Socio-economic status influences chronic kidney disease prevalence in primary care: a community-based cross-sectional analysis.

BACKGROUND: Primary care chronic kidney disease (CKD) registers report widely varying prevalence within the UK. We examined the effects of laboratory ascertainment and adjusting for practice-level variables on the variation in CKD prevalence. We carried out an Ayrshire-wide laboratory database analysis of primary care practices (PCPs). METHODS: We analysed 54 PCPs with 313 639 registered patients aged ≥ 18. All patients with a low estimated glomerular filtration rate (<60 mL/min/1.73 m(2)) had their serum creatinine values extracted from 1st January 2009 to 31st March 2012. Individuals with CKD stage 3-5 were identified with an algorithm that confirmed chronicity. These data were linked to PCP attributes from Information Services Division, Scotland. Using laboratory-ascertained CKD prevalence, we examined whether adjusting for practice-level factors [socio-economic status (SES), rurality and patients to general practitioner ratio (PGR)] and patient-level factors (age, gender) explained some of the observed variation among PCPs. Individual and combined hierarchical multilinear regression models were used. RESULTS: Eighteen thousand two hundred and eighty-five (5.8%) had CKD stage 3-5 on 31 March 2011. SES, rurality and PGR predicted 39% (F(3,50) = 12.37, P < 0.001) of the variation in prevalence with SES exerting the most influence (25%). With the stepwise addition of explanatory variables, variation between practices fell from 3.9-fold using PCP register prevalence to laboratory ascertained (3.1-fold variation), with age and gender adjustment (further fall to 2.1-fold), and lastly to 1.8-fold variation with adjustment for SES. Funnel plots using these adjustments reduced the number of outliers outside of 3 SD from 15 to 7 to 6, and outliers between 2 and 3 SD by 16 to 13 to 5. CONCLUSIONS: Laboratory ascertainment is practicable, reduces variation and facilitates benchmarking. PCP attributes other than age and gender impact on prevalence. Over a third of variation in CKD prevalence among PCPs can be explained by rurality, PGR and especially SES even after age and gender stratification.

Comparison of urinary albumin and urinary total protein as predictors of patient outcomes in CKD.

BACKGROUND: Proteinuria is common and is associated with adverse patient outcomes. The optimal test of proteinuria to identify those at risk is uncertain. This study assessed albuminuria and total proteinuria as predictors of 3 patient outcomes: all-cause mortality, start of renal replacement therapy (RRT), and doubling of serum creatinine level. STUDY DESIGN: Retrospective longitudinal cohort study. SETTING & PARTICIPANTS: Nephrology clinic of a city hospital in Scotland; 5,586 patients with chronic kidney disease (CKD) and proteinuria measured in random urine samples (n = 3,378) or timed urine collections (n = 1,808). PREDICTORS: Baseline measurements of albumin-creatinine ratio (ACR), total protein-creatinine ratio (PCR), 24-hour albuminuria, and total proteinuria. OUTCOMES: All-cause mortality, start of RRT, and doubling of serum creatinine level were assessed using receiver operating characteristic curves and Cox proportional hazards models. MEASUREMENTS: Blood pressure, serum creatinine level, ACR, PCR, date of death, date of starting RRT. RESULTS: Patients were followed up for a median of 3.5 (25th-75th percentile, 2.1-6.0) years. For all outcomes, adjusted HRs were similar for PCR and ACR (derived from random urine samples and timed collections): death, 1.41 (95% CI, 1.31-1.53) vs 1.38 (95% CI, 1.28-1.50); RRT, 1.96 (95% CI, 1.76-2.18) vs 2.33 (95% CI, 2.06-3.01); and doubling of serum creatinine level, 2.03 (95% CI, 1.87-2.19) vs 1.92 (95% CI, 1.78-2.08). Receiver operating characteristic curves showed almost identical performance for ACR and PCR for the 3 outcome measures. Adjusted HRs for ACR and PCR were similar when derived from random urine samples or timed collections and compared with 24-hour total protein and albumin excretion for each outcome measure. LIMITATIONS: This is a retrospective study. CONCLUSIONS: Total proteinuria and albuminuria perform equally as predictors of renal outcomes and mortality in patients with CKD. ACR and PCR were as effective as 24-hour urine samples at predicting outcomes and are more convenient for patients, clinicians, and laboratories. Both ACR and PCR stratify risk in patients with CKD.

Outcomes in patients on home haemodialysis in England and Wales, 1997-2005: a comparative cohort analysis.

