RESUMO
Glomerulonephritis are the result of an inflammatory hit to the glomerulus. They are rare and heterogeneous renal diseases. Each glomerular compartment can be affected. The clinical manifestations present with hematuria, proteinuria and/or impaired renal function, either isolated or combined. Two main clinico-biological syndromes are described: nephrotic syndrome and nephritic syndrome. The latter can present in a more severe form i.e. rapidly progressive glomerulonephritis with the worst prognosis. These different clinical pictures are related to specific glomerular lesions. Thus, podocytic damage is mainly responsible for nephrotic syndromes, mesangial damage is responsible for proteinuria and hematuria and, finally, endothelial damage is responsible for nephritic syndrome and rapidly progressive glomerulonephritis. Therapeutic approaches include non-specific measures, combining both life-style and pharmacological interventions with the aim to reduce risk factors, and specific measures with the use of different immunosuppressive agents.
: Les glomérulonéphrites sont des atteintes inflammatoires du glomérule. Il s'agit de pathologies rénales rares et hétérogènes. Tous les compartiments glomérulaires peuvent être touchés. Les répercussions cliniques sont diverses. Elles se manifestent par une hématurie, une protéinurie et/ou une altération de la fonction rénale, présente chacune de manière isolée ou combinée. Deux principaux syndromes clinico-biologiques sont décrits : le syndrome néphrotique et le syndrome néphritique. Au sein de cette dernière entité, on distingue une forme plus sévère, les glomérulonéphrites rapidement progressives grevées du plus mauvais pronostic. Ces différents tableaux cliniques sont en lien avec des lésions glomérulaires spécifiques. Ainsi, les atteintes podocytaires sont principalement responsables des syndromes néphrotiques, les atteintes mésangiales sont responsables de protéinurie et d'hématurie et les atteintes endothéliales sont responsables de syndromes néphritiques et de glomérulonéphrites rapidement progressives. Les approches thérapeutiques comprennent des mesures non spécifiques, hygiéno-diététiques et pharmacologiques, visant à réduire les différents facteurs de risque, et des mesures spécifiques avec l'utilisation de divers médicaments immunosuppresseurs.
Assuntos
Glomerulonefrite , Nefropatias , Síndrome Nefrótica , Glomerulonefrite/diagnóstico , Glomerulonefrite/terapia , Hematúria/etiologia , Hematúria/patologia , Humanos , Nefropatias/complicações , Glomérulos Renais/patologia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapia , Proteinúria/etiologiaRESUMO
Renal allograft rejection involves many mechanisms of innate and adaptive immunity, responsible for parenchymal inflammatory lesions that negatively impact the long-term outcomes of the renal allograft. The heterogeneous presentations of rejections in terms of clinical, biological and histological aspects make them difficult to manage in daily clinical practice. Indeed, current therapeutic strategies are disappointing in term of long-term outcomes, including graft survival. In this article, we will discuss the main effector mechanisms of rejection and their histological classification, as well as the existing treatments and those currently under evaluation.
: Le rejet du greffon rénal fait intervenir de nombreux mécanismes de l'immunité innée et adaptative, responsables de lésions inflammatoires parenchymateuses impactant négativement le devenir au long cours du greffon rénal. La grande hétérogénéité dans la présentation clinique, biologique et histologique des rejets de greffe en fait des entités difficiles à prendre en charge en pratique clinique quotidienne. En effet, les stratégies thérapeutiques actuelles montrent des résultats assez décevants pour le traitement des rejets, ce qui a comme conséquence une diminution significative de la survie des greffons. Nous aborderons dans cet article les principaux mécanismes effecteurs des rejets, leur classification histologique ainsi que les traitements existants et en cours de validation.
