Brain-dead patients are an important source of kidneys for transplantation; however, graft survival is poor compared to living donors, probably due to cold preservation, and variations in blood pressure and hormone balance in the brain-dead patients could lead to inflammation of the kidneys. A recent randomized, open-label trial has concluded that the administration of low-dose dopamine to brain-dead kidney donors prior to transplantation improves outcome in renal transplant recipients. The results of the multicenter, parallel group study were published in the latest issue of The Journal of the American Medical Association.

Peter Schnuelle, University Medical Centre Mannheim, Germany, and colleagues, conducted the study on 264 brain-dead heart-beating donors with normal serum creatinine on admission and stable on low dose norepinephrine, and 487 renal transplants performed across 60 European centers, between March 2004 and August 2007. The donors were randomized to receive 4 µg/kg/min of dopamine. The last follow up of the recipients was on December 31, 2008. The primary outcome measure was the requirement for dialysis in the recipient during the first week after transplantation.

Compared to donors who did not receive dopamine, it was observed that fewer recipients who received dopamine-treated graft required multiple dialyses (92/260; 35.4% vs. 56/227; 24.7%; P=0.01). Patients receiving multiple dialyses posttransplantaton were at a risk of allograft failure after 3 years but not those who received single dialysis (HR= 3.61; P<0.001 vs.0.67, P=0.51 ). Other independent explanatory variables in a multiple logistic regression model included cold ischemic time (OR=1.07; P=0.001), recipient body weight (OR=1.02; P=0.009) and donor age (OR=1.03; P<0.001). Other factors, which did not affect the outcome, included a clinically meaningless but significant increase in donor blood pressure (3.8 mm Hg; P=0.02) and urinary output prior to surgical recovery of the transplanted kidneys (29 mL; P= 0.009).

Dopamine has been used in low doses for decades to prevent or modify the course of acute renal failure. However, a review by Schenarts et al (Current Surgery, 2006) reported that dopamine may not be beneficial in such cases and may actually negatively affect the renal oxygen kinetics, impair the feedback mechanisms which prevent renal ischemia leading to worsening of tubular damage. They further stated that it may cause several complications related to gastrointestinal, cardiovascular, pulmonary, immune and endocrine systems.

The ‘renoprotective’ effect of low-dose dopamine has also been disproved by Lauschke et al (Kidney International, 2006) through their study on patients in the intensive care unit. Low-dose dopamine (2 µg/kg/min) or placebo was administered to 40 patients; 30 of whom had acute renal failure (ARF). It was observed that although dopamine reduced the vascular resistance in patients without ARF, as assessed by the median ratio of resistive index to pulsative index (median RI/PI from 0.70 to 0.65/1.20 to 1.07; P<0.01), it increased the resistance in patients with ARF (median RI/PI from 0.77 to 0.81/1.64 to 1.79; P<0.01) without the effects on systemic hemodynamics. They concluded that dopamine worsens renal perfusion in patients with acute renal failure and should be avoided in critically ill patients.

Renal transplantation has come a long way since the first successful transplant in 1954 from one twin to the other. According to the National Institute of Diabetes and Digestive and Kidney Diseases, the number of renal transplants conducted in the United States in the year 2006 was 18,052. Improvements in the surgical technique now allow laparoscopic nephrectomy, which reduces morbidity in the donor. Newer immunosuppressants have minimized acute graft rejection, and research is underway to further improve the long-term success rates. Better ‘tailor-made’ immunosuppressant regimens are expected to reduce transplant-related morbidity. The current findings of the efficacy of low-dose dopamine in enhancing transplant outcomes in kidney recipients requires further evaluation, particularly in the light of the drug losing favor in the treatment of acute renal failure.

References

1. Schnuelle P, Gottmann U, Hoeger S, et al. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial. JAMA. 2009 Sep 9;302(10):1067-75.

2. Schenarts PJ, Sagraves SG, Bard MR, et al. Low-dose dopamine: a physiologically based review. Curr Surg. 2006 May-Jun;63(3):219-25.

3. Lauschke A, Teichgräber UK, Frei U, Eckardt KU. ‘Low-dose’ dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006 May;69(9):1669-74.

4. Kidney and Urologic Diseases Statistics for the United States. National Kidney and Urologic Diseases Information Clearinghouse. Last accessed September 14, 2009