Some Antibiotics Linked To Increased Risk of Kidney Stones

MedicalResearch.com Interview with:

A kidney stone (yellow) composed of calcium oxalate: Wikipedia Image

A kidney stone (yellow) composed of calcium oxalate: Wikipedia Image

Gregory Tasian MD, MSc, MSCE
Assistant Professor of Urology and Epidemiology
University of Pennsylvania Perelman School of Medicine
Division of Urology and Center for Pediatric Clinical Effectiveness
The Children’s Hospital of Philadelphia

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

Response:  We found that five classes of commonly prescribed antibiotics were associated with an increased risk of kidney stones. These classes were sulfa drugs (e.g. Bactrim), fluoroquinolones (e.g. Cipro), cephalosporins (e.g. cephalexin), nitrofurantoin, and broad-spectrum penicillins (e.g. augmentin).  For those five classes of antibiotics, the greatest risk was found among younger patients. However, the increased risk was still significant across all ages, including for older adults with the exception of broad-spectrum penicillins, which were not associated with an increased risk of kidney stones among patients >75 years of age.

We conducted this study because:

1) Prior investigations have demonstrated that changes in the gut microbiome were associated with kidney stones,

2) Antibiotics are prescribed frequently, and

3) The number of people affected by kidney stone disease has increased 70% over the last 30 years and the greatest increases have been found among children and adolescents.

Our results were consistent with these previous studies, so we were not surprised with the findings although we did not know which specific classes of antibiotics would be associated with an increased risk of stones and which ones would not.

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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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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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Marked Increase in Number of US Patients With Kidney Stones

MedicalResearch.com Interview with:
Li Hao Richie Xu MD

Division of Mineral Metabolism
University of Texas Southwestern Medical Center
Dallas, Texas, United States

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

Response: Over the past three decades, the prevalence of the kidney stones has escalated in the United States. Changes in dietary patterns, increasing body weight and obesity likely contributed to this significantly higher prevalence of kidney stone. In this study, we explored temporal changes in stone composition, demographic characteristics, and in serum and urinary kidney stone risk profile in kidney stone forming population for the last 35 years.

The proportion of uric acid stones has been almost doubled during this period. Although age and body mass index (BMI) increased over time in both uric acid and calcium stone formers, uric acid stone formers were consistently older, had higher BMI, and lower urinary pH than calcium stone formers. In addition, over time, the proportion of female vs. male increased in calcium stone formers, but not in uric acid stone formers. The most significant urinary parameter differentiating uric acid stone formers from calcium stone formers is 24-hour urinary pH.

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Tamsulosin (Flomax) Improves Passage of Some Kidney Stones

MedicalResearch.com Interview with:
Ralph Wang, MD, MAS

Associate Clinical Professor, Department of Emergency Medicine
University of California, San Francisco

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

Response: Medical expulsive therapy, most notably tamsulosin, has been studied extensively to improve stone passage in patients diagnosed with ureteral stone. Prior trials and meta-analyses have identified a benefit. In fact, tamsulosin is
recommended by the American Urologic Association for patients diagnosed with ureteral stones < 10mm that do not require intervention. However, recent well-conducted multi-center randomized trials have not found any improvement in stone passage.

Thus we conducted a systematic review and meta-analysis of all double blinded, placebo controlled randomized trials of tamsulosin to determine whether it improves stone passage.

