COVID-19 and Survival in Maintenance Dialysis.

To the Editor:

The end-stage kidney disease (ESKD) population receiving maintenance dialysis is highly vulnerable to the devastating consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated coronavirus disease 2019 (COVID-19). Although uremia itself is associated with an immune-incompetent state, patients with ESKD are generally older and often have comorbid conditions that increase the risk for poor outcomes in COVID-