Hemodialysis.com ASN 2012 Nephrology Kidney Disease Interviews

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
November 26 2012

For Informational Purposes Only: Not for Specific Medical Advice.

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Long-term effects of daily hemodialysis on vascular access outcomes: A prospective controlled study

Juan Carlos Ayus, M.D., F.A.C.P., F.A.S.N.
Director of Clinical Research
Renal Consultants of Houston
2412 Westgate Street, Houston, TX 77019

• Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

• The study's main findings suggest that daily dialysis is not associated with increased
vascular access complications, or increased vascular access failure rates.

• Hemodialysis.com: Were any of the findings unexpected?

• Yes and no. Yes because we thought that more frequent use of vascular access will
increase the rate of thrombosis of infection. No because our previous finding that
daily dialysis reduces inflammation (JASN 2005, 16:2778-2788) raises the possibility
that reduction of inflammation will improve endothelial function and improve the
lifespan of the vascular access.

• Hemodialysis.com: What should clinicians and patients take away from your report?
• That problems with vascular access should not deter practitioners or patients from
choosing daily dialysis.
• Read the rest of the interview on Hemodialysis.com

Decline in renal functioning is associated with longitudinal decline in global cognitive functioning,
abstract reasoning and verbal memory
Hemodialysis.com Author Interview:
Hemodialysis.com Author Interview: Adam Davey Ph.D


• We found that decreases in kidney functioning over a 5-year period predicted decline
in global cognitive ability as well as in two specific abilities: verbal memory, and
abstract reasoning.


• Decreased kidney function has been associated with longitudinal decline in Global
mental status measures, but we do not know which specific abilities are most
affected. This was the first study describing change in multiple domains of cognitive
functioning in order to determine which specific abilities are most affected in
individuals with impaired renal function.

Protective Effects of Reducing Renal Ischemia-reperfusion Injury During Renal Hilar Clamping: Use of
Allopurinol as a Nephroprotective Agent
Benjamin R. Lee, MD, FACS

• Isoprostane is a prostaglandin compound formed as a result of cellular oxidative damage.
• It is formed in vivo from free radical catalyzed peroxidation of archidonic acid independent of
cyclooxygenase enzyme.
• We studies isoprostane as a marker of damage to the kidney during clamping of the renal artery
and periods of ischemia.
• At 60 minutes was the greatest level of damage to the kidney.
• We then gave Allopurinol, a xanthine oxidase inhibitor, is believed to reduce reperfusion injury by
scavenging free radicals produced during reperfusion of ischemic tissues.
• Xanthine oxidase is a potential source of oxygen-derived free radicals during ischemic- reperfusion
injury.
• In our animal model of reperfusion injury where we had given allopurinol, the levels of isoprostane
returned back to normal control levels, indicating that allopurinol may provide protection to the
kidney during periods of ischemia.

• Yes, for 20 years during kidney cancer surgery, when the tumor is cut out from the kidney, we
temporarily stop the blood flow through the kidney to perform the surgery. Ischemia times greater
than 30 minutes were believed to result in long term damage to the kidney. Prior to clamping of the
renal artery in surgery, we give Furosemide and Mannitol in order to induce a diuresis and prevent
ATN.
• Allopurinol may be a new nephroprotective agent which may represent an additional level of
protection to the kidney.

Albuminuria and Rapid Loss of GFR and Risk of New Hip and Pelvic Fractures
Joshua Barzilay MD
Kaiser Permanente

• We know that bone disease and fracture are co-morbidities that accompany chronic renal disease.

• What has not been examined is the association of albuminuria (an early marker of renal disease) with fracture risk,
especially if the eGFR is preserved (eGFR >60 ml/min/1.73 m2). In this study, which was a re-analysis of the
ONTARGET/TRANSCEND studies, we found that albuminuria (>30 mg/g creatinine) (1.35 [95% CI 1.00, 1.82], p=.048) ,
and especially proteinuria (>299 mg/g) (1.71 (1.01-2.91),p= 0.047), are associated with an increased risk of new hip and
pelvic fractures, independent of a low eGFR status (<60 ml/min/1.73 m2).

We also found that a rapid decline in eGFR (>5%/year) was a statistically-significant risk factor for fracture risk over 2.5
years of follow up (osteoporosis-risk-adjusted HR 1.47 (1.05, 2.04), p= 0.02) in a model which accounted for baseline
albuminuria and change in albuminuria over the course of follow up.
• These findings were not unexpected. The microvascular circulation plays an important role in bone health and
physiology. In adult bone formation, endothelial cells from capillaries at sites of bone remodeling release factors
associated with mineralization and the coupling of osteoclast and osteoblast function.

Albuminuria is a marker of perturbed microvascular function and of oxidative stress.

We posit that rapid loss of eGFR/ year is also an indicator of microvascular disease. Given these inimical effects of
albuminuria, and the extensive microvasculature in bone, that bone disease (as measured by fracture risk) can be a
consequence of early markers of kidney disease.

Erythrocyte and reticulocyte indices in the assessment of erythropoiesis activity and iron availability
Eloísa Urrechaga, PhD
Clinical Analysis Consultant
Hospital Galdakao Usansolo
48960 Galdakao, Vizcaya Spain

• Hemodialysis.com Author Interview: What is the background for your study?
• Anemia is one of the most characteristic manifestations of CKD. The most important question regarding anemia
therapy in these patients is which are the best Laboratory parameters to assess the iron available for
erythropoiesis; the need for predictors and indicators of effectiveness has not abated.

The modern hematological parameters contribute to the advanced study of the anemia but depend on the technology
applied and which analyzer the Laboratory is employing.

