The Whitaker test, a useful tool in renal grafts?

ADULT UROLOGY

THE WHITAKER TEST, A USEFUL TOOL IN RENAL GRAFTS? HERBERT SPERLING, GEROLD BECKER, UWE HEEMANN, GERD LU¨MMEN, THOMAS PHILIPP, HERBERT RU¨BBEN

AND

ABSTRACT Objectives. To evaluate the Whitaker test, a pressure flow examination, for its prognostic value in dilated renal transplants because urologic complications, such as ureteral stenosis, are significant problems after kidney transplantation. Methods. Twenty-five patients with obstruction of the renal transplant and subsequent percutaneous nephrostomy were evaluated with a urodynamic pressure flow test (Whitaker test) in combination with antegrade pyeloureterography. The results of the Whitaker test were related to the serum creatinine values. Results. The Whitaker test demonstrated normal pressure flow (less than 15 cm H2O) in 7 patients, pressure flow between 15 and 25 cm H2O in 10, and pathologic results (greater than 25 cm H2O) in 8 patients. After percutaneous nephrostomy, the serum creatinine level decreased in 22 of 25 patients, although the urodynamic pressure flow revealed a significant obstruction (Whitaker test greater than 25 cm H2O) in only 8 patients. The sensitivity of the Whitaker test to indicate the relevance of post-renal transplant stenosis in comparison to the declining serum creatinine level after successful percutaneous nephrostomy was 79%; the specificity was 50%. Conclusions. The results of our study indicate that a decreasing creatinine level in correlation with radiologic results is the leading finding in dilation of transplanted kidneys without rejection. The Whitaker test, as a pressure flow examination, provided no additional information. UROLOGY 56: 49–52, 2000. © 2000, Elsevier Science Inc.

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n kidney transplantation, any urologic complication such as stenosis or leakage of the ureter must be taken seriously.1 In large contemporary series, urologic problems after renal transplantation occur with an incidence of 4% to 13% during the first year.2– 4 A frequent complication after renal transplantation is obstruction, with subsequent dilation of the renal pelvis. After percutaneous nephrostomy of the dilated graft, we performed the Whitaker test in all patients as a standard procedure. The rationale for performing this examination was the good experiences we had had with the Whitaker test in the dilated kidneys of children. It had provided additional and predictive information. To evaluate the prognostic value of the Whitaker test, we retrospectively examined the results of the Whitaker test and the development of lowFrom the Departments of Urology and Nephrology, University of Essen, Essen, Germany Reprint requests: Herbert Sperling, M.D., Department of Urology, University of Essen, Hufelandstrasse 55, D-45122 Essen, Germany Submitted: December 6, 1999, accepted (with revisions): February 10, 2000 © 2000, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED

ered creatinine levels after treatment by percutaneous nephrostomy in our patients with dilation of a transplanted kidney. MATERIAL AND METHODS All patients who received a kidney graft between 1987 and 1997 who were treated with percutaneous nephrostomy because of suspected obstruction (n ⫽ 35) were evaluated. During this period, 948 patients received a kidney graft. Retrospectively, 25 of them could be completely evaluated. Ten patients were excluded because of missing data. The data of the Whitaker test, x-ray findings, creatinine level before and after intervention, and operative treatment were collected and analyzed. The percutaneous nephrostomy was performed under ultrasound guidance with a 5F nephrostomy set usually used for orthotopic, percutaneous nephrostomy of children. After treatment and a decreasing serum creatinine level, the Whitaker test was performed; rejection episodes were excluded by biopsy. The Whitaker test was performed with radiologic guidance using the inlaid nephrostomy tube for infusion. A 16F catheter was introduced into the bladder to measure the intravesical pressure continuously during the examination. The nephrostomy tube was connected to a second pressure measuring unit and infusion pump. The renal pelvic pressure and the intravesical pressure were continuously measured, and the pressure difference was calculated by computer assis0090-4295/00/$20.00 PII S0090-4295(00)00541-0 49

