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International audience; Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients. Index Words: end-stage renal disease, medication management, pharmacy

Background The optimal treatment algorithm for iron therapy and the use of erythropoiesis-stimulating agents (ESA) in anemic hemodialysis (HD) patients has not been established. Hemoglobin (Hb) target levels can be achieved through more frequent intravenous (IV) iron use with lower ESA dose, or with less iron dosing but higher ESA. ESA therapy to correct anemia may result in severe arterial and venous thrombotic complications and the evidence base evaluating hard clinical outcomes related to the use of IV iron is sparse. Methods A total of 1247 maintenance HD patients from 12 dialysis centers in Portugal (n = 730) and Poland (n = 517) were considered. We assessed achievement of KDIGO renal anemia targets with focus on treatment strategies, which typically differ between countries. In Poland the use and dose of IV iron was 35–72% higher than that in Portugal (p 20 and > 50% were both significantly higher in patients in Poland (88.8 and 14.6%) than in Portugal (76.3 and 5.7% respectively, p 800 μg/L (35.6%) compared to Portugal (15.8%, p

The omission of outcomes that are of relevance to patients, clinicians, and regulators across trials in autosomal dominant polycystic kidney disease (ADPKD) limits shared decision making. The Standardized Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD) Initiative convened an international consensus workshop on October 25, 2018, to discuss the identification and implementation of a potential core outcome set for all ADPKD trials. This article summarizes the discussion from the workshops and the SONG-PKD core outcome set. Key stakeholders including 11 patients/ caregivers and 47 health professionals (nephrologists, policy makers, industry, and researchers) attended the workshop. Four themes emerged: "Relevance of trajectory and impact of kidney function" included concerns about a patient's prognosis and uncertainty of when they may need to commence kidney replacement therapy and the lack of an early prognostic marker to inform long-term decisions; "Discerning and defining pain specific to ADPKD" highlighted the challenges in determining the origin of pain, adapting to the chronicity and repeated episodes of pain, the need to place emphasis on pain management, and to have a validated measure for pain; "Highlighting ADPKD consequences" encompassed cyst-related complications and reflected patient's knowledge because of family history and the hereditary nature of ADPKD; and "Risk for life-threatening but rare consequences" such as cerebral aneurysm meant considering both frequency and severity of the outcome. Kidney function, mortality, cardiovascular disease, and pain were established as the core outcomes for ADPKD.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although tests to detect anti-SARS-CoV-2 antibodies have been developed, their sensitivity and specificity in hemodialysis patients have not been previously assessed.MethodsAs part of a quality improvement (QI) initiative, nasopharyngeal swabs and predialysis blood samples were collected on the same day from adult patients receiving routine hemodialysis care at clinics managed by a large dialysis organization in the greater Miami, Florida region (23 – 30 Apr 2020). Polymerase chain reaction (PCR) tests for SARS-CoV-2 and chemiluminescence immunoassays for anti-SARS-CoV2 antibodies were performed according to manufacturer-specified protocols.ResultsOf 715 participants in the QI initiative, 38 had symptomatology consistent with COVID-19 prior to or during the initiative. Among these, COVID-19 was PCR-confirmed in 14 and ruled out in 20, with the remaining 4 being inconclusive. Among the 34 patients with known COVID-19 status, the sensitivity and specificity of the antibody test were 57.1% and 85.0% when either antibody was considered. The remaining 677 patients had no record of symptoms consistent with COVID-19, nor any known exposure. Of these, 38 patients (5.6%) tested positive for anti-SARS-CoV-2 antibodies.ConclusionsThe operational characteristics of the laboratory-based antibody test make it sufficient to rule in, but not rule out, SARS-CoV-2 infection in the appropriate clinical circumstance. A substantial proportion of dialysis patients may have had asymptomatic SARS-CoV-2 infection.

