Sunday, December 27, 2009
Monday, December 14, 2009
Morbidity and Mortality in 1022 Consecutive Living Donor Nephrectomies: Benefits of a Living Donor Registry
Mjøen, Geir; Øyen, Ole; Holdaas, Hallvard; Midtvedt, Karsten; Line, Pål-Dag
Transplantation: 15 December 2009 - Volume 88 - Issue 11 - pp 1273-1279
Background. We assessed postoperative complication rates in living donor nephrectomies (LDN) during the last decade (1997-2008).
Methods. Postoperative complications were classified by the Clavien grading system. We defined Clavien grade more than or equal to 3 as major complications. A total of 1022 LDNs performed during the period 1997-2008 were included.
Results. Median age at donation was 47.7 years (range 18.4-78.9), and mean body mass index was 25.4 (SD 3.2). There was no peri- or postoperative mortality. Laparoscopic nephrectomy was performed in 244 (23.9%) donors. Three of these needed surgical conversion. A total of 30 major (2.9%) and 184 (18%) minor complications were registered. There was a higher frequency of major complications in the laparoscopic group (4.1% vs. 2.6%), but the difference was not statistically significant. Twenty-three donors underwent early re-operations. Wound infection developed in 3.7% of donors. Increased risk was associated with body mass index more than 25 (OR 4.03; 95% CI 1.80, 9.04) and smoking (OR 4.38; 95% CI 2.30, 9.96). Significant perioperative bleeding occurred in 1.6%. There were seven cases of renal artery laceration. Increased risk for a combined endpoint of intraoperative incidents, major complications and significant bleeding were seen in relation to laparoscopic surgery (OR 2.63; 95% CI 1.33, 5.19).
Conclusion. The risk of major complications related to LDN is low, but do represent a potential hazard to the donor. The special nature of LDN and the constantly evolving operative technique requires vigilant surveillance, by the use of national or supranational registries/databases.
Tuesday, November 3, 2009
Byetta (exenatide) - Renal Failure
FDA notified healthcare professionals of revisions to the prescribing information for Byetta (exenatide) to include information on post-marketing reports of altered kidney function, including acute renal failure and insufficiency. Byetta, an incretin-mimetic, is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
From April 2005 through October 2008, FDA received 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal insufficiency), in patients using Byetta. Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems. Labeling changes include:
•Information regarding post-market reports of acute renal failure and insufficiency, highlighting that Byetta should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease.
•Recommendations to healthcare professionals that caution should be applied when initiating or increasing doses of Byetta from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min).
•Recommendations that healthcare professionals monitor patients carefully for the development of kidney dysfunction, and evaluate the continued need for Byetta if kidney dysfunction is suspected while using the product.
•Information about kidney dysfunction in the patient Medication Guide to help patients understand the benefits and potential risks associated with Byetta.
Read the complete MedWatch 2009 safety summary, including a link to the Healthcare Professional information sheet, at:
http://www.fda.gov/Safety/ MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalPro ducts/ucm188703.htm
Long-Term Use of Trimethoprim-Sulfamethoxazole May Reduce UTIs in At-Risk Children
October 29, 2009 — Use of long-term, low-dose trimethoprim-sulfamethoxazole may reduce urinary tract infections in at-risk children, according to the results of a study reported in the October 29 issue of the New England Journal of Medicine.
"Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking," write Jonathan C. Craig, MB, ChB, PhD, from University of Sydney in Sydney, Australia, and colleagues from the Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators. "This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children."
Children younger than 18 years with at least 1 microbiologically proven urinary tract infection were randomly selected to receive either daily trimethoprim-sulfamethoxazole suspension (2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The main endpoint of the study was symptomatic, microbiologically confirmed urinary tract infection, based on intent-to-treat analyses with the use of time-to-event data.
Although planned sample size was 780, a total of 576 children (64% girls) were recruited and randomly selected from December 1998 to March 2007. At study entry, median age was 14 months; 71% were enrolled after the first diagnosis of urinary tract infection, and 42% had known vesicoureteral reflux, which was grade 3 or higher in 53% of these participants.
Of 288 patients in the antibiotic group, urinary tract infection developed in 36 (13%) during the study vs 55 (19%) of 288 patients in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 - 0.93; P= .02 by the log-rank test).
Lower absolute risk for urinary tract infection in the antibiotic group (6 percentage points) appeared to be consistent across all subgroups of patients (P ≥ .20 for all interactions).
"Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children," the study authors write. "The treatment effect appeared to be consistent but modest across subgroups."
Limitations of this study include lower recruitment than planned, study not designed to estimate the effect of trimethoprim-sulfamethoxazole on the progression of renal damage, and inability to determine the incremental effect of trimethoprim-sulfamethoxazole vs circumcision.
"Since the rate of adverse events did not differ between the two study groups and the risk of infections other than urinary tract infection that were severe enough to require the use of antibiotics was lower in the antibiotic group, it would be reasonable for clinicians to recommend the use of trimethoprim-sulfamethoxazole in children who are at high risk for infection or whose index infection was severe," the study authors conclude. "In children who have had a single symptomatic urinary tract infection, prophylaxis with trimethoprim-sulfamethoxazole should be considered but not routinely recommended. The modest size of the benefit and the possibility of rare but serious complications from the use of trimethoprim-sulfamethoxazole, such as the Stevens-Johnson syndrome, suggest that the drug should not be used prophylactically in children who have never had a symptomatic urinary tract infection (e.g., those with congenital hydronephrosis or siblings with reflux)."
In an accompanying editorial, Alejandro Hoberman, MD, from the Children's Hospital of Pittsburgh in Pittsburgh, Pennsylvania, and Ron Keren, MD, MPH, from the Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, note that the time-to-event analysis showed that the effect of long-term antibiotics was not sustained, and the number of children who would need to have been treated to prevent 1 infection was relatively large.
"Given the modest overall effect size, a one-size-fits-all approach may not be appropriate," Drs. Hoberman and Keren write. "The need to detect vesicoureteral reflux is probably the most important issue facing parents and clinicians....Early diagnosis and treatment of urinary tract infection and treatment of dysfunctional voiding, which predisposes many children to urinary tract infection, are likely to go a long way toward preventing long-term renal damage."
The National Health and Medical Research Council of Australia, the Financial Markets Foundation for Children of Australia, and a private donation by J.T. Honan of the Manildra Group supported this study. The study authors and editorialists have disclosed no relevant financial relationships.
N Engl J Med. 2009;361:1748-1759, 1804-1806.
Thursday, October 22, 2009
Strict Blood-Pressure Control and Progression of Renal Failure in Children
Background Although inhibition of the renin–angiotensin system delays
the progression of renal failure in adults with chronic kidney
disease, the blood-pressure target for optimal renal protection is
controversial. We assessed the long-term renoprotective effect of
intensified blood-pressure control among children who were receiving a
fixed high dose of an angiotensin-converting–enzyme (ACE) inhibitor.
Methods After a 6-month run-in period, 385 children, 3 to 18 years of
age, with chronic kidney disease (glomerular filtration rate of 15 to
80 ml per minute per 1.73 m2 of body-surface area) received ramipril
at a dose of 6 mg per square meter of body-surface area per day.
Patients were randomly assigned to intensified blood-pressure control
(with a target 24-hour mean arterial pressure below the 50th
percentile) or conventional blood-pressure control (mean arterial
pressure in the 50th to 95th percentile), achieved by the addition of
antihypertensive therapy that does not target the renin–angiotensin
system; patients were followed for 5 years. The primary end point was
the time to a decline of 50% in the glomerular filtration rate or
progression to end-stage renal disease. Secondary end points included
changes in blood pressure, glomerular filtration rate, and urinary
protein excretion.
Results A total of 29.9% of the patients in the group that received
intensified blood-pressure control reached the primary end point, as
assessed by means of a Kaplan–Meier analysis, as compared with 41.7%
in the group that received conventional blood-pressure control (hazard
ratio, 0.65; confidence interval, 0.44 to 0.94; P=0.02). The two
groups did not differ significantly with respect to the type or
incidence of adverse events or the cumulative rates of withdrawal from
the study (28.0% vs. 26.5%). Proteinuria gradually rebounded during
ongoing ACE inhibition after an initial 50% decrease, despite
persistently good blood-pressure control. Achievement of
blood-pressure targets and a decrease in proteinuria were significant
independent predictors of delayed progression of renal disease.
Conclusions Intensified blood-pressure control, with target 24-hour
blood-pressure levels in the low range of normal, confers a
substantial benefit with respect to renal function among children with
chronic kidney disease. Reappearance of proteinuria after initial
successful pharmacologic blood-pressure control is common among
children who are receiving long-term ACE inhibition
Wednesday, September 2, 2009
Wearable artificial kidney WAK
Technology Brings "Wearable Artificial Kidney" Closer to Reality
NEW YORK (Reuters Health) Aug 20 - A new wearable artificial kidney (WAK) should soon be ready for clinical trials. Technical breakthroughs have allowed construction of an 8-pound prototype that continuously dialyzes patients' blood.
