Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review

Table 1 Native kidney biopsy outcomes of collapsing glomerulopathy in coronavirus disease 2019 cases

Ref.	Age	Sex	Ethnicity	Comorbidities		Renal Px	Baseline creatinine (mg/dL)	Presentation creatinine (mg/dL)	Presentation proteinuria (g/day)	Presentation albumin (g/L)	Treatment received	Outcome (renal and survival)	RRT needed	Time to biopsy	Haematuria
Kudose et al[13]	46	M	B	Obesity		AKI, NS	1.1	12.5	5.8	3.1	Tocilizumab/Steroids	DD	Yes	-	< 10
Kudose et al[13]	62	M	B	HTN, prostate cancer, CKD		AKI, NS	2	10.7	12.1	3.1	None	DI	No	-	< 10
Kudose et al[13]	62	M	B	HTN, DM, prostate Cancer		AKI, NRP	1	11.6	19	2.4	HCQ, Steroids	DI	No	-	-
Kudose et al[13]	57	M	B	HTN, hepatitis C, CKD		AKI, NRP	1.1	4.9	6.2	2.5	None	DI	No	-	< 10
Kudose et al[13]	61	M	B	HTN, obesity		AKI, NRP	Normal	15	9	2.5	-	DD	Yes	-	-
Sharma et al[14]	77	F	B	HTN		AKI	1	8.15	1.5	-	HCQ, Steroids	DI	Yes	-	No
Wu et al[16]	63	M	B	HTN, DM		-	1.3	4.9	12.7	-	-	DD	Yes	-	< 10
Wu et al[16]	64	F	B	HTN, DM		-	1.5	4.2	4.6	-	-	DI	No	-	Negative
Wu et al[16]	65	F	B	HTN, DM		-	1.3	2.9	13.6	-	-	Died	Yes	-	Negative
Wu et al[16]	44	M	B	-		-	1.4	11.4	25	-	-	DD	Yes	-	50-100
Wu et al[16]	37	M	B	-		-	1	9	-	-	-	Died	Yes	-	< 10
Wu et al[16]	56	M	B	HTN		-	1.2	6.7	3.6	-	-	DI	Yes	-	> 100
Akilesh et al[17]	46	M	B	HTN		AKI, NS	-	8.7	13.7	-	-	DD	Yes	2 wk	No
Akilesh et al[17]	60	F	B	HTN		AKI, NRP	-	5.7	21	-	-	-	-	4 wk	No
Akilesh et al[17]	58	F	B	HTN		AKI, NS	-	10.2	20	-	-	DD	Yes	-	-
Akilesh et al[17]	44	M	H	-		AKI, NRP	-	12	11.4	-	-	DD	Yes	6 wk	No
Akilesh et al[17]	58	M	B	-		AKI, NRP	-	11.3	4	-	-	DI	Yes	Day 4	Yes
Akilesh et al[17]	47	M	B	HTN		AKI, TMA	-	6.6	7.6	-	-	DD	Yes	Day 25	Yes
Akilesh et al[17]	63	F	B	HTN		AKI, NRP, TMA	-	6	20	-	-	DD	Yes	Day 10-14	Yes
Gupta et al[18]	71	M	I	HTN, DM		AKI, NS	1.19	4.49	18.46	2	Steroid (Prednisolone 60mg OD)	DD	Yes	1st-D6, 2nd 2 mo	No
Gupta et al[18]	54	M	B	HTN, DM		AKI, NS	1.08	4.67	16	1.6	None	-	No	Day 30	No
