Discussion
In this study, the renal volume of the diabetic patients was significantly higher than that of the nondiabetic controls. The kidney volume corrected for body surface area (renal area index) was increased by 26% in the diabetic patients. Stratifying for the degree of proteinuria, the greatest degree of nephromegaly was present in the normoalbuminuric patients with normal renal function (Figures 2 and 3). Diabetic kidney hypertrophy-hyperfunction syndrome is a well-established phenomenon that precedes changes in albuminuria by several years and predicts progression into microalbuminuria and overt renal disease. Renal enlargement occurs shortly after the induction of hyperglycemia, and it has been shown that the protein content rises in parallel to the kidney weight. Similarly, an increased protein to DNA ratio has been measured after a few days, indicating hypertrophy of the cells. In a longitudinal study of 146 normoalbuminuric patients, an increased kidney volume at baseline, but not hyperfiltration, was a predictor of progression to microalbuminuria in 27 patients.
The increase in renal volume during the early phase of diabetic nephropathy observed in diabetic patients could be associated with a reduction in the surface ratio of capillaries to tubules and might cause reduced perfusion and interstitial fibrosis. Hyperfiltration and hypertrophy are the first abnormalities seen in the kidneys in both types of diabetes and can be ideal parameters for intervention because the GFR is well preserved. The structural and functional changes are all reversible and can be decreased by improving metabolic control, strict blood pressure control, and treatment with angiotensin-converting enzyme inhibition or angiotensin 2 receptor blockade. From a clinical viewpoint, hyperfiltration is not a parameter of practical value for daily management of patients because it is too problematic to measure, whereas kidney volume measurement could be a potential tool for early identification of diabetic nephropathy. In this study, nephromegaly was the only detectable alteration in the diabetic patients during the prealbuminuric phase, when renal abnormalities are not detectable by the noninvasive methods normally used and recommended by the scientific community for diabetic nephropathy screening.
In animal models, prevention of early hypertrophy-hyperfunction has already been shown to avoid the development of diabetic nephropathy. Future studies will need to address the independent role of nephromegaly not only in the evolution of albuminuria but also in the subsequent decline of the GFR and whether it is a marker of glycemic control or exerts a pathogenetic role in human diabetic nephropathy.
In this study, higher RI values were also observed on Doppler sonography in the diabetic patients (Figures 1B and 4). Major variations were detected at advanced stages of diabetic nephropathy but less so in the early course of nephropathy (Figure 4 and Table 2).
The RI used to grade intrarenal resistance with sonography represents the intrarenal resistance downstream of the measuring site. It is the easiest of all known resistance parameters to record, correlates with biopsy results, and might aid in the management of renal disease. Radermacher et al reported an RI of 0.8 or higher to be the strongest predictor of allograft loss among risk factors included in a multivariate analysis, and the RI was correlated with several histologic markers of intrarenal damage.
The RI increase in our group of diabetic patients did not depend on the chronologic age but on the duration of diabetes. This finding can be an indication of a disease-specific alteration. How much the 3 different renal vascular beds (preglomerular vessels, glomerular capillaries, and postglomerular vessels) contribute to the elevated RI is unclear. In diabetic patients, renal artery disease is more frequent in the intrarenal vessels than in the main renal artery, and it is possible that during the very early prealbuminuric phase, patients have more pronounced vasoconstriction, even without overt nephropathy.
A possible explanation for our study results may be the following: (1) at an early stage of the disease, renal damage is located primarily in the glomeruli, in which case, a normal RI would be expected; and (2) at an advanced stage of the disease, the glomeruli become sclerotic, and tubules become atrophic with increasing interstitial fibrosis. All of these factors can lead to an increase in the RI. Moreover, advanced arteriosclerosis in intrarenal arteries at an advanced stage of diabetic nephropathy may contribute to the increase in the RI. Therefore, renal hypertrophy and the increase in the RI could represent two different phases: renal enlargement is a prealbuminuric reversible step of renal involvement in diabetes mellitus, whereas the RI increase indicates the progression of disease with renal scarring, which precedes the appearance of albuminuria.
There is evidence that suggests that the risk of developing diabetic nephropathy begins when urinary albumin excretion values are still in the normoalbuminuric range; however, excluding biopsy, no humoral or imaging parameter exists that can reveal earlier stages of nephropathy. Diabetic nephropathy is a progressive condition that often heralds increasing creatinine as the final manifestation, and as it evolves, the risk of cardiovascular complications increases. At present, treatment during the later stages of the condition is unable to preserve renal function or alter the burden of cardiovascular events. Future research could evaluate whether the progression of nephropathy and cardiovascular morbidity and mortality could be prevented by early treatment in patients with an increased renal volume, a higher RI, or both. Sonography may identify patients with nephropathy at a very early stage and may contribute to early diagnosis and prevention of disease progression.
