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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 533-538
Comparison between doppler ultrasound resistive index, serum creatinine, and histopathologic changes in patients with kidney transplant dysfunction in early posttransplantation period: A single center study with review of literature


1 Department of Radiology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India
2 Department of Radiology, Suryam- The World of Imaging Center, Ahmedabad, Gujarat, India

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Date of Web Publication13-May-2016
 

   Abstract 

To determine the relationship between resistive index (RI) measured by Doppler ultrasound, serum creatinine (SCr), and histopathological changes on biopsy during kidney trans- plant dysfunction in early postoperative period, we studied 47 kidney transplant patients; 61% of the patients had acute transplant rejection, 19% had acute tubular necrosis, 4% had calcineurin inhibitor toxicity, 11% had normal morphology in biopsy, and 5% had changes compatible with pyelonephritis. None of the study patients had interstitial fibrosis or tubular atrophy on biopsy. We found that the sensitivity and specificity of RI in diagnosing transplant dysfunction was highly variable depending on the selected cutoff value. Sensitivity of RI decreased and its specificity increased with increasing the RI thresholds. Using an RI threshold of 0.7 resulted in a high sensitivity of 78% at a cost of very low specificity 40%, whereas using an RI threshold of 0.9 resulted in 100% specificity at a cost of very low sensitivity 16%. Acceptable specificity was only achieved at the expense of very low sensitivity, resulting in poor utility of RI as a screening tool for dysfunction. We found that there were no significant differences in the mean RI value between patients with and without biopsy-proven transplant dysfunction. However, we found a significant correlation between SCr value and RI of 0.383, P = 0.007.

How to cite this article:
Patel KN, Patel NA, Gandhi SP. Comparison between doppler ultrasound resistive index, serum creatinine, and histopathologic changes in patients with kidney transplant dysfunction in early posttransplantation period: A single center study with review of literature. Saudi J Kidney Dis Transpl 2016;27:533-8

How to cite this URL:
Patel KN, Patel NA, Gandhi SP. Comparison between doppler ultrasound resistive index, serum creatinine, and histopathologic changes in patients with kidney transplant dysfunction in early posttransplantation period: A single center study with review of literature. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Jul 17];27:533-8. Available from: http://www.sjkdt.org/text.asp?2016/27/3/533/182391

   Introduction Top


To evaluate allograft dysfunction in kidney transplant patients, clinicians usually resort to ultrasonography as a first line investigation tool.[1]However, morphological changes of sono- graphic appearance in the evaluation of renal failure lack specificity.[2]Moreover, it has been reported that renal morphologic alteration appears much later than biochemical changes such as a rising serum creatinine (SCr) level.[3]Tublin et al argued that Doppler ultrasound ability to detect the different renal pathology is based on the assumption that changes in intra renal arterial waveform accurately reflect the subtle changes in renal vascular resistance (RVR) that occur with renal disease.[1]These changes are generally quantified using the so- called Doppler ultrasounds resistive index (RI). Kidney biopsy is considered an essential tool that provides histopathological information about an impaired renal transplant. However, biopsy is invasive and may be contraindicated in patients with certain disorders such as coa- gulopathy. Moreover, it has many complica- tions, which may eventually result in renal failure.[4]Some publications have found RI a valuable Doppler parameter in the assessment of renal transplant dysfunction, whereas other studies have been inconclusive.

The aim of our study was to determine the relationship between RI, SCr, and the histo- pathological changes on biopsy during renal transplant dysfunction in the early postopera- tive period.


   Patients and Methods Top


We retrospectively reviewed the record of 47 patients who had undergone renal transplant biopsy in our institute from October 1, 2012 to March 31, 2013. No consent form was needed because this was a record review. The study was approved by the Institutional Review Board.

Only patients who had kidney transplantation and transplant biopsy performed within one month posttransplantation were included in this study. A total 157 kidney transplants were performed during this period, and 151 post kidney transplant biopsies were done in the same period. We included only 47 patients with allograft dysfunction in this study. Renal transplant biopsies were requested by nephro- logists at our institution in case of a persistent increase in SCr. All the study patients had Doppler ultrasound, and the intervals between the transplant Doppler studies and allograft biopsies were <2 days. SCr values were deter- mined on the day of biopsy.