Noble et al[43]	54	M	B	HTN, obesity		AKI, NRP	125	6.54	4.08	-	None	DI	Yes	Day 16	Yes
Kissling et al[19]	63	M	B	HTN		AKI, NRP	-	1.2	5	-	None	DI	No	Day 8	-
Magoon et al[21]	28	M	B	-		AKI	-	0.99	2	-	None	DI	Yes	Day 7-34	Yes
Magoon et al[21]	56	M	B	HTN, CKD		AKI, NRP	-	3.17	21	-	None	DI	Yes	-	Yes
Gaillard et al[20]	79	M	B	HTN, MGUS, CKD		AKI, NRP	-	2.55	11.4	2.9	Dexamethasone, lopinavir/ritonavir, PLEX	DD	Yes	Day 5	No
Sharma et al[15]	67	M	B	HTN, DM		AKI, NRP	1	2.2	3.2	-	HCQ/steroids	DD	Yes	Day 8-8/52	< 10
Sharma et al[15]	49	M	B	HTN		AKI	0.95	4.85	2.59	-	HCQ/steroids	DD	Yes	> Day 4	< 10
Nlandu et al[22]	48	M	B	HTN, DM		AKI, NS	0.72	15.9	18	-	Chloroquine, azithromycin, vitamin C	DI	Yes	Day 30	No
Deshmukh et al[23]	42	M	I	-		NS	-	1	8	'hypoalbuminaemia' noted	Ramipril	-	No	Day 24	Yes
Kadosh et al[24]	56	M	B	CKD		AKI, NRP	-	1.86 (peak 7.78)	1.97 (peak 7.35)	-	MMF and steroids stopped, azithromycin, nitozaxonide	DI	No	> Day 7	-
Coutourier et al[25]	53	M	B	HTN		AKI, NRP	1.02	1.89 (peak 2.20)	5.64 (peak 18.7)	1.3 (day 3)	Oseltamivir, HCQ, chloroquine, azithromycin	DI	No	Day 3-11	No
Couturier et al[25]	53	M	B	HTN, Hepatitis B		AKI, NRP	1.35	5.34 (peak 6.01)	1.5 (peak 2.65)	-	-	-	No	> Day 7	No
Larsen et al[26]	44	M	B	HTN, DM, CKD		AKI, NRP	1.4	4	3.9 (peak 25)	2.5	None	DD	Yes	Day 8	Yes
Malhotra et al[27]	64	M	B	HTN, DM, CKD, HIV on HAART		AKI, NRP	-	2.3	2.74	-	Solumedrol, zinc, Vitamin C, Oxitris Filter	DD	Yes	Day 11	Yes
Izzedine et al[28]	49	F	B	CKD, heart transplant, type 2 diabetes, HTN, obesity		AKI, NS	1.78	2.39	6.6	1.7	-	DI	Yes	Day 8	< 10
Izzedine et al[28]	38	F	B	CKD, SLE, HTN, obesity		AKI, NS	14.64	11.7	-	1.9	-	DI	No	-	< 10
Laboux et al[29]	47	M	B	HTN		AKI	0.8	30.3	1.2	2.5	Dialysis	DI	Yes	Day 30	-
Malik et al[30]	57	M	B	-		AKI, NS	-	2.0 then 3.4	14.9	3.4	Antibiotics, oseltamivir, oxygen	DD	Yes	-	-
FSGS with podocytopathy
Akilesh et al[17]	59	M	B	HTN, DM	AKI, NRP		-	11.9	> 12	-	Unknown	-	Unknown	Day 11	-