tance using a urodynamic unit (Wiest, Munich, Germany). The infusion was started with body-temperature isotone x-ray contrast medium under control of the urodynamic unit after calibration of the system at an infusion rate of 10 mL/min. The perfusion was continued until a steady-state pressure was reached, and the contrast medium was visible in the bladder by radiography. The infusion was stopped if the patient felt pressure in the transplant region or the renal pelvic pressure exceeded 50 cm H2O. We used the findings of Whitaker5 for the transplanted kidney. A pressure less than 15 cm H2O was regarded as normal, pressure between 15 and 25 cm H2O was diagnostically equivocal, and an increased pressure of more than 25 cm H2O indicated obstruction.6 All pressure results were related to antegrade pyeloureterography, the creatinine trend, and the operative findings.

FIGURE 1. Decrease of serum creatinine after nephrostomy related to the Whitaker test results.

RESULTS PATIENTS The median age of the 25 patients was 36.6 years (range 12 to 60). Obstruction of the ureter with subsequent dilation of the pelvis was suspected by ultrasound in 10 patients within the first month, in 11 between 2 and 12 months, and in 4 patients more than 12 months after transplantation. The median period was 3 months (range l to 87) after transplantation. ANTEGRADE PYELOURETEROGRAPHY Antegrade pyeloureterography revealed radiologic signs of obstruction in 18 patients. The location was in the proximal ureter in 5 patients and in the distal ureter in 13 patients; 7 patients had no radiologic signs of obstruction. CREATININE LEVEL At the time of the primary investigation (ie, dilated renal pelvis before nephrostomy), the serum creatinine level was up to 2.0 to 9.9 mg/dL, and the calculated increase was between 0 and 6.5 mg/dL (median 2.0). After decompression (percutaneous nephrostomy), the serum creatinine level decreased, with a median of 1.2 mg/dL (range 0.6 to 5.6) within a mean of 7.3 days in 22 patients. The creatinine levels did not decrease after nephrostomy in 3 patients. WHITAKER TEST During the Whitaker test, a pathologic pressure (greater than 25 cm H2O) was observed in 8 patients, and a pressure between 15 and 25 cm H2O was found in 10 patients. Normal results were obtained in 7 patients (less than 15 cm H2O; Fig. 1). Two patients developed complications from the Whitaker test due to the nephrostomy: bleeding in one patient and an increasing creatinine level in the other. WHITAKER TEST AND CREATININE LEVEL In all patients with pathologic Whitaker test results, the creatinine level decreased after nephros50

TABLE I. Patient stratification according to the Whitaker test and creatinine level after nephrostomy Whitaker Test (cm H2O) ⬍15 15–25 ⬎25

Creatinine Level Decrease

No Change

5 9 8

2 1 0

tomy. In 9 of the 10 patients with Whitaker test results between 15 and 25 cm H2O (suspicious Whitaker test), the creatinine level decreased. Five patients with normal results in the Whitaker test had a decreasing creatinine level (greater than 20% creatinine decrease); in 2 patients, the creatinine level was not influenced by the nephrostomy (Table I). No statistically significant correlation between the Whitaker test results and the serum creatinine changes after nephrostomy was found. However, a tendency for a higher decrease in the creatinine level was observed with elevated Whitaker test results (Fig. 1). OPERATIVE TREATMENT At the time of stable creatinine levels after nephrostomy, the catheter was closed to test the clinical relevance. In 6 patients, the creatinine level did not increase thereafter and no further treatment was initiated. The other 19 patients had clinically relevant signs of increasing creatinine levels after testing. Therefore, in 14 patients, ureteroneocystostomy or pyelocystostomy was performed to treat ureteral stricture or necrosis. Only 11 of these 14 patients had suspicious or significantly elevated values according to the Whitaker test. In 3 patients, extrinsic reasons (lymphocele or ureteral scars) were seen and treated. All of them had elevated pressure-flow values. In 2 patients, explantation of the graft was necessary; 1 patient had stable elevated creatinine levels after nephrostomy because of a later diagnosed rejection episode withUROLOGY 56 (1), 2000

TABLE II. Patient stratification according to the Whitaker test and subsequent operative treatment Whitaker Test (cm H2O) No treatment UCN Ureterolysis/lymphocele Explantation

