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Editorial
Maria Rosa Costanzo , Jonathan Barasch
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Circulation. 2018; 137: 2029-2031
Maria Rosa Costanzo
Advocate Heart Institute, Naperville, IL (M.R.C.).
Jonathan Barasch
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (J.B.).

Article, see p

The current perception, based on data from earlier studies, is that worsening renal function (WRF) during diuresis of patients with acute heart failure (HF) means that the therapy is overzealous and exposes the patients to permanent kidney injury and increased mortality. Massimo MatteoStamped Leather Bit Driver ACwSUP0eE
Underlying this view is the assumption that increased serum creatinine (sCr)/cystatin C and acute kidney injury (AKI) are interchangeable terms. Giorgio BrutiniCrawley btK8qkBny
Recent findings, however, suggest that transient increases in sCr may instead reflect a benign and potentially reversible hemodynamically driven reduction in glomerular filtration rate (GFR), reflective of effective decongestion that is associated with improved outcomes. LArtiste by Spring StepLouann jttisXA2
Thus, serious harm continues to be perpetrated against patients with acute illnesses, including HF, by referring to increased sCr/cystatin C, WRF, and AKI as if they were merely different names of the same pathological entity. Ahmad and colleagues in this issue of Circulation , while attempting to determine if renal tubular injury is the primary mechanism for WRF resulting from aggressive diuresis, came face-to-face with the reality that increases in either sCr or markers of tubular damage are, at best, poorly correlated with each other and with the diuretic effect and, at worse, may worsen outcomes because of the premature cessation of decongestive therapies. 3

For myocardial infarction, cardiac troponins (I and T) are widely considered adequate diagnostic biomarkers based on their myocardial tissue specificity and their association with important clinical outcomes. Hush Puppies Liza Heather fmyV2yfFN
In contrast, assessment of renal status by sCr is not straightforward, because defective excretion of sCr can result from extrarenal hypovolemia, impaired blood perfusion, intrinsic kidney causes (attributable to sepsis, ischemia, drugs, toxins, interstitial or glomerular causes, or a combination of these conditions), or postrenal disease. Pleaser Amuse 25 Womens pBtmI16
It is implausible, therefore, that creatinine, an end-product of muscle catabolism freely filtered by the glomerulus and secreted by the tubule, can discriminate between causes of renal dysfunction. Although measurement of sCr is cheap, widely available, and standardized, its disadvantages include not only the many inducers of elevated sCr, but also the large number of conditions affecting its non-GFR determinants, including renal reserve, muscle metabolism, protein intake, volume of distribution, medications, and extrarenal degradation. In fact, equations estimating GFR using sCr have variable bias across populations, and are imprecise despite standardization of sCr assays and inclusion of age, sex, race, and body size as surrogates for creatinine generation. Toe Warmers Oslo Boot Womens DllAk69Le
These equations assume that sCr is a steady-state marker of creatinine production and disposal, conditions that do not apply to AKI. An alternative to creatinine, cystatin C, is a protein produced in all nucleated cells and distributed in extracellular fluid. It is freely filtered and mostly reabsorbed and catabolized by the proximal tubule. Cystatin C is not affected by muscle mass or diet and is less strongly associated with age, sex, and race than creatinine, but smoking, inflammation, adiposity, thyroid diseases, malignancy, and glucocorticoids influence cystatin C levels, diminishing their value as a measure of renal excretory performance. Pour La Victoire Ellura Leather Sandal MeQ6jB5yR
In addition, international standardization of the cystatin C assay is not finalized. 5 Estimation of GFR using creatinine, cystatin C, or both has not been validated in acutely ill patients, in whom these estimates appear to be inaccurate in comparison with 4-hour urinary creatinine clearance for detection of renal function changes. 6 It is disappointing, therefore, that the severity of AKI is predominantly classified according to sCr changes or cystatin changes. 5 , Rialto Golda Loafer Womens KhvmF
This is because, in the absence of steady state, a patient may have florid tubular damage at presentation without significant changes in sCr attributable to renal reserve and consequent delay in achievement of detectable changes in this analyte. Conversely, the correlation of an increase in sCr levels with better outcomes during the treatment of HF suggests that elevation of this analyte identifies physiological, volume-sensitive responses to diuretics, rather than tubular damage. SORELMadson Oxford Waterproof PoEBzPL2YY

Hourly analysis revealed that obese subjects had higher HRs between 3 pm and 3 am but lower HRs between 7 and 10 am (Figure 1 English Laundry Bridport Ghost Printed Sneaker jivwgNALo
). Whereas LF power was depressed essentially throughout the 24-hour period, HF power was reduced during the late afternoon through the first half of the night (Figure 2 Sorel Snow Angel Lace Snow Boot Womens HWhAG
). As a consequence, the LF/HF ratio was detectably increased in the obese group at individual time points during the afternoon.

Figure 1.

Hourly profile of HR (top) and LF/HF ratio (bottom) in lean and obese subjects. Data are mean±SEM. Shaded area highlights nocturnal period. *Time points at which difference between 2 groups achieved statistical significance (<0.05 or less).

Figure 2.

Hourly profile of LF (top) and HF (bottom) power in lean and obese subjects. Shaded area highlights nocturnal period. *Time points at which difference between 2 groups achieved statistical significance (<0.05 or less).

In the whole data set, higher daytime LF/HF ratios were associated with higher fasting plasma insulin concentrations independent of sex, age, HR, and BMI; quantitatively, a tripling of fasting insulin predicted a doubling of the LF/HF ratio (Figure 3 Hoka One One Speedgoat Mid Waterproof Trail Shoe Womens ryw9fvb
).

Figure 3.

Association between daytime LF/HF ratio (residuals after adjustment for sex, age, HR, and BMI) and fasting plasma insulin concentration. Inset shows model-predicted change in LF/HF ratio associated with tripling of fasting plasma insulin levels ([I]). resds indicates residuals.

In the weight-reduced patients, indexes of body mass and fat distribution improved significantly, cardiac output decreased, and TPVR rose (Table 4 PUMA BOG Limitless Hi Denim Lo0RK0rJp
). Urinary catecholamine excretion tended to decrease (although the change was not statistically significant). Baseline 24-hour LF power (608 [420] ms 2 ) returned toward the normal range (to 824 [799] ms 2 ; P <0.05). The 24-hour hourly profile of HR was generally decreased, whereas that of LF powers was increased (Figure 4 ); the LF/HF ratio was not significantly changed.

Figure 4.

Hourly profile of HR (top) and LF power (bottom) in 9 obese subjects before and after weight loss.

View this table:
Table 4.

Effects of Weight Loss

In this study, obesity was of moderate to severe degree (BMI, 30 to 45 kg/m 2 ), with all the metabolic changes typical of this condition. To avoid the confounding effects of structural vascular changes, the obese subjects were selected to have normal glucose tolerance and blood pressure levels. In addition, clinical tests of autonomic function were within normal limits. Our results therefore apply to uncomplicated obesity.

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