AKI: Acute kidney injury; B: Black; CKD: Chronic kidney disease; DM: Diabetes mellitus; DD: Dialysis dependent at hospital discharge; DI: Dialysis independent at hospital discharge; F: Female; H: Hispanic; HAART: Highly active antiretroviral therapy; HCQ: Hydroxychloroquine; HIV: Human immunodeficiency virus; HTN: Hypertension; I: Indian; M: Male; MGUS: Monoclonal gammopathy of undetermined significance; MMF: Mycophenolate mofetil; NRP: Nephrotic range proteinuria; NS: Nephrotic syndrome; PLEX: Plasma exchange; SLE: Systemic lupus erythematosus; TMA: Thrombotic microangiopathic anemia; FSGS: Focal Segmental Glomerulosclerosis.

Table 2 Native kidney biopsy outcomes of acute tubular injury and necrosis in coronavirus disease 2019 cases

Ref.	Age	Sex	Ethnicity	Comorbidities	Renal presentation	Baseline creatinine (mg/dL)	Presentation Creatinine (mg/dL)	Presentation proteinuria (g/day)	Presentation albumin (g/L)	Treatment received	Outcome (renal and survival)	RRT needed	Time to biopsy	Haematuria
Sharma et al[14]	62	M	Hispanic	T2DM	AKI and proteinuria	-	1.2	3	-	Steroid, HCQ, anakinra, plasma	Died	Yes	-	Yes
Sharma et al[14]	69	M	Hispanic	HTN	AKI, proteinuria, anti-cardiolipin positive	-	0.9	2.4	-	Steroid, HCQ, anakinra, plasma	Died	Yes	-	Yes
Sharma et al[14]	76	F	Caucasian	T2DM, HTN	Severe AKI and Proteinuria	-	1 (peak 4.4)	0.9	-	None	DI	No	-	No
Sharma et al[14]	59	M	Black	HTN, CCF	AKI, Proteinuria and raised K:L ratio	-	4.5 (peak 6)	2.8	-	None	DI	No	-	Yes
Sharma et al[14]	69	F	Black	HTN, Hyperlipidaemia	AKI NRP	-	1.9	7.6	-	Steroids	DD	Yes	-	No
Kudose et al[13]	43	F	Black	T2DM, HLD, streptococcal infection, obesity (BMI 52.5)	AKI	-	3.5 (peak 6.7)	1	-	None	DD	Yes	-	Yes
Kudose et al[13]	67	M	Caucasian	HTN, Gout, Obese	AKI on CKD	-	5.7	0.3	-	Tocilizumab, HCQ, azithromycin	DD	Yes	-	Yes
Kudose et al[13]	51	M	Black	HTN, AF, HLD, CVA, BPH	AKI on CKD	1.8	4.8	0.5	-	HCQ	DI	No	-	Yes
Akilesh et al[17]	34	F	Caucasian	HTN, T2DM	AKI NS	-	1.2	7	-	-	DI	No	Day 4	No
Akilesh et al[17]	67	F	Hispanic	HTN	AKI	-	1.4	1	-	-	DI	No	Day 5	Yes
Lenti et al[31]	25	M	Caucasian	-	AKI NS	-	3.8	0.48	-	-	-	-	-	-
Rossi et al[32]	49	M	Caucasian	Obesity	AKI	-	-	-	-	HCQ, Lopinavir/Ritonavir	DI	Required when in hospital	-	-
Papadimitriou et al[33]	52	M	-	HIV, HTN, coronary artery disease, Factor V deficiency	AKI	Normal	7.5	1.85	-	-	DD	Yes	Day 10	-
Papadimitriou et al[33]	64	M	-	AF, hyperlipidaemia, gout	AKI	1	1.4	-	-	I&V, IV heparin then apixaban (AF), 4 units blood following haematemesis, meropenem (E. coli in sputum), RRT day 22 to 33, MRSA > linezolid	DI	Yes	Day 84	-

AKI: Acute kidney injury; AF: Atrial fibrillation; BPH: Benign prostatic hypertrophy; CCF: Congestive cardiac failure; CKD: Chronic kidney disease; CVA: Cerebrovascular accident; DD: Dialysis dependent at hospital discharge; DI: Dialysis independent at hospital discharge; DSA: Donor specific antibodies; HCQ: Hydroxychloroquine; HIV: Human immunodeficiency virus; HLD: Hyperlipidaemia; HTN: Hypertension; I&V: Intubated and ventilated; K:L ratio: Kappa:lambda light chain ratio; RRT: Renal replacement therapy; T2DM: Type 2 diabetes mellitus.