Abbreviations:
GFR=glomerular filtration rate, MR=magnetic resonance, RI=resistive index
© 2013 by the American Institute of Ultrasound in Medicine
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Thứ Sáu, 31 tháng 5, 2013
Thứ Tư, 29 tháng 5, 2013
Cervical Elastography for Prediction of Successful Induction of Labor at Term
Discussion
The exact process from cervical ripening to effacement and dilatation
is not clearly established. However, several elements, including ecorin,
hyaluronic acid, hormones,cytokines, and proteases, are involved in this
process, reducing collagen levels and cell components within the cervix while increasing the water content, all leading to
the softening of the cervix. Cervix
shortening may follow ripening but not always, as seen in cases of term
deliveries with a reduced cervical length measured from the mid second
trimester. Thus, evaluation of not only
the cervical length but also the mechanical properties of the cervix should be included to predict successful induction of labor.
Only a few attempts have been made to objectively evaluate the
cervical consistency with sonography.
One study reported that cervical
consistency can be evaluated by measuring the difference of echogenicity in the
anterior and posterior cervical lips on a vaginal grayscale sonographic histogram.
A disadvantage is that the echogenicity of the cervix can be affected by gain
and artifacts such as reverberation. Thus, another way to measure cervical
consistency is needed, based on the physical properties of the cervix. The
main issue with elastography of the cervix is the lack of reference tissue for
comparison. Elastography is most useful when there is adjacent tissue of
differing stiffness (ie, tumor imaging). Thus, elastography of malignant tumors
can be useful because it increases the contrast between adjacent tissues of differing stiffness. However, the
cervix is nearly uniform and changed in toto. Considering the limitations of
cervical elastography, this study was performed and showed that it was possible
to quantify the whole elastographic data of the cervix and that imaging analysis
could be applied to cervical elastography to predict successful induction of labor in nulliparous women at term.
Moreover, the intraobserver and interobserver variability for cervical elastographic
data shows that imaging analysis was reliable and reproducible.
The application of elastography in the cervix of pregnant
woman is at a rudimentary stage. In particular, the elastographic method used
to evaluate solid tumors in the prostate, breast, and thyroid gland cannot be
directly transferred to measuring the cervix in a pregnant woman.
A tumor in a solid organ is relatively round and can be compared
with surrounding normal tissue. However, a normal cervix in a pregnant woman
has no abnormal tissue or a typical shape that is different from round. In
addition, to adequately assess the status of the cervix, data obtained from the
entire cervix are needed. If the analytic method of elastography used for solid tumors is applied to the cervix
of a pregnant woman, the predicted problems are as follows: the color in a
cervical elastographic image is not homogeneous, and the area colored the same
is not circular but very irregularly shaped. Thus, the scoring method using
color in small circular areas of the cervix in previous studies seldom reflects the whole cervix and is subjective.
Especially, if the uterine cervix is shortened or funneled, it is difficult to
select and score the several small circular areas in the cervix. However, these
problems can be resolved by the imaging analysis technique introduced in this
study. By using a different imaging analysis technique, the whole cervix can be
included for evaluation; the area can be selected regardless of shape; and the
data are objective and automatically calculated by a computer.
During the prenatal period, the main changes in the cervix
include softening, ripening, and dilatation. If the cervical length or cervical area is
correlated with cervical dilatation, the softening and ripening of the cervix
can be reflected by cervical elastography. In this study, the combinations of
cervical length or cervical area + mean elastographic index or cervical hard
area were modeled to improve prediction. This study indicates that elastography
is a technique that can be applied to examine the cervix of pregnant women.
Although the imaging analysis used in this study was able to
resolve some problems originated by the application of elastography in the
cervix of pregnant women, other limitations remain. There were no reference
data to show the elastographic status of the cervix according to the gestational
age in normal pregnant women. The physiologic modifications of breathing and arterial pulsation could play
a role in the variability of tissue displacement. The elastographic image can
be changed by pressing the probe with different pressure levels. To overcome
this problem, we tried to apply no pressure and just touch the cervix with the
probe after insertion. Of course, although we tried to maintain steady
pressure, we could not stop all minimal shaking. Therefore, to evaluate whether
the changes made by this minimal shaking could affect the elastographic
results, we performed the intraobserver and interobserver reproducibility test
for imaging analysis of the elastographic results. There were 2 limitations to
the intraobserver and interobserver test in this study. For intraobserver reproducibility,
a minimum 2-week interval is required between reviews of the same image to
avoid recall bias. The periods between each review in our study were just 20
minutes. The other limitation was that there were some large 95% CI values.
Nevertheless, imaging analysis of cervical elastography can be a good method
for evaluating the cervical status when used together with the cervical length.
This finding can be applied to other clinical studies, such as the prediction
of preterm birth, breast cancer detection, and thyroid mass evaluation.
In conclusion, imaging analysis of cervical elastography to
predict successful induction of labor in nulliparous women at term is
objectively quantifiable, reliable, and reproducible. Future studies should be
performed to determine the effect of the combination of cervical length and
cervical elastographic parameters and to resolve the remaining limitations of
cervical elastography.
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