Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

Objective: The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods: In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results: 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions: In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)

Yoga, Physical Therapy, or Education for Chronic Low Back Pain: A Randomized Noninferiority Trial

Background: Yoga is effective for mild to moderate chronic low back pain (cLBP), but its comparative effectiveness with physical therapy (PT) is unknown. Moreover, little is known about yoga\u27s effectiveness in underserved patients with more severe functional disability and pain. Objective: To determine whether yoga is noninferior to PT for cLBP. Design: 12-week, single-blind, 3-group randomized noninferiority trial and subsequent 40-week maintenance phase. (ClinicalTrials.gov: NCT01343927). Setting: Academic safety-net hospital and 7 affiliated community health centers. Participants: 320 predominantly low-income, racially diverse adults with nonspecific cLBP. Intervention: Participants received 12 weekly yoga classes, 15 PT visits, or an educational book and newsletters. The maintenance phase compared yoga drop-in classes versus home practice and PT booster sessions versus home practice. Measurements: Primary outcomes were back-related function, measured by the Roland Morris Disability Questionnaire (RMDQ), and pain, measured by an 11-point scale, at 12 weeks. Prespecified noninferiority margins were 1.5 (RMDQ) and 1.0 (pain). Secondary outcomes included pain medication use, global improvement, satisfaction with intervention, and health-related quality of life. Results: One-sided 95% lower confidence limits were 0.83 (RMDQ) and 0.97 (pain), demonstrating noninferiority of yoga to PT. However, yoga was not superior to education for either outcome. Yoga and PT were similar for most secondary outcomes. Yoga and PT participants were 21 and 22 percentage points less likely, respectively, than education participants to use pain medication at 12 weeks. Improvements in yoga and PT groups were maintained at 1 year with no differences between maintenance strategies. Frequency of adverse events, mostly mild self-limited joint and back pain, did not differ between the yoga and PT groups. Limitations: Participants were not blinded to treatment assignment. The PT group had disproportionate loss to follow-up. Conclusion: A manualized yoga program for nonspecific cLBP was noninferior to PT for function and pain. Primary Funding Source: National Center for Complementary and Integrative Health of the National Institutes of Health

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

ObjectiveThe objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).MethodsIn a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.Results26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.ConclusionsIn ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153)

Spearman correlation coefficients between biomarkers.

<p>All values were log transformed except serum creatinine (Screat) and blood urea nitrogen (BUN), NT-proBNP, N-terminal pro-brain natriuretic peptide; BNP, brain natriuretic peptide-BNP; eGFR, estimated glomerular filtration rate; pNGAL, plasma neutrophil gelatinase associated lipocalin; uNGAL, urine neutrophil gelatinase associated lipocalin; KIM-1, kidney injury molecule-1; NAG, urine N-acetyl-beta-D-glucosaminidase.</p><p>Spearman correlation coefficients between biomarkers.</p

Logistic regression analysis for the primary endpoint of WRF.

<p>In univariable analysis, several candidates were significant predictors. Optimal cutoffs were determined using the value providing optimal sensitivity and specificity balance. Amino-terminal pro-B type natriuretic peptide, NT-proBNP; B type natriuretic peptide, BNP; Estimated glomerular filtration rate, eGFR; Neutrophil gelatinase-associated lipocalin, NGAL, urine kidney injury molecule-1, KIM-1, urine N-acetyl-beta-D-glucosaminidase, NAG; urine Cystatin C, uCyst C.</p><p>Logistic regression analysis for the primary endpoint of WRF.</p

Receiver operating curve of biomarkers of cardiac stretch (1A), renal function (1B) and renal injury (1C).

<p>Receiver operating curve of biomarkers of cardiac stretch (1A), renal function (1B) and renal injury (1C).</p

Results of baseline biomarkers in patients who developed worsening renal function and those who did not.

<p>Amino-terminal pro-B type natriuretic peptide, NT-proBNP; B type natriuretic peptide, BNP; Estimated glomerular filtration rate, eGFR; Neutrophil gelatinase-associated lipocalin, NGAL, urine kidney injury molecule-1, KIM-1, urine N-acetyl-beta-D-glucosaminidase, NAG. Urine biomarkers are expressed per gram urinary creatinine.</p><p>Results of baseline biomarkers in patients who developed worsening renal function and those who did not.</p

Baseline characteristics of study subjects as a function of the subsequent development of WRF.

<p>Few differences between the groups existed.</p><p>Baseline characteristics of study subjects as a function of the subsequent development of WRF.</p