<15

15–25

>25

3 3 0 1

3 5 2 0

0 6 1 1

KEY: UCN ⫽ ureteroneocystostomy.

out response to the usual treatment. The other patient had a poor vascular condition between the transplanted kidney and ureter, without the possibility of restoring the organ (Table II). SENSITIVITY AND SPECIFICITY The sensitivity of the Whitaker test was 79% (95% confidence interval 54% to 94%). The specificity was 50% (95% confidence interval 12% to 88%). The positive prognostic value of the Whitaker test in dilated renal transplants was not calculated because of the small cohort. COMMENT Ureteral complications are not rare in the immunosuppressed renal transplant population. The therapeutic approaches, including a temporary percutaneous nephrostomy, vary.7 Dilation of the renal transplant can occur in all periods after transplantation. In our series, as shown elsewhere by the same method, 40% of the patients experienced dilation of the kidney transplant, which led to further operative treatment within the first month after transplantation. Early strictures seem to be caused by technical problems, later ones by extrinsic compression or ureteral ischemia.4,8,9 After renal transplantation dilation must be treated immediately if transplant function is not to be irretrievably lost. The first step is ultrasoundguided percutaneous nephrostomy. Percutaneous nephrostomy is a safe and effective treatment that provides a valuable alternative to immediate operative treatment in renal transplant recipients with ureteral obstruction. Also, the nephrostomy may obviate the need for subsequent operative therapy, because it allows for additional examination.10 –13 After restoring the former graft function by use of the percutaneous nephrostomy set, the inlaid catheter was used for diagnostic evaluation. Using this procedure, 22 patients demonstrated a decrease in the creatinine level to acceptable values before radiographic and pressure studies (Whitaker test). This result corresponded with those of others, in UROLOGY 56 (1), 2000

which the protection of the graft function was also the most important issue.10 –14 Antegrade pyelography can reveal the location of the obstruction. In our study, antegrade pyelography demonstrated relevant stenosis of the ureter in 18 patients. However, other investigators found the value of this procedure to be uncertain.4,10 –14 The borderline result (between 15 and 25 cm H2O) of the Whitaker test should be considered critically, because five of our patients with normal pressure results (less than 15 cm H2O) had a decrease in creatinine levels (Table I). These patients should not have had obstruction according to the definition.15 In our small series, the Whitaker test was not able to define the obstruction in more than 8 (70%) of the 25 patients. On the other hand, an alternative examination such as renal scintigraphy more clearly reveals kidney obstruction. However, a disadvantage of renal scintigraphy is that it cannot discriminate among arterial stenosis, inflammation, and ureteral obstruction. And even when there is no doubt about the presence of ureteral obstruction, renal scintigraphy cannot localize the obstruction.16,17 Because of the retrospective data collection, other examinations such as serial creatinine clearance levels or renal scintigraphy were not performed in this series. Keller et al.9 showed that a “modified Whitaker test” was able to verify all 27 of the obstructed ureters by the increasing pressure in the renal pelvis. Because their modification was not standardized, a comparison of their results with our data was not possible. The modified Whitaker test was performed with a freehand application of contrast medium under radiographic control without pressure measurement. Therefore, the value of this “modified” test is controversial. A comparable evaluation was performed by Zollikofer et al.,18 who reported on 18 patients with dilation of the renal pelvis and used a similar method with percutaneous nephrostomy, pyelography, and Whitaker test after kidney transplantation. They assumed, as we did, that the decrease in creatinine level was the most important factor, because kidneys with persistent or rising creatinine levels did not benefit from surgical relief of the obstruction. Kashi et al.19 had conflicting results with the Whitaker test. The results of all 19 of their pressure-flow studies correlated with the radiographic findings. Their study was different from ours in that they included patients with acute rejection in the examination; we excluded such patients in our study. CONCLUSIONS The most important information and leading indication, despite our not including the patients 51