Direct consequence of an imbalance between the erythroid marrow iron requirements and the actual supply is a
reduction of red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. Reticulocyte
hemoglobin content (CHr) and the percentage of hypochromic red blood cells (%Hypo) reflect iron availability and are
reliable markers of functional iron deficiency, are incorporated to National Kidney Foundation (NKF-K/DOQI) guidelines
for the monitoring of recombinant human erythropoietin rHuEPO therapy. Since recently the measurement of CHr and
%Hypo has been restricted to the analysers of a single manufacturer, Siemens (Siemens Medical Solutions
Diagnostics, Tarrytown N.Y, USA).

The debate about other parameters with the same clinical meaning and potential utility as CHr and %Hypo reported by
Siemens analyzers is open. Actually there are other choices (CellDyn Sapphire, Abbott Diagnostics, Santa Clara, Ca
USA; Sysmex XE 5000, Sysmex Corporation, Kobe, Japan).

The Symex XE 5000 analyzer reports reticulocyte hemoglobin equivalent (Ret He) and the so-called RBC extended
parameters, percentages of erythrocyte subsets so percentages of hypochromic red cells are mearured (%Hypo He).

The aim of the present work was to establish the sensitivity and specificity of the reticulocyte and erythrocyte
parameters reported by the Sysmex XE 5000 analyzer in the evaluation of erythropiesis activity and iron availability;
the investigation concerned patient with iron deficiency, uremia and patients in dialysis.

Altered Taste Perception and Nutritional Status Among Hemodialysis Patients
Steven M. Brunelli, MD, MSCE
Harvard Medical School, Boston, Massachusetts
Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Katherine E. Lynch MD
Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Harvard Medical School, Boston, Massachusetts

• The main findings of the study are alterations in taste as reported by patients are associated with
worse nutritional status and increased mortality as compared to normal taste perception.

• We were surprised that the effects of taste appeared to be independent of appetite.

In fact, the effects of altered taste were essentially identical among patients who had normal and
sub-adequate appetites.
• Altered taste perception is a frequent finding among chronic hemodialysis patients.

Hemodialysis patients with taste alteration are at higher risk for nutritional compromise.

Clinicians should consider asking about taste when assessing nutritional status of hemodialysis
patients.


Role of Nutrition Impact Symptoms in Predicting Nutritional Status and Clinical Outcome in
Hemodialysis Patients: A Potential Screening Tool
lHemodialysis.com Author Interview: Katrina Campbell PhD AdvAPD
Senior Research Fellow | Princess Alexandra Hospital Nutrition & Dietetics Department Brisbane,
Queensland, Australia


• This study identified that the simple assessment of nutrition impact symptoms is effective in
identifying patients who are likely to be at risk of malnutrition and/or experience decline in nutrition
status and clinical outcomes in the following 6 to 12 months.

This simple assessment is therefore presented as an alternative screening tool, providing a trigger
warranting further assessment and nutrition intervention.

This tool is advantageous as it does not require any objective measurements, including
anthropometry or biochemistry results and can be undertaken by any of the healthcare team.


• We found the simple question of nutrition impact symptoms outperformed the more comprehensive
assessment, which was not anticipated.

What is great about this tool is it is simply formalizing typical questions asked by many of the
healthcare team, thereby likely to be straightforward when implementing into practice.

Read the rest of the interview on Hemodialysis.com

Phosphate handling in CKD-MBD from stage 3 to dialysis and the three strengths
of lanthanum carbonate

Mario Cozzolino, MD, PhD

• This is a review paper in which we considered the following points:
• 1. Serum phosphate levels are associated with unfavorable
outcomes in the general population, chronic kidney disease (CKD), and end-stage renal disease
(ESRD).
• 2.Hyperphosphatemia is a late phenomenon in the natural history of CKD and insensible phosphate
overload may prompt the beginning of CKD-mineral bone disorder (MBD) in normophosphatemic
subjects.
• 3) Fibroblast Growth Factor 23 (FGF23) may represent an early biomarker of phosphate load in
predialysis patients or even an effector in CKD-MBD process.

• 4) Tubular resorption of phosphate has been purposed as
a surrogate marker of the activation of FGF23 cascade.

• 5) Phosphate load proceeds together with protein intake:
low protein diet in predialysis patients favors a better
control of phosphate intake while the recommended
high protein diet exposes dialysis patients to a considerable risk of phosphorus overload.


Combination hemodialysis and centrifugal therapeutic plasma exchange:
18 years of Canadian experience.

• Combining hemodialysis and TPE is an efficient method of providing these treatments, when
needed.

The combination therapy reduces staff requirements and reduces patient treatment time.

• Not at all. We had no indication that the combination treatment as done in our unit reduced the
therapeutic benefit of the individual treatments.

• A carefully designed extracorporeal circuit and trained staff can provide a safe and effective
combination therapy without any added risk to the patient and no reduction in therapeutic efficacy.


Protocol adherence and the progression of cardiovascular calcification in the ADVANCE study
Dr. Pablo A. Ureña-Torres
Clinique du Landy, Saint Ouen, France

• Hemodialysis.com Editor Marie Benz: What are the main findings of the
study?

• The main findings of this study, which is a post-hoc analysis of the
ADVANCE study, are that the annual progression (expressed as the
median percentage change) of the calcification score (Agatston) of
coronary artery is less in hemodialysis patients with secondary
hyperparathyroidism treated by cinacalcet and respecting the prescription
of low doses of active vitamin D (< 6 mcg/week paricalcitol equivalent),
compared with the control group, 17.8% versus 31.3%, respectively.

