Hemodialysis.com Author Interviews Dec 6 2012

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
December 6 2012

For Informational Purposes Only: Not for Specific Medical Advice.

Experiences of Care Among Medicare Beneficiaries With ESRD: Medicare Consumer Assessment of Healthcare Providers and Systems
(CAHPS) Survey Results
Hemodialysis.com Author Interview:
Marc N. Elliott, PhD, RAND Corporation, 1776 Main St,
Santa Monica, CA 90401-3208

• Hemodialysis.com Editor Marie Benz: What are the main findings of the study?
• Dr. Elliott:
• Medicare beneficiaries with ESRD reported better experiences of care than non-ESRD beneficiaries for 7 of 10 patient
experience measures -rating of care, rating of physician, rating of prescription drug plan, getting prescription drugs,
getting needed care, customer service, and getting care quickly. However, the magnitude of these differences between
ESRD and non-ESRD beneficiaries is small (<3 points difference on a scale of 0-100). Beneficiaries with ESRD did not
report worse experiences of care than their non-ESRD counterparts on any of the 10 measures.
• Among ESRD beneficiaries, black Medicare beneficiaries indicated poorer experiences than white beneficiaries for 6 of 10
measures (rating of care, rating of physician, rating of specialist, rating of prescription drug plan, getting prescription
drugs, and physician communication).

Also among ESRD beneficiaries, those without a high school degree were more likely to report worse experiences than
high school graduates.

• Hemodialysis.com: Were any of the findings unexpected?
• Dr. Elliott:
• It may be surprising that, on average, beneficiaries with ESRD did not report worse care experiences than non-ESRD
beneficiaries for any of the 10 measures examined, though there is some evidence that this can occur in other settings
with longstanding patient-physician relationships that arise in the treatment of chronic conditions such as ESRD.

Experiences of Care Among Medicare Beneficiaries With ESRD: Medicare Consumer Assessment of Healthcare Providers and
Systems (CAHPS) Survey Results
Marc N. Elliott, PhD, RAND Corporation, 1776 Main St,
Santa Monica, CA 90401-3208
(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?
• Dr. Elliott:
• Given that black ESRD patients and those without a high school degree report worse experiences than other
ESRD patients, clinicians may want to make extra efforts to communicate effectively with such ESRD patients
and ensure that their needs are met.
Ensuring that discussions and materials are appropriate for the health literacy levels of all patients may be an
important consideration.

• Hemodialysis.com: What recommendations do you have for future research as a result of this study?
• Dr. Elliott:
• Further research that explores the reasons why Medicare beneficiaries with ESRD tend to report better
experiences of care than those without ESRD is needed. Also needed is research that further examines
disparities in experiences of care by race/ethnicity and education, including the reasons behind such
disparities.
The CMS-sponsored In-Center Hemodialysis CAHPS Survey, which began implementation as of late 2012, could
be a source of data for additional research.
• Reference:
• Experiences of Care Among Medicare Beneficiaries With ESRD: Medicare Consumer Assessment of Healthcare
Providers and Systems (CAHPS) Survey Results
Charlotte A.M. Paddison, Marc N. Elliott, Amelia M. Haviland, Donna O. Farley, Georgios Lyratzopoulos, Katrin
Hambarsoomian, Jacob W. Dembosky, Martin O. Roland
American Journal of Kidney Diseases - 23 November 2012 (10.1053/j.ajkd.2012.10.009)

Comparison of alteplase (tissue plasminogen activator) high-dose vs. low-dose protocol in restoring hemodialysis catheter
function: The ALTE-DOSE study
Dr. A. Kadri
Chief of Medicine Hotel Dieu- Grace Hospital Windsor, Ontario

• Dr. Kadri:
• Prior to this study, it was not entirely clear according to the available literature, what the optimal dose of TPA
was for catheter malfunction.
Because this is a very expensive medication some centers were using low dose TPA (1mg per port) as a cost
saving measure as there was no clear information that higher dose TPA (2mg per port) was more effective in
resolving catheter malfunction in the dialysis population. Prior to our study, we reviewed the available
literature and there was some suggestion that 1 mg dosing might be as effective as 2-mg dosing of TPA for
catheter malfunction.
Our study suggests that the 2-mg dose seems to be superior in resolving catheter malfunction and prolonging
catheter survival in this population.
Importantly, this seems to be independent of the frequency and total TPA dose during the life of the catheter
ie.

• A single 2-mg dose is more effective than repeatedly administering 1 mg doses in treating catheter malfunction.

