Hemodialysis.com Kidney Disease Interviews March 24 2013

Hemodialysis.com

Hemodialysis research, author interviews, dialysis updates and information on chronic
kidney disease and end stage renal failure.

Editor: Marie Benz, MD
info@hemodialysis.com
March 24 2013

For Informational Purposes Only: Not for Specific Medical Advice.

For Informational Purposes Only. Not for
Read more interviews on Hemodialysis.com
Specific Medical Advice

Hemodialysis.com Interviews
March 24 2013


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Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis Patients
Hemodialysis.com Interview with Dr. Grahame J. Elder
Clinical A/Professor (Sydney and UNDA)
Department of Renal Medicine, Westmead Hospital
Osteoporosis and Bone Biology Programme, Garvan Institute Sydney

• Hemodialysis.com: What are the main findings of the study?
• Dr. Elder: This study is one of very few randomized controlled trials in patients on
hemodialysis.assessing the effect of cholecalciferol use to improve levels of 25-hydroxyvitamin
D After 6 months, patients treated with cholecalciferol had higher values of both 25-
hydroxyvitamin D and calcitriol (1,25-dihydroxyvitamin D), the most active form of vitamin D than
patients treated with placebo. This was achieved without adverse effects on calcium or phosphorus
levels.
• However, after 6 months treatment we could not discern any effect of supplementation on muscle
strength or function, pulse wave velocity (an indicator of vascular stiffness and surrogate for
vascular calcification) or on quality of life Whether this is because the period of supplementation
was too short, the patients selected had higher values of 25-hydroxyvitamin D than many patients
on dialysis, or because cholecalciferol will not influence these outcomes are questions that cannot
be answered by our data.

• Hemodialysis.com: Were any of the findings unexpected?
• Dr. Elder: We were interested to see that phosphorus levels and phosphate binder use were lower
at 6 months in patients treated with cholecalciferol. Also the rise in the TRAcP-5b, an osteoclast
marker, was a surprise because we had thought that if anything, cholecalciferol might reduce
parathyroid hormone levels, osteoclast activation and bone turnover. However, recent human and
animal studies have reported that both osteoblasts and osteoclasts can metabolize 25-
hydroxyvitamin D to 1,25-dihydroxyvitamin D, so perhaps this might have been expected. We were
of course surprised to find no effect on muscle strength, which we had designated the primary
outcome for the study, or on functional testing,


Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis Patients
Hemodialysis.com Interview with Dr. Grahame J. Elder
Clinical A/Professor (Sydney and UNDA)
Department of Renal Medicine, Westmead Hospital
Osteoporosis and Bone Biology Programme, Garvan Institute Sydney
(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?
• Dr. Elder: Cholecalciferol treatment increased levels of 25-hydroxyvitamin D in patients on hemodialysis. Patients
receiving this treatment have higher levels of calcitriol than those who do not and the treatment is unlikely to
cause adverse effects on levels of calcium or phosphorus. The baseline data indicating positive associations of 25-
hydroxyvitamin D and functional testing and an inverse relationship or 25-hydroxyvitamin D to pulse wave velocity,
although of course this does not prove any benefit will derive from treatment. But on the other hand, it certainly
supports the contention that treatment will do no harm.

• Hemodialysis.com: What recommendations do you have for future research as a result of your study?
• Dr. Elder: At baseline we found positive associations of 25-hydroxyvitamin D values and distance covered in a 6
minute walk and an inverse relationship of 25-hydroxyvitamin D values and pulse wave velocity. These findings are
consistent with associations reported in a number of other studies, so it remains possible that longer studies, or
studies recruiting patients with lower levels of vitamin D in the ‘deficient’ range, might find that functional tests
and vascular stiffness improve over time. A number of cross sectional and some longitudinal studies have now
reported that hemodialysis patients with higher 25-hydroxyvitamin D levels or calciferol (cholecalciferol or
ergocalciferol) supplementation have higher levels of calcitriol as we also reported In turn, improved calcitriol
levels may have positive influences on vascular tissue and cardiovascular outcomes, providing hypercalcemia and
hyperphosphatemia are avoided. A longer and much larger study to assess the influence of calciferol
supplementation on cardiovascular events and mortality is long overdue.
• Citation:
• Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis
Patients
• Nathan A. Hewitt, Alicia A. O’Connor, Denise V. O’Shaughnessy, and Grahame J. Elder
• CJASN CJN.02840312; published ahead of print March 14, 2013, doi:10.2215/CJN.02840312


Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five decades.
Hemodialysis.com Author Interview with Sandra J. Taler, M.D.
Consultant, Division of Nephrology/Hypertension
Associate Professor of Medicine | College of Medicine |
Mayo Clinic | 200 First Street SW | Rochester, MN 55905


• Dr. Taler: We reviewed the medical records of all living kidney donors (8951 total) from 3 large
transplant centers (Mayo Clinic, University of Alabama in Birmingham and University of Minnesota)
since the beginning of living donation in 1963 through 2007.
• We examined trends in the metabolic profile of accepted living donors by quartiles of this 44 year
timespan. We saw a trend to higher donor age with fewer donors in their 20s but only 4% of
donors were older than age 60 years at the time of donation. Using a consistent definition for
hypertension, we found the percentage of donors with hypertension remained low and was stable
over time. We did find an increasing proportion of donors were obese or had glucose intolerance
in the more recent time quartiles however most had mild elevations in glucose that met acceptance
criteria. There was greater tolerance for one or more metabolic abnormalities in older donors but
the percentage of older donor remained quite low.


• Dr. Taler: Yes. We thought we might find a higher rate of hypertensive donors accepted in the more
recent time quartiles. However, using the same numerical cutoffs, this was not the case. The
difference relates to changes to a more strict definition for hypertension over time.


Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five decades.
Hemodialysis.com Author Interview with Sandra J. Taler, M.D.
Consultant, Division of Nephrology/Hypertension
Associate Professor of Medicine | College of Medicine |
Mayo Clinic | 200 First Street SW | Rochester, MN 55905
(cont)


• Dr. Taler: As the entire United States population is aging and becoming more obese, accepted
kidney donors also reflect these trends.

• Hemodialysis.com: What recommendations do you have for future research as a result of your
study?
Dr. Taler: We are looking at outcomes for the donors in this study. It is important that living kidney
donors have access to medical care so they can be evaluated and treated for hypertension, diabetes
or other metabolic abnormalities should they develop.

• Citation:
• Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five
decades.
• Taler SJ, Messersmith EE, Leichtman AB, Gillespie BW, Kew CE, Stegall MD, Merion RM, Matas
AJ, Ibrahim HN; RELIVE Study Group.
• Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
• Am J Transplant. 2013 Feb;13(2):390-8. doi: 10.1111/j.1600-6143.2012.04321.x. Epub 2012 Nov 8.


Single Pediatric Kidney Transplantation in Adult Recipients
: Comparable Outcomes With Standard-Criteria Deceased Donor Kidney Transplantation
Hemodialysis.com Interview with: Dr Amit Sharma MD. MPhil
Assistant Professor Director, Transplant Surgery Fellowship Program
Hume-Lee Transplant Center
Virginia Commonwealth University Richmond, Virginia, USA

• Dr. Sharma: Single pediatric kidney transplantation (SKT) in to adult recipients has traditionally been considered
high risk due to concerns of technical complications leading to poor graft outcomes. As a result many transplant
centers hesitate to utilize these kidneys for transplantation. We retrospectively compared outcomes in adult
recipients after SKT (n=31), standard criteria deceased donor kidney transplantation (SCDKT, n=283), pediatric en
bloc, (EBKT, n=21), living donor (LDKT, n=275) and extended criteria donor, (ECD, n=100) kidney transplantation.

