcome, although risk of AKI remained significant when unadjusted (OR 1.73, 95%CI 1.42-2.11, p<0.001), after full adjustment there was no increased risk (OR 0.83, 95%CI 0.63-1.09) in those taking RAS antagonists. However, when analysed by indication AKIN2/AKIN3 was significantly more likely in those prescribed RAS antagonists without indication (OR 2.04, 95%CI 1.41-2.94, p<0.001). LIMITATIONS: Observational database study. No information concerning hospitalisation. Prescribing assumptions and potential inaccurate coding. Potential survival bias; patients surviving longer will contribute more data. CONCLUSIONS: Use of RAS antagonists increased the risk of AKI, independent of common confounding variables. After correction for confounders the risk fell away and became non-significant for moderate and severe AKI. However, where there was no evidence-based indication for RAS antagonists the risk of AKI, whether mild, moderate or severe, remained greater.

CONTEXTE: Vu l'abondance de données probantes en la matière, le recours aux inhibiteurs du système rénine-angiotensine-aldostérone (SRAA) est de plus en plus répandu. Il existe certaines préoccupations quant au rôle de ces agents dans la genèse de l'insuffisance rénale aiguë (IRA) évitable. OBJECTIF DE L'ÉTUDE: Examiner, au sein d'une cohorte en soins de santé primaires, la présence de liens entre l'IRA et l'utilisation d'inhibiteurs du SRAA. TYPE D'ÉTUDE: Une analyse hiérarchique multiniveaux d'une vaste cohorte de patients suivis par des médecins généralistes du Royaume-Uni. CONTEXTE: Cliniques de soins de santé primaires situées dans l'est et l'ouest du comté du Kent, au Royaume-Uni. PATIENTS: Les données ont été recueillies auprès d'une cohorte de 244 715 patients en soins primaires, provenant de 27 cliniques de soins primaires dans l'est et l'ouest du comté du Kent. MESURES: Données démographiques, cliniques, biochimiques et issues d'ordonnances. MÉTHODES: L'analyse des données recueillies entre le 2004/03/02 et le 2012/04/17 a été effectuée par régression logistique multiniveaux afin de déterminer la relation entre l'IRA et l'utilisation d'inhibiteurs du SRAA, et ensuite par indication de traitement avec des inhibiteurs du SRAA. RÉSULTATS: Une quantité suffisante de données relatives à la créatininémie était disponible pour évaluer l'IRA chez 63 735 patients, qui avaient eu au total 208 275 prélèvements sanguins. Chez 95 569 sujets, un inhibiteur du SRAA a été prescrit, et 5,4% (5 194) de ces derniers ont eu un épisode d'IRA. Chez les patientsrecevant un traitement fondé sur des indications probantes, 5,8% (4473 sur 76 517) ont eu un épisode d'IRA. Le risque relatif non ajusté (RR) d'IRA associé à l'utilisation d'un inhibiteur du SRAA était de 1,93 (1,81-2,06, 95% IC), diminuant à 1,11 (1,02-1,20, 95% IC) lorsqu'ajusté pour l' âge, le sexe, la comorbidité, la catégorie de débit de filtration glomérulaire, la protéinurie, la pression artérielle systolique et le traitement diurétique. Chez les patients recevant un traitement par inhibiteurs du SRAA fondé sur des indications probantes, il n'y avait aucune différence de risque absolu d'IRA. Par contre, il semblait y avoir un lien entre la prescription d'inhibiteurs du SRAA en l'absence d'indications probantes et un risque accru d'IRA. Lorsque l'analyse a été répétée avec l'AKIN2/AKIN3 comme critère de jugement, le risque d'IRA associé à l'utilisation d'un inhibiteur du SRAA restait significatif dans le modèle non ajusté (RR 1,73, 95% IC 1,42-2,11, p < 0,001), mais aucune augmentation de risque n'a été observée après ajustement (RR 0,83, 95% IC 0,63-1,09). Par contre, le risque d'AKIN2/AKIN3 lié à l'utilisation d'un inhibiteur du SRAA était significativement plus élevée chez les patients qui recevaient ces agents sans indications probantes (RR 2,04, 95% IC, 1,41-2,94, p < 0,001). LIMITES DE L'ÉTUDE: Étude par observation de données prises dans des cliniques de soins primaires. Aucune information d'hospitalisation disponible (base de données de soins primaires). Interprétation des prescriptions et possibilité de codes erronés. Biais de temps d'immortalité possible : les patients qui vivent plus longtemps contribuent davantage à l'analyse par les prélèvements sanguins. CONCLUSIONS: Notre analyse montre que l'utilisation d'inhibiteurs du SRAA augmente le risque d'IRA. Le risque est indépendant de diverses variables de confusion, dont l'âge, la mesure de base de la fonction rénale, la présence de comorbidité pertinente et la pression artérielle systolique. Après correction pour les variables confusionnelles, le risque diminuait toujours : il devenait non significatif pour l'IRA modérée et sévère. Par contre, le risque d'IRA légere, modérée ou sévère demeurait élevé lorsque l'utilisation d'inhibiteurs du SRAA ne s'appuyait sur aucune indication probante. Renin angiotensin system blockade is known to be associated with acute kidney injury. This is the first study to examine this association by evidence-based indication. Although renin angiotensin system blockade increases the risk of acute kidney injury overall, in those with an evidence-based indication the majority of the effect is explained by underlying co-morbidity. In people with no evidence-based indication prescription of renin angiotensin blockade is an independent predictor of acute kidney injury.