They also show that Agatston calcification score of aortic valve progress
much lesser in the cinacalcet treated patients than in control (6.0% versus
51.1%).

An angiotensin II receptor blocker-calcium channel blocker combination prevents cardiovascular events
in elderly high-risk hypertensive patients with chronic kidney disease better than high-dose angiotensin
II receptor blockade alone

Shokei Kim-Mitsuyama

• (Answer)
The main finding of the study is that angiotensin II receptor blocker (ARB) plus calcium channel
blocker (CCB) combination is more beneficial in prevention of cardiovascular (CV) events in elderly
high-risk hypertensive patients with chronic kidney disease (CKD) compared with up-titration of
ARB (high-dose ARB alone).
• (Answer)
Up-titration of ARB is demonstrated to lead to more reduction of urinary albumin and protein
excretions in patients with CKD. However, there is no report as to whether up-titration of ARB
exerts more benefit in prevention of CV events in patients with CKD. In contrast to more benefit of
high-dose ARB therapy in suppression of CKD, the present result showed that the prevention of CV
event was less in high-dose ARB therapy than in ARB+CCB combination.
• (Answer)
• Clinicians and patients should know that strict blood pressure control by ARB+CCB combination is
useful for the prevention of CV diseases in elderly hypertensive patients.

Clinical effects of buttonhole cannulation method on hemodialysis patients.
Mi- Kyoung Kim RN., Ph.D.
Hee- Seung Kim RN., Ph.D.


• The buttonhole method shortened hemostasis time, decreased cannulation pain and
nurse's stress compared to the rope-ladder method.

• There was not an unexpected fact from this research.

• The buttonhole cannulation method improves hemostasis time, cannulation pain, and
nurses' stress without change of vascular access bood flow rate and dialysis
adequacy in HD patients.


Associations of kidney disease measures with mortality and end-stage renal disease in individuals with
and without hypertension: a meta-analysis

Professor Josef Coresh, MD, PhD, MHS and
Bakhtawar K Mahmoodi MD PhD

• This meta-analysis of more than one million participants from 45 studies shows that the presence
of chronic kidney disease (CKD), measured by low kidney function or elevated protein in the urine,
is an important risk factor for mortality and kidney failure, regardless of whether an individual has
hypertension.

Whereas the association of CKD measures with kidney failure was similar in hypertensives versus
non-hypertensives, the association of CKD with both mortality outcomes was stronger in non-
hypertensives.

Prior to this study the importance of CKD in the presence of hypertension was well studied, but the
importance of mild to moderate CKD in the absence of hypertension was questionable.

Risk assessment in a single study of subjects with CKD without hypertension is hampered by the
strong coexistence of CKD with hypertension, leaving insufficient numbers of individuals with only
CKD without hypertension.

By pooling multiple studies together, we were able to have sufficient numbers of non-hypertensive
individuals with CKD.


Activity of Daily Living Disability and Dialysis Mortality: Better Prediction Using Metrics of Aging
Mara McAdams DeMarco, PhD


• We studied 143 patients undergoing dialysis, all recruited from a dialysis center in Baltimore
between January 2009 and March 2010. They were followed until Nov. 15, 2011. There were 33
deaths during the study period, and the risk of death did not vary with age.

• The prevalence of disability in the activities of daily living of kidney failure patients of all ages -- 41
percent in this study – is strikingly higher than in older adults in the community at-large (5 to 8.1
percent of non-institutionalized adults over age 65).
• Those who needed assistance with one or more basic activities of daily living -- feeding, dressing,
walking, grooming, using a toilet and bathing -- were more than three times more likely to die than
their more independent counterparts.

• The findings were not completely unexpected. Needing assistance with basic activities of daily
living has been well documented in the geriatrics field as a predictor of adverse outcomes. We
extended these findings to patients on dialysis of all ages.


Chronic kidney disease alters intestinal microbial flora
N.D. Vaziri M.D., MACP
Professor of Medicine, Physiology and Biophysics Division of Nephrology and Hypertension
Schools of Medicine & Biological Sciences University of California, Irvine

• Response: The enormous community of microbes that resides in the intestinal tract (microbiome)
constitutes a symbiotic ecosystem which provides protection against invasion by pathogenic
organisms and contributes to nutritional balance by facilitating absorption of complex
carbohydrates, and production of amino acids and various micronutrients including vitamin K, and
group B vitamins. The integrity and proper function of the gut microbiome is essential for health
and alteration in the composition or function of the microbiome is associated with various illnesses
such as inflammatory bowel disease, diabetes, cardiovascular diseases, cancer, obesity, chronic
inflammation, lipid disorders, and allergic disorders.
Biochemical milieu plays a decisive role in shaping the composition and function of the
microbiome. Renal failure results in marked alteration of the biochemical environment of the
gastrointestinal tract. For instance, accumulation of urea in the body fluids of patients with renal
failure leads to its heavy influx into the gastro-intestinal tract where its hydrolysis by microbial
urease produces large quantities of ammonia [CO(NH2)2 +H2O à CO2+2NH3] Ammonia is, in turn,
converted to ammonium hydroxide [NH3 + H2OàNH4OH] (the main ingredient of the window
cleaning liquids) which elevates the gut‟s luminal pH and causes mucosal irritation In addition
significant amounts of uric acid and oxalate are secreted in the colon in an adaptive response to
the loss of their renal excretion. Besides altering the biochemical milieu of the intestinal lumen,
introduction of massive quantities of urea and uric acid can serve as a source of nutrient for the gut
microbial flora and accommodate domination of microbes capable of utilizing these substrates.
Finally the dietary and medicinal interventions commonly used in the tre.atment of CKD patients
can significantly impact the biochemical milieu of the gastrointestinal tract


Administered paricalcitol dose and survival in hemodialysis patients:
A marginal structural model analysis
Kamyar Kalantar-Zadeh, MD, MPH, PHD
Professor & Chief Div. of Nephrology & Hypertension
University of California Irvine, School of Medicine
Miklos Zsolt Molnar, MD, PhD
Research AssociatLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

• Higher doses of injectable paricalcitol (≥10 µg/week) appears causally associated with greater
survival as compared to lower doses (<10 µg/week ) in a contemporary cohort of more than 15,000
maintenance hemodialysis patients across the US.

