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Nature Reviews. Disease Primers Nov 2023IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN... (Review)
Review
IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis. IgAN has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring. IgAN can only be diagnosed by kidney biopsy. Extensive, optimized supportive care is the mainstay of therapy for patients with IgAN. For those at high risk of disease progression, the 2021 KDIGO Clinical Practice Guideline suggests considering a 6-month course of systemic corticosteroid therapy; however, the efficacy of systemic steroid treatment is under debate and serious adverse effects are common. Advances in understanding the pathophysiology of IgAN have led to clinical trials of novel targeted therapies with acceptable safety profiles, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components.
Topics: Humans; Glomerulonephritis, IGA; Antigen-Antibody Complex; Galactose; Immunoglobulin A
PubMed: 38036542
DOI: 10.1038/s41572-023-00476-9 -
Nature Reviews. Disease Primers Apr 2017Bladder cancer is a highly prevalent disease and is associated with substantial morbidity, mortality and cost. Environmental or occupational exposures to carcinogens,... (Review)
Review
Bladder cancer is a highly prevalent disease and is associated with substantial morbidity, mortality and cost. Environmental or occupational exposures to carcinogens, especially tobacco, are the main risk factors for bladder cancer. Most bladder cancers are diagnosed after patients present with macroscopic haematuria, and cases are confirmed after transurethral resection of bladder tumour (TURBT), which also serves as the first stage of treatment. Bladder cancer develops via two distinct pathways, giving rise to non-muscle-invasive papillary tumours and non-papillary (solid) muscle-invasive tumours. The two subtypes have unique pathological features and different molecular characteristics. Indeed, The Cancer Genome Atlas project identified genetic drivers of muscle-invasive bladder cancer (MIBC) as well as subtypes of MIBC with distinct characteristics and therapeutic responses. For non-muscle-invasive bladder cancer (NMIBC), intravesical therapies (primarily Bacillus Calmette-Guérin (BCG)) with maintenance are the main treatments to prevent recurrence and progression after initial TURBT; additional therapies are needed for those who do not respond to BCG. For localized MIBC, optimizing care and reducing morbidity following cystectomy are important goals. In metastatic disease, advances in our genetic understanding of bladder cancer and in immunotherapy are being translated into new therapies.
Topics: Biomarkers; Cystectomy; DNA-Binding Proteins; E2F3 Transcription Factor; Humans; Neoadjuvant Therapy; Occupational Exposure; Quality of Life; Receptor, Fibroblast Growth Factor, Type 3; Retinoblastoma Binding Proteins; Risk Factors; Smoking; Tuberous Sclerosis Complex 1 Protein; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Urinary Bladder Neoplasms
PubMed: 28406148
DOI: 10.1038/nrdp.2017.22 -
Pediatric Clinics of North America Feb 2019The causes of macroscopic and microscopic hematuria overlap; both are often caused by urinary tract infections or urethral/bladder irritation. Coexistent hypertension... (Review)
Review
The causes of macroscopic and microscopic hematuria overlap; both are often caused by urinary tract infections or urethral/bladder irritation. Coexistent hypertension and proteinuria should prompt investigation for glomerular disease. The most common glomerulonephritis in children is postinfectious glomerulonephritis. In most patients, and especially with isolated microscopic hematuria, the diagnostic workup reveals no clear underlying cause. In those cases whereby a diagnosis is made, the most common causes of persistent microscopic hematuria are thin basement membrane nephropathy, immunoglobulin A nephropathy, or idiopathic hypercalciuria. Treatment and long-term prognosis varies with the underlying disease.
Topics: Child; Diagnosis, Differential; Glomerulonephritis, IGA; Hematuria; Humans; Hypercalciuria; Hypertension; Kidney Diseases; Proteinuria; Urinary Tract Infections
PubMed: 30454740
DOI: 10.1016/j.pcl.2018.08.003 -
Nature Reviews. Disease Primers Feb 2016Globally, IgA nephropathy (IgAN) is the most common primary glomerulonephritis that can progress to renal failure. The exact pathogenesis of IgAN is not well defined,... (Review)
Review
Globally, IgA nephropathy (IgAN) is the most common primary glomerulonephritis that can progress to renal failure. The exact pathogenesis of IgAN is not well defined, but current biochemical and genetic data implicate overproduction of aberrantly glycosylated IgA1. These aberrant immunoglobulins are characterized by galactose deficiency of some hinge-region O-linked glycans. However, aberrant glycosylation alone is insufficient to induce renal injury: the participation of glycan-specific IgA and IgG autoantibodies that recognize the undergalactosylated IgA1 molecule is required. Glomerular deposits of immune complexes containing undergalactosylated IgA1 activate mesangial cells, leading to the local overproduction of cytokines, chemokines and complement. Emerging data indicate that mesangial-derived mediators that are released following mesangial deposition of IgA1 lead to podocyte and tubulointerstitial injury via humoral crosstalk. Patients can present with a range of signs and symptoms, from asymptomatic microscopic haematuria to macroscopic haematuria. The clinical progression varies, with 30-40% of patients reaching end-stage renal disease 20-30 years after the first clinical presentation. Currently, no IgAN-specific therapies are available and patients are managed with the aim of controlling blood pressure and maintaining renal function. However, new therapeutic approaches are being developed, building upon our ever-improving understanding of disease pathogenesis.
