Hematuria: Deep on the DDx

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Recently at our biopsy conference we had the case of a healthy middle aged man presented who had come to medical attention with episodes of painless gross hematuria. He had consistent rbcs on UAs, normal renal imaging, a serum creatinine of 1.1 mg/dl, 360 mg per day of proteinuria and unremarkable serologies. An extensive urologic evaluation had been unrevealing and a kidney biopsy was normal.

When the usual suspects of urologic and glomerular causes of relatively isolated hematuria (IgA nephropathy, Thin Basement Membrane Disease, Alport’s Syndrome) are not around you sometimes have to go a bit deeper down the differential diagnostic list.

Along those lines RFN has had a couple of posts on some of the more unusual painful causes of hematuria including renal infarction, Loin Pain-Hematuria Syndrome and the Nutcracker Syndrome (also covered on PBF).

As mentioned, our patients hematuria was painless. He had no history of diabetes, NSAID use, infection or obstruction to implicate renal papillary necrosis. There was no travel history to suggest Schistosoma haematobium or Tuberculosis. His ethnicity made Sickle cell unlikely. He only exercised as much as the average first year renal fellow (ie not much) so exercise hematuria seemed out. The room was a little stumped.

A metabolic possibility that came up after conference was hypercalciuria and or hyperuricosuria in the absence of nephrolithiasis.

In a small series of patients without nephrolithiasis and with persistent microscopic hematuria in the setting of normal renal function, urinary protein excretion and renal imaging published in KI, hypercalciuria was defined as greater than 4 mg/kg/day and hyperuricosuria was defined as greater than 800 mg/day in men and greater than 750 mg/day in women.

37 patients were identified who fit the above description and had hypercalciuria, hyperuricosuria or both. 43% of them reported having episodes of gross hematuria in addition to their known microscopic hematuria. The authors went on to treat the entire group with HCTZ and or allopurinol with the goal of normalizing urinary calcium and uric acid excretion which was achieved in all patients. Hematuria completely resolved in 59.4% of cases.

In the discussion the authors speculated that perhaps microlithiasis was the cause of the hematuria in some of their cases. Of the patients who did not respond to lowering of urinary calcium and uric acid they all persisted with microscopic hematuria and at about a year followup a reasonable alternate cause (IgA nephropathy, Thin Basement Membrane Disease ect) was ultimately found or strongly suspected in all but four cases.

Another small case series of 12 similar patients in familial clusters was subsequently published in AJKD. Here again 30% had reported episodes of gross hematuria in addition to microscopic hematuria and all patients were able to normalize their urinary calcium and uric acid excretion through medication and dietary measures. All 12 patients were able to achieve resolution of their hematuria.


  1. Hi Gearoid,

    Thanks for the comment. No, not common practice. I agree, that on the merits of the clinical data presented many would not biopsy.

    I believe the primary nephrologist performed the biopsy at the patient's request after the urologic workup was negative but distressing intermittent gross hematuria was still present.

  2. Hi Graham,

    Interesting case. I don't think that I would have done a renal biospy as the yield in someone with microhematuria and minimal proteinuria would be small. Is it the practice in your institution to biopsy all cases of unexplained hematuria?


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