Development of a Conceptual Model for the Patient Experience of Immunoglobulin A Nephropathy (IgAN): A Qualitative Literature Review.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is a kidney disorder that can lead to progressive kidney disease. Currently, there lacks a comprehensive overview of the symptoms and impacts experienced by those living with IgAN that would help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in clinical trials. The aim of this study was to develop a conceptual model of the adult and pediatric patient experience of IgAN, including disease signs and symptoms, treatment side effects, and impact on functioning and well-being. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and children diagnosed with IgAN. Data sources were identified through an electronic database search of journal articles (MEDLINE, Embase, PsycINFO; June 2021), hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from articles. Extracted data were qualitatively analyzed, aided by ATLAS.ti v7. Codes were applied to data; concepts (i.e., symptoms) were identified, named, and refined. A conceptual model was developed by grouping related concepts into domains. RESULTS: In total, five sources were identified for analysis: two journal articles, two online anthologies of patient stories, and one patient organization-sponsored "Voice of the Patient" meeting report. Conceptual model symptom domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight gain, sleep problems, urinary problems, and gastrointestinal problems. Impact domains included emotional/psychological well-being, physical functioning/activities of daily living, social functioning, work/school, and relationships. CONCLUSIONS: Secondary analysis of published qualitative literature permitted development of a novel conceptual model depicting the patient experience of IgAN; however, its depth is limited by a lack of available literature. Further qualitative research is recommended to refine and/or confirm the concepts and domains, determine any relationships between them, and explore the outcomes that are most meaningful to patients. The refined model will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future IgAN clinical trials.

Pericardial Tamponade and Berger's Disease: An Unusual Association.

Cardiac tamponade is considered a medical emergency because a patient can deteriorate easily and die of cardiac arrest if the fluid is not drained immediately. The most common etiologies are the same as pericarditis as fluid accumulates due to pericardial inflammation, including infection, malignancy, trauma, iatrogenic, autoimmune, post-myocardial infarction, radiation, and renal failure. Although the treatment is pericardiocentesis or pericardial window, finding the etiology responsible for the development of pericardial effusion is important. Here, we describe the case of a 40-year-old female who presented to the emergency department with a chief complaint of severe epigastric pain of a two-day duration that was associated with multiple episodes of nausea, vomiting, dysphagia, and severe shortness of breath (New York Heart Association III). The patient was eventually diagnosed with cardiac tamponade as a cause of her dyspnea, as a two-dimensional cardiac echocardiogram detected a large pericardial effusion (>2 cm) with echocardiographic indications for cardiac tamponade with severe pulmonary hypertension. The patient underwent a therapeutic pericardial window with drainage of 250 mL of pericardial fluid. Ultrasound of the abdomen focusing on the kidneys showed an atrophic and echogenic right kidney with a bidirectional flow in the hepatic veins, suggestive of right heart failure. Subsequently, she underwent a kidney biopsy that showed diffuse mesangial proliferative glomerulonephritis with segmental sclerosing features consistent with IgA nephropathy, associated with tubular atrophy, interstitial fibrosis, interstitial inflammation, and moderate arteriosclerosis. The patient was diagnosed with stage V chronic kidney disease secondary to IgA nephropathy. IgA nephropathy is usually common in Caucasian or Asian males in their teens and late 30s, with hematuria as a usual presentation. This case is unique as cardiac tamponade with renal failure is rarely the presenting symptom of IgA nephropathy.

A young boy with severe pulmonary-renal syndrome: Will you suspect IgA nephropathy?

