Kidney Biopsy Findings in Patients with COVID-19

Satoru Kudose; Ibrahim Batal; Dominick Santoriello; Katherine Xu; Jonathan Barasch; Yonatan Peleg; Pietro Canetta; Lloyd E. Ratner; Maddalena Marasa; Ali G. Gharavi; M. Barry Stokes; Glen S. Markowitz; Vivette D. D’Agati

doi:10.1681/ASN.2020060802

Article Figures & Data

Figures

Tables
Additional Files

Download figure
Open in new tab
Download powerpoint
Download figure
Open in new tab
Download powerpoint
Figure 1.
Kidney biopsy findings in patients with COVID-19. (A) Light microscopy demonstrates a lesion of collapsing glomerulopathy characterized by hyperplasia of glomerular epithelial cells and collapse of the underlying glomerular capillaries. Jones methanamine silver. Magnification, ×600. (B) Diffuse foot process effacement and endothelial TRIs (arrow and inset) in a patient with minimal change disease. Electron micrograph. Magnification, ×8000. (C) Subepithelial electron dense deposits in PLA2R-associated membranous glomerulopathy. Electron micrograph. Magnification, ×15,000. (D) Multiple glomeruli with circumferential cellular crescents (arrows) in a patient with class 4+5 lupus nephritis. Periodic acid–Schiff. Magnification, ×100. (E) A glomerulus compressed by a crescent with global linear GBM staining for IgG in a patient with anti-GBM nephritis. Immunofluorescence for IgG. Magnification, ×400. (F) Tubular simplification and focal shedding of degenerating epithelial cells into the tubular lumina in a patient with isolated ATI. Hematoxylin and eosin. Magnification, ×400. (G) Severe lymphocytic tubulitis in a patient with acute T cell–mediated rejection. Periodic acid–Schiff. Magnification, ×600. (H) ISH for the virus by automated method showing undetectable viral RNA in the kidney (inset shows positive lung control). Automated ISH with hematoxylin counterstain. Magnification, ×400.

View popup

Table 1.

Clinical findings in patients with COVID-19 who underwent kidney biopsy

Pt	Age	Sex	Race	Comorbidities	IS	Temperature, °C	SpO₂ on RA	BP	Edema	COVID-19 Manifestations	Renal Presentation/Biopsy Indications
1	46	M	B	OSA, obesity (BMI=44)	N	37.1	94	144/100	Y	Cough, fever, sore throat	AKI, NS
2	62	M	B	HTN, prostate carcinoma	N	37.2	98	126/79	Y	Fever, myalgia, weakness	AKI on CKD, NS
3	62	M	B	HTN, DM, prostate carcinoma	N	36.8	91	122/82	N	Fever, hypoxemia, bilateral perihilar and basilar infiltrates on CXR	AKI, NRP
4	57	M	B	HTN, untreated hepatitis C virus	N	38.1	97	173/92	N	Flu-like symptoms with ground glass opacities and patchy consolidation on CXR	AKI on CKD, NRP
5	61	M	B	HTN, obesity (BMI=31.1)	N	38.5	99	134/79	N	Cough, fever	AKI, NRP
6	25	M	B	Obesity (BMI=32.2)	N	38.5	95	117/79	Y	Cough, fever, myalgia, infiltrates on CXR	AKI, NS
7	43	F	B	DM, HLD, streptococcal infection, obesity (BMI=52.5)	N	37.6	96	107/67	N	Cough, fever, sore throat, weakness, patchy LUL infiltrates on CXR	AKI
8	28	M	B	None	N	38.6	96 (on O₂)	143/62	N	Cough, fever, hypoxemia, bilateral infiltrates on CXR, elevated troponin and CPK	AKI
9	67	M	W	HTN, gout, history of tobacco use, obesity (BMI=34.9)	N	36.5	95	135/75	N	Cough, diarrhea, lethargy, multifocal infiltrates on CXR	AKI on CKD
10	51	M	B	HTN, DSA+ OHTx for NICM 1 yr ago, atrial fibrillation, CVA, BPH, HLD	Y	36.8	96	117/81	N	Predominantly nausea, vomiting, abdominal pain, with cough	AKI on CKD
11	72	M	W	HTN, DM, HLD, gout, spinal stenosis, atrial fibrillation	N	36.8	97 (on O₂)	125/73	Y	Cough, pleural effusion on CT	NS
12	70	F	B	HTN, CAD, PVD, cervical carcinoma, GERD, HLD, obesity (BMI=39.4)	N	38.1	92	118/58	Y	Cough, fever, shortness of breath	AKI, NRP
13	27	F	A	SLE with class 2 lupus nephritis	Y	36.9	93	130/80	Y	Cough, fever, shortness of breath, hypoxemia, bilateral infiltrates on CXR, required intubation and ICU admission	AKI, NS
14	48	F	B	GERD, history of tobacco use, obesity	N	37.6	98	185/80	N	Cough, myalgia, infiltrates on CXR	AKI
15	54	M	W	ESKD secondary to IgAN s/p DSA+ LURTx 1 mo ago, HTN, obesity (BMI=30.7)	Y	36.8	99	116/75	N	Asymptomatic	AKI
16	22	M	B	ESKD likely secondary to PLA2R+ MGN s/p DDRTx 2 years ago, HTN	Y	37.7	95	178/127	N	Cough, fever, bilateral infiltrates on CXR, required intubation and ICU admission	CKD
17	54	F	H	ESKD secondary to PCKD s/p DDRTx 2 months ago, HTN	Y	98.8	100	104/70	N	Fever, dry throat	AKI

