Indinavir crystallization around the loop of Henle: Experimental evidence

Objective: To determine the probable site of the nephron and the plasma ind inavir (IDV) concentration at which intrarenal IDV crystallization occurs. Design: We performed in vitro crystallization experiments in IDV solutions simulating conditions found in the nephron. Methods: To determine intrarenal IDV concentrations at which conditions in the nephron allow crystallization, several concentrations of IDV basic solu tions (0-800 mM) were titrated from pH 4.0 to higher pH values until crysta ls formed within 1 minute. Based on the combination of pH and ionic strengt h at which crystals formed, we determined the site of the nephron at which this combination was first attained. Based on the capacity for concentratio n at that site, we were able to measure the corresponding plasma IDV concen tration. Results: Under conditions normally found at the proximal tubule (i.e., pH 6 .7 and ionic strength of 200 mM), IDV crystallized at 200 mg/L. Under condi tions applying to the loop of Henle, pH 7.4 and ionic strength of 200 mM, I DV crystallized at 125 mg/L, which would correspond to a plasma IDV concent ration of 8 mg. Conclusions: IDV crystallization is most likely in the loop of Henle and ma y already start at plasma IDV concentrations as low as 8 mg/L. Increasing h ydration does not reduce the risk of IDV crystallization in the loop of Hen le but instead prevents IDV crystallization and aggregation in the lower ur inary tract. It remains to be confirmed whether prevention of high IDV plas ma concentrations will reduce the risk of IDV crystallization in the loop o f Henle.