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IgA Nephropathy in Adults: A Review

Author/s: 
Sinead Stoneman, Jia Wei Teh, Michelle Marie O'Shaughnessy

Importance: IgA nephropathy (IgAN) is a chronic kidney disease involving deposition of IgA-containing immune complexes in the glomerulus, causing glomerular inflammation and scarring. It is the most common immune-mediated glomerular disease worldwide, and affects an estimated 198 887 to 208 184 persons in the US. Up to 50% of patients with IgAN develop kidney failure within 10 years of diagnosis.

Observations: IgAN typically presents with nephritic syndrome and usually occurs in younger adults, with a mean age at diagnosis of 34 to 45 years. Incidence is highest in East Asia. Approximately 60% of cases are detected incidentally with hematuria or proteinuria on urinalysis. Up to 30% of patients present with episodic visible hematuria, often concomitantly with an upper respiratory or gastrointestinal tract infection (synpharyngitic hematuria). Less common presentations include nephrotic syndrome (<5%) and rapidly progressive glomerulonephritis (<5%). When IgAN is suspected (due to hematuria, proteinuria, or reduced kidney function), initial workup should include quantification of proteinuria and assessment for other causes of nephritic syndrome (eg, lupus nephritis). Adults with suspected IgAN and proteinuria greater than or equal to 0.5 g per day should undergo kidney biopsy. The diagnosis of primary IgAN is based on presence of IgA-dominant immune deposits in the glomerular mesangium after excluding other causes of this histologic appearance, ie, IgA vasculitis, IgA-dominant infection-related glomerulonephritis, and secondary IgAN from diseases such as cirrhosis, inflammatory bowel disease, celiac disease, infection (eg, viral hepatitis), and autoimmune diseases (eg, axial spondyloarthritis). Based on the Kidney Disease: Improving Global Outcomes 2025 clinical practice guideline for the management of IgAN, treatment for patients with proteinuria greater than 0.5 g per day includes behavioral modifications (eg, dietary sodium <2 g/d, smoking cessation, weight control, exercise), antihypertensive medications for goal blood pressure less than 120/70 mm Hg, and therapies to reduce the formation of IgA-containing immune complexes (eg, targeted-release budesonide), decrease glomerular injury (eg, systemic glucocorticoids, iptacopan), and manage existing IgAN-induced nephron loss (eg, renin-angiotensin system inhibitor or dual endothelin angiotensin receptor antagonist [eg, sparsentan] alone or in combination with a sodium-glucose cotransporter 2 inhibitor).

Conclusions and relevance: IgAN is the leading cause of immune-mediated glomerular disease worldwide. Patients with suspected IgAN and proteinuria greater than or equal to 0.5 g per day should undergo kidney biopsy to confirm the diagnosis. Treatment of IgAN includes behavioral modifications, blood pressure management, and therapies to decrease formation of IgA-containing immune complexes (eg, targeted-release budesonide), reduce immune complex-mediated glomerular injury (eg, systemic glucocorticoids, iptacopan), and manage IgAN-induced nephron loss (eg, renin-angiotensin system inhibitor, dual endothelin angiotensin receptor antagonist, and sodium-glucose cotransporter 2 inhibitor).

Keywords 
Glomerulonephritis IGA Renal Insufficiency nephropathy glomerulus

Lower Urinary Tract Symptoms in Men: A Review

Author/s: 
John T Wei, Casey A Dauw, Casey N Brodsky

Importance: Up to 40% of men older than 50 years have lower urinary tract symptoms, including urinary urgency, nocturia, and weak urinary stream, due to disorders of the bladder and prostate. These symptoms negatively affect quality of life and may be associated with urinary retention, which can cause kidney insufficiency, bladder calculi, hematuria, and urinary tract infections.

