#6846 CHRONIC CMV DIARRHOEA IN RENAL TRANPLANT RECIPIENTS - AN UNDERRECOGNISED SPECTRUM OF COMPARTMENTALISED GUT INVASIVE CMV DISEASE
Authors: Shanmugham Sabarinath , Bhadauria Dharmandr , Prasad Narayan , Kaul Anupma , Patel Manas Ranjan , Yachha Monika , Kushwaha Ravi Sankar , Behera Manas Ranjan 
Published: June 2023

Abstract

Background and Aims
Chronic diarrhoea in post-renal transplant recipients due to Cytomegalovirus (CMV) presents as Blood CMV PCR (polymerised chain reaction) positive chronic diarrhoea and Gut-invasive (rectal tissue PCR positive, blood PCR-negative) compartmentalised CMV. The available literature on compartmentalised gut CMV is scarce. The aim is to study the clinical presentation and outcome of patients with compartmentalized gut invasive CMV when compared with Blood CMV positive chronic diarrhea in renal transplant recipients.

Method
This is a retrospective single-centre follow-up study of patients with CMV disease who were transplanted between 2000 and 2020. Diagnostic variables like blood CMV PCR (polymerised chain reaction) positivity with constitutional symptoms, presence or absence of chronic diarrhoea, tissue PCR positivity and site of tissue biopsy were given harmony codes and 6 syndromes were identified – CMV diarrhoea (Blood PCR positive, presence of diarrhoea), compartmentalized gut invasive CMV (Blood PCR negative, presence of diarrhoea, rectal tissue quantitative CMV PCR positive), Acute CMV syndrome, CMV Esophagitis, CMV nephropathy, CMV cystitis. Out of which patients presenting with diarrhoea (first two groups) were included for analysis. The baseline descriptive statistical measures were carried out using analysis of variance. The time to CMV disease from transplant was computed by identifying the pattern of distribution at 10%, 50% and 90% between groups using reliability models. The time to death from diagnosis was analyzed by identifying the pattern by parametric log-logistic distribution. Survival analysis was done by a parametric reliability model identifying location, scale and threshold parameters, from which month-wise prediction of probabilities was found for survival. The proportion of adverse outcomes (relapse, death and graft loss) between the two groups were analyzed by one-way ANOVA and Tukey pairwise comparison. All the patients were followed up till death or last follow-up.

Results
Out of 2208 renal transplants done between 2000 and 2020, 118 (5.3%), patients developed CMV disease. Chronic diarrhoea was the presentation in 88 (57%), of which 47 had manifestations of CMV diarrhoea, and 41 had compartmentalized gut CMV. Induction agents used (CMV diarrhoea Vs compartmentalized gut CMV) were basiliximab (51% Vs 56%), ATG (27% Vs 17%), Grafalon (0% Vs,2.4%) and no induction (21%,24%). Only 31.9% and 26.8% received Valganciclovir prophylaxis for pre-specified indications respectively. The time to CMV diagnosis from transplant for 10%, 50% and 90% of patients (in months) was 12,63,154 for CMV diarrhoea;12,52 and 139 months for compartmentalized gut CMV. The mean duration (weeks) of diarrhoea was similar in both groups (7 Vs 7.3). Associated opportunistic infections causing diarrhoea were higher in compartmentalized gut CMV (28% Vs 46% p = 0.08); the commonest being cryptosporidium. Quantitative PCR in the blood ranged from 1245 to 2511345 copies/ml; whereas in gut tissue, it ranged from 1325 to 3517920/25 mg. The major histopathological finding in compartmentalized gut CMV was active inflammatory pathology in 34 (83%) patients. The probability of survival was significantly lower (72.6%; CI 60% to 83%) in CMV diarrhoea when compared with compartmentalized Gut CMV (87.2%; CI 76% to 94%) for initial 12 months (p&lt;0.05); however at 5 years (56.2%, Vs 58.5%) and 10 years (48.5% Vs 42.7%) the survival was similar. Compartmentalized gut CMV was associated with a higher relapse rate (19.5%) when compared with CMV diarrhoea (6.4%) on follow-up (p = 0.06). The mortality (36% Vs 29%; p = 0.490) and graft loss (25% Vs 22%; p = 0.692) were similar between both the group.

Conclusion
Compartmentalized gut invasive CMV represents a larger proportion of chronic diarrhoeal illness with a higher relapse rate, which needs invasive gut tissue PCR analysis, despite negative blood PCR, for early diagnosis and management.