IgA nephropathy is a renal-limited form of systemic vasculitis, and pulmonary manifestations are uncommon. An initial presentation with severe diffuse alveolar hemorrhage (DAH) or pulmonary-renal syndrome is rare and only confined to a few case reports. Herein, we present a young male admitted with acute-onset dyspnea, hemoptysis, and rapidly progressive renal failure. With an initial diagnosis of an immune-mediated pulmonary-renal syndrome, he was treated with high-dose corticosteroids and therapeutic plasmapheresis along with intensive organ support (including hemodialysis, red cell transfusion, and high-flow oxygen). After a detailed laboratory evaluation and kidney biopsy, IgA nephropathy was diagnosed. The patient continued to worsen with persistent DAH and died. IgA nephropathy-associated severe DAH or pulmonary-renal syndrome is rare but increasingly recognized. The condition is difficult to diagnose early and has no proven disease-targeted therapy.

Severe bilateral visual loss as the first sign of IgA nephropathy / Perda visual bilateral grave como o primeiro sinal da nefropatia por IgA

ABSTRACT We describe a case of a 33-years-old woman who presents with severe acute bilateral visual loss secondary to massive exudative hypertensive maculopathy as the first sign of immunoglobulin A nephropathy. The patient's ophthalmic examination showed bilateral cotton-wool spots, flame-shaped retinal hemorrhages, diffuse narrow arterioles, optic disk edema, and exudative maculopathy. Systemic workup demonstrated a systolic and diastolic blood pressure of 240 mmHg and 160 mmHg, respectively, proteinuria, and hematuria, suggesting kidney disease as the causative condition. A kidney biopsy confirmed immunoglobulin A nephropathy. She was treated with systemic corticosteroids, antihypertensive drugs, and a single bilateral intravitreal injection of aflibercept. There was a prompt resolution of macular edema and vision improvement. Our case draws attention to the fact that severe bilateral visual loss can be the first sign of severe hypertension. Secondary causes, such as immunoglobulin A nephropathy, should be ruled out.

RESUMO Nosso objetivo é descrever uma paciente de 33 anos de idade, com perda visual bilateral grave por maculopatia hipertensiva exsudativa como o primeiro sinal da nefropatia por imunoglobulina A. A fundoscopia revelou a presença de manchas algodonosas, hemorragias em chama-de-vela, estreitamento arteriolar difuso, edema de disco óptico e maculopatia exsudativa bilateral. A pressão arterial sistólica foi de 240mmHg e a diastólica de 160 mmHg associado a proteinúria e hematúria, sugerindo a presença de doença renal. A biópsia renal confirmou a nefropatia por imunoglobulina A. A paciente foi tratada como corticoide sistêmico, drogas anti-hipertensivas e uma única dose intravítrea de Aflibercept em ambos os olhos. Houve rápida melhora do edema macular e da acuidade visual. Nosso caso chama a atenção para o fato de que a perda visual bilateral grave pode ser a primeira apresentação de uma doença hipertensiva sistêmica. Causas secundárias como a nefropatia por imunoglobulina A devem ser afastadas.

Immunoglobulin A nephropathy in paediatrics: An up-to-date.

Immunoglobulin A nephropathy is the main cause of glomerulonephritis globally and an important aetiology of end-stage renal disease in children. It has been considered an autoimmune disease that can lead to the production of autoantibodies against abnormal IgA1 and formation of immune complexes. These autoantibodies and immune complexes deposit in the glomeruli, resulting in renal injury. At the beginning of IgA nephropathy course, most patients are asymptomatic and the first clinical manifestations in children are macroscopic hematuria and proteinuria. The diagnosis is defined by the detection of IgA mesangial deposits in kidney biopsy using immunofluorescence techniques. The Oxford MEST-C score is the most used classification to associate histological findings and clinical outcomes, being validated for application in children. Recommended treatment options are antihypertensive and antiproteinuric therapy, corticosteroids, immunosuppressive agents, and other non-pharmacological approaches. There is no ideal prognosis indicator but new perspectives are in science's scope to find possible biomarkers of the disease through OMICS's research. This review aims to summarize and to up-to-date the scientific literature on paediatric IgA nephropathy, focusing on pathophysiology, clinical findings, histopathology, current treatment, prognosis, and future perspectives.

