Non-profit organization committed to improvement and dissemination of knowledge regarding the pathology and pathophysiology of renal disease

CLINICAL HISTORY

The patient is a 72-year-old female who had baseline normal serum creatinine of approximately 0.5 mg/dL.  In the setting of only mild COVID-19 bronchopneumonia, she presented with acute kidney injury with creatinine up to 4.5 mg/dL, requiring initiation of hemodialysis.  At the time of kidney biopsy, a repeat COVID-19 PCR was negative.  The patient is a recent immigrant from West Africa.

KIDNEY BIOPSY FINDINGS

Figure 1. Collapsing glomerulopathy with prominence of podocytes overlying the collapsing capillary loops. Jones stain.

Figure 2. Three different patterns of acute tubular injury: epithelial attenuation (A), tubules engorged with lysosomes/reabsorption droplets (B) and microcystic tubular changes (C). Jones stain.

The immunofluorescence studies were negative.

Figure 3. Diffuse podocyte foot process effacement seen by electron microscopy. Some capillary loops also show subepithelial electron lucency as can be seen with severe podocyte injury.

FINAL DIAGNOSIS

Kidney biopsy:

 

DISCUSSION

The SARS-CoV-2 pandemic has infected millions of individuals in the US and caused hundreds of thousands of deaths.  Individuals with kidney disease are at increased risk of morbidity and mortality (1, 2). Three pathologies have frequently been detected in autopsy and biopsy-based studies of kidney impairment in COVID-19 patients. These include acute tubular injury (“acute tubular necrosis”), collapsing glomerulopathy and acute endothelial cell injury/acute thrombotic microangiopathy (Figure 4). The association of COVID-19 with collapsing glomerulopathy, a usually rare and devastating kidney disease is particularly striking and has been termed COVAN (COVID-19 Associated Nephropathy) (3-6). As seen with HIV associated nephropathy (HIVAN), COVAN is strongly associated with high-risk APOL1 genotypes (6, 7), which have increased prevalence in Black and some Hispanic populations (8, 9).  In addition, most of COVAN patients had mild COVID-19 symptoms and did not require intensive care (3, 4, 6, 10, 11), suggesting that the development of COVAN is independent of severe lung manifestations and other life-threatening complications. COVAN does appear to be devastating for the kidney, and the majority of reported COVAN patients progressed to end stage kidney disease and are dialysis-dependent (3, 4, 6, 10, 11). Though she was not genotyped, this patient was from West Africa, which has high prevalence of high risk APOL1 genotypes (12). At the time of this writing, she is dialysis-dependent and has been listed for transplant.

Figure 4.The three most common histologic patterns of kidney injury seen in COVID-19 patients.

REFERENCES

1. Y. Cheng, R. Luo, K. Wang, M. Zhang, Z. Wang, L. Dong, J. Li, Y. Yao, S. Ge, G. Xu, Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 97, 829-838 (2020).
2. G. Pei, Z. Zhang, J. Peng, L. Liu, C. Zhang, C. Yu, Z. Ma, Y. Huang, W. Liu, Y. Yao, R. Zeng, G. Xu, Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. J Am Soc Nephrol 31, 1157-1165 (2020).
3. S. Akilesh, C. C. Nast, M. Yamashita, K. Henriksen, V. Charu, M. L. Troxell, N. Kambham, E. Bracamonte, D. Houghton, N. I. Ahmed, C. C. Chong, B. Thajudeen, S. Rehman, F. Khoury, J. E. Zuckerman, J. Gitomer, P. C. Raguram, S. Mujeeb, U. Schwarze, M. B. Shannon, I. De Castro, C. E. Alpers, B. Najafian, R. F. Nicosia, N. K. Andeen, K. D. Smith, Multicenter Clinicopathologic Correlation of Kidney Biopsies Performed in COVID-19 Patients Presenting With Acute Kidney Injury or Proteinuria. Am J Kidney Dis,  (2020).
4. S. Kudose, I. Batal, D. Santoriello, K. Xu, J. Barasch, Y. Peleg, P. Canetta, L. E. Ratner, M. Marasa, A. G. Gharavi, M. B. Stokes, G. S. Markowitz, V. D. D'Agati, Kidney Biopsy Findings in Patients with COVID-19. J Am Soc Nephrol 31, 1959-1968 (2020).
5. P. Sharma, N. N. Uppal, R. Wanchoo, H. H. Shah, Y. Yang, R. Parikh, Y. Khanin, V. Madireddy, C. P. Larsen, K. D. Jhaveri, V. Bijol, N. N. C.-R. Consortium, COVID-19-Associated Kidney Injury: A Case Series of Kidney Biopsy Findings. J Am Soc Nephrol 31, 1948-1958 (2020).
6. H. Wu, C. P. Larsen, C. F. Hernandez-Arroyo, M. M. B. Mohamed, T. Caza, M. Sharshir, A. Chughtai, L. Xie, J. M. Gimenez, T. A. Sandow, M. A. Lusco, H. Yang, E. Acheampong, I. A. Rosales, R. B. Colvin, A. B. Fogo, J. C. Q. Velez, AKI and Collapsing Glomerulopathy Associated with COVID-19 and. J Am Soc Nephrol 31, 1688-1695 (2020).
7. J. C. Q. Velez, T. Caza, C. P. Larsen, COVAN is the new HIVAN: the re-emergence of collapsing glomerulopathy with COVID-19. Nat Rev Nephrol 16, 565-567 (2020).
8. G. Genovese, D. J. Friedman, M. D. Ross, L. Lecordier, P. Uzureau, B. I. Freedman, D. W. Bowden, C. D. Langefeld, T. K. Oleksyk, A. L. Uscinski Knob, A. J. Bernhardy, P. J. Hicks, G. W. Nelson, B. Vanhollebeke, C. A. Winkler, J. B. Kopp, E. Pays, M. R. Pollak, Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329, 841-845 (2010).
9. H. J. Kramer, A. M. Stilp, C. C. Laurie, A. P. Reiner, J. Lash, M. L. Daviglus, S. E. Rosas, A. C. Ricardo, B. O. Tayo, M. F. Flessner, K. F. Kerr, C. Peralta, R. Durazo-Arvizu, M. Conomos, T. Thornton, J. Rotter, K. D. Taylor, J. Cai, J. Eckfeldt, H. Chen, G. Papanicolau, N. Franceschini, African Ancestry-Specific Alleles and Kidney Disease Risk in Hispanics/Latinos. J Am Soc Nephrol 28, 915-922 (2017).
10. R. Noble, M. Y. Tan, T. McCulloch, M. Shantier, C. Byrne, M. Hall, M. Jesky, Collapsing Glomerulopathy Affecting Native and Transplant Kidneys in Individuals with COVID-19. Nephron 144, 589-594 (2020).
11. S. H. Nasr, M. P. Alexander, L. D. Cornell, L. H. Herrera, M. E. Fidler, S. M. Said, P. Zhang, C. P. Larsen, S. Sethi, Kidney Biopsy Findings in Patients With COVID-19, Kidney Injury, and Proteinuria. Am J Kidney Dis,  (2020).
12. G. N. Nadkarni, C. R. Gignoux, E. P. Sorokin, M. Daya, R. Rahman, K. C. Barnes, C. L. Wassel, E. E. Kenny, Worldwide Frequencies of APOL1 Renal Risk Variants. N Engl J Med 379, 2571-2572 (2018).