Patient with congestive heart failure, major stenosis of aorta, iliac artery or transplanted artery, existing intrarenal arteriovenous fistula, large perinephric collection, and hydroneph- rosis were excluded from the study because these conditions may affect the intrarenal blood flow velocity during systole and diastole. Most of the patients were on triple drug immuno- suppressant (prednisolone + tacrolimus/cyclos- porine + mycophenolate mofetil).

All color Doppler sonography examinations were performed by a radiologist using a 3-5 MHz phased array sector transducer (on IU 22 Philips machine or Acuson Siemens machine). There was no special preparation before renal transplant sonography. The patients were scanned in a supine position to achieve an ultrasound beam as nearly parallel to the blood flow direction as possible. An ultrasound probe covered with transmitting gel was gently placed on the skin over the transplanted kid- ney. Minimal pressure was applied during scanning to avoid mechanical compression on the kidney allograft which could cause false positive elevation of RI.[5]A low pulse repeati- tion frequency and filter were used to detect low-velocity flow. Doppler angle correction of <60°, a 2-4 mm spectral gate, and a low scale without aliasing were standard for sampling blood flow velocity with spectral Doppler. A RI from three consecutive spectral Doppler waveforms from one region of transplant was measured manually with built-in software in ultrasound scanner. The mean RI of each exa- mined kidney was determined from averaging the RIs of at least four distinct sites.

Percutaneous kidney biopsies were performed with 18-gauge biopsy needles under sono- graphic localization of the upper pole of the transplant kidney allografts. All biopsies were performed after excluding arteriovenous fis- tulas and pseudoaneurysms in the transplants. The kidney biopsies were done in Radiology Department of our institute and specimens were sent to the pathology laboratory of our institute. The site of pathological changes and dominant process (fibrosis, atrophy, edema, or arteriosclerosis) were classified depending on findings primarily located in interstitium, tubules, vessels, or glomeruli according to Banff update 07 renal allograft pathological classification. When multiple coexistent ab- normal findings were reported, they were categorized according to the predominant abnormality.


   Statistical analysis Top


We evaluated different cutoff values for RI (0.7, 0.8, and 0.9) by dichotomizing patients into two groups around each cutoff value; patients with RI more than the cutoff value were considered to be test positive and those with RI less than cutoff were considered test negative. Sensitivity, specificity, positive pre- dictive values, and negative predictive values were calculated.

Pearson product-moment correlation test was used to determine if there was any correlation between RI and SCr; this test produces percen- tage correlation, with 100% representing direct correlation and 0% representing a complete lack of correlation. P <0.05 was considered statistically significant.


   Results Top


The study included 47 patients. The overall characteristics of the study population are shown in [Table 1].
Table 1. Clinical Doppler ultrasound and biopsy findings of the study population (n = 47)

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Of the 47 studied patients, 29 (61%) patients had acute transplant rejection, nine (19%) had acute tubular necrosis, and two (4%) had calci- neurin inhibitor toxicity, five (11 %) had normal morphology in biopsy, and two (5%) had changes compatible with pyelonephritis, none of our patients had changes of interstitial fibrosis or tubular atrophy on biopsy.

For the various resistive indices, we mea- sured sensitivity, specificity, positive predic- tive value, and the negative predictive values. [Table 2] shows that the sensitivity of RI in diagnosing transplant dysfunction decreased and its specificity increased with increasing RI thresholds. Using an RI threshold of 0.7 re- sulted in a high sensitivity of 78% at a cost of very low specificity 40%, whereas using an RI threshold of 0.9 resulted in 100% specificity at the cost of very low sensitivity 16%.
Table 2. Accuracy of detecting renal transplant dysfunction at a chosen cutoff value of resistive index

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[Table 3] shows that there was no significant difference in RI between patients with and without biopsy-proven transplant dysfunction and also those stratified within the Banff 07 classification.
Table 3. Serum creatinine and mean resistive index values for different types of graft biopsy findings