• The mean donor age and weight for pediatric single kidney donors were 6.3 years and 27.6 kg. The recipients
selected for SKT weighed significantly less (67.6 ± 21.4 kg), p<0.0001) compared to the SCDKT recipients. There
were no re-transplant candidates in SKT group while 14.5% of SCDKT recipients had previous kidney
transplants. The superior quality of single pediatric kidneys was reflected by the serum creatinine which at 1-year
was significantly lower than ECD, and by 5-years was lower than both SCDKT and ECD (p<0.0001). Compared to
standard criteria donors (SCDKT), the single pediatric kidney transplant (SKT) group had a higher incidence of renal
arterial anastomotic stenosis (6.8% vs. 0.4%, p=0.02), hydronephrosis (12.9% vs. 5.3%, p=0.02) and a higher
incidence of acute rejection (9.7% vs. 6.0%, p=0.03). Subgroup analysis of the SKT cohort by donor age below 5 vs.
6-10 years (mean weight 16.4 kg vs. 32.7 kg) revealed that there were no differences in serum creatinine, patient
survival or death-censured graft survival.
• Dr. Sharma: We did not see any significant difference in the incidence of delayed graft function between SKT
(45.2%) and SCDKT (50.5%) groups. This indicates good donor-recipient weight matching that may have prevented
problems due to low nephron mass. Patient survival at 1- and 5-years after single pediatric kidney transplants
(SKT) was lower than SCDKT at both time points (p=0.02). Despite the higher rate of vascular and urological
complications, the 5- year death-censored graft survival after SKT (81.4 ± 7.6%) was significantly superior to both
SCDKT (74.5 ± 3.4%) and ECD (74.6 ± 5.8%, p=0.02).


Single Pediatric Kidney Transplantation in Adult Recipients
: Comparable Outcomes With Standard-Criteria Deceased Donor Kidney Transplantation
Hemodialysis.com Interview with: Dr Amit Sharma MD. MPhil
Assistant Professor Director, Transplant Surgery Fellowship Program
Hume-Lee Transplant Center
Virginia Commonwealth University Richmond, Virginia, USA
(cont)

Dr. Sharma: With careful donor and recipient selection, single pediatric kidney transplantation in to adult recipients offers
superior long-term graft outcomes compared to standard criteria deceased donor kidney transplantation. Kidneys from
pediatric donors who weigh more than 15 kg or with kidney size greater than 6 cm should be split and transplanted singly in
order to optimize resource utilization. Recipients with certain high-risk criteria should be avoided to ensure successful graft
outcomes after SKT. Post-transplant management of SKT recipients should include strict control of hypertension, aspirin for
at least one year and vigilant immunosuppression monitoring to prevent rejections. In our experience, complications like
arterial stenosis and hydronephrosis can be successfully managed by experienced interventional radiologists. Use of
pediatric donor kidneys needs to be continuously encouraged to address the problem of organ shortage.


• Dr. Sharma: We have proposed a few strategies to optimize both the utilization and outcomes after transplantation of single
pediatric kidneys in to adult recipients. These include the need for policies to expedite pediatric kidney placement in order
to minimize cold ischemia times. Facilitating organ procurement and transplantation by experienced operators could reduce
the technical complications. Future res
earch should also focus on newer immunosuppressive strategies to lower rejection rates and further improve pediatric
kidney allograft survival.

• Citation:
• Single Pediatric Kidney Transplantation in Adult Recipients: Comparable Outcomes With Standard-Criteria Deceased-Donor
Kidney Transplantation
• Sharma, Amit; Ramanathan, Rajesh; Behnke, Martha;
Fisher, Robert; Posner, Marc
• Transplantation:
• POST AUTHOR CORRECTIONS, 15 March 2013 doi: 10.1097/TP.0b013e31828a9493


Modifiable Patient Characteristics and Racial Disparities in Evaluation Completion and Living Donor Transplant
Hemodialysis.com Interview with: Dr. Amy D. Waterman
General Medical Sciences, Washington University School of Medicine
Campus Box 8005, 660 S. Euclid Avenue, St. Louis, MO 6311

• Dr. Waterman:
• In an analysis of 695 Black and White patients in kidney failure who presented for
transplant and were followed over 6 years, Black patients initially presented for
evaluation having received less transplant education, being less knowledgeable
about transplantation, and less willing to pursue deceased or living donor
transplantation than Whites.
• Patients who began their transplant evaluation process with a greater knowledge
of transplantation and greater motivation to receive living donor transplants were
ultimately more successful at receiving a living donor transplant six year later.
• Dr. Waterman:
• Though we knew that modifiable patient characteristics, like how much knowledge
or education of transplant a patient has, were important in understanding whether
patients will pursue or get a transplant, we were surprised to see that, in our
analysis, these were some of the most important predictors of whether patients
would pursue or get a transplant.


Modifiable Patient Characteristics and Racial Disparities in Evaluation Completion and Living Donor Transplant
Hemodialysis.com Interview with: Dr. Amy D. Waterman
General Medical Sciences, Washington University School of Medicine
Campus Box 8005, 660 S. Euclid Avenue, St. Louis, MO 6311
(cont)

• Dr. Waterman:
• These findings suggest that improved education, especially for patients of color, may help more
patients successfully get transplants. Educational interventions focused on helping improve
patients’ transplant knowledge and motivation when patients’ kidneys are starting to fail or
afterwards may reduce or overcome racial disparities in transplantation. Education in dialysis
centers about transplant could be incredibly beneficial to patients’ transplant success years later.
study?
• Dr. Waterman:
• Future research should compare the potential for different educational interventions in dialysis
centers and community nephrologists’ offices to help patients, especially patients of color, obtain
more knowledge of transplant and become more willing to get a transplant. Research should also
look at the best ways to deliver these interventions so that they can help all patients move toward
transplant more quickly, easily, and cost-effectively.
• Citation:
• Modifiable Patient Characteristics and Racial Disparities in Evaluation Completion and Living Donor
Transplant
• Amy D. Waterman, John D. Peipert, Shelley S. Hyland, Melanie S. McCabe,
Emily A. Schenk, and Jingxia Liu
• CJASN CJN.08880812; published ahead of print March 21, 2013, doi:10.2215/CJN.08880812


Estimated GFR reporting is associated with decreased NSAID drug prescribing and increased renal function
Hemodialysis.com Author Interview: Dr Li Wei
Senior Lecturer Department of Practice and Policy
UCL School of Pharmacy Tavistock Square London WC1H 9JP


• Dr. Li: The study was a population-based longitudinal analysis using a record-linkage database in Tayside, Scotland, UK. The aim of the study was to
determine NSAID prescribing before and after the implementation of estimated eGFR reporting and to evaluate renal function in patients who used
NSAIDs but stopped these after the first eGFR report. The study found that prescriptions for NSAIDs significantly decreased after the implementation
of eGFR reporting. eGFR reporting was associated with reduced NSAID prescriptions (adjusted OR, 0.78 95%CI 0.75-0.82). NSAID prescribing rates in
the 6 months prior to April 2006 were 18.8%, 15.4% and 7.0% in patients with CKD stages 3, 4, and 5 and 15.5%, 10.7% and 6.3% respectively, after
eGFR reporting commenced. In patients who stopped NSAID treatment, eGFR significantly increased from 45.9 to 46.9, 23.9 to 27.1, and 12.4 to 26.4
ml/min per 1.73m2 in 1340 stage 3 patients, 162 stage 4 patients, and 9 stage 5 patients, respectively.


