Wednesday, February 19, 2014

Technique Creates Functional Platelets from Human Pluripotent Stem Cells

Researchers have genetically manipulated human induced pluripotent stem cells to become stable immortalized lines of megakaryocyte progenitors, which could subsequently produce large quantities of platelets with clotting capabilities similar to those of donated platelets. The technique involved expression of BMI1BCL-XL, and c-MYC genes to suppress senescence and apoptosis and to promote proliferation. Unlike freshly donated platelets, the immortalized megakaryocyte progenitors could be expanded and frozen for long-term storage. The advance, which is described in a Cell Stem Cell article, could possibly eliminate platelet supply shortages.

AKI Increases Risks of Kidney Disease and Death Well Beyond Hospital Discharge

New research indicates AKI patients face increased risks of kidney disease and death after receiving renal replacement therapy, which are not altered by increased dialysis intensity. A study of 1464 ICU patients with AKI randomized to receive 25 mL/kg/hour or 40 mL/kg/hour of continuous hemodiafiltration found 63% of lower-intensity patients and 72% of higher-intensity patients had died at a median of 3.7 years post-randomization. Among survivors to day 90, only 5.1% of lower-intensity patients and 5.8% of higher-intensity patients required maintenance dialysis. The PLOS Medicine study noted albuminuria was observed in 40% of lower-intensity survivors and 44% of higher-intensity survivors.

Noninvasive Test Predicts Contrast-Induced AKI in Stable Coronary Artery Disease Patients

Bioimpedance vector analysis (BIVA), a noninvasive method for measuring fluid status, could predict the development of contrast-induced AKI in a study of 900 patients scheduled to undergo coronary angiography. Patients in the highest quartile of fluid depletion based on BIVA, which is typically used to monitor fluid volume of patients on dialysis or with heart failure, had a nearly 3-fold higher risk of developing AKI within 3 days after contrast administration. The findings are published in the Journal of the American College of Cardiology.

Intensive Dialysis in Pregnant Women with Kidney Failure Benefits Mothers and Babies

In a study of 42 pregnant women with kidney failure, those who underwent dialysis for more than 36 hours per week had a live birth rate of 85%, compared with 48% in women dialyzed for 20 hours or less per week. Infants were a healthier weight at birth when women were dialyzed for more than 20 hours per week than when women were dialyzed for 20 hours or less per week. Pregnancy complications were few and manageable in patients receiving intensive dialysis. The findings are published in JASN.

Increased Intensity of Renal Replacement Therapy Does Not Reduce Premature Mortality in Patients with AKI

Among 1464 patients with AKI in an intensive care unit who required renal replacement therapy (RRT), mortality rates and quality of life among those who survived were essentially the same in patients receiving low intensity RRT or high intensity RRT (63% vs. 62%). Albuminuria was common among survivors, with similar rates in both groups (40% in the low intensity group and 44% in the high intensity group). Patients in the Randomized Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study were followed for a median of 43.9 months. The findings are published in PLOS ONE.

Daily Hemodialysis Improves Height Gain in Children with ESRD

Daily hemodialysis favored a 0.5 gain in standard deviation scores for height in a third of children with ESRD who were followed for an average of 9.3 months. Patients did not receive growth hormone treatment. The cumulative probability of gain in height for age at 12 months was 40% in the 24-patient group receiving daily hemodialysis vs. 15% in the 26-patient group receiving concurrent conventional hemodialysis. Dialysis intensification was not a cause for treatment dropouts. The Pediatric Nephrology findingssuggest that daily hemodialysis should be considered as a treatment for selected cases, especially small children.

High Dietary Acid Load Linked to CKD Progression

A study of 217 elderly CKD patients on a low-protein diet with normal serum bicarbonate levels found high dietary acid load, in terms of net endogenous acid production (NEAP), was associated with CKD progression. Compared with patients in the lowest quartile of NEAP, those in the second, third, and fourth quartiles had 3.9 times, 4.7 times, and 4.3 times increased odds of experiencing a 25% decline in eGFR or starting dialysis, according to the American Journal of Nephrology study. An accompanying editorial notes the need to assess whether reduced NEAP should be standard care for patients with reduced eGFR.

