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Keywords:

  • Biopsy;
  • complication;
  • kidney transplant

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References

The acute Page kidney phenomenon occurs as a consequence of external compression of the renal parenchyma leading to renal ischemia and hypertension. Between January 2000 and September 2007, 550 kidney transplants and 518 ultrasound-guided kidney biopsies were performed. During that time, four recipients developed acute oligo-anuria following ultrasound-guided allograft biopsy. Emergent doppler-ultrasounds were performed demonstrating absence of diastolic flow as well as a sub-capsular hematoma of the kidney. Prompt surgical exploration with allograft capsulotomy was performed in all cases. Immediately after capsulotomy, intraoperative Doppler study demonstrated robust return of diastolic flow. Three patients maintained good graft function, and one kidney was lost due to acute antibody-mediated rejection. We conclude that postbiopsy anuria associated with a subcapsular hematoma and acute absence of diastolic flow on doppler ultrasound should be considered pathognomonic of APK. All renal transplant specialists should be able to recognize this complication, because immediate surgical decompression can salvage the allograft.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References

The Page kidney phenomenon refers to any extra-renal process causing significant compression of the parenchyma, leading to hypoperfusion and ischemia with subsequent activation of the renin-angiotensin-aldosterone axis. Although hypertension is the most common presenting clinical picture, renal insufficiency can occur in the setting of a diseased contralateral kidney or a single functional kidney. In 1939, Page first described this phenomenon in an experiment whereby he induced hypertension by wrapping a canine kidney with cellophane. This caused a severe inflammatory reaction leading to constrictive perinephritis (1). Since then, there have been many reports describing various etiologies for Page kidney.

The Page kidney phenomenon has been poorly described in the renal transplant literature and consists of individual case reports that relate different transplant-associated factors to the development of a Page kidney (2–9). Specifically, the renal allograft biopsy is associated with a risk of peri-renal or subcapsular hematoma that could cause compression-induced renal ischemia and an acute Page kidney (APK) phenomenon (4,5,8,9). Herein, we report a series of four patients who developed APK as a consequence of allograft biopsy-induced subcapsular hematoma. The goal of this report is to revisit this complication and to discuss the diagnosis and management of APK in order to raise awareness among renal transplant specialists.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References

Between January 2000 and September 2007, 534 kidney and 16 simultaneous kidney and pancreas (SKP) transplants were performed at our center. Kidney transplants were usually performed via a retroperitoneal Gibson incision with end-to-side vascular anastamoses to the external iliac vessels; for SKP transplants, a midline incision with implantation of the kidney into the left iliac fossa and pancreas into right iliac fossa is most commonly employed. A total of 518 ultrasound (US)-guided kidney transplant biopsies were performed in the context of allograft dysfunction and protocol biopsies. Standard immunosuppression at our center included use of a calcineurin inhibitor, an antiproliferative and steroids. Induction therapy was used in high-immunologic risk patients and in patients at risk for delayed graft function. Although heparin was not given routinely to our transplant recipients, 81 mg of acetylsalicylic acid was uniformly administered.

The allograft biopsies were performed under real-time ultrasound guidance after complete blood count and INR/PTT were confirmed to be within safe limits. The optimal biopsy site was chosen under real time guidance; the convex lateral surface of the lower or upper pole was usually chosen. After injection of local anesthesia into the biopsy tract, the biopsy was performed tangentially to the cortex using an 18 gauge spring-loaded biopsy device. Manual pressure was placed over the site for 5 min. Four hours of bed rest along with urinary examination for hematuria and complete blood counts were part of our postbiopsy surveillance protocol.

During this period, four (0.8%) patients developed biopsy-induced subcapsular hematomas leading to the APK phenomenon. The clinical presentation of each patient is summarized in Table 1.

Table 1.  Characteristics of patients with acute page kidney
 Case 1Case 2Case 3Case 4
  1. BMI = body mass index; FSGS = focal segmental glomerulosclerosis; DM = diabetes mellitus; DD = deceased donor; Tac = tacrolimus; CsA = cyclosporine A; MMF = mycophenolate mofetil; Pred = prednisone; AMR = acute antibody-mediated rejection; CNI = calcineurin inhibitor; N/V = nausea and vomiting; PLEX = plasma exchange; SCr = serum creatinine; HD = hemodialysis; SKP = simultaneous kidney and pancreas transplant.