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

BACKGROUND: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. METHODS: The study cohort was identified by using hospital data bases over a six month period. INCLUSION CRITERIA: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy.The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed.Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. RESULTS: The total study population was 61,432. 57,300 subjects with 'no AKI', mean age 64.The number (mean age) of acute serum creatinine rises overall were, 'AKI 1' 3,798 (72), 'AKI 2' 232 (73), and 'AKI 3' 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with 'no AKI', compared to 98.6%, 90.1% and 82.3% in those with 'AKI 1', 'AKI 2' and 'AKI 3' respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. CONCLUSIONS: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function.

The impact of pay for performance on the control of blood pressure in people with chronic kidney disease stage 3-5.

BACKGROUND: The implementation of national estimated glomerular filatration rate reporting and the inclusion of renal-specific indicators in a primary care pay for performance (P4P) system since April 2006 has promoted identification and better management of risk factors related to chronic kidney disease (CKD). In the UK, the P4P framework is known as the Quality and Outcomes Framework (QOF). One of the key targets for intervention in primary care was hypertension. It is clear that hypertension is a major predictor of development and progression of CKD; thus, targeting better blood pressure control is likely to have a positive impact on outcomes in CKD. The aim of this study was to evaluate the effectiveness of renal indicators outlined in P4P on the management of hypertension in primary care. To estimate the cost implications of the resulting changes in prescribing patterns of antihypertensive medication following introduction of such indicators. METHODS: We performed a prospective cohort study using a large primary care database. This cohort was taken from a database collated as part of a clinical decision support system used to assist the management of CKD in primary care. We investigated a total population of 90 250 individuals on general practitioner (GP) registers with a valid serum creatinine estimation in the 6-year study period. A total of 10 040 patients had confirmed stage 3-5 CKD in the 2 years pre-QOF and formed the study cohort. Patients were studied over three time periods, pre-QOF (1 April 2004 to 31 March 2006), 2 years post-QOF (1 April 2006 to 31 March 2008) and finally the two subsequent years (1 April 2008 to 31 March 2010). The mean systolic and diastolic blood pressures (BP) together with antihypertensive medication were analysed over the three time periods. Cost calculation was based on 2009 British National Formulary list prices for antihypertensives. RESULTS: The mean age of the cohort at the start of the study period was 64.8 years, 55% were female. In those patients with stage 3-5 CKD 83.9% were hypertensive, defined by a pre-P4P BP of >140/85 or currently taking antihypertensive medication. The proportion of patients with CKD 3-5 attaining the BP target of 145/80 increased from 41.5% in the pre-QOF period to 50.0% in the post-QOF period. This increase was even more marked for those with hypertension in the pre-QOF period (28.8-45.1%). In the hypertensive patients, mean BP fell from 146/79 mmHg to 140/76 in the first 2 years post-P4P [P < 0.01, analysis of variance (ANOVA)]. This BP reduction was sustained in the last 2 years of the study, 139/75 (P < 0.01, ANOVA). The proportion of hypertensive patients taking angiotensin-converting enzyme inhibitors or angiotensin blockers increased, this was also sustained in the third time period. An increase in the prescribing of diuretics, calcium channel blockers and ß-blockers was also observed. The additional cost of increased prescribing was calculated to be €25.00 per hypertensive patient based on GP prescription data. CONCLUSIONS: Population BP control has improved since the introduction of P4P renal indicators, and this improvement has been sustained. This was associated with a significant increase in the use of antihypertensive medication, resulting in increased prescription cost. Longer-term follow-up will establish whether or not this translates to improved outcomes in terms of progression of CKD, cardiovascular disease and patient mortality.

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.

Is high body mass index independently associated with diminished glomerular filtration rate? An epidemiological study.

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.

Referral patterns to renal services: what has changed in the past 4 years?

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.

The cost of implementing UK guidelines for the management of chronic kidney disease.

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. 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. 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>or=5 ml/min/1.73 m2/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 euro 6111; and euro 7836 for nephrology referral. Total costs of euro 17 133 in the first year were increased to euro 29,790 through the effect of creatinine calibration. 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.