Assuntos
Rejeição de Enxerto , Transplante de Rim , Aloenxertos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversosRESUMO
PURPOSE: [18F]FDG PET/CT may predict the absence of acute allograft rejection (AR) in kidney transplant recipients (KTRs) with acute kidney injury (AKI). Still, the proposed threshold of 1.6 of the mean of mean standardized uptake values (mSUVmean) in the renal parenchyma needs validation. METHODS: We prospectively performed 86 [18F]FDG PET/CT in 79 adult KTRs who underwent per-cause transplant biopsy for suspected AR. Biopsy-proven polyoma BK nephropathies (n = 7) were excluded. PET/CT was performed 192 ± 18 min after administration of 254.4 ± 30.4 MBq of [18F]FDG. The SUVmean was measured in both upper and lower poles of the renal allograft. One-way analysis of variance (ANOVA) and Tukey's studentized range test were sequentially performed. The receiver operating characteristic (ROC) curve was drawn to discriminate "AR" from non-pathological ("normal" + "borderline") conditions. RESULTS: The median age of the cohort was 55 [43; 63] years, with M/F gender ratio of 47/39. The mean eGFR was 31.9 ± 14.6 ml/min/1.73m2. Biopsies were categorized in 4 groups: "normal" (n = 54), "borderline" (n = 9), "AR" (n = 14), or "others" (n = 2). The median [min; max] mSUVmean reached 1.72 [1.02; 2.07], 1.97 [1.55; 2.11], 2.13 [1.65, 3.12], and 1.84 [1.57; 2.12] in "normal," "borderline," "AR," and "others" groups, respectively. ANOVA demonstrated a significant difference of mSUVmean among groups (F = 13.25, p < 0.0001). The ROC area under the curve was 0.86. Test sensitivity and specificity corresponding to the threshold value of 1.6 were 100% and 30%, respectively. CONCLUSION: [18F]FDG PET/CT may help noninvasively prevent inessential transplant biopsies in KTR with AKI.
Assuntos
Fluordesoxiglucose F18 , Transplante de Rim , Adulto , Aloenxertos , Rejeição de Enxerto/diagnóstico por imagem , Humanos , Rim , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos RadiofarmacêuticosRESUMO
COVID-19 has been the center of global attention and concern for the last months. Patients undergoing dialysis and especially those treated at the hospital are likely to be infected, due to their mandatory presence at the hospital several times a week and due to their intrinsic fragility in regard of chronic kidney disease, often an older age, and the presence of many associated comorbidities. Thereby, patients with chonic kidney disease treated by haemodialysis have higher odds of a more severe COVID-19 infection with a high mortality rate. Prevention is thus a high priority for these patients.
Au cours des derniers mois, la COVID-19 a été au centre des préoccupations et de l'attention de chacun. Les patients dialysés, et surtout ceux hémodialysés en centre, représentent une population particulièrement à risque de contamination vu la nécessité de se rendre à l'hôpital plusieurs fois par semaine et compte tenu de leur fragilité intrinsèque liée au statut de malade rénal chronique, un âge souvent plus avancé, et de nombreuses comorbidités. Ils ont donc un risque de développer une infection grave et potentiellement mortelle. Dès lors, la stratégie de prévention est d'une importance capitale pour ces patients.
Assuntos
Infecções por Coronavirus , Falência Renal Crônica , Pandemias , Pneumonia Viral , Diálise Renal , Idoso , Betacoronavirus , COVID-19 , Humanos , Falência Renal Crônica/terapia , SARS-CoV-2RESUMO
The SARS-CoV-2 virus causes a respiratory distress syndrome, the main symptom of COVID-19 (for "COronaVIrus Disease 2019"). This infectious disease has been causing a major health and socio-economic pandemic since December 2019. The pulmonary alveolus is regarded as the main target of SARS-CoV-2. However, this coronavirus is capable of directly or indirectly affecting other organs, including the kidneys. Here, we summarize the presumed pathophysiology of COVID-19 renal disease. The incidence of acute kidney injury ranges from 0,5 to 22 % of all patients infected with SARS-CoV-2. The need for renal replacement therapy is reported in 5-9 % of patients in intensive care. Histological analysis of renal biopsies mainly shows acute tubular necrosis of varying severity, as well as the congestion of glomerular and peri-tubular capillaries. Endothelitis has been described in few cases. Evidence for a factual inflammation of the glomerulus remains controversial. The medium/long term consequences of COVID-19 nephropathy are unknown and will deserve a tight follow-up.
Le virus SARS-CoV-2 provoque un syndrome de détresse respiratoire aiguë, le symptôme principal de l'infection COVID-19 (pour «COronaVIrus Disease 2019¼). Cette maladie infectieuse provoque une pandémie de gravité sanitaire et socio-économique majeure depuis décembre 2019. La cible principale du SARS-CoV-2 serait l'alvéole pulmonaire. Néanmoins, ce coronavirus est capable d'affecter directement ou indirectement d'autres organes, y compris les reins. Nous résumons ici la physiopathologie présumée de l'atteinte rénale de la COVID-19. L'incidence de l'insuffisance rénale aiguë varie entre 0,5 à 22 % de tous les patients infectés par le SARS-CoV-2. La nécessité d'une épuration extra-rénale est rapportée chez 5-9 % des patients pris en charge aux soins intensifs. L'analyse histologique de biopsies rénales montre, principalement, une nécrose tubulaire aiguë de sévérité variable, ainsi qu'une congestion des capillaires glomérulaires et péri-tubulaires. Une endothélite a parfois été décrite. L'atteinte inflammatoire du glomérule reste débattue. Les conséquences à moyen/long termes de la néphropathie COVID-19 sont inconnues et mériteront un suivi étroit.
