Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health

MedicalResearch.com Interview with:
John W. Stanifer, MD MSc
Duke Health

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The key take home for me is that Perfluorinated Chemicals (PFAS) are a globally ubiquitous pollutant with high human exposure and concerning chemical properties that appear to be capable of kidney kidney disease through several plausible different mechanisms; yet, we know almost nothing about long term kidney health outcomes, who is at greatest risk for adverse outcomes, or which communities may be most negatively impacted.

The original impetus for the study was the discovery of GenX in the drinking water of Wilmington NC, a pollutant from a company upstream (see: https://www.newsobserver.com/news/politics-government/state-politics/article199846619.html ). It has been a huge story in NC and every day more and more is being discovered about how pervasive the pollution has become (https://www.usnews.com/news/best-states/north-carolina/articles/2017-12-05/genx-compound-now-detected-in-food-product-in-n-carolina). While this was what caught my attention, as a North Carolinian, I quickly realized that these news stories are all over the place as any quick google search will reveal towns and communities contaminated with these from truly all of the United States. As a health disparities researcher in kidney disease,

I have been studying disparate rural populations in North Carolina, including American Indians, who live in communities with exceptionally high rates of kidney disease, which does not appear to be fully explained by “traditional” risk factors alone such as diabetes, hypertension, obesity, etc. So with that context in mind, I really have begun to focus on these chemicals as potential second-hits or augmenters of kidney disease; we have been doing preliminary studies, in which we have found them in the serum of individuals from these areas, but before we can go further, we really needed to understand what all is known about them and the plausibility that they could cause kidney disease. Therefore, we conducted this comprehensive study to characterize what the potential mechanisms between these chemicals and kidney disease are and where the biggest gaps are.

MedicalResearch.com: Were you surprised by any of the findings?

Response: I was actually surprised by a few things about it. I thought that the link between these chemicals and kidney disease would be pretty weak, with very little to suggest these could be primary drivers of kidney disease. And while the epidemiological studies provided conflicting evidence that mostly but not overwhelmingly pointed toward an association, the toxicology and pharmacokinetic studies demonstrated several key mechanisms that could explain how these chemicals cause kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2– related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.

It was also very interesting to learn that these compounds are taken up by the very same proximal tubule transporters that several known nephrotoxic drugs are taken up, including most notably the herb Aristocholic Acid which was of course responsible for the Balken Endemic Nephropathy that perplexed everyone for so long.

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: Many gaps still exist. The biggest ones to me are that there are literally 1000s of these compounds, with only slight chemical variations, which make detection and regulation challenging. In fact most are still under proprietary aegis which prevents any type of study on them, and several of the “alternative” or “newer” PFCs (e.g. GEnX) have chemical properties that are particularly concerning, despite being marketed as “less toxic”. It is also very concerning to me that children and adolescents have the highest exposure; yet the long-term consequences are completely unknown and life-course epidemiology studies are very much needed. Finally, in the context of kidney disease, these are like so many other environmental toxins in that we don’t know how they interact to worsen or augment kidney disease in people with other risk factors such as diabetes or hypertension. So for example, wonder if you have diabetic nephropathy and are being exposed to these in high quantities? What does that mean for disparities in kidney disease and outcomes??

None of the authors have any disclosures with regards to this work.

 

Citation:

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health
A Scoping Review

John W. Stanifer, Heather M. Stapleton, Tomokazu Souma, Ashley Wittmer, Xinlu Zhao and L. Ebony Boulware

CJASN September 2018, CJN.04670418; DOI: https://doi.org/10.2215/CJN.04670418 

Sep 19, 2018 @ 2:20 pm 

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Study Finds Protective Effect of Caffeine in Chronic Kidney Disease

MedicalResearch.com Interview with:

Coffee Wikipedia image

Coffee
Wikipedia image

Miguel Bigotte Vieira  MD
Nephrology and Renal Transplantation Department
Centro Hospitalar Lisboa Norte
Lisbon, Portugal

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains unclear. We examined the association between varying levels of caffeine consumption and mortality among 4863 patients with CKD in a prospective nationwide cohort, using the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2010.