• In the conventional and propensity scored matched survival models, low dose paricalcitol showed
no difference compared to high dose.

However, compared to high dose of paricalcitol, low dose was associated with a 26% higher risk of
in the so-called causal models, aka “marginal structural model”.
• In our large and contemporary cohort of more than 15,000 maintenance hemodialysis patients,
higher dose of paricalcitol appeared causally associated with greater survival.

The association between dose of paricalcitol and mortality was robust across different subgroups
of patients.


Quality of life among women with sexual dysfunction undergoing hemodialysis: a cross-sectional
observational study.
Hemodialysis.com Author Interview: Paulo Santos MD, PhD
Universidade Federal do Ceará · Faculdade de Medicina

Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

• A very high prevalence of sexual dysfunction among women undergoing regular hemodialysis, with
a low mean age of 38.9 years, with physical functioning being the main quality of life domain
affected among women with sexual dysfunction.

Physical functioning was lower among women with sexual dysfunction, and also physical
functioning and sexual function scores were positively correlated.


• Yes. First, there are data in the literature showing no association of female sexual dysfunction with
quality of life. Instead, we found the main association of sexual dysfunction with physical
functioning, as well as with social activities, as assessed by SF-36. Second, based on our previous
study comprising men with erectile dysfunction [1], we expected an association of female sexual
dysfunction with mental health.
However, there was no significant difference in mental health among women with and without
sexual dysfunction.


Determinants and Consequences of Adherence to the Dietary Approaches to Stop Hypertension Diet in
African-American and White Adults with High Blood Pressure: Results from the ENCORE Trial

James A. Blumenthal, PhD, Professor of Behavioral Medicine in the Department of Psychiatry and Behavioral
Sciences at Duke University Medical Center in Durham, NC.

• The main findings of this study were that greater adherence to the DASH eating plan was
associated with larger reductions in blood pressure, independent of weight loss or improved
aerobic fitness; also, we observed that ethnicity was the only significant predictor of adherence to
the DASH diet, with African Americans generally less adherent compared to their white
counterparts.
• The findings were unexpected--actually, we has assumed that psychological factors would allow us
to predict who would be most adherent--but none of the psychological factors that we measured
turned out to predict adherence in our ENCORE study.

African Americans actually started out with lower DASH adherence scores compared to whites, and
the African Americans assigned to the two DASH groups (DASH-alone and DASH+Weight
Management) significantly increased their consumption of DASH friendly foods--such as fruits,
vegetables and low fat dairy products, but they still did not reach the same levels of DASH
adherence as the white participants.


Targeted complement inhibition as a promising strategy for preventing inflammatory
complications in hemodialysis

John D. Lambris, Ph.D., and Robert A. DeAngelis, Ph.D.

• Our review was influenced by our recent study published in Blood (vol. 116: 631-9) demonstrating
that biomaterials used in hemodialysis in patients with end-stage renal disease (ESRD), especially
the polysufone fibers used in many hemodialysis filters, are capable of inducing activation of the
complement cascade and generation of the anaphylatoxin C5a, which can promote tissue factor
production and procoagulant activity by polymorphonuclear cells (neutrophils) in the blood.

Importantly, treatment with compstatin, a small peptide inhibitor of complement that acts upstream
of C5a generation, was able to prevent or significantly reduce the activation of neutrophils, their
production of tissue factor, and their procoagulant activity normally induced by blood circulation
through an extracorporeal circuit (similar to that used in hemodialysis).

Compstatin treatment also reduced the production of the pro-inflammatory cytokines IFN-γ, IL-1RA
and G-CSF by neutrophils.

These results suggest that inhibiting complement activation can reduce the tissue factor-dependent
procoagulant activity of polymorphonuclear cells during hemodialysis, as well as the production of
pro-inflammatory cytokines, which can contribute to thrombosis and other complications.


The Effects of High-Load Strength Training With Protein- or Nonprotein-Containing Nutritional
Supplementation in Patients Undergoing Dialysis

Stig Molsted, Ph.d., post doc Kardiologisk, Nefrologisk & Endokrinologisk


• A main finding of our study of high load strength training in patients undergoing
dialysis was that the patients achieved an increase in physical function tested objectively and also
assessed by the patients themselves. We think that it is an important result that the patients also
reported this increase, since this may be a motivational factor toward staying physical active.

The improved physical function was a result of a massive effect on muscle strength and muscle
power. Especially muscle power is important since it is tested as dynamic movements which is
related to activities in daily living.