FDA panel votes against changing naproxen heart risk label.

USA Today (2/11, Weise) reported that the painkiller naproxen, sold as Aleve, “does not pose a lower risk of cardiovascular blood clots than other common pain medications such as Advil,” an advisory committee of the FDA voted Tuesday. The advisory panel “reviewed FDA labeling rules that require pain medications known as non-steroidal anti-inflammatory drugs” to carry cardiovascular warning. The panel voted 16-9 “that the available data don’t support a conclusion that naproxen” carried a lower risk of heart risks compared with the other NSAIDs, the article noted.
        The Wall Street Journal (2/12, Burton, Subscription Publication) highlighted the significance of the vote, noting Bayer and others makers of naproxen won’t get any marketing advantage when they offer their medicines on the shelves. The paper noted the FDA had called for the two-day advisory panel meeting because recent medical research seems to suggest that naproxen poses less risk to the heart than other pain relievers.
        The New York Times (2/12, Tavernise, Subscription Publication) and the AP (2/12, Perrone) also cover the story.

Kidney donors may face slightly higher risk of ESRD.

The CNN (2/12) “The Chart” blog reports that research published in the Journal of the American Medical Association suggests that individuals who donate a kidney “may face a slightly increased risk of suffering from end-stage renal disease themselves.” Researchers “compared living kidney donors to healthy individuals who would also likely qualify to donate but never did.” The investigators found that “while the actual donors had an estimated lifetime risk of 90 out of 10,000 for end-stage renal disease (ESRD), the nondonors’ risk was slightly lower at 14 out of 10,000.”
        HealthDay (2/12, Preidt) reports that the likelihood of “kidney failure among donors varied by race, with a rate of 51 per 10,000 among black donors and 23 per 10,000 among white donors.” This “greater risk among black donors is not fully understood, the study authors noted.”
        MedPage Today (2/12, Fiore) reports, “In an accompanying editorial, John Gill, MD, of the University of British Columbia, and Marcello Tonelli, MD, of the University of Alberta, both in Canada, said the findings suggest that prospective donors ‘should be informed that (should they develop a condition after donation that causes loss of kidney function) their lower residual kidney function after donation may increase the risk of future ESRD.’”

Poor Eating Habits May Contribute to Health Risks of Shift Work

In an analysis of NHANES data from 2005 to 2010, shift workers were more likely to have diets that promote chronic inflammation. When researchers calculated a “dietary inflammatory index” (DII) for each individual using data from a 24-hour dietary recall, average DII scores were 1.01 for shift workers, 1.07 for rotating shift workers, and 0.86 for day workers. Women had higher DII values than men: evening/night shift workers had an average DII of 1.48, compared with 1.17 for day workers. The Journal of Occupational and Environmental Medicine findings suggest that poor eating habits may contribute to some of the health risks associated with shift work.

Study Reveals Similar Survival Rates for Early vs. Conventional Timing of Dialysis Initiation

Among 652 patients with advanced CKD, timing of dialysis therapy initiation was not associated with premature mortality when accounting for lead time bias and survivor bias. Most of the patients (71.3%) did not initiate dialysis during the timeframe of theAmerican Journal of Kidney Diseases study (2005 to 2009). Patients who did not initiate dialysis were older, more likely to be white, and had more favorable laboratory profiles. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to below 10mL/min/1.73m². A total of 426 participants were censored prior to attaining a clear treatment strategy and were considered undeclared.

Creatine in Meat Causes Significant Increases in Serum Creatinine after Consumption

Consumption of a standardized cooked meat meal significantly increased serum creatinine and resulted in a significant fall in eGFR in all stages of CKD studied; 6 of 16 CKD 3a patients were misclassified as CKD 3b. This effect of cooked meat on serum creatinine disappeared after 12 hours of fasting. The Diabetes Care study included 80 participants: volunteers and diabetic patients with CKD stages 1 and 2, 3a, 3b, and 4 (16 per group). Each participant was given a meat meal and nonmeat meal, each providing 54 g protein, together with 250 mL water, on separate days.