Age (years)27393533
GenderFFMF
BMI (kg/m2)27283925
Primary renal diseaseRenal dysplasiaFSGSReflux nephroType 1 DM
Previous transplant1020
Type of allograftDDDDDDDD
ImmunosuppressionTac, MMF, predTac, MMF, predCsA, MMF, predSir, Tac, pred
Reason for biopsyDysfunctionDysfunctionDysfunctionProtocol
Coagulation parameters at time of biopsy
 Platelet count (×109/L)14226993322
 INR1.21.61.20.9
 PTT (seconds)38324924
Diagnosis on biopsyAMRCNI toxicityAMRNormal
Time from bx to symptoms5 days3 days2 days4 h
SymptomsHypotension anuriaHypertension flank pain hematuria anuriaHypotension flank pain anuriaHypertension flank pain N/V anuria
Contributing factors?PLEXElevated BMI IV heparin/PLEX
sCr at biopsy (μmol/L)68126549889
sCr at discharge (μmol/L)26882588133
sCr at last visit (μmol/L)131163Chronic HD75
Follow-up (months)2412614
NotesRecurrent FSGSSKP

Cases

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References

Case 1

A 27-year-old woman with end-stage renal disease secondary to renal dysplasia underwent a second deceased-donor kidney transplant. After a failed first transplant, peak Panel Reactive Antibody (PRA) was 93%. Preoperatively, she had negative CDC and flow cytometric T-cell and B-cell cross-matches. Induced with Thymoglobulin, she had immediate graft function. On postoperative day (POD) 11, she developed biopsy-proven acute antibody-mediated rejection (AMR). Intravenous immunoglobulin (IVIg) and plasmapheresis were initiated. Five days following the biopsy, she developed acute anuria with hypotension, and her hemoglobin dropped from 95 to 55 g/L over 24 h. Urgent Doppler-US and CT-scan of the abdomen were performed. Ultrasound demonstrated a biconvex subcapsular hematoma, elevated resistive indices (RI) of 1.0, absence of diastolic flow and a patent allograft renal vein. Nonenhanced CT-scan revealed a subcapsular hematoma compressing the parenchyma of the allograft in addition to a retroperitoneal hematoma. The combined clinical and radiologic findings were pathognomonic of the APK phenomenon induced by tense subcapsular hematoma. Prompt surgical exploration via an ipsilateral Gibson incision and an extraperitoneal approach was used. Intraoperative Doppler-US confirmed the preoperative findings (Figure 1A), and the subcapsular hematoma was evacuated through an incision of the overlying renal capsule. Immediate improvement in Doppler-US characteristics was observed, with normalization of the RIs and return of diastolic flow (Figure 1B). The bare area of the renal parenchyma was covered with oxidized regenerated cellulose (Surgicel®) and the caspule was reapproximated loosely to keep the hemostatic agent in place. After repositioning the kidney, the capsulotomy was covered with a fibrin sealant (Tisseal®) to further ensure hemostasis. A large closed suction drain was placed lateral to the allograft. Lastly, a generous piece of Marlex® mesh was used for abdominal fascial closure to provide compression-free coverage of the swollen kidney and prevent renal allograft compartment syndrome (RACS) (Figure 2) (10). At follow-up, the humoral rejection was successfully treated, and the sCr was 112 μmol/L 6 months later.

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Figure 1. Intraoperative doppler of the kidney transplant: (A) before the capsulotomy with absence of diastolic flow, (B) just after capsulotomy with instant return of diastolic flow and normalization of the resistive index.

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image

Figure 2. (A) Perioperative swollen appearance of the graft with extensive subcapsular hematoma. (B) Marlex mesh fascial closure and drain before closure.

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Case 2

A 39-year-old female with end-stage renal disease secondary to focal segmental glomerulosclerosis (FSGS) and prior treatment with pegylated-interferon for hepatitis C underwent an uneventful deceased donor kidney transplant. No induction therapy was used and immediate allograft function was observed. Several days posttransplant she developed allograft dysfunction and underwent an US-guided biopsy, revealing tubular vacuolization with a component of mild acute tubular necrosis (ATN). Three days thereafter, she developed increasing pain over her graft, gross hematuria and oliguria. Blood pressure (initially well-controlled) rose to 195/105 mmHg and hemoglobin dropped from 115 to 80 g/L. There was no improvement in urine output despite several intravenous fluid challenges. Repeat Doppler-US revealed a biconvex subcapsular hematoma, elevated RI of 1.0, absence of diastolic flow and a patent allograft renal vein. Urgent exploration via an extraperitoneal approach and intraoperative Doppler-US confirmed the diagnosis. Capsulotomy led to immediate improvement in Doppler-US parameters. Surgicel® and Tisseal® were used to reapproximate the capsule and ensure hemostasis, a drain was placed, and the abdominal wall fascia was reconstituted with Marlex® mesh. The patient was discharged home one week following evacuation of the hematoma with sCr 82 μmol/L. At 6-month follow-up, she developed recurrence of FSGS with nephrotic-range proteinuria and a slowly rising sCr (163 μmol/L).