• Dr. Kadri:
• I must admit, these findings were a bit surprising in that our center has been using 1 mg dosing as a cost saving
measure as there was no clear evidence that 2-mg dosing with superior.

Comparison of alteplase (tissue plasminogen activator) high-dose vs. low-dose protocol in restoring hemodialysis catheter function: The
ALTE-DOSE study
Dr. A. Kadri
Chief of Medicine Hotel Dieu- Grace Hospital Windsor, Ontario
Continued

• Dr. Kadri:
• I think it is important to realize that the available data at this point seems to suggest that 2-mg dosing may be
more effective in restoring catheter function and prolonging catheter survival in the dialysis population than 1
mg dosing of TPA.
To date, we believe this is the largest analysis regarding this issue. It should be noted however that this is a
retrospective analysis and further investigation is definitely warranted in our opinion.

• Dr. Kadri:
• I believe it would be an extremely worthwhile endeavor to embark on a prospective, randomized clinical trial
analyzing this issue.
It would be of great importance in the dialysis community given the enormous cost of TPA.
• Reference:
• Comparison of alteplase (tissue plasminogen activator) high-dose vs. low-dose protocol in restoring
hemodialysis catheter function: The ALTE-DOSE study
Yaseen, O., El-Masri, M. M., El Nekidy, W. S., Soong, D., Ibrahim, M., Speirs, J. W. and Kadri, A. (2012), Comparison
of alteplase (tissue plasminogen activator) high-dose vs. low-dose protocol in restoring hemodialysis catheter
function: The ALTE-DOSE study. Hemodialysis International. doi: 10.1111/hdi.12004

End-stage renal failure due to amyloidosis: outcomes in 490 ANZDATA registry cases.
Professor David Johnson
MB BS (Hons), FRACP, PhD (Syd), PSM
Metro South and Ipswich Nephrology & Transplant Services (MINTS)

• The main findings of the study were that, compared to patients with end-stage renal failure
secondary to other causes, those with end-stage renal failure due to amyloidosis experienced
inferior survival on dialysis (median 2.09 vs 4.45 years, respectively), inferior first renal allograft
survival (median 4.55 vs 10.7 years) and inferior patient survival following renal transplantation
(median 6.03 vs 16.8 years).
53 (13.8%) of amyloidosis patients on dialysis died of amyloidosis-related complications and
16.4% of amyloidosis patients undergoing renal transplantation experienced amyloidosis
recurrence in the renal allograft.

• Previous small observational cohort studies had observed inferior survival of amyloidosis patients
on dialysis compared with that of patients with other causes of end-stage renal failure.
However, there had not been a large, comprehensive, multi-centre evaluation of the clinical
outcomes of amyloidosis patients on dialysis. Furthermore, information on renal transplant
outcomes was extremely limited and conflicting, with some studies favouring transplantation for
these individuals and other studies not. The present study clearly demonstrates that the dialysis
and renal transplant outcomes of amyloidosis patients are poor.

End-stage renal failure due to amyloidosis: outcomes in 490 ANZDATA registry cases.
Professor David Johnson
MB BS (Hons), FRACP, PhD (Syd), PSM
Metro South and Ipswich Nephrology & Transplant Services (MINTS)
Continued

• Amyloidosis is associated with poor patient survival following dialysis and/or renal
transplantation, poor renal allograft survival and a significant incidence of disease recurrence in
the allograft. An appreciable proportion of amyloid ESRF patients die of amyloidosis
complications.

• Hemodialysis.com: What recommendations do you have for future research as a result of this
study?
• Future studies should examine dialysis and renal transplant outcomes amongst patients with
different subtypes of amyloidosis (AL, AA or other types).

• Reference:
• End-stage renal failure due to amyloidosis: outcomes in 490 ANZDATA registry cases.
• Tang W, McDonald SP, Hawley CM, Badve SV, Boudville N, Brown FG, Clayton PA, Campbell SB, de
Zoysa JR, Johnson DW.
1 ANZDATA Registry, Adelaide, SA, Australia.
Nephrol Dial Transplant. 2012 Nov 25. [Epub ahead of print]

Uremic Versus Idiopathic Restless Legs Syndrome: Impact on Aspects Related to Quality of Life
Christoforos D. Giannaki PhD Department of Life and Health Sciences University of Nicosia Cyprus

• Restless legs syndrome (RLS) is very common in the hemodialysis population.
Briefly, RLS is characterized by an irresistible urge to move the legs, usually accompanied by
unpleasant sensations.
The syndrome’s symptoms begin or worsen during rest periods and mainly in the night, whereas
a temporary relief occurs by movement. We found that the patients with uremic RLS seem to
experience lower levels of quality of life, have an increased score in depression symptoms, and
report more severe RLS symptoms compared with the patients with idiopathic RLS. In addition,
the patients with both types of RLS were found to experience significantly lower quality of life
levels compared with healthy non-RLS individuals.


