Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Variation in centre-specific survival in patients starting renal replacement therapy in England is explained by enhanced comorbidity information from hospitalization data

Background Unadjusted survival on renal replacement therapy (RRT) varies widely from centre to centre in England. Until now, missing data on case mix have made it impossible to determine whether this variation reflects genuine differences in the quality of care. Data linkage has the capacity to reduce missing data. Methods Modelling of survival using Cox proportional hazards of data returned to the UK Renal Registry on patients starting RRT for established renal failure in England. Data on ethnicity, socioeconomic status and comorbidity were obtained by linkage to the Hospital Episode Statistics database, using data from hospitalizations prior to starting RRT. Results Patients with missing data were reduced from 61 to 4%. The prevalence of comorbid conditions was remarkably similar across centres. When centre-specific survival was compared after adjustment solely for age, survival was below the 95% limit for 6 of 46 centres. The addition of variables into the multivariable model altered the number of centres that appeared to be ‘outliers’ with worse than expected survival as follows: ethnic origin four outliers, socioeconomic status eight outliers and year of the start of RRT four outliers. The addition of a combination of 16 comorbid conditions present at the start of RRT reduced the number of centres with worse than expected survival to one. Conclusions Linked data between a national registry and hospital admission dramatically reduced missing data, and allowed us to show that nearly all the variation between English renal centres in 3-year survival on RRT was explained by demographic factors and by comorbidity

Estimating kidney function in adults using formulae

With increasing emphasis on the earlier detection and management of chronic kidney disease (CKD), estimation of the glomerular filtration rate (GFR) has assumed greater importance. It is accepted that use of serum creatinine concentration alone as a marker of kidney function is inadequate; in particular, it has a poor sensitivity for detecting CKD. International recommendations favour the reporting of creatinine-based estimates of GFR using formulae which also take into account age, gender and other variables that affect the relationship between serum creatinine and GFR: in particular, the four-variable formula derived from the Modification of Diet in Renal Disease study (4-v MDRD) is increasingly being used. We have reviewed the literature supporting the use of this formula compared with the well-established Cockcroft and Gault formula. Overall, evidence supports the use of the 4-v MDRD formula as an improved estimate of GFR in people with moderate/advanced CKD. Neither formula performs well in people with normal and mildly reduced kidney function. However, there remain significant problems with this approach and areas where further research is required. In particular, the widespread adoption of estimated GFR reporting has refocused attention on the limitations of creatinine measurement and highlighted clinical situations in which the formulae are inadequate

The 'centre effect' in nephrology: What do differences between nephrology centres tell us about clinical performance in patient management?

Improving the quality of care provided by nephrology centres to patients with kidney disease requires a clear understanding of how to compare performance after adjustment for case mix, combined with a detailed understanding of the structure and processes that are associated with the achievement of good clinical results. In this review, we discuss how to measure quality of care (using process or outcome measures), how to take case mix into account, how best to display comparisons between nephrology centres, and how to study the causes of real variations in quality between centres. This is a narrative review; we include examples from other fields in which the centre effect has been studied, including education. <br/

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, &gt;?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 &lt; 0.001]. In crude analyses, there was a marked survival advantage of home haemodialysis patients compared with other modalities (log-rank P-value &lt; 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. <br/

Ethnicity, socioeconomic status, and attainment of clinical practice guideline standards in dialysis patients in the United Kingdom

Background and objectives: the role of socioeconomic status (SES) and its contribution to ethnic differences in standards attainment among dialysis patients is not known.Design, setting, participants, &amp; measurements: we examined associations between area- level SES (Townsend index) and ethnicity (white, black, South Asian) and standards attainment in 14,117 incident dialysis patients (1997–2004) in the UK.Results: deprived patients were less likely to achieve hemoglobin (Hb) ? 10g/dl (trend P &lt; 0.001) but not after controlling for patient and center characteristics (trend P = 0.1). There was no association with hemodialysis dose and parathyroid hormone (PTH) standard but deprived patients had better attainment of phosphate (PO4) &lt;5.6 mg/dl, calcium (Ca) and Calcium-phosphate (CaPO4) standard (e.g., most deprived versus least deprived adjusted odds ratio [OR] 1.25, 95% confidence intervals [CI] 1.12, 1.38). There was no association with SES using a lower limit for PO4 (3.5 – 5.5 mg/dl). Compared with Whites, Blacks had lower attainment of Hb (adjusted OR 0.57, 95% CI 0.45, 0.71) and PTH standards (adjusted OR 0.27, 95% CI 0.22, 0.33) but better attainment of PO4 and CaPO4, while South Asians experienced better or comparable outcomes for most standards except Ca and PTH.Conclusions: there was no evidence of socioeconomic inequity in standards attainment or a consistent pattern of inequity by ethnic group. The lower attainment of some standards in ethnic minorities may reflect biologic differences rather than ethnicity-related inequity of car

Association between glycemia and mortality in diabetic individuals on renal replacement therapy in the U.K.

OBJECTIVE: In the U.K., one-third of patients receiving treatment with dialysis have diabetes. Guidelines from organizations representing patients with renal disease or diabetes advocate tight glycemic control in patients with end-stage renal disease, despite glucose-lowering trials having excluded these patients. RESEARCH DESIGN AND METHODS: Using national U.K. Renal Registry data, we tested whether glycemia as measured by hemoglobin (Hb) A(1c) (HbA(1c)) level is associated with death in adults with diabetes starting hemodialysis or peritoneal dialysis between 1997 and 2006, and observed for at least 6 months. Of 7,814 patients, we excluded those who had died within 6 months; had received transplants; were lost/recovered; or lacked measures of HbA1c, ethnicity, or Hb. Categorizing HbA1c measured in the first 6 months of starting dialysis as 8.5% was 1.5 (1.2-1.9). The projected difference in median survival time between younger patients with a reference HbA1c value versus >8.5% was 1 year. CONCLUSIONS: In the absence of trials, and confounding notwithstanding, these observational data support improved glycemic control in younger patients prior to and during dialysis