Our study showed a protective effect of caffeine consumption among patients with chronic kidney disease. The reduction in mortality was present even after considering other important factors such as age, gender, race, smoking, other diseases, and diet.  Continue reading

Artificial Antibody Knocks Out Kidney Inflammation

MedicalResearch.com Interview with:

Michael P. Madaio, MD Sydenstricker Professor and Chairman Department of Medicine Medical College of Georgia at  Augusta University

Dr. Madaio

Michael P. Madaio, MD
Sydenstricker Professor and Chairman
Department of Medicine
Medical College of Georgia at
Augusta University

MedicalResearch.com: What is the background for this study?

Response: Glomerulonephritis is a inflammatory disease of the kidney.  Glomeruli are the filtering units in the kidney. This is most often immunologically mediated and are autoimmune.

Most therapies are directed at inhibiting the Immune/autoimmune process (immunotherapy) systemically.

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Hepatitis C Treatment After Kidney Transplant May Extend Lives and Decrease Costs

MedicalResearch.com Interview with:

Mark H. Eckman, MD Posey Professor of Clinical Medicine Director, Division of General Internal Medicine Director, Center for Clinical Effectiveness University of Cincinnati Medical Center Cincinnati, OH

Dr. Eckman

Mark H. Eckman, MD
Posey Professor of Clinical Medicine
Director, Division of General Internal Medicine
Director, Center for Clinical Effectiveness
University of Cincinnati Medical Center
Cincinnati, OH 

MedicalResearch.com: What is the background for this study?

Response: People who are infected with hepatitis C virus and have kidney failure need a kidney transplant.

Recent studies have found that it is possible to transplant kidneys from donors who are infected with hepatitis C virus into patients who need a transplant and are already infected with the virus. In addition, drugs are available to cure most patients of hepatitis C virus, including those who have kidney failure. Infected patients who need a kidney transplant have 2 options. One option is to receive an infected kidney and then use drugs after the transplant to cure themselves and the transplanted kidney of the virus. Another option is to use the drugs first to get rid of the virus and then to receive a kidney from a donor who does not have hepatitis C virus infection.

For the more than 500,000 patients receiving dialysis for end-stage renal disease (ESRD), less than 4% receive kidney transplants. Because of the limited organ availability, hemodialysis is the final treatment for most patients with ESRD. Of the 10% or so of U.S. patients receiving dialysis who are infected with the hepatitis C virus (HCV), some are willing to accept HCV-infected kidneys, in part, because the wait times for such kidneys are shorter than those for HCV-uninfected kidneys. Because the yearly mortality rate for patients receiving hemodialysis is so high, between 4% and 16%, reducing the time to kidney transplant can have a dramatic effect on both survival and quality of life.

Because it may not be possible to do this type of research with actual people, we created a model that allowed us to estimate possible outcomes without using actual people.

The model was a computer program that combined the best available information to approximate what might happen to participants in a real-world clinical trial. Continue reading

Gabapentin and Pregabalin Should Be Used Cautiously in Hemodialysis Patients

MedicalResearch.com Interview with:

Dr. Julie H. Ishida MD Department of Medicine, Division of Nephrology University of California, San Francisco and San Francisco Veterans Affairs Medical Center

Dr. Ishida

Dr. Julie H. Ishida MD
Department of Medicine, Division of Nephrology
University of California, San Francisco and
San Francisco Veterans Affairs Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Gabapentin and pregabalin are used for the management of symptoms such as neuropathic pain, itching, and restless leg syndrome in patients receiving hemodialysis. However, hemodialysis patients may be particularly vulnerable to adverse events related to these agents, which are cleared by the kidney, but there is limited data evaluating their risk in this population.

Gabapentin and pregabalin use were associated with risk for altered mental status, fall, and fracture, and in some cases, even at doses that would be considered safe for use in this population.  Continue reading

Does Drinking More Water Preserve Kidney Function?

MedicalResearch.com Interview with:
“Glass of Water” by Greg Riegler is licensed under CC BY 2.0Dr. William Clark
Lawson Health Research Institute 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  This study is about the use of increased water intake in people with chronic kidney disease (CKD).