Assuntos
Injúria Renal Aguda , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Injúria Renal Aguda/complicações , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , SARS-CoV-2RESUMO
Chronic kidney disease (CKD) impairs the quality of life and increases the risk for cardiovascular morbimortality. Intensive research is conducted in order to slow down CKD development and progression. During the past decade, a better understanding of the pathophysiological mechanisms of glomerular diseases has highlighted the benefits of rituximab. Progresses have also been made in the understanding of the mechanisms of autosomal polycystic kidney disease, the most frequent inherited kidney disease. These observations led to the discovery and validation of tolvaptan, a blocker of the V2 receptor of the antidiuretic hormone as an innovative treatment. Type 2 diabetic disease is the leading cause worldwide of endstage kidney disease and dialysis. The development of new drugs, such as the gliflozins (inhibiting the sodium glucose reabsorption in the proximal tubule), has contributed to an improvement in the management of the cardiovascular and renal risks especially reducing congestive heart failure rate. Another important progress in nephrology since the beginning of the new century concerns a more precise estimation of the kidney function, which allows to better evaluate the slope of CKD progression and test the influence of different therapeutic approaches aiming at correcting anemia, hyperkalemia, metabolic acidosis and disturbances of calcium and phosphate. The present review summarizes all of these major advances in the field of CKD diagnosis and treatment, and envisions the future of nephrology for the next decade.
L'insuffisance rénale chronique (IRC) altère la qualité de vie, expose à une morbi-mortalité cardiovasculaire majorée, et peut conduire à la dialyse chronique et/ ou la transplantation rénale. Tout progrès qui freinerait le développement et la progression de cette IRC est le bienvenu. Au cours de ces dernières années, une meilleure compréhension des mécanismes physiopathologiques de certaines maladies glomérulaires a permis l'utilisation d'un traitement plus ciblé, le rituximab, qui apporte une nouvelle option dans des situations difficiles. Des progrès ont également été faits dans la compréhension des mécanismes expliquant la perte de fonction rénale chez le patient atteint de polykystose rénale autosomique dominante, la maladie rénale génétique la plus fréquente. Les études cliniques ont permis de démontrer la néphro-protection du tolvaptan, un antagoniste des récepteurs V2 de l'hormone antidiurétique. Dans le domaine du diabète de type 2, première cause mondiale de prise en charge en dialyse, l'avènement des gliflozines (inhibiteurs de la réabsorption tubulaire rénale de glucose et de sodium) a été une réelle révolution thérapeutique pour freiner l'évolution de l'insuffisance rénale chronique et limiter le risque cardiovasculaire (surtout la décompensation cardiaque) de ces patients. Enfin, une meilleure estimation de la fonction rénale a permis de mieux situer le patient dans sa vitesse de progression à travers les différents stades de l'IRC. Ce faisant, la gestion des anomalies métaboliques rencontrées au cours de celle-ci, telles qu'anémie, hyperkaliémie, acidose, troubles du métabolisme phosphocalcique, s'est améliorée. Cette revue fait état des avancées majeures dans le domaine du diagnostic de l'IRC et de ses traitements et envisage le futur de la néphrologie dans les 10 prochaines années.
Assuntos
Nefrologia , Insuficiência Renal Crônica , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Rim , Nefrologia/tendências , Qualidade de Vida , Insuficiência Renal Crônica/terapia , TolvaptanRESUMO
Diabetic nephropathy is a complication of diabetes that affects 25-40 % of diabetic patients. This complication is usually associated with other microangiopathic disorders. We describe a case of a patient suffering from type 2 diabetes with proteinuria, and no signs of retinopathy. This case allows us to discuss and review different etiologies of proteinuria in diabetic patients, particularly in patients who don't suffer from retinopathy.
