Eculizumab as first-line treatment for patients with severe presentation of complement factor H antibody-mediated hemolytic uremic syndrome.

BACKGROUND: Complement factor H (FH) antibody-mediated hemolytic uremic syndrome (HUS) has varying prevalence globally. Plasmapheresis and immunosuppressive drugs are the standard treatment. Recently, eculizumab has been reported as an effective alternative. This study aims to report four children with FH antibody-mediated HUS managed with eculizumab plus immunosuppression as first-line therapy. METHODS: A retrospective chart review was conducted for children aged ≤ 18 years old with complement-mediated HUS in two referral centers. Patients with FH antibody-mediated HUS treated with eculizumab as first-line therapy were included. RESULTS: Four children (aged 6-11 years old) were included. Dialysis was necessary in three patients. Eculizumab was administered 5-23 days after onset. None of them received plasmapheresis. Prednisone and mycophenolate mofetil were added after receiving positive FH antibody results. Hematological signs and kidney function improved after the second eculizumab dose. Eculizumab was discontinued in three patients after 6 months. One patient required rituximab due to persistent high FH antibody titers; discontinuation of eculizumab occurred after 15 months without recurrence. No treatment-related complications were observed. During a mean 12-month follow-up (range 6-24 months), no relapses were recorded and all patients ended with normal GFR. CONCLUSION: Our data suggest that a short course of 6 months of C5 inhibitor might be sufficient to reverse thrombotic microangiopathy symptoms and improve kidney function in patients with severe FH antibody-mediated HUS. Simultaneously, adding immunosuppressive agents might reduce the risk of relapse and allow cessation of C5 inhibition in a shorter period of time.

Fluid restriction versus volume expansion in children with diarrhea-associated HUS: a retrospective observational study.

BACKGROUND: Fifty percent of patients with typical diarrhea-associated hemolytic uremic syndrome (D+HUS) require kidney replacement therapy (KRT). In these patients, dehydration worsens disease prognosis. We evaluated dialysis requirement, presence of seizures, and mortality rate among patients diagnosed with D+HUS treated with volume expansion (VE) versus fluid restriction (FR). METHODS: Thirty-five patients with D+HUS were enrolled; 16 received VE and 19 were historical patients who received conventional FR. RESULTS: Upon admission or during treatment, neither group presented evidence of fluid overload. The VE group received higher volumes of saline (VE 27 ml/kg [10-30] over a 3-h period vs. FR 0 ml), had higher urine output after 12 h (VE vs. FR: OR 6.2 [1.2-41.6], P = 0.03), and required less dialysis (VE 2 [12.5%, CI 95% 0-29] vs. FR 9 [47.4%, CI 95% 24-70], P = 0.035). The VE group had an absolute risk reduction of 0.34 (CI 95% 0.07-0.63); hence, three patients treated with VE were required to avoid one KRT. VE also corrected initial hyponatremia and maintained serum sodium within normal ranges. No statistical differences were observed regarding number of patients with seizures (P = 0.08) or mortality (P = 1.0). CONCLUSIONS: VE markedly reduces the number of patients requiring KRT and keeps serum sodium within a normal range. We propose to initially hydrate every patient with D+HUS and without signs of fluid overload, with 10 ml/kg/h 0.9% saline solution IV, over a 3-h period. Afterwards, if urine output is ≥ 0.5 ml/kg/h, it is recommended to not dialyze and continue IV hydration schedule with isotonic (D5) saline solution, according to their needs.

Acute peritoneal dialysis, complications and outcomes in 389 children with STEC-HUS: a multicenter experience.

BACKGROUND: Management of acute kidney injury (AKI) in children with hemolytic uremic syndrome induced by a Shiga toxin-producing Escherichia coli infection (STEC-HUS) is supportive; however, 40 to 60% of cases need kidney replacement therapy (KRT). The aim of this study was to analyze procedure complications, especially peritonitis, and clinical outcomes in children with AKI secondary to STEC-HUS treated with acute PD. METHODS: This is a multicenter retrospective study conducted among thirty-seven Argentinian centers. We reviewed medical records of 389 children with STEC-HUS hospitalized between January 2015 and February 2019 that required PD. RESULTS: Complications associated with PD were catheter malfunction (n = 93, 24%), peritonitis (n = 75, 19%), fluid leaks (n = 45, 11.5%), bleeding events (n = 23, 6%), and hyperglycemia (n = 8, 2%). In the multivariate analysis, the use of antibiotic prophylaxis was independently associated with a decreased risk of peritonitis (hazard ratio 0.49, IC 95% 0.29-0.81; p = 0.001), and open-surgery catheter insertion was independently associated with a higher risk (hazard ratio 2.8, IC 95% 1.21-6.82; p = 0.001). Discontinuation of PD due to peritonitis, severe leak, or mechanical complications occurred in 3.8% of patients. No patient needed to be transitioned to other modality of KRT due to inefficacy of the technique. Mortality during the acute phase occurred in 2.8% patients due to extrarenal complications (neurological and cardiac involvement), not related to PD. CONCLUSIONS: Acute PD was a safe and effective method to manage AKI in children with STEC-HUS. Prophylactic antibiotics prior to insertion of the PD catheter should be considered to decrease the incidence of peritonitis.

Caída del filtrado glomerular secundario a hipotiroidismo autoinmune / Impaired estimated glomerular filtration rate in a patient with autoimmune hypothyroidism

El hipotiroidismo adquirido se presenta en alrededor del 0,3% de los niños en edad escolar y su principal causa es la tiroiditis linfocitaria crónica, de etiología autoinmune. Desde mediados del siglo XX, se conoce el papel de las hormonas tiroideas en el crecimiento y mantenimiento de las funciones del riñón. Se presenta una paciente con caída de filtrado glomerular secundario a hipotiroidismo primario que normalizó la función renal con suplencia hormonal y se realiza una revisión sobre los mecanismos fisiopatológicos involucrados

Acquired hypothyroidism occurs in about 0.3% of schoolage children and its main cause is autoimmune chronic lymphocytic thyroiditis. Since the mid-twentieth century, the role of thyroid hormones in the growth and maintenance of kidney functions has been well known. A patient with glomerular filtration rate secondary to primary hypothyroidism who normalized renal function with hormonal replacement is presented and the pathophysiological mechanisms involved are analyzed