Author Interview: Sylvia Ramirez, MD, MPH, MBA, FASN
Vice-President, Global Research and Development
Arbor Research Collaborative for Health
Ann Arbor, Michigan USA
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American Society of Nephrology November 2011 Presentation:
Hemoglobin A1c levels and Mortality in the ESRD Population: Findings from the DOPPS Study
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What are the main findings of the study? |
As a background for our study, diabetes mellitus is the leading cause of chronic kidney failure in the US, and it is also a co-morbidity in 65% of US patients on dialysis. It is important to control blood sugar levels among all patients with diabetes, but particularly among those with kidney disease, because of the association with increased risk of heart disease, peripheral vascular disease (such as amputation), and other complications. Despite this, evidence in the management of diabetes in dialysis patients is limited. Current Clinical Practice Guidelines are based on studies in the non-kidney failure population and evidence for dialysis patients is unclear.
Hemoglobin A1c levels, or HbA1c, indicate blood sugar control for the prior 2-3 month period, and is commonly used as a target for management of diabetes mellitus. In patients with diabetes, but not on dialysis, the target HbA1c level is below 7%, and this target is suggested by current clinical practice guidelines. However, the value of maintaining this HbA1c goal in diabetic patients who have already progressed to kidney failure is unclear as only a limited number of studies have addressed the benefits and risks of intensive control of blood sugar in patients with kidney failure.
Our study evaluated the relationship between blood sugar control, based on mean HbA1c levels, and mortality in an international study known as the Dialysis Outcomes and Practice Patterns Study (DOPPS). The DOPPS is a prospective cohort study of hemodialysis practices based on the collection of longitudinal data for a random sample of patients from a representative and random sample of units in 12 countries. Since 1996, data collection has yielded detailed information on more than 38,000 patients in over 900 dialysis facilities.
The most important findings from our study are the following:
There is a “U-shaped” relationship between HbA1c levels and mortality risk with increased risk of mortality at Hb1c levels below 6.0 and 9.0%. The increases in risk observed at both low and high levels of HbA1c are statistically significant even after adjusting for other factors that may affect overall mortality risk such as presence of other co-morbidities, among others. A key conclusion from this study therefore is that target HbA1C levels may be higher among patients with diabetes mellitus on dialysis as compared to patients with diabetes mellitus without kidney failure since mortality risk appears to be lowest at A1C levels of 6- 9% (rather than below 7%).
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We also found that the use of diabetes medications is common among patients with HbA1C <6%; avoiding excessively low blood glucose levels by tapering these medications may be a readily modifiable practice to improve outcomes
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We also evaluated whether dialysis patients who have diabetes mellitus and have evidence of poor nutrition are particularly at risk for low blood sugar. Our findings did not show a statistically significant difference between these patients and those without evidence of poor nutrition, however, an increased risk for mortality for low HbA1c was more notable among those with evidence of poor nutrition.
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Were any of the findings unexpected? |
The conclusion from this study that target HbA1C levels may be higher among patients with diabetes mellitus on dialysis as compared to patients with diabetes without kidney failure is somewhat unexpected since this suggests that the approach to managing this group of patients may be different.
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What should clinicians and patients take away from this study? |
The management of diabetes mellitus among patients may differ from those without kidney failure. Doctors may need to watch closely patients with diabetes mellitus on dialysis with HbA1c levels in the lower ranges. At the same time, the impact of relatively high blood sugar levels on dialysis patients may be less harmful since we observed that the lowest mortality risk was in a higher range of HbA1c as compared to previous treatment targets.
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What recommendations do you have for nephrology health care providers as a result of your study? |
It would be valuable to conduct further studies to evaluate the upper bound of the target HbA1c range. Although it seems that patients with diabetes mellitus on dialysis may be able to tolerate relatively higher blood sugar levels as compared to patients not on dialysis, the actual higher bound for HbA1c levels is less clear. In addition, the long-term impact of relatively higher blood sugar levels in this population will require further study.