Most current scoring tools to predict allograft and patient survival upon kidney transplantion are based on variables collected posttransplantation. We developed a novel score to predict posttransplant outcomes using pretransplant information including routine laboratory data available before or at the time of transplantation.Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 15 125 hemodialysis patients who underwent first deceased transplantion. Prediction models were developed using Cox models for (a) mortality, (b) allograft loss (death censored), and (c) combined death or transplant failure. The cohort was randomly divided into a two thirds set (Nd = 10 083) for model development and a one third set (Nv = 5042) for validation. Model predictive discrimination was assessed using the index of concordance, or C statistic, which accounts for censoring in time-to-event models (a-c). We used the bootstrap method to assess model overfitting and calibration using the development dataset.Patients were 50 ± 13 years of age and included 39% women, 15% African Americans, and 36% persons with diabetes. For prediction of posttransplant mortality and graft loss, 10 predictors were used (recipients' age, cause and length of end-stage renal disease, hemoglobin, albumin, selected comorbidities, race and type of insurance as well as donor age, diabetes status, extended criterion donor kidney, and number of HLA mismatches). The new model (www.TransplantScore.com) showed the overall best discrimination (C-statistics, 0.70; 95% confidence interval [95% CI], 0.67-0.73 for mortality; 0.63; 95% CI, 0.60-0.66 for graft failure; 0.63; 95% CI, 0.61-0.66 for combined outcome).The new prediction tool, using data available before the time of transplantation, predicts relevant clinical outcomes and may perform better to predict patients' graft survival than currently used tools.

BackgroundLimited well-controlled research exists examining the impact of different formulations of oral vitamin D on clinical outcomes in dialysis patients, specifically those on peritoneal dialysis. For this retrospective mortality analysis, we compared mortality rates of patients on 3 of the most commonly prescribed vitamin D agents.MethodsWe examined 2 years (7/1/2008 to 6/30/2010) of oral medication records of peritoneal dialysis patients from a large US dialysis organization. Patients were identified whose physicians prescribed a single form of vitamin D (calcitriol, paricalcitol, or doxercalciferol) for ≥ 90% of all patient-months. We excluded incident patients (< 90 days on dialysis) and patients whose physicians treated < 5 peritoneal dialysis patients at a dialysis facility, and we assessed mortality.ResultsThe analysis inclusion criteria identified 1,707 patients. The subset in this analysis included 12.6% of all prevalent peritoneal dialysis patients and 11.8% of prevalent patient-months. Patients with physicians who predominately prescribed calcitriol had a lower mortality rate: 9.33 (confidence interval (CI) 7.06, 11.60) deaths per 100 patient-years than the doxercalciferol, 12.20 (CI 9.34, 15.06) or paricalcitol, 12.27 (CI 9.27, 15.28) groups. However, these differences were not statistically significant. A Cox proportional hazards model, adjusting for differences in age, vintage, gender, race, body mass index, and comorbidities also showed no significant differences.ConclusionsFor this peritoneal dialysis population, instrumental variable analyses showed no significant difference in mortality in patients taking the most common oral vitamin D formulations (calcitriol, doxercalciferol, paricalcitol).

Author(s): Molnar, Miklos Z; Foster, Clarence E; Sim, John J; Remport, Adam; Krishnan, Mahesh; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar | Abstract: BackgroundPrevious studies have indicated U-shaped associations between blood pressure (BP) and mortality in dialysis patients. We hypothesized that a similar association exists between pre-transplant BP and post-transplant outcomes in dialysis patients who undergo successful kidney transplantation.MethodsData from the Scientific Registry of Transplant Recipients were linked to the five-yr cohort of a large dialysis organization in the United States. We identified all dialysis patients who received a kidney transplant during this period. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined.ResultsA total of 13 881 patients included in our study were 47 ± 14 yr old and included 42% women. There was no association between pre-transplant systolic BP and post-transplant mortality, although a decreased risk trend was observed in those with low post-dialysis systolic BP. Compared to patients with pre-dialysis diastolic BP 70 to l80 mmHg, patients with pre-dialysis diastolic BP l50 mmHg experienced lower risk of post-transplant death (hazard ratios [HR]: 0.74, 95% CI: 0.55-0.99). However, compared to patients with post-dialysis diastolic BP 70 to l80 mmHg, patients with post-dialysis diastolic BP ≥100 mmHg experienced higher risk of death (HR: 3.50, 95% CI: 1.57-7.84). In addition, very low (l50 mmHg for diastolic BP and l110 mmHg for systolic BP) pre-transplant BP was associated with lower risk of graft loss.ConclusionsLow post-dialysis systolic BP and low pre-dialysis diastolic BP are associated with lower post-transplant risk of death, whereas very high post-dialysis diastolic BP is associated with higher mortality in kidney transplant recipients. BP variations in dialysis patients prior to kidney transplantation may have a bearing on post-transplant outcome, which warrants additional studies.

