Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

BACKGROUND: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. METHODS: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018. RESULTS: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. CONCLUSION: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.

Norovirus: a novel etiologic agent in hemolytic uremic syndrome in an infant.

BACKGROUND: Hemolytic uremic syndrome is a rare thrombotic microangiopathy usually seen in infants and children below the age of 5 years. It usually follows a bout of bloody diarrhea caused by Shiga toxin producing E coli and is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. We report the first case of hemolytic uremic syndrome in an infant following Norovirus gastroenteritis. CASE PRESENTATION: A nine-month-old male infant, was admitted with an 8-day history of watery, non-bloody diarrhea, vomiting and decreased oral intake. Physical exam revealed normal blood pressure, pallor and generalized edema. Laboratory findings were significant for microangiopathic hemolytic anemia, thrombocytopenia and azotemia. Stool studies with Multiplex Qualitative reverse transcriptase PCR were positive for Norovirus GI/G II. His clinical course was unusually severe, complicated by oligoanuria and worsening uremia requiring peritoneal dialysis but with eventual complete recovery. CONCLUSIONS: To our knowledge this is the first case of Norovirus associated HUS in an infant. Given the ubiquity of this virus as a major cause of diarrhea, together with the increased availability of Multiplex Qualitative PCR in reference laboratories, it is quite possible that we shall be seeing more such cases in the future.

Haemolytic-uremic syndrome due to infection with adenovirus: A case report and literature review.

RATIONALE: Haemolytic-uremic syndrome is a rare but serious complication of bacterial and viral infections, which is characterized by the triad of: acute renal failure, microangiopathic haemolytic anemia and thrombocytopenia, sometimes severe, requiring peritoneal dialysis. In Europe, hemolytic-uremic syndrome (HUS) in paediatric pathology is primarily caused by Shiga toxin-producing Escherichia coli (STEC) O157, followed by O26. Beside these etiologies, there are other bacterial and viral infections, and also noninfectious ones that have been associated to lead to HUS as well: in the progression of neoplasia, medication-related, post-transplantation, during pregnancy or associated with the antiphospholipid syndrome, systemic lupus erythematosus or family causes with autosomal dominant or recessive inheritance. In terms of pathogenesis, HUS is the result of endothelial injury, most commonly being a result of the action of Shiga toxin. The unfavorable prognosis factors being represented by the age of more than 5 years old, different etiologies from STEC, persistent oligoanuria, central nervous system and glomerular impairment, the association of fever with leukocytosis. HUS is responsible for 7% of cases of hypertension in infants, and an important cause of significant kidney damage in adults. PATIENT CONCERNS: We present one case of HUS caused by adenovirus in a boy of 1 year and 7 months old with severe evolution, which required peritoneal dialysis. DIAGNOSE: Stool sample repeated examination for adenovirus antigen was positive in 2 samples. INTERVENTION: During hospitalization, the patient required 8 peritoneal dialysis sessions. OUTCOME: The renal function was corrected on discharge, the patient required cardiovascular monitoring 1 month after discharge. LESSON: Although the most common cause that leads to HUS remains STEC, other etiologies like viral ones that may be responsible for severe enteric infection with progression into HUS should not be neglected.

Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection.

Prophage induction is enhanced and required for renal disease and lethality in an EHEC mouse model.

Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production.

Is complement a culprit in infection-induced forms of haemolytic uraemic syndrome?

Haemolytic uraemic syndrome (HUS) accounts for the most common cause of childhood acute renal failure. Characterized by the classical triad of a microangiopathic haemolytic anaemia, thrombocytopaenia and acute renal failure, HUS occurs as a result of Shiga-toxin producing microbes in 90% of cases. The remaining 10% of cases represent a heterogeneous subgroup in which inherited and acquired forms of complement dysregulation have been described in up to 60%. Emerging evidence suggests that microbes associated with HUS exhibit interaction with the complement system. With the advent of improved genetic diagnosis, it is likely that certain cases of infection-induced HUS may be attributed to underlying defects in complement components. This review summarises the interplay between complement and infection in the pathogenesis of HUS.

Pandemic H1N1 influenza A viral infection complicated by atypical hemolytic uremic syndrome and diffuse alveolar hemorrhage.

We report here on a case of a 27-year-old man with atypical hemolytic uremic syndrome and diffuse alveolar hemorrhage associated with influenza A H1N1 infection. Treatment with oseltamivir, plasma exchange and hemodiafiltration for the hemolytic uremic syndrome and meticulous supportive care with steroid pulse therapy for the pulmonary alveolar hemorrhage was successful in this case. We discuss the relationship between hemolytic uremic syndrome and influenza A and the underlying immunologic factors that should be tested in a patient with atypical hemolytic uremic syndrome. We also discuss using steroid therapy for patients with H1N1-related diffuse alveolar hemorrhage.

Viral-associated thrombotic microangiopathies.

