Nephrology Hypertension

Kidney Transplantation: Diagnosis and Management of Early Graft Dysfunction - Pre-Renal Causes and Treatments

Does this patient have early graft dysfunction related to pre-renal causes?

What is early graft dysfunction?

Kidney transplantation is the preferred mode of renal replacement therapy for end stage renal disease, with dramatic improvements in patient and graft survival over the last 50 years. In the modern era of immunosuppression, one year patient survival is close to 98%, and one-year allograft survival rates have improved to 90% for deceased donor kidney transplants and 95 % for living donor kidney transplants with some inter-center variability. However, fluctuations in serum creatinine, which is the primary method for monitoring graft function, are frequent, particularly in the first year of transplantation.

Definition: early graft dysfunction

A rise in serum creatinine of 15% or more above baseline defines allograft dysfunction. Urine output, especially in the first few days of transplantation, may also be monitored and a decline to levels of oliguria or anuria may also define early graft dysfunction.

What causes early graft dysfunction

Early graft dysfunction can be divided into three categories based on the different risk factors :

(1) immediate post-operative graft dysfunction (within the first week of transplantation) (Figure 1)

Figure 1.

Management of oliguria/anuria after transplant.

(2)graft dysfunction in the first 3 months after transplantation (Figure 2)

Figure 2.

Management of elevated serum creatinine in early pre-transplant period (1 week-12 weeks).

(3) graft dysfunction after 3 months of transplantation.

Much like the causes of acute kidney injury, allograft dysfunction can be considered using the pre-renal, post-renal and intrinsic-renal etiologies. This chapter will cover pre-renal etiologies; specifically, volume depletion and hypotension, renal artery/vein thrombosis, renal artery stenosis, and calcineurin inhibitor (CNI) drug toxicity Differential diagnosis is impacted based on the timing post-operatively.

What tests to perform?

Renal artery.vein thrombosis

As rapidly increasing serum creatinine may be the only sign of thrombosis in patients with oliguria or anuria due to poor graft function due to reperfusion injury, renal imaging is important in these patients. Diagnosis is often made by use of duplex ultrasonography or isotope renal scan.

Renal artery stenosis

Diagnosis is usually established by duplex ultrasonography, but renal angiography still remains the gold standard.

How should patients with early graft dysfunction related to pre-renal causes be managed?

Volume depletion and hypotension

  • In the immediate post-operative period, adequate volume resuscitation with appropriate hemodynamic monitoring is important, especially to maintain a mean arterial systemic pressure as there is little role of intrinsic or extrinsic auto-regulation of blood flow to the allograft. Intra-operative losses, insensible losses and third space losses secondary to cytokine release syndrome should be replaced.

  • Urine output should be monitored hourly for at least first 24 hours and replaced. Some centers use dopamine and fenoldapam in post- operative period to improve the renal blood flow, but these have not been shown to improve graft function or short term allograft outcomes. After discharge, volume depletion is related to inability to keep up with fluid intake, be it due to lack of intake or increased losses from vomiting/diarrhea.

  • Post- transplant hypotension could be secondary to volume depletion, cytokine release syndrome associated with some antibody treatments used for immunosuppression such as anti-thymocyte globulin, post-operative bleeding, cardiac causes, pulmonary embolism, sepsis syndrome or medications and needs to be addressed on a case- to case basis.

Renal artery/vein thrombosis

  • Thrombosis of renal vessels usually occurs in the first 48-72 hrs and is one of the most devastating complications leading to graft loss. The reported incidence varies from 0.6-3.4% of transplants

  • Thrombosis usually occurs as a result pre- existing hypercoagulable state, surgical technique, thrombocytosis or hyperacute rejection. Renal artery thrombosis usually presents with oliguria or sudden anuria, rapidly increasing creatinine, graft swelling and pain over the allograft. Hyperkalemia, elevated serum LDH and thrombocytopenia may also seen.

  • As rapidly increasing serum creatinine may be the only sign of thrombosis in patients with oliguria or anuria due to poor graft function due to reperfusion injury, renal imaging is important in these patients. Diagnosis is often made by use of duplex ultrasonography or isotope renal scan. Transplant kidney does not have any collateral supply, so unless repaired emergently, thrombosis can result in graft loss requiring allograft nephrectomy. In some case reports, kidney allografts have been salvaged by emergent thrombectomy and use of fibrinolytic agents.

Renal artery stenosis

  • Transplant renal artery stenosis (TRAS) is usually a late complication that presents within 3 months to 2 years after transplant. The incidence of TRAS has been reported to range from 1% to 23%. Causes include rejection of the donor artery, atherosclerosis of the recipient vessel, clamp injury or perfusion pump clamp injury, suture technique, end to end anastamosis with vessel size disproportion, angulation due to disproportionate length between the graft artery and iliac artery and established iliac artery atherosclerotic lesion.

  • Older donor and recipient age, expanded criteria donor kidney, delayed graft function, coronary artery disease in recipient, and induction immunosuppression are reported to be independent risk factors for TRAS. Allograft dysfunction and poorly controlled hypertension is a common presentation in these patients. Diagnosis is usually established by duplex ultrasonography, but renal angiography still remains the gold standard.

  • Management includes anti-hypertensives and percutaneous trans-luminal angioplasty with intra-arterial stent placement. The long term benefit of invasive therapy in management of TRAS remains controversial, when compared to medical therapy. Surgical repair is necessary in cases where above therapy is not successful, but usually is associated with higher graft loss likely due to technical difficulties.

Calcineurin inhibitor drug toxicity

  • The use of calcineurin inhibitor can lead to graft dysfunction secondary to its vasoconstrictive properties. Hence, monitoring and maintaining adequate drug levels is crucial. Early use of CNI may lead to delayed recovery of tubular injury.

What happens to patients with early graft dysfunction related to pre-renal causes?

If properly managed, and the appropriate etiology addressed, renal function should return to normal.

How to utilize team care?

Confering with the transplant surgical team is warrented at this time. All action taken should be performed as an agreed upon management scheme.

Other considerations

Vital sign monitoring, intake and output, and renal function measurements are warranted during this time period.

What is the evidence?

Boulanger, H, Haymann, JP, Fouqueray, B, Mansouri, R, Metiver, F, Sarfati, I, Gilotz, D. "Renal vein thrombosis after renal transplantation – early diagnosis by duplex sonography prevented fatal outcome Nephrol. Dial". Transplant. vol. 21. March 2006. pp. 825-826.

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