DIABETIC nephropathy is one of the common causes of native kidney dysfunction and is the commonest cause of end-stage renal disease in the United States. Renal changes that are associated with diabetes mellitus are complex, ranging from early hyper filtration with an increased glomerular filtration rate (GFR) to late nephro sclerosis and fibrosis with azotaemia. Presently, radiologic imaging doesn’t have an important role in diagnosing or follow-up of possible diabetic nephropathy. With conventional ultrasonography (US), renal enlargement (in the early stages of disease) and renal parenchymal loss (in the later stages of disease) have been described, but these observations have limited clinical sensitivity and specificity. Renal duplex Doppler USG is useful, both to detect renal dysfunction before obtaining results of conventional clinical and laboratory tests and to predict subsequent renal status.

AIMS & OBJECTIVES

To evaluate the diagnostic usefulness of renal resistive index by duplex Doppler ultrasonography for detection of renal dysfunction in diabetic patients and also to compare renal RI as a diagnostic tool for diagnosis of diabetic nephropathy with the biochemical diagnosis.

MATERIALS AND METHODS

A cross-sectional study was done for a duration of one and half year on 50 patients who were admitted in Chengalpattu Medical College.

INCLUSION CRITERIA: Only those patients biochemically diagnosed as having diabetic nephropathy are included.

EXCLUSION CRITERIA: Those with incomplete data, hydronephrosis and renal calculus are excluded.

Clinically diagnosed diabetic patients having diabetic nephropathy will be taken as a sample. Diabetic nephropathy will be diagnosed by the Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least two occasions 3-6 months apart, Progressive decline in the glomerular filtration rate (GFR) and Elevated arterial blood pressure by the physician. However, Serum creatinine level more than 1.3mg/dl will be considered as having diabetic nephropathy.

DATA COLLECTION METHOD: By using Questionnaire, comprehensive clinical examination, biochemical investigation and appropriate Imaging.

RESULTS

Table-1: Bar Diagram Showing Distribution of the Study Patients by Resistive Index:

Table-2: Sex Wise Distribution of Pathological Resistive Index:

Table-3: Duration of Diabetes Wise Distribution of Pathological RI:

Table-4: Microalbuminuria wise Distribution of Pathological Ri:

Table-5: Creatinine wise Distribution of Pathological Ri

Table-6: Usg wise Distribution of Pathological Ri.

Table-7: Diabetic Retinopathy Wise Distribution of Resistive Index:

DISCUSSION

Diabetic nephropathy is a frequent microvascular complication of Diabetes mellitus. Early functional and structural abnormalities may be present a few years after the onset of the disease. In these last decades, Doppler ultrasonography has provided an easily applicable and non-invasive method for investigating renal hemodynamic. The renal resistive index reflects intracranial vascular resistance. The mechanisms for increased RI values in patients with decreased glomerular function is unknown. In advanced DN, glomeruli become sclerotic, tubule become atrophic, and interstitial fibrosis is increased. Sclerotic glomeruli may cause increased blood flow resistance measurable at an upstream interlobar artery. Increased interstitial fibrosis may cause elevated RI values. The RI of interlobar arteries seems to be a dependable marker of intracranial changes. Activation of the renin-angiotensin system is reported to contribute to intracranial hemodynamics abnormality in diabetic patients. ACE inhibitors have been shown to delay the progression of DN by decreasing the intraglomerular capillary pressure. The duplex Doppler ultrasonography has made advancement in the field of diagnostic imaging with emerging importance as a diagnostic modality. The R/I index is significantly correlated with increased blood pressure and decreased renal function (1-4). We suggest that R/I index can predict the outcome of renal function in type 2 diabetic patients with microalbuminuria. This finding might be important from three different points of view.  

First, ischemic atherosclerotic injury, at the level of renal small vessels, might accelerate the decay of GFR, possibly further deteriorating the molecular structural characteristics of endothelial-podocyte system. Second, R/I index can be used to predict the outcome of renal function in type 2 diabetic patients with microalbuminuria. Third, an increased R/I index is closely associated, in type 2 diabetic patients with microalbuminuria, with patterns of glomerular lesions of typical or atypical diabetic nephropathy.  The latter observation resembles the close relationship between proliferative diabetic retinopathy and patterns of glomerular and renal lesions typical of diabetic nephropathy that we have described previously (5). However, diabetic retinopathy appears to be a less specific marker of the progression of renal damage, because a nontrivial fraction of the patients who haveno proliferative background retinopathy may not develop overt nephropathy (6). In fact, only type 2 diabetic patients with proliferative retinopathy are bound to show a rapid decline of GFR, but only 10 –20% of type 2 diabetic patients have proliferative retinopathy (6). Moreover, the ophthalmoscopic examination, although mandatory to prevent and to treat diabetic proliferative retinopathy, is not less cumbersome than the evaluation of R/I to prevent and predict diabetic nephropathy. 