"The important thing is that we finally have (a dialysis device) that is wearable, works on batteries, and requires very little water as compared to the regular devices that use many gallons of water for each treatment," lead author Dr. Victor Gura explained to Reuters Health in email correspondence.
"The WAK is intended to be worn as a belt, under the patient's clothing," he added. "It works 24/7, and in as much as nobody takes out his own kidneys, we would hope patients would wear it continuously."
Dr. Gura is on faculty at Cedars-Sinai Medical Center in Beverly Hills, California, and is Chief Medical Officer of Xcorporeal Inc. in Los Angeles. In the August 20 early online issue of the Clinical Journal of the American Society of Nephrology, he and his associates describe the solute-removal capabilities of the sorbent-dialysate-regenerating WAK.
The machine works with intermittent flow changes in blood and dialysate, such that the dialysate circulates in countercurrent flow to the blood, in order to increase fluid flux across the dialysis membrane.
Because the volume of dialysate is small, before returning to the dialyzer most of it is recycled through canisters containing the sorbents urease, zirconium phosphate, hydrous zirconium oxide, and sodium bicarbonate.
Other features that improve its capability include a larger surface area high-flux dialyzer and a higher dialysate pH. Activated charcoal is used to remove beta-2 microglobulin from blood.
Dr. Gura commented that so far, the device appears to be very safe and efficient, but further studies will be required.
"Renal failure is too costly to allow society to treat all comers," he continued. "These patients are subject to great suffering and have a high mortality. We hope that new technologies will alleviate the plight of these patients and improve their survival. We also hope to reduce the enormous cost associated with treating end stage renal disease."
Clin J Am Soc Nephrol 2009.
Saturday, April 25, 2009
Genetically Modified Pig Raises Hope for Organ Transplants
Tuesday, April 21, 2009
Mobile phone may be source of nosocomial infection
NEW YORK Mar 05 - The mobile phones of hospital healthcare workers are frequently contaminated with bacteria and fungi, including nosocomial pathogens, a Turkish research team reports in the BMC journal Annals of Clinical Microbiology and Antimicrobials.
Dr. Fatma Ulger and colleagues at Ondokuz Mayis University, Samsun, cultured the dominant hand and the mobile phones of 200 physicians, nurses, and other healthcare staff working in intensive care units and operating rooms.
They found that 95% of telephones were contaminated, often with more than one species. Approximately half of the Staphylococcus aureus isolates were resistant to methicillin, while one third of Gram negative rods were resistant to ceftazidime. Isolated microorganisms from hands and phones were similar.
Of the nosocomial pathogens isolated from phones in intensive care units, the report indicates, 33% were staphylococci, 21% were nonfermentative Gram negative rods, 21% were coliforms, 7% were enterococci, and 12% were yeasts.
Upon questioning the study participants, Dr. Ulger's team found that 90% never cleaned their mobile phones. Thus, they conclude, mobile phones "may facilitate transmission of bacterial isolates from patient to patient in wards or hospitals."
They recommend routine decontamination of mobile phones with alcohol-containing disinfectants. "In the future," they add, "another way of reducing bacterial contamination on mobile phones might be the use of antimicrobial additive materials."
Ann Clin Microbiol Antimicrob 2009.
Thursday, April 16, 2009
Plastic bottles - Breast cancer
Wednesday, April 8, 2009
Pregnancy Outcomes After Kidney Donation
been viewed to be favorable. We determined fetal
and maternal outcomes in a large cohort of kidney
donors. A total of 2102 women have donated a
kidney at our institution; 1589 donors responded to
our pregnancy surveys; 1085 reported 3213 pregnancies
and 504 reported none. Fetal and maternal outcomes
in postdonation pregnancies were comparable
to published rates in the general population. Postdonation
(vs. predonation) pregnancies were associated
with a lower likelihood of full-term deliveries (73.7%
vs. 84.6%, p = 0.0004) and a higher likelihood of fetal
loss (19.2% vs. 11.3%, p < 0.0001). Postdonation
pregnancies were also associated with a higher risk
of gestational diabetes (2.7% vs. 0.7%, p = 0.0001),
gestational hypertension (5.7% vs. 0.6%, p < 0.0001),
proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia
(5.5% vs. 0.8%, p < 0.0001). Women who had both
pre- and post-donation pregnancies were also more
likely to have these adverse maternal outcomes in their
postdonation pregnancies. In this large survey of previous
living donors in a single center, fetal and maternal
outcomes and pregnancy outcomes after kidney
donation were similar to those reported in the general
population, but inferior to predonation pregnancy
outcomes.