• Dr. Li: no

• Dr. Li: GFR reporting may result in safer prescribing. The study shows the enormous benefit to the NHS of the processing of routinely captured data.
Careful monitoring of eGFR in patients taking NSAIDs is the key component of safe clinical practice.

• Dr. Li: The study was confined to a single NHS region, and a further study on different populations and a further questionnaire survey of physician
behavior would strengthen the study finding.
• Citation:
• Estimated GFR reporting is associated with decreased nonsteroidal anti-inflammatory drug prescribing and increased renal function
• Wei L, Macdonald TM, Jennings C, Sheng X, Flynn RW, Murphy MJ.
• of Practice and Policy, UCL School of Pharmacy, London, UK [2] Medicines Monitoring Unit, Division of Medical Sciences, University of
Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
Kidney Int. 2013 Mar 13. doi: 10.1038/ki.2013.76. [Epub ahead of print]


Effect of serum FGF-23, MGP and fetuin-A on calcium-phosphate metabolism in maintenance hemodialysis patients
Hemodialysis.com Interview with Jian-Ying Niu
Division of Nephrology
the Fifth People’s Hospital of Shanghai 200240 China

• Answer: In this study, we enrolled 64 patients (30 males,34 females,
60.6+-11.3 years of age) who received an average dialysis vintage of 6.88+-
2.94 years, and evaluated the serum level of FGF-23, MGP and fetuin-A, as
well as the coronary artery calcification score (CACS) with coronary artery
computed tomography scan.
• There were 13 (20.31%), 16 (25%), and 35 (54.69%) patients exhibited a
CACS of 0–100, 100–400, and >400, respectively. The dialysis vintage,
serum FGF-23, fetuin-A, phosphorus and high-density lipoprotein-C levels
were identified as independent variables of CACS by stepwise multiple
regression analysis. The area under receiver operating characteristic curve
indicated that serum FGF-23 and fetuin-A were useful for identifying CAC
in MHD patients. The cut-off value corresponding to the highest Youden’s
index was serum FGF-23 ≥ 256 pg/mL and fetuin-A ≤ 85mg/mL, which was
defined as the optimal predictors of CAC.


(cont)

• Answer: Our study did not find that MGP was closely related to CAC in MHD patients. This may be
due to small sample size, measurement of overall serum MGP without differentiation between
ucMGP and active MGP, and unknown vitamin K status in MHD patients.
• It is reported in literature[1] that increased serum uncarboxylated MGP (ucMGP) is associated with
the severity of aorta calcification.
• ucMGP can be used as a surrogate marker of vascular calcification in CKD patients. The ucMGP level
is inversely correlated with CAC. A study in 53 MHD patients[2] documented that the baseline
ucMGP level in MHD patients was 4.5 times higher than that in normal subjects. This confirms that
vitamin K deficiency is prevalent in MHD patients. Daily supplementation of exogenous vitamin K
can reduce ucMGP level, which provides support for improving vascular calcification in MHD
patients.
• [1]Schurgers LJ, Barreto DV, Barreto FC, et al. The circulating inactive form of matrix gla protein is a
surrogate marker for vascular calcification in chronic kidney disease: a preliminary report.
Clin J Am Soc Nephrol..2010; 5:568–575.
• [2]Westenfeld R, Schafer C, Smeets R, et al. Fetuin-A
(AHSG) prevents extraosseous calci fication induced by uraemia and phosphate challenge in mice.
Nephrol Dial Transplant. 2007; 22:1537–1546.


(cont)

• Answer: CAC is prevalent in MHD patients. In this study, stepwise multiple regression analysis found
that serum FGF-23 and fetuin-A levels are closely associated with the severity of CAC in MHD
patients. ROC curve also confirmed that both serum FGF-23 and Fetuin-A are biomarkers for
identifying CAC in MHD patient with good sensitivity and specificity. These two markers are useful
for clinical prediction of CAC, especially in combination or in series.They are expected to be used as
promising diagnostic markers for predicting CAC in MHD patients.
study?
• Answer: As mentioned before, our study did not find that MGP was closely related to CAC in MHD
patients. This may be due to small sample size, measurement of overall serum MGP without
differentiation between ucMGP and active MGP, and unknown vitamin K status in MHD patients.
Therefore, further study is required to clarify the exact role of MGP in CAC in MHD patients.
• Citation:
• Effect of serum FGF-23, MGP and fetuin-A on calcium-phosphate metabolism in maintenance
hemodialysis patients
• Xiao DM, Wu Q, Fan WF, Ye XW, Niu JY, Gu Y.
• Division of Nephrology, the Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, China;
Division of Internal Medicine,
Ningbo First Hospital, Medical School of Ningbo University, Ningbo, China.
Hemodial Int. 2013 Mar 12. doi: 10.1111/hdi.12033. [Epub ahead of print]


High incidence of mild hypernatremia in females using ecstasy at a rave party
Hemodialysis.com Interview with Geetruida D. van Dijken
Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, the Netherlands


• Answer: We decided to study the incidence of hypernatremia in subjects
using 3, 4–methylenedioxymethamphetamine (MDMA) at an indoor rave
party. Only 3% of males, but no less than ~25% of females attending a rave
party and using MDMA developed mild hypernatremia during the event.
Especially females are therefore probably also at risk of developing severe
symptomatic hypernatremia. Not using MDMA is obviously the best
option to prevent MDMA–induced hypernatremia. However, accepting the
fact that millions use the drug every weekend, strategies should also be
developed to prevent hypernatremia in subjects choosing to take MDMA.
This would include matching the electrolyte content of the fluids and food
ingested to that of the fluids that are lost during the use of MDMA, mainly
by perspiration. Users of MDMA and emergency health care workers
should become more aware of the relatively high incidence of MDMA–
induced hypernatremia and of potential strategies to prevent this
complication.


(cont)

• Answer: An intriguing observation is that the mean plasma sodium concentration
in females not using MDMA at the rave party was significantly lower than in males
not taking the drug, although there were no frank cases of hypernatremia in these
females. Due to the design of the study, the plasma sodium concentrations at
entry are not known, and it cannot be excluded that the initial values in females
were already lower than in males.

• Although the plasma sodium concentration appears to be slightly lower in females
in the luteal phase compared with males, there is no gender specific normal range
for the plasma sodium concentration in females not stratified for the phase of the
luteal cycle and males. Consequently, it is possible that exercise and stress-induced
ADH secretion combined with intake of hypotonic fluids caused the reduction in
plasma sodium concentration in female ravers not using MDMA. In this respect,
the situation may be similar to the hypernatremia induced by long distance
running, which also occurs more frequently in females than males and may have a
similar pathophysiology.


(cont)

• Answer: When you see a patient in your hospital that feels unwell after using ecstasy / MDMA
please remember that hyponatremia could be a cause.

• Even a low dose of ecstasy can cause hyponatremia and after a short time of ingestion. Especially
in women we found a high percentage of hyponatremia. Advising users to drink a lot of fluids
seems unwise. Normal saline should not be administered readily by healthcare workers. If
necessary for resuscitation hypertonic fluids can be considered.

study?
• Answer: We would like to research preventative measurements, for instance drinking soup
when using MDMA.
• Citation:
• High incidence of mild hypernatremia in females using ecstasy at a rave party
• Geetruida D. van Dijken, Renske E. Blom, Ronald J. Hené,
and Walther H. Boer
• Nephrol. Dial. Transplant. first published online March 8, 2013 doi:10.1093/ndt/gft023


Association Between Aristolochic Acid and CKD: A Cross-sectional Survey in China.
Hemodialysis.com Interview with Authors Wenke Wang and Jian Zhang
Hospital Authority Toxicology Reference Laboratory
Princess Margaret Hospital, Hong Kong SAR, China

• Response: Altogether, 467 participants reported long-term AA intake, with an adjusted prevalence
of 1.5% (95% CI, 1.2%-1.7%).
• After adjusting for age and sex, long-term AA intake was associated with eGFR < 60 mL/min/1.73
m2 and albuminuria, with ORs of 2.20 (95% CI, 1.51-3.12) and 1.67 (95% CI, 1.27-2.20), respectively.