Limiting Animal Protein Intake May Be Beneficial for Kidney Stone Formers

In a crossover study of 15 individuals consuming different diets during 3 one-week phases, beef was linked with lower serum uric acid values than chicken or fish (6.5 mg/dL vs. 7.0 mg/dL and 7.3 mg/dL, respectively), and fish (741 mg/day) was associated with higher urinary uric acid levels than beef (638 mg/day) or chicken (641 mg/day). No significant differences in urinary pH, sulfate, calcium, citrate, oxalate, or sodium were observed in the Journal of Urology study. Average saturation index for calcium oxalate was highest for beef (2.48), although the difference reached significance only compared with chicken (1.67), not fish (1.79).

Saturday, February 8, 2014

New Method Generates Large Numbers of Insulin-Secreting Beta Cells

Researchers have found that when they treat mouse fibroblasts with a unique cocktail of molecules and reprogramming factors, the cells transform into endoderm-like cells. Then, when they treat these new cells with other compounds, they transform into pancreatic progenitor-like cells (PPLCs). Researchers also discovered that they could coax PPLCs cultured in laboratory dishes to mature into insulin-secreting cells. When the team transplanted PPLCs into mice with hyperglycemia, the animals’ glucose levels started to decrease gradually after 1 week. Eight weeks post-transplant, the PPLC’s had given rise to fully functional insulin-secreting beta cells, according to the Cell Stem Cellresearch.

Seafood Toxin Causes Kidney Damage in Mice at Levels Considered Safe for Consumption

The neurotoxin domoic acid, which can accumulate in seafood and is cleared from the body by the kidneys, causes kidney damage in mice at levels considered safe for human consumption, according to a new JASN study. By giving mice varying doses of domoic acid and then assessing the animals’ kidney health, investigators found that the kidney is much more sensitive to the toxin than the brain. The findings suggest that the FDA, which has set a legal limit of domoic acid in seafood based primarily on its adverse neurological effects, may need to reconsider what levels of the toxin are safe.

Thursday, February 6, 2014

ESRD Patients with Renal Cell Carcinoma Have Favorable Prognoses

In a study of renal cell carcinoma (RCC) patients, those with ESRD had smaller tumors and a lower prevalence of advanced disease. ESRD was associated with decreased tumor recurrence and clear cell pathology, and no ESRD patients had metastatic disease. The differences may be due to favorable histopathologic tumor characteristics in ESRD patients, as well as their likelihood of receiving early diagnoses. There was no difference in overall or cancer-specific mortality between the groups. The Clinical Transplantation study included 84 ESRD patients who underwent nephrectomy and were found to have RCC since 1999, compared with 243 RCC patients without ESRD.

Wednesday, February 5, 2014

Canadian Guidelines Recommend an “Intent-to-Defer” Approach to Dialysis

New Canadian Society of Nephrology guidelines published in CMAJ recommend that nephrologists closely monitor patients with an eGFR <15 mL/min/1.73 m², and that dialysis does not need to start until a patient’s eGFR drops to 6 mL/min/1.73 m² or has clinical worsening. This should allow patients to avoid the burden of earlier dialysis initiation when clinical indications are not present, while avoiding complications of uremia. The recommendation is based on a review of 23 studies, including the IDEAL trial, which found that early initiation did not improve survival, quality of life, or hospital admission rates compared with deferred initiation.

Testosterone supplements linked to increased heart attack risk in men.

The CBS Evening News (1/29, story 9, 1:45, Pelley) reported that new research suggests “a link between testosterone supplements and heart attacks.”

        USA Today (1/30, Szabo) reports that the study, published in PLOS One, found that “taking testosterone therapy doubled the risk of heart attack among men over age 65 and nearly tripled the risk in younger men with a history of heart disease.” This research, “which involved 56,000 men, is the latest in a series of studies raising concerns about the heart attack risk from testosterone therapy, whose popularity has ballooned in recent years.”

