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    <recommendedItem id="20100101_19_325"
                     title="MRI Reveals Risk for Kidney Failure in Diabetic Patients (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18195?impressionId=1265764749661"
                     
      So-called silent strokes, visible on cerebral MRI scans, predict kidney failure in patients with type 2 diabetes, Japanese researchers said.&lt;br&gt;
&lt;br&gt;After an average follow-up of 7.5 years, diabetic patients with evidence of small cerebral infarctions at baseline later suffered death or kidney failure at more than twice the rate seen in patients who had not had silent strokes, reported Takashi Uzu, MD, of Shiga University of Medical Sciences in Shiga, Japan, and colleagues.&lt;br&gt;
&lt;br&gt;Silent strokes are a consequence of cerebral microvascular disease and thus may logically accompany the development of similar abnormalities in renal blood vessels, ultimately leading to kidney failure, the researchers explained online in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;It is important to identify individuals who are at risk of progression of diabetic renal disease,&quot; Uzu and colleagues wrote.&lt;/p&gt;
&lt;p&gt;The current standard prognostic test is the albumin-creatinine ratio, but it is not entirely adequate for the purpose, they suggested: &quot;Recent clinical studies have shown that renal insufficiency can occur in the absence of microalbuminuria in patients with type 2 diabetes.&quot;&lt;/p&gt;
&lt;p&gt;But they acknowledged that brain MRI scans would be too expensive and inconvenient for routine prognostic testing.&lt;/p&gt;
&lt;p&gt;&quot;New strategies are needed to determine the presence of renal and/or extrarenal microvascular diseases,&quot; Uzu and colleagues wrote.&lt;/p&gt;
&lt;p&gt;Their study involved 608 patients with type 2 diabetes who had no clinical signs of cerebrovascular or cardiovascular disease or overt nephropathy. Their mean age at baseline was about 60 and the average glycated hemoglobin level was about 8.6%.&lt;/p&gt;
&lt;p&gt;Participants underwent cerebral MRI scans at baseline, with 177 showing evidence of silent cerebral infarctions, defined as focal lesions of at least 3 mm in diameter with low signal intensity on T1-weighted images and high intensity with T2 weighting. Dilated perivascular spaces were distinguished from infarcts with proton density scans. Patients with positive findings who had a history of stroke or transient ischemic attack were excluded.&lt;/p&gt;
&lt;p&gt;Those with silent infarctions at baseline differed significantly from other participants according to several parameters. Not surprisingly, patients with cerebral infarcts on average were somewhat older (63 versus 57), had had diabetes for a longer period of time (9.8 years versus 7.6), had higher blood pressure (146.8 mm Hg systolic versus 136.5 ), and were more likely to have a history of smoking (58% versus 46%). All differences were significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01.&lt;/p&gt;
&lt;p&gt;On the other hand, baseline fasting plasma glucose and glycated hemoglobin levels were both significantly lower in the patients who&apos;d had silent infarctions: mean 163 mg/dL versus 176 for glucose and 8.3% versus 8.7% for HbA1c (&lt;em&gt;P&lt;/em&gt;&amp;#8804;0.01 for both).&lt;/p&gt;
&lt;p&gt;Patients were followed for up to 10 years, with a mean of 7.5. The primary outcome was end-stage renal disease or death, and Uzu and colleagues chose a secondary outcome combining dialysis with doubling of serum creatinine.&lt;/p&gt;
&lt;p&gt;Kaplan-Meier curves for the patients with and without silent infarctions at baseline indicated that the primary outcome occurred at equal rates through the first four years of follow-up, but then the curves diverged abruptly.&lt;/p&gt;
&lt;p&gt;At year eight, approximately 6% of the noninfarcted group had experienced the primary outcome, compared with 21% of those who&apos;d had silent strokes (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), according to Uzu and colleagues.&lt;/p&gt;
