Approach to hematuria (pediatrics): Clinical sciences

Hematuria is the presence of microscopic or macroscopic blood in the urine. Healthy kidneys filter blood by removing waste products while retaining important molecules and blood elements, while kidneys that have lost their filtering ability allow red blood cells, or RBCs, to pass into the urine. Hematuria can be benign and transient, while in other cases kidney damage causes persistent hematuria, which can be categorized as glomerular or non-glomerular in origin.

When a pediatric patient presents with hematuria, your first step is to obtain a urine dipstick to confirm the presence of blood.

Here’s a clinical pearl to keep in mind! At first glance, pink or red urine is suspicious for hematuria, but if a urine dipstick is negative for blood, be sure to consider other causes of discolored urine, such as beet ingestion; rifampin use; in porphyria due to oxidation of porphyrins; or build up of urate crystal precipitation in newborns.

Okay, if the urine dipstick is positive for blood, obtain a focused history and physical examination, and order a urinalysis with microscopy to assess the quantity of RBCs. If microscopy reveals more than five RBCs per high-power field, you can confirm an abnormal amount of blood in the urine.

Now, here’s a clinical pearl! If your patient presents with discolored urine that tests positive for blood on a urine dipstick, but no RBCs are seen on urine microscopy, evaluate for myoglobinuria and hemoglobinuria.

Myoglobinuria can be seen in conditions like rhabdomyolysis, extreme exercise, or myopathies, in which myoglobin is excreted in the urine due to increased skeletal muscle breakdown. On the other hand, hemoglobinuria is caused by rapid hemolysis, which results in the excretion of hemoglobin in the urine; in this case, your patient may also be anemic or appear jaundiced.

Once you confirm the presence of RBCs on urine microscopy, repeat the urinalysis twice more, one week apart. If the hematuria resolves, meaning the repeat urinalysis reveals no RBCs, you can diagnose transient hematuria, which could be related to conditions such as fever, exercise, trauma, or a urinary tract infection.

On the flip side, if the repeat urinalysis with microscopy continues to be positive for RBCs, diagnose persistent hematuria. This is defined as more than four to six weeks of ongoing hematuria in the absence of exercise, menses, or trauma.

Next, assess for nephritic syndrome. Nephritic syndrome is characterized by cola- or tea-colored urine and a decrease in urine output, while the physical examination reveals elevated blood pressure and edema. Take another look at the urinalysis and microscopy, and you’re likely to see RBC casts and possibly proteinuria. If these findings are present, diagnose nephritic syndrome.

Then assess for an underlying cause of glomerulonephritis. Begin your workup by ordering additional labs. Labs include serum creatinine, complements C3 and C4; antistreptolysin O, or ASO, titer; as well as serum IgA and galactose-deficient IgA1.

Additionally, don’t forget to check autoantibodies, more specifically cytoplasmic antineutrophil cytoplasmic antibody, or c-ANCA; perinuclear antineutrophil cytoplasmic antibody, or p-ANCA; anti-glomerular basement membrane, or anti-GBM antibody; anti-nuclear antibody, or ANA; anti-double stranded DNA, or anti-dsDNA antibody; and anti-Smith antibody.

You should also consider obtaining a renal biopsy and evaluating the specimen using light microscopy, immunofluorescence, and electron microscopy, as well as H&E and PAS stains. Your next step is to assess for a history of a recent infection.

Okay, let’s start by discussing patients who had a recent Group A streptococcal infection. This should make you consider poststreptococcal glomerulonephritis. Labs usually reveal a low C3, normal C4, and a positive ASO titer. Based on these findings, diagnose post-streptococcal glomerulonephritis.

While a kidney biopsy is not generally indicated to make this diagnosis, but, if it is performed, immunofluorescence will show a granular appearance from the IgG, IgM, and C3 deposits, which is referred to as “lumpy bumpy” or “starry sky.”

Now, here’s a high-yield fact! Although treating strep pharyngitis with penicillin can prevent strep complications, such as rheumatic fever and the spread of the nephritogenic streptococci, but keep in mind that it does not prevent post-streptococcal glomerulonephritis!

Okay, now let’s say your patient has a recent viral URI instead. Here, consider IgA nephropathy. Labs may reveal elevated levels of galactose-deficient IgA1 and serum IgA; as well as an increased IgA-to-C3 ratio. If the renal biopsy with immunofluorescence reveals mesangial IgA immune deposits, diagnose IgA nephropathy.

Alright, let’s say your patient did not have a recent acute infection. You will then want to assess for hearing loss. Alright, for patients who have sensorineural hearing loss, consider Alport Syndrome. Your patient might have a family history of deafness and renal failure. Lab findings are usually non-specific, so use a renal biopsy to confirm the diagnosis.

Electron microscopy will reveal glomerular basement membrane splitting; as well as thinning and thickening of the glomerular basement membrane with a “basket-weave” appearance. Additionally, immunofluorescence will show the absence of the type IV collagen chain. With these findings, you can diagnose Alport syndrome.

Here’s a clinical pearl! Alport syndrome can also be diagnosed from a skin biopsy, which demonstrates the absence of type IV collagen, or through genetic testing, which may reveal the COL4A5 mutation.