Topics: Genetic Predisposition to Disease; Glomerulonephritis, IGA; Hematuria; Humans; Hypertension; Immunoglobulin A; Kidney; Proteinuria; Renal Insufficiency
PubMed: 27189177
DOI: 10.1038/nrdp.2016.1 -
Indian Journal of Pediatrics Aug 2020Hematuria is one of the alarming manifestations of a renal disease. It can present as macroscopic hematuria or microscopic hematuria due to either glomerular or... (Review)
Review
Hematuria is one of the alarming manifestations of a renal disease. It can present as macroscopic hematuria or microscopic hematuria due to either glomerular or non-glomerular disorders. Clinical presentation and urine microscopy can differentiate glomerular from non-glomerular hematuria. In the majority, a good clinical examination and basic investigations including a urine microscopic examination with sophisticated tools like phase contrast and automated microscopes can help differentiate glomerular from non-glomerular causes for hematuria. Drug induced hematuria, especially secondary to use of analgesics needs to be recognized in routine clinical practice. Rarer causes of hematuria may need more detailed evaluation with a renal biopsy, electron microscopy, urine biochemical testing and imaging. There is no specific treatment to resolve or prevent hematuria. Resolution of hematuria usually occurs with appropriate management of the underlying disorder. Persistent microscopic hematuria indicates the presence of a renal disease that warrants close monitoring and evaluation. Prompt referral to a pediatric nephrologist is indicated in situations when hematuria does not resolve within 2 weeks of onset of glomerulonephritis, there is a need for a renal biopsy, in the presence of persistent microscopic hematuria and need for specific urine biochemistry testing or imaging studies.
Topics: Child; Glomerulonephritis; Hematuria; Humans; Kidney Diseases; Microscopy; Urinalysis
PubMed: 32026313
DOI: 10.1007/s12098-020-03184-4 -
Clinical Journal of the American... Nov 2020Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman-Tukey double-arcsine transformations were used to stabilize variance as complications were rare.
RESULTS
A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location.
CONCLUSIONS
Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.
Topics: Blood Transfusion; Hematoma; Hematuria; Hemostasis, Surgical; Hospitalization; Humans; Image-Guided Biopsy; Kidney; Kidney Diseases; Pain; Risk Factors
PubMed: 33060160
DOI: 10.2215/CJN.04710420 -
British Journal of Hospital Medicine... May 2021Haematuria is a common finding in children and can be macroscopic or microscopic. In contrast to adults, haematuria in children very rarely indicates an underlying... (Review)
Review
Haematuria is a common finding in children and can be macroscopic or microscopic. In contrast to adults, haematuria in children very rarely indicates an underlying malignant pathology. The differential diagnosis is broad, with the most common underlying causes being infection, glomerulonephritis and hypercalciuria. It is useful to distinguish between nephrological or upper urinary tract and lower urinary tract pathologies, as this will guide investigations and referral. This review discusses the causes of haematuria in the paediatric population.
Topics: Adult; Child; Diagnosis, Differential; Hematuria; Humans; Referral and Consultation; Urinary Bladder
PubMed: 34076519
DOI: 10.12968/hmed.2021.0046 -
Indian Journal of Pediatrics Oct 2017Dysuria and/or hematuria are common and worrisome symptoms for most parents. Dysuria results from excessive bladder muscle contraction and peristaltic activity of the... (Review)
Review
Dysuria and/or hematuria are common and worrisome symptoms for most parents. Dysuria results from excessive bladder muscle contraction and peristaltic activity of the edematous and inflamed urethral mucosa. Though urinary tract infection remains the commonest cause for dysuria, non-infectious causes should also be kept in mind. Equating all cases of dysuria to urinary infection is not incorrect. Hematuria can be both macroscopic and microscopic and an important sign of genitourinary tract disease. However, systemic causes like bleeding disorder or malignancy can also present with hematuria. A thorough history and physical examination is important for arriving at a diagnosis. The investigations for both the symptoms and the urgency with which the tests are required are dictated by the patient's clinical presentation.
Topics: Algorithms; Child; Dysuria; Hematuria; Humans
PubMed: 28875437
DOI: 10.1007/s12098-017-2448-4 -
Medicina 2019Nutcracker syndrome is a vascular anomaly consisting in the compression of the left renal vein between the superior mesenteric artery and the aorta. Clinical features in...
Nutcracker syndrome is a vascular anomaly consisting in the compression of the left renal vein between the superior mesenteric artery and the aorta. Clinical features in nutcracker syndrome include pelvic pain, flank pain, haematuria, gonadal varices or simply asymptomatic. We are presenting two cases, one of them with macroscopic haematuria and flank pain and the other was studied for hypertension but with previous antecedents of left renal vein embolization in the setting of varicocele. We discuss the clinical presentation as well as diagnostic and therapeutic aspects related to this syndrome.
Topics: Adolescent; Adult; Computed Tomography Angiography; Female; Hematuria; Humans; Renal Nutcracker Syndrome; Renal Veins
PubMed: 31048282
DOI: No ID Found