La néphropathie diabétique est une complication qui affecte 25 à 40 % des patients diabétiques. Cette complication est classiquement associée à d'autres atteintes microangiopathiques. Nous rapportons ici l'histoire d'un patient diabétique de type 2 présentant une protéinurie sans signes de rétinopathie. Ce cas permet de discuter des différentes étiologies d'une protéinurie chez les patients diabétiques, en particulier chez les patients sans rétinopathie.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Glomerulonefrite/etiologia , Neoplasias Pulmonares/diagnóstico , Idoso , Diabetes Mellitus Tipo 2/complicações , Evolução Fatal , Glomerulonefrite/diagnóstico , Humanos , Masculino , Proteinúria/etiologiaRESUMO
Alemtuzumab is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease. Multiple sclerosis (MS) patients treated with alemtuzumab are at increased risk for autoimmune adverse events (thyroid disorders, immune thrombocytopenia, and renal disease). The use of alemtuzumab has been associated with the development of renal immune-mediated adverse events in 0.3% of patients in clinical trials in MS, which generally occurred within 39 months of the last administration. Both anti-GBM disease and membranous nephropathy have been associated with the use of alemtuzumab. Early detection is necessary to allow for early diagnosis and prevent adverse renal and patient outcomes. Through the implementation of the risk minimization measures, patients can be diagnosed, and treated if needed, early allowing for generally favorable outcomes. This important goal can be reached through health care professional and patient education, careful analysis of the monthly lab tests, and close collaboration between the patient, neurologist, and the nephrologist. This article presents the consensus of Belgian MS specialists and nephrologists on the practicalities of diagnosis, management, and treatment of alemtuzumab-associated renal adverse events based on good clinical practice.
Assuntos
Alemtuzumab/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Consenso , Gerenciamento Clínico , Nefropatias , Esclerose Múltipla/tratamento farmacológico , Bélgica/epidemiologia , Diagnóstico Precoce , Feminino , Humanos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Nefropatias/terapia , Masculino , Esclerose Múltipla/epidemiologiaRESUMO
Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary biopsy. AR involves recruitment of leukocytes avid for fluorodeoxyglucose F(18) ((18) F-FDG), thus (18) F-FDG positron emission tomography (PET) coupled with computed tomography (CT) may noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 (18) F-FDG PET/CT scans in 31 adult KTRs with suspected AR who underwent transplant biopsy. Biopsies were categorized into four groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6, including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all groups. PET/CT was performed 201 ± 18 minutes after administration of 3.2 ± 0.2 MBq/kg of (18) F-FDG, before any immunosuppression change. Mean standard uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs reached 1.5 ± 0.2, 1.6 ± 0.3, 2.9 ± 0.8, and 2.2 ± 1.2 for the normal, borderline, AR, and other groups, respectively. One-way analysis of variance demonstrated a significant difference of mean SUVs among groups. A positive correlation between mean SUV and acute composite Banff score was found, with r(2) = 0.49. The area under the receiver operating characteristic curve was 0.93, with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In conclusion, (18) F-FDG PET/CT may help noninvasively prevent avoidable transplant biopsies in KTRs with suspected AR.
Assuntos
Fluordesoxiglucose F18/administração & dosagem , Rejeição de Enxerto/diagnóstico por imagem , Transplante de Rim , Imagem Multimodal/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons/métodos , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Transplante Homólogo , Adulto JovemRESUMO
We report the case of an acute renal failure due to an acute interstitial nephropathy (ATIN) induced by non steroidal anti-inflammatory drugs (NSAID). Even though this pathology is a rare cause of acute renal failure, it still requires special attention in view of the fact that it induces a high risk of acute morbidity but it also can evolve into chronic renal failure. Its differential diagnosis with other causes of acute renal failure becomes essential because of the different therapeutic care. In this article, we are going to briefly sum up the reasoning to adopt in order to diagnose an acute renal failure.
Assuntos
Injúria Renal Aguda/etiologia , Nefrite Intersticial/diagnóstico , Anti-Inflamatórios não Esteroides/efeitos adversos , Feminino , Humanos , Nefrite Intersticial/induzido quimicamente , Adulto JovemRESUMO
We report the case of a patient diagnosed with a villous adenoma of the duodenum showing high degree dysplasia who developed a nephrotic syndrome (NS) due to a membranous nephropathy (MN), demonstrated by renal biopsy. Only the endoscopic resection of the duodenal adenoma could control the NS. The first manifestation of a MN is often the development of a NS. Up to 20% of patients older than 65 years who develop a MN have cancer. Tumours most often identified are those of lung, prostate and digestive tract. A renal biopsy is required to identify this type of nephropathy. If a diagnosis of MN is made, an associated tumour should be looked for.
