Supplementary Table 1 |Findings indicative of iron-related kidney injury in haem-related diseases
Disease or insult / Findings
Red blood cell aplasia / ↑Urinary haemosiderin(method not specified); ↑CMJ iron (MRI); not haemolysing1
Chronic haemolytic anaemia / Urinary haemosiderin↑(Prussian reaction of Perls); kidney iron ↑ (Turnbull iron reaction); hepatic iron↔1,2
Antibody haemolytic anaemia / Kidney iron↑(Prussian blue staining); histological kidney damage3
HO1 deficiency / Proximal tubule iron↑(Prussian blue staining); histological kidney damage; HO1 caused haemolytic anaemia4
HIV–HUS / Urinaryiron↑(ferrozine staining); glomerular and tubular damage; transferrin, haemopexin, haptoglobin, lactotransferrin, NGAL↑5
Thalassemia major,mechanical haemolysis, pernicious anaemia / Urinaryiron ↑(benzidine method of Crosby and Furth and reaction with dipyridyl); pernicious anaemia is a type of megaloblastic anaemia6
Sickle cell disease / Urinaryiron ↑(benzidine method of Crosby and Furth and reaction with dipyridyl); proximal tubule iron MRI↑(MRI); histological kidney damage6-8
PNH / Urinary haemosiderin↑(Prussian reaction of Perls, benzidine method of Crosby and Furth and reaction with dipyridyl); kidney iron↑ (Turnbull iron reaction, MRI Prussian blue staining); proteinuria2,6,9-12
Hereditary spherocytosis / Urinary haemosiderin↑(Prussian reaction of Perls); kidney iron↑(Turnbull iron reaction)2
Haemolysis after cardiac surgery / Kidney iron↑(Prussian blue staining); histological kidney damage(electron microscopy); AKI13
Rhabdomyolysis / Myoglobin in urine↑(immunoassay); myoglobinuria predicted kidney failure after rhabdomyolysis14-16
-thalassaemia / Kidney iron↑ (MRI)17
Patients who complied badly with chelation therapy had higher serum ferritin levels and kidney dysfunction than did patients who complied well
Haemolytic anaemia in mice / Kidney iron↑ (Prussian blue staining)18
Glycerol-induced myoglobinuric AKI (rhabdomyolysis) / Urinaryiron↑(bleomycin assay); kidney iron↑(bleomycin assay, immunoperoxidase method to detect myoglobin); glomerular and tubular damage(histologic, malondialdehyde, PAS); renal cortical haemopexin mRNA↑;
AKIin rat by plasma creatinine and plasma nitrogen urea, partly in vitro
Deferoxamine infusion attenuated kidney dysfunction and oxidative stress19-25
Haem protein infusion in rat / Large haem-filled endolysosomes in proximal tubule; haem casts in distal nephron; proximal tubule damage(histologic)26
HO1 deficiencyleading tohaemolytic anaemia / Proximal tubule iron↑(Prussian blue staining); histological kidney damage; CD163, ferritin light chain, ferritin heavy chain, ferroportin mRNA↑; haemopexin protein↑27
In vitro studies
Cells exposed to haem / DNA damage in distal tubule (MCDK) cellsbut not proximal tubule (LLC-PK1) cells20
Proximal tubule cells exposed to myoglobin / Cell damage (LDH); HK-2 cells and extracted proximal tubule cells used28
Proximal tubule cells exposed to haemoglobin / Cell damage (MTT assay); human proximal tubule cells used29
Abbreviations: ↑, increased; ↔, unchanged; AKI,acute kidney injury; AKF,acute kidney failure; CMJ, corticomedullary junction; HK-2, human kidney 2; HO1, haem oxygenase 1; HUS, haemolytic uremic syndrome; LDH,lactate dehydrogenase; LLC–PK1,pig kidney epithelial cells;MDCK, Madin–Darby canine kidney; MTT, PAS,pernicious anaemia staining; PNH,paroxysmal nocturnal haemoglubinuria.
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