ABSTRACT
Introduction: Collapsing focal segmental glomerulosclerosis (cFSGS) refers to a distinct pattern of glomerulopathy characterized by a glomerular capillary collapse in a segmental global manner, podocyte proliferation, and tubulointerstitial injury. Viral infections like HIV, Parvovirus B19, and CMV seem to be prominent triggers for the development of a conventional histological pattern of FSGS. CMV-associated renal disease has been described only in transplant and immunocompromised patients. Case Description: Case 1 18-year-old female with history of asthma and HbSS disease presented with fever, nausea, vomiting, and neck pain Physical examination revealed a temperature of 102 F, icterus, negative meningeal signs, no rales, rhonchi or wheezing. Initial creatinine 0.2 mg/dL. COVID-19 PCR was negative but IgG antibodies positive. Patient developed non-oliguric AKI with fluid overload requiring hemodialysis. CMV IgM and CMV PCR were positive. She recieved antibiotic therapy and also ganciclovir. Biopsy revealed collapsing FSGS with acute tubular injury. A week after completion of ganciclovir therapy creatinine returned to baseline of 1.7 mg/dL. Case 2 40-year-old African American male with history of diabetes and asthma presented with fever, fatigue, epigastric pain and chest pain. Initial creatinine 1.2 mg/dl, hepatic function (AST 333 U/L, ALT 265 U/L, ALK 207 U/L), ferritin (13682 ng/ml), triglycerides (276 mg/dl) and proteinuria (urine protein /creatinine ratio: 2, urine albumin/creatinine:1016 mg/gm). Patient developed anuric renal failure which required hemodialysis. Biopsy revealed collapsing FSGS with diffuse podocyte effacement, moderate tubular atrophy, and interstitial fibrosis. CMV DNA antibodies were positive. Methylprednisolone and valganciclovir were started with patient creatinine trending down to 3.7 mg/dL. Three weeks following discharge, creatinine levels were 1.5 mg/dL with decreased proteinuria. Discussion(s): Collapsing FSGS in immunocompetent patients is uncommon. Reports mention benefits of ganciclovir and steroid therapy for CMV infection in immunocompromised patients. CMV infection should be considered in patients with systemic inflammatory disease and severe renal failure, as early treatment with steroids and antivirals helps preserve renal function.
ABSTRACT
Introduction: Collapsing Glomerulopathy is a morphological variant of focal segmental glomerulosclerosis (FSGS) characterized by rapidly progressive renal failure and nephrotic range proteinuria. CMV-associated renal infections are usually seen in post-transplant and immunocompromised patients. We present a case of severe collapsing FSGS and acute CMV infection in an immunocompetent host. Case Description: A 19-year-old woman with HbSS sickle cell disease and infrequent vaso occlusive crisis was hospitalized with febrile illness. During hospitalization she developed non-oliguric acute kidney injury (AKI) and volume overload and started on intermittent hemodialysis. Chest x-ray showed cardiomegaly, pulmonary venous congestion, infiltrates and bilateral pleural effusions. 24h Urine protein was 17,291 mg/24h. Urine and serum myoglobin were elevated. Relevant investigations include positive CMV IgM, CMV PCR 7000 international unit(s)/ml, positive mycoplasma IgM. SARS-CoV-2 RT-PCR & NAT were negative but antibodies were positive. A diagnosis of COVID associated Multisystem inflammatory syndrome in children (MIS-C) was made and she received methylprednisolone. She received piperacillin/tazobactam, azithromycin, ganciclovir, meropenem, and linezolid for CMV infection and pneumonia. Renal biopsy revealed collapsing FSGS, moderate and acute tubular injury, interstitial edema, focal tubular microcysts and podocyte effacement. Renal function improved after ganciclovir therapy and hemodialysis was discontinued. Prednisone and losartan were started for persistent proteinuria. Discussion: Active CMV infection in immunocompetent hosts is uncommon. The mechanism of CMV associated with collapsing FSGS is unclear as direct viral infection is not always seen on biopsy. CMV is not routinely tested for in immunocompetent patients and should be considered in AKI and nephrotic syndrome with multi-system involvement. Our patient had lung infiltrates and rhabdomyolysis which could be explained by CMV infection. Anti-viral therapy may be effective. As opposed to primary collapsing FSGS steroids are not routinely needed. Some patients have persistent proteinuria and nephrotic syndrome may respond to steroids, with tacrolimus in refractory cases. It is unclear if prior COVID infection or MIS-C contributed to activation of CMV infection and FSGS.