Although there are a large number of benefits claimed most are not substantiated by evidence. However there is a growing body of evidence (animal and human observational studies) that increased hydration with the suppression of antidiuretic hormone preserves kidney function in CKD. This led to our current randomised clinical trial of 631 patients with stage 3 CKD and proteinuria to determine if drinking an extra 4-6 glasses of water per day for 1 year would slow their progressive loss of kidney  function as measured by eGFR.

The main findings were that those coached to increase their water intake versus those coached to sustain their normal fluid intake suffered no ill effects from the intervention and on average were able to sustain an average increase of approximately 3 glasses of water per day. At the end of 1 year the increased hydration group had suppressed their antidiuretic hormone levels (copeptin) significantly but did not demonstrate a greater preservation in their eGFR.

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Electronic Pillbox May Improve Adherence To Complicated Medication Regime

MedicalResearch.com Interview with:

Bethany J. Foster, MD MSCE Montreal Children’s Hospital Department of Pediatrics,  Department of Epidemiology, Biostatistics, and Occupational Health McGill University, Montreal, QC, Canada

Dr. Foster

Bethany J. Foster, MD MSCE
Montreal Children’s Hospital
Department of Pediatrics,
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University, Montreal, QC, Canada

MedicalResearch.com: What is the background for this study?

Response: Adolescent and young adult kidney transplant recipients have the highest risk of graft loss of any age group. One of the main reasons for this is not taking their anti-rejection medications as prescribed. Our study had the goal of testing an intervention to try to improve young patients’ adherence to their strict medication schedule. The intervention included feedback of how well they were taking their medications (which was monitored electronically), text message reminders for medication doses, and individualized coaching to address their personal barriers to taking their medications.

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Standardization and Collaboration Reduced Use of Costly CRRT Treatment for Critically Ill Patients

MedicalResearch.com Interview with:

Rodrigo F. Alban, MD FACS Associate Director Performance Improvement Associate Residency Program Director NSQIP Surgeon Champion Department of Surgery Cedars-Sinai Medical Center

Dr. Alban

Rodrigo F. Alban, MD FACS
Associate Director Performance Improvement
Associate Residency Program Director
NSQIP Surgeon Champion
Department of Surgery
Cedars-Sinai Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Continuous Renal Replacement Therapy (CRRT) is a modality of hemodialysis commonly used to manage renal failure in critically ill patients who have significant hemodynamic compromise.  However, it is also resource-intensive and costly and its usage is highly variable and lacks standardization.

Our institution organized a multidisciplinary task force to target high value care in critically ill patients requiring CRRT by standardizing its process flow, promoting cross-disciplinary discussions with patients and family members, and increasing visibility/awareness of CRRT use.  After our interventions, the mean duration of CRRT decreased by 11.3% from 7.43 to 6.59 days per patient.  We also saw a 9.8% decrease in the mean direct cost of CRRT from $11642 to $10506 per patient.  Finally, we also saw a decrease in the proportion of patients expiring on CRRT, and an increase in the proportion of patients transitioning to comfort care.

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Kids with Kidney Disease Likely To Experience Lower IQ and Educational Outcomes Into Adulthood

MedicalResearch.com Interview with:

L-R: Kerry Chen, Anita van Zwieten, Madeleine Didsbury, Germaine Wong

L-R: Kerry Chen, Anita van Zwieten, Madeleine Didsbury, Germaine Wong

Dr. Kerry Chen
Centre for Kidney Research, The Kids Research Institute
The Children’s Hospital at Westmead, Sydney School of Public Health,
The University of Sydney
Sydney, New South Wales, Australia

MedicalResearch.com: What is the background for this study?

Response: Chronic kidney disease is a major public health issue, with end-stage disease often requiring a combination of complex medication regimens, dialysis and/or transplant surgery. In children, the major causes of CKD are genetic and congenital. The consequences of CKD in children can be long-term and debilitating especially as they transition into adulthood, affecting their physical, intellectual and emotional well-being.

To better understand these changes, the Kids Health and Wealth Study (KCAD) is the largest longitudinal cohort study of children and adolescents with CKD in Australia and New Zealand. Spread across 5 paediatric nephrology centres so far, the KCAD Study takes a life-course approach to collecting and analysing data pertaining to the interactions between reduced renal function and associated clinical, socio-economic, quality of life, psychological, cognitive and educational outcomes in children, especially as they progress in CKD stage and also as they transition into adulthood.

