Cytomegalovirus nephritis in kidney transplant recipients: Epidemiology and outcomes of an uncommon diagnosis

Abstract

Background: Data on epidemiology and outcomes of cytomegalovirus (CMV) nephritis in kidney transplant patients are limited due to the rarity of this condition. Methods:A retrospective review of all kidney transplant recipients (KTR) (n = 6490) and biopsy-proven CMV nephritis between 1/1997 and 12/2020 was performed. Results:The prevalence of CMV nephritis was low: 13/6490 (0.2%). The diagnosis was made at a median of 7.0 months (range 2.6-15.6 months) after transplant. 6 of 13 (46%) patients were CMV (D+/R−). Median CMV DNA load at biopsy was 376,000, IU/mL (range 87,000-6,460,000 IU/mL). Main biopsy features were CMV glomerulitis (n = 7/13, 54%) followed by CMV tubulointerstitial nephritis (6/13; 46%). Mean eGFR at biopsy (22.7 ± 12 mL/min/1.73 m 2 ) was significantly decreased compared to baseline eGFR (38.7 ± 18.5 mL/min/1.73 m 2 , p = 0.02). The vast majority, 11 of 13 (85%), experienced graft failure including 5 of 13 (38%) death-censored. 5 of 13 (38%) patients were diagnosed with acute rejection: three had concurrent acute rejection, and two had rejection within 3 months of index biopsy, respectively. Patients with tubulointerstitial CMV nephritis were significantly more likely to have rejection at the time of biopsy (50% vs. 0%, p < 0.05) compared to those with glomerular CMV nephritis. There were no significant differences between these groups in terms of eGFR at all time points, death, graft failure, immunosuppression changes or rejection after biopsy. Conclusion:CMV nephritis is rare but appears to be associated with poor patient/allograft outcomes. Early identification and timely treatment of CMV infection may prevent end-organ involvement and improve patient and allograft-related outcomes.

Optimizing the approach to monitoring allograft inflammation using serial urinary CXCL10/creatinine testing in pediatric kidney transplant recipients

“…Most cases were not treated with IV steroids and instead resolved with antiviral treatment. CMV nephritis has been reported post‐kidney transplant but may be difficult to diagnose conclusively due to histologic features overlapping with acute rejection 63–65 . The viral cytopathic effect may not always be seen and were not identified in these cases, 65 and we did not perform PCR to identify whether CMV viral particles were present within the tissue.…”

“…CMV nephritis has been reported post-kidney transplant but may be difficult to diagnose conclusively due to histologic features overlapping with acute rejection. [63][64][65] The viral cytopathic effect may not always be seen and were not identified in these cases, 65 and we did not perform PCR to identify whether CMV viral particles were present within the tissue. Unless there is progressive functional decline, our practice has generally been to defer treatment with steroids until the CMV viremia has resolved.…”

Pathological Approach to Kidney Allograft Infection

“…CMV is commonly presented as a viremia or systemic infection, and direct infection in the kidney allograft is less common than BKV infection [8,65,66]. In the case of CMVassociated nephropathy, pathology shows allograft interstitial inflammation and tubulitis, predominantly with mononuclear cell infiltration (Figure 5) [65].…”

“…Characteristics of conditions presenting with interstitial inflammation or cellular infiltrations in the kidney allograft[6,9,13,33,53,66,68,76,78,79].…”

Virus-Associated Nephropathies: A Narrative Review

“…In an Indian cohort, only 10 allograft biopsies out of 2,900 demonstrated CMV nephropathy (including seven for tubulointerstitial nephritis) and the majority of these evolved favorably after antiviral therapy [ 192 ]. A more recent American cohort study reported CMV nephritis prevalence of 0.2% and poorer allograft outcomes [ 193 ]. Typical cytomegalic inclusion bodies (owl’s eye looking) are rarely observed and are usually very focal; they are most often seen in tubular epithelial cells or endothelial cells and rarely in mononuclear inflammatory cells [ 194 , 195 , 196 , 197 ].…”