Case 3

A 35-year-old male with kidney failure secondary to reflux nephropathy received a deceased donor kidney transplant. The patient had two prior failed transplants, both secondary to early humoral rejection and arterial thrombosis. A subsequent diagnosis of antiphospholipid antibody syndrome was made, and he was placed on long-term warfarin therapy. His preoperative percentage of PRA was 100%, and CDC and flow cytometric cross-matches were both negative. However, donor-specific antibodies via preoperative multi-bead solid-phase assay (Luminex platform) were detected. He received Thymoglobulin induction, plasmapheresis and IVIg pre- and postoperatively for 5 days. Through a transabdominal midline incision, the allograft was positioned within the peritoneal cavity with anastomoses to the inferior vena cava and common iliac artery. Intravenous heparin was started 6-h postoperatively to minimize the risk of systemic and allograft thrombosis. An US-guided biopsy was performed on postoperative day 4 for poor allograft function. Intravenous heparin was stopped and recommenced 6 h postbiopsy. Hypotension and severe right flank pain developed 2 days later. With adequate volume resuscitation, his blood pressure rose to 180/100 mmHg. Pathognomic findings of APK, as described in the above two cases, were discovered on urgent Doppler-US and CT-scan imaging. Emergency exploration and decompression of hematoma with capsulotomy improved Doppler-US parameters. Surgicel® and Tisseal® were used for renal capsule reconstitution, and the midline- fascial incision was closed primarily with running No. 1 PDS suture. Despite aggressive treatment of AMR with IVIg, plasmapharesis, rituximab and cyclophosphamide, no discernible function of the graft was observed and the patient is currently back on hemodialyis.

Case 4

A 33-year-old woman, who had a successful SKP transplant 9 months earlier, underwent an uneventful US-guided protocol biopsy. Renal and pancreatic function were excellent with sCr 89 μmol/L and normal glycemic control. In recovery, 4 h after the biopsy, she developed severe left flank pain, nausea, vomiting and a hypertensive crisis with a systolic blood pressure of 200 mmHg. The patient was admitted for intravenous antihypertensive therapy and monitoring. The following morning sCr had increased to 243 umol/L and her hemoglobin fell from 147 to 116 g/L. Anuria refractory to volume resuscitation ensued. Doppler-US revealed a compressive subcapsular hematoma, RI of 1.0, lack of diastolic flow and a patent renal vein. Exploration through a small transverse paramedian incision was performed and the hematoma was released with capsulotomy. Intraoperative US confirmed return of flow to the allograft. Surgicel® and Tisseal® were used to reconstitute the capsule loosely as described for the previous cases above. The fascia was closed with a running continuous No. 1 PDS suture. The patient was sent home on postoperative day 2, and the sCr 6 months later was 75 μmol/L.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References

The Page kidney entity has been recognized since the 1930s when an experimental model was first created (1). Numerous clinical etiologies for Page kidney have been described in the past, including blunt trauma, spontaneous bleeds and iatrogenic causes (11,12).

In the renal transplant literature, the Page kidney phenomenon has been previously described in a few case reports. Cromie et al. (2) first described a case of renal allograft pseudorejection in a 35-year-old male who developed refractory hypertension following living related renal transplantation. Postoperative US confirmed a perinephric hematoma. Evacuation and capsulotomy was performed and the patient became normotensive with normal renal function on follow-up. Vanwalleghem et al. (7) described a case of peritransplant lymphocele as a cause of Page kidney. Approximately 1 year after a deceased donor renal transplant, the patient became hypertensive and was found to have a lymphocele on MR angiography, which was successfully treated with percutaneous drainage over 2 weeks. Furthermore, Yussim et al. (3) described a patient who developed hypertension, oliguria and elevated serum creatinine secondary to perinephric fibrosis, which developed following surgical treatment for a peritransplant lymphocele. Surgical reexploration and removal of the fibrotic tissue resulted in return of renal function and normalization of blood pressure with antihypertensives on follow-up.