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Low Sodium Levels Linked To Cognitive Impairment in Older Adults

MedicalResearch.com Interview with:

Dr. Kristen L. Nowak PhD Division of Renal Diseases and Hypertension University of Colorado Anschutz Medical Campus Aurora, CO 80045

Dr. Nowak

Dr. Kristen L. Nowak PhD
Division of Renal Diseases and Hypertension
University of Colorado Anschutz Medical Campus
Aurora, CO 80045

MedicalResearch.com: What is the background for this study?  

Response: Subtle impairments in cognition are common with aging, even in the absence of clinically apparent dementia. Mild hyponatremia is a common finding in older adults; however, the association of lower serum sodium with cognition in older adults is currently uncertain.

We hypothesized that lower normal serum sodium would be associated with prevalent cognitive impairment and the risk of cognitive decline over time in asymptomatic, community-dwelling older men.

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NOACs For Atrial Fib Anticoagulation May Have Lower Risk of Kidney Side Effects

Atrial Fibrillation - Wikipedia image

Normal rhythm tracing (top) Atrial fibrillation (bottom) Wikipedia

Interview with:
Dr Xiaoxi Yao PhD
Assistant Professor
Researcher
Mayo Clinic

What is the background for this study? What are the main findings?

Response: Lifelong oral anticoagulation, either with warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), is indicated for stroke prevention in most patients with atrial fibrillation (AF). Emerging evidence suggests that NOACs may be associated with better renal outcomes than warfarin.

The study found renal function decline is common among patients with atrial fibrillation treated with oral anticoagulants. NOACs, particularly dabigatran and rivaroxaban, may be associated with lower risks of adverse renal outcomes than warfarin.

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Common Antidepressant Sertraline Does Not Improve Depression in Chronic Kidney Disease Patients

MedicalResearch.com Interview with:

Dr. Susan Hedayati MD University of Texas Southwestern Dallas, Texas

Dr. Hedayati

Dr. Susan Hedayati MD
Yin Quan-Yuen Distinguished Professorship in Nephrology
University of Texas Southwestern
Dallas, Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We previously showed that Major Depression is associated with a significantly higher risk of death, dialysis initiation, and hospitalization among patients with Chronic Kidney Disease (CKD). Now we show that a common antidepressant medication, a selective serotonin reuptake inhibitors (SSRI), sertraline, does not improve depression in this patient population, a chronically ill group that is not only at significantly increased risk for developing depression but also its serious complications.

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Kidney Failure From Diabetes Decreasing Across US

MedicalResearch.com Interview with:
Nilka Ríos Burrows, MPH, MT (ASCP)
Lead, Chronic Kidney Disease Initiative
CDC Division of Diabetes Translation. 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Kidney failure treated with dialysis or a kidney transplant is called end-stage renal disease (ESRD).  ESRD is a costly and disabling condition often resulting in premature death.

During 2000–2014, kidney failure from diabetes among U.S. adults with diabetes decreased by 33%, and it declined significantly in most states, the District of Columbia, and Puerto Rico. No state experienced an increase in kidney failure from diabetes. Continued awareness and interventions to reduce risk factors for kidney failure, improve diabetes care, and prevent type 2 diabetes might sustain these positive trends.

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Vasopressin-Inhibitor Tolvaptan Reduces Kidney Function Decline in Polycystic Kidney Disease

MedicalResearch.com Interview with:
Dr. TorresVicente E. Torres, M.D., Ph.D.

Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease.

This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan.

Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD.

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Non-Medical Factors Affect Racial Disparities in Kidney Transplant Wait Lists

MedicalResearch.com Interview with:
Yue-Harn Ng,
MD
University of New Mexico

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​African Americans (AA) have a higher incidence of end-stage renal disease but lower rates of kidney transplantation (KT) compared to whites (WH).  Disparities persist after adjusting for medical factors.  We assessed the relationship of non-medical (eg. cultural, psychosocial, knowledge) factors with kidney transplantation wait-listing (WL) within the context of racial differences.

​In this longitudinal cohort study, we found that African American patients were less likely to be wait-listed compared to White patients.  This difference was influenced by factors including age, comorbidities, socio-economic status, being on dialysis, having a living donor, transplant knowledge and social support.

