Thrombotic microangiopathy associated with arboviral infection: Report of 3 cases

Abstract

Dengue fever and chikungunya are viral diseases that have spread rapidly throughout the world in recent decades. The occurrence of complications is well known, including prerenal acute kidney injury (AKI), which is usually thought to be caused by dehydration and fluid loss. Thrombotic microangiopathy (TMA) is an uncommon aggravation of dengue fever and chikungunya, with only a few cases described in the medical literature. The aim of this study is to present 3 cases of TMA associated with arboviral infection. Three patients with clinical history, laboratory test, and kidney biopsy results compatible with TMA were selected for the study, 2 of whom had a serological diagnosis of dengue fever and 1 of chikungunya. The 3 patients were followed up at the Federal University of Maranhão Hospital’s Nephrology Service in 2018. A targeted gene panel sequencing (TGPS) plus multiple to atypical hemolytic uremic syndrome (aHUS) multiplex ligation–dependent probe amplification (MLPA) was performed in 2 of the patients and revealed in the patient 1 a heterozygous pathogenic variant in the gene THBD, as well as heterozygous deletions in CFH, CFHR1, and CFHR3. In the patient 2, there were heterozygous pathogenic variant in the genes CFI and CFB, in addition to heterozygous deletions in the genes CFHR1 and CFHR3. Both received treatment with eculizumab and undergone recovery of renal function. The third patient had TMA not classified as either aHUS or thrombotic thrombocytopenic purpura (TTP); he abandoned the treatment and returned to the service after 2 years for a dialysis emergency. Patients with arboviral infectious disease and changes that suggest TMA should have appropriate support to establish early diagnosis and useful treatment.

The relationship between chikungunya virus and the kidneys: A scoping review

“…The renal histopathological findings described include acute interstitial nephritis with mononuclear infiltrates, glomerular congestion, nephrosclerosis, as well as glomerulopathies, pigment cast nephropathy and thrombotic microangiopathy. [46][47][48][49][50]52 Despite the identification of viral antigen in renal tissue, no evident cytopathic effect was demonstrated. 48,49 There are many case reports of CHIK associated with atypical and severe manifestations such as AKI, with some patients experiencing rapid deterioration and death from multisystem failure.…”

Virus-Associated Nephropathies: A Narrative Review

“…No antiviral is currently available, but some DENV inhibitors are in the development pipeline [ 245 ]. Of note, other arbovirus infections have also been associated with renal damage, mainly ATN and thrombotic microangiopathy [ 257 , 262 , 263 ].…”

Acute kidney injury in the tropics

“…There are 4 serotypes, DEN‐1 to DEN‐4. Immunity provides lifelong protection to that specific serotype and a few months protection from the remaining serotypes 74–76 . The annual number of infections is estimated at 390 million globally with approximately 50–100 million at risk 77–79 .…”

“…Kidney involvement includes AKI, proteinuria, GN, atypical hemolytic uremic syndrome (aHUS) and electrolyte abnormality 74,80,81 . The prevalence of dengue‐associated AKI varies from 0.2% to 35.7% in the Caribbean, LA and SEA depending on the definition of AKI, age group and severity 61,82–88 .…”

“…The use of parenteral corticosteroids for severe dengue is still controversy. Eculizumab had been shown to be effective in case with aHUS 74 . Acetaminophen and non‐steroidal anti‐inflammatory drugs (NSAIDs) must be avoided.…”