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| More Author Interview from Hemodialysis.com |
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Author Interviews: hemodialysis
- Dialysis - ESRD - CKD |
| Vitamin D Therapy & Cardiac Structure & Function in CKD Dr. Thadhani JAMA |
| A model to predict optimal dialysate flow Dr. Ahmed: Therapeutic Apheresis & Dialysis |
Low Molecular Weight Iron Dextran Increases FGF-23 with PTH Decrease in Hemodialysis: Dr. Hryszko
Therapeutic Apheresis & Dialysis |
| Differences Between Dialysis Modality Selection and Initiation Dr. Liebman Amer J. Kidney Diseases |
| Right intra-atrial catheter placement for hemodialysis in patients with multiple venous failure Dr. Oguz Hemodialysis Int'l |
| Acute dialysis risk in living kidney donors Dr. Lam: Nephrology Dialysis Transplant |
| Mortality Associated with Dose Response of Erythropoiesis-Stimulating Agents in Hemodialysis vs Peritoneal Dialysis Drs. Molnar & Dr. Kam Kalantar-Zadeh Amer J Nephrology |
| Event-related distress in kidney disease patients: S. Ramer Nephrology Dialysis Transplant |
Impact of nephrotic edema of lower limbs on obstructive sleep apnea: Drs Lai & Tang
Nephrology Dialysis. Transplant |
Geriatric Nutritional Risk Index as Predictor of Mortality in Korean Hemodialysis: Dr. Shin
Therapeutic Apheresis & Dialysis |
| Decreased Kidney Function Among Agricultural Workers in El Salvador: Dr. Wesseling Am J Kidney Dis. |
| Protein Oxidative Stress & Dyslipidemia in Dialysis: M.de Mattos Therapeutic Apheresis & Dialysis |
| Effect of hemodialysis and hemofiltration on plasma C.E.R.A. concentrations : Dr.Reigner Hemodialysis International |
| Intake of Antioxidants and their Status in Chronic Kidney Disease : Dr. Gupta J Renal Nutrition |
| Antidepressive Agents & Mortality in ESRD : Dr. Tsai Nephrology |
| Overweight, obesity & intentional weight loss in CKD : NHANES Dr. Navaneethan Int'l J. of Obesity |
| Variation in Oral Calcitriol Response in Patients With Stages 3-4 CKD: Dr. Shoben: Amer J Kidney Diseases |
| Calcium balance in normal individuals & CKD patients on low &high-calcium diets: Dr. Spiegel Kidney International |
Depressive symptoms associate with high mortality risk & dialysis withdrawal in incident hemodialysis patients:
Dr. Lacson Nephrology Dialysis Transplant |
| Global Trends in Rates of Peritoneal Dialysis: Dr. Jain JASN |
Structural Equation Modeling Highlights the Potential of Kim-1 as CKD Biomarker: Dr. Gardiner
Am J Nephrology |
| Protective effects of PPARγ agonist in acute nephrotic syndrome: Dr. Fogo Nephrology Dialysis Transplant |
| A Computerized Treatment Algorithm Trial to Optimize Mineral Metabolism in ESRD: Dr. Spiegel CJASN |
Development/Validation of Expedited 10g Protein Counter for Dietary Protein Intake : SL Lim
J.Renal Nutrition |
| IL-6-independent risk factor for ESAs resistance in hemodialysis pts without iron deficiency: Dr. Kim Hemodialysis Int'l |
| Troponin I & Postoperative Myocardial Infarction after Renal Transplantation : Dr. Shroff Amer J Nephrology |
| Longitudinal Progression Trajectory of GFR in CKD: Dr. Li : AJ Kidney Disease |
| Predictors of eGFR Decline in Type 2 Diabetes & Preserved Kidney Function: Dr. Chonchol CJASN |
| Tenecteplase for improvement of blood flow in dysfunctional hemodialysis catheters: Dr. Goldman Clin Neph |
| Religious coping, psychological distress and quality of life in hemodialysis: Dr. Carvalho J Psychosom Res. |
| Effect of captopril on recuperation from ischemia/reperfusion-induced AKI Nephrology Dialysis Transplant |
| Restless legs syndrome in dialysis: comparison of hemodialysis & CAPD: Dr. Merlino Neurol Sci. |