As expected we saw a decrease in the number of type 2X muscle fibres. This result may have
clinical implications in terms of higher insulin sensitivity, since type 2X muscle fibres have lower
insulin sensitivity compared to type 1 and 2A muscle fibres.
• Finally, we find it important to report that we saw no side effects and that the included patients
were able to conduct a relative demanding kind of exercise


Factors in Career Choice among US Nephrologists
Julie Lin, MD, MPH, FASN
Associate Physician


• WE OBSERVED A NUMBER OF IMPORTANT DIFFERENCES BETWEEN NEPHROLOGISTS WHO
CHOSE ACADEMIC CAREERS COMPARED TO THOSE WHO DID NOT, NAMELY AN EARLY
INTEREST IN RENAL RESEARCH AND RESEARCH MENTORSHIP.

ALSO, THE DEMOGRAPHICS OF U.S. NEPHROLOGISTS HAS BEEN CHANGING OVER TIME WITH
AN INCREASE IN THE PROPORTION OF WOMEN AND INTERNATIONAL MEDICAL GRADUATES IN
RECENT YEARS.

• THE FINDINGS WERE CONSISTENT WITH WHAT WE HAD EXPECTED.

• THIS STUDY IS MOST RELEVANT FOR MEDICAL EDUCATORS AND ACADEMIC FACULTY RATHER
THAN CLINICIANS OR PATIENTS.

THE REPORT SUGGESTS THAT EARLIER EXPOSURE TO NEPHROLOGY WITH ACTIVE AND
POSITIVE MENTORING BOTH CLINICALLY AND IN RESEARCH PROJECTS ARE KEY
COMPONENTS IN ATTRACTING AND RETAINING FUTURE NEPHROLOGISTS IN THE FACE OF OUR
ANTICIPATED WORKFORCE SHORTAGE.

Hemoglobin A1c Levels and Mortality in the Diabetic Hemodialysis Population: Findings from the
Dialysis Outcomes and Practice Patterns Study (DOPPS)
Sylvia Ramirez, MD, MPH, MBA, FASN
Vice-President, Global Research and Development
Arbor Research Collaborative for Health
Ann Arbor, Michigan USA

• 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
particularly among patients with kidney disease, because of the association with increased risk of
heart disease, peripheral vascular disease (such as amputation), and other
complications. However, studies on the management of diabetes in patients with ESRD are limited,
and current Clinical Practice Guidelines are based on studies in the non-kidney failure population
and evidence for dialysis patients is unclear.
• Hemoglobin A1c levels (HbA1) are 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.

A New Approach for Measuring Gender Disparity in Access to Renal Transplantation Waiting Lists
Dr Cécile COUCHOUD Coordination nationale de REIN Agence de la biomédecine
1 avenue du Stade de France 93212 SAINT DENIS LA PLAINE CEDEX FRANCE

• After taking potential confounders into account (age, work status, and 11 comorbidities or
disabilities), our study shows that women starting dialysis have a lower probability of being
registered on the national transplant waiting list (OR =0.69, 95%CI 0.62-0.78) and a longer time from
dialysis start to registration (HR 0.89, 95%CI 0.84-0.95) than men.

This disparity affects predominantly older nonworking and diabetic women and is more
pronounced in some zones than in others.
• Among non-medical factors influencing access to renal transplantation, gender inequity, favoring
men, has been regularly found in US data analyses.

Because in the US patients must have a source of funding for transplantation before being listed,
lower access to the transplant waiting list might be due to a problem of affordability.

Because the national health insurance system covers the entire population in France, access to
transplantation should not be limited by poverty, and there is no reason it should disadvantage
women. Two previous investigations France found no association between gender and access to
transplantation.

Evaluation of immature hemodialysis arteriovenous fistulas based on 3-French retrograde
micropuncture of brachial artery
Scott O. Trerotola, BA, MD


• Diagnostic imaging of immature hemodialysis arteriovenous fistulas (AVF) performed via a 3-
French retrograde puncture of the brachial artery is safe and reveals the fistula‟s arterial and
venous anatomy in its physiologic state.

• Yes, we found a much higher than expected incidence of venous spasm (40%) at the site of
venipuncture for intervention.

This has important implications for the study of immature AVF.

• The ability to image a fistula in its undisturbed state, before venous puncture causes spasm or
other disturbances is a key benefit of 3F arterial micropuncture fistulography.

Indeed, for this reason, it is becoming the standard of care in imaging immature AVF.


Transplantation rates for living- but not deceased-donor kidneys vary with
socioeconomic status in Australia
Blair Grace PhD ANZDATA Registry
North Wing, Royal Adelaide Hospital North Terrace, Adelaide, 5000


• Patients who receive renal replacement therapy in Australia are more likely to receive a living-donor
transplant if they live in advantaged areas (those with overall higher income, more education and
higher levels of employment).

This was most pronounced for pre-emptive transplants. Socio-economic status was not associated
with deceased-donor transplantation.

All Australians have access to subsidized healthcare.

• Yes, we expected to find an association between socio-economic status and deceased-donor
transplantation.

Patients from advantaged areas are more likely to receive a deceased-donor kidney in several other
countries, including England, which also provides universal access to healthcare.


Assessment of Management Policies and Practices for Occupational Exposure to Bloodborne
Pathogens in Dialysis Facilities

Chukwuma Mbaeyi BDS (DDS), MPH

• We conducted a survey of randomly selected outpatient dialysis centers nationally and found that
nearly all centers had written policies for managing bloodborne pathogen exposures among
healthcare personnel.

Ninety-five percent of centers provided occupational exposure management services during the
daytime on weekdays, but services were not consistently provided on weekday nights and
weekends.

Overall, 10 – 15% of centers reported having personnel with occupational exposures to hepatitis B
virus, hepatitis C virus and human immunodeficiency virus (HIV) in the 12 months prior to the
survey.

Hospital-based and not-for-profit dialysis facilities were more likely to report having staff with
occupational exposures to bloodborne pathogens relative to free-standing and for-profit dialysis
facilities.