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Researchers Search for Probiotic Factors To Reduce Risk of Calcium Oxalate Kidney Stones

MedicalResearch.com Interview with:

Dr. Hatim A. Hassan Section of Nephrology, Department of Medicine The University of Chicago Chicago, IL 60637

Dr. Hatim A. Hassan

Dr. Hatim A. Hassan MD PhD
Section of Nephrology, Department of Medicine
The University of Chicago
Chicago, IL 60637

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

Response: Nephrolithiasis is the second most prevalent kidney disease in USA after hypertension, with a rising prevalence and complications including advanced chronic kidney disease (CKD) and end stage renal disease (ESRD). It remains a major source of patient discomfort and disability, lost working days, and health-care expenditure, with an annual economic cost approaching $10 billion. Hyperoxaluria is a major risk factor for kidney stones (KS), and 70-80% of KS are composed of calcium oxalate. Urinary oxalate is an important determinant of supersaturation, and the risk for stone formation is affected by small increases in urine oxalate. Oxalate is a metabolic end product that cannot be further metabolized and is highly toxic. The mammalian intestine plays a crucial role in oxalate homeostasis, by regulating the amount of absorbed dietary oxalate and providing an avenue for enteric oxalate excretion. Anion exchanger SLC26A6 (A6)-mediated intestinal oxalate secretion plays a critical role in preventing hyperoxaluria and calcium oxalate kidney stones (COKS). Inflammatory bowel disease patients have a significantly increased risk of kidney stones due to the associated enteric hyperoxaluria. Obesity is a risk factor for KS and obese stone formers often have mild to moderate hyperoxaluria. Hyperoxaluria is also emerging as a major complication (developing in > 50% of patients) of bariatric surgery for obesity. With the rising prevalence of obesity and increased utilization of bariatric surgery, it is expected that the incidence of hyperoxaluria and related COKS (including the associated cost burden) will continue to increase at a significant rate. Primary hyperoxaluria (PH) is an inherited disease in which there is endogenous oxalate overproduction, which leads to recurrent KS and/or progressive nephrocalcinosis, ESRD, as well as significant hyperoxalemia, systemic oxalosis and premature death. Systemic deposition of calcium oxalate (oxalosis) leads to bone disease, cardiac arrhythmias, cardiomyopathy, skin ulcers, erythropoietin refractory anemia, and digital gangrene. The only treatment known to fully correct the underlying metabolic defect is liver transplantation or combined kidney-liver transplantation once ESRD develops. In addition, significant hyperoxalemia is also seen in ESRD. Cardiovascular diseases are the leading cause of morbidity and mortality in ESRD patients, and a recent report raised the possibility that the ESRD-associated hyperoxalemia might contribute to this increased risk. Lowering serum oxalate might improve cardiovascular outcomes in ESRD patients if these findings are confirmed.

Unfortunately, there is currently no specific therapy that effectively lowers urine and/or plasma oxalate level(s), and the risk of recurrent COKS, nephrocalcinosis, oxalate nephropathy, ESRD, & systemic oxalosis remains substantial in the absence of treatment.

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Fruit Extract Hydroxycitrate Shows Promise As Potential Therapy To Prevent Kidney Stones

MedicalResearch.com Interview with:

Dr-Jeffrey-RimerJeffrey D. Rimer PhD
Ernest J. and Barbara M. Henley Associate Professor
University of Houston
Department of Chemical and Biomolecular Engineering
Houston, TX 77204-4004

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

Response: This project’s origin can be traced back to preliminary results obtained by Dr. John Asplin at Litholink Corporation revealing an organic acid, hydroxycitrate (HCA), was a promising inhibitor of calcium oxalate monohydrate (COM) crystallization. COM is a principle component of human kidney stones. Interestingly, HCA is a molecular analogue of citrate (CA), the current therapy for stone disease. My research group at the University of Houston began collaborating with Dr. Asplin to explore the effects of HCA in more detail. We conducted in vitro assays using two techniques: bulk crystallization studies to quantify HCA efficacy and more detailed in situ atomic force microscopy (AFM) studies to assess the growth of COM crystal surfaces in real time.

