<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_373"
                     title="Protein in Urine Presages More Severe Problems (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Nephrology/ESRD/tb/18265?impressionId=1265793901893"
                     
      &lt;p&gt;The three-year risk of death, heart attack, and kidney failure was markedly increased in patients with baseline proteinuria, regardless of their estimated glomerular filtration rate (eGFR), researchers said.&lt;/p&gt;
&lt;p&gt;In a population-based study of nearly 1 million people, mortality was approximately doubled with heavy proteinuria among individuals stratified according to their eGFR, reported Brenda R. Hemmelgarn, MD, PhD, of the University of Calgary in Canada, and colleagues.&lt;/p&gt;
&lt;p&gt;Rates of myocardial infarction were increased by about 50% with heavy proteinuria, and end-stage renal disease and doubled levels of serum creatinine were as much as 30 times more common, the researchers reported in the Feb. 3 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Prognosis associated with a given level of eGFR varies substantially based on the presence and severity of proteinuria,&quot; Hemmelgarn and colleagues concluded.&lt;/p&gt;
&lt;p&gt;&quot;In fact, patients with heavy proteinuria but without overtly abnormal eGFR appeared to have worse clinical outcomes than those with moderately reduced eGFR but without proteinuria.&quot;&lt;/p&gt;
&lt;p&gt;They added that the findings were important because current recommendations for managing chronic kidney disease rely on eGFR for staging purposes without consideration of proteinuria.&lt;/p&gt;
&lt;p&gt;&quot;Future revisions of the classification system for chronic kidney disease should incorporate information from proteinuria,&quot; the researchers urged.&lt;/p&gt;
&lt;p&gt;The results emerged from a laboratory registry covering some 921,000 adults in the province of Alberta who had had measurements of eGFR, serum creatinine, and urinary protein from 2002 to 2007.&lt;/p&gt;
&lt;p&gt;Proteinuria was measured with a urine dipstick or the albumin-creatinine ratio. Dipstick readings of at least 2 points were considered heavy proteinuria. Readings showing at least trace protein but less than 2 points were classed as mild; negative readings were considered normal.&lt;/p&gt;
&lt;p&gt;The stratifications of albumun-creatinine ratio were greater than 300 mg/g, 30 to 300 mg/g, and less than 30 mg/g for heavy, mild, and normal, respectively.&lt;/p&gt;
&lt;p&gt;Other registry data for the province provided outcomes in these individuals, with median follow-up of 35 months.&lt;/p&gt;
&lt;p&gt;Among individuals with eGFR rates of at least 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, death rates were 7.2 per 1,000 for those with dipstick-measured heavy proteinuria (95% CI 6.6 to 7.8) and 5.8 per 1,000 for mild proteinuria (95% CI 5.5 to 6.0) compared with 2.7 per 1,000 for those with normal urine protein (95% CI 2.6 to 2.8).&lt;/p&gt;
&lt;p&gt;At the other end of the eGFR spectrum  --  those with levels of 15 to 29.9 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;  --  proteinuria remained an independent predictor of death: Mortality rates were 10.4 per 1,000 with heavy proteinuria (95% CI 9.3 to 11.6) and 9.1 per 1,000 with mild proteinuria (95% CI 8.2 to 10.0) versus 6.7 per 1,000 with normal urine protein (95% CI 6.2 to 7.3).&lt;/p&gt;
&lt;p&gt;These death rates reflected adjustments for a host of potential confounding factors and comorbidities, including age, sex, diabetes, hypertension, liver disease, and cardiovascular conditions.&lt;/p&gt;
&lt;p&gt;Proteinuria also predicted myocardial infarction in patients stratified by eGFR, but not as strongly. In the group with eGFR above 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, rates of MI were 1.6 per 1,000 (95% CI 1.3 to 2.0) and 0.9 (95% CI 0.9 to 1.0) for heavy and normal urinary protein, respectively, as measured by dipstick.&lt;/p&gt;
&lt;p&gt;MI rates were also increased with proteinuria in participants with eGFR below 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, the researchers reported.&lt;/p&gt;
&lt;p&gt;End-stage renal disease was enormously more common with dipstick-measured heavy proteinuria, independent of baseline eGFR.&lt;/p&gt;
&lt;p&gt;Individuals with eGFR above 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; were diagnosed with the condition at a rate of 1.0 per 1,000 (95% CI 0.7 to 1.4) if they had heavy proteinuria, compared with 0.03 per 1,000 (95% CI 0.02 to 0.09) among those with normal urine protein.&lt;/p&gt;
&lt;p&gt;A five-fold difference in rates of end-stage renal disease was still apparent among those with eGFR below 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;: 65.9 (95% CI 52.3 to 82.9) versus 12.7 per 1,000 (95% CI 9.3 to 17.3) for heavy versus normal protein, respectively.&lt;/p&gt;
&lt;p&gt;These results were confirmed when cross-checked against the more accurate albumin-creatinine ratio, Hemmelgarn and colleagues indicated.&lt;/p&gt;
&lt;p&gt;Each 10-fold increase in albumin-creatinine ratio was associated with the following relative rates of the major study outcomes, after adjusting for eGFR:&lt;ul&gt; &lt;li&gt;Death: 1.22 (95% CI 1.21 to 1.24)&lt;/li&gt; &lt;li&gt;MI: 1.18 (95% CI 1.14 to 1.21)&lt;/li&gt; &lt;li&gt;Doubling of serum creatinine: 1.76 (95% CI 1.70 to 1.82)&lt;/li&gt; &lt;li&gt;End-stage renal disease: 1.92 (95% CI 1.81 to 2.04)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Hemmelgarn and colleagues noted several limitations to the study including the fact that the sample was restricted to outpatients undergoing laboratory evaluations for kidney function and urinary protein, and the data were based on single measurements. Missing were data on alcohol, tobacco, and antihypertensive drug use, which might have affected the findings.&lt;/p&gt;
&lt;p&gt;The researchers also indicated that the follow-up period may have been too short to fully evaluate risks of progression to kidney failure.&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;Support for the study came from the Alberta Heritage Foundation for Medical Research, the Canadian Institutes of Health Research, Alberta Health and Wellness, and internal funds.&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_325"
                     title="MRI Reveals Risk for Kidney Failure in Diabetic Patients (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18195?impressionId=1265793901893"
                     
      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="0.001"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265793901893"
                     
      &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>
    <recommendedItem id="20090101_10_123"
                     title="Peritoneal Dialysis Death Risk Higher Than Hemodialysis"
                     score="-0.005"
                     href="