BACKGROUND: The UK national policy promotes expansion of home haemodialysis, but there are no recent data on characteristics and outcomes of a national home haemodialysis population. METHODS: We compared incident home haemodialysis patients in England and Wales (n = 225, 1997-2005) with age- and sex-matched incident peritoneal dialysis, hospital haemodialysis and satellite haemodialysis patients with follow-up until 31 December 2006. Cox regression analyses included time-dependent changes of wait-listing for transplantation (a proxy for health status), start of home haemodialysis and transplantation. RESULTS: There was a median delay of 12 months between starting renal replacement therapy (RRT) and home haemodialysis. During that first year of RRT, > 50% of home haemodialysis patients were wait-listed for kidney transplantation; hospital haemodialysis patients had a lower rate of wait-listing over time [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.70; P < 0.001]. In crude analyses, there was a marked survival advantage of home haemodialysis patients compared with other modalities (log-rank P-value < 0.001). In adjusted analyses, being on home haemodialysis yielded a long-term survival benefit compared with peritoneal dialysis (HR 0.61, 95% CI 0.40-0.93), and a borderline advantage compared with hospital haemodialysis (HR 0.68, 95% CI 0.44-1.03). There was no evidence of an advantage compared with satellite haemodialysis (HR 0.94, 95% CI 0.65-1.37). CONCLUSIONS: Home haemodialysis patients have better survival compared with other dialysis modalities. Some of this crude survival advantage is due to selection of a healthier patient cohort as evidenced by higher transplant wait-listing rates. The advantage over peritoneal dialysis persisted after adjustment for wait-listing and transplantation over time.

A Randomized, Controlled Trial of the Effect of Allopurinol on Left Ventricular Mass Index in Hemodialysis Patients.

INTRODUCTION: Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease. This study investigated whether allopurinol would regress LVMI in hemodialysis patients. METHODS: This was a randomized placebo-controlled double-blind multicenter trial funded by the British Heart Foundation (PG/12/72/29743). A total of 80 patients undergoing regular maintenance hemodialysis were recruited from NHS Tayside, NHS Greater Glasgow and Clyde and NHS Ayrshire and Arran in Scotland, UK. Participants were randomly assigned on a 1:1 ratio to 12 months of therapy with allopurinol 300 mg or placebo after each dialysis session. The primary outcome was change in LVMI, as assessed by cardiac magnetic resonance imaging (CMRI) at baseline and 12 months. Secondary outcomes were change in BP, flow-mediated dilation (FMD), augmentation indices (AIx), and pulse wave velocity (PWV). RESULTS: A total of 53 patients, with a mean age of 58 years, completed the study and had CMRI follow-up data for analysis. Allopurinol did not regress LVMI (change in LVMI: placebo +3.6 ± 10.4 g/m2; allopurinol: +1.6 ± 11 g/m2; P = 0.49). Allopurinol had no demonstrable effect on BP, FMD, AIx, or PWV. CONCLUSION: Compared with placebo, treatment with allopurinol did not regress LVMI in this trial.

Assessing proteinuria in chronic kidney disease: protein-creatinine ratio versus albumin-creatinine ratio.

BACKGROUND: Quantification of proteinuria is important in the assessment of chronic kidney disease (CKD). The aim of this study was to investigate the optimal test to identify significant proteinuria. METHODS: We retrospectively assessed the relationship between total protein:creatinine ratio (TPCR), albumin:creatinine ratio (ACR) and 24-h urine total protein in 6842 patients with CKD focusing on performance at thresholds of 0.5 and 1 g/day of proteinuria. RESULTS: The relationship between ACR and TPCR is non-linear. TPCR is highly correlated with 24-h urine protein (Spearman's rho = 0.91), though ACR also performs well (rho = 0.84). Using receiver-operator characteristic curve analysis, TPCR outperforms ACR at predicting 0.5 g/day [area under the curve (AUC) 0.967 vs 0.951, P < 0.001] and 1 g/day of proteinuria (AUC 0.968 vs 0.947, P = 0.004). A TPCR threshold of 100 mg/mmol had a higher sensitivity (94% vs 79%) but lower specificity (88% vs 95%) than an ACR of 70 mg/mmol to predict 1 g/day of total proteinuria. To achieve comparable sensitivity, the ACR threshold falls to 17.5 mg/mmol, with lower specificity than TPCR (69.8%). Sensitivity of TPCR rose with increasing age, and in females: to achieve 95% sensitivity in a man <49 years, requires a TPCR of 65 mg/mmol, compared to 179 mg/mmol in a woman >79 years. Non-albumin proteinuria was a lower proportion of total proteinuria in patients receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockade than in those who were not (P < 0.001). CONCLUSIONS: TPCR is a more sensitive screening test than ACR to predict clinically relevant proteinuria. The diagnostic performance of both tests varies substantially with age and gender, and should be taken into consideration when interpreting results. Total proteinuria cannot be adequately predicted from ACR, and our results suggest that caution is appropriate before utilizing ACR in patients with non-diabetic CKD.

