Prevención primaria de enfermedad renal en diabeticos

Primary Prevention of Diabetic Kidney Disease: Thumbs Up/Down

Bruce Jancin

August 21, 2014

Bruce Jancin, Family Practice News Digital Network

LAS VEGAS – Contrary to conventional wisdom, neither ACE inhibitors nor angiotensin receptor blockers have any role to play in primary prevention of diabetic kidney disease, according to Dr. Robert C. Stanton, chief of nephrology at the Harvard University’s Joslin Diabetes Center, Boston.

"I don’t see any unique indication for ACE inhibitors and ARBs for the primary prevention of kidney disease in diabetic patients, especially given that around 70% of diabetes patients will never develop kidney disease. They’re perfectly fine blood pressure pills. But as a magic kidney disease prevention drug, I don’t see any evidence for that. Of course, patients with proteinuria are another issue entirely. Those drugs absolutely are beneficial in that setting," he said at a meeting sponsored by the National Kidney Foundation.

When Dr. Stanton polled his audience electronically during the course of his talk, however, the majority of physicians indicated that they believe ACE inhibitors and ARBs are indeed useful for primary prevention of diabetic kidney disease. The evidence, Dr. Stanton emphasized, shows otherwise.

For example, a well-conducted, randomized, multicenter, placebo-controlled, 5-year clinical trial showed no benefit for enalapril or losartan in preventing kidney disease in patients with type 1 diabetes ( N. Engl. J. Med. 2009;361:40-51). And three randomized controlled trials showed no primary preventive benefit for candesartan in more than 5,000 patients with type 1 or type 2 diabetes (Ann. Intern. Med. 2009;151:11-20).

Dr. Stanton noted that lots of other interventions have been proposed for the primary prevention of kidney disease in diabetes patients. Some are supported by solid evidence of benefit, others are not.

Here is his view of the preventive landscape:

• Intensive blood glucose control. "This is the easy one," he said. "A lot of us in the diabetes world feel that a hemoglobin A 1c of 7% is the appropriate target for preventing many complications. It’s a reasonable target and should be achieved whether you’re talking about type 1 or type 2 patients."

The nephrologist noted that recent 25-year follow-up data from the landmark Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study showed that fully 18 years after the intervention ended, patients assigned to intensive blood glucose control still showed highly impressive 50% reductions in the cumulative incidence of both microalbuminuria and end-stage renal disease compared with patients placed on less intensive control (Diabetes Care 2014;37:24-30).

• Smoking cessation. Smoking has been linked to a several-fold increased risk of diabetic kidney disease. "I think of diabetes as an endothelial cell disease, and smoking is the greatest endothelial cell poison we’ve come up with. So stopping smoking is something well worth doing," Dr. Stanton said.

• Blood pressure control. No question exists regarding its renoprotective effect. But recent guidelines are dizzyingly all over the map in terms of target pressure recommendations.

"I’m getting a major headache reading these articles right now. I can show you the data. Good luck! I personally like a target of 130/80 mm Hg or less, particularly when it’s not that hard to get there. But I’d let you decide what particular target you favor," he said.

He prefers 130/80 mm Hg as a target blood pressure for primary prevention of diabetic kidney disease in large part because of a meta-analysis showing that it was associated with a 10% reduction in the risk of developing microalbuminuria and an 11% decrease in end-stage renal disease (PloS Med 2012;9(8):e1001293).

• Weight loss. The growing bariatric surgery literature supports weight loss as a primary preventive strategy.

• Protein intake. There is no role for a low-protein diet –say, less than 0.8 g/kg per day – for primary prevention of kidney disease in diabetes patients. And Dr. Stanton believes a high-protein diet in the range of more than 1.5 or 2 g/kg per day is best avoided in patients with diabetes, although he stressed that the evidence on this score remains sketchy.

Still, "I would not go on a body-building diet or an Atkins-type diet," he cautioned.

• Targeting glomerular hyperfiltration. Studies have shown conflicting results. "For me, there’s no clear role for targeting hyperfiltration," said Dr. Stanton, who cited a comprehensive review that he finds persuasive (Diabetologia 2010;53:2093-104).