Monitoring Immune Responses in IgA Nephropathy: Biomarkers to Guide Management.

IgA nephropathy (IgAN) is the commonest biopsy-reported primary glomerulonephritis worldwide. It has an incidence which peaks among young adults, and 30 to 40% of patients' progress to end stage kidney disease within twenty years of diagnosis. Ten-year kidney survival rates have been reported to be as low as 35% in some parts of the world. The successful management of IgAN is limited by an incomplete understanding of the pathophysiology of IgAN and a poor understanding of how pathophysiology may vary both from patient to patient and between patient groups, particularly across races. This is compounded by a lack of rigorously designed and delivered clinical trials in IgAN. This is slowly changing, with a number of Phase 2 and 3 clinical trials of novel therapies targeting a number of different putative pathogenic pathways in IgAN due to report in the next 5 years. From our current, albeit limited, understanding of the pathophysiology of IgAN it is unlikely a single therapy will be effective in all patients with IgAN. The successful management of IgAN in the future is, therefore, likely to be reliant on targeted therapies, carefully selected based on an individualized understanding of a patient's risk of progression and underlying pathophysiology. The potential role of biomarkers to facilitate personalization of prognostication and treatment of IgAN is immense. Here we review the progress made over the past decade in identifying and validating new biomarkers, with a particular focus on those that reflect immunological responses in IgAN.

Renal failure in thalassemia: Thinking outside the box.

Berger's disease should be considered an imperative cause of renal dysfunction in thalassemia. This case highlights the importance of early diagnosis, clinicopathological correlation and prompt therapy in Berger's disease.

Is it possible to predict parameters of the Oxford classification of primary IgA Nephropathy from clinical laboratory data? Focus on the role of segmental glomerulosclerosis subtypes.

INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and has a broad range of histological and clinical manifestations, ranging from morphologically normal to globally sclerotic glomeruli with clinical manifestations varying from isolated hematuria to end stage renal disease. This study aims to assess sensitivity, specificity and accuracy of clinical data at the time of biopsy in predicting 2017 updated Oxford classification parameters and to investigate if subtypes of segmental sclerosis (FSGS) influence clinical presentation. MATERIAL AND METHODS: Renal biopsies from 103 patients with IgAN were analyzed. Oxford classification was updated and FSGS lesions were subclassified. ROC curves, univariate and multivariate logistic regression were used. RESULTS: In Oxford classification, the majority of patients had mesangial hypercellularity in less than a half of glomeruli (M0), did not have endocapillary hypercellularity (E0), had segmental glomerulosclerosis (S1), had interstitial fibrosis and tubular atrophy in more than a half of the sample (T2) and had no crescents (C0). Hypertension increases the chance of M1 in 2.54x (p = 0.02). For each unit of increased creatinine, 2.6x more chances of E1 (p = 0.001). S1 is predicted by proteinuria with 75% sensitivity and 90.9% specificity (p < 0.0001). For each unit of increase in GFR, there is a reduction of 6% in the chance of T2 in relation to T0 (p = 0.0001). If hypertension, there is 5x more chances of T2 than T0 (p = 0.01). For each unit of increase in creatinine, there are 2.8x more chances of crescents- C (p = 0.003). Creatinine also showed 75.8% sensitivity and 75% specificity for prediction of C (p = 0.002). Inversely, for each unit of GFR, the chance of C is reduced by 4% (p = 0.007). Other clinical data related with C are hypertension (p = 0.03) and proteinuria (p = 0.02). To determine the role of FSGS subtypes in clinical presentation, we divided patients in S0 and S1 groups. Proteinuria was the only clinical parameter with significative difference, respectively, 0.3 (0-2.1) and 1.6 (0.02-16.2) g/24 h (p < 0.0001). FSGS subtypes related to proteinuria were cellular (p = 0.03) and peri-hilar (p = 0.02). Subtypes classically related to podocytopathies showed no correlation with clinical data. CONCLUSION: In the future, with noninvasive methods for diagnosis of IgAN, it will be essential to predict Oxford classification parameters using clinical laboratory data for establishment of prognosis and therapeutics. We showed that Oxford classification parameters correspond to some clinical laboratory data, making this approach possible. FSGS lesions not specifically related to podocytopathies may also influence clinical parameters that affect renal disease progression.