Author(s): Molnar, Miklos Z; Bunnapradist, Suphamai; Huang, Edmund; Krishnan, Mahesh; Nissenson, Allen R; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar | Abstract: BackgroundThe role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear.MethodsLinking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively.ResultsPatients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected.ConclusionsHigher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.

Author(s): Molnar, Miklos Z; Kovesdy, Csaba P; Rosivall, Laszlo; Bunnapradist, Suphamai; Hoshino, Junichi; Streja, Elani; Krishnan, Mahesh; Kalantar-Zadeh, Kamyar | Abstract: BackgroundDelayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF.MethodsLinking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF.ResultsPatients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ≥13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34).ConclusionsPre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.

Summary Background and objectives The influence of pretransplant dialysis modality on post-transplant outcomes is not clear. This study examined associations of pretransplant dialysis modality with post-transplant outcomes in a large national cohort of kidney transplant recipients. Design, setting, participants, & measurements Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, 12,416 hemodialysis and 2092 peritoneal dialysis patients who underwent first kidney transplantation were identified. Mortality or graft failure and delayed graft function risks were estimated by Cox regression (hazard ratio) and logistic regression (odds ratio), respectively. Results Recipients treated with peritoneal dialysis pretransplantation had lower (21.9/1000 patient-years [95% confidence interval: 18.1–26.5]) crude all-cause mortality rate than those recipients treated with hemodialysis (32.8/1000 patient-years [30.8–35.0]). Pretransplant peritoneal dialysis use was associated with 43% lower adjusted all-cause and 66% lower cardiovascular death. Furthermore, pretransplant peritoneal dialysis use was associated with 17% and 36% lower unadjusted death-censored graft failure and delayed graft function risk, respectively. However, after additional adjustment for relevant covariates, pretransplant peritoneal dialysis modality was not a significant predictor of death-censored graft failure delayed graft function, respectively. Similar trends were noted on analyses using a propensity score matched cohort of 2092 pairs of patients. Conclusions Compared with hemodialysis, patients treated with peritoneal dialysis before transplantation had lower mortality but similar graft loss or delayed graft function. Confounding by residual selection bias cannot be ruled out.

Background: It is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD). Objectives: We hypothesized that ESRD patients with relative thrombocytosis (platelet count .300 · 10 3 /lL) have a higher mortality rate and that this association may be related to malnutritioninflammation cachexia syndrome (MICS). Design: We examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001‐2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis. Results: The patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 6 78 · 10 3 /lL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 · 10 3 /lL (reference), the allcause (and cardiovascular) mortality rate with platelet counts between 300 and ,350, between 350 and ,400, and 400 ·10 3 /l Lw ere 6% (and 7%), 17% (and 15%), and 24% (and 25%) higher (P , 0.05), respectively. The associations persisted after control for case-mix adjustment, but adjustment for MICS abolished them. Conclusions: Relative thrombocytosis is associated with a worse MICS profile, a lower dialysis dose, and higher all-cause and cardiovascular disease death risk in hemodialysis patients; and its all-cause and cardiovascular mortality predictability is accounted for by MICS. The role of platelet activation in cachexia-associated mortality warrants additional studies. Am J Clin Nutr 2011;94:945‐54.

To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m(2). After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22-24.99 kg/m(2), overweight patients (BMI 25-29.99 kg/m(2)), mild obesity patients (BMI 30-34.99 kg/m(2)), and moderate-to-severe obesity patients (BMI 35 kg/m(2) and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF.

