Delayed Graft Function
One of the most common complications occurring in the early post-transplant period is delayed graft function (DGF). Clinically, the patient is oliguric, fails to demonstrate an improvement in renal function, and will often require haemodialysis. It is important to note that allograft oliguria may not be obvious in renal transplant recipients who have significant residual native urine output. In such cases, the patient may return from theatre passing good volumes of urine (resulting from the intravenous fluids given intra-operatively), all of which originate from their own kidneys. It is therefore important to ascertain from the patient their usual urine output and interpret post-transplant urine output in light of this information.
Causes of DGF
The absence of graft function immediately post-transplant may be due to a number of causes:
1. Pre-renal causes:
• arterial/venous thrombosis
• systemic hypotension.
2. Renal causes:
- acute tubular necrosis (ATN)
- hyperacute rejection
- aggressive recurrence of a primary GN.
3. Post-renal causes:
- ureteric obstruction/leak
- catheter blockage.
ATN is by far the most common cause of DGF, but this diagnosis should not be assumed, and other, more serious pathologies must be excluded.
Prevalence of DGF
DGF is relatively common, occurring in around 30% of kidneys donated after brainstem death (DBD), ≥50% of kidneys donated after circulatory death (DCD), but it is rare (<5%) in living donor kidneys.
Risk factors for post-transplant DGF
With the ever-increasing number of patients on the renal transplant waiting list, there has been an increasing use of less than ideal donor kidneys (that is, donors with increasing age or co-morbidi- ties). This is inevitably associated with an increase in the rates of DGF. Donor risk factors for DGF include:
· higher donor age
· acute renal impairment
· treatment with nephrotoxins
· prolonged donor hypotension
· marked catecholamine storm during brainstem death.
· Prolonged warm ischaemia.
· Prolonged cold ischaemia.
· Prolonged anastomosis time.
· HLA-antibodies (sensitisation).
· Post-operative hypotension.
Diagnosis of post-transplant ATN
The diagnosis is usually one of exclusion. An ultrasound (US) scan allows the assessment of perfusion and venous drainage and whether there is dilatation of the pelvi-caliceal system (indicative of urinary obstruction). If these diagnoses are excluded, then a transplant biopsy should be performed in patients with persistent (>5 days) DGF to exclude rejection and to assess the severity of ATN and its recovery. As in native kidneys, transplant ATN is characterised by the presence of tatty-looking tubular cells, many of which lack nuclei and begin to slough off into the tubular lumen.
Performing a transplant renal biopsy
The main complication of renal transplant biopsy is haemorrhage. Therefore it is important to minimise the risk of this by ensuring the following.
• The patient has normal clotting and platelets (>100 × 109/L).
Most patients will be receiving low molecular weight heparin, but this should be omitted on the night before biopsy.
• The patient’s blood pressure (BP) is reasonably controlled (<160/90 mmHg).
The patient should also have an adequate haemoglobin level (8 g/L) and an US scan to exclude obstruction. Once consent is obtained, the patient is placed supine and an US scanner is used to locate the kidney. It is usually fairly superficial (2–5 cm beneath the skin) and extra-peritoneal, so there is no overlying bowel. Local anaesthetic is applied and a spring-loaded needle inserted into the upper pole (avoiding the vessels and ureter, which are at the lower pole). A single core is usually adequate for diagnosis. Pressure is applied to the site, and the patient placed on bed rest for 6 hours, with frequent monitoring of BP and heart rate. Macroscopic haematuria occurs in <5% and bleeding usually stops spontaneously. Occasionally, radiological embolisation of a bleeding vessel may be required.
Management of post-transplant ATN
It is important to optimise fluid balance to ensure adequate renal perfusion but avoid fluid overload. The latter often necessitates the removal of large amounts of fluid during dialysis, precipitating hypotension and further exacerbating ATN. The recovery from ATN is slowed by the presence of nephrotoxins, such as calcineurin inhibitors (CNIs). Therefore patients are often given reduced doses of CNIs while they have ATN, or in some cases, CNIs are completely withdrawn. Immunosuppression is maintained with oral steroids, mycophenolate and/or induction agents.
Clinical course of post-transplant ATN
The recovery from ATN in transplant kidneys (as in native kidneys) is variable and may take days to weeks, or very occasionally a number of months. Around 5% of patients with DGF never develop graft function. This is termed as primary non-function.
DGF does carry long-term prognostic significance for allografts. In DBD donor kidneys, it is associated with an increased risk of acute rejection and a reduction in long-term graft survival.