BP is in millimeters of Hg. Pt, patient; IS, immunosuppression at presentation; SpO₂, oxygen saturation (percentage); RA, room air; M, man; B, black; OSA, obstructive sleep apnea; BMI, body mass index; N, no; Y, yes; NS, nephrotic syndrome; HTN, hypertension; AKI on CKD, AKI superimposed on CKD; DM, diabetes mellitus; CXR, chest x-ray; NRP, nephrotic-range proteinuria; F, woman; HLD, hyperlipidemia; LUL, left upper lobe; O₂, oxygen; CPK, creatine phosphokinase; W, white; DSA, donor-specific antibody; OHTx, orthotopic heart transplantation; NICM, nonischemic cardiomyopathy; CVA, cerebrovascular accident; BPH, benign prostatic hyperplasia; CT, computed tomography; CAD, coronary artery disease; PVD, peripheral vascular disease; GERD, gastroesophageal reflux disease; A, Asian; ICU, intensive care unit; IgAN, IgA nephropathy; s/p, status post; LURTx, living unrelated renal transplantation; MGN, membranous glomerulopathy; DDRTx, deceased donor renal transplantation; H, Hispanic; PCKD, polycystic kidney disease.

View popup

Table 2.

Laboratory findings and follow-up information in patients with COVID-19 who underwent kidney biopsy

