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DOPPLER ULTRASONOGRAPHY IN THE EVALUATION OF RENAL TRANSPLANTS

J T Jagose, S G Kulkarni, T J Vachharajani, A L Kirpalani, A K Dalal*, U G Oza**,
A G Phadke**
Dept. of Nephrology, Ultrasonography* and Transplantation** Bombay Hospital Institute of Medical Sciences, Mumbai, India.

Doppler ultrasonography (US) is a useful, non-invasive method of monitoring renal allograft dysfunction. Thirty-eight living donor transplant recipients had 90 Doppler and real time US studies during the postoperative period. Fifty of these were performed in 18 patients with a normally functioning allograft and 40 studies in 20 patients with renal dysfunction. The resistive indices (RI) measured at the arcuate arteries were 0.56 to 0.7 in those with normal renal function and ranged from 0.70 to 0.88 in allografts with dysfunction. The waveform pattern which was classified into 6 types revealed that types 2,4 and 6 were seen during renal dysfunction; type 1 was not diagnostic of normal, whereas type 3 excluded an abnormality.

We concluded that although renal biopsy remains the gold standard for diagnosis of renal dysfunction, Doppler US was a useful, non-invasive, but costly imaging modality for evaluating renal allografts and a useful adjunct to real time US.

INTRODUCTION

Doppler ultrasonography (US) has been used in medicine as an imaging method for many years. The early investigations into the nature of the Doppler effect were performed by Christian Andreas Doppler about 150 years ago and because of his work, the effect was named after him. [1]

Applications of Doppler US in nephrology include the investigation of patients with suspected renovascular hypertension, follow-up after renal revascularisation and assessment of renal transplants. [2-4] Arima et al. [5] were the first to report the application of Doppler US in the assessment of the arterial blood flow pattern in the normal and transplanted kidney.

AIMS

The aims of the present study were:-

  1. To record the blood flow pattern in normally functioning renal allografts.
  2. To record the blood flow pattern in acute allograft dysfunction.
  3. To correlate the results of Doppler US with the clinical features and/or histopathological changes in patients with graft dysfunction.
  4. To monitor the efficacy of anti-rejection therapy.
  5. To detect allograft vascular stenosis and/or occlusion.

MATERIAL AND METHODS

Thirty-eight patients who underwent a live donor renal transplant were included in the study. Clinical and biochemical parameters were monitored daily for the first 10 days post-operatively and then on alternate days until day 18. Whole blood trough cyclosporin concentrations (monoclonal RIA method) were measured on days 5,12 and 18 post-operatively. Doppler US was undertaken on days 3,10 and 18 post-operatively and additionally if the serum creatinine concentration rose 30% or more above the baseline value.

The immunosuppressive regimen included prednisone, azathioprine and cyclosporin for 13 patients and prednisone and azathioprine alone for the remaining 25 patients. Acute rejection episodes were treated with pulses of methylprednisolone 1g iv daily for three days. An allograft biopsy was done if there was no fall in the plasma creatinine after a reduction in the cyclosporin dose.

The clinical diagnosis was categorised as follows:-

  1. Cyclosporin toxicity - graft dysfunction with a fall in plasma creatinine after cyclosporin dose reduction.
  2. Acute rejection (cellular and vascular)
  3. Recurrence of original renal disease.
  4. Acute tubular necrosis.
  5. Indeterminate renal dysfunction (no cause found).

The histopathological findings were classified as follows:-

  1. Acute rejection (cellular and vascular)
  2. Chronic rejection
  3. Cyclosporin nephrotoxicity
  4. Acute tubular necrosis
  5. Normal histology in the face of graft dysfunction.

Doppler US Examination

A triplex colour Doppler machine (Acuson 128 x P/10) with a 3.5 mHz probe with pulsed wave Doppler was used. Real time scanning was performed to determine renal size, cortical thickness and echotexture and to detect hydronephrosis, perirenal collections, urinary calculi or renal cysts. The pulsed Doppler signal was used to assess the renal blood flow in the internal iliac artery, transplant renal artery and arcuate arteries, and was evaluated both quantitatively and morphologically.

Doppler signals from a normal renal allograft are characterised by a continuous flow extending throughout diastole, with the initial diastolic velocity being at least half that of the peak systolic velocity and then decreasing, but never approaching zero velocity. [5-9] In acute allograft rejection, there is decreased blood flow velocity in diastole, with an increase in the ratio of peak systolic to diastolic velocities. During severe acute rejection, diastolic flow is obliterated or even reversed, with dampening of systolic flow. In chronic rejection, neither systolic nor diastolic flow undergo an abrupt change, and a concomitant dampening and broadening of the systolic waveform corresponding to deterioration of blood flow is seen.[10]

For quantitative analysis of Doppler signals the resistive index (RI) was calculated in each case as proposed by Pourcelot.[10]

RI = Peak systolic
frequency shift		 — End diastolic
frequency shift
Peak systolic frequency shift

Analyses of Doppler waveform patterns were based on the classification of Renowden et al. [9] and are included in the statistical significance of the RIs between the groups with normal renal function and renal dysfunction was determined using the unpaired ‘t’ test.