• We found no significant differences in sleep quality between the uremic and the idiopathic RLS
patients. We believe that the lack of significant differences may be due to the lack of an overnight
polysomnographic evaluation which is considered the gold standard technique for the
assessment of sleep parameters as well as due to the low number of patients involved in the
study.

Uremic Versus Idiopathic Restless Legs Syndrome: Impact on Aspects Related to Quality of Life
Christoforos D. Giannaki PhD Department of Life and Health Sciences University of Nicosia Cyprus

Continued

• Severity of the RLS symptoms is greater in the uremic patients compared to the idiopathic
patients. Similarly, quality of life and depression score appeared to be worst in the uremic RLS
patients compared to the idiopathic ones.
Taking into account the high prevalence as well as the great negative impact of RLS in the
hemodialysis patients’ overall health and quality of life parameters, the syndrome should receive
special attention both by the nephrologists and the hemodialysis patients.

study?
• The comparison of more health related parameters between the two RLS group of patients.
Examination of the efficacy of pharmacological and non-pharmacological treatment options in
hemodialysis patients with RLS.

• Reference:
• Uremic Versus Idiopathic Restless Legs Syndrome: Impact on Aspects Related to Quality of Life
• Gkizlis V, Giannaki CD, Karatzaferi C, Hadjigeorgiou GM, Mihas C, Koutedakis Y, Stefanidis I, Sakkas
GK. Uremic Versus Idiopathic Restless Legs Syndrome: Impact on Aspects Related to Quality of
Life. ASAIO J. 58(6):607-611. 2012

Fibroblast growth factor 23 and soluble klotho in children with Chronic Kidney Disease
Hemodialysis.com Authors' Interview:
Dr. Rukshana Shroff, Research Registrar, Nephrourology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Mandy Wan
Lead Paediatric Research Pharmacist | London & South East MCRN Local Research Network

• Our study shows that even in a population of children with well-controlled serum phosphate,
high fibroblast growth factor 23 (FGF23) and low soluble-klotho (s-klotho) levels are seen with
progressive decline in estimated glomerular filtration rate (eGFR).
No association was seen between serum phosphate or PTH and FGF23, but FGF23 showed a
positive association with serum calcium levels. FGF23 levels increased over a 12 months period,
particularly in children with CKD stage 3b.
• Our multivariate regression analysis demonstrated a strong relationship between FGF23 and
eGFR, whereas the association between s-klotho and eGFR as observed in univariate analysis was
lost following adjustment for confounders.
• We found novel associations between FGF23 and serum calcium as well as 25-hydroxyvitamin D
[25(OH)D]: there was a positive association between FGF23 and serum calcium, and 25(OH)D
deficiency was associated with higher FGF23 levels.
Also, this study is the first to report on s-klotho levels in children with CKD, suggesting that low
25(OH)D and high PTH are associated with s-klotho deficiency in CKD.

Fibroblast growth factor 23 and soluble klotho in children with Chronic Kidney Disease
Hemodialysis.com Authors' Interview:
Dr. Rukshana Shroff, Research Registrar, Nephrourology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Mandy Wan
Lead Paediatric Research Pharmacist | London & South East MCRN Local Research Network
Continued

• Our report adds to the emerging data, which suggests progressive increase in FGF23 production starting at the
earliest stage of chronic kidney disease (CKD), and that FGF23 may be a key contributor to the disturbances in
mineral and bone metabolism in patients with CKD. Equally, one must not forget s-klotho and its potential
involvement in this pathophysiologic process which may or may not be dependent of FGF23.
• The potential association between calcium levels and high FGF23 suggest that mechanisms other than
phosphate and PTH regulate FGF23 levels, and careful attention to maintaining normocalcaemia must be
emphasized.
Importantly, our data shows a potential association with 25(OH)D levels, highlighting yet another role of FGF23
in cardiovascular health.
• A positive correlation between serum calcium and FGF23 suggests that the calcaemic effects of activated
vitamin D analogues and calcium-based phosphate binders need to be examined in future randomised
controlled trials.
The effect of 25(OH)D on FGF23 should be investigated to further explore the therapeutic role of 25(OH)D.
Furthermore, additional research is required to examine FGF23-klotho mediated signaling before s-klotho levels
in CKD patients can be accurately interpreted.
• Reference:
• Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease
• Mandy Wan,Colette Smith, Vanita Shah, Ambrose Gullet,
David Wells, Lesley Rees, and Rukshana Shroff
• Nephrol. Dial. Transplant. first published online November 23, 2012 doi:10.1093/ndt/gfs411