New strategies and perspectives on managing IgA nephropathy.

IgA nephropathy is an inflammatory renal disease characterised by the deposition of IgA in the glomerular mesangium and is the most commonly reported primary glomerulonephritis worldwide. Thirty to forty percent of patients with the disease develop progressive renal function decline, requiring renal replacement therapy within two decades of diagnosis. Despite this, accurate individual risk stratification at diagnosis and predicting treatment response remains a challenge. Furthermore, there are currently no disease specific treatments currently licensed to treat the condition due to long standing challenges in the nature and prevalence of the disease. Despite this, there have been exciting recent advances in the field that may represent paradigm shifts in the way IgA nephropathy is managed in the near future. In this review, we explore the evidence base informing current approaches to management and explore new strategies and future directions in the diagnosis and management of IgA nephropathy.

Epidemiology of IgA Nephropathy: A Global Perspective.

IgA nephropathy (IgAN), or Berger's disease, is the most common primary glomerular disease worldwide, but varies largely in its geographic distribution. A systematic review of 1,619 publications from the five continental regions of the world was performed to assess the prevalence of IgAN in different worldwide regions and analyze factors responsible for geographic differences. All observational studies that described the prevalence and incidence data on glomerulonephritis were considered. IgAN is more frequent in Asian populations (45 cases per million population/y in Japan) than in Caucasians (31 cases per million population/y in France). These differences are owing to some relevant aspects: (1) systematic mass screening of urine in populations, as occurring in some Asian countries (Hong Kong, Japan, Korea, and Singapore), is not common in Western countries; (2) general practitioners and health care professionals in Western countries underestimate persistent microscopic hematuria and/or mild proteinuria in apparently healthy individuals causing late referral to a nephrologist; and (3) nephrologists adopt different indications for kidney biopsy in individuals with persistent urinary abnormalities. In addition, differences also are owing to the source of data, because the frequency of IgAN observed in a nephrology center with a high incidence of kidney biopsies is higher than in a regional renal biopsy registry that receives data from many centers. In conclusion, greater efforts should be made to diagnose IgAN earlier in individuals who manifest persistent microhematuria and/or mild proteinuria and to introduce less stringent indications for kidney biopsies. This preventive approach, followed by early therapy, may reduce the global burden of end-stage kidney disease caused by IgAN.

Nefropatía por IgA. revisión y conducta terapéutica a propósito de un caso clínico / Therapeutic management of an IgA nephropathy case and disease review

La Nefropatía por Inmunoglobulina A (NIgA), también conocida como enfermedad de Berger, fue descrita por primera vez en 1968 por Berger e Hinglais. Se trata de una enfermedad heterogénea, tanto desde el punto de vista clínico, como histológico, caracterizada por la presencia de depósitos mesangiales de IgA. La clínica de presentación es extremadamente variable, pudiendo manifestarse desde microhematuria aislada hasta un deterioro agudo de la función renal por una glomerulonefritis extracapilar superpuesta. Inicialmente se la consideraba una entidad de buen pronóstico, pero con el paso del tiempo y a partir de un mayor conocimiento de la NIgA, se constató que la realidad era otra y que del 20 al 30% de los pacientes a los 20 años evolucionaban a la insuficiencia renal crónica (IRC) terminal y otro 20% mostraba una pérdida significativa de la función renal. En el presente artículo se describe un caso clínico de un paciente en el que se detectan casualmente marcadores de daño renal en la orina, y en quien los hallazgos histológicos observados en la biopsia renal modificaron su pronóstico y la conducta terapéutica. A partir de este caso clínico se realiza una actualización sobre la Nefropatía por IgA