Background Inflammation in an ESRD patient may impact responsiveness to erythropoiesis-stimulating agent (ESA) therapy. We sought to investigate the association between C-reactive protein (CRP) levels and average per-administration epoetin alfa (EPO) dose over 3 months following a CRP measurement. Methods The study is a retrospective cohort study of hemodialysis patients >or=18 years of age receiving care at a Fresenius Medical Care-North America facility between 1 July 2000 and 30 June 2002 who had no history of peritoneal dialysis. All patients had >or=1 CRP measurement and >or=3 months of recorded information before the CRP measurement (entry period). We evaluated the association between CRP levels and average hemoglobin (Hb) and per-administration EPO dose over the 3 months following the CRP measurement. Results We identified 1754 patients with a CRP measurement; mean age was 62.6 years (SD 14.1), 51.5% were male, 56.2% were white and the median CRP value was 2.04 mg/dL (20.4 mg/L). Patients in the upper CRP quartiles were more likely to be older, recently hospitalized; have a catheter vascular access; have lower albumin, Hb and transferrin saturation levels and greater EPO doses. In the subsequent 3 months, EPO doses but not Hb levels were significantly higher for patients in the highest CRP quartile [3.21 mg/dL (32.1 mg/L)] (P = 0.01). Conclusions Inflammation as measured by an elevated CRP level appears to be an independent predictor of greater ESA dose requirements. Patients with the highest CRP levels required significantly higher ESA doses to achieve comparable Hb levels even after controlling for potential confounding variables.

Objective To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti–double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

Background and objectives: Among hemodialysis patients, achieved hemoglobin is associated with Epoetin alfa dose and erythropoietin responsiveness. A prospective erythropoietin responsiveness measure was developed and its association with mortality evaluated. Design, setting, participants, & measurements: Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality. Results: Erythropoietin responsiveness values ranged from −2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87). Conclusion: Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.

It is unknown to what degree physicians adjust erythropoietin doses to achieve hemoglobin levels (11.0 to 12.0 g/dL [110 to 120 g/L]) recommended by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) for patients with end-stage renal disease receiving hemodialysis. Our objective is to examine epoetin alfa prescribing patterns for achieving the target hemoglobin level range in this population.Monthly hemoglobin levels and epoetin alfa doses from 2 large databases were retrospectively analyzed. One data set comprised 31,267 patients from the Fresenius Medical Care-North America (FMC-NA) database, and the other comprised 128,761 patients based on claims for Medicare services.Longitudinal evaluation of the FMC-NA data set showed that hemoglobin levels in patients administered epoetin alfa cycled in and out of the NKF-K/DOQI hemoglobin target range, and doses were decreased in 98.8% of patients with persistent hemoglobin levels greater than 12.0 g/dL (120 g/L). Hemoglobin levels in patients from the Medicare data set that initially were outside the target range migrated into the range with epoetin alfa dose titration. FMC-NA patients with a 3-month average hemoglobin level less than 11.0 g/dL (110 g/L) were administered significantly greater epoetin alfa doses than those with average hemoglobin levels greater than 12.0 g/dL (120 g/L; 21,838 versus 13,503 U/wk; P0.0001). Less than 0.4% of patients administered epoetin alfa were persistently anemic (hemoglobin11.0 g/dL [110 g/L]) and were administered persistently high doses (30,000 U/wk), but failed to respond with a 0.5-g/dL or greater (or = 5-g/L) increase in hemoglobin levels.In these analyses, few hemodialysis patients experienced persistent anemia while being administered high epoetin alfa doses. Physicians appeared to appropriately adjust doses to achieve hemoglobin levels recommended by the NKF-K/DOQI guidelines.