Thrombotic microangiopathies encompass a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia associated with hyaline thrombi (comprised primarily of platelet aggregates in the microcirculation), and varying degrees of end-organ failure. Many primary (genetic) and secondary etiological predisposing factors have been described-namely pregnancy, autoimmune disorders, cancer, drugs and antineoplastic therapy, bone marrow transplantation/solid organ transplantation, and infections. In the setting of infectious diseases, the association with Shiga or Shiga-like exotoxin of Escherichia coli 0157:h7 or Shigella dysenteriae type 1-induced typical hemolytic uremic syndrome is well known. Recently however, an increasing body of evidence suggests that viruses may also play an important role as trigger factors in the pathogenesis of thrombotic microangiopathies. This is a comprehensive review focusing on the current understanding of viral associated/induced endothelial stimulation and damage that ultimately leads to the development of this life-threatening multisystemic disorder.

Pandemic H1N1 influenza A infection and (atypical) HUS--more than just another trigger?

Atypical hemolytic uremic syndrome (aHUS) is caused by mutations resulting in an exceedingly active alternative complement pathway. While today more than half a dozen genes are involved in aHUS pathology, only about 50% of carriers precipitate the disease. The reason for this phenomenon remains unclear, and triggering events like intercurrent infections have been postulated. In this context, reports on the development of (a)HUS in patients concomitantly diagnosed with pandemic H1N1 influenza A (pH1N1) infection are of great interest. They establish--for the first time in the literature--the link between aHUS and pH1N1 infection. While illnesses associated with pH1N1 infections during the recent pandemics were generally mild, secondary bacterial infections (e.g. Streptococcus pneumoniae) are known in patients with influenza A infections to not only aggravate the disease course, but also serve as a possible HUS trigger. Assuming pH1N1 was the cause of HUS in the cases reported here, it remains an interesting but unanswered hypothesis whether an underlying complement defect served as a susceptibility factor, at least in a subgroup of patients. In the future, pH1N1, but also pH1N1-associated, bacterial infections will have to be considered in (a)HUS patients, and further studies will be required to examine the role of the complement system in this condition.

Triggering of atypical hemolytic uremic syndrome by influenza A (H1N1).

We report a case of atypical hemolytic uremic syndrome (aHUS) triggered by influenza A (H1N1) in a 17-year-old boy with a mutation in the gene (CD46) encoding the transmembrane complement regulator membrane cofactor protein. The patient recovered completely following treatment with oseltamivir, plasma exchange, and hemodialysis. We describe the case and discuss this unusual association of diseases.

Phylogeny and disease association of Shiga toxin-producing Escherichia coli O91.

The diversity and relatedness of 100 Shiga toxin-producing Escherichia coli O91 isolates from different patients were examined by multilocus sequence typing. We identified 10 specific sequence types (ST) and 4 distinct clonal groups. ST442 was significantly associated with hemolytic uremic syndrome.

Iron-related proteins: candidate urine biomarkers in childhood HIV-associated renal diseases.

BACKGROUND: Because of the risk of performing renal biopsies in children with co-morbid conditions, we carried out this study to identify candidate protein biomarkers in the urine of HIV-infected children with renal disease. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Urine samples from HIV-infected children with biopsy proven HIV-nephropathy (HIVAN; n = 4), HIV-associated Hemolytic Uremic Syndrome (HIV-HUS; n = 2), or no renal disease (n = 3) were analyzed by two-dimensional electrophoresis (2-DE) and proteomic methods. Positive findings were confirmed in HIV-infected children with (n = 20) and without (n = 10) proteinuria using commercially available assays. RESULTS: By 2-DE analysis, a single urine marker was not sufficient to distinguish children with HIVAN from the others. High urine levels of beta(2)-microglobulin and retinol-binding protein (RBP) suggested the presence of tubular injury. In addition, we found elevated urine levels of iron and the iron-related proteins, transferrin, hemopexin, haptoglobin, lactoferrin, and neutrophil gelatinase-associated lipocalin (NGAL), in children with HIVAN and HIV-HUS. Furthermore, we detected a significant accumulation of iron in the urine and kidneys of HIV-transgenic (Tg) rats with renal disease. CONCLUSION: These findings suggest that iron and iron-related proteins might be promising candidate urine biomarkers to identify HIV-infected children at risk of developing HIVAN and HIV-HUS. Moreover, based on the results of previous studies, we speculate that the release or accumulation of iron in the kidney of HIV-infected children may contribute to the rapid progression of their renal disease, and could become a new therapeutic target against HIVAN and HIV-HUS.

Environmental prevention of human disease from verocytotoxin-producing Escherichia coli.

Verocytotoxin-producing Escherichia coli (VTEC) haemolytic uraemic syndrome (HUS) is an important cause of mortality and renal failure worldwide. For those patients who need medical attention, no treatment aside from supportive care has proven effective for this disease. This has prompted a broader look at environmental prevention, with a particular emphasis on the transmission of bacteria from animal carriers to human beings. Here, we review animal- and meat-handling strategies to reduce the burden of VTEC human disease.