RESULTS

The cause of chronic renal failure in the 38 patients studied were chronic glomerulonephritis 10; nephrosclerosis 4; diabetic nephropathy, membrano-proliferative glomerulonephritis and polycystic kidney disease 3 each; chronic pyelonephritis 4, minimal change nephropathy, membranous nephropathy and Alport’s syndrome 1 each and uncertain in 8.

The patients were divided into two groups on the basis of their renal function. Of the 38 patients 18 (13 male; mean age 40.2 yr; age range 20-60 yr) had a plasma creatinine concentration of 0.6-1.2 mg% (normal renal function) and the remaining 20 (15 male; mean age 35.6 yr; age range 18-60 yr) had a serum creatinine > 1.2 mg% (graft dysfunction).

The most common abnormalities observed onreal time US were prominence of the medullary pyramids and increased cortical echogenicity. In 20 of 40 studies performed during renal dysfunction, there were no abnormalities seen on real time US (Table 1).

TABLE 1
Waveform pattern analysis based on Renowden et al. [8] classification
Type Pattern No. of US scans
    No dysfunction
(50) 		Dysfunction
(40)
1. Ski-slope 45 22
2. Mid-diastolic notch 0 10
3. Steep systolic descent 5 0
4. Rapid fall off at end-diastole 0 3
5. High systolic peak 0 3
6. Absent/reversed flow 0 2

The clinical correlation and the results of the Doppler scans in all patients are included in Table 2. The mean RI values were statistically significant between the groups with normal renal function and the remaining patients with renal dysfunction (p < 0.001). No increase in RI was observed in patients with transplant glomerulopathy, acute tubular necrosis or cyclosporin toxicity (Table 2).

TABLE 2
Relationship between clinical diagnosis and RI on Doppler US
Diagnosis No. of scans (90) RI
    Mean + SD
Normal 50 0.56 + 0.07
Rejection 26 0.70 + 0.11
Indeterminate dysfunction 8 0.68 + 0.09
Transplant glomerulopathy 1 0.45
Acute tubular necrosis 2 0.42 + 0.03
Cyclosporin toxicity 3 0.57 + 0.08

Among the patients with normal renal function, 47 of the 50 Doppler US scans had RI values between 0.50-0.70 and 3 had a value > 0.70 (0.72, 0.74, 0.77). In contrast, among those with renal dysfunction, 26 of the 40 Doppler scans had RI values between 0.50-0.70, with the remaining 14 having a value > 0.70 (Table 3).

TABLE 3
Correlation between RI and graft function in all patients
RI No. of scans of those with normal renal function (50) No. of scans in those with graft dysfunction (40)
< 0.50 6 5
0.51-0.60 24 4
0.61-0.70 17 17
0.71-0.80 3 8
0.81-0.90 0 4
> 0.91 0 2

DISCUSSION

Conventional real time US is used routinely for assessing renal allograft dysfunction. The role of Doppler US, however, needs to be established.

The present study demonstrated that of the 50 scans performed in normally functioning allografts, 47 had an RI value in the 0.50-0.70 range. In contrast, among the 40 scans performed during episodes of renal dysfunction, 14 had an RI value > 0.70.

All RI values measured at the level of the arcuate arteries > 0.80 were observed in patients with graft dysfunction. No RI value was identified below which it could be stated with confidence that the graft was functioning normally. Therefore, an RI value > 0.80 was highly suggestive of acute rejection, while a value between 0.70 and 0.80 occurred significantly more frequently in those with graft dysfunction, but was not diagnostic of acute rejection.

Some studies11 have demonstrated that an RI value â 0.70 is unlikely to be associated with rejection. Other workers,12,13 however have shown that a significant number of patients with acute rejection had normal RI values. Our study showed that 56% of Doppler US scans performed during a biopsy-proven acute rejection had normal RI values between 0.50 and 0.70.

Of the various waveform patterns observed in our study, types 2, 4 and 6 were observed only in renal dysfunction, while types 1 and 3 were seen in those with normal renal function. However, 22 of 67 (33%) scans which showed a type 1 pattern were seen in patients with renal dysfunction, and hence this waveform could not be taken as conclusive evidence of normality.