The key to developing more effective primary prevention strategies, according to Dr. Stanton, will be first to establish markers that clearly identify the 30% or so of diabetes patients who will go on to develop renal disease, then test novel interventions specifically in that high-risk group.

Promising biomarkers include circulating tumor necrosis factor alpha receptor levels, von Willebrand factor, monocyte chemoattractant factor, asymmetrical dimethylarginine, interleukin-6 and -8, and Fas receptor.

For example, one study showed that patients with type 2 diabetes in the top quartile for circulating TNF receptor 1 had a cumulative 12-year incidence of end-stage renal disease of 54%, compared to just 3% in patients in the other quartiles ( J. Am. Soc. Nephrol. 2012;23:507-15).

"Lots of companies are looking at these now. These markers may be coming our way as indicators of people with diabetes who are likely to progress to kidney disease," Dr. Stanton said.

He reported serving as a consultant to Boehringer Ingelheim.

bjancin@frontlinemedcom.com

Copyright © 2014 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.

Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates.

Int J Clin Pract. 2013 Jun;67(6):544-51. doi: 10.1111/ijcp.12135. Epub 2013 Feb 15. Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates. Capitanio U , Salonia A, Briganti A, Montorsi F.

Abstract As the clinical effects of the available α1-adrenoceptors (ARs) blockers are usually considered comparable for treatment in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic enlargement, officially recognised guidelines do not make specific recommendations regarding the choice of which agent should be considered according to the patient's characteristics.

To analyse data supporting the use of silodosin, a highly selective once-daily dosing α1-ARs blocker, in different daily clinical practice scenarios.

A structured literature review was performed using data retrieved from articles assessing the role of silodosin in the management of LUTS secondary to benign prostatic hyperplasia (BPH). A literature search of English language publications was performed using MEDLINE(®) and Web of Science from 2000 to 2012 using the terms LUTS; BPH; silodosin; α1-ARs blockers. The papers with the highest level of evidence were identified and represent the basis of the present review.

Available data coming from basic research analyses, randomised trials and prospective studies showed that silodosin is efficacious for the initial management of patients with LUTS. Clinical developmental safety data from patients receiving silodosin with concomitant antihypertensive therapy do not indicate an increase in risk of orthostatic hypotension. In this context, a recent study demonstrated that silodosin can be safely administered to patients who are consensually assuming phosphodiesterase type 5 inhibitors. A recent randomised crossover study comparing the efficacy of silodosin and tamsulosin in patients with LUTS showed that further significant improvement was observed after switching to silodosin treatment, while worsening or little improvement was observed after switching to tamsulosin treatment. Preliminary results seem to demonstrate a potential role of silodosin in the treatment of chronic prostatitis/chronic pelvic pain syndrome and to facilitate ureteral stone passage, as well.

When considering the above cited pharmacological and clinical characteristics of the drug, silodosin can be considered in the following clinical scenario: patients suffering from moderate-severe nocturia, patients with low normal blood pressure levels and patients concomitantly treated with antihypertensive medications, patients concomitantly treated with phosphodiesterase type 5 inhibitors, patients not satisfied (for efficacy or tolerability) with previous treatment with other α1-ARs blockers.

Silodosin is efficacious for the initial management of patients with LUTS. Silodosin has a good cardiovascular safety profile and can be considered an option in patients with cardiovascular co-morbidities. It seems to be especially beneficial in patients with nocturia alone or presenting with the symptomatic trial nocturia-frequency-incomplete emptying. Patients on phosphodiesterase type 5 inhibitors treatment can be safely managed with silodosin.

© 2013 John Wiley & Sons Ltd.

Lowering Systolic BP Below 120 is Not Necessarily Better for People With Hypertension

Lowering Systolic BP Below 120 is Not Necessarily Better for People With Hypertension Tags: Hypertension Read/Add Comments | Email This | Print This

WINSTON-SALEM, NC-- June 16, 2014-- In a study published in the June 16 online edition of JAMA Internal Medicine, researchers at Wake Forest Baptist Medical Center, Winston Salem, North Carolina, found that lowering systolic blood pressure below 120 does not appear to provide additional benefit for patients.