&lt;p&gt;Curves for the secondary outcome began diverging by year three. At year eight, about 6% of the noninfarct participants had gone to dialysis or had serum creatinine levels double, whereas these endpoints occurred in nearly 30% of the infarct group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;Overall, the hazard ratio associated with baseline silent cerebral infarctions for the primary outcome during follow-up was 2.44 (95% CI 1.36 to 4.38).&lt;/p&gt;
&lt;p&gt;The hazard ratio for death alone was somewhat smaller (1.61, 95% CI 0.71 to 3.62), indicating that most of the risk measured by the primary outcome was actually in end-stage renal disease.&lt;/p&gt;
&lt;p&gt;For the secondary outcome, the hazard ratio was 4.79 (95% CI 2.72 to 8.46).&lt;/p&gt;
&lt;p&gt;All the hazard ratios reflected adjustments for age, sex, duration of diabetes, body mass index, smoking status, HbA1c, blood pressure, serum lipids, and standard lab indices of kidney function at baseline.&lt;/p&gt;
&lt;p&gt;Estimated glomerular filtration rate (eGFR) during follow-up also decreased faster in patients with silent strokes. After five years, mean eGFR had fallen by 8 ml/min/m&lt;sup&gt;2&lt;/sup&gt; in the patients without silent infarcts at baseline compared with 10.5 ml/min/m&lt;sup&gt;2&lt;/sup&gt; in those with cerebral microvascular disease.&lt;/p&gt;
&lt;p&gt;The researchers noted that the study was conducted at two clinical sites, which used somewhat different MRI procedures. But they also indicated that the prevalence of silent infarctions did not differ between the sites.&lt;/p&gt;
&lt;p&gt;Other limitations included use of an older creatinine assay, inclusion of larger silent infarcts which could reflect macrovascular disease, and more patients in the cerebral infarct group who were taking renin-angiotensin system blocking drugs, which have renal impairment as an adverse effect.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;External funding for the study was not reported.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_280"
                     title="Better Overall Diabetes Care Lowers Nephropathy Risk (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265764749661"
                     
      &lt;p&gt;Simultaneously achieving tight glucose control and other targets in diabetes reduces the risk of kidney complications, researchers found.&lt;/p&gt;
&lt;p&gt;An aggressive multifactorial intervention appeared to delay diabetic nephropathy better when more targets were achieved (&lt;em&gt;P&lt;/em&gt;=0.002 for trend) in a longitudinal study of Chinese patients led by Ming-Chia Hsieh, MD, PhD, of Kaohsiung Medical University Hospital in Kaohsiung, Taiwan.&lt;/p&gt;
&lt;p&gt;The risk of new-onset microalbuminaria dropped 27.1% for those who met the American Diabetes Association-recommended goal of less than 7% glycosylated hemoglobin (&lt;em&gt;P&lt;/em&gt;=0.03), the researchers reported in the Jan. 25 &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Reaching the systolic blood pressure goal of less than 130 mm Hg reduced this risk 35.5% (&lt;em&gt;P&lt;/em&gt;=0.002). Achieving the HDL cholesterol goal  --  over 50 mg/dL for women and 40 mg/dL for men  --  reduced the risk by 28.5% (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;&quot;The control of microalbuminuria may halt progress to overt nephropathy and reduce occurrence of cardiovascular events in these patients,&quot; Hsieh&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;They suggested that this type of intensive intervention &quot;can be used at the very early stages of diabetic renal disease.&quot;&lt;/p&gt;
&lt;p&gt;Prior studies had suggested that intensive therapy could prevent nephropathy in patients who had already started showing signs of progression.&lt;/p&gt;
&lt;p&gt;So to see if starting earlier would be as effective, Hsieh and colleagues initiated a longitudinal cohort study of 1,290 patients with type 2 diabetes and normoalbuminuria in which participants received intensified treatment to meet ADA-recommended goals on glucose, blood pressure, cholesterol, and triglycerides.&lt;/p&gt;