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Poor Functional Status Predicts Increased Mortality After Dialysis Initiation

MedicalResearch.com Interview with:

Silvi Shah, MD, FACP, FASN Assistant Professor, Division of Nephrology University of Cincinnati Cincinnati, OH

Dr. Shah

Silvi Shah, MD, FACP, FASN|
Assistant Professor
Division of Nephrology
University of Cincinnati
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Elderly represent the fastest growing segment of incident dialysis patients in Unites States. The annual mortality in end stage renal disease (ESRD) patients is very high ~ 20%.

Since most of the deaths occur in the first year of dialysis, it is possible that health conditions present prior to initiation of dialysis may impact long-term outcomes. In this study, we determined the impact of poor functional status at the time of dialysis initiation and pre-dialysis health status on type of dialysis modality, type of hemodialysis access and one-year mortality in elderly dialysis patients. We evaluated 49,645 adult incident dialysis patients (1/1/2008 to 12/31/2008) from the United Data Renal Data System (USRDS) with linked Medicare data for at least 2 years prior to dialysis initiation. Mean age of our study population was 72 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% has pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. Patients with poor functional status had higher odds of being initiated on hemodialysis than peritoneal dialysis, lower odds of using arteriovenous access as compared to central venous catheter for dialysis and higher risk of one-year mortality.

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PPIs for Reflux Linked To Increased Risk of Chronic Kidney Disease

MedicalResearch.com Interview with:
Charat Thongprayoon, MD

Bassett Medical Center
Cooperstown, NY 13326

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a meta-analysis including 5 observational studies with 536,902 patients to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs).

We found a statistically significant association between the use of PPI and 1.3-fold increased risk of CKD or ESRD development. Compared with H2Ras, the use of proton pump inhibitors was significantly associated with 1.3-fold higher risk for CKD development.

Conversely, there was no significant association between the use of H2RAs and chronic kidney disease.

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Elderly Frail Patients At Higher Risk Of Mortality After Dialysis Initiation

MedicalResearch.com Interview with:

Silvi Shah, MD, FACP, FASN Assistant Professor, Division of Nephrology University of Cincinnati Cincinnati, OH

Dr. Shah

Silvi Shah, MD, FACP, FASN
Assistant Professor, Division of Nephrology
University of Cincinnati
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Elderly represent the fastest growing segment of incident dialysis patients in Unites States. The annual mortality in end stage renal disease (ESRD) patients is very high ~ 20%. Since most of the deaths occur in the first year of dialysis, it is possible that health conditions present prior to initiation of dialysis may impact long-term outcomes.

In this study, we determined the impact of poor functional status at the time of dialysis initiation and pre-dialysis health status on type of dialysis modality, type of hemodialysis access and one-year mortality in elderly dialysis patients. We evaluated 49,645 adult incident dialysis patients (1/1/2008 to 12/31/2008) from the United Data Renal Data System (USRDS) with linked Medicare data for at least 2 years prior to dialysis initiation. Mean age of our study population was 72 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% has pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. Patients with poor functional status had higher odds of being initiated on hemodialysis than peritoneal dialysis, lower odds of using arteriovenous access as compared to central venous catheter for dialysis and higher risk of one-year mortality.

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Chronic Insomnia Associated With Higher Risk of End Stage Kidney Disease and Mortality

MedicalResearch.com Interview with:
Dr. Jun Ling (Lucy) Lu, MD, CCRP
Senior Clinical Research Coordinator in the Department of Medicine

Csaba P Kovesdy MD FASN
Fred Hatch Professor of Medicine
Director, Clinical Outcomes and Clinical Trials Program

Division of Nephrology, University of Tennessee Health Science Center
Nephrology Section Chief, Memphis VA Medical Center
Memphis TN, 38163 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Around one third of the world’s population suffers from insomnia. Previous studies showed that sleep disorders affect the hypothalamic–pituitary–adrenal axis and the sympatho-adrenal system, which may cause abnormalities in several organ systems and pathways causing metabolic or cardiovascular abnormalities. However, there is inadequate evidence of an association between chronic insomnia and adverse renal outcomes.