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The percentage correlation by the Pearson product-moment correlation test [Figure 1] between SCr value and RI was 0.383 and P = 0.007 which suggests a significant correlation between SCr and RI to diagnose transplant dysfunction.
Figure 1. Percentage correlation by the Pearson product-moment correlation test between serum creatinine value and resistive index

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   Discussion Top


Sonography and SCr level are commonly used to assess the function and condition of renal transplants. Doppler USG has been stea- dily improved over the past five years and is now frequently used as the first-line screening test for kidney transplant recipients.[5],[6]During renal transplant dysfunction, the changes that result in an increase in RVR and RI probably occur as a direct result of the impedance of blood flow caused by the external pressure exerted on blood vessels by expanding inters- titium, infiltration by inflammatory cells, edema, and the process of fibrosis. In acute rejection due to their direct effect on the kidney vascula- lature, it might have a direct effect on RVR and RI.[7]

Many different values have been reported in the literature for the sensitivity of Doppler ultrasound in diagnosing transplanted kidney dysfunction. In our study, the Doppler sensi- tivity was greatly affected by the chosen RI threshold. Sensitivity was found to be 78% at an RI threshold of 0.7; as this threshold was increased, sensitivity dropped sharply reaching a value of 16% at an RI threshold of 0.9. The same findings were reported by Dupont et al,[8]who used a threshold RI value of 0.9, which resulted in a specificity for acute rejection of 89%, but a sensitivity of just 6%. They also stated that average RI in the rejection group was not higher than in controls (0.73 ± 0.11 vs. 0.74 ± 0.11, respectively). Accordingly, they concluded that measurement of RI by Doppler study does not contribute to the diagnosis of acute allograft dysfunction.

Furthermore, Allen et al[9]compared sono- graphy and scintigraphy with concurrent radio-nuclide examinations, which revealed similar sensitivities for rejection. Differentiation of acute tubular necrosis from rejection was more reliable with scintigraphy than with sono- graphy.[9]Osman et al studied 188 patients with Doppler sonography within two months of transplant biopsy. They concluded that Doppler measured RI lacked accuracy in diagnosing transplant kidney rejection; the low accuracy may be attributed to many extrarenal and intra- renal factors.[10]

To find out how the RI failed to live up to its promise as a parameter for measuring changes in renal transplant, we reviewed the theoretical explanations for understanding the meaning, usefulness, and limitations of the RI.[1],[11],[12]The RI is the ratio of difference between the peak systolic velocity and end-diastolic velocity to the peak systolic velocity. These velocity are sometimes altered in response to changes caused by extrarenal (prerenal and postrenal) conditions, intrarenal conditions, or both. Extra renal conditions include fever, heart rate, car- diac output, blood pressure, right-sided heart function, donor's age, and vascular conditions of recipients, whereas intrarenal conditions include glomerulopathy, interstitial fibrosis, tubular atrophy, and arteriosclerosis.[10],[13]Mostbeck et al stated that an increase in heart rate decreases the RI.[14]Pozniak et al also stated that bradycardia and general hypoten- sion affect RI value.[15]Many transplant pa- tients are under antihypertensive medications that can lower blood pressure and heart rate. This pharmacological effect may be equivalent to hypotension, and may lead to variations in RI values.[10]

Congruent with our findings, Ardalan et al showed a significant correlation between RI and SCr level during first month of posttrans- plantation.[16]Furthermore, Nezami et al[6]studied 273 patients and concluded that Doppler ultra- sound could be used as a tool to predict kidney function in association with SCr.[6]Finally, Radermacher et al have recently reported that the RI is the strongest predictor of declining in creatinine clearance as compared to other parameters.[17]

The limitations of our study included inter observer variation in Doppler ultrasound due to the retrospective nature of the study and small sample size. In addition, there was a lack of normal distribution of transplant duration, allograft types (living or deceased), recipient age, donor age, graft age, and underlying etio- logy of renal failures such as lupus nephritis and diabetes nephropathy.

We conclude that the sensitivity and specificity of Doppler measure RI in diagnosing trans- plant dysfunction are highly variable depen- ding on the chosen cutoff value. There were no significant differences in the mean RI value between patients with and without biopsy- proven transplant dysfunction. However, the correlation between RI and SCr can predict renal transplant dysfunction.