Background Patient outcomes have been compared on the basis of the profit status of the dialysis provider (for-profit [FP] and not-for-profit [NFP]). In its annual report, United States Renal Data System (USRDS) provides dialysis provider level death and hospitalization rates adjusted by age, race, sex, and dialysis vintage; however, recent analyses have suggested that other variables impact these outcomes. Our current analysis of hospitalization and mortality rates of hemodialysis patients included adjustments for those used by the USRDS plus other potential confounders: facility geography (end-stage renal disease network), length of facility ownership, vascular access at first dialysis session, and pre-dialysis nephrology care. Methods We performed a provider level, retrospective analysis of 2010 hospitalization and mortality rates among US hemodialysis patients exclusively using USRDS sources. Crude and adjusted incidence rate ratios (IRRs) were calculated using the 4 standard USRDS patient factors plus the 4 potential confounders noted above. Results The analysis included 366,011 and 34,029 patients treated at FP and NFP facilities, respectively. There were statistical differences between the cohorts in geography, facility length of ownership, vascular access, and pre-dialysis nephrology care (p

It is not clear whether in old people with end-stage renal disease kidney transplantation is superior to dialysis therapy.We compared mortality rates between kidney transplant recipients (KTRs) and the general population across different age categories. We also examined patient and allograft survival in 15 667 elderly KTRs (65-90 yr old, 36% female) within three age subgroups (65-70, 70-75, and ≥75 yr).The rise in the relative risk of death in older age groups was substantially less in KTRs than in the general population, that is, 1.8 and 2.0 vs. 21.4 and 76.6 in those aged 65-75 and ≥75 yr, respectively, compared with 15- to65-yr-old people (reference group). In 65- to70-yr-old KTRs, obesity (BMI30 kg/m(2) ) was associated with 19% higher risk of graft failure (HR: 1.19 [1.07-1.33], p = 0.002). Diabetes was a predictor of worse patient survival in all age groups but poorer allograft outcome in the youngest age group (65-70 yr old) only. None of the examined risk factors affected allograft outcome in the oldest group (≥75 yr old) although there was a 49% lower trend of graft failure in very old Hispanic recipients (HR: 0.51 [0.26-1.01], p = 0.05).Kidney transplantation may attenuate the age-associated increase in mortality, and its superior survival gain is most prominent in the oldest recipients (≥75 yr old). The potential protective effect of kidney transplantation on longevity in the elderly deserves further investigation.

Author(s): Molnar, Miklos Z; Kovesdy, Csaba P; Bunnapradist, Suphamai; Streja, Elani; Krishnan, Mahesh; Mucsi, Istvan; Norris, Keith C; Kalantar-Zadeh, Kamyar | Abstract: BackgroundAfrican Americans are at greater risk to reach end-stage renal disease and this risk may carry over in a kidney transplant recipient after kidney transplantation.MethodsLinking the five-yr patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 13 692 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function risks were estimated by Cox's regression (hazard ratio [HR] and 95% confidence interval) and logistic regression, respectively.ResultsPatients were 48 ± 14 yr old and included 39% women and 26% patients with diabetes. After adjusting for several relevant clinical and transplant-related variables, African American donor race was associated with higher all-cause mortality, with HR of 1.39 (1.09-1.78) for all-cause mortality, 1.80 (1.17-2.76) for cardiovascular mortality, 1.30 (1.03-1.64) for death-censored graft loss and 1.31 (1.10-1.57) for combined outcome over the six-yr observation period. In the non-African American recipient subcohort, but not in the African American recipient subcohort, African American donor race was associated with higher risk of death-censored graft loss (2.24 [1.44-3.49]) in our fully adjusted model.ConclusionsAfrican American donor race was associated with increased all-cause and cardiovascular mortality and graft loss.

