Challenging the Concept of “Benign” Microscopic Hematuria: How Far Do We Go?

Eric Ryan, MD

Eric Ryan recently completed fellowship and is joining the nephrology faculty at Oregon Health and Science University. He has an early career interest in medical education, critical care nephrology, and multidisciplinary process improvement.



Vanderlene Liu Kung, MD PhD 

Vanderlene Liu Kung is a renal pathologist at Oregon Health & Science University. Her research interests are in applying transcriptional techniques to formalin fixed paraffin embedded tissue to understand native and allograft kidney diseases.



Rupali Avasare, MD

Rupali Avasare is a nephrologist and glomerular disease specialist at Oregon Health & Science University. Her clinical and research interests involve glomerular disease and triggers of autoimmunity.

Isolated microscopic hematuria (>2-5 RBCs / high-powered field) is detected across all populations and has an estimated prevalence of 2.4 – 31.1%. Preliminary workup for microscopic hematuria involves a careful history and physical examination to rule out several common causes, including urinary tract infection, kidney stones, and menstruation. Clues that point to glomerular hematuria include dysmorphic red blood cells or acanthocytes, red blood cell casts, decreased glomerular filtration rate (GFR), and/or proteinuria.

The most common causes of glomerular hematuria are IgA nephropathy (IgAN) and type IV collagen disorders (Figure 1), and less commonly other nephritic processes.  Traditionally, kidney biopsy is recommended in those with high-risk features, such as proteinuria, decline in kidney function, and new hypertension. Experts in Alport syndrome propose genetic testing for COL4A3, COL4A4, and COL4A5 variants in those with persistent hematuria, their first-degree relatives, and those with suspected inherited focal and segmental glomerulosclerosis, familial IgAN, and kidney failure of unknown cause. At minimum, patients with glomerular hematuria should be monitored once or twice yearly.

Ultrastructural findings associated with type IV collagen gene mutations. A) Thin glomerular capillary basement membranes (GBMs) are associated with a broad spectrum of clinical phenotypes related to type IV collagen gene mutations, including a “benign/non-progressive” autosomal dominant lesion (thin basement membrane nephropathy), early stage autosomal recessive or dominant Alport syndrome, a heterozygous (carrier) state of autosomal recessive or X-linked Alport syndrome, and a subset of both sporadic and familial cases of IgAN. B) In addition to GBM thinning, ultrastructural features of Alport syndrome include irregular GBM thickening, subepithelial scalloping and lifting, remodelling conferring a basket-weave and lamellated appearance (dotted circles) and lamina densa splitting (arrow).  © Eric Ryan, Vanderlene Liu Kung, Rupali Avasare

Urologic evaluation involves a CT urogram – cross sectional imaging both with and without contrast — to evaluate for structural abnormalities, stones, and large masses. Special consideration is necessary for young patients who may not require contrast studies, pregnant patients who may begin with ultrasound evaluation, and advanced chronic kidney disease (CKD) patients who may begin with non-contrast CT or MR urogram. In patients with increased risk for malignancy, cystoscopy is recommended.

A recently published retrospective cohort study by Um et al investigates the association between microscopic hematuria of any cause (four distinct groups, including persistent or single episode) and incident CKD, defined as GFR < 60 mL/min/1.73 m2 or proteinuria of 1+ or more on dipstick in relatively healthy Korean adults without known kidney disease or malignancy. The study included 2,392 participants, 58.9% male, with an average age of 38.2 years. The major finding was a strong association between microscopic hematuria and incident CKD with hazard ratios as high as 5.34 (95% CI, 4.15 – 6.59) for the persistent hematuria group and as low as 1.85 (95% CI, 1.35 – 2.53) for those with hematuria that regressed on follow-up urine examination. Notably, the association between persistent microscopic hematuria and incident CKD was higher in men than in women (p < 0.001). This study is in line with other large cohort studies that have demonstrated an association between microscopic hematuria and CKD. Major weaknesses include using dipstick proteinuria, without quantification, as a surrogate for incident CKD which may have led to higher than expected rate of incident CKD.

Um et al., along with others, and the newly proposed guidelines on genetic testing in patients with microscopic hematuria have the potential to transform clinical care of adults with microscopic hematuria. Because screening for asymptomatic hematuria for cancer and/or kidney disease detection is not recommended by any major US-based organization including the American Academy of Pediatrics, the American College of Physicians, and the U.S. Preventive Services Task Force, most US cases of asymptomatic hematuria will be incidentally discovered. We anticipate that because of recent findings and recommendations from expert nephrologists, more patients with asymptomatic microscopic hematuria will undergo genetic testing and that the frequency of proteinuria and GFR monitoring will increase in this population. Future studies evaluating the impact of more rigorous evaluation on incident CKD and end-stage kidney disease in different patient populations is essential to understanding whether glomerular hematuria is ever truly “benign.”

– Post prepared by Eric Ryan, Vanderlene Kung, and Rupali Avasare


To view Um et al, please visit

Title: Risk of CKD Following Detection of Microscopic Hematuria: A Retrospective Cohort Study
Authors: Yoo Jin Um, Yoosoo Chang, Yejin Kim, Min-Jung Kwon, Hyun-Suk Jung, Kyu-Beck Lee, Kwan Joong Joo, In Young Cho, Sarah H. Wild, Christopher D. Byrne, and Seungho Ryu.
DOI: 10.1053/j.ajkd.2022.09.012

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