Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review

Figures & data

Figure 1 PRISMA study flow diagram. Adapted from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.²²

Table 1 Design Characteristics of Studies Examining Incidence and Prevalence of Atypical Hemolytic Uremic Syndrome

Study Name	Study Type	Country	Source of Data	Study Design	Study Period	Study-Reported aHUS Case Definition	Case Selection	Age
Bayer 2019^Citation24	Full-text article	France	Four-hospital institution in France	Retrospective	2009–2016	TMA/kidney failure with no evidence of drug use known to be associated with TMAs, transplantations, no STEC infection, cancers, autoimmune disease, and severe/malignant hypertension (hypertensive retinopathy and diastolic arterial pressure over 120 mmHg).	Patients hospitalized in our four-hospital institution (Centre Hospitalier Universitaire [CHU] Tours, France) who were suspected of having a first episode of TMA were included. CHU Tours includes four hospitals of the Centre area of France.	All ages
Ardissino 2016^Citation25	Full-text article	Italy	HUS network containing 56 pediatric units in Lombardy	Retrospective	2003–2012	HUS with no evidence of diarrhea or STEC infection	The study includes all of the incident cases occurring in patient’s resident within the administrative boundaries of the Lombardy Region of Italy who experienced a documented first episode of HUS before the age of 18 years	≤18 years old
Durkan 2016^Citation28	Full-text article	Australia	Australian Pediatric Surveillance Unit (National Surveillance)	Prospective	1994–2001	HUS with no evidence of STEC infection or Streptococcus pneumoniae infection	Active surveillance programme of all cases of HUS in children aged less than 15 years	≤15 years old
Jenssen 2014^Citation26	Full-text article	Norway	24 pediatric hospitals	Retrospective	1999–2008	HUS with no evidence of diarrhea or STEC infection	Patients <16 years and all hospitals with capacity, competence, or supportive care of HUS and/or AKI patients were included.	<16 years old
Mallett 2014^Citation29	Full-text article	Australia/NZ	CKD.QLD Registry	Cross-sectional	2013	aHUS defined in the registry	All patients with clinically diagnosed CKD, were 18 years or older and had attended public nephrology practices in Queensland	>18 years old
Wuhl 2014^Citation27	Full-text article	Austria, Denmark, Spain, Finland, France, Greece, Netherlands, Norway, Romania, Sweden, Scotland	ERA–EDTA Registry	Retrospective	2007–2011	aHUS PRD diagnostic code	Patients of all ages with aHUS were extracted from the ERA–EDTA Registry	All ages
Fremeaux-Bacchi 2013^Citation13	Full-text article	France	French National Study	Retrospective	2000–2008	No HUS secondary to drugs, autoimmune diseases, due to the number of infections (STEC, Streptococcus pneumoniae, or HIV), bone marrow or solid organ transplantation, and cobalamin deficiency	Included patients with atypical HUS excluding all cases of secondary aHUS except pregnancy. Excluded patients with HUS secondary to drugs, autoimmune diseases, infections (caused by STEC, Strep. pneumoniae, or HIV), bone marrow/organ transplant, and cobalamin deficiency	All ages
Zimmerhackl 2006^Citation23	Full-text article	Austria, Germany, Czechia, Hungary, Switzerland, UK, Italy, Turkey, Netherlands, Israel, Sweden, France	European registry	Cross-sectional (Prospective after 2001)	1974–2005	HUS with no evidence of diarrhea or STEC infection	Patients <18 years old with aHUS were extracted from the European Registry	<18 years old

Abbreviations: UK, United Kingdom; NZ, New Zealand; STEC, Shiga toxin-producing E. coli; HUS, hemolytic uremic syndrome; aHUS, atypical hemolytic uremic syndrome; TMA, thrombotic microangiopathy.