        On its website, NBC News (1/30, Fox) reports that “to be sure,” the researchers “compared the men getting testosterone to those getting prescriptions for erectile dysfunction drugs, as the two groups are similar in many ways.” The investigators found that the ED medications “only very slightly raised the risk of heart attack.”

        The New York Times (1/30, O'Connor) “Well” blog reports, “By itself, the new study, which was not a randomized trial...’may not tell us very much,’ said Dr. Michael Lauer, the director of cardiovascular sciences at the National Heart, Lung and Blood Institute, who was not involved in the study.” However, added Dr. Lauer, “when you put this together with the rest of the medical literature, this tells us that we potentially have a problem.” Meanwhile, “in a statement, Andrea Fischer, an F.D.A. spokeswoman, said the agency was reviewing the new findings.”

        On its website, TIME (1/30, Sifferlin) reports that although it is unclear “why testosterone can harm the heart, some studies suggest that it can lower levels of HDL, or good cholesterol, and therefore increase the risk of heart disease.”

        Meanwhile, on the CBS News (1/30) website, CBS’ Dr. Jon Lapook writes that a “possible way testosterone might be causing problems is by increasing clotting within arteries supplying the heart.”

        Forbes (1/30) contributor Ed Silverman points out that these “findings come amid years of aggressive promotion of testosterone treatments.” Research “published last fall in the Journal of the American Medical Association noted that annual prescriptions for these elixirs rose more than five-fold from 2000 to 2011, reaching 5.3 million prescriptions.”

        The Los Angeles Times (1/30, Healy) “Science Now” blog also covers the story.

Rheumatoid Arthritis May Increase Risk for Loss of Kidney Function

Patients with rheumatoid arthritis (RA) are more likely to develop reduced kidney function over time, and cardiovascular disease (CVD) appears to play a role. AnAJKD study of 813 patients with RA and 813 non-RA individuals found the 20-year cumulative incidence of reduced kidney function was higher in patients with RA compared with non-RA participants for eGFR below 60mL/min/1.73m² (25% vs. 20%), but not eGFR below 45mL/min/1.73m² (9% vs. 10%). In RA patients, those with CVD at baseline were 77% more likely to experience a drop in kidney function to below 60 mL/min/1.73m².

Naproxen may be safer than rival painkillers, FDA says.

ABC World News (1/28, story 6, 0:25, Sawyer) reports in its broadcast that an FDA report said naproxen found in Bayer AG’s Aleve painkiller could be a safer alternative for people with heart diseases compared with its rivals. “The FDA found the key ingredient may provide a lower risk of heart attack and stroke than a rival medication, Ibuprofen,” ABC News said.

        The Wall Street Journal (1/29, Burton, Dooren, Subscription Publication) reports proof that naproxen, found in Bayer AG’s Aleve and other generic medications, is safer comes from a number of studies the FDA reviewed since 2005.

        The AP (1/29, Perrone) reports FDA staffers backed “relabeling naproxen to emphasize its safety.” The labeling changes “could make Aleve and other naproxen drugs the first choice for patients with a higher risk for heart problems,” according to Ira Loss, a pharmaceutical analyst with Washington Analysis.

        Bloomberg News (1/28, Edney) reports the FDA is asking advisers to consider whether to block the ongoing safety study of Pfizer Inc. arthritis medicine Celebrex (celecoxib) “compared with ibuprofen and naproxen” since naproxen “is seen as safer.” Bloomberg also notes that a study published in medical journal Lancet last year also showed naproxen was safer compared with other painkillers.

Trial suggests obeticholic acid may be effective treatment for nonalcoholic steatohepatitis.

The New York Times (1/10, Pollack, Subscription Publication) reports that a clinical trial suggests that obeticholic acid may be “the first effective treatment for” nonalcoholic steatohepatitis (NASH). The trial “was stopped earlier than expected because the drug was working so well.”