| International practice patterns & non-conventional hemodialysis utilization : Dr. Sood BMC Nephrology |
| Decreased PON1 in hemodialyzed & renal transplanted patients. Dr. Paragh Nephrol. Dial. Transplant |
| Preoperative Proteinuria & Long-Term Progression to Chronic Dialysis & Mortality after CABG: Drs. Chao & Ko : PLoS ONE |
| Creatinine generation is reduced in CVHD & predicts mortality: Dr. Wilson: Nephrology Dialysis Transplant |
Importance of normohydration for the long-term survival in hemodialysis : Dr. Wabel
Nephrology Dialysis Transplant |
| Local Tissue Renin-Angiotensin System Activation in Cardiorenal Metabolic Syndrome & Type 2 Diabetes: Dr.Hayden Cardiorenal Med |
| Group I nonreciprocal inhibition in restless legs syndrome secondary to CKD : Dr. Marconi Parkinsonism & Related Disorders |
Low-Dose ESAs and CV Geometry in CKD: Is Darbepoetin-α More Effective than Expected? Dr. Di Lullo
Cardiorenal Med |
Pharmacotherapy to improve outcomes in vascular access surgery: Dr. Jackson
Nephrology Dialysis Transplant |
| Parathyroidectomy for the attainment of NKF-K/DOQI™ and KDIGO recommended values for bone & mineral metabolism in dialysis with uncontrollable secondary hyperparathyroidism. Langenbecks Arch Surg |
| Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: Dr. Perkins |
| Losartan prevents the development of the pro-inflammatory monocytes CD14+CD16+ in hemodialysis : Dr. Merino Nephrology Dialysis Transplant |
| Does Dialysis Modality Influence the Oxidative Stress of Uremia? Dr. Capusa Kidney Blood Press Res |
| Treatment of Periodontal Diseases Reduces Inflammation in Hemodialysis : Dr. Siribamrungwong |
| Declining Rates of Deceased Donor Renal Transplantation in the US Over Successive Years of Listing: Dr. Trivedi |
| When Is the Best Moment to Assess the Ankle Brachial Index: Pre- or Post-Hemodialysis?Dr. RM Elias |
| Role of Race and Poverty on Steps to Kidney Transplantation in the Southeastern US |
| Validity & Reliability of the MUST and MST Nutrition Screening Tools in Renal Inpatients : C. Lawson |
| Target-Orientated Algorithm for Regional Citrate-Calcium Anticoagulation in Extracorporeal Therapies: Dr. Brandl |
| Evaluation of bone microarchitecture by HR-pQCT in hemodialysis : Dr. Negri |
| Erectile Dysfunction in Chronic Hemodialysis : Dr. Strippoli |
| Have Renal Dietitians Successfully Implemented Evidence-Based Guidelines Into Practice? E. Joy |
| Regional Citrate Versus Heparin Anticoagulation for CRRT: Drs. Tam & Wu |
| von Willebrand factor predicts mortality in CRRT : Dr. Péquériaux |
| Clinical Outcome of Twice-Weekly Hemodialysis Patients in Shanghai | Dr. Qian |
| Persistently low intact PTH levels predict aortic arch calcification progression in hemodialysis patients : Dr. Song |
| Lack of Awareness among Future Medical Professionals about the Risk of Consuming Hidden Phosphate-Containing Processed Food & Drinks : Dr. Razzaque |
| 51Cr-EDTA plasma & urinary clearance as a measure of residual renal function in dialysis :Dr. Kjaergaard |
| Obesity and Mortality Risk among Younger Dialysis Patients: Dr. Hoogeveen |
| Solar-Assisted Hemodialysis: Dr. Agar |
| Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells Drs. Lee & Kasinath |
| Mineral, bone disorders, survival in hemodialysis with & without PKD : Drs. Molnar & Kalantar-Zadeh |
| Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells Drs. Lee & Kasinath |
| Mineral, bone disorders, survival in hemodialysis with & without PKD : Drs. Molnar & Kalantar-Zadeh |
| Downregulation of the renal & hepatic hydrogen sulfide-producing enzymes and capacity in CKD - Dr. Vaziri |
| A predictive algorithm for management of anemia in hemodialysis based on ESA pharmacodynamics : Dr. Lines |