They were also more likely to provide hepatitis B virus postexposure prophylaxis and have a
preselected primary HIV postexposure prophylaxis regimen compared with free-standing and for-
profit facilities.

Effects of Phosphate Binders in Moderate CKD
Dr. Geoffrey A. Block MD CCRI
Director of Clinical Research at Denver Nephrology

Hemodialysis.com Editor Marie Benz: What are the main findings of the study?
• I believe this study has several important findings, some of which were quite unexpected.
• Our results demonstrate the importance of having placebo controls in clinical trials with Phosphate
binders. While many in the community view these drugs as „safe‟ or „benign‟ our study highlights
that there is the potential for harm associated with these medications. Some in the community
have even suggested that placebo controls are „unethical‟ in trial designs of elevated phosphorus
on the basis of observational data; however our trial reinforces that while lowering Phosphorus
may indeed be a worthy goal- that does not mean that drugs used to lower serum Phosphorus are
not associated with potential harm above and beyond the risks associated with serum Phosphorus
itself.

• Our data support the conclusion that the use of Phosphate binders in CKD may be associated with
harm and that the universal practice of giving these patients calcium containing Phosphate binders
in particular is associated with a host of unfavorable effects including: reductions in 1,25D,
increases in intact FGF23, and accelerated calcification among patients who are calcified.

All of this while having only modest effects on serum Phosphorus levels. There was an increase in
bone mineral density among calcium treated patients and the trial was not powered to specifically
address differences in outcomes among sub-groups of Phosphate binder categories.
The trial reinforces that there is much to learn about phosphorus physiology!

Preexisting Venous Calcification Prior to Dialysis Vascular Access Surgery
Timmy Lee, M.D., M.S.P.H., F.A.C.P., F.A.S.N.


• Our main findings are that calcification is present in about 1/3 of veins used to create new vascular
access, and among those with calcification, calcification was present predominately in the media
and intima layers of the vein.


• While there are several studies showing calcification in CKD and ESRD patients in lower extremity
arteries in vessels used to create arteriovenous acces, our study is one of the first to show
calcification in veins of advanced CKD patients.


• Our study shows that their are different vascular injuries that can occur prior to creation of an
arteriovenous access as part of the CKD process, and venous calcification is one important factor
that may play an important role in arteriovenous fistula maturation failure.


Is early virological response as predictive of the hepatitis C treatment
response in dialysis patients as in non-uremic patients?

• Hemodialysis.com Author Interview: Patricia da Silva Fucuta Pereira
Hepatitis Section, Division of Gastroenterology,
Federal University of Sao Paulo, Rua Botucatu
• Division of Gastroenterology, Hepatitis Section, Federal University of São Paulo, São Paulo, Brazil.
• Hemodialysis.com: What are the main findings of the study?
• The main finding of this study was to determine a stopping rule for antiviral treatment with
interferon in hemodialysis patients with hepatitis C.

The analysis at week 12 avoids unnecessary treatment in non-responder patients preventing
additional side effects.

Furthermore, determining stopping rules is extremely important for kidney transplant candidates
because transplantation is delayed during interferon treatment.
• The few previous studies on this issue have suggested that the patients who did not respond to
interferon during the first months of treatment did not reach sustained virological response.

The present study supported these data and could demonstrate that week 12 analysis had a
negative predictive value of 100%.


Advanced age affects the outcome-predictive power of RIFLE
classification in geriatric patients with acute kidney injury
Ming-Shiou Wu, Division of Nephrology, Department of Internal Medicine, National Taiwan
University Hospital

• What are the main findings of the study?

• Our study is the first one to demonstrate the effects of aging on the use of the RIFLE
classification in the prediction of in-hospital mortality in geriatric postoperative acute kidney
injury (AKI). A less severe categorization of AKI per RIFLE classification may not truly reflect
the adverse effects of AKI in elderly patients.

• In patients≦76-years of age, RIFLE-R, -I, or –F AKI classifications were able to significantly
predict increasingly worse outcomes.

• However, the predictive efficacy between patients with RIFLE-R and RIFLE-I AKI
disappeared in those > 76-years of age.
• the training had a high or good impact and relevance to the needs of their home institution
or country.


Training Nephrologists From Developing Countries: does it have a positive
impact?
David CH Harris MD

• One of the global outreach efforts of the International Society of Nephrology (ISN) is its
Fellowship Program, which since the mid 1980’s has sponsored nephrology training of
almost 600 young nephrologists or trainees from over 80 developing nations.

• Data from the past decade were obtained from a survey sent to 329 fellows with a survey
return rate of 70%, and compared to data from prior periods.

• An important objective of the program is to ensure that fellowships are of value to the home
unit and country, and not just to the fellow, while avoiding a ‘brain-drain’ of fellows to
developed countries.

• In the last decade more than 90% of fellows returned to their home units, and this
percentage has been increasing steadily. 90% of fellows reported that the training had a
high or good impact and relevance to the needs of their home institution or country.


Association of High Blood Pressure with Renal Insufficiency: Role of Albuminuria from NHANES,
1999-2006

Qi Dai, M.D., Ph.D.


• We found that association between high blood pressure and reduced renal function was
modified by albuminuria status among healthy participants without diabetes, CKD or
cardiovascular disease, using data from the National Health and Nutrition Examination
Survey (NHANES) 1999-2006, a population-based study conducted in the general US
population.

• Overall, we found a moderate association between high blood pressure and renal function
insufficiency in all participants analyzed. However, no association between hypertension
and renal insufficiency was observed among those without albuminuria in this population.

