Renal failure following cardiac transplantation.

drawback to its use. The early studies by Myers et al. In addition to the studies by Myers et al. [1–3], seven [1] described the renal structural and functional retrospective long-term analyses and one case control changes in the native kidneys of heart transplant study regarding renal function in cardiac transplant recipients. Repeated haemodynamic investigations recipients have been published during the 1990s [4–10]. revealed a progressive decrease in glomerular filtration These studies have shown that the renal function rate (GFR), a concomitant drop in renal plasma flow, post-transplant, determined either by serial measureand an increase in renal vascular resistance associated ments of serum creatinine or by regular clearance with systemic hypertension. Renal biopsies in a subset measurements, revealed a biphasic response with a of patients disclosed glomerulosclerosis, striped interrapid decline up to 12 months and a slower deteriorastitial fibrosis, and afferent arteriolopathy. In the orition of renal function thereafter. A similar pattern of ginal study a high starting dose of cyclosporin was renal response was reported in 100 consecutive heartused (17 mg/kg), which was later decreased to lung transplant recipients [11]. The early loss of renal 10 mg/kg. However, when these two groups were comfunction (within 12 months) apparently depends on pared, both of them had developed hypertension and the cyclosporin dose [1] and appears to be the key a decreased GFR. Even with a low dose of cyclosporin indicator of poor late outcome. Cyclosporin-induced the decline in GFR was approximately 45% from nephrotoxicity is characterized by an initially reversible baseline, as compared with historical controls treated decline in GFR, which is most probably caused by a with azathioprine and prednisone without cyclosporin. direct drug-induced afferent arteriolar vasoconstricPatients treated with low doses of cyclosporin had tion. The mechanisms underlying renal vasoconstricslightly lower mean serum (s-) creatinine concentration and hypofiltration remain unknown, but tions, but similar pathological changes according to abnormalities in endogenous vasoconstrictor and vasorenal biopsies, than those treated with higher doses dilator mechanisms may be responsible [12]. In this [2,3]. In addition, it was demonstrated that sequential respect, it is of interest to note that a single oral dose biopsies of the native kidney in the two cyclosporin of cyclosporin (5 mg/kg) caused a profound impairgroups revealed progressive histopathological changes. ment in renal haemodynamics. This was true for chronFurthermore there was an approximately 10% cumulaically treated renal transplant patients [13] as well as tive incidence of end-stage renal disease during 10 for healthy volunteers in whom 10 mg/kg of cycloyears. The renal dysfunction could not be explained sporin resulted in an 18% decrease of GFR [14].