| Factors Associated With Intradialytic Systolic Blood Pressure Variability: Dr. Flythe |
| Safety and predictors of complications of renal biopsy in the outpatient setting : Dr. Jiang |
| Heparin induced antibodies in chronic hemodialysis patients and cardiac surgery patients: Dr. Shavit |
| Atrial Fibrillation in Medicare/Medicaid-eligible dialysis patients: Dr. Wetmore |
| Newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: J. Saldanha |
| Correction of Post kidney Transplant Anemia Reduces Progression of Allograft Nephropathy: Dr. Choukrou |
| Mild and moderate pre-dialysis CKD is associated with increased coronary artery calcium: Dr. Budoff |
| Endogenous factors modified by hemodialysis and accuracy of blood glucose-measuring device: Dr. Ogawa |
| Narrow-band UVV increases serum vitamin D levels in hemodialysis patients Dr. Ala-Houhala |
| Predicting hospital cost in CKD patients through blood chemistry values: Dr. Bessette |
| Nutritional vitamin D supplementation in hemodialysis: a potential vascular benefit? D. Mason |
| Volume excess in chronic hemodialysis effects of treatment frequency & treatment spacing : Dr. Schneditz |
| Acid reduction with fruits/veges or bicarb attenuates kidney injury in hypertensive nephropathy with reduced GFR |
Predicting Number of US Medical Graduates Entering Adult Nephrology Fellowships
Using Search Terms Dr. Desai |
| Potential influence of sevelamer hydrochloride on responsiveness to ESAs in hemodialysis patients: Dr. Ikee |
| Anemia Management in Dialysis : ESAs vs Transfusions: Clinical & Economic Consequences :Dr. Naci |
| Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury: Dr. Perkins |
DOPPS Practice Monitor: Update on Trends in US Hemodialysis Care Following Launch of Bundled Payment System and Revisions to ESA Labels |
Emerging trends in hemodialysis care through August 2011, based on a sample of US dialysis facilities, are included in the latest update to the DOPPS Practice Monitor (DPM, at http://www.dopps.org/DPM), run by the Dialysis Outcomes and Practice Patterns Study (DOPPS) at Arbor Research Collaborative for Health.
Ongoing Changes in the US Dialysis Environment – Recent changes in dialysis payment and regulatory guidance are expected to affect hemodialysis practice. In January 2011, the Centers for Medicare & Medicaid Services (CMS) launched a new Prospective Payment System (PPS) with the intent to control dialysis costs through bundled payments. In June 2011, the FDA approved revised prescribing information for erythropoiesis-stimulating agents (ESAs), used to treat anemia in most dialysis patients. Previously, the label recommended a hemoglobin target range of 10-12 g/dL. The June 2011 update removed the target range, advising instead to start ESA therapy for dialysis patients at hemoglobin less than 10 g/dL, and to reduce or interrupt the dose when the hemoglobin approaches or exceeds 11 g/dL.
Most Recent Trends in Care – Over the August 2010 to August 2011 time period, many hemodialysis practices have remained stable; examples include nutrition measures and hemodialysis treatment time and dose. There have been notable trends in the following practice areas:
- Anemia: Hemoglobin levels have decreased since the June 2011 ESA label update. While the mean hemoglobin level declined by 0.12 g/dL over 12 months from August 2010 to July 2011, it declined in August 2011 by another 0.10 g/dL to 11.26 g/dL. The percentage of patients with hemoglobin levels greater than 12 g/dL declined sharply (from 28% to 23%) in July/August 2011, while the percentage with hemoglobin levels less than 10 g/dL increased slightly from 8.5% to 10% and the percentage with hemoglobin levels less than 9 g/dL remained under 3%.