Pt	Baseline sCr	Renal Function at Presentation					Complete Blood Counts			Other Laboratory Tests	Follow-Up Information
Pt	Baseline sCr	sCr	Dialysis	Urine Prot	sAlb	Urine RBC	Hgb	WBC	Plt	Other Laboratory Tests	Duration, d	Therapy	Outcome
1	1.1	12.5	Y	5.8	3.1	2	16.6	7.7	242	LDH 1504 U/L, ESR>130 mm/h, hsCRP 49.4 mg/L ferritin 1147 ng/ml, IL-6 12 pg/ml, IL-2R 1530 pg/ml	24	Tocilizumab, steroids	Dialysis dependent with sCr 14.2 mg/dl, UPCR 10.2 g/g, repeat COVID-19 negative
2	2	10.7	N	12.1	3.1	0–5	14.2	7.1 (with lymphopenia)	235	ESR 125 mm/h, ferritin 340.3 ng/ml	30	None	sCr 3.8 mg/dl, UACR 5.5 g/g, repeat COVID-19 negative
3	1	11.6	N	19	2.4		11.7	14.4 (with lymphopenia)	355	ESR 130 mm/h, CRP 232 mg/L, ferritin 5000 ng/ml	12	Steroids, hydroxychloroquine, ceftriaxone, doxycycline	sCr 2.3 mg/dl, UPCR 4 g/g, decreased ferritin, ESR, IL-6
4	1.1	4.9	N	6.2	2.5	0	9.8	7	257	elevated ESR, CRP 11.1 mg/L, ferritin 907 ng/ml, elevated IL-6 and d-dimer, CK 3200 U/L, +HCV Ab	11	Azithromycin, ceftriaxone	sCr 4.9 mg/dl, UPCR 4.1 g/g, repeat COVID-19 negative
5	Normal	15	Y	9	2.5		8.3	21	368	ESR 41 mm/h, CRP 229 mg/L, ferritin 2542 ng/ml	5		Dialysis dependent, repeat COVID-19 negative
6	Normal	2.2	N	21	<1.5	3–5	13.9	8.5	408	LDH 590 U/L, CRP 33.4 mg/L, ferritin 374 ng/ml	27	Azithromycin, hydroxychloroquine, steroids	sCr 0.8 mg/dl, UPCR 4.3 g/g, decreased CRP
7	3.5 (at adm)	6.7	Y	1+ on UA		21–50	11.4	14	250	None
8	2 (at adm)	9	Y	100 mg/dl on UA	2.6	0	10.6	13.1 (with lymphopenia)	320	LDH 3075 U/L, CRP 4.7 mg/L, ferritin >7500 ng/ml, CK 3309 U/L	<30	Tocilizumab, hydroxychloroquine, ceftriaxone, azithromycin	sCr 1.2 mg/dl
9		5.7	Y	300 mg/dl on UA	2.7	>5	12.8	9.2 (with lymphopenia)	454	LDH 309 U/L, CRP 13 mg/L, ESR>100 mm/h, ferritin 924 ng/ml, CK 128 U/L	30	Tocilizumab, hydroxychloroquine, ceftriaxone, azithromycin	Dialysis dependent
10	1.5–1.8	4.8	N	0.5	4.2	3	11.5	3.2	107	LDH 524 U/L, CRP 50.8 mg/L, ESR 33 mm/h, ferritin 2282 ng/ml, IL-6 21.4 pg/ml, +ANA	1	Hydroxychloroquine	sCr 2.5 mg/dl, urine prot 100 mg/dl on UA, repeat COVID-19 positive
11	Normal	0.8	N	8.8	1.7	6–15	12.3	14.8	283	LDH 300 U/L, CRP 153 mg/L, ferritin 397 ng/ml	18	Tacrolimus	sCr 1.3 mg/dl, repeat COVID-19 positive
12		2.9	N	6.8	3.0	Present	9	6.1	183	LDH 1019 U/L, ESR 127 mm/h, ferritin 635 ng/ml, +ANA, +anti-dsDNA Ab	35	None	sCr 2.4 mg/dl, UPCR 5–6 g/g, improved edema
13	0.9	2.5	N	9.2	2.0	20–50	8	6.8	182	IL-6 79 pg/ml	6	Steroids	Died from multiorgan failure secondary to COVID-19
14	0.9	20	Y	>300 mg/dl on UA	3.1	>182, with RBC casts	9.5	9.1	167	CRP 143 mg/L, CK 1460 U/L, +anti-GBM Ab	16	PLEX, steroids, cyclophosphamide	Dialysis dependent with sCr 6.7 mg/dl, repeat COVID-19 negative
15	1.7	2.6	N	0.2	4.5	60	8.1	3.9	211	IL-6 6.6 pg/ml	55	Tocilizumab, IVIG, steroids, thymoglobulin	sCr 2 mg/dl, UPCR 0.1 g/g, repeat COVID-19 negative
16	Dialysis dependent	9.4	Y		3.4		4.4	6.1	202	LDH 333 U/L, ESR 79 mm/h, CRP 195.6 mg/L, ferritin 1630 ng/ml	4	Tocilizumab, hydroxychloroquine, piperacillin-tazobactam, azithromycin	Dialysis dependent with sCr 6.7 mg/dl
17	2.5	2.9	N	0.2	4.4	3	10.1	3.3	286	CRP 0.49 ng/ml, ferritin 1677 ng/ml (previously)	7	None	sCr 2.2 mg/dl