Biofeedback dialysis for hypotension and hypervolemia: a systematic review and meta-analysis
Gihad Nesrallah, MD, M.Sc.(c), FRCPC

• Hypotension on dialysis is a major source of patient discomfort, and may
contribute to organ damage and premature death in dialysis patients.
Biofeedback systems may improve blood pressure stability during hemodialysis
by creating a better match between the rate of fluid removal and the
replacement of blood volume from the body's tissues during dialysis.
This systematic review and meta-analysis found that across 8 randomized studies
of biofeedback dialysis, there was a large and consistent improvement in the
frequency of blood pressure drops during dialysis.
• The findings are not altogether unexpected. Several small studies have
suggested improved blood pressure stability with biofeedback for many years.
The consistency of this treatment effect across a number of randomized studies
was not expected, and suggests a true treatment effect.

Biofeedback dialysis for hypotension and hypervolemia: a systematic review and meta-analysis
Gihad Nesrallah, MD, M.Sc.(c), FRCPC
Continued

• Biofeedback dialysis has not received a great deal of attention over the last couple of decades
that it has been in use. Recently, more studies are suggesting that drops in blood pressure carry
harmful effects, including heart and brain injury and loss of residual kidney function.
Clinicians should be mindful of the significant harm associated with hypotension on dialysis, and
the need for strategies to improve hemodynamic stability during dialysis. Biofeedback software
is now available on most commercially available dialysis machines, and clinicians should be aware
of its potential utility in hypotension-prone patients.
study?
• Larger studies with blinding of study participants and outcome adjudicators are needed to
confirm these promising preliminary results, and to further evaluate the effects of biofeedback
on more important patient outcomes, including quality of life, hospitalizations and survival.
• Reference:
• Biofeedback dialysis for hypotension and hypervolemia: a systematic review and meta-analysis.
Nesrallah GE, Suri RS, Guyatt G, Mustafa RA, Walter SD, Lindsay RM, Akl EA.
1Department of Medicine, The University of Western Ontario, London, Canada.
Nephrol Dial Transplant. 2012 Nov 29. [Epub ahead of print]

Association between use of renin-angiotensin system antagonists and mortality
in patients with heart failure and preserved ejection fraction.
Hemodialysis.com Author Interview: Lars H. Lund, MD, PhD,
Associate Professor Dep. of Cardiology, Section for Heart Failure
Karolinska University Hospital, N305 171 76 Stockholm Sweden

• Hemodialysis.com Editor Marie Benz: What are the main findings of the
study?
• In patients with heart failure and preserved ejection fraction, renin-
angiotensin system antagonists (ACE-inhibitors and ARBs) were
associated with reduced mortality.

• The findings wre unexpected in that they were in contrast to previous
negative randomized placebo-controlled trials.
But we believe these trials may have been underpowered and entailed
considerable cross-over to active treatment, and there were signals
toward benefit.
Therefore we hypothesized that in a larger, un-selective population, RAS-
antagonists would in fact be associated with reduced mortality.

Association between use of renin-angiotensin system antagonists and mortality
Hemodialysis.com Author Interview: Lars H. Lund, MD, PhD,
Associate Professor Dep. of Cardiology, Section for Heart Failure
Karolinska University Hospital, N305 171 76 Stockholm Sweden
Continued

• Hemodialysis.com: What should clinicians and patients take away from your
report?
• In patients with heart failure and preserved ejection fraction, RAS-antagonists
may be considered, particularly with concomitant hypertension.

• Hemodialysis.com: What recommendations do you have for future research as a
result of this study?
• Ideally, a large, publicly funded, randomized trial.

• Reference:
• Association between use of renin-angiotensin system antagonists and mortality
Lund LH, Benson L, Dahlström U, Edner M.
Department of Medicine, Unit of Cardiology, Karolinska Institutet, Stockholm,
Sweden
JAMA. 2012 Nov 28;308(20):2108-17. doi: 10.1001/jama.2012.14785.

Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease
Godela M. Fick-Brosnahan MD
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA

• The main finding is that ADPKD patients who had higher uric acid levels at their
study visit had an increased risk of reaching ESRD, independent of gender, body
mass index and renal function (measured by the average of 2 in-hospital
creatinine clearances).
They also had larger kidneys at their visit after adjusting for age, gender and
creatinine clearance, and younger age at onset of hypertension.


• These findings were not entirely unexpected, however the effect of
hyperuricemia on progression had never been studied in ADPKD.
Hyperuricemia has been associated with early onset of hypertension in the
general population, as well as with initiation and progression of chronic kidney
disease.

Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease
Godela M. Fick-Brosnahan MD
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA

• The findings are preliminary since this was a retrospective analysis.
Therefore this article should not change general practice yet.

study?

• An intervention trial of uric acid lowering is needed to examine whether this treatment slows the
progression of ADPKD.
• Reference:

• Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease
• Imed Helal, Kim McFann, Berenice Reed, Xiang-Dong Yan, Robert W. Schrier, and Godela M. Fick-
Brosnahan
• Nephrol. Dial. Transplant. first published online December 4, 2012 doi:10.1093/ndt/gfs417

Temporal Changes in Incidence of Dialysis-Requiring AKI
Hemodialysis.com Author's Interview:
Dr. Hsu, Chi-yuan and Chi-yuan Hsu MD MS
Division of Nephrology, University of California-San Francisco, 521 Parnassus Avenue, C443, Box 0532, San Francisco, CA

• Dr. Raymond Hsu:

• The main finding is that severe cases of acute kidney injury, characterized as an abrupt decline in
kidney function warranting initiation of acute dialysis therapy, are becoming more common in the
United States, rising 10% per year and doubling over the past decade. Total number of in-hospital
deaths associated with severe acute kidney injury more than doubled as well, from 18,000 in
2000 to nearly 39,000 in 2009. (Raymond Hsu)


• Dr. Chi-yuan Hsu:

• We expected to see some rise in the occurrence of severe acute kidney injury, but were surprised
at how rapid the rate of rise was over the past decade.
• We were also somewhat surprised that only about 30% of the increase can be attributed to some
of the commonly known causes of acute kidney injury, such as severe infections, ventilator use,
acute heart failure, and cardiac catheterizations. Therefore, further research is needed to uncover
the causes behind the rapid rise in acute kidney injury.

Temporal Changes in Incidence of Dialysis-Requiring AKI
Hemodialysis.com Author's Interview:
Dr. Hsu, Chi-yuan and Chi-yuan Hsu MD MS
Division of Nephrology, University of California-San Francisco, 521 Parnassus Avenue, C443, Box 0532, San Francisco, CA
Continued

• Dr. Raymond Hsu:

• We hope that clinicians, researchers and the general public can gain a higher appreciation of the devastating impact of acute kidney injury that is
comparable to other forms of acute organ injury, such as heart attack and stroke. Clinicians should pay close attention to identifying patients who
are at risk for acute kidney injury--such as those with underlying chronic kidney disease, hypertension, diabetes, and elderly individuals--and
judiciously manage those patients' fluid status, and reduce exposure to medications and procedures that may be toxic to the kidneys.
• Since individuals with baseline chronic kidney disease are the ones most likely to suffer acute kidney injury, those individuals should discuss
carefully with their doctors the risk and benefits of procedures and interventions which may trigger acute kidney injury. They should
communicate to all their providers such as surgeons or emergency room doctors that they do have underlying chronic kidney disease, so that
appropriate decisions are made regarding procedures and medications in those settings.


• We certainly need more intervention trials on how to prevent acute kidney injury in specific high-risk settings.
• We should also examine whether there are differences in the occurrence of acute kidney injury across geographic areas and different types of
healthcare systems to explore whether practice pattern differences may play a role in triggering acute kidney injury.
• Because the overall incidence is rising, we also need to further study the longterm outcomes in individuals who survive severe acute kidney injury
and investigate strategies to prevent recurrence of acute kidney injury.
•

• Reference:
• Temporal Changes in Incidence of Dialysis-Requiring AKI
Raymond K. Hsu, Charles E. McCulloch, R. Adams Dudley, Lowell J. Lo, and Chi-yuan Hsu
JASN ASN.2012080800; published ahead of print December 6, 2012
doi:10.1681/ASN.2012080800

Hemodialysis.com Author Interviews Dec 6 2012

Hemodialysis.com Author Interviews Dec 6 2012

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Hemodialysis.com Author Interviews Dec 6 2012