Clinical management of chronic kidney disease.

CKD is common and its prevalence may be increasing. It carries with it a substantial cardiovascular risk but the vast majority of patients will never require dialysis. The minority requiring further investigation or complex management should be promptly identified and referred to a nephrologist. The remaining patients require lifelong monitoring in primary care and careful attention to their cardiovascular risk factors.

Chronic maintenance hemodialysis: making sense of the terminology.

During the early decades, the hemodialysis (HD) terminology for modality, technique and function altered little as the widely accepted regime of thrice-weekly, 4-hourly dialysis varied little. In the last decade, however, a wide range of new options have emerged in all facets of HD therapy. This has led to a sudden expansion in terminology, some duplicating, some contradictory, some superfluous. The definitions used in 1 geographical region may mean something entirely different elsewhere, increasing cross-continental misunderstanding and misinterpretation and raising the often-asked question: "What exactly did the authors mean by that?" Although clearly the definitions used in this paper are also only the authors' opinion, we have sought to explore the use and sometimes confusing application of many commonly used terms, and we propose a number of possible deletions. Finally, we offer a descriptive data set that we believe should be used for all HD-related papers. Our conclusions will not always be welcomed--particularly by those who use terms we have rejected. Despite this, we believe it pertinent to fully review the dialysis terminology we use. Primarily, we hope to stimulate debate about which terms should be globally adopted and what those terms should mean when used. Although not all will agree with our conclusions, we hope this paper may provide a framework for a more streamlined, efficient, and globally acceptable nomenclature.

Factors predicting outcome in a cohort of patients with atherosclerotic renal artery disease diagnosed by magnetic resonance angiography.

BACKGROUND: Atherosclerotic renal artery disease increasingly is recognized as a cause of chronic kidney disease and associated with high morbidity and mortality. We investigated factors predicting patient and renal survival in a cohort of patients with atherosclerotic renal artery disease diagnosed by means of magnetic resonance angiography (MRA). METHODS: We retrospectively analyzed a cohort of patients attending our unit in whom atherosclerotic renal artery disease was identified by means of MRA from 1998 to 2001. One hundred nine patients were followed up for a median of 2.3 years. Baseline clinical and laboratory data were assessed as predictors of outcome by using multivariate Cox proportional hazards analysis. RESULTS: Seventeen patients (16%) required dialysis and 37 patients (34%) died during a median follow-up of 841 days (interquartile range, 326 to 1,206). On multivariate Cox proportional hazards analysis, increased peripheral-blood eosinophil count (hazard ratio, 3.39; 95% confidence interval [CI], 1.45 to 7.88; P = 0.0097), creatinine clearance (hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P = 0.0128), and peripheral arterial disease (hazard ratio, 2.09; 95% CI, 1.04 to 4.18; P = 0.0371) were associated with subsequent death. Only creatinine clearance (hazard ratio, 0.91; 95% CI, 0.87 to 0.96; P = 0.0004) was associated with the need for dialysis. There was no association between eosinophil count and other markers of inflammation. Severity of atherosclerotic renal artery disease was not associated independently with either the need for dialysis or death. CONCLUSION: An increased peripheral-blood eosinophil count predicts patient survival in those with atherosclerotic renal artery disease at the time of diagnosis. This novel risk factor may help identify a group of patients who could benefit from intensive medical therapy by using an assay readily available to most clinicians worldwide.

A prospective open-label randomised trial of quinapril and/or amlodipine in progressive non-diabetic renal failure.

BACKGROUND: Treatment of hypertension slows the progression of non-diabetic nephropathies, but the optimal regimen is unknown. Angiotensin-converting enzyme inhibitors are more effective than beta-blockers, but their merits relative to calcium channel blockers are less clear. METHODS: 73 hypertensive patients with progressive non-diabetic nephropathies were prospectively randomised to open-label quinapril (Q, n = 28), amlodipine (A, n = 28) or both drugs (Q&A, n = 17). Therapy was increased to achieve a diastolic blood pressure < 90 mm Hg. Patients were followed for 4 years or until death. The primary outcome was the combined endpoint of doubling serum creatinine, starting renal replacement therapy or death. RESULTS: There was no significant difference in the primary outcome, or in the change of glomerular filtration rate. Blood pressure was equally controlled throughout the study period. 29 (40%) patients were withdrawn from the allocated therapy (Q 39%, A 36%, Q&A 47%). Because of the large crossover between trial arms, the data were re-analysed per protocol. The effect on preventing the need for renal replacement therapy then approached significance between the groups (p = 0.089) and the combined quinapril-containing groups were less likely than the amlodipine group to achieve the primary endpoint (p = 0.038), or the individual endpoints of renal replacement therapy (p = 0.030) or doubling creatinine (p = 0.051). CONCLUSIONS: Quinapril is more effective than amlodipine at reducing the incidence of dialysis in patients with progressive renal failure, but only if they can tolerate the drug. The tolerability of these drugs in patients with advanced renal failure is poor.