Another issue that has been addressed in various studies is that diabetic nephropathy has been demonstrated to have higher renal vascular resistance than other causes of CKD [5]. This led to the postulation that there is some specific pathophysiology to diabetes that causes this raised renal vascular resistance.  Although diabetic nephropathy has been classically described as a microvascular complication, however there is another school of thought that thinks that diabetic nephropathy and raised renal resistance are a part of accelerated diffuse atherosclerotic process and widespread endothelial dysfunction that accompanies diabetes. This is based on several observations that renal vascular resistance is particularly higher in patients with lower limb vascular disorders in diabetes.  Also pathological studies have shown arterial sclerosis in kidney biopsy of medium-sized arteries perpendicular to the kidney surface.  Therefore, several studies have tried to correlate RI with markers of macro vascular disease such as Carotid intimo-medial thickness (IMT) and aortic stiffness parameters like brachial ankle pulse wave velocity (ba-PWV) and ankle brachial pressure index (ABI). Among our 100 patients ,27 were between ages 41-50years and out of them 18had pathological RI (23%);35 were between ages 51-60years and out of them 28 had pathological RI (36%);38 were more than 60years of age and out of them 32 had pathological RI (41%). Mean age of the patients with Diabetes in our study – 50.5 yrs. In our current study it was observed that majority of the patients were in sixth decade with the mean age of 50.5±7.6 years, ranging from 38 to 65 years.  A recent study has shown in their series, the mean age of patients with diabetes as 57.4±7.6 years. In another study it was showed the mean (±SD) age of the patients having diabetes as 55.9±12.8 years which is comparable with the current study.  Researchers found the mean age of the patients with diabetes 47.8±11.34 years.  Similarly, another study had revealed the mean±SD age of patients with having diabetes was 43.6±3.1 years (p=0.019). Similar age range was also obtained in another study.

Among our study population of 100, there were 28,45,27 with duration of diabetes of <5years, 5-10years and >10years respectively and among them 20(26%), 38(49%), 20(25%) had pathological RI respectively. Mean duration of diabetes in our study – 3 yrs. Our study group totally consists of 100 samples, 56 were in Males among them 45(58%) had pathological RI. 44 were in Females among them 33(42%) had pathological RI. In this present study it was observed that male was predominant in both groups, where male was found as 56%. Male to female ratio was 1.2:1 in the study patients. Researchers found male 69.6% in patients with diabetes which is closely resembled with the present study. Similarly, male predominance was also observed by researchers.  However, a comparable study found female 57.1% in patients with diabetes. Among our study population,78 % shows pathological resistive index and 22 % shows Normal resistive index. Mean resistive index was found to be 0.71±0.04 and varied from 0.60 to 0.82. Similarly, it was found RI significantly higher in diabetic patients (0.69±0.05). In another study it was showed the mean RI value (0.69±0.1) in patients with diabetes. Similar results about the resistive index were also made by other researchers. In another study it was seen that mean RI of 0.64 +/- 0.09 in 23 patients with early diabetic nephropathy. Patients with established nephropathy had a mean RI of 0.83 +/- 0.11.5. Spomenka et al. showed that Doppler ultrasound can help in early diagnosis of diabetic nephropathy by measuring intra-renal artery resistance index and found a direct relationship between intra-renal RI and diabetic nephropathy which was consistent with our study (7). Their results indicate that the increased RI of the renal arteries is associated with the severity of systemic atherosclerosis. Among 100 patients, 82 were in microalbuminuria among them 66(85%) had pathological RI. 18 were in without microalbuminuria among them 12(15%) had pathological RI. There is a strong positive association between microalbuminuria and resistive index. In our study 100 patients, 60 were in increased creatinine among them 42(54%) had pathological RI. 40 were in normal creatinine among them 36(46%) had pathological RI. A positive correlation (r=0.581, p<0.01) was found between resistive index with serum creatinine and albuminuria which indicates deterioration of renal function, i.e. progression of the disease. In previous study it was shown that the correlation between serum creatinine and RI values in diabetic nephropathy to be (r=0.84). Similarly, study found correlation between the two to be R2=0.67(p<0.001). Another study conducted by Milovanceva et al. showed an association between intra-renal RI and serum creatinine and creatinine clearance consistent with the results of our study (8). Narooeinejad et al. showed that RI can be used to estimate 24-hour urine protein especially in those patients who are not compliant for 24-hour urine collection (9). Soldo et al. also showed a relationship between RI and serum creatinine (10). Masulli et al. failed to find a relationship between RI and albuminuria which was inconsistent with the results of our study.