After examining 938,473 US veterans (4.4% of them had chronic insomnia) with baseline estimated eGFR >60 ml/min/1.73m2, we found that chronic insomnia is associated with a 43% higher risk of all-cause mortality, a 2.5-fold higher incidence of eGFR ≤45ml/min/1.73m2, a 2.3-fold higher ESRD risk, and with rapid loss of kidney function.

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Caffeine Linked To Decrease in All-Cause Mortality in Chronic Kidney Disease Patients

MedicalResearch.com Interview with:

Miguel Bigotte Vieira MD Centro Hospitalar Lisboa Norte Lisbon, Portugal

Dr. Bigotte Vieira

Miguel Bigotte Vieira MD
Centro Hospitalar Lisboa Norte
Lisbon, Portugal 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains unclear. We examined the association between varying levels of caffeine consumption and mortality among 2328 patients with CKD in a prospective nationwide cohort, using the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2010.

A dose-dependent inverse association between caffeine and all-cause mortality was observed in patients with CKD. This association was independent of influential factors including age, gender, race, annual family income, education level, estimated GFR, albumin/creatinine ratio, hypertension, smoking status, dyslipidemia, body mass index, previous cardiovascular events and diet: consumption of alcohol, carbohydrates, polyunsaturated fatty acids and fibers.

Comparing with 1st quartile of caffeine consumption, adjusted HR for death was 0.88 (95% CI, 0.68-1.44) for 2nd quartile, 0.78 (95% CI, 0.60-1.01) for 3rd quartile and 0.76 (95% CI, 0.59-0.97) for 4th quartile (p=0.027 for trend across quartiles)

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Prebiotin™ Fiber Supplement Tested in NIH/NIDDK Pilot Study In End-Stage Kidney Disease Patients

MedicalResearch.com Interview with:

Ron Walborn Jr. Prebiotin CEO

Ron Walborn Jr.

Ron Walborn Jr.
Prebiotin CEO 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The product Prebiotin™ Prebiotic Fiber was brought to market in 2007 by Dr. Frank Jackson, a gastroenterologist out of Harrisburg, PA. He found through 40 years of experience with his patients that a variety of digestive issues benefitted from daily supplementation with a soluble prebiotic fiber, specifically, oligofructose-enriched inulin (OEI) derived from chicory root.

In the late summer of 2012, Prebiotin caught the attention of Dr. Dominic Raj at the Internal Medicine Department of George Washington University. Dr. Raj’s laboratory showed that patients with kidney disease may have a higher level of release of endotoxins like p-Cresol sulfate and indole from the bacteria in the gut, which can move into the bloodstream and promote inflammation.

This early work was the basis of a successful grant application. Researchers were interested in investigating the therapeutic potential of altering the composition and/or function of the gut microbiome in this patient population, based on the understanding that by building up the levels of healthy bacteria in the gut, undesirable bacteria is eventually crowded out, thereby reducing the release of harmful endotoxins into the system.

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Human Kidney Organoids Underscore Importance of Microenvironment in Polycystic Kidney Disease

MedicalResearch.com Interview with:
Benjamin Freedman, Ph.D
.
Assistant Professor | University of Washington
Department of Medicine | Division of Nephrology
Member, Kidney Research Institute
Member, Institute for Stem Cell and Regenerative Medicine
Seattle WA 98109 

MedicalResearch.com: What is the background for this new technology and study? What are the main findings?

Response: Polycystic kidney disease (PKD) is the leading genetic cause of end stage renal disease, affecting approximately twelve million people. The hallmark of the disease is the massive expansion of kidney tubules into large, fluid-filled cysts. Although we know the genes that are mutated in this disease, we do not have a firm grasp on what they do to protect the body from disease.

We used a new system, human kidney organoids with gene-edited PKD mutations, to discover how factors outside the cell affect cyst formation. We found that liberating the organoids from plastic dishes into floating cultures greatly increased the number and size of cysts that formed. We also found that PKD organoids had problems in their ability to change the shape of collagen scaffolds surrounding them, compared to control organoids of the same genetic background.