Assuntos
Adenoma Viloso/cirurgia , Neoplasias Duodenais/cirurgia , Duodenoscopia , Síndrome Nefrótica/cirurgia , Adenoma Viloso/complicações , Adenoma Viloso/patologia , Idoso de 80 Anos ou mais , Neoplasias Duodenais/complicações , Neoplasias Duodenais/patologia , Feminino , Glomerulonefrite Membranosa/complicações , Humanos , Síndrome Nefrótica/complicações , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/patologia , Resultado do TratamentoRESUMO
Glomerular diseases remain frequent causes of end-stage renal failure. Immunosuppressive drugs in association with corticosteroids induce remission of proteinuria and stabilize renal function, as well as prevent relapses, but are responsible for severe potential side-effects: infections, secondary malignancies, sterility and alopecia, and even nephrotoxicity. Mycophenolate mofetil (MMF), a well-known drug in transplantation, presents interesting characteristics potentially useful in the treatment of glomerulopathies. Moreover, its side-effect profile is safer. The present review of the literature suggests that MMF is efficient for the treatment of glomerular disease, even if the results of the different studies remain limited and require further confirmation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Anti-Inflamatórios não Esteroides/farmacologia , Humanos , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêuticoRESUMO
Dapsone is a sulfone essentially used to treat leprae. We describe, here, a somewhat rare indication of dapsone: corticoid sparing in the treatment of particular forms of Henoch-Schönlein.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dapsona/uso terapêutico , Vasculite por IgA/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Dapsona/administração & dosagem , Resistência a Medicamentos , Quimioterapia Combinada , Humanos , MasculinoRESUMO
AL amyloidosis is a rare systemic disease resulting from tissue accumulation of amyloid fibrils derived from monoclonal immunoglobulin light chains. It can disrupt the tissue architecture and consequently cause organ dysfunction. The prognosis is poor with a median survival of 13 months in untreated patients. By illustrating the case of a patient whose AL amyloidosis was detected after presenting a nephrotic syndrome, the characteristics of the disease are reviewed as well as diagnostic criteria and current available therapeutics.
Assuntos
Amiloidose/complicações , Amiloidose/diagnóstico , Síndrome Nefrótica/etiologia , Biópsia por Agulha , Progressão da Doença , Evolução Fatal , Humanos , Imuno-Histoquímica , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/terapia , Índice de Gravidade de Doença , Ultrassonografia DopplerRESUMO
Primary aldosteronism is a rare cause of hypertension. However, its incidence seems to be underestimated. It is important to identify this syndrom since the disease is potentially curable. In the present paper, we depict different forms of primary aldosteronism as well as the diagnostic procedures. When the diagnosis is suspected (hypertension associated to spontaneous or diuretic-induced hypokaliemia), the more efficient screening test is the determination of the aldosteron/renin ratio. Saline infusion or posture tests can thereafter confirm the diagnosis. Differential diagnosis between bilateral and unilateral forms of primary aldosteronism can be made by CT-scanner and the response of aldosterone to the posture test. Such a complex assessment leads to the identification of patients who can be surgically treated. This treatment consists in a unilateral adrenalectomy which can be realised by laparoscopy.
Assuntos
Hiperaldosteronismo/complicações , Hipertensão/etiologia , Aldosterona/fisiologia , Árvores de Decisões , Humanos , Hipertensão/diagnóstico , Hipertensão/terapiaRESUMO
UNLABELLED: Factors determining the percentage of hypochromic red blood cells determines iron status in hemodialysis patients. BACKGROUND: Determination of the percentage of hypochromic red blood cells (RBC; %HYPO) has been advocated as a sensitive index of functional iron deficiency during erythropoietin (EPO) therapy in hemodialyzed patients. METHODS: The significance of %HYPO in chronic renal failure was evaluated in 64 chronically hemodialyzed patients. The linear correlation was determined between %HYPO and 13 variables, including age, sex, weight, C-reactive protein (CRP), ferritin, transferrin (Tf), Tf saturation, soluble Tf receptor (sTfR), serum iron (SI), urea, parathormone, dialysis dose (Kt/V), dose of EPO administered (EPO), and absolute reticulocyte count. Multiple regression analyses were then performed to select the parameters that jointly provide the best prediction of %HYPO. RESULTS: Univariate analysis showed significant correlations between %HYPO and iron parameters (sTfR, Tf saturation, SI, and ferritin, in decreasing order), EPO, reticulocyte count, and CRP. Multivariate analysis yielded an equation showing that the variation of %HYPO is essentially associated with the combined changes in sTfR, CRP, and EPO dosage. CONCLUSIONS: %HYPO is a meaningful and inexpensive parameter that reflects the integrated effects of iron stores, inflammation, and erythropoietic stimulation on iron availability in hemodialyzed patients. Among iron exchange parameters, sTfR is the best predictor of %HYPO, followed by Tf saturation, SI, and ferritin.