• Adjusting for other covariates attenuated the ORs, which were 1.83 (95% CI, 1.22-2.74) and 1.39
(95% CI, 1.03-1.87) for eGFR < 60 mL/min/1.73m2 and albuminuria, respectively.
• A positive association between accumulated time of AA intake and kidney damage also was
observed, with fully adjusted ORs of 1.07 (95% CI, 1.03-1.12) per 6-month longer intake for eGFR <
60 mL/min/1.73 m2 and 1.04 (95% CI, 1.01-1.08) per 6-month longer intake for albuminuria.

• Response: AA has been shown to be associated with urothelial cancer in many studies, which might
be related to the formation of AA-DNA adducts. Hematuria is one of the major clinical
manifestations of urothelial cancer. However, we did not observe an association between long-term
AA intake and hematuria in our study.


Association Between Aristolochic Acid and CKD: A Cross-sectional Survey in China.
Hemodialysis.com Interview with Authors Wenke Wang and Jian Zhang
Hospital Authority Toxicology Reference Laboratory
Princess Margaret Hospital, Hong Kong SAR, China
(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?

• Response: Our nationwide study showed long-term intake of medications containing AA is prevalent in China and
is associated with the presence of CKD.
• Strategies to eliminate those medications from the market should be strengthened, which could constitute a cost-
effective way to cope with the challenge of CKD in China.
• Hemodialysis.com: What recommendations do you have for future research as a result of this study?

• First, if use of medications containing AA information can be reported from prescriptions would be more reliable.
• Second, we would get more information about more and more herbs containing AA, and try our best to estimate
the mean dose of AA, so that the dose-related effects may be assessed.
• Third, we would get more information on markers of tubular injury.
• Finally, the cross-sectional design of the study makes inference of a causal relationship between CKD and AA
impossible. Maybe we can carry out a cohort study or A case-control study to reveal the causal relationship
between CKD and AA.

• Citation:
• Association Between Aristolochic Acid and CKD: A Cross-sectional Survey in China.
• Zhang J, Zhang L, Wang W, Wang H; China National Survey of Chronic Kidney Disease Working Group.
• Division of Nephrology, Chifeng Second Hospital; Chifeng, China.
Am J Kidney Dis. 2013 Mar 2. pii: S0272-6386(13)00032-2. doi: 10.1053/j.ajkd.2012.12.027.
[Epub ahead of print]


Stress and Burnout Among Nephrology Dialysis Staff
Hemodialysis.com Author Interview: Macaulay Onuigbo MD MSc FWACP FASN MBA
Associate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, MN.
Nephrologist, Mayo Clinic Health System, Eau Claire, WI
Vice Chairman, Nephrology department, MCHSEC. MBA Executive.
(cont)

• Hemodialysis.com: Why was the study carried out in the first place?
• Dr. Onuigbo: The concept of burnout in the workplace was introduced in the late
1970s, mainly in a US context. Healthcare delivery is generally acknowledged to be
a stressful industry but few studies in this area are available. Even far less reported
is stress or burnout in nephrology and/or dialysis practices.
• The potential impact of the recent increasing role of the EMR in the healthcare
workplace was also investigated here especially with reference to the effects of an
EMR on provider perceptions of work stress and burnout. This was even more
pertinent following our recent report in the Wisconsin Medical Journal of the new
unrecognized syndrome of “Physician Cognitive Drift” as it relates to some
unintended consequences of the EMR and as a major source of physician stress in
the healthcare workplace.

• Hemodialysis.com: What is the Methodology of the study?
• Dr. Onuigbo: This was a cross-sectional hand delivered questionnaire-based survey
of physicians, nurses, dialysis technicians, social workers and dieticians in a
nephrology-dialysis practice in a Northwestern Wisconsin Mayo Clinic Dialysis Unit.
The questionnaire used for this survey is the Oldenburg Burnout Inventory (OLBI)
and the survey was carried out in January 2012.


(cont)

• Dr. Onuigbo: Eighteen survey questionnaires were distributed across the clinic and
16 (89%) were returned in a completed form, giving a response rate of 89%. The
participating staff was mostly female nurses, age range 30-60, average age about
40 years.
• The average emotional exhaustion score on the OLBI was 2.66, consistent with a
low level of emotional exhaustion. The average disengagement score was 2.45,
consistent with a low level of disengagement.
• One recurring source of stressors for the staff revolved around the non user-
friendliness of the EMR system(s) – the so-called EMR-induced stresses – including
too much time spent on data entry, the simultaneous use of multiple and non-
interlined EMR systems, slow EMR systems and so on.
• Dr. Onuigbo: We were surprised at the low level of stress and burnout, in general,
evident from this dialysis staff survey. The low level of emotional exhaustion and
disengagement reported amongst was pleasantly surprising. Higher levels had
been anticipated, especially with the inclusion of the dialysis nurses who have
often expressed higher levels of anxiety about work-related stressors.


(cont)

• Hemodialysis.com: What should clinicians and patients take away from your
report?
• Dr. Onuigbo: The urgent need for solutions to healthcare related stress and
burnout calls for more studies. Stress and burnout among healthcare personnel is
an understudied phenomenon and demands more studies. Staff stress and
burnout could lead to reduced staff retention, medical and other errors and overall
poor employee productivity. Furthermore, the mixture of both clerical staff and
clinical staff may have diluted down the average stress and burnout scores
obtained from this dialysis staff survey. Moreover, the near absent participation of
physicians may have also affected the study results,
• The addition of the EMR has often led to an escalation of staff stress and burnout
and requires close monitoring. Some solutions offered by participating staff to
ease EMR-induced stress included the following:
• v More robust, user-friendly, fast, agile, nimble and flexible EMR (No Cognitive
Drift).
• v Reduced redundancy of multiple EMRs requiring multiple data entry procedures.
• v The involvement of providers early in the IT design, implementation and ongoing
review of the EMR.


Vice Chairman, Nephrology department, MCHSEC.
MBA Executive.

• Hemodialysis.com: What recommendations do
you have for future research as a result of this
study?
• Dr. Onuigbo: Larger studies, focused on specific
healthcare professionals with significant
emphasis on stressful work-arounds for
nurses, EMR-induced stress for physicians and
other providers, and better EMR training to
reduce staff stress and burnout would be
necessary.

Vice Chairman, Nephrology department, MCHSEC.
MBA Executive.

• REFERENCES
• Onuigbo MA. Physician ‘cognitive drift’ and medication
errors–unintended consequences of the modern EMR.
WMJ. 2012 Oct;111(5):198.
• Halbesleben JRB, Wakefield DS, Wakefield BJ. Work-
arounds in health care settings: Literature review and
research agenda. Health Care Management Review:
January/March 2008 – Volume 33 – Issue 1 – pp 2-12
• Dahlin M, Runeson B, Jönsson M, Öjehagen A. Stress in
medical students at KI and Lund University. What do we
have in common and what is different?
http://ki.se/ki/jsp/polopoly.jsp?d=1274&a=2274&cid=1289
&l=en.