There are also a paucity of reports describing APK phenomenon following allograft transplant biopsy (4,5,8,9). When compared to native kidneys, transplant kidneys are at increased risk for complications after biopsy (13). The incidence of perinephric hematomas has been shown to range from 0.7% to as high as 30% of biopsied renal allografts (13–15).

We have reported on four cases (incidence of 0.8%) of allograft biopsy-induced APK, in order to characterize presentation of this syndrome, and to outline diagnostic and treatment plans.

In the classical Page kidney phenomenon, hypertension is a hallmark presentation. The mechanism is similar to that described by Goldblatt et al. (16) whereby renal artery constriction results in ischemia and hypertension. Similarly, external compression of the parenchyma in Page kidney causes renal ischemia and subsequent renin-induced hypertension. With a normal contralateral kidney, renal failure does not occur in this patient population. Conversely, patients with solitary transplant kidneys are at significant risk of developing acute renal failure following APK. The clinical presentation common to our four patients included altered blood pressure control and reduction of urine output after renal biopsy. Three of four patients also developed pain over the allograft.

In order to maintain renal function and to avoid chronic complications, including hypertension, early recognition is of utmost importance. The diagnosis of APK relies on a high clinical suspicion and the use of appropriate imaging studies. Given its rarity, the diagnosis of APK can be easily missed; in our center, two cases were not properly identified by radiologists reviewing the cases. In our case series, several pathognomonic findings were evident. Both Doppler-US and nonenhanced CT scan demonstrated a frank subcapsular hematoma compressing the allograft parenchyma. Doppler-US further demonstrated acute absence of diastolic flow and an elevated RI of 1.0. Doppler-US is an invaluable tool in the monitoring and management of renal transplants. By itself, elevated RI, although present in APK, can also be seen in renal vein thrombosis, ureteral obstruction, acute rejection, pyelonephritis, acute tubular necrosis and may be an artifact secondary to manual compression by the US transducer (17,18). Assessment of the kidney with intraoperative Doppler-US before and after surgical therapy confirmed the diagnosis of APK and demonstrated proper decompression of the kidney. Although not always necessary, computerized tomography may be able to assess concomitant perinephric hematomas and may be able to better define the subcapsular hematoma of the transplanted kidney.

Treatment of the traditional Page kidney phenomenon may range from observation to medical to surgical management. In transplant patients, aggressive management is often necessary to ensure optimal viability of the allograft. In three of our four patients, successful treatment was achieved with prompt surgical decompression of the hematoma through capsulotomy and achievement of hemostasis. Closure with Marlex® mesh was used in two of the cases to avoid secondary RACS, which may also lead to an elevated RI (19) with compression of the kidney parenchyma or the main vessels (20). The patient with the APK who remained dialysis-dependent postdecompression had ongoing acute humoral rejection demonstrated on biopsies postdecompression. We believe that it was our inability to successfully treat the rejection that led to graft failure despite decompression of the APK.

Risk factors for the development of APK in the transplant population are not well-established (13). However, we believe that caution must be used in patients with coagulopathy, with uncontrolled hypertension, and in those patients who have a body habitus that precludes easy US-guided targeting. Two of the patients in this small series were receiving scheduled plasmapheresis for AMR at the time of their biopsy. Plasmapheresis, with or without plasma exchange, has been shown to deplete a number of coagulation factors without necessarily altering routine laboratory values, including prothrombin time and partial thromboplastin time (21,22). The treating physician should be aware of this and exercise caution and careful observation in the peribiopsy period in this subset of patients. In addition, heparin was restarted 6 h after biopsy in case 3. A longer period of observation should be considered prior to restarting anticoagulation in this patient population.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References

APK is a rare but serious complication of renal allograft biopsy. Up to this point, no clear recommendations are available for the diagnosis and treatment of postbiopsy APK. In our experience, acute pain over the graft, alteration in blood pressure control, reduction of urine output, doppler US evidence of subcapsular hematoma and elevated RI were pathognomonic of this phenomenon. Surgical treatment of the hematoma by evacuation via capsulotomy and compression-free abdominal closure resulted in good clinical outcomes. Thus, APK, when recognized and diagnosed appropriately, represents a treatable complication of renal allograft biopsy, and transplant professionals should be alert to its possibility.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Cases
  6. Discussion
  7. Conclusion
  8. References