The readiness and safety of duplex Doppler may enable us to examine renal exacerbation in the proper timing and lead to effective treatment. In this regard, even if renal function is well preserved at baseline when RI is greater, we should observe these patients carefully in the follow-up period because they have significant vascular lesions. Moreover, RI may be one of the clinical parameters that should be checked regularly in an outpatient clinic. In the present study, we showed that renal vascular resistance was higher in patients with microalbuminuria. After an adjustment of eGFR, RI remained significant and was an independent risk factor for the presence of albuminuria.

Therefore, RI is a useful marker for the presence of any type of nephropathy found in type 2 diabetes. When we consider the stages of diabetic nephropathy, it is plausible that there is a stage in which albuminuria and GFR do not always correspond to each other. Recent results regarding the pathophysiology of renal disease in type 2 diabetes have challenged the concept that a decline in renal function in patients with diabetes is always accompanied by increased albuminuria.

1. MacIsaac RJ, Panagiotopoulos S, McNeilKJ, Smith TJ, Tsalamandris C, HaoH, Matthews PG, Thomas MC, Power DA, Jerums G: Is nonalbuminuricrenal insufficiency in type II diabetes related to an increase in intrarenalvascular disease? Diabetes Care 29:1560–1566,2006.
2. Sonmez K, Eskisar AO, Demir D, Yazicioglu MV, Mutlu B, Dogan Y, IzgiA, Mansuroglu D, Bakal RB, ElonuOH, Turan F: Increased urinary albumin excretion rates can be a marker of coexisting coronary artery disease in patients with peripheral arterial disease. Angiology57:15–20,2006.
3. Ohta Y., Fujii K., Arima H., Matsumura K., Tsuchihashi T., Tokumoto M., Tsuruya K., Kanai H., Iwase M., Hirakata H., Iida M. (2005): Increased renal resistive index in atherosclerotic and diabetic nephropathy assessed by Doppler sonography. J Hypertens; 23: 1905– 1911.
4. Hostetter TH. Diabetic nephropathy. In: Brenner BM, Rector FC, eds. The kidney.3rd ed. Philadelphia, Pa: Saunders, 1986;1377-1402.
5. Nelson RG. BennetPH, Beck GJ et al. Development and progression of renal disease in Pima Indians with NIDDM.Diabetic renal disease study group. NEJM 1996;335L 1636-1642.
6. Robbins and Cotran Pathologic Basis of Disease,7th Ed.991-992.
7. Paisley KE, Beaman M, Tooke JE, Mohamed-Ali V, Lowe GDO, Shore AC: Endothelial dysfunction and inflammation in asymptomatic proteinuria. Kidney Int63:624–633, 2003
8. Reinitz ER., Goldmann MH., Sais J. et al. (1983): Evaluation of transplant artery blood flow by Doppler sound-spectrum analysis. Arch Surg; 118: 415–419.
9. Platt JF., Ellis JH., Rubin JM., DiPIetro MA., Sedman AB. (1990): Intrarenalarterial Doppler sonography in patients with nonobstructive renal disease: correlationof resistive index with biopsy findings. AJR;154: 12231227.
10. Taniwaki H., Ishimura E., Kawagishi T., Matsumoto N., Hosoi M, Emoto M., Shoji T., Shoji S., Nakatani T., Inaba M., Nishizawa Y. (2003): Intrarenal hemodynamic changes after captopril test in patients with type 2 diabetes: a duplex Doppler. sonography study. Diabetes Care; 26: 132–137.