Experience of HeRO Dialysis Graft Placement in a Challenging Population
Hemodialysis.com Interview with: Harry Schanzer, M.D., F.A.C.S.
Clinical Professor of Surgery
Division of Vascular Surgery
Mount Sinai School of Medicine

• Dr. Schanzer: Eleven patients with central venous occlusive disease
underwent 12 HeRO placements as a last ditch effort for long-term
hemodialysis access. At one year, primary and secondary patencies were
9.1% and 45.5%. Four HeRO grafts were never cannulated, and the
remaining 11 had a functional patency of an average of 14 months

• Dr. Schanzer: These findings were surprising for us, since recent published
studies demonstrated a secondary patency at 24 months as high as
86.7%.1 It is possible that our subset of patients had more severe central
venous occlusive disease than in the other studies, although it is difficult
to compare since detailed descriptions of the patient population in the
studies with higher patency were not included. Our inferior results may
also be due to the small sample size and less than aggressive approach to
maintaining secondary patency with declotting procedures.


(cont)

• Dr. Schanzer: The group of patients who require the HeRO graft for dialysis is especially challenging.
In order for the HeRO to be a consideration, all other upper extremity hemodialysis accesses
excluding catheters, must have been exhausted.2 Furthermore, each of these patients is
unique, and we believe that the range in patency rates is likely due to the variety of anatomic
hurdles that must be overcome. The most important concept to be taken away from this study is
that even if the HeRO only remains functional for 1 year, that is one year without a catheter. Studies
have reported tunneled dialysis catheter rates of infection-associated mortality up to 34%,3 thus
fewer days with a catheter may reduce morbidity and mortality. Finally, in order to maintain
secondary patency in these devices, close follow-up and aggressive declotting is necessary.

study?
• Dr. Schanzer: Prospective studies with larger samples of patients need to be conducted. It is
imperative that the patients be stratified according to their anatomic difficulty of creating a
successful permanent hemodialysis access. Consequently, determining which patients will benefit
the most from the HeRO may contribute to improved patency rates and longer functionality.


(cont)

• Citation:
• Experience of HeRO Dialysis Graft Placement in a Challenging Population.
• Kokkosis AA, Abramowitz SD, Schwitzer J, Schanzer H, Teodorescu VJ.
Vasc Endovascular Surg. 2013 Mar 10. [Epub ahead of print]
• References:
• 1. Gage SM, Katzman HE, Ross JR, Hohmann SE, Sharpe CA, Butterly DW, Lawson
JH. Multi-center experience of 164 consecutive Hemodialysis Reliable Outflow
[HeRO] graft implants for hemodialysis treatment. Eur J Vasc Endovasc Surg. 2012
Jul;44(1):93-9
• 2. Steerman SN, Wagner J, Higgins JA, Kim C, Mirza A, Pavela J, Panneton
JM, Glickman MH. Outcomes comparison of HeRO and lower extremity
arteriovenous grafts in patients with long-standing renal failure. J Vasc Surg. 2013
Mar;57(3):776-83. doi: 10.1016/j.jvs.2012.09.040. Epub 2013 Jan 11.
• 3. Danese M, Griffiths R, Dylan M, Yu H, Dubois R, Nissenson A. Mortality
differences among organisms causing septicemia in haemodialysis patients.
Hemodial Int, 10 (2006), pp. 56–62


he Associations between Race and Geographic Area and Quality-of-Care Indicators in Patients Approaching ESRD
Hemodialysis.com: Interview with
Guofen Yan, Ph.D.
Associate Professor
Department of Public Health Sciences, School of Medicine
University of Virginia Charlottesville, Virginia 22908-07

• Dr. Yan: A body of evidence has established that timely receipt of care from a kidney specialist over
the course of chronic kidney disease (CKD) is important for receiving optimal kidney care, including
slowing the disease, improving survival while on long-term dialysis, and increasing the likelihood of
receiving a kidney transplant. While clinical guidelines recommend that all patients in later stages
of CKD be under the care of kidney specialists, 25% to 50% of patients on dialysis in the United
States had not received such care before they developed kidney failure, or end-stage renal disease
(ESRD).

• We undertook a national study to examine whether geography plays any role in access to pre–ESRD
care among black and white CKD patients. We analyzed information from 404,622 white and black
adult patients receiving dialysis between 2005 and 2010 and residing in 3,076 counties across the
United States. The counties were grouped into large metropolitan, medium/small metropolitan,
suburban, and rural counties.
• We found that pre-ESRD care measures are highly variable among geographic areas defined by
urban/rural characteristics. Fewer patients received nephrologist care for more than 12 months
before developing ESRD in large-metro (25.7%) and rural (26.9%) counties than in medium/small-
metro counties (31.6%). In all four geographic areas, black patients received less pre-ESRD care
than their white counterparts. In large-metro counties, black patients were 27% less likely than
whites to receive nephrologist care for more than 12 months before developing ESRD. In rural
counties, they were 16% less likely. In suburban and rural counties, black patients were 30% to 52%
less likely than whites to see a dietitian before developing ESRD.


Guofen Yan, Ph.D. Associate Professor
(cont)

• Dr. Yan: We found that for all the pre-ESRD care measures examined, the difference across the four
types of geographic areas was much greater for black patients than white patients. For example, in
large-metro counties, the proportions of receiving dietitian care for white and black patients were
both about 19%; however, in rural counties, only 8% of rural black patients (more than a 50%
reduction from 19% in large-metro) received such care, compared with 16.8% of rural white
patients. Consequently, in certain geographic areas black patients were substantially less likely to
have received kidney specialist care than white patients, such as very limited access to dietitian
care for black patients living in rural counties.

• Dr. Yan: A Healthy People 2020 objective is to increase the proportion of CKD patients who receive
nephrologist care at least 12 months before the start of renal replacement therapy. Our study
shows that currently the proportion ranges from 21% to 33%, depending on the geographic
location and race. Possible explanations for the lower proportions include differences in referral
patterns between healthcare providers in different geographic areas, noncompliance of patients to
the referral, limited access to kidney specialists in some geographic areas, or financial constraints
for patients with low socioeconomic status. We need national concerted efforts, from health care
providers, policy makers, and patients, to identify and remove the barriers to access to kidney
specialists.


(cont)

• Hemodialysis.com: What recommendations do you have for future
research as a result of your study?
• Dr. Yan: The significant geographic differences in receiving pre-kidney
failure care and the substantially large racial differences in certain
geographic areas highlight the complexity of the issue. Many health care
policies are driven by the degree of urbanization of a given county, but the
recommendations are often based on limited data. Our findings suggest
improving receipt of key pre-ESRD indicators will require more refined
regional characterization of health care needs and resources, working with
kidney organizations around employment opportunities for new
graduates. Healthcare polices directed at eliminating pre-ESRD care
disparities must take these complexities and granular data into
consideration. Future studies to delineate the factors that are responsible
for urban-rural differences as well as variations within counties may allow
for more strategic and public health oriented approaches to improve care
for all Americans with CKD.


