We thank Kay Choy for the nterest in our Correspondence,1 in which we described an association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) renal tropism and acute kidney injury in autopsy cases with COVID-19 diagnosis.
We analysed data from a large autopsy series of 63 patients. Since an individual's disease course, comorbidities, and complications of severe COVID-19 disease are highly variable, we depicted three different cases as supplemental information exemplifying this variation.1 The first example had initially stable renal function and presented an abrupt decline before death, shortly after COVID-19 diagnosis (case 50). The second example presented with declining renal function before COVID-19 diagnosis, which aggravated over the following weeks (case 52). The third example had signs of acute kidney injury shortly after admission and later a positive respiratory swab for SARS-CoV-2 (case 45). As we expected, these cases have sparked some interesting discussions.
Case 45 was used by Choy as an example that merits clarification regarding the adherence to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the acute kidney injury definition. This patient developed an increase in serum creatinine from 102·57 μmol/L at admission to 197·18 μmol/L within 48 h, meeting KDIGO criteria for acute kidney injury.2 Notably, this patient was not tested for COVID-19 due to respiratory symptoms, but was instead diagnosed following a routine diagnostic procedure on the ward. Given the complex clinical context of COVID-19 and the dynamic nature of indications for testing, establishing the link between acute kidney injury and SARS-CoV-2 infection remains challenging. In this case, we chose to use temporal proximity to COVID-19 diagnosis as a key defining parameter. Although there is no available consensus or guidelines to conclusively define COVID-19-associated acute kidney injury, the high frequency of acute kidney injury among patients with SARS-CoV-2 infection might serve as a catalyser for such discussions.
Another important point is the definition of chronic kidney disease. Cases 17 and 48 indeed presented with an estimated glomerular filtration rate (eGFR) above the threshold for chronic kidney disease according to the KDIGO guidelines.3 However, the possibility of a careful organ examination allowed us to grade structural kidney changes associated with chronic kidney disease (ie, fibrotic parenchymal remodelling, thinned kidney cortex, or decreased organ weight), which clearly indicated abnormalities of kidney structure as per KDIGO guidelines.3 In contrast, determination of kidney function using a single measurement of eGFR can be limited by multiple causes (eg, case 48 had a measured body-mass index of 17; hence eGFR could be overestimated). Thus, autopsy studies provide a unique opportunity to extend clinical definitions with additional layers of structural information.
In summary, although the KDIGO guidelines have provided the framework for reliable and reproducible nomenclature of acute kidney injury and chronic kidney disease, autopsy studies can add further anatomical and pathological information and help to identify renal tropism and COVID-19-related acute kidney injury.1, 4, 5 The association of SARS-CoV-2 infection and kidney injury opens potential new avenues for early diagnostics, prediction, and prevention of COVID-19-related kidney disease.6
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Acknowledgments
FB reports grants and personal fees from Amicus Therapeutics; personal fees from Takeda/Shire; and travel support from Sanofi Genzyme and Astellas. VGP reports grants from the German Research Foundation (DFG: CRC/1192) and the Federal Ministry of Education and Research (BMBF: eMed Consortia Fibromap). TBH reports grants from the German Research Foundation (CRC/1192, HU 1016/8-2, HU 1016/11-1, and HU 1016/12-1), the Federal Ministry of Education and Research (STOP-FSGS-01GM1518C), and European Research Council (grant 616891); grants and personal fees from Fresenius Medical Care; grants from Amicus Therapeutics and Sanofi Genzyme; and personal fees from Boehringer Ingelheim, Goldfinch Bio, Novartis, DaVita Germany, and Bayer Vital. CE declares no competing interests.
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