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Excessive Intake Non-Dairy Protein Could Raise Risk of Kidney Stones

MedicalResearch.com Interview with:

Pietro Manuel Ferraro, MD MSc PhD Assistant Professor Fondazione Policlinico Universitario A. Gemelli Catholic University of the Sacred Heart Senior Collaborator in the Nurses' Health Study Brigham and Women's Hospital Channing Division of Network Medicine

Dr. Ferraro

Pietro Manuel Ferraro, MD MSc PhD
Assistant Professor
Fondazione Policlinico Universitario A. Gemelli
Catholic University of the Sacred Heart
Senior Collaborator in the Nurses’ Health Study
Brigham and Women’s Hospital
Channing Division of Network Medicine

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

Response: In our study, we looked at the association between dietary intake of different sources of protein (vegetable, dairy and non-dairy animal), potassium (a marker of fruits and vegetables) and their interaction and the risk of forming kidney stones. We looked at their interaction because some protein is a source of acid, whereas fruits and vegetables are a source of alkali, thus their relationship could potentially impact acid-base status and in turn the risk of stones by modifying the metabolism of calcium and other elements such as urine citrate and uric acid.

We found that the risk of forming stones depends not only on the amount of protein but also on the source, with no risk associated with intake of vegetable and dairy protein, and a modestly higher risk for excessive non-dairy animal protein; on the other hand, intake of potassium was associated with a markedly lower risk. Interestingly, the interaction between intake of protein and potassium, the so called net acid load, was also associated with higher risk of forming kidney stones, suggesting that the effect of acid intake is modulated by that of alkali and vice versa.

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Multiple Kidney Stones Linked to Increased Coronary Artery Calcium

MedicalResearch.com Interview with:
Dr. Ryan Hsi MD
Clinical Fellow, UCSF Medical School and
Mathew Sorensen, MD, MS
Residency Program Director
Department of Urology
University of Washington
Director, Comprehensive Metabolic Stone Clinic
Puget Sound VA

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

Response: Kidney stones affect 1 in 11 people, and the incidence is rising.  When kidney stones pass, they can be very painful, and if they obstruct urinary flow as they pass, they can be a cause of kidney injury and sepsis.  It is well-known that kidney stones are associated with diseases such as coronary artery disease, obesity, diabetes, and hypertension.  Less well established is the relationship with kidney stones and pre-clinical markers of these diseases.  That is, before a person has a heart attack, a person may develop atherosclerosis first – are kidney stones associated with these early warning signs of future disease?

MedicalResearch.com: What are the main findings?

Response: This study evaluated the association of coronary artery calcium and kidney stones.  Coronary artery calcium is a measure of calcification of the blood vessels that supply the heart, and it is a predictor of future cardiovascular events.  Our study of the Muli-Ethnic Study of Atherosclerosis evaluated individuals who had coronary artery calcium measured and compared those who had a history of none, one, or multiple kidney stones.  We found that individuals who had a history of multiple kidney stones were associated with higher levels of coronary artery calcium.

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Calcium Supplements Linked To Increased Risk of Kidney Stones

MedicalResearch.com Interview with:
Christopher Loftus M.D. candidate
Cleveland Clinic Lerner College of Medicine

Medical Research: What is the background for this study? What are the main findings?

Response: Most kidney stones are made, at least partially, of calcium composite. In a prospective study of nurses in the post-menopausal age, it was found that diets that contained high amounts of calcium were beneficial in preventing kidney stones in this population. In the gut, calcium can bind to oxalate which prevents it from being absorbed into the body and decreases the concentration of calcium in the urine. However there has been debate as to whether supplemental calcium (calcium pills) has the same beneficial effects as calcium in the diet. Supplemental calcium enters the gut in large quantities all at once so it may enter the blood stream in higher concentrations over smaller amounts of time. By the same token, vitamin D plays a role in the management and balance of calcium in the body and could potentially have an effect on stone formation as well.  It has also been debated whether vitamin D supplementation has major effect on patients who are known to be stone formers.  So we reviewed CT scans of patients and 24 hour urine collections (both male and female of adult age) who were known to have kidney stones and measured the growth of stones over a period of time.

Our main findings were that supplementary calcium increased the rate of stone formation in these patients. We also found that vitamin D had a protective effect and patients taking only vitamin D had a slower rate of stone progression.

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