     The Wall Street Journal (1/10, Loftus, Subscription Publication) reports that the study, which included more than 280 participants, was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

        The AP (1/10) reports that the trial “compared a daily 25-millligram oral dose of obeticholic acid with a placebo.” Those given the medication “for 72 weeks were more likely to have a significant reduction in disease.” Also covering the story are Bloomberg News (1/10, Armstrong), Reuters(1/10, Manocha) and Forbes (1/10, Solomon).

Antihypertensive’s Effects Not Reduced in Patients with Low Kidney Function

A new study reports that low kidney function does not reduce the short-term effects of the antihypertensive chlorthalidone. The Hypertension study compared the effects of 8-week treatment with 25 mg chlorthalidone in addition to ongoing treatment in 60 hypertensive control patient and 60 hypertensive patients with low kidney function. By week 8, blood pressure decreased in both groups without significant between-group differences. Incidence of adverse events was similar in the two groups. Baseline estimated GFR did not predict blood pressure changes and adverse events in either group.

Vitamin K May Help Prevent Vascular Calcification in Dialysis Patients

A Vitamin K supplementation may help prevent vascular calcification in hemodialysis patients, according to aNephrology Dialysis Transplantation study. The vitamin K-dependent matrix Gla protein (MGP) is a powerful inhibitor of vascular calcification, and dialysis patients are known to have high levels of the inactive form of the protein. To test whether vitamin K2 (menaquinone) might improve the calcification inhibitory activity of MGP, researchers randomized 200 dialysis patients to receive 360, 720, or 1080 µg of menaquinone-7 (MK-7) thrice weekly for eight weeks. MK-7 supplementation reduced inactive MGP, with levels decreasing by 17%, 33%, and 46% in the respective groups.

Additives in Processed Foods Boost Sodium and Phosphorus Intake

A recent study found that additives in processed foods can augment total sodium and phosphorus content by approximately 60% per day. The additive-enhanced diet contained the same food items as a low-additive diet except that highly processed foods were substituted for minimally processed foods. When averaged over 4 days, the measured phosphorus content of the additive-enhanced diet was 606 mg higher and the sodium content was 1329 mg higher than the low-additive diet. The Journal of Renal Nutrition findings indicate that food additives present a significant barrier to lowering sodium and/or phosphorus intake in CKD patients.

New recommendations on hypertension management in older people released.

The New York Times (12/19, A23, Kolata, Subscription Publication) reports that “new guidelines suggest that people over 60 can have a higher blood pressure than previously recommended before starting treatment to lower it.” The guidelines committee, “composed of 17 academics, was tasked with updating guidelines last re-examined a decade ago.” The recommendations were “published online on Wednesday in The Journal of the American Medical Association.”

        The AP (12/19) reports that “the panel completed its work earlier this year, around the same time that the National Heart, Lung and Blood Institute announced that it was getting out of the guidelines business and turning the job over to the American Heart Association and American College of Cardiology.”

        The Wall Street Journal (12/19, A2, Winslow, Subscription Publication) points out that neither the American College of Cardiology nor the American Heart Association vetted the document, nor did the NHLBI.

        The Los Angeles Times (12/19, Kaplan) “Science Times” blog reports that “rather than aim for a target blood pressure of 140/90 mm Hg, the target will be relaxed slightly to 150/90 mm Hg, according to” the “new guidelines.” The guidelines’ authors “emphasized that they were not changing the definition of high blood pressure.” Instead, “they are recognizing that data from randomized clinical trials do not show that using drugs to nudge down systolic blood pressure from 150 to 140 provides any health benefit.”

        Bloomberg News (12/19, Cortez) reports that individuals aged “60 and older were focused on in the guidelines because they ‘are a unique population and we are concerned about the number of medications that may be required,’ said Paul James, the lead author of the article.”

        According to the Boston Globe (12/19, Kotz), “a number of cardiologists...complained that the new guideline was not issued by any major medical group or government entity.”

        Harlan Krumholz, MD, discusses the guidelines in the New York Times (12/19) “Well” blog. Also covering the story are CNN (12/19, Willingham), MedPage Today (12/19, Neale), and HealthDay (12/19, Thompson).