Hemolytic uremic syndrome in a developing country: Consensus guidelines

Bagga, Arvind; Khandelwal, Priyanka; Mishra, Kirtisudha; Thergaonkar, Ranjeet; Vasudevan, Anil; Sharma, Jyoti; Patnaik, Saroj Kumar; Sinha, Aditi; Sethi, Sidharth Kumar; Hari, Pankaj; Dragon-Durey, Marie-Agnès

doi:10.1007/s00467-019-04233-7

Cited by 51 publications

(34 citation statements)

References 109 publications

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“…While free FH is presently a research tool and not available widely, close monitoring of anti-FH antibody titers is required with more careful assessment if elevated >1,300 AU/ml during the first 12–24 months (37). Relapses usually follow minor infectious illnesses during which close clinical and biochemical monitoring is required.…”

Section: Discussionmentioning

confidence: 99%

“…Education and dissemination of management protocols through scientific meetings and efforts for consensus guidelines (37) has resulted in prompt recognition, early referral, and protocol based management, improving patient outcomes. While PEX and immunosuppression are considered primary therapies for patients with anti-FH associated HUS, the duration of therapy is empirical (41).…”

Section: Discussionmentioning

confidence: 99%

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Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database

et al. 2019

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Background: Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required. Methods: Of 781 patients <18-year-old of aHUS in the nationwide database from 2007 to 2018, 436 (55.8%) had anti-FH antibodies. Clinical features and outcome of patients managed in the last 6-year ( n = 317) were compared to before ( n = 119). In plasma samples of 44 patients, levels of serial circulating FH immune complexes (CIC), free FH, soluble terminal complement complex (sC5b-9), sheep red blood cell (SRBC) lysis and epitope specificity ( n = 8) were examined. Functional renal reserve, ambulatory hypertension, left ventricular hypertrophy (LVH), and proteinuria were evaluated in a subset. Results: Patients presented with markedly elevated anti-FH titers (10,633.2 ± 998.5 AU/ml). Management varied by center, comprising plasma exchange (PEX; 77.5%) and immunosuppression (73.9%). Patients managed in the last 6-year showed better renal survival at mean 28.5 ± 27.3 months (log rank P = 0.022). Mean anti-FH titers stayed 700–1,164 AU/ml during prolonged follow-up, correlating with CIC. Patients with relapse had lower free-FH during remission [Generalized estimating equations (GEE), P = 0.001]; anti-FH levels ≥1,330 AU/ml and free FH ≤440 mg/l predicted relapse (hazards ratio, HR 6.3; P = 0.018). Epitope specificity was similar during onset, remission and relapse. Antibody titer ≥8,000 AU/ml (HR 2.23; P = 0.024), time to PEX ≥14 days (HR 2.09; P = 0.071) and PEX for <14 days (HR 2.60; P = 0.017) predicted adverse renal outcomes. Combined PEX and immunosuppression improved long-term outcomes (HR 0.37; P = 0.026); maintenance therapy reduced risk of relapses (HR 0.11; P < 0.001). At 4.4±2.5 year, median renal reserve was 15.9%; severe ambulatory, masked and pre-hypertension were found in 38, 30, and 18%, respectively. Proteinuria and LVH occurred in 58 and 28% patients, respectively. Conclusion: Prompt recognition and therapy with PEX and immunosuppression, is associated with satisfactory outcomes. Free-FH predicts early relapses in patients with high anti-FH titers. A significant proportion of impaired functional reserve, ambulatory hypertension, proteinuria and LVH highlight the need for vigilant long-term follow-up.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database

et al. 2019

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“…The American Society for Apheresis assigns level I category to anti-FH associated HUS, implying that PE is a primary therapeutic intervention. Guidelines from expert groups72 recommend combined therapy with PE and immunosuppressive agents for patients with anti-FH antibodies. Prompt initiation and continued PE for at least 3–5 weeks are thus advised.…”