Table 3 Transplant kidney biopsy findings in coronavirus disease 2019 cases

Ref.	Age		Sex	Ethnicity	Comorbidities	Renal Presentation	Baseline creatinine (mg/dL)	Presentation creatinine (mg/dL)	Presentation proteinuria (g/day)	Presentation albumin (g/L)	Treatment received	Outcome (renal and survival)	RRT needed	Time to biopsy	Haematuria
T-cell mediated rejection
Kudose et al[13]	54		F	Caucasian	IgA Nephropathy, Donor Specific Ab +ve, HTN, obesity	AKI	1.7	2.6	0.2	-	Steroids, Tocilizumab, thymoglobulin, IVIG	DI	No	-	Yes
ABMR
Akilesh et al[17]	47		F	Black	HIV-associated Nephropathy, Deceased Donor Tx 2015, Vascular Rejection Post-Tx, HTN	AKI	-	1.63	2	-	Renal transplantation, 5-MTP, PLEX IVIG	-	-	6 wk	No
Akilesh et al[17]	54		M	Asian	Chronic Transplant Glomerulopathy, C4d –ve, HTN, T2DM	AKI with Proteinuria	1.9	5.2	3	-	Regular MMF withheld, regular tacrolimus dose reduced, steroids	DI	No	6 wk	No
Abuzeineh et al[44]	54		M	Black	Diabetic nephropathy, Tx, HTN	AKI	1.4	2.6	-	-	IVF, MMF discontinued, NHF oxygen, antibiotics, antifungals, tocilizumab	DI	No	73 d	-
Acute tubular injury
Akilesh et al[17]	42		M	Hispanic	Live Donor Tx 2019, HTN	AKI	1.27	1.53	0.15	-	-	DI	No	7 wk	No
Kudose et al[13]	54		F	Hispanic	ADPKD, Deceased Donor Tx 2020, HTN	AKI	2.5	2.9	0.2	-	None	DI	No	-	-
Westhoff et al[50]	69		M	-	Diabetic nephropathy	AKI	1.1	2.2	-	-	IV hydrocortisone, tacrolimus and MMF held, HCQ, levetiracetam	DI	No	14 d	-
FSGS
Doevelaar et al[45]		35	M	Black	Deceased donor Tx 2019	AKI, Normothermic Regional Perfusion	-	1.7	3.29	-	Steroids (Hydrocortisone 200 mg/d)	DI	No	34 d	-
Oniszczuk et al[48]		49	M	Black	Renovascular disease, deceased donor Tx 2020	AKI, Nephrotic Syndrome	1.47	2.17	3.27	2.7	Steroids, ACE Inhibitor	DI	No	2 wk	-
Yamada et al[51]		49	F	Black	Pre-eclampsia, Live donor Tx 1995 (from sibling)	AKI, Normothermic Regional Perfusion	1.6	3.4	6.3	3.8 at diagnosis with COVID-19	ACE Inhibitor, Steroids (Prednisolone 60 mg with quick wean due to side effects)	DI	No	5 d	-
Collapsing FSGS
Noble et al[43]	45		M	Black	Malignant HTN, Obesity (BMI 42.6), Live Donor Tx 2016	AKI, Nephrotic syndrome	3.22	4.69	1.09	-	MMR withheld on admission, restarted after 14 d. Steroid (Prednisolone dose doubled from 10 mg OD to 20mg OD)	DD	Yes	12 d	Yes
Lazareth et al[47]	29		M	Black	Urinary Schistosomiasis, Deceased Donor Tx 2015, Previous ABMR in Jan 2020	AKI, Nephrotic Syndrome	3.18	6.06	0.49	2.8	MMF withheld temporarily	DI	No	2 d	-
Transplant infarction
Kudose et al[13]	22		M	Black	Membranous Nephropathy PLA2R +ve, Deceased Donor Tx 2018, HTN	AKI	-	9.4	-	-	Tocilizumab, HCQ, Azithromycin	DD	Yes	-	-
Webb et al[49]	49		M	-	Chronic glomerulonephritis, HTN, DCD renal transplant 2001 with subsequent ABMR, CMV	AKI	0	2.03	-	-	Nasal high flow oxygen, prednisolone, enoxaparin, ertapenem	DD	Yes	27 d	-
TMA
Jespersen et al[46]	49		F	-	FSGS	AKI	-	2.81	-	-	Supportive	DI	No	> 22 d	-

5-MTP: 5-methoxytryptophan; Ab: Antibody; ABMR: Antibody mediated rejection; ADPKD: Autosomal dominant polycystic kidney disease; AKI: Acute kidney injury; CMV: Cytomegalovirus; DCD: Donor after circulatory death; DD: Dialysis dependent at hospital discharge; DI: Dialysis independent at hospital discharge; FSGS: Focal and segmental glomerulosclerosis; HCQ: Hydroxychloroquine; HIV: Human immunodeficiency virus; HTN: Hypertension; IVF: Intravenous fluids; IVIG: Intravenous immunoglobulin; MMF: Mycophenolate mofetil; NHF: Nasal high flow; PLA2R: Phospholipase 2 receptor antibody; PLEX: Plasma exchange; T2DM: Type 2 diabetes mellitus; Tx: Transplant.