• On the other hand, among participants with albuminuria ACR≥30mg/g), the prevalence of
moderate-severe renal insufficiency substantially and progressively increased from normal
subjects to prehypertensive and undiagnosed hypertensive subjects.


Randomized Controlled Trial of Cholecalciferol Suplementation in
CKD Patients with Hypovitaminosis
Author Interview on Hemodialysis.com
Peter Marckmann, MDp


• The study showed that vitamin D supplementation of predialysis patients has a favorable
effect on their bone metabolism raising their level of endogenously produced actived vitamin
D (1,25-diOHD) and lowering PTH. In HD patients, this effect was absent.

• We searched for favorable pleiotropic effects of vitamin D supplementation, but could not
demonstrate such effects which is in contrast to some earlier, smaller and uncontrolled
studies.

• As an important side effect, mild hypercalcemia developed in 20% of the actively treated
patients, demonstrating that calcium must be monitored with high-dose vitamin D
supplementation.
• It was surprising that none of a number of putative pleiotropic effects could not be
demonstrated, and that hypercalcemia was a problem despite vitamin D dosing within the
recommend range.


Author Interview: Kate Ellingson, PhD,Epidemiologist

Vascular access hemorrhages contribute to deaths among hemodialysis patients

Kidney International , (13 June 2012)

• This study describes fatal instances of vascular access hemorrhage among chronic dialysis
patients and is the first study to examine risk factors for this devastating complication.

• In order to receive life-saving hemodialysis treatment, patients require a
catheter, arteriovenous (AV) fistula, or AV graft. These three types of vascular access are a
way to reach the bloodstream in order to remove toxins from the blood.

• Unfortunately, in rare instances, a problem with the vascular access can cause the site to
rupture and bleed uncontrollably, in some cases, resulting in death. These fatal instances of
vascular access hemorrhage constitute a rare but potentially preventable cause of death in
hemodialysis patients.

• The majority of the 88 events reviewed between 2000-2007 in Maryland, District of
Columbia and Virginia involved patients who experienced major hemorrhages at home or in
a nursing home, and the majority of these patients had experienced complications of their
vascular access in the six months prior to death.


Author Interview:
Odds of Missed Hemodialysis Sessions Are Increased
During Holiday Periods Among In-Center Hemodialysis Patients

Stephen Crawford ISPOR poster 2012

What are the main findings of the study?
•
•
•
•
•
•
• The data suggest that there was an increasing trend in the proportion of missed
sessions from 2006 to 2010, particularly during the Thanksgiving and Christmas
holiday travel periods.
•
•
•
•

Author Interview:

Antibiotic lock solutions allow less systemic antibiotic exposure and less catheter malfunction without
adversely affecting antimicrobial resistance patterns. Hemodialysis International.
A. M. Onder, MD

• We looked at our data by breaking the timeline into three separate periods; no antibiotic lock
(ABL) use, ABL use as needed and ABL use per protocol in the unit.

• By looking at our 10 years retrospective data, we were able to demonstrate that the use of
antibiotic locks (mainly tobramycin-tissue plasminogen activator (TPA) locks) as protocol in
our unit, there was a significant decrease in total systemic antibiotic exposure and the
percentage of catheters lost to malfunction.

• This was achieved with similar CRB prevalence between the three ERAs and there was no
noted increase in the infection-related complications.

• Therefore, addendum of ABL to systemic antibiotics for treatment and using them for
prevention in the high risk population offered similar CRB treatment success rates with less
exposure to cumulative dose of systemic antibiotics.


Author Interview:

Pregnancy in CKD: whom should we follow and why?
Barbara Giorgina Piccoli MD


• CKD is a risk factor in pregnancy in all stages. Also stage 1 CKD patients are at increased risk for
adverse pregnancy outcomes, such as Caesarean section, preterm delivery and need for NICU (Neonatal
Intensive Care Unit). The risk for adverse pregnancy related events increases along with the CKD stage.
• Pregnancy is a important occasion for early diagnosis of CKD in stage 1 patients. In our series the
prevalence of new diagnosis was high (over 40%).

• In this study, our analysis was focused on CKD stage 1 patients, both in comparison with a cohort of 267
low-risk pregnancies, and with 49 patients in later CKD stages.

• At difference with our previous study, in which the results recorded in stage 1 and stage 2 CKD were almost
equal, the stepwise increase along stages is more clear and statistical difference is reached between stage
1 and 2 CKD as for birth weight and gestational age.

• Therefore, even minor differences in kidney function (stage 2 vs stage 1) increase the risk for adverse
pregnancy related outcomes.


Author Interview:
Comparing the association of GFR estimated by the CKD-EPI and MDRD study equations and
mortality: the third national health and nutrition examination survey (NHANES III) examination
survey (NHANES III).
Tariq Shafi, MBBS, MHS, FACP, FASN, FNKF


• The Chronic Kidney Disease Epidemiology Collaboration equation for estimation of glomerular filtration rate (eGFR-CKDEPI)
improves GFR estimation from serum creatinine compared to the Modification of Diet in Renal Disease Study equation (eGFR-
MDRD). We wanted to assess if this improvement in GFR estimation translates into better prediction of the risk of death among
those with reduced eGFR.

• We first categorized the population into five eGFR groups based on the current standard which is eGFR-MDRD. The
eGFR groups were >120, 90-119, 60-89, 30-59 and <30 ml/min/1.73 m2. We then calculated eGFR-CKDEPI and re-categorized
the population using the same cut-offs but basing it on eGFR-CKDEPI instead of eGFR-MDRD.