&lt;p&gt;To this end, patients got the combined efforts of a physician, nurse, and dietitian working together on counseling and patient education to modify behavior.&lt;/p&gt;
&lt;p&gt;By the end of the intervention patients were more likely to have switched from single agent glucose-lowering treatment to insulin plus an oral hypoglycemic agent and to have gone on an antihypertensive (74% versus 48% baseline), statin (58.1% versus 28.0% baseline), and fibrate (14.0% versus 3.0% baseline).&lt;/p&gt;
&lt;p&gt;By the end of the study period, the mean glycosylated hemoglobin was 7.3%, while blood pressure averaged 129.3/74.4 mm Hg. Mean LDL cholesterol was 98.6 mg/dL, triglycerides were at 116.0 mg/dL, and mean HDL cholesterol was 53.6 mg/dL.&lt;/p&gt;
&lt;p&gt;Over the 4.5 years of follow-up, 16.4% of patients developed new-onset microalbuminuria.&lt;/p&gt;
&lt;p&gt;Unlike attainment of HDL cholesterol, glycosylated hemoglobin, and systolic blood pressure goals, reaching those for LDL cholesterol, diastolic blood pressure, and triglycerides appeared to have little impact on kidney function.&lt;/p&gt;
&lt;p&gt;But the more targets patients reached, the less likely they were to develop microalbuminuria (&lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;The majority of participants in the study reached one or two of the treatment targets (71.4%) and 8.1% achieved three.&lt;/p&gt;
&lt;p&gt;Those who did reach two or three of the goals were at significantly lower risk of new-onset microalbuminuria than the 20.5% who didn&apos;t reach any of the goals (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Those who reached one target tended to be at lower risk as well, but the effect was not significant compared with reaching none of the goals (&lt;em&gt;P&lt;/em&gt;=0.35).&lt;/p&gt;
&lt;p&gt;One of the concerns with the tight glucose control goal has been hypoglycemia. In the study, 217 patients had at least one episode. Four cases involved major hypoglycemia, though without clinical morbidity or mortality.&lt;/p&gt;
&lt;p&gt;Overall, 37 patients died from any cause during the study period.&lt;/p&gt;
&lt;p&gt;A &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; target=&quot;_blank&quot;&gt;review&lt;/a&gt; of recent large trials of aggressive glycemic control  --  U.K. Prospective Diabetes Study (UKPDS) and the U.S.-based ACCORD, ADVANCE, and VA Diabetes trials  --  suggested a two- to threefold increased risk of severe hypoglycemia without macrovascular benefits.&lt;/p&gt;
&lt;p&gt;In the recent &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; target=&quot;_blank&quot;&gt;ACCORD&lt;/a&gt; trial, tight glucose control that brought hemoglobin A1c close to 6%, with a target of less than the standard 7.0%, resulted in 22% excess mortality risk.&lt;/p&gt;
&lt;p&gt;The search for a reason behind this risk has yet to turn up a culprit. &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; target=&quot;_blank&quot;&gt;Analyses&lt;/a&gt; have suggested that hypoglycemia isn&apos;t to blame and that the lower A1c levels themselves aren&apos;t a problem.&lt;/p&gt;
&lt;p&gt;In the wake of the negative findings from ACCORD, ADVANCE, and the VA trials, leading diabetologists had suggested that pushing too hard in people who couldn&apos;t reach the targets might have been at fault.&lt;/p&gt;
&lt;p&gt;Rather than a one-size-fits all approach, the ADA guidelines suggest individualizing treatment targets.&lt;/p&gt;
&lt;p&gt;Hsieh&apos;s group acknowledged that &quot;even with close attention, not all our patients could achieve the ADA-recommended goals,&quot; but re-emphasized that for patients who could achieve targets, there were benefits.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that their study was limited by lack of a comparison group, no data on genetic factors, and use of potentially arbitrary treatment target cutoff points.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
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                     title="Meta-Analysis Finds No Kidney Benefit for ACE-Inhibitors or ARBs"
                     score="-0.005"
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