“Frequently we treat patients’ blood pressure to the lowest it will go, thinking that is what’s best,” said lead author Carlos J. Rodriguez, MD, Wake Forest Baptist Medical Center.

“Our observational study found that treating to low pressures doesn’t provide any benefit to patients with regard to reducing risk of dangerous heart events like heart attack, heart failure and stroke. This calls into question the notion that lower is better,” Dr. Rodriguez added.

Previous studies had documented a progressive increase in heart disease risk as systolic blood pressure (SBP) rose above 115, but it was not known whether SBP lower than 120 in patients with hypertension lowered the risk of heart failure, stroke and myocardial infarction.

In this study, a total of 4,480 participants from the Atherosclerosis Risk in Communities Study were followed for 21 years for development of a cardiovascular event. Measurements of SBP were taken at baseline and at 3-year intervals. SBP was categorised as elevated (140 or greater), standard (120 -139) or low (less than 120). The study findings were independent of baseline age, gender, diabetes status, body mass index, cholesterol level, smoking status and alcohol intake. A cardiovascular event was defined as heart failure, ischaemic stroke, heart attack or death related to coronary heart disease.

The researchers found that among people with hypertension, once SBP is below 140, lowering it below 120 did not further reduce the risk of cardiovascular events.

“Our study found that the optimal blood pressure range for people with hypertension is120-139, which significantly reduces the risk of stroke, heart attack or heart failure,” Dr. Rodriguez said. “These findings suggest that you don’t need to go lower than that to have the benefits.”

Rodriguez said that his study was not a clinical trial and its results need to be confirmed; noting that a large clinical trial under way called SPRINT should either confirm or refute the findings.

SOURCE: JAMA Internal Medicine

Embarazo :hipertension y riesgo de enfermedad renal

Pregnancy: Hypertension and Risk for Kidney Disease

Renal Consult

RENAL CONSULT

2013;23(11):26-27

Mandy Trolinger, MS, RD, PA-C

Q If a pregnant woman has mild hypertension (eg, 140/90 mm Hg) but no albuminuria, is she at higher risk for kidney disease as she ages?

Gestational hypertension and preeclampsia are two types of hypertension that occur during pregnancy. Both occur after 20 weeks’ gestation and include a blood pressure reading greater than 140/90 mm Hg and no maternal history of hypertension. Proteinuria does not occur in gestational hypertension as it does in preeclampsia (proteinuria ≥ 300 mg in a 24-h urine collection).

One study evaluated more than 26,000 Taiwanese women with hypertension during pregnancy and compared them to more than 200,000 women without hypertension during pregnancy. It was found that hypertension during pregnancy increased the risk for chronic kidney disease (CKD) and end-stage renal disease (ESRD) later in life. Preeclampsia and eclampsia were even more likely to increase the risk for ESRD, ‐compared with gestational hypertension.

Preeclampsia occurs after 20 weeks’ gestation and includes elevated blood pressure (≥ 140 mm Hg systolic or ≥ 90 mm Hg diastolic) and proteinuria (≥ 0.3 g in 24 h). Severe preeclampsia develops with the addition of worsening hypertension and proteinuria, oliguria less than 500 mL in 24 h, thrombocytopenia, hemolysis, elevated liver enzymes, low platelets, pulmonary edema, and fetal growth restriction. Eclampsia is when seizures occur in addition to preeclampsia. Gestational hypertension has also been linked with a higher risk for ischemic heart disease, myocardial infarcts and death, heart failure, ischem-ic stroke, kidney disease, and diabetes.

Because of the association between hypertension during pregnancy and subsequent development of CKD, it is very important that mothers who have hypertension during pregnancy continue to have their renal function monitored after delivery.

Mandy Trolinger, MS, RD, PA-C

Denver Nephrology Denver, CO

Personal Note: Mandy is a two-time kidney transplant recipient. She delivered a healthy baby boy in 2012.