Fractional Excretion of Uric Acid?

All nephrologists, and most physicians and medical students are very familiar with the fractional excretion of sodium (FENa). The FENa (Urine Na x Plasma Creatinine / Plasma Na x Urine Creatinine) helps to differentiate the cause of acute renal failure (sorry, acute kidney injury). It is classically used in separating the differential diagnosis of AKI into three categories: pre-renal, intra-renal and post-renal.

A problem arises when a patient is on diuretics and renal perfusion is decreased. On diuretics, FENa is less accurate and useful. I have used the FE of urea in his setting. The utility of the FE Urea has been questioned, but is considered a better measurement in this circumstance. This month in the American Journal of Kidney Diseases, they report on the possibility of another calculation in these cases, the fractional excretion of uric acid (FEUA). The study was small (44 patientes) and needs to be validated, but the FEUA may just be more useful in the diagnosis of AKI caused by decreased kidney perfusion.

This Just In... Salt Still Stinks

This is not a new revelation, but a met-analysis examining studies relating salt intake to stroke and cardiovascular disease has just been published by the British Medical Journal. 

Included in this review were 19 independent cohort samples from 13 studies, with 177,025 participants (follow-up 3.5-19 years) and over 11,000 vascular events. Higher salt intake was strongly associated with a higher incidence of stroke and cardiovascular disease:

• STROKE: 1.23 risk, 95% confidence interval 1.06 to 1.43, P = 0.007
• CARDIOVASCULAR DISEASE: 1.14 risk, 95% CI 0.99 to 1.32, P = 0.07

The longer the study and the larger the difference in salt intake yielding the greatest differences in risk. To no ones surprise, the conclusion of the study was that high salt intake increases the risk of stroke and cardiovascular disease. A goal of less than 2000 mg a day should be considered for all, especially those with other risk factors.

Does a Low Protein Diet Help Halt CKD Progression?

Another blow to those who are steadfast in their recommendation of a low protein diet for patients with CKD....

A study published in the American Journal of Kidney Disease takes a look prospectively at stage 4 and 5 patients comparing low protein diet (LPD) to moderate protein diet (MPD). The study included 423 patients with advanced CKD. They were randomly assigned between January 1999 and January 2003 and followed up until December 2006 or death. The groups were split to LPD defined as 0.55 g/kg/day and MPD which was 0.8 g/kg/day. We can debate the validity of these definitions, but it seems to be reasonable based upon the literature.

The LPD did not decrease the risk of death or dialysis therapy initiation compared with the MPD. This was a relatively small study from Italy with an overall low event rate. Nevertheless, I can still feel justified in not recommending a very difficult to adhere to LPD (or very low protein diet depedning on your definition).

Genzyme Scraps Plans for More Potent Phosphorous Binder

Well, I just had the "delicious" powder form of Renvela today. The citrusy taste isnt too bad, but I still feel the particles in the back of my throat. I am curious to see what dialyzors think about this new form of Renvela. My Genzyme rep has been quick to point to the problems with the unconventional Fosrenol, but now he seems to believe this will be a hit. I am skeptical.

One thing my Genzyme representative did not tell me about was the failure of its new proposed APB (advanced phosphate binder). Hmmmm, he must have forgotten. The makers of Renvela (and formerly, Renagel) were seeking to develop a higher potency phosphous binder that would maintain the clinical benefits of Renvela. Woops, this new formulation proved to be no more effective than Renvela. Apparently, Genzyme is "not planning to pursue further clinical development of the APB".

For more information, see the press release.
 

Medpage: More on Renal Artery Stenosis (ASTRAL Trial)

NEJM: Revascularization vs. Medical Therapy for RAS

This week, the New England Journal of Medicine printed a report by the ASTRAL investigators regarding the management of patients with renal artery stenosis (RAS). This is a topic that has been hotly debated in not only the nephrology literature, but has filtered into cardiovascular, intertentional radiology, vascular, hypertension as well as general medicine journals.

Is a conservative or invasive approach to atherosclerotic renal artery stenosis best? If there is a blockage or narrowing it should be corrected, right? Not necessarily. The enthusiasm for revascularization whether by angioplasty (with or without stent) or surgically has waned considerably over the last few years.