Disclosure: Financial support: None

Conflict of interests: None.



 
   References Top

1.
Tublin ME, Tessler FN, Murphy ME. Corre- lation between renal vascular resistance, pulse pressure and the resistive index in isolated perfused rabbit kidneys. Radiology 1992;213: 258-64.  Back to cited text no. 1
    
2.
Par SB, Kim JK, Cho KS. Complication of renal transplantation: Ultrasonographic evalua- tion. J Ultrasound Med 2007;26:615-33.  Back to cited text no. 2
    
3.
Langer JE, Jones LP. Sonographic evaluation of renal transplant. Ultrasound Clin 2007;2:73- 88.  Back to cited text no. 3
    
4.
Gao J, Ng A, Shih G, et al. Intrarenal color duplex ultrasonography: A window to vascular complications of renal transplants. J Ultra- sound Med 2007;26:1403-18.  Back to cited text no. 4
    
5.
Krumme B. Renal Doppler sonography - Update in clinical nephrology. Nephron Clin Pract 2006;103:c24-8.  Back to cited text no. 5
    
6.
Nezami N, Tarzamni MK, Argani H, Nourifar M. Doppler ultrasonographic indexes in kidney transplant recipients: Its relationship with kidney function. Iran J Kidney Dis 2007;1:82-7.  Back to cited text no. 6
    
7.
Solez K, Colvin RB, Racusen LC, et al. Banff 07 classification of renal allograft pathology: Updates and future directions. Am J Transplant 2008;8:753-60.  Back to cited text no. 7
    
8.
Dupont PJ, Dooldeniya M, Cook T, Warrens AN. Role of duplex Doppler sonography in diagnosis of acute allograft dysfunction-time to stop measuring the resistive index? Transpl Int 2003;16:648-52.  Back to cited text no. 8
    
9.
Allen KS, Jorkasky DK, Arger PH, et al. Renal allografts: Prospective analysis of Doppler sonography. Radiology 1988;169:371-6.  Back to cited text no. 9
    
10.
Osman OA, Griffith B, Classick S. Comparison between Doppler ultrasound and biopsy findings in patients with suspected kidney transplant rejection. Arab J Nephrol Transplant 2010;3:23-8.  Back to cited text no. 10
    
11.
Platt JF, Rubin JM, Ellis JH. Lupus nephritis: Predictive value of conventional and Doppler US and comparison with serologic and biopsy parameters. Radiology 1997;203:82-6.  Back to cited text no. 11
    
12.
Murphy ME, Tublin ME. Understanding the Doppler RI: Impact of renal arterial distensi- bility on the RI in a hydronephrotic ex vivo rabbit kidney model. J Ultrasound Med 2000; 19:303-14.  Back to cited text no. 12
    
13.
Gao J, Rubin JM, Xiang DY, et al. Doppler parameters in renal transplant dysfunction: Correlations with histopathologic changes. J Ultrasound Med 2011;30:169-75.  Back to cited text no. 13
    
14.
Mostbeck GH, Gossinger HD, Mallek R, Siostrzonek P, Schneider B, Tscholakoff D. Effect of heart rate on Doppler measurements of resistive index in renal arteries. Radiology 1990;175:511-3.  Back to cited text no. 14
    
15.
Pozniak MA, Kelcz F, Stratta RJ, Oberley TD. Extraneous factors affecting resistive index. Invest Radiol 1988;23:899-904.  Back to cited text no. 15
    
16.
Ardalan MR, Tarzamani MK, Mortaazavi M, Bahloli A. Relation between resistive index and serum creatinine level in first month after renal transplantation. Transplant Proc 2003;35: 2628-9.  Back to cited text no. 16
    
17.
Radermacher J, Mwbgel M, Ellis S, et al. The renal arterial resistive index and renal allograft survival. N Engl J Med 2003;349:115-24.  Back to cited text no. 17
    

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Correspondence Address:
Kajal N Patel
Department of Radiology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad - 380 016, Gujarat
India
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DOI: 10.4103/1319-2442.182391

PMID: 27215246

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