Inmunoglobulin A (NIgA) Nephropathy also known as Berger disease, was described for the first time in 1968 by Berger and Hinglais. It is a heterogeneous disease, not only from clinical point of view but also from the histologicalone. Characterized by the presence of IgA mesangials deposits. Clinical presentation is extremely variable and can vary from isolated microhematuria up to a severe damage of renal function due to superimposed extracapillary glomerulonephritis. Initially it was considered an entity with good prognosis, but over time and more knowledge about IgAN, it was shown that 20 to 30% of 20 years old patients evolved to end stage renal failure and other 20% had important renal function loss. In the present article we describe a case of a patient in whom we detected by chance renal damage markers in the urine, and then the histologic findings observed in renal biopsy, modified the prognosis and therapeutic procedure. From this clinical case, we performed an update on IgA Nephropathy

IgA nephropathy in Brazil: apropos of 600 cases.

IgA nephropathy (IgAN) is th e commonest primary glomerular disease worldwide. Studies on its prevalence in Brazil are however scarce. Databases and clinical records from 10 reference centres were retrospectively reviewed. Clinical and laboratory features at the moment of the biopsy were retrieved (age, gender, presence of hematuria, serum creatinine [mg/dL], proteinuria [g/24 h]). Renal biopsy findings were classified according to Haas single grade classification scheme and the Oxford Classification of IgAN. 600 cases of IgAN were identified, of which 568 (94.7 %) were on native kidneys. Male to female ratio was 1.24:1. Patients averaged 32.76 ± 15.12 years old (range 4-89, median 32). Proteinuria and hematuria were observed, respectively in 56.63 and 72.29 % of patients. The association of both these findings occurred in 37.95 % of the cases. Serum creatinine averaged 1.65 ± 0.67 mg/dL (median 1.5 mg/dL) at diagnosis. Segmental sclerosis and mesangial hypercellularity were the main glomerular findings (47.6 and 46.2 %) The commonest combination by Oxford Classification of IgAN, was M0 E0 S0 T0 (22.4 %). Chronic tubulo-interstitial lesions with an extension wider than 25 % of the renal cortex could be identified in 32.2 % of the cases. Tubular atrophy and interstitial fibrosis were more strongly associated with higher 24-h proteinuria and serum creatinine levels. Segmental sclerosis (S1) showed a stronger tendency of association with the presence of tubulo-interstitial lesions (T1 and T2) than other glomerular variables. To the best of our knowledge this is the largest series of IgAN in Brazil. It depicts the main biopsy findings and their possible clinical correlates. Our set of data is comparable to previous reports.

Caso clínico-anatomopatológico: las diversas presentaciones de la nefropatía por IgA / Clinicopathological case: the various presentations of IgA nephropathy

Se trata de una paciente de 58 años, sexo femenino, que se presenta con hematuria, proteinuria severa y función renal normal. Pocas semanas después, ella desarrolla una trombosis de vena renal, embolia pulmonar secundaria y un episodio de insuficiencia renal aguda. Este caso clínico ilustra las distintas presentaciones clínicas de una nefropatía por IgA grave, incluyendo hematuria, síndrome nefrótico y trombosis de vena renal. Además muestra otras complicaciones serias, como embolia pulmonar y falla renal aguda. La paciente fue sometida a 2 biopsias renales, que permitieron una correlación adecuada entre las manifestaciones clínicas y la patología renal.

This is a female, 58 years old patient, who presented with hematuria, heavy proteinuria and normal kidney function. Few weeks later she developed a renal venous thrombosis, pulmonary embolism and acute kidney injury. This clinical case illustrates the variable presenting features of a severe IgA nephropathy including hematuria, nephrotic syndrome and renal venous thrombosis. Further it shows its possible severe complications such as lung embolism and acute renal failure. The patient was kidney biopsied in two opportunities, which allows assessing the correlation between the variable clinical characteristics and the renal pathology.