• We found that by using eGFR-CKDEPI compared with eGFR-MDRD, 26.9% of the US population will be reclassified into higher
eGFR categories and 2.2% will be reclassified to lower eGFR categories. Our next goal was to determine the effect of this
reclassification on the risk of death from any cause and death from cardiovascular disease (CVD).

• When we looked at those with eGFR-MDRD 30-59 ml/min/1.73 m2, we found that 19.4% of this population was reclassified to a
higher eGFR-CKDEPI category and these individuals had a lower risk of death; 47% lower risk of death from any cause and 49%
lower risk of death from CVD. We then looked at those with eGFR-MDRD >60 ml/min/1.73 m2. In this group, 0.5% were
reclassified to lower eGFR-CKDEPI and these individuals had a higher risk of death; 31% higher risk of death from any cause and
42% higher risk of death from CVD.

• So, in summary, we found that categorizing individuals based on eGFR-CKDEPI improves risk prediction compared with
categorization based on eGFR-MDRD.


Author Interview:
Anorexia nervosa and the kidney
Drs. Pierre Delanaye and Antoine Bouquegneau


• AN and eating disorders are frequent and affect a young population.

• Kidney diseases are very frequent and various in these patients: CKD, AKI, lithiasis and electrolytes
disturbance.
• However, all these kidney injuries are underestimated.

• When we did the literature review for this paper, we noticed that the prevalence of eating disorders is blurry.

• This is due to the different definitions of these disorders used by the physicians. Also, it is difficult to
diagnose CKD in patients with eating disorders. The frequency and the mechanics of kidney disturbances
are neither up to date, nor fully understood.

• Once again, it seems that this type of patients is somewhat neglected.


Author Interview:
A Cause Analysis of Absence of Functional Arterio-Venous (AV)
Access in a Prevalent Hemodialysis Patients Cohort
Drs. Mireille El TersM.D and Marie Hogan M.D. Ph.D


• We found in this study a strong and independent association between PICC use and lack of a functioning AVF and this
association persisted after adjustment for confounders, including upper-extremity vein and artery diameters, sex, and history of
central venous catheter.
• We also found that PICC use is common among our end stage renal disease (ESRD) population evaluated (30% of our studied
hemodialysis patients) with 54% of these placed after dialysis therapy initiation.


• We hypothesized that prior history of PICC is associated with a higher likelihood of lack of functioning arterio-venous fistula (AVF)
by way of venous injury, such as venous thrombosis and stenosis.

• So the finding of a strong and independent association between prior PICC use and a lack of functioning AVF was not
unexpected.

• We were however surprised by the high proportion of ESRD patients receiving a PICC (30%),especially that the majority occurred
after initiation of dialysis (54%).

• It is worthy to note that the most common indication for PICC in our population was antibiotic use,which could arguably be
administered during hemodialysis and thus sparing the patient the need for a PICC line placement.


Author Interview:
Urolithiasis and the Risk of ESRD
CJASN
Ziad M. El-Zoghby, M.D.


• In this large population-based study, we found that symptomatic stone formers are at increased risk of
developing end-stage renal disease (ESRD) compared to matched controls.

• The mechanism of renal failure in stone former appears to be related to their kidney stones and related
urological co-morbidities and procedures, rather than other risk factors known to cause ESRD
(hypertension, diabetes, etc.) that are commonly found in stone formers.


• We previously reported that stone formers have an increased risk of chronic kidney disease (CKD). Hence
it is not surprising that they also have an increased risk of ESRD.
• Furthermore, our new finding that certain urologic conditions which predispose to stone disease (i.e.
hydronephrosis, recurrent urinary tract infection, acquired single kidney, obstruction, neurogenic bladder)
associate with ESRD also was not surprising.
• However, the risk of ESRD attributable to stone disease (5.1%) was much higher than expected. In
fact, this figure is 20-fold above previous estimates (0.2%) that were based upon primary cause of ESRD
reported to the United States Renal Data System.


Author Interview:
Quality of Care and Outcomes Among Patients With Acute Myocardial Infarction by Level of Kidney Function at
Admission: Report From the Get With The Guidelines Coronary Artery Disease Program.CJASN
Deepak L. Bhatt, MD


• Among patients presenting with ST-elevation myocardial infarction (STEMI), patients with abnormal kidney
function received less guideline-recommended care and had higher in-hospital mortality.


• Of note, patients with STEMI who had severe renal dysfunction (GFR 15–30 mL/min/1.73 m2) had adjusted
in-hospital mortality rates that were as high as patients on dialysis (in other words, a very high rate of
mortality).


• In patients with STEMI and various degrees of renal dysfunction, the treating physicians need to make sure
that the patients are getting appropriate evidence-based care.


Author Interview:
Treatment Intensity at the End of Life in Older Adults Receiving Long-term Dialysis
Susan Wong MD

• In this large retrospective mortality study, we present end-of-life care practices among older Medicare
beneficiaries receiving chronic dialysis.

• We found that older dialysis patients experience very aggressive care at the end-of-life, and
hospitalization, intensive care unit admission, and use of intensive procedures (mechanical
ventilation, cardiopulmonary resuscitation, and feeding tube placement) during the final month of life are
common.

• Intensity of care at the end-of-life is more strongly and consistently associated with regional healthcare
spending than with individual patient characteristics in older dialysis patients.

• Rates of hospitalization and use of intensive procedures at the end-of-life in this population also greatly
exceed those reported for other Medicare patients with life-limiting illnesses, such as cancer and heart
failure.


Hemodialysis.com ASN 2012 Nephrology Kidney Disease Interviews

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