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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