with acute rejection, was the decreasing creatinine level after percutaneous nephrostomy and before additional operative treatment. Antegrade pyelography provided adjunct information, especially for the location of the stricture or compression of the ureter before definite treatment. The Whitaker test itself did not give any certain, prognostic information (sensitivity 79%, specificity 50%) about the situation at the ureteral-bladder junction. Therefore, we believe that after nephrostomy, the decrease in the serum creatinine level is the finding that should lead to operative revision.16,20 ACKNOWLEDGMENT. To Mrs. Renzing-Ko¨hler for statistical help. REFERENCES 1. Wagner M, Dieckmann KP, Kla¨n R, et al: Rescue of renal transplants with distal ureteral complications by pyelopyelostomy. J Urol 151: 578 –581, 1994. 2. Mundy AR, Podsta ML, Bewick M, et al: The urological complications of 1000 renal transplants. Br J Urol 53: 397– 402, 1987. 3. Loughlin KR, Tilney NIL, and Richie JP: Urologic complications in 718 renal transplant patients. Surgery 95: 297– 302, 1984. 4. Shoskes DA, Hanbury D, Cranston D, et al: Urological complications in 1000 consecutive renal transplant recipients. J Urol 153: 18 –21, 1995. 5. Whitaker RH: The Whitaker test. Urol Clin North Am 6: 529 –539, 1979. 6. Jakobsen H, Nordling J, Munck O, et al: Sensitivity of 131 J-hippuran diuresis renography and pressure flow study (Whitaker test) in upper urinary tract obstruction. Urol Int 43: 89 –92, 1988. 7. Goldstein L, Cho SI, and Olsson CA: Nephrostomy drainage for renal transplant complications. J Urol 126: 159 – 163, 1981. 8. Jaskowski A, Jones RM, Murie JA, et al: Urological com-

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plications in 600 consecutive renal transplants Br J Surg 74: 922–925, 1987. 9. Keller H, No¨ldge G, Wilms H, et al: Incidence, diagnosis, and treatment of ureteric stenosis in 1298 renal transplant patients. Transplant Int 7: 253–257, 1994. 10. Streem SB, Novick AC, Steinmuller DR, et al: Percutaneous techniques for the management of urological renal transplant complications. J Urol 135: 456 – 459, 1986. 11. Beer M, Fornara P, Laible V, et al: Stellenwert perkutaner Diagnostik und Therapieverfahren bei obstruktiver Uropathie nach Nierentransplation. Urol A 26: 137–141, 1987. 12. Oosterhof GON, Hoitsma AJ, Witjes JA, et al: Diagnosis and treatment of urological complications in kidney transplantation. Urol Int 49: 99 –103, 1992. 13. Irving HC, and Kashi SH: Complications of renal transplantation and the role of interventional radiology. J Clin Ultrasound 20: 545–552, 1992. 14. Rickards D: Percutaneous nephrostomy and antegrade pyelography, in O’Reilly PH (Ed): Diagnostic Techniques in Urology. Philadelphia, WB Saunders, 1990, pp 119 –134. 15. Witherow ROX, and Whitaker RH: The predictive accuracy of antegrade pressure flow studies in equivocal upper tract obstruction. Br J Urol 53: 496 – 499, 1981. 16. Turner AG, Howlett KA, Eban R, et al: The role of antegrade pyelography in the transplant kidney. J Urol 123: 812– 814, 1980. 17. Diethelm AG, Dubovsky EV, Whelchel JD, et al: Diagnosis of impaired renal function after kidney transplantation using renal scintigraphy, renal plasma flow and urinary excretion of hippurate. Ann Surg 191: 604 – 616, 1980. 18. Zollikofer CL, Bru¨hlmann WF, Baumgartner D, et al: Antegrade pyelography, percutaneous nephrostomy and ureteral perfusion (Whitaker test) for the renal transplant recipient. ROFO Fortschr Geb Rontgenstr Nuklearmed 142: 193– 200, 1985. 19. Kashi SH, Irving HC, and Sadek SA: Does the Whitaker test add to antegrade pyelography in the investigation of collecting system dilatation in renal allografts? Br J Radiol 66: 877– 881, 1993. 20. Cullmann HJ, and Prosinger M: Necrosis of the allograft ureter— evaluation of different examination methods in early diagnosis. Urol Int 45: 164 –169, 1990.

UROLOGY 56 (1), 2000