Alteplase Instillation for Upper Urinary Tract Clot Dissolution

Abstract

Background: We report the first case of instillation of alteplase, a tissue plasminogen activator, to dissolve occlusive upper urinary tract blood clot.

Case Presentation: A 67-year-old Caucasian man with a solitary kidney became dialysis dependent because of upper urinary tract clot obstruction after ureteral stent placement for obstructing ureterolithiasis. After failure of more conservative measures, 10 mg of alteplase was instilled through nephrostomy tube daily for 2 consecutive days 30 minutes before manual irrigation with physiologic saline. After alteplase instillation, the occlusive blood clot dissolved with rapid improvement in urinary output and creatinine.

Conclusions: Alteplase instillation through nephrostomy tube is a viable option to dissolve obstructing upper urinary tract blood clots.

Background

Nephrostomy tubes serve several purposes including upper urinary tract decompression, tamponade, and access for contrast imaging and procedures. The consequences of nephrostomy tube occlusion can be devastating and warrant urgent nephrostomy exchange or placement of a second tube. There are limited reported cases of the use of thrombolytics in the case of nephrostomy tube occlusion secondary to clot. Herein, we describe the effective use of alteplase, a thrombolytic that converts plasminogen to plasmin, to dissolve occlusive upper urinary tract blood clot.

Presentation of Case

A 67-year-old Caucasian man presented with an extensive medical history including prior left nephroureterectomy for upper tract urothelial carcinoma, severe aortic stenosis, chronic kidney disease (baseline creatinine 1.44 mg/dL), coronary artery disease, and deep vein thrombosis with pulmonary embolus anticoagulated with warfarin. He presented to our emergency department with an 8 mm obstructing right proximal ureteral stone,creatinine of 5.73 mg/dL, and International Normalized Ratio (INR) of 2.6. He was taken for ureteroscopic stone extraction, however, his ureter did not accommodate a 10F dual-lumen catheter. In our practice, we do not routinely dilate anticoagulated patients; therefore, a 7F × 28 cm JJ ureteral stent was placed to allow passive dilation and a staged return for definitive management.

The patient had minimal improvement in urine output; therefore, retroperitoneal ultrasonography was obtained and demonstrated renal caliceal dilation suggestive of stent failure. The following day, the patient underwent stent upsizing to 8F × 28 cm. During the procedure, retrograde pyelogram showed a small amount of contrast extravasation from the proximal ureter, thus we suspect wire trauma from initial stent placement provoked the bleeding. The patient was also noted to have a large clot burden within the bladder and was placed on continuous bladder irrigation.

The following day, the patient's urine cleared and continuous bladder irrigation was discontinued. However, over the next 2 days, the patient became progressively oliguric (urine output: 500 cc and 140 cc, respectively), whereas serum creatinine level rose to 8.40 mg/dL.

Owing to concern for stent obstruction, a 10F miniclose loop pigtail catheter right nephrostomy tube was placed and the patient underwent emergent dialysis. The patient's INR was reversed with fresh frozen plasma (5 U) and vitamin K (10 mg) before nephrostomy placement. After nephrostomy tube placement, urine output improved with 3.85 L through nephrostomy tube and 1.8 L from the Foley catheter.

Despite scheduled nephrostomy tube irrigations (10 cc every 4 hours), urine output declined over the following 2 days (1900 cc then 400 cc), whereas creatinine increased to 10.22 mg/dL. Five days after initial nephrostomy tube placement, the nephrostomy tube was upsized to 12F Mac-Loc catheter with no improvement in urine output (60 cc). Imaging showed an irregular right renal pelvis filled with a significant amount of clot and an occluded ureteral stent (Fig. 1). The patient continued to require dialysis. Given the degree of clot burden within the renal pelvis and inability to manually aspirate, we attempted clot dissolution through instillation of alteplase through nephrostomy tube. A 10 mL solution of 10 mg (1 mg/mL) of alteplase was instilled through the nephrostomy tube over a period of 30 seconds, followed by a 3 mL flush of physiologic saline. The nephrostomy tube was then clamped for 30 minutes to allow the alteplase to dwell within the renal pelvis. After 30 minutes, 10 mL of clot was aspirated followed by two 10 mL irrigations with physiologic saline. This process was repeated again the following day.