Monday, April 6, 2009
How Effective Are ACE Inhibitors for Hypertension? A Best Evidence Review
Angiotensin-converting enzyme (ACE) inhibitors are some of the most commonly prescribed medications for hypertension. Indeed, they were cited in a recent survey of primary care supervisors in Australia[1] as the treatment most often recommended by guidelines and favored over other antihypertensive drugs as first-line agents. This enthusiasm for ACE inhibitors is somewhat inconsistent with current recommendations,[2] which prefer thiazide diuretics as first-line medication for uncomplicated cases of hypertension. ACE inhibitors are seen as more appropriate for first-line use when other high-risk conditions are present, such as diabetes. Still, given clinicians' favorable experience with ACE inhibitors and the increasing prevalence of type 2 diabetes in the population, it is clear that ACE inhibitors will maintain an important role in the treatment of hypertension.
With the popularity of ACE inhibitors in mind, investigators conducted a systematic review of published studies to determine how effective the drugs actually are in reducing blood pressure. They also examined dose effectiveness, adverse effects, and the role of co-occurring conditions.
The Study Findings
Researchers looked for double-blind studies comparing ACE inhibitors and placebo. All included studies were at least 3 weeks in duration and measured blood pressure as an endpoint at 3-12 weeks. Studies that featured a response-dependent titration of medications were included in the review. Only research that focused on patients with a blood pressure above 140/90 mm Hg was reviewed.
The review included 92 trials with a total of 12,954 participants (mean age, 54 years). Mean baseline blood pressure was 157/101 mm Hg and mean pulse pressure was 56 mm Hg. The majority (75%) of included studies was industry-sponsored, and 82% of the trials examined fixed-dose ACE inhibitors. The duration of trials was generally short, which limited data with regard to adverse events and study withdrawals.
The main potential source of bias in the research was a lack of information with regard to how the studies were blinded. In addition, the reviewers suggested that the researchers could have preferentially selected patients more likely to respond to ACE inhibitors. This selection bias could make ACE inhibitors appear more effective than they truly are.
The studies covered 14 ACE inhibitors. The degree of homogeneity with regard to their efficacy in reducing blood pressure was remarkable. No one medication appeared superior to others.
Overall, ACE inhibitors had a modest collective effect in reducing blood pressure. The mean reduction in systolic blood pressure ranged between 6 mm Hg and 9 mm Hg, and the mean reduction in diastolic blood pressure was 4-5 mm Hg. Less data were available with regard to the blood pressure effects of ACE inhibitors at 1-12 hours after dosing, but the average decrease in blood pressure with ACE inhibitors around their peak concentration was greater than their average efficacy (11.4/6.4 mm Hg).
Dose Effectiveness
The study provided some important information about the relationship between the dose of ACE inhibitors and their effect on blood pressure. Doses lower than the manufacturers' maximum recommended dosage had the same blood pressure-lowering effect as the maximum dose. For example, doses of one eighth to one quarter of the maximum achieved the blood pressure-lowering effect of the maximum dose in 60% to 70% of cases. Half of the maximum dose achieved it 90% of the time. There was no blood pressure-lowering effect at or below one sixteenth of the maximum suggested dose. These data suggest that use of the maximum dosage of ACE inhibitors to achieve greater blood pressure control is usually unnecessary.
The research also identified dosing information for individual ACE inhibitors and suggested that the manufacturers' recommended starting doses of benazepril, moexipril, and ramipril are higher than the minimum dose needed to reduce blood pressure. Conversely, captopril did not appear effective in reducing blood pressure at the manufacturers' recommended starting dose. Most of the maximum blood pressure-lowering effect of lisinopril was achieved at only one eighth of the recommended maximum dose.
ACE inhibitor dosing was also one of the biggest deficits in the current review. It was clear to the review authors that not all data in regard to the efficacy of different doses of ACE inhibitors were published. Instead, the data were supplied to regulators privately to determine the appropriate dosing range of ACE inhibitors.