Table 4 Post-mortem kidney biopsy findings in coronavirus disease 2019 cases

Ref.	Number in series	Number with kidney histology	Age-median (range)	Gender (male), n (%)	Comorbidities, n (%)	AKI, n (%)	RRT, n (%)	Covid treatment, n (%)	Pathological findings, n (%)
Bradley et al[52]	14	14	73.5 (42-84)	6	Diabetes 5, HTN 9, CKD 5	6 (1 at presentation)		-	ATI 11, FSGS 1, chronic inflammation 1, renal vein thrombus 1
Su et al[67]	26	26	69 (39-87)	19	Diabetes 3, HTN 11, CKD 2	-	5 (6 no record)	Arbidol 10, Ribavirin 2, Lopinavir/ritonavir 5, steroids 15	ATI 26, TMA 1, FSGS 2, pigment nephropathy 3, IgA 1, pyelonephritis 2, PIGN 1
Santoriello et al[64]	42	31 (11 excluded due to autolysis)	71.5 (38-97)	29	Diabetes 17, HTN 30, CKD 8	31 (94)-stage (38.1)	8 (36)	Plaquenil 36, steroids 22 (61% combination), tocilizumab 6 (17%)	ATI 31, TMA 6, collapsing FSGS 1, chronic inflammation 27, IgA 1
Farkash et al[55]	1	1	53	-	-	1	1	HCQ, IL-6 blinded trial	ATI 1
Werion et al[68]	49	6	64 (54-74)	34	Diabetes 10, HTN 23, CKD 7	11 (22)	2 (4)	HCQ 48 (98%), azi 7 (14%), steroids 7 14%), IL-7: 8 (16.5%), tocilizumab 1 (2%)	ATI 5, FSGS 1, chronic inflammation 2
Lax et al[60]	11	11	N/A	8	Diabetes 5, HTN 8	6 (54.5)	-	Azi/HCQ 2	ATI 11, chronic inflammation 2
Golmai et al[56]	12	12	75 (49-92)	10	Diabetes 4, HTN 9, CKD 1	9	8	Tocilizumab/HCQ/steroids 7, HCQ/steroids 4	ATI 9, oxalosis 1
Falasca et al[54]	18	9	76.5 (27-92)	12	Diabetes 4, HTN 4 , CKD 2	-	-		Chronic inflammation 12
Schurink et al[65]	21	21	68 (41-78)	16	Diabetes 1	15 (71); 10 stage 3	5	Chloroquine 10 (48%), antiviral 4 (19%), steroids 5 (24%)	ATI 12, TMA 1
Hanley et al[58]	10	9	73 (IQR 52-79)	7	HTN 4	-	-	-	ATI 9, TMA 5
Rapkiewicz et al[62]	7	7	60 (44-65)	3	Diabetes 5, HTN 6, CKD 1	-	-	Azi/HCQ 2, Azi/HCQ/Tocilizumab 2, Azi/HCQ/Anakinra	ATI 7, TMA 1
González Pessolani et al[57]	4	2	78	2	Diabetes 1, HTN 1	2		-	ATI 2, TMA 1
Jacobs et al[59]	1	1	78	1	HTN 1	1	1	Azi/HCQ/steroids	ATI 1, Oxalosis 1
Sekulic et al[66]	2	2	(54-81)	2	Diabetes 2, HTN 2, CKD 1	2	-	Remdesivir 1	ATI 2
Remmelink et al[63]	17	17	72 (62-77)	12	Diabetes 9, HTN 10, CKD 3	15	-	HCQ 15, Steroids 2, Lopinavir/ritonavir 2, Remdesivir 2, Oseltamivir 1	-
Brook et al[53]	5	3	75 (58-82)	1	Diabetes 2, HTN 3, CKD 1	-	-	-	ATI 3
Menter et al[61]	21	17	76 (53-96)	17	Diabetes 7, HTN 21, CKD 4	-	-	-	ATI 14, TMA 2

AKI: Acute kidney injury; ATI: Acute tubular injury; Azi: Azithromycin; CKD: Chronic kidney disease; FSGS: Focal and segmental glomerulosclerosis; HCQ: Hydroxychloroquine; HTN: Hypertension; IgA: Immunoglobulin A; IL-6: Interleukin-6; PIGN: Post infectious glomerulonephritis; RRT: Renal replacement therapy; TMA: Thrombotic microangiopathy.