Damage to the renal cortical microcirculation, an early event in the course of acute rejection crisis (ARC), usually precedes measurable functional derangements in the transplanted kidney. Direct assessment of cortical blood flow by radionuclide renography may provide a sensitive and reliable index to the diagnosis of ARC, with particular regard to the differential diagnosis of ARC and ATN. Computer generated time-activity curves of global, cortical, and medullary renal blood flow were analyzed in 67 instances (35 patients) of renal allograft dysfunction and correlated with needle biopsy of these kidneys. No increase in cortex perfusion index (CPI), i.e., decrease in cortical perfusion, was found when the patients were suffering from ureteral obstruction or drug and viral nephropathy (mean perfusion index (PI) increase (8%). In contrast, a marked increase in CPI of 193% was noted in ARC. Global and medullary PI increased only 116%. As a result, global and medullary PI were capable of diagnosing ARC in only 73% and 55% of the cases, respectively, whereby cortex PI correctly diagnosed ARC in 94% of the cases. Selective analysis of cortical perfusion may thus enhance the accuracy of [99mTc]DTPA scans (radionuclide renograph) for the early detection of ARC and in differentiating ARC from nonimmunological causes of kidney allograft dysfunction.

Graft Rejection↗

PubMed1985

Immunological consequence of renal transplantation and immunosuppression. I. Alterations in human natural killer-cell activity.

The role and activity of natural killer (NK) cells following renal transplantation remain unknown. To monitor NK activity, a 51Cr release of K-562 targets in prednisone- and azathioprine-treated patients receiving renal allografts was utilized. In 18 patients in whom NK activity was measured prior to and after transplantation, a significant diminution in NK activity within 3 weeks following transplantation was demonstrated compared to pretransplant values (34.71 vs 12.20%, respectively; P less than 0.001). In 11 subjects who had NK activity assayed at various intervals after transplantation but not prior to allografting, mean NK values were markedly lower (mean, 14.2%) than those of normal volunteers or patients maintained on hemodialysis (P less than 0.001). The latter two control groups demonstrated no difference (P = NS) in mean NK activity (39.46 vs 35.82%, respectively). In 5 of the 29 patients evaluated with good long-term graft function (mean, 2.7 years), restitution of normal NK activity was demonstrated. In two patients with bacterial infections, NK activity increased from 39.29 to 51.7% and from 13.54 to 20.00%. After infection, these values were 35.3% in the former and 3.39% in the latter. Viral infection did not appear to affect NK activity significantly. NK activity was increased in only one of seven patients with documented rejection episodes. In three of such patients, NK activity declined significantly following pulse methylprednisolone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Effect of renal allograft dysfunction upon cyclosporine trough levels in host blood.

Cyclosporine (CsA) dose adjustment after renal transplantation is generally based on serum, plasma, or whole-blood trough level values. In the face of increased levels, the dosage is reduced in order to prevent CsA-induced nephrotoxicity. There is a paucity of data, however, on the kinetics of CsA in association with dysfunction of the transplanted kidney. This study documents dramatic rises in serum cyclosporine trough levels at the time of rejection crises, as well as following periods of nonimmunological allograft oliguria. Decreases in CsA dosage in such patients failed to result in a significant lowering in trough levels. Therapeutic CsA trough levels were generally at the 70-140 ng/ml level; at the time of rejection, the same doses of CsA resulted in a rise of trough levels to 300-500 ng/ml. As the rejection crises resolved and kidney function improved, the CsA serum trough levels returned to their lower levels. These results suggest that the urinary elimination of CsA and its metabolites may be a key determinant of CsA trough levels, and that the status of renal function at the time of testing must be considered in the interpretation of the data. In support of this observation, the CsA concentrations in 4-6 hr post-CsA-administration urine samples ranged from 400 ng/ml to 4500 ng/ml, as measured by high pressure liquid chromatography. The data suggest that rising CsA trough levels in a previously stable recipient may serve as a valuable early warning index of impending allograft dysfunction (rejection, infection, and obstruction). This appears particularly true during the first 30 days after renal transplantation, when the incidence of rejection is the greatest in this patient population.

Adolescent↗

PubMed1985