Abstract :
[en] Case discussion
We report here 7 Caucasian patients with very uncommon crystalluria. There were 3 female and 4 male of 54 to 86 years-old. Patients had no relevant medical record in common. However, they all were hospitalized for different types of infections: three patients had urinary infection, two had osteitis, and the two last had sepsis. The patients had all been first treated with different antibiotherapy, which had then been replaced by cotrimoxazole after antibiogram. The administrated doses varied from 800mg to 4800mg a day of Sulfamethoxazole.
Crystalluria description
In all patients, the urine microscopic analysis revealed unusual crystals of various shapes including rectangles, thick parallelepipeds, truncated lozenges, spheroids, mushrooms, or “flowers”. Some crystals were incorrectly identified by the urinary sediment analyzer as uric acid, but we sought to determine them accurately. Most of the crystals were strongly birefringent and measured between 20 and 100µm. Urine pH varied from 5.0 to 6.5 on strip analysis. After urine centrifugation, we performed infrared spectrophotometry analysis on dried residue. In all cases, the infrared spectra allowed us to identify the N-acetyl-Sulfamethoxazole, the main metabolite of Sulfamethoxazole. Crystalluria was observed between 1 and 26 days after Sulfamethoxazole treatment initiation. The serum creatinine increased from 16% to 88% in 3 patients between the first day of Sulfamethoxazole treatment and the day of crystalluria. These considerations raised concern for drug implication in renal failure in some of these patients.
Teaching points for the clinical condition
Drug-induced kidney failure is well-known, but the direct precipitation of drug crystals into tubules is rare, and also probably under-evaluated. Even if Sulfamethoxazole tubular precipitation was probably not the main cause of renal failure in these cases, we suspect it could have played a role. N-Acteyl-Sulfamethoxazole can precipitate in urine in many uncommon crystals shapes that raise suspicion for drug nephrotoxicity. Automated urine analyzers may misidentify these rare crystals. Crystal’s recognition may be difficult even with polarized light microscopy. This is why they must be identified by infrared spectrophotometry to avoid misdiagnosis.
These renal failures linked to Sulfamethoxazole precipitation are more susceptible to appear with high dosage of drug, hypovolemia and pre-existing renal failure. Hypoalbuminemia has also been described as a risk factor and was present in our four patients (between 26 to 39g/l, range laboratory: 43-54). Thus, prevention of Sulfamethoxazole precipitation consists in hydratation to maintain urine flow, and require adaptation of cotrimoxazole dosage in regard of renal function. Urine alkalinization (pH >7.0) is also possible in order to increase Sulfamethoxazole metabolite solubility.