(cont)

• Citation:
• The Associations between Race and Geographic Area and Quality-
of-Care Indicators in Patients Approaching ESRD
• Yan G, Cheung AK, Ma JZ, Yu AJ, Greene T, Oliver MN, Yu W, Norris
KC.
• Department of Public Health Sciences and , ‖Department of Family
Medicine, University of Virginia School of
Medicine, Charlottesville, Virginia;, †Division of Nephrology &
Hypertension and, §Division of Epidemiology, University of
Utah, Salt Lake City, Utah;, ‡Dornsife College of Letters, Arts, and
Sciences and Keck School of Medicine, University of Southern
California, Los Angeles, California, ¶Charles R. Drew University of
Medicine and Science, Los Angeles, California.
Clin J Am Soc Nephrol. 2013 Mar 14. [Epub ahead of print]


The CKD Enigma – Statistics and Myths about CKD: Conflicting ESRD and Death Rates in the Literature
Hemodialysis.com Interview with Macaulay Onuigbo MD MSc FWACP FASN MBA
Vice Chairman, Nephrology department, MCHSEC.MBA Executive

• Hemodialysis.com: Why was the study carried out in the first place?
• Dr. Onuigbo: Over the years, the CKD literature had demonstrated a huge disparity
in the reported annual death rates and annual ESRD rates among different CKD
cohorts both here in the USA and around the world. There is this unproven yet
commonly accepted consensus that “most CKD patients die (of CV events) before
they reach ESRD”. Yet there are reports out there in the nephrology literature
showing much higher ESRD rates than death rates in CKD cohort studies. Keith et al
(2004) reported an ESRD Rate of 20% and a higher Death Rate of 50% after 5
years, among a CKD cohort of 27,998 patients in a managed care organization.
Quite the opposite, Menon et al (2008) demonstrated a higher ESRD Rate of 60%
and a Death Rate of 15% after 88 months in 1,666 patients in the Modification of
Diet in Renal Disease (MDRD) study. Onuigbo & Onuigbo (2009), in a single-center
Mayo Clinic study revealed an ESRD Rate of 18% and a Death Rate of 13% after 4
years among a 100-patient high risk CKD cohort in an angiotensin inhibition
withdrawal study.
• We therefore set out to compare projected annual ESRD incidence among the
general US CKD population based on current literature versus actual US ESRD
incidence as reported in the United States Renal Data System (USRDS) for the year
ending December 2008.


(cont)

• Hemodialysis.com: What was the Methodology of the study?
• Dr. Onuigbo: In mid-2012, we carried out a snap shot cross-sectional US 2007 CKD
population-wide analysis of projected annualized ESRD incidence based on the
weighted rates from the three cited sources. We then compared these estimates
with actual US ESRD incidence as reported in USRDS 2010 report for 2008.
• A 2007 US CDC report indicated that 16.5% of the U.S. population 20 years of age
and older had CKD with eGFR <60 ml/min/1.73 sq m BSA, thus affecting >20
million adult Americans.
• The above 3 cited studies combined, give a weighted average annualized ESRD
Rate of ~4.2% among the US CKD population.
• Dr. Onuigbo: Projections for new ESRD resulted in an estimated 840,000 new ESRD
cases in 2008.
• According to the 2010 USRDS Annual Data Report, the actual reported new ESRD
incidence in 2008 was in fact only 112,476 (FIGURE). This represented a gross
overestimation by about 650% of the ESRD incidence in the US for the year ending
2008 – clearly a colossal failure of epidemiological analysis.


(cont)

• Dr. Onuigbo: The magnitude of the disparity between estimated
ESRD rates and the actual ESRD incidence for 2008 was mind-
boggling. Similar results would be obtained for annual death rates
comparisons. Thus, the natural history of CKD remains unclear and
the nephrology literature is rife with very dissimilar and conflicting
data regarding ESRD Rates and Death Rates among different
reported CKD cohorts.
• Moreover, these results simply confirm the conclusions of the
recently released (August 2012) US Preventive Services Task Force
(USPSTF) Report on CKD screening which concluded that we know
surprisingly little about whether screening adults with no signs or
symptoms of CKD will improve health outcomes and that clinicians
and patients deserve better information on CKD.


(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?
• Dr. Onuigbo: That we as physicians in general, and nephrologists in particular, still do not understand the true natural history of CKD, its
prognostication, ESRD prediction, and the true ESRD Rates and Death Rates among CKD cohorts.
• The clear heterogeneity of the so-called “CKD patient” is brought into prominence as we review the very misleading concept of classifying and
prognosticating all CKD patients as if CKD represented one homogenous patient population.
• Current consensus that ‘most CKD patients all die of cardiovascular events before reaching ESRD’ is simply a myth, is unfounded, and untrue.
• Bansal and Hsu in a 2008 analysis of the long-term outcomes of patients with chronic kidney disease echoed the observation that the disparate ESRD
and mortality rates in various CKD populations as reported by various studies in the literature only emphasized the heterogeneity of CKD populations.
• No one-size-fits-all approach in medicine can be dangerous.
• Patient care, more so CKD care, MUST be individualized, one CKD patient at a time.
• More studies into the ramifications of these findings as they relate to CKD care, CKD planning and management call for more studies.
• Hemodialysis.com: What recommendations do you have for future research as a result of this study?
• More critical investigation of longitudinal patient-level analysis of renal, morbidity and mortality outcomes among CKD patients is needed here in the
USA and worldwide.
• Furthermore, the notion that CKD represented a single disease entity is dangerous and must be abandoned.
• The role of the nephrologist in enhancing CKD outcomes and the role of CKD screening, we as nephrologists must acknowledge, remain unclear and
unknown, respectively, and these questions urgently demand further objective dispassionate study.
• Finally, in a recent publication, we had introduced the new concept of “Symptomatic” versus “Asymptomatic” CKD – this again calls for more studies
and validation.


(cont)

• REFERENCES
• 1. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a
population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659–63.
• 2. Centers for Disease Control and Prevention (CDC): Prevalence of chronic kidney disease and associated risk
factors – United States, 1999–2004. MMWR Morb Mortal Wkly Rep 2007; 56: 161–165.
• 3. Menon V, Wang X, Sarnak MJ, et al. Long-term outcomes in nondiabetic chronic kidney disease. Kidney Int
2008;73:1310–15.
• 4. Bansal N, Hsu CY. Long-term outcomes of patients with chronic kidney disease. Nat Clin Pract Nephrol
2008;4:532–3.
• 5. Onuigbo MA. The natural history of chronic kidney disease revisited–a 72-month Mayo Health System
Hypertension Clinic practice-based research network prospective report on end-stage renal disease and death
rates in 100 high-risk chronic kidney disease patients: a call for circumspection. Adv Perit Dial. 2009;25:85-8.
• 6. Editorial on this article. Ian H de Boer. Chronic Kidney Disease – A Challenge for all ages. JAMA
2012;308(22):2401-2402.
• 7. Moyer VA; on behalf of the U.S. Preventive Services Task Force. Screening for Chronic Kidney Disease: U.S.
Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2012 Aug 28. doi: 10.7326/0003-
4819-157-8-201210160-00533. [Epub ahead of print].
• 8. Onuigbo MA. The CKD Enigma with Misleading Statistics and Myths about CKD, and Conflicting ESRD and Death
Rates in the Literature: Results of a 2008 US Population-Based Cross-Sectional CKD Outcomes Analysis. State-of-
the-Art-Review. Ren Fail. 2013 Feb 8. [Epub ahead of print].


Disentangling the Ultrafiltration Rate–Mortality Association: The Respective Roles of Session Length and Weight Gain
Hemodialysis.com Author Interview: Dr. Jennifer E. Flythe
Renal Division, Department of Medicine, Brigham and Women’s Hospital
75 Francis Street, MRB-4, Boston, MA 02115

• Dr. Flythe: High ultrafiltration rates during hemodialysis (HD) have been
associated with increased all-cause and cardiovascular mortality. The
ultrafiltration rate, however, is determined by both dialysis session length
(DSL) and interdialytic weight gain (IDWG). Both short DSL and high IDWG
have been linked to increased mortality, but these variables are often
collinear so their independent associations with mortality have not been
adequately investigated. We undertook this study to determine the
associations of DSL and IDWG (independently of each other) with
mortality in a population of chronic HD patients with adequate clearance.

