LONGITUDINAL ANALYSIS OF CYTOMEGALOVIRUS LOAD IN RENAL-TRANSPLANT RECIPIENTS USING A QUANTITATIVE POLYMERASE CHAIN-REACTION - CORRELATION WITH DISEASE

Serial surveillance samples of urine collected from 103 renal transpla nt recipients were analysed by polymerase chain reaction (PCR) for the presence of human cytomegalovirus (HCMV) DNA. The PCR results were co nsistently negative in 70 patients, none of whom developed HCMV diseas e, and PCR positive in 33 patients of whom 10 developed HCMV disease ( P < 0.001). In 12 patients, PCR results were positive in three or more consecutive samples indicating extensive HCMV replication. HCMV load in 104 samples from these patients was analysed using a quantitative c oamplification PCR system. The maximal viral burden in the symptomatic patients ranged from 10(5.9) to 10(7.12) genomes/ml urine (median 10( 6.5) and in the asymptomatic patients from 104 to 10(5.7) genomes/ml u rine (median 10(5.2)). The 10(1.3) difference between these median val ues was significant (P < 0.01). Individual kinetic profiles of viral b urden showed that high levels of HCMV correlated with clinically appar ent disease. In the majority of the asymptomatic individuals HCMV load remained between 10(4) and 10(5.1) genomes/ml urine; however, in two patients fluctuations in viral load were observed involving higher vir al levels (up to 10(5.7) genomes/ml urine) suggesting that immune resp onses able to modulate viral replication could be studied in individua l patients. Analysis of the temporal appearance and quantity of HCMV i n the urine with alterations in white cell numbers showed that leukope nia occurred following the appearance of HCMV in the urine of symptoma tic patients but preceded HCMV in the urine of asymptomatic patients ( P = 0.01). Overall, these results show that longitudinal analysis usin g fully quantitative PCR methods for HCMV can provide insight into the natural history of HCMV disease in renal transplant recipients.