Only half of trials provided data in regard to the rate of withdrawal due to adverse events. Collectively, there was no difference between ACE inhibitors and placebo in this critical outcome. ACE inhibitors did not significantly affect patients' heart rate.
The Role of ARB Inhibitors
The main finding of the current review is that ACE inhibitors as a class of medications have a fairly weak effect in reducing blood pressure in hypertension. Physicians might therefore consider an alternative inhibitor of the renin-angiotensin system, an angiotensin receptor blocker (ARB). These newer medications have been heavily promoted for the treatment of hypertension, and they are not associated with cough, which is one of the most prevalent side effects of ACE inhibitors.
However, a systematic review of the efficacy of ARBs for hypertension,[3] published concurrently with the review of ACE inhibitors, suggested that these medications have very similar efficacy. The reviewers studied 46 randomized controlled trials examining 9 ARBs, and found that the overall efficacy in reducing systolic and diastolic blood pressure was -8 mm Hg and -5 mm Hg, which was similar to an ACE inhibitor. The peak effect of ARBs was also similar, with an average blood pressure reduction of approximately 12/7 mm Hg. Much like ACE inhibitors, ARBs were effective at one eighth to one half of the manufacturers' recommended doses.
Addressing Other Health Issues
Physicians might choose ACE inhibitors to treat hypertension for other possible health benefits associated with these medications, especially the potential to prevent type 2 diabetes. ACE inhibitors can have a positive effect on glucose metabolism through multiple mechanisms, and previous research suggested that they could prevent incident diabetes compared with other antihypertensive medications. Specifically, the Captopril Prevention Project[4] demonstrated a 14% relative reduction in this outcome among participants receiving captopril vs a diuretic or beta-blocker. This benefit, associated with captopril, was evident regardless of the baseline risk for diabetes, although the incidence of diabetes was not a primary outcome of the study.
The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial[5] directly examined the effect of ramipril vs placebo on the incidence of diabetes. This study examined patients with impaired fasting glucose levels or reduced insulin sensitivity but no history of cardiovascular disease. After a median of 3 years of treatment, ramipril was not associated with a significantly lower incidence of diabetes compared with placebo. Median fasting plasma glucose levels were also similar at the end of the trial. However, ramipril was associated with a higher rate of return to normoglycemia. An editorial[6] accompanying this article concluded that ACE inhibitors could not be recommended to reduce the risk for incident diabetes, although they might still confer some benefit on glucose metabolism.
Physicians might also consider using ACE inhibitors for hypertension in order to prevent incident heart failure. However, although ACE inhibitors are associated with numerous positive outcomes, including reduced mortality, among patients with known heart failure,[7] little evidence exists that they provide special protection against new heart failure. In a study of quinapril and placebo initiated shortly after myocardial infarction, there was no difference between treatment groups in a composite outcome of cardiovascular death and significant cardiovascular events.[8] Specifically, no difference was found in the risk for heart failure among those patients at high cardiovascular risk. Similarly, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Hearth Attack Trial (ALLHAT), the incidence of heart failure was similar among patients receiving lisinopril and chlorthalidone.[9]
Commentary
Although ACE inhibitors may not provide special protection against diabetes or heart failure among patients with hypertension, physicians should still consider these medications when managing hypertension. In fact, the nature of hypertension management dictates that they have to because most patients require more than 1 medication initially. In a recent study of men receiving care at a Veteran Affairs hospital, 60.4% of subjects with hypertension and significant cardiovascular risk were receiving multiple antihypertensive medications.[10] Nevertheless, only 28% of these same patients had reached their goal blood pressure levels, indicating that they needed titration of their medications, if not the addition of other antihypertensive drugs.
If most patients require multiple medications, physicians would be wise to spend more time focusing on which combinations of medications work best, as opposed to fretting about the choice of initial treatment. The current review of ACE inhibitors (and ARBs) is also a reminder that physicians should consider adding another medication prior to prescribing the full dose of these drugs. With these principles in mind, both physician and patient will get the maximum benefit from the chosen antihypertensive regimen.
Clinical Pearls
In the current review, ACE inhibitors were associated with an average reduction in systolic blood pressure between 6 mm Hg and 9 mm Hg and in diastolic blood pressure of 4-5 mm Hg;
ACE inhibitors achieved most of their power in reducing blood pressure at half of the maximum recommended dose, or less;
ARBs provide similar reductions in blood pressure compared with ACE inhibitors; and
There is no strong evidence that ACE inhibitors can prevent incident diabetes mellitus or heart failure.