• Our study results demonstrate that among chronic HD patients, both short
DSL and high IDWG play important roles in the UFR–mortality association.
Short DSL is associated with increased mortality independently of IDWG,
and high IDWG is associated with increased mortality, independently of
DSL. We also showed that these relationships follow dose-response
patterns.


(cont)

• Dr. Flythe: Interestingly, our analyses showed no statistical
interaction between DSL and IDWG, suggesting that the extension
of DSL (to at least 240 minutes) would be favorable regardless of
the patient’s IDWG and that limiting IDWG (to <3 kg) would be
favorable regardless of the patient’s session length.
• Hemodialysis.com: What should clinicians and patients take away
from this study?
• Dr. Flythe: Since both IDWG and DSL are independently associated
with mortality, targeting either (or both) may be favorable for
patients. Extending DSL to at least 240 minutes and reducing weight
gain to <3kg should be considered for all patients regardless of
baseline adequate clearance and ambient IDWG (or DSL). One
potential intervention is to titrate DSL on a session-to-session basis
based on interval IDWG.


(cont)

• Dr. Flythe: Prospective studies of the efficacy of targeted
interventions are needed. Assessment of patient opinion regarding
potential interventions is also needed.

• Citation:
• Disentangling the Ultrafiltration Rate–Mortality Association: The
Respective Roles of Session Length and Weight Gain
• Jennifer E. Flythe, Gary C. Curhan, and Steven M. Brunelli
• Disentangling the Ultrafiltration Rate–Mortality Association: The
Respective Roles of Session Length and Weight Gain
CJASN CJN.09460912; published ahead of print March
14, 2013, doi:10.2215/CJN.09460912


Value of Myocardial Perfusion Imaging in Renal Transplant Evaluation
Angina.com Interview with: Dr. Chong Ghee Chew
Department of Nuclear Medicine, PET and Bone Mineral Densitometry, Royal Adelaide Hospital, Adelaide, SA

• Angina.com: What are the main findings of the study?
• Answer: This is a retrospective audit of the cardiac outcomes of renal
failure patients who had been transplanted in South Australia between
1999 to 2009, who had myocardial perfusion SPECT scan for the transplant
assessment. The results represent ”real world” outcomes as the scans
were performed in the 3 major teaching hospitals in SA. 2 endpoints –
“soft” = inpatient care with angina +/- PCI +/- CABG, and “hard” =
inpatient care with myocardial infarction or cardiac death. With a negative
scan this cohort had a statistically significant lower soft endpoint event
rate than a positive scan …3.9% vs 20.8%, hazard ratio of 4.4 at 5 years
post scan. The hard endpoint event rate was also lower for those with a
negative scan but the difference did not reach statistical significance. The
event rates of hard and soft endpoints were no different for the negative
scans that were performed with a tachycardic stress (treadmill exercise,
dobutamine or external wire right atrial pacing) versus dipyridamole
induced coronary vasodilatation.


Value of Myocardial Perfusion Imaging in Renal Transplant Evaluation
Angina.com Interview with: Dr. Chong Ghee Chew
Department of Nuclear Medicine, PET and Bone Mineral Densitometry, Royal Adelaide Hospital, Adelaide, SA
(cont)

• Angina.com: Were any of the findings unexpected?
• Answer: No
• Angina.com: What should clinicians and patients take away from this
study?
• Answer: Myocardial perfusion SPECT scan is a good predictor of cardiac
events in renal failure patients who are being considered for
transplantation.
• This is a valid test for transplant assessment.
• Angina.com: What further research do you recommend as a result of
your study?
• The study did not include patients who were assessed but were not
transplanted. We are planning another similar audit to look at this cohort.
• Citation:
• ACC 2013 American College Cardiology Presentation Spring 2013


Association of BP Variability with Mortality among African Americans with CKD
Hemodialysis.com Interview with Dr. Ciaran J. McMullan
Renal Division and Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital
41 Avenue Louis Pasteur, Suite 121, Boston, MA 02115


• Dr. McMullan: A person’s blood pressure may change up and down
from day to day. Some people have small day to day changes in
blood pressure, and some people have large day to day changes. In
a population of African Americans with kidney disease, we found
that large day to day changes in blood pressure predicted a much
greater risk of dying, even after controlling for other things that
predict death. Thus, larger changes in blood pressure from day to
day could identify a high risk group of African Americans with
kidney disease; in addition, it means that scientists should examine
why people have large day to day changes in blood pressure, as this
may turn out to be a new area of therapy research.


(cont)

• Dr. McMullan: In our study of African Americans who had kidney
disease, we found that the people whose blood pressure changed a lot
from day to day were three times more likely to die that those people
whose blood pressure only changed a little. In addition, people in the
group with large day to day blood pressure changes were particularly
susceptible to cardiovascular deaths with rates of cardiovascular mortality
almost five times that of the group with small day to day changes in blood
pressure.

• Hemodialysis.com: What should clinicians and patients take away from
this study?
• Dr. McMullan: Clinicians involved in the care of patients with kidney
disease should pay attention to the fluctuations seen in blood pressure
measured from clinic visit to clinic visit. These fluctuations may not simply
be random but may carry important information about risk.


(cont)

• Dr. McMullan: We need to first understand why people’s blood
pressure changes from day to day. Second, we need to understand
if these ups and downs in blood pressure actually cause damage to
the heart and blood vessels or, rather, are just of marker of
something else that is causing damage.
• Citation:
• Association of BP Variability with Mortality among African
Americans with CKD
• Ciaran J. McMullan, George L. Bakris, Robert A. Phillips, and John P.
Forman
• Association of BP Variability with Mortality among African
Americans with CKD CJASN CJN.10131012; published ahead of print
March 14, 2013, doi:10.2215/CJN.10131012


Antimicrobial Use in Outpatient Hemodialysis Units
Hemodialysis.com Interview with: Dr. Graham Snyder
Beth Israel Deaconess Medical Center 110 Francis St
Boston, MA 02215

• Dr. Snyder: We looked at antimicrobial use in two Boston-area hemodialysis units in two ways: over
a nearly three-year retrospective time period, we calculated the total amount of antimicrobials
used, and prospectively over a one-year time period we analyzed each dose of parenteral
antimicrobial administered in the hemodialysis units.

• Over a 35-month retrospective period there were over 2,300 antimicrobial doses given in the two
hemodialysis units, which equates to an overall antimicrobial use rate of 33 doses per 100 patient-
months. For any given month, the range of antimicrobial use was between 5 doses and 67 doses
per 100 patient-months. Vancomycin was the most commonly administered antimicrobial,
accounting for approximately two-thirds of doses (overall, 22 doses per 100 patient-months),
followed by cefazolin (5 doses per 100 patient-months) and third/fourth-generation cephalosporins
(3 doses per 100 patient-months); other antimicrobials were given less frequently.
In the 12-month prospective period, we followed 278 patients in the two hemodialysis units, 89
(32%) of whom received at least one parenteral dose of antimicrobial. Of the 1,003 doses given
during that time, we could determine the appropriateness of indication in 926 (92%). Nearly 30%
(276/926) of these doses had an inappropriate indication, including prescribing for conditions not
meeting guidelines-based criteria to diagnose infection (146, 53%), use when a more narrow
spectrum antimicrobial could have been chosen (74, 27%), and for surgical prophylaxis beyond
recognized indication for prophylaxis (58, 20%). Over one-third of vancomycin and third/fourth-
generation cephalosporin doses were inappropriately indicated.


