Common etiologies of Hematuria

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Elsevier ClinicalKey Clinical Overview

Diagnosis Could indicate benign causes of hematuria or (in the case of certain foods or drugs) discoloration that looks like (but is not) hematuria Streptococcal cellulitis or upper respiratory tract infection associated with glomerulonephritis Precedes hematuria Polycystic kidney disease or medullary sponge kidney Conditions or diseases that cause hypercalciuria Urinary tract endometriosis Accompanies cyclic hematuria Sickle cell trait or disease More common in Black patients Travel to the Middle East or Africa Could indicate schistosomiasis Patients with associated renal failure may have symptoms related to fluid overload (eg, dyspnea, edema) or anemia (eg, palpitations, lightheadedness, fatigue) Consider common conditions that cause micro- or macroscopic hematuria first Urinary tract infection (25% of all cases of atraumatic hematuria; 50% of cases in children) Suprapubic discomfort Urinary frequency Dysuria Urolithiasis (20% of all cases of atraumatic hematuria) Acute onset of severe, colicky flank pain Accompanied by nausea and vomiting Uncommon conditions causing hematuria can be suggested by additional history Infection-related glomerulonephritis (eg, postinfectious glomerulonephritis, poststreptococcal glomerulonephritis) Suggested by a recent skin or upper respiratory tract infection with hematuria after 10 to 21 days IgA nephropathy is suggested if hematuria occurs earlier than 10 days after infection of the upper respiratory tract or other infection (usually 1-2 days after infection develops) Hypercalciuria in children (30% incidence in children with isolated hematuria [only hematuria, no proteinuria])

Diagnosis Origin can be either glomerular or nonglomerular Typically, microscopic hematuria is glomerular in origin and macroscopic hematuria is nonglomerular (urologic) No cause is found in approximately 60% of patients Most common causes of hematuria: Urinary tract infection Bladder cancer Intrinsic renal disease Urolithiasis Most common causes of glomerular hematuria include IgA nephropathy and thin basement membrane disease

Diagnosis Table Title: Causes of hematuria. Table Heads: Table Rows: **Glomerular** _Primary glomerulonephritis_ • Alport syndrome • Thin basement membrane disease • IgA nephropathy • Pauci-immune (ANCA-related) vasculitis/anti-glomerular basement membrane disease _Secondary glomerulonephritis_ • Henoch-Schonlein purpura • Systemic lupus erythematosus • Infection-related glomerulonephritis • Thrombotic microangiopathies (eg, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, scleroderma renal crisis, malignant hypertension) _Associated with other glomerular pathology_ • Diabetic nephropathy • Focal segmental glomerular sclerosis • Minimal change disease • Membranous nephropathy **Tubular/interstitial** • Interstitial nephritis • Papillary necrosis • Analgesic nephropathy • Pyelonephritis **Structural kidney disease -related** • Acquired or hereditary cystic disease • Medullary sponge kidney **Vascular** • Renal vein thrombosis • Renal infarct/necrosis • Arteriovenous malformations • Nutcracker syndrome **Urothelial** • Malignancy (involving the kidney, ureters, bladder, or prostate) • Nephrolithiasis • Nephrocalcinosis • Hypercalciuria • Strictures • Indwelling catheters • Benign prostatic hypertrophy • Bladder or ureteral polyps **Medications** • Cyclophosphamide/ifosfamide

Diagnosis Past or current cigarette smoking Overuse of analgesics (eg, aspirin, NSAIDs) History of gross hematuria History of pelvic irradiation History of irritative voiding symptoms History of urologic disorder History of chronic urinary tract infection History of chronic indwelling foreign body Exposure to carcinogenic agents or chemotherapy (eg, alkylating agents) Family history of urothelial cancer or Lynch syndrome Antithrombotic medications may trigger hematuria (evaluation still required) Among anticoagulants and antiplatelet agents, warfarin is associated with the greatest risk but is unlikely to cause major hematuria Novel antithrombotic agents (eg, dabigatran, rivaroxaban, apixaban) are more commonly associated with major hematuria

2.

Food and Drug Administration (DailyMed).

Publish date: January 4, 2021.

Clinical Studies 14 CLINICAL STUDIES 14.1 Intravenous Mesna Hemorrhagic cystitis produced by ifosfamide is dose dependent ( Table 4 ). At a dose of 1.2 g/m 2 ifosfamide administered daily for 5 days, 16 to 26% of the patients who received conventional uroprophylaxis (high fluid intake, alkalinization of the urine, and the administration of diuretics) developed hematuria (>50 RBC per hpf or macrohematuria) (Studies 1, 2, and 3). In contrast, none of the patients who received mesna injection together with this dose of ifosfamide developed hematuria (Studies 3 and 4). In two randomized studies, (Studies 5 and 6), higher doses of ifosfamide, from 2 g/m 2 to 4 g/m 2 administered for 3 to 5 days, produced hematuria in 31 to 100% of the patients. When mesna was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%. Table 4. Percent of Mesna Patients Developing Hematuria (≥50 RBC/hpf or macrohematuria) *Ifosfamide dose 1.2 g/m 2 d x 5 †Ifosfamide dose 2 g/m 2 to 4 g/m 2 d x 3 to 5 Study Conventional Uroprophylaxis (number of patients) Standard Mesna Intravenous Regimen (number of patients) Uncontrolled Studies* Study 1 16% (7/44) - Study 2 26% (11/43) - Study 3 18% (7/38) 0% (0/21) Study 4 - 0% (0/32) Controlled Studies † Study 5 31% (14/46) 6% (3/46) Study 6 100% (7/7) 0% (0/8)

3.

Wu J, Cui Y, Liu T, et al. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2024;:117795. doi:10.1016/j.cca.2024.117795.

Publish date: January 0, 2024.

BACKGROUND: Hematuria is a common condition in clinical practice of pediatric patients. It is related to a wide spectrum of disorders and has high heterogeneity both clinically and genetically, which contributes to challenges of diagnosis and lead many pediatric patients with hematuria not to receive accurate diagnosis and early management. METHODS: In this single center study, 42 children with hematuria were included in Tianjin Children' Hospital between 2019 and 2020. We analyzed the clinical information and performed WES (Whole exome sequencing) for all cases. Then the classification of identified variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines for interpreting sequence variants. For the fragment deletion, qPCR was performed to validate and confirm the inherited pattern. RESULTS: For the 42 patients, 16 cases had gross hematuria and 26 had microscopic hematuria. Molecular genetic causes were uncovered in 9 (21.4%) children, including 7 with Alport syndrome (AS), one with polycystic nephropathy and one with lipoprotein glomerulopathy. The genetic causes for other patients were not related with hematuria. CONCLUSIONS: WES is a rapid and effective way to evaluate patients with hematuria. The analysis of genotype-phenotype correlations of patients with AS indicated that severe variants were associated with early kidney failure. Secondary findings is not rare in Chinese children, thus the clinician should pay more attention to the clinical interpretation of sequencing results and properly interaction with patients and their family.