In hemodialysis patients, lower body mass index and weight loss have been associated with higher mortality rates, a phenomenon sometimes called the obesity paradox. This apparent paradox might be explained by loss of muscle mass. The authors thus examined the relation to mortality of changes in dry weight and changes in serum creatinine levels (a muscle-mass surrogate) in a cohort of 121,762 hemodialysis patients who were followed for up to 5 years (2001-2006). In addition to conventional regression analyses, the authors conducted a ranking analysis of joint effects in which the sums and differences of the percentiles of change for the 2 measures in each patient were used as the regressors. Concordant with previous body mass index observations, lower body mass, lower muscle mass, weight loss, and serum creatinine decline were associated with higher death rates. Among patients with a discordant change, persons whose weight declined but whose serum creatinine levels increased had lower death rates than did those whose weight increased but whose serum creatinine level declined. A decline in serum creatinine appeared to be a stronger predictor of mortality than did weight loss. Assuming residual selection bias and confounding were not large, the present results suggest that a considerable proportion of the obesity paradox in dialysis patients might be explained by the amount of decline in muscle mass.

Recent studies show a survival advantage with kidney transplant in elderly patients compared with those on dialysis therapy.In our present study, we examined and compared the association of expanded criteria donor (ECD) kidney and living kidney donation with the outcome of kidney transplant across different ages, including elderly recipients.Using the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplant patients. Mortality and death-censored transplant failure risks were estimated by Cox proportional regression analyses during follow-up with a median of 3.9 years.ECD kidney and living kidney donation and age compared with others.Mortality and death-censored transplant failure risk.Patients were aged 45 ± 16 years and included 40% women and 19% patients with diabetes. Compared with transplant recipients 55 to younger than 65 years, the fully adjusted death-censored transplant failure risk was higher in patients 75 years and older (HR, 1.30; 95% CI, 1.09-1.56), 35 to younger than 55 years (HR, 1.13; 95% CI, 1.08-1.17), and 18 to younger than 35 years (HR, 1.64; 95% CI, 1.57-1.71). Compared with non-ECD kidneys, ECD kidneys were significant predictors of mortality in nonelderly patients (18-35 years: HR, 1.46 [95% CI, 1.19-1.77]; 35-55 years: HR, 1.23 [95% CI, 1.14-1.32]; and 55-65 years: HR, 1.26 [95% CI, 1.15-1.38]) and patients 65 to younger than 70 years (HR, 1.20; 95% CI, 1.05-1.36), but not in other groups of elderly patients (HRs of 1.12 [95% CI, 0.93-1.36] for 70-75 years and 1.04 [95% CI, 0.74-1.47] for ≥75 years). Similar results were found for risk of transplant loss. Compared with deceased donor kidneys, a living donor kidney was associated with better survival in all age groups and lower transplant loss risk in patients younger than 70 years.Unmeasured confounders cannot be adjusted for.For deceased donors, ECD kidneys are not associated with increased mortality or transplant failure in recipients older than 70 years. For all types of donors, the persistent association between living donor kidneys and lower all-cause mortality across all ages suggests that, if possible, elderly patients gain longevity from living donor kidney transplant.

Serum phosphorus levels are associated with mortality, cardiovascular disease, and renal function loss in individuals with and without chronic kidney disease. The association of pretransplant serum phosphorus levels with transplant outcomes is not clear.Data of the Scientific Registry of Transplant Recipients (SRTR) up to June 2007 were linked to the database (2001 through 2006) of one of the U.S.-based large dialysis organizations (DaVita). The selected 9384 primary kidney recipients were divided into five groups according to pretransplant serum phosphorus levels (mg/dl):3.5, 3.5 to5.5 (reference group), 5.5 to7.5, 7.5 to9.5, and ≥9.5. Unadjusted and multivariate adjusted risks for transplant outcomes were compared.Patients were 48 ± 14 years old and included 37% women and 27% African Americans. After multivariate adjustment, all-cause and cardiovascular death hazard ratios were 2.44 (95% confidence interval: 1.28 to 4.65) and 3.63 (1.13 to 11.64), respectively, in recipients in the ≥9.5 group; allograft loss hazard ratios were 1.42 (1.04 to 1.95) and 2.36 (1.33 to 4.17) in recipients with 7.5 to9.5 and ≥9.5, respectively. No significant association with delayed graft function was found.Pretransplant phosphorus levels 7.5 to9.5 mg/dl and ≥9.5 mg/dl were associated with increased risk of functional graft failure and increased risk of all-cause and cardiovascular deaths, respectively, when compared with 3.5 to5.5 mg/dl. Additional studies are needed to examine whether more aggressive control of pretransplant serum phosphorus may improve posttransplant outcomes.

