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
Donor factors
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
·
hypertension
·
acute renal impairment
·
treatment with nephrotoxins
·
prolonged donor
hypotension
·
marked catecholamine
storm during brainstem death.
Allograft factors
·
Prolonged warm ischaemia.
·
Prolonged cold ischaemia.
·
Prolonged anastomosis
time.
Recipient factors
· 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.