Empiricism or rationalism: how should we measure proteinuria?

Proteinuria is the cardinal sign of renal disease, therefore accurate identification of clinically significant proteinuria is essential to the diagnosis and management of kidney disease. Spot samples are now widely used, namely protein: creatinine ratio (uPCR) and albumin: creatinine ratio (uACR). In this article we review the evidence comparing uPCR and uACR including clinical, laboratory and financial arguments. uPCR has a superior performance to uACR to predict 24-hour total proteinuria, the measurement on which the evidence for interventions in chronic kidney disease is based. Furthermore a retrospective study comparing uPCR and uACR as predictors of renal outcome found comparable performance to predict all-cause mortality, commencement of renal replacement therapy and doubling of serum creatinine. Only uPCR takes account of non-albumin proteinuria which has been shown to have prognostic significance. uACR was been thought to be superior at low levels (where there is less 'noise' from physiological urinary proteins), but uPCR has recently been shown to perform well at levels equivalent to <0.5 g/day (and even within the reference range) as a predictor of outcomes. uACR is measured using an immunoassay that may be technically superior, but is not without shortcomings (such as antigen excess) and is 2-10 times more expensive than uPCR. The theories explaining the superiority of albumin are appealing. However, the available comparative data do not seem to support the theory. We cannot explain the disparity, but in science, if the data do not fit the existing theory, then maybe it's time for a new theory.

Echinocandin resistance due to simultaneous FKS mutation and increased cell wall chitin in a Candida albicans bloodstream isolate following brief exposure to caspofungin.

Echinocandins are first-line agents for treating severe invasive candidiasis. Glucan synthase gene (FKS1) mutations lead to echinocandin resistance but the role of enhanced chitin expression is not well recognized in clinical isolates. We report a case of bloodstream Candida albicans infection with both Fks1 hotspot mutation and elevated cell wall chitin.

Outcomes on home haemodialysis: registry challenges.

Health care policy is encouraging expansion of home haemodialysis, aiming to improve patient outcomes and reduce cost. However, most patient outcome data derive from retrospective observational studies, with all their inherent weaknesses. Conventional thrice weekly home haemodialysis delivers a 22-51% reduction in mortality, but why should that be? Frequent and/or nocturnal haemodialysis reduces mortality by 36-66%, with comparable outcomes to deceased donor kidney transplantation. Approaches which might improve the quality of future observational studies are discussed. Patient-relevant outcomes other than mortality are also discussed.

Home haemodialysis-international trends and variation.

BACKGROUND: Home haemodialysis (HD) has the best patient outcomes and is the most cost-effective of any dialysis modality, but its use has been declining in many countries. METHODS: Point prevalence rates of different dialysis modalities and transplantation were obtained from national and regional registries for the most recent available year (2001-03) for 21 high-income and 12 middle-income countries. Relationships with median age and prevalence of diabetic nephropathy, healthcare expenditure and population density were assessed. Long-term trends in the use of home HD during the last two to four decades were obtained for seven countries. RESULTS: The prevalence of home HD varies from 0 to 58.4 per million population, and varies between countries, more than any other renal replacement therapy (RRT) modality. There is a positive association between the use of peritoneal dialysis and home HD (Spearman's rho = 0.531, P = 0.013), but no correlation with transplantation prevalence. There is a negative correlation with median age of the renal replacement population (rho = -0.552, P = 0.018). There is no association with prevalence of diabetic nephropathy, healthcare expenditure or population density. Temporal trends in home HD prevalence are dramatically different in different countries, with several countries expanding its use in the last few years. CONCLUSION: The use of home HD varies dramatically between and within countries. The variation cannot be explained by the variation in the use of other RRT modalities, nor by prevalence of diabetic nephropathy, national wealth or population density. The inverse correlation with median age is difficult to explain. Significant expansion of home HD is likely to be possible in most countries, and will be increasingly important as the impressive results of more frequent HD gain credence.