The study reiterated something most nephrologists have believed for a while now, there is NO WORTHWHILE CLINICAL BENEFIT FROM REVASCULARIZATION IN PATIENTS WITH ATHEROSCLEROTIC RENAL VASCULAR DISEASE.

Another Blow to ESA Advocates

A study printed in the Journal of the National Cancer Institute has taken a look at cancer patients using erythrocyte stimulating agents (ESA)... and it is not good news for Johnson & Johnson and Amgen.

The study examined patient with cancer, not CKD. They evaluated 56,210 patients who were diagnosed with lymphoma, breast cancer, non-small cell lung cancer, or colon cancer over a 10-year period who were treated with chemotherapy.  From 1991 through 2002, 15,346 (27%) of this patients received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Despite the expected decrease in the need for red blood cell transfusions with the increased use of ESAs... the rate of transfusion for these patients between 1991 and 2002 remained constant at 22.%

Although this study was done in cancer patients, the widespread use of ESAs has been under a great deal of scrutiny. This is another example of how the promise of increased ESA use has not lived up to expectations.

New NephSAP Download Available

As I previously wrote....

I love NephSAP as much as the next nephrologist. I think the ASN does a great job and the booklets are phenomenal. That said, I can't make it through more than 5 minutes of the audio versions of NephSAP's. I feel they are absolutely brutal to listen all the way through.

I much prefer and recommend the print version.. unless you suffer from debilitating insomnia and are all out of Ambien.

Nevertheless, the latest installment is available: Volume 8, Number 6 - Transplantation

Enjoy

FDA Warns About Byetta Induced Renal Failure

FDA has 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. 

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. The report states that, "Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems". However, as we know everyone who would be on Byetta has diabetes and thus inherently has at least one risk factor for CKD.

The 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.

Cross off another diabetes medication for patients with advanced CKD....

High Fructose Linked to Hypertension

More from Renal Week in San Diego....

Lead investigator Diana I. Jalal, MD, assistant professor of renal medicine at the University of Colorado Health Sciences Center in Aurora and her colleagues used the NHANES data to evaluate median fructose intake from food high in added sugar, including bakery products, dairy desserts, chocolate and other candy, dried fruits, honeys, jams, jellies, syrups, and sugar-sweetened soft drinks (these soft drink account for 33-40% of fructose consumption in the USA as per Dr Jalal).

An analysis of data from more than 4500 NHANES participants  showed that consuming 74 grams or more of fructose per day  (equivalent to about 2.5 cans of 12-ounce sugary soda) correlated significantly with hypertension. Those with the high intake of fructose had a 28% increased risk for blood pressure of 135/85 mm Hg or higher, a 36% increased risk for blood pressure of 140/90 mm Hg or higher, and an 87% increased risk for blood pressure of 160/100 mm Hg or higher.

The relation was seen only between systolic blood pressure and fructose intake, Dr. Jalal said. There was no correlation between fructose consumption and diastolic blood pressure. Again, this is an observational report and further studies are indicated. Nevertheless, whether a strong link to hypertension is proven or not,  I think it is safe to recommend a diet of low fructose intake to everyone.

Low Vitamin D and CKD link?

Another report coming out of ASN's Renal Week details the possible link between low levels of Vitamin D in African Americans to their higher incidence of ESRD.

Michal L. Melamed, MD, MHS, associate professor of medicine and epidemiology at Albert Einstein College of Medicine in the Bronx, New York, and her coauthors analyzed data from 13,328 participants in the National Health and Nutrition Examination Survey (NHANES) III Follow-Up Study, in which 25(OH)D levels were measured from 1988 through 1994, and then participants were followed for up to 12 years. Serum 25(OH)D deficiency was defined as anything below 15 ng/mL.

After adjustment for clinical, demographic, and socioeconomic factors, the incidence of ESRD was 2.6 times greater in people whose serum 25(OH)D was less than 15 ng/mL than in those with higher levels. When the investigators adjusted for clinical covariates other than 25(OH)D, the risk of developing ESRD was 2.83 times higher among the black than among the white participants. Adjusting for ESRD reduced the risk by 58%, leading the authors to conclude that low serum 25(OH)D levels might account for a significant proportion of the ESRD risk experienced by the black participants.

Before putting everyone on 400- 1000 IU Vitamin D to prevent ESRD, we must understand this is an observational study and must be interpreted as such. Whether there is an association or a cause - effect relationship is as of yet, unknown.