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Heavy Marijuana Use May Harm Kidneys, But More Study Needed

MedicalResearch.com Interview with:

Dr. Julie H. Ishida MD Division of Nephrology, Department of Medicine San Francisco and San Francisco Veterans Affairs Medical Center University of California

Dr. Ishida

Dr. Julie H. Ishida MD
Division of Nephrology, Department of Medicine
San Francisco and San Francisco Veterans Affairs Medical Center
University of California

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Marijuana is becoming increasingly accepted in the United States, and animal studies suggest that marijuana could affect kidney function. However, data in humans are limited to case reports of acute kidney injury related to synthetic cannabinoid use and small cohort studies of relatively short duration.

Among 3,765 participants with normal kidney function in the Coronary Artery Risk Development in Young Adults or CARDIA study, my colleagues and I found that higher marijuana use was associated with lower kidney function at the start of the our study. However, we did not find that marijuana was associated with change in kidney function or albuminuria, which is a sign of kidney damage, over long-term follow-up.

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Deceased Donor Kidneys Offered Median of 7 Times Before Acceptance For Transplant

MedicalResearch.com Interview with:

Dr. Anne Huml MD Center for Reducing Health Disparities Case Western Reserve University MetroHealth Medical Center Cleveland, Ohio

Dr. Huml

Dr. Anne Huml MD
Center for Reducing Health Disparities
Case Western Reserve University
MetroHealth Medical Center
Cleveland, Ohio 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Overall, about 600,000 Americans have end stage renal disease and require chronic dialysis treatment or a kidney transplant to survive. Compared to chronic dialysis, kidney transplantation results in better survival and quality of life and lower health care costs. Approximately 100,000 patients are listed for a kidney transplant. However, only 17,000 transplants occur per year with two-thirds of these coming from deceased donor organs. Annually, over 8,000 patients either die waiting for a kidney transplant or are removed from the waiting list for being too ill. Waiting times vary based on geography, but it is not unusual for patients to wait upwards of 5 years for a kidney transplant. There are sizeable race, gender, and socioeconomic disparities in access to kidney transplantation.

In this study, we evaluated the outcomes of deceased donor kidney offers and their association with donor and waitlisted patient characteristics. Differences in kidney offer outcomes to patients at the top of the waiting list may contribute to disparities in transplantation.

When a deceased donor organ becomes available, a match run list is created that ranks potential recipients in priority order based upon several characteristics, including waiting time and immunologic criteria. At the discretion of the transplant center, organ offers to patients on their waiting list can be accepted for transplant, or refused for a particular patient. The offers continue down the match run list in sequential order. For each potential recipient in whom the organ is not transplanted, a refusal code is generated and catalogued with the United Network of Organ Sharing, or UNOS. UNOS identifies 37 unique refusal codes and categorizes them into donor-related, transplant center bypassed for pre-specified criteria, recipient-related, histocompatibility-related, program-related, or other reasons for refusal.

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Loss of Sense of Smell, Malnutrition Common in Kidney Disease Patients

MedicalResearch.com Interview with:

Dr. Nigwekar and Dr. Paunescu

Dr. Nigwekar and                 Dr. Paunescu

Teodor Paunescu, PhD and
Sagar Nigwekar, MD
Division of Nephrology
Massachusetts General Hospital

 MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Over 25 million people in the U.S. have chronic kidney disease, and the number of deaths caused by this disease has doubled between 1990 and 2010. It is projected that by 2030 more than 1 in 3 adults over 65 years old will be diagnosed with chronic kidney disease.

Many patients with kidney disease are also malnourished, which negatively impacts their quality of life, overall health, and even survival. However, no effective treatments are currently available to address malnutrition in these patients.

The sense of smell plays an important role in determining food flavor. If a patient’s ability to smell is impaired, this could affect the taste of food, for example, foods that used to appeal to the patient may no longer do so. Given the relation between the sense of smell and appetite, we set out to investigate the loss of smell in patients with kidney disease, and to test an intervention aimed at alleviating their smell deficits.

Our first goal was to determine if patients with various degrees of kidney disease suffer smell losses and whether smell issues might affect their nutritional status. We found that, while most kidney disease patients do not perceive a problem with their sense of smell, deficits in the ability to smell are actually common among these patients, and the severity of these deficits increases with the severity of their kidney disease. Moreover, our study found that reductions in several markers of nutrition (such as cholesterol and albumin levels) correlate with the impairment in these patients’ sense of smell.

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