Lopinavir-Ritonavir Associated Acute Kidney Injury Is Not Related to Crystalluria in Critically Ill COVID-19 Patients.

To the Editor:

We read with interest the study of Binois et al. showing a potential link between lopinavir/ritonavir (LPN/r) therapy and acute kidney injury (AKI) in patients with coronavirus disease 2019 (COVID-19).

The high rate of AKI observed in our intensive care unit during the pandemic (65% of patients and 80% of Kidney Disease: Improving Global Outcomes stage 3), and the use of LPN/r in 37% of our patients (unpublished data) made us explore this potential association.

LPN/r has been shown to be associated with nephrolithiasis, leading us to hypothesize a crystalluria-related AKI mechanism.

We explored 3 patients with COVID-19 hospitalized in our intensive care unit who developed a Kidney Disease: Improving Global Outcomes stage 3 AKI in the 2 days following the LPN/r onset. All of them needed dialysis, mechanical ventilation, and vasopressors. We observed a significant proteinuria (mean proteinuria/creatininuria ratio of 630 mg/mmol) with a tubular pattern (albuminuria/proteinuria ratio <50%). Crystalluria and urine sediment analysis revealed the presence of many granular casts and cellular debris but no specific crystals (Figure 1). After centrifugation, urine pellets were dried and analyzed by Fourier transform infraRed spectroscopy, revealing the presence of urea, proteins, and glucids, but no evidence for drugs.

Figure 1

Optic microscopy of urine from patient 2 showing granular casts and cellular debris (arrows) but no specific crystals.

LPN/r-related AKI rises as a major concern because the DISCOVERY study stopped the inclusion in the LPN/r arm because of a significant rate of serious adverse events related to renal function alteration. However, the pathophysiological process of this potential association remains to be determined, and seems not to be associated with crystalluria.