OBJECTIVE Observational studies have yielded inconsistent findings regarding the association of hemoglobin A1c (HbA1c) with survival in diabetic patients on dialysis. The association between pretransplant glycemic control and short- and long-term posttransplant outcomes in kidney transplant recipients is not clear. RESEARCH DESIGN AND METHODS Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 2,872 diabetic dialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (odds ratio), respectively. RESULTS Patients were 53 ± 11 years old and included 36% women and 24% African Americans. In our fully adjusted model, allograft failure–censored, all-cause death HR and 95% CI for time-averaged pretransplant HbA1c categories of 7 to CONCLUSIONS Poor pretransplant glycemic control appears associated with decreased posttransplant survival in kidney transplant recipients, whereas allograft outcomes may not be affected.

End-stage renal disease causes dysregulation of bone and mineral metabolism, including increased serum phosphorus levels. Kidney Foundation Kidney Disease Outcome Quality Initiative 2003 guidelines recommend maintaining phosphorus levels between 3.5 and 5.5 mg/dL in dialysis patients. We examined the effects of a focused phosphorus management pilot program designed to improve the percentage of hemodialysis patients achieving phosphorus levels5.5 mg/dL. DESIGN, SETTING, SUBJECTS, AND INTERVENTION: We conducted a prospective, multicenter, single-arm study at 8 geographically diverse at-risk facilities (n = 702 hemodialysis patients) in a large U.S. dialysis organization. The focused phosphorus management program provided in-service training to staff members, and provided patients with diet and phosphorus management through in-center, 1:1 education and support, direct-to-patient adherence communications, benefit management assistance, and adherence support specific to lanthanum carbonate over a 6-month period.Facility-level markers of bone and mineral metabolism (phosphorus, parathyroid hormone, corrected calcium) and nutritional status (serum albumin, normalized protein catabolic rate) were assessed before and after program implementation.There was a significant increase in the percentage of patients per facility achieving phosphorus levels5.5 mg/dL (mean ± SD at baseline = 61.6% ± 5.2%; month 6 = 71.3% ± 9.0%; P.01) and parathyroid hormone (150 to 300 pg/mL; mean ± SD at baseline = 39.1% ± 2.4%; month 6 = 44.5% ± 7.0%; P = .04). During the course of the evaluation, mean calcium, albumin, and normalized protein catabolic rate levels did not change significantly.These results show proof-of-concept that a focused phosphorus management program targeting both staff members and patients can significantly improve patient outcomes without compromising nutritional status.

Background A key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation. Methods This was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation. Results First to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges. Conclusions Frequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.

The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated.

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.

Erythropoiesis-stimulating agents (ESAs) have had a positive effect on anemia treatment in dialysis patients. However, several events in recent years, including new clinical study results, ESA product label revisions, and coverage and reimbursement policy changes, have had an impact on ESA dosing patterns and consequently on hemoglobin (Hb) distribution characteristics in this patient population.Retrospective observational study using patient-level data from approximately 87% of dialysis centers in the United States.Dialysis patients who were receiving outpatient care at dialysis facilities during June 2006-November 2008 were included in this study.Recent events affecting ESA treatment practice patterns in US dialysis patients.Hb level distribution.Mean Hb level decreased by 0.37 g/dL during the indicated period. Additionally, standard deviation (SD) of the Hb level distribution decreased by 0.14 g/dL and skewness increased by -0.10. Hb measurements in specific ranges changed as follows:12 g/dL, decreased by 11.3 percentage points;10-12 g/dL, increased by 9.4 percentage points; and10 g/dL, increased by 1.9 percentage points. The percentage of patients with Hb level13 g/dL foror =3 months decreased by 2.9 percentage points.Potential bias in dialysis center selection and lack of information for patient characteristics.Recent events affecting ESA use in dialysis patients have had the desired effect of increasing the proportion of Hb measurements within the US Food and Drug Administration recommended target range of 10-12 g/dL and decreasing the proportion of Hb measurements12 g/dL. However, the proportion of Hb measurements10 g/dL also has increased. Benefits of a decrease in Hb measurements in the12 g/dL range need to be considered, together with risks of having low Hb levels.