Boston, MA 02215
(cont)

• Dr. Snyder: To date, there has been very little data reported on antimicrobial prescribing practices
in the hemodialysis setting.
• From nationwide data collected through the United States Renal Data System (USRDS), we know
that approximately 40% of patients receiving chronic hemodialysis have at least one billing claim for
an antimicrobial each year, and that vancomycin constitutes about two-thirds of prescribed
antimicrobials. Our data showing that approximately 32% of patients receive a parenteral dose of
antimicrobials and approximately two-thirds of the antimicrobial doses are vancomycin is
consistent with USRDS data.
• Lastly, two prior studies (Green K, Am J Kidney Dis 2000;35:64-68; Zvonar R, Nephrol Dial Transplant
2008;23:3690-3695) have shown that for vancomycin, at least 10-33% of antimicrobials are
inappropriately indicated, and most frequently for not choosing an antimicrobial with a more
narrow spectrum of activity and for treating conditions unlikely to be a true infection.
• The data from our study is in agreement with these findings, and expands on the findings in these
studies. A significant novel finding of our study was the substantial (and frequently inappropriately
indicated) use of third/fouth-generation cephalosporins.
• This is important because based on USRDS data the use of these agents is increasing, and the use of
these agents relates very closely to antimicrobial resistant gram-negative bacterial infections, which
have a high and increasing prevalence among the dialysis population.


Boston, MA 02215
(cont)

• Dr. Snyder: There is room for improvement in antimicrobial prescribing practices, including
reducing use when not indicated and choosing the most appropriate antimicrobial for a given
infectious condition.
• In addition to minimizing the risk of adverse effects directly attributable to the
antimicrobials, limiting inappropriate use of antimicrobials has the potential to lead to a decrease
in the emergence and spread of antimicrobial resistant bacteria among patients receiving
hemodialysis. This effect on resistant bacteria may subsequently reduce the spread of these
bacteria from patients receiving hemodialysis to other hospitalized patients and individuals in the
community as well.
study?
• Dr. Snyder: In addition to confirming these findings in other hemodialysis populations, our results
may be used to help tailor antimicrobial stewardship interventions.
• Interventions particularly worthy of investigation may include vancomycin and cephalosporin
prescribing, decision support for surgical prophylaxis, and clinical management of skin/soft tissue
infections. Future studies may identify patient populations among those receiving chronic
hemodialysis who are particularly likely to receive antimicrobials and inappropriately indicated
antimicrobials, and therefore also guide antimicrobial stewardship efforts.


Boston, MA 02215
(cont)

• Citation:
• Antimicrobial Use in Outpatient Hemodialysis
Units
• Snyder GM, Patel PR, Kallen AJ, Strom JA, Tucker
JK, D’Agata EM.
• Division of Infectious Diseases, Beth Israel
Deaconess Medical Center, Harvard Medical
School, Boston, Massachusetts.
Infect Control Hosp Epidemiol. 2013
Apr;34(4):349-57. doi: 10.1086/669869. Epub
2013 Feb 18.

Cinacalcet Improves Endothelial Dysfunction and Cardiac Hypertrophy in Patients on Hemodialysis with Secondary Hyperparathyroidism
Hemodialysis.com Interview with: Cheol Whee Park, M.D.
Professor of Internal Medicine Seoul St. Mary’s Hospital
Division of Nephrology, Department of Internal Medicine The Catholic University of Korea
Seoul, Republic of Korea


• Answer: Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal
failure and it is associated with high morbidity and mortality. Furthermore, SHPT affects the
cardiovascular system related to cardiovascular calcification and cardiomyopathy. The calcium-
sensing receptor (CaSR) is expressed in cardiomyocytes, endothelial cells and vascular smooth
muscle cells, which raises the possibility that this receptor may be implicated in the
pathophysiology of cardiovascular disease and constitute a potential therapeutic target.
• The recently published EVOLVE trial did not support the notion that cinacalcet, a calcimimetic of
the second generation, reduces the risk of death or major cardiovascular event in hemodialysis
patients with moderate-to-severe secondary hyperparathyroidism (SHPT). However, the findings
from the EVOLVE trial are probably inconclusive because of low statistical power. Therefore,
important questions regarding the clinical benefits of cinacalcet on cardiovascular system in
hemodialysis patients in the setting of SHPT are remained to solve.
• In this regard, our prospective, open-labeled, controlled, crossover clinical study found that
cinacalcet hydrochloride treatment without vitamin D ameliorates endothelial dysfunction and
inflammation, cardiac diastolic dysfunction, and cardiac hypertrophy by decreasing oxidative stress
and improving endothelial dysfunction with increasing the serum nitric oxide (NOx) production in
hemodialysis patients with SHPT.


(cont)

• Answer: We were interested in the evidence that cinacalcet without Vit D could improve vascular
endothelial dysfunction and inflammation.
• The combination treatment with cinacalcet and low dose vitamin D are found to be associated with
the attenuation of cardiovascular calcification in hemodialysis patients; however, the effects of
cinacalcet alone (without vitamin D) on cardiac and endothelial functions have not been well
defined in hemodialysis patients with SHPT. In contrast, we demonstrated that cinacalcet along
significantly improves vascular endothelial dysfunction and inflammation, diastolic cardiac
dysfunction, and LVH. These findings suggest that cinacalcet itself might improve the endothelial
dysfunction, arterial stiffness and cardiac diastolic dysfunction, and left ventricular hypertrophy
related to ameliorate oxidative stress and NOx production in the hemodialysis patients with SHPT.
Recent studies also demonstrated that cinacalcet protects vascular damage in the nerve by
improving NOx production and vasodilation.
• Answer: Despite effective improvement of biochemical parameters of dialysis patients with
SHPT, the intention-to-treat analysis of the EVOLVE trial did not support the notion that cinacalcet
significantly reduces the risk of death or major cardiovascular events in dialysis patients with
moderate-to-severe SHPT. In contrast, the simultaneous reduction of serum calcium, phosphorus
and intact parathyroid hormone (iPTH) as well as the increased CaSR in the cardiovascular system
are favorable mechanisms for attenuating the progression of vascular calcification and cardiac
hypertrophy in dialysis patients with SHPT. Our study added some favorable data to the question
regarding whether cinacalcet without Vit D might reduce oxidative stress and improve endothelial
function in hemodialysis patients in SHPT.


(cont)

• Hemodialysis.com: What recommendations do you have for future research as a
result of your study?
Answer: Our study has some limitations including the small number of study
patients and the short time interval of the study period. Therefore, a
prospective, multicenter, large-scale study with a longer follow-up period is
required to yield more informative data in terms of the cardiovascular effects of
cinacalcet. Researches are also needed to assess the cinacalcet treatment
commonly used in hemodialysis patients with SHPT over a broad spectrum of
SHPT. Moreover, future randomized controlled and open label extension trials are
needed to directly evaluate the long-term comparative effects of cinacalcet along
or with Vit D (or analogues) in hemodialysis patients with SHPT.
• Citation:
• Cinacalcet Improves Endothelial Dysfunction and Cardiac Hypertrophy in Patients
on Hemodialysis with Secondary Hyperparathyroidism
Choi S.R. · Lim J.H. · Kim M.Y. · Hong Y.-A. · Chung B.H. · Chung S. · Choi B.S. ·
Yang C.W. · Kim Y.-S. · Chang Y.S. · Park C.W.
Nephron Clin Pract 2012;122:1-8 (DOI: 10.1159/000347145)


Hemodialysis.com Kidney Disease Interviews March 24 2013

Hemodialysis.com Kidney Disease Interviews March 24 2013

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Hemodialysis.com Kidney Disease Interviews March 24 2013