Pt, patient; sCr, serum creatinine (milligrams per deciliter); urine prot, urine protein-creatinine ratio or 24-h urine protein; sAlb, serum albumin (grams per deciliter); RBC, red blood cell (per high-power field); Hgb, hemoglobin (grams per deciliter); WBC, white blood cell count (10³ per microliter); Plt, platelet (10³ per microliter); Y, yes; LDH, lactate dehydrogenase; ESR, erythrocyte sedimentation rate; hsCRP, high-sensitivity C-reactive protein; IL-2R, IL-2 receptor; UPCR, urine protein-creatinine ratio; repeat COVID-19, repeat PCR testing for severe acute respiratory syndrome coronavirus 2; N, no; UACR, urine microalbumin-creatinine ratio; CRP, C-reactive protein; CK, creatine kinase; +, positive; HCV Ab, Ab for hepatitis C virus; adm, admission; UA, urinalysis; ANA, antinuclear antibody; dsDNA, double-stranded DNA; PLEX, plasmapheresis; IVIG, intravenous Ig.

View popup

Table 3.

Pathologic findings in patients with COVID-19 who underwent kidney biopsy

Pt	Diagnosis		Light Microscopy									Electron Microscopy
Pt	Diagnosis	Other Findings	No. Glom	No. GS	No. Collapse	No. Noncollapsed FSGS	Hypercellularity	Microcysts	II	IFTA	VS	FPE	TRI	Viral Particles
1	Collapsing FSGS	ATI	20	0	14	0	N	Y	Focal	Mild	Mild	NA^a	NA^a	N
2	Collapsing FSGS	ATI	8	3	2	0	N	Y	Focal	Moderate	Moderate to severe	100	Y	N
3	Collapsing FSGS	ATI	18	4	4	1	N	Y	None	Moderate	Moderate	30	N	N
4	Collapsing FSGS	ATI	10	1	5	0	N	N	Focal	Severe	Mild	NA	NA	NA
5	Collapsing FSGS	ATI	11	3	7	0	N	Y	Focal	Severe	Moderate to severe	90	N	N
6	MCD	ATI	17	0	0	0	N	Y	None	None	None	100	Y	N
7	ATI		15	0	0	0	N	N	Focal	None	Mild	15	Y	N
8	ATI	Pigment casts	22	0	0	0	N	N	None	None	Mild	10	Y	N
9	ATI		2	1	0	0	N	N	None	Mild	Moderate	NA^a	NA^a	N
10	ATI		8	0	0	0	N	N	None	None	Moderate	5	N	N
11	MGN	PLA2R stain positive^b	15	3	0	4	N	N	Focal	Mild	Mild to moderate	100	N	N
12	MGN	PLA2R stain negative^b	3	2	0	0	N	Y	Focal	Moderate	Moderate to severe	30	Y	N
13	LN class 4+5		35	9	0	0	Mes, Endo, Crescents	N	Diffuse	Mild	Mild	90	Y	N
14	Anti-GBM GN	ATI, RBC casts	32	1	0	0	Crescents	Y	Diffuse	Mild	Moderate	NA^a	NA^a	N
15	TCMR grade 2A		11	1	0	0	N	N	Focal	None	Mild	NA	NA	NA
16	Infarction^c		NA	NA	NA	NA	NA	N	Focal	Severe	NA	NA	NA	NA
17	ATI		20	1	0	0	N	N	None	None	Mild	NA	NA	NA

Pt, patient; glom, No., number; glomerulus or glomeruli; GS, global sclerosis; II, interstitial inflammation; IFTA, tubular atrophy and interstitial fibrosis; VS, vascular sclerosis; FPE, foot process effacement (percentage); N, no; Y, yes; NA, not available; MCD, minimal change disease; LN, lupus nephritis; Mes, mesangial hypercellularity; Endo, endocapillary hypercellularity; RBC, red blood cell; TCMR, T cell–mediated rejection.
↵a All glomeruli were involved by crescents in the patient with anti-GBM GN, and no glomeruli were available for ultrastructural examination in two patients with native kidney biopsies.
↵b Performed by tissue staining.
↵c Nephrectomy specimen.