FIG. 1.

(A) Nephrostomy tube contrast imaging performed before alteplase instillation demonstrating irregular kidney with significant clot burden (arrow). (B) Nephrostomy tube contrast imaging performed after alteplase instillation (arrow). No clot burden observed.

After initial alteplase instillation, urine output increased to 1.23 L. Figure 2 depicts the trend in urine output and alteplase instillation. Urine output peaked after the second alteplase instillation at 5.4 L. The patient did not require further dialysis, and on day 6 after initial instillation, nephrostogram was performed, which demonstrated significant improvement in clot burden (Fig. 1), and the nephrostomy tube was clamped. The patient was discharged the following day with a serum creatinine of 2.23 mg/dL. At discharge, Lovenox was used for bridging until his INR was therapeutic.

FIG. 2.

Daily cumulative urine output (nephrostomy tube and Foley catheter output) and creatinine changes documented in the patient's chart over the course of his hospital stay. ^ADay of alteplase instillation in nephrostomy tube. ^XDay of nephrostomy tube exchange.

Discussion

Urinary obstruction in a solitary kidney is a urologic emergency, with failure to obtain adequate drainage resulting in acute renal injury and the need for dialysis. As reported in our case, despite multiple attempts to obtain drainage, the patient formed obstructing upper tract clot that precluded adequate decompression. Urokinase, normally found in urine, is a physiologic plasminogen activator, allowing the body to lyse clots. However, given the oliguric renal failure secondary to clot burden, the patient likely did not have adequate urokinase to auto-lyse the clot. Therefore, we elected a trial of alteplase instillation through nephrostomy tube to lyse the suspected blood clots prohibiting proper drainage. After alteplase instillation, the patient had rapid improvement in both urine output and renal function with no adverse effects or recurrent bleeding.

Alteplase is not Food and Drug Administration approved for use in the urinary tract, and caution should be exercised before proceeding with this off-label use. In this case, wire trauma in the setting of systemic anticoagulated likely led to the clot obstruction. The clot functions to tamponade bleeding, so the risk of rebleeding after alteplase administration must be considered. For this patient, the bleeding had been confined to the renal pelvis/ureter and the patient remained hemodynamically stable, so a recurrent bleed was unlikely to be life threatening. In addition, the bleeding occurred while the patient was systemically anticoagulated. His INR had normalized by the time we instilled the alteplase, which we felt may limit additional bleeding caused by clot disruption.

Alteplase is a recombinant tissue plasminogen activator, which cleaves plasminogen to its active form plasmin. Plasmin subsequently degrades fibrin, dissolving clots. Alteplase and other recombinant forms of tissue plasminogen activator are established management options in the setting of myocardial infarction and stroke. There are few reported cases utilizing thrombolytics in the urinary tract in the modern era. Previously, Pautler et al.¹ described effective resolution of upper urinary tract clot after urokinase instillation through an obstructed nephrostomy tube. However, urokinase, which was previously used for thrombolysis, was taken off the market in 1999 after the introduction of alteplase. More recently, there is a reported case of intravesical clot lysis through instillation of alteplase through a Foley catheter with no adverse side effects.² In addition, there are reported cases of bladder clot dissolution with alteplase instillation in animal and in vitro settings.^3,4 However, to our knowledge, this is the first reported case of effective alteplase instillation for upper urinary tract clot obstruction.

Conclusion

Upper urinary tract clot obstruction, particularly in a solitary kidney, may present a urologic emergency with few described therapeutic options. In this study, we present an effective case report of resolution of renal failure secondary to obstruction with instillation of alteplase. Alteplase instillation through nephrostomy tube may provide a safe and viable option to relieve upper tract clot obstruction.

Disclosure Statement

No competing financial interests exist.

Cite this article as: Mahmoud A, Manka M, Lipworth R, Heslop D, Sharma V, Husmann D, Westerman ME (2019) Alteplase instillation for upper urinary tract clot dissolution, Journal of Endourology Case Reports 5:1, 16–18, DOI: 10.1089/cren.2018.0088.