Observations: In men, lower urinary tract symptoms can be caused by bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), an overactive bladder detrusor (a syndrome of urinary urgency and frequency), or both. Behavioral therapy, including pelvic floor physical therapy, timed voiding (voiding at specific intervals), and fluid restriction, can improve symptoms. Medications including α-blockers (such as tamsulosin), 5α-reductase inhibitors (such as finasteride), and phosphodiesterase 5 inhibitors (such as tadalafil) improve lower urinary tract symptoms (mean improvement, 3-10 points on the International Prostate Symptom Score [IPSS], which ranges from 0-35, with higher scores indicating greater severity) and can prevent symptom worsening measured by increased IPSS greater than or equal to 4 points or development of secondary sequelae, such as urinary retention. Combination therapies are more effective than monotherapy. For example, α-blockade (eg, tamsulosin) combined with 5α-reductase inhibition (eg, finasteride) lowers progression risk to less than 10% compared with 10% to 15% with monotherapy. Treatment for overactive bladder detrusor, including anticholinergics (eg, trospium) and β3 agonists (eg, mirabegron), reduces voiding frequency by 2 to 4 times per day and reduces episodes of urinary incontinence by 10 to 20 times per week. Surgery (eg, transurethral resection of the prostate, holmium laser enucleation of the prostate) and minimally invasive surgery are highly effective for refractory or complicated cases of BPH, defined as persistent symptoms despite behavioral and pharmacologic therapy, and these therapies can improve IPSS by 10 to 15 points. Minimally invasive procedures, such as water vapor therapy (endoscopic injection of steam into BPH tissue) and prostatic urethral lift (endoscopic insertion of nonabsorbable suture implants that mechanically open the urethra), have lower complication rates of incontinence (0%-8%), erectile dysfunction (0%-3%), and retrograde ejaculation (0%-3%) but are associated with increased need for surgical retreatment (3.4%-21%) compared with transurethral resection of the prostate (5%) and holmium laser enucleation of the prostate (3.3%).

Conclusions and relevance: Lower urinary tract symptoms, defined as urinary urgency, nocturia, or weak stream, are common among men and are usually caused by BPH, overactive bladder detrusor, or both. First-line therapy consists of behavioral intervention, such as pelvic floor physical therapy and timed voiding, as well as pharmacologic therapy, including α-adrenergic blockers (tamsulosin), 5α-reductase inhibitors (finasteride), phosphodiesterase inhibitors (tadalafil), anticholinergics (trospium), and β3 agonists (mirabegron).

Keywords 
prostate Lower Urinary Tract Symptoms

Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians

Author/s: 
Nielsen, Matthew, Qaseem, Amir, High Value Care Task Force of the American College of Physicians

Background: The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria.

Methods: A narrative review of available clinical guidelines and other relevant studies on the evaluation of hematuria was conducted, with particular emphasis on considerations for urologic referral.

High-value care advice 1: Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria.

High-value care advice 2: Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults.

High-value care advice 3: Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults.

High-value care advice 4: Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited.

High-value care advice 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause.

High-value care advice 6: Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy.

High-value care advice 7: Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.

Cancer Prevalence and Risk Stratification in Adults Presenting With Hematuria: A Population-Based Cohort Study

Author/s: 
Takeuchi, Mitsuru, McDonald, Jennifer S., Takahashi, Naoki, Frank, Igor, Thompson, R. H., King, Bernard F., Kawashima, Akira

Abstract

Objective

To calculate the prevalence of renal cell carcinoma (RCC), upper urinary tract urothelial carcinoma (UT-UC), and lower urinary tract urothelial carcinoma (LT-UC) in patients with gross asymptomatic microhematuria (AMH) and symptomatic microhematuria (SMH).

Patients and Methods

This study was a population-based retrospective descriptive study. The study was approved by both the Mayo Clinic Institutional Review Board and the Olmsted Medical Center Institutional Review Board, and the population used was Olmsted County residents. A total of 4453 patients who presented with an initial episode of hematuria from January 1, 2000, through December 30, 2010, were included. Of the 4453 patients (median age, 58 years; interquartile range, 44.6-73.3 years), 1487 (33.4%) had gross hematuria, 2305 (51.8%) had AMH, and 661 (14.8%) had SMH.

Results

In the 1487 patients with gross hematuria, the prevalence of RCC, UT-UC, and LT-UC was 1.3%, 0.8%, and 9.0%, respectively. In the 2305 patients with AMH, the prevalence of RCC, UT-UC, and LT-UC was 0.2%, 0.3%, and 1.6%, respectively. In the 661 patients with SMH, the prevalence of RCC, UT-UC, and LT-UC was 0.6%, 0.2%, and 0.3%, respectively. Age was the most relevant risk factor for any hematuria type.

Conclusion

This unique cohort study reported that the prevalence of RCC or UC in patients with AMH and SMH was low, especially in the young cohort, and a large number of intense work-ups, such as cystoscopy and computed tomography urography, currently conducted could be omitted if stratified by hematuria type and age.

Keywords 
cancer Hematuria Adults RCC Carcinoma, Renal Cell
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