Background. The Dialysis Outcomes and Practice Patterns Study (DOPPS) database was used to develop and validate a practice-related risk score (PRS) based on modifiable practices to help facilities assess potential areas for improving patient care. Methods. Relative risks (RRs) from a multivariable Cox mortality model, based on observational haemodialysis (HD) patient data from DOPPS I (1996-2001, seven countries), were used. The four practices were the percent of patients with Kt/V >= 1.2, haemoglobin >= 11 g/dl (110 g/l), albumin >= 4.0 g/dl (40g/l) and catheter use, and were significantly related to mortality when modelled together. DOPPS II data (2002-2004, 12 countries) were used to evaluate the relationship between PRS and mortality risk using Cox regression. Results. For facilities in DOPPS I and II, changes in PRS over time were significantly correlated with changes in the standardized mortality ratio (SMR). The PRS ranged from 1.0 to 2.1. Overall, the adjusted RR of death was 1.05 per 0.1 points higher PRS (P < 0.0001). For facilities in both DOPPS I and II (N = 119), a 0.2 decrease in PRS was associated with a 0.19 decrease in SMR (P = 0.005). On average, facilities that improved PRS practices showed significantly reduced mortality over the same time frame. Conclusions. The PRS assesses modifiable HD practices that are linked to improved patient survival. Further refinements might lead to improvements in the PRS and will address regional variations in the PRS/mortality relationship.

Correction of metabolic acidosis is one of the goals of effective dialysis. The KDOQI guidelines recommend serum bicarbonate >22 meq/L irrespective of dialysis modality. Since the measured bicarbonate reflects the steady state in PD patients and the lowest inter-dialytic value in HD patients, we compared the survival predictability of serum bicarbonate 10,400 PD and 110,951 HD patients treated in DaVita facilities from 7/2001-6/2006 with follow-up through 6/2007. PD patients were substantially less likely to have lower serum bicarbonate (adjusted odds, 22 meq/L for all end-stage renal disease irrespective of dialysis modality.fx1

EFFECT OF MAINTENANCE IRON PROTOCOLS ON ESA DOSING AND ANEMIA OUTCOMES Mahesh Krishnan; Joe Weldon; Steve Wilson; Irina Goyhkman; David Van Wyck; DaVita Inc., Denver, CO, USA Although intravenous (IV) iron was initially for use as a bolus, over half of the hemodialysis population receives IV iron for maintenance dosing. We determined the association between various maintenance iron protocols and anemia management outcomes by constructing a facility level analysis for maintenance iron use. IV iron sucrose dosing patterns were assessed in facilities with ≥10 prevalent (≤90 days) patients in 01/10. Facilities were categorized to a dosing pattern if >40% of patients received the same dose [25 mg 1x/wk (n=234), 50 mg 1x/wk (n=180) or 100 mg 1x/wk (n=285)]. Medication and laboratory values were then summarized across all patients in those clinics in each category. Reported lab values lagged by one month to allow for the effect of iron dosing patterns from the previous month. The anemia management outcomes are listed by pattern (Table). Median ESA dose was significantly lower in facilities dosing 100 mg than 25 mg/wk (P = 0.002). Hb levels did not differ. Dosing Pattern/ wk Median ESA Dose (U/month) Mean Iron Dose (mg/month) TSAT (%) mean±SD Ferritin (ng/ml) mean±SD 25 mg reference reference 30.0 ± 13.0 531 ± 320 50 mg -1,100 +66 30.6 ± 13.4 606 ± 352 100 mg -2,200 +123 32.4 ± 15.1 728 ± 429 This retrospective analysis suggests that monthly ESA requirements to maintain target hemoglobin may be lower with larger doses of maintenance iron. More detailed analyses and prospective studies are indicated to explore this possibility.