Renowden et al [8] demonstrated a type 1 pattern in two-thirds of patients with graft dysfunction and in 80% of those with normally functioning allografts. This group of workers found a type 2 pattern in 12 of 71 patients with renal dysfunction due to acute cellular rejection, type 5 in 4 of 71 patients with graft dysfunction and type 6 in 11 of 71 patients including 1 patient with a normal biopsy and aortic incompetence, emphasising the need to be aware of co-existing cardiac abnormalities when interpreting Doppler signals.

Due to contradictory results in the literature, most groups now use an elevated RI (> 0.80) as a non-specific parameter for renal transplant dysfunction. Differentiation between differing causes for graft failure (acute rejection - cellular and vascular chronic rejection, acute tubular necrosis, cyclosporin toxicity) is made largely by percutaneous biopsy. [14]

The following observations were made from this study

  1. Waveform pattern 1 may be seen in both normal and abnormally functioning grafts.

    Waveform pattern 3 was uncommon and not seen in the presence of graft dysfunction.

  2. RI > 0.80 - abnormal.

    RI 0.70-0.80 - highly suggestive of abnormality

    RI < 0.70 - no diagnostic significance

  3. RI < 0.80 with waveform pattern 1 seen frequently in renal dysfunction of any aetiology.

  4. Doppler US was found to be a useful adjunct to real time US, however its routine use in normally functioning allografts is not justifiable due to its high cost.

  5. Renal allograft biopsy remains the gold standard for the diagnosis of renal dysfunction. However, it need not be mandatory to biopsy all patients with graft dysfunction. When appropriate clinical and laboratory data strongly point to acute rejection and the RI is > 0.80 with abnormal waveform patterns 2,4,5 or 6, it is justifiable to give empiric anti-rejection therapy.

REFERENCES

  1. Kenneth JW, Taylor D, Strandness E (Jr). Clinics in diagnostic ultrasound - duplex Doppler ultrasound. New York : Churchill Livingston. 1990.
  2. Avasthi PS, Voyles WF, Greene ER. Noninvasive diagnosis of renal artery stenosis by echo-Doppler velocimetry. Kid Int 1984; 25 : 824-29.
  3. Robertson R, Murphy A, Dubbins PA. Renal artery stenosis : the use of duplex ultrasound as a screening technique. Br J Radiol 1988; 61 : 196-201.
  4. Fleischer AC, Hinton AA, Glick AD, Johnson HK. Duplex Doppler sonography of renal transplants. Correlation with histopathology. J Ultrasound Med 1989; 8 : 89-94.
  5. Arima M, Ishibashi M, Usami M, et al. Analysis of the arterial blood flow patterns of normal and allografted kidneys by directional ultrasonic doppler technique. J Urol 1979; 122 : 587-91.
  6. Reinitz ER, Goldman MH, Sais J, et al. Evaluation of transplant renal artery blood flow by Doppler sound-spectrum analysis. Arch Surg 1983; 118 : 415-19.
  7. Hricak H, Cruz C, Eyler WR, Madrazo BL, Romanski R, Sandler MA. Acute post-transplantation renal failure : differential diagnosis by ultrasound. Radiol 1981; 139 : 441-49.
  8. Renowden SA, Griffiths DF, Nair S, Krishnan H, Cochlin DL. Renal transplant sonography : correlation of Doppler and biopsy results in cellular rejection. Clin Radiol 1992; 46 : 265-269.
  9. Berland LL, Lawson TL, Adams MB, Melrose BL, Foley WD. Evaluation of renal transplant with pulsed Dopplerduplex sonography. J Ultrasound Med 1982; 1 : 215-22.
  10. Murphy AM, Robertson RJ, Dubbins PA. Duplex ultrasound in the assessment of renal transplant complications. Clin Radiol 1987; 38 : 229-34.
  11. Rifkin MD, Needleman L, Pasto, et al. Evaluation of renal transplant rejection by duplex Doppler examination : value of the resistive index. Am J Roentgenol 1987; 148 : 759-62.
  12. Genkins SM, Sanfilippo FP, Carroll BA. Duplex Doppler sonography of renal transplants : lack of sensitivity and specificity in establishing pathologic diagnosis. Am J Roentgenol 1989; 152 : 535-39.
  13. Kelcz F, Pozniak MA, Pirsch JD, et al. Pyramidal appearance and resistive index : insensitive and non-specific sonographic indictors of renal transplant rejection. Am J Roentgenol 1990; 155 : 531-35.
  14. Tublin ME, Dodd GD. Sonography of renal transplantation. Radiol Clin North Am 1995; 33 : 447-59.

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