Table 2 Baseline Population Characteristics of Studies Examining Incidence and Prevalence of Atypical Hemolytic Uremic Syndrome

Study Name	Study Period	Study Population	Incident Cases	Age at Onset (Range)	Male, n (%)	Acute Dialysis n (%)	Neurological Involvement n (%)	Serum Creatinine umol/L (Range)	Hemoglobin, g/dL (Range)	Platelets 10^9/L (%)	Anemia, n (%)	Diarrhea n (%)	Respiratory Infection n (%)
Bayer 2019^Citation24	2009–2016	All ages	15	35* (23–46)^#	4 (27)	13 (86)^√	5 (33)	4.6* (1.7–7.9)^#Ψ	7.6* (6.2–9.9)^#	71* (40–80)^#	14 (95)	3 (19)	–
Ardissino 2016^Citation25	2003–2012	≤18 years	12	–	–	4 (33.3)	–	–	–	–	–	0	–
Durkan 2016^Citation28	1994–2001	≤15 years	14	1.1* (0.28–14.7)^Ω	5 (36)	10 (71)	4 (29)	219* (99–1253)	3.8* (7.1–14.0)	54* (9–147)	14 (100)	9 (64.3)	–
Jenssen 2014^Citation26	1999–2008	<16 years	9	–	–	–	–	–	–	–	–	0	–
Mallett 2014^Citation29	2013	>18 years	3	36.66	–	–	–	–	–	–	–	0	–
Wuhl 2014^Citation27	2007–2011	All ages	288	–	–	–	–	–	–	–	–	0	–
Fremeaux-Bacchi 2013^Citation13	2000–2008	<16 years	89	1.5 (0–15)	47 (52.8)	48 (59)	14 (16)	257 (28–990)	6.8 (3.0–12.0)	–	79 (94)	35 (39)	7 (8)
		≥16 years	125	31 (15–85)	32 (25.6)	93 (81)	10 (8)	640 (111–2408)	7.2 (5.0–11.8)	–	83 (89)	19 (15)	1 (1)
Zimmerhackl 2006^Citation23	1974–2005	<18 years	167	–	94 (56.2)	–	–	–	–	–	–	0	–

Notes: All values displayed as mean (range) or otherwise specified; *Median, ^#IQR, ^Ωconverted from months, ^√reported as acute kidney injury, ^Ψmg/dL.

Figure 2 Studies reporting countries with reported incidence estimates by age group.

Note: *Jenssen 2014 reported incidence <1 per million annually (Range: 0–3).

Figure 3 Studies reporting countries with reported prevalence estimates by age group.

Table 3 Incidence and Prevalence of Atypical Hemolytic Uremic Syndrome

Study	Country	Study Period	Age	Total aHUS Cases	Incidence per Million Annually (Range)	Prevalence per Million
Bayer 2019*^Citation24	France	2009–2016	All ages	15	1.9	–
Ardissino 2016^Citation25	Italy	2003–2012	≤18 years old	12	0.75	9.4
Durkan 2016^Citation28	Australia	1994–2001	≤15 years old	14	0.44	–
Jenssen 2014^Citation26	Norway	1999–2008	<16 years old	9	<1 (0–3)	–
Mallett 2014^Citation29	Australia/New Zealand	2013	>18 years old	3	–	2.4
Wuhl 2014^Citation27	Austria, Denmark, Spain, Finland, France, Greece, Netherlands, Norway, Romania, Sweden, Scotland	2007–2011	All ages	815	0.39	4.96
		2007-2011	<20 years old	81	0.26	2.21
		2007–2011	>20 years old	734	0.42	5.75
Fremeaux-Bacchi 2013^Citation13	France	2000–2008	All ages	214	0.23	–
Zimmerhackl 2006^Citation23	Austria, Germany, Czechia, Hungary, Switzerland, United Kingdom, Italy, Turkey, Netherlands, Israel, Sweden, France	1974–2005	<18 years old	167	–	3.3

Note: *One pediatric case in the study.

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