Mean prescribed epoetin dose (among patients receiving epoetin) decreased by 15%, from 21,100 units/wk to 17,900 units/wk, from August 2010 to August 2011, with the greatest decline in June-August 2011. Epoetin doses at the higher end of the dose range have decreased most notably. IV iron use increased from August 2010 to August 2011 though has recently stabilized. In keeping with greater IV iron use, serum ferritin levels (indicative of iron stores) continue to rise. Serum ferritin concentration exceeded 500 ng/mL in 65% of patients, 800 ng/mL in 34% of patients, and 1,200 ng/mL in 11% of patients in August 2011.
- Mineral & Bone Disorder: In our last report, we noted a 29% increase in serum parathyroid hormone (PTH) levels through April 2011, and differences by race were described. Since then, PTH levels have remained stable or declined slightly in both black and non-black patients. In August 2011, 22% of black patients and 12% of non-black patients had very high PTH values (defined here as PTH >600 pg/mL). The percentage of hemodialysis patients for whom PTH is measured has declined slightly since August 2010. There have been no clear changes in serum calcium or serum phosphorus levels.
- Clinical Outcomes: Preliminary data indicate that the 30-day hospitalization rate has increased somewhat from August 2010 to August 2011. The DPM does not report yet on trends in red blood cell transfusions, as dialysis units are often unaware of transfusions occurring in the inpatient setting. Additional efforts to comprehensively monitor trends in transfusions are warranted. To date mortality rate has not changed appreciably, though further follow-up time is necessary as we continue to track this outcome.
Future monitoring of these trends, confirmation with national data when eventually available, and understanding their effect on clinical outcomes, if any, is required.
DPM data are aggregated across dialysis organizations and facilities. Aggregated trends may not reflect trends in individual dialysis organizations or facilities, and are not intended to provide oversight of performance in individual dialysis organizations or facilities.
Read the rest of the DOPPS Practice Monitor: Update on Trends in US Hemodialysis Care Following Launch of Bundled Payment System and Revisions to ESA Labels Press Release |
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Hemodialysis Research Interview of the Week |
Dr. Miklos Z Molnar MD, PhD and Dr. Kam Kalantar-Zadeh MD, MPH, PhD
Harold Simmons Center at Harbor-UCLA. |
Mortality Associated with Dose Response of Erythropoiesis-Stimulating Agents in Hemodialysis versus Peritoneal Dialysis Patients
Duong U, Kalantar-Zadeh K, Molnar MZ, Zaritsky JJ,
Teitelbaum I, Kovesdy CP, Mehrotra R:
Am J Nephrol 2012;35:198-208 (DOI: 10.1159/000335685)
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What are the main findings of the study? |
The analysis of the data was from a large and contemporary cohort of 10,527 peritoneal dialysis and 139,103 hemodialysis patients in a single dialysis provider with relatively uniform anemia management practice patterns between 7/2001 and 6/2006, i.e., during the era with the highest ESA dose administration in the United
States.
We found that peritoneal dialysis patients with the same achieved hemoglobin levels received substantially lower dose of ESA than hemodialysis patients, and the
differential was even wider among African Americans.
We also found that in peritoneal dialysis patients an ESA dose below 10,000 U/week was not associated with higher mortality, but a 28% higher death risk in those receiving significantly higher dose (>15,000 U/week).
In contrast, higher ESA dose was linearly and incrementally associated with higher all-cause and cardiovascular mortality in hemodialysis.
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Were any of the findings unexpected?
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While the administered ESA dose was linearly and incrementally associated with higher mortality in hemodialysis patients, the dose was used in everyday clinical practice in PD patients was not associated with mortality.
Only large doses (>15,000 U/week) were associated with higher mortality risk in PD
population.
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What should clinicians and patients take away from this study?
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PD patients require substantially lower ESA dose than hemodialysis to achieve same hemoglobin levels.
In both PD and hemodialysis patients Lower ESA dose (< 15,000 U/week) are safer than higher doses.
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