Section: Challenges Of Eculizumabmentioning

confidence: 99%

<p>Optimal management of atypical hemolytic uremic disease: challenges and solutions</p>

Raina¹,

Grewal²,

Radhakrishnan³

et al. 2019

IJNRD

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Atypical hemolytic uremic syndrome (aHUS) is a chronic life threatening condition that arises from genetic abnormalities resulting in uncontrolled complement amplifying activity. The introduction of eculizumab, the humanized monoclonal antibody, has brought about a paradigm shift in the management of aHUS. However, there are many knowledge gaps, diagnostic issues, access and cost issues, and patient or physician challenges associated with the use of this agent. Limited data on the natural history of aHUS along with the underlying genetic mutations make it difficult to predict the relapses and thereby raising concerns about the appropriate duration and monitoring of treatment. In this review, we discuss the safety and efficacy of eculizumab in patients with aHUS and its associated challenges.

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“…Schistocytes are defined as circulating RBC fragments (George and Nester, 2014). The presence of schistocytes in peripheral blood smears is critically important for the prognosis of thrombotic microangiopathy (Moake, 2002) and hemolytic uremic syndrome (Bagga et al, 2019). These RBC fragments are increased in cardiac prosthesis-related hemolytic anemia (Alkhouli et al, 2019) and mechanical heart valve recipients (Mecozzi et al, 2002), or during dialysis treatment (Pradhan et al, 2015;Schapkaitz and Mezgebe, 2017) and extracorporeal membrane oxygenation support due to mechanical damage (Mlinarić, 2016).…”

Section: Introductionmentioning

confidence: 99%

A Novel Fragmentation Sensitivity Index Determines the Susceptibility of Red Blood Cells to Mechanical Trauma

et al. 2021

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Supraphysiological shear stresses (SSs) induce irreversible impairments of red blood cell (RBC) deformability, overstretching of RBC membrane, or fragmentation of RBCs that causes free hemoglobin to be released into plasma, which may lead to anemia. The magnitude and exposure tisme of the SSs are two critical parameters that determine the hemolytic threshold of a healthy RBC. However, impairments in the membrane stability of damaged cells reduce the hemolytic threshold and increase the susceptibility of the cell membrane to supraphysiological SSs, leading to cell fragmentation. The severity of the RBC fragmentation as a response to the mechanical damage and the critical SS levels causing fragmentation are not previously defined. In this study, we investigated the RBC mechanical damage in oxidative stress (OS) and metabolic depletion (MD) models by applying supraphysiological SSs up to 100 Pa by an ektacytometer (LORRCA MaxSis) and then assessed RBC deformability. Next, we examined hemolysis and measured RBC volume and count by Multisizer 3 Coulter Counter to evaluate RBC fragmentation. RBC deformability was significantly impaired in the range of 20–50 Pa in OS compared with healthy controls (p < 0.05). Hemolysis was detected at 90–100 Pa SS levels in MD and all applied SS levels in OS. Supraphysiological SSs increased RBC volume in both the damage models and the control group. The number of fragmented cells increased at 100 Pa SS in the control and MD and at all SS levels in OS, which was accompanied by hemolysis. Fragmentation sensitivity index increased at 50–100 Pa SS in the control, 100 Pa SS in MD, and at all SS levels in OS. Therefore, we propose RBC fragmentation as a novel sensitivity index for damaged RBCs experiencing a mechanical trauma before they undergo fragmentation. Our approach for the assessment of mechanical risk sensitivity by RBC fragmentation could facilitate the close monitoring of shear-mediated RBC response and provide an effective and accurate method for detecting RBC damage in mechanical circulatory assist devices used in routine clinical procedures.

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Hemolytic uremic syndrome in a developing country: Consensus guidelines

Cited by 51 publications

References 109 publications

Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database

Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database

<p>Optimal management of atypical hemolytic uremic disease: challenges and solutions</p>

A Novel Fragmentation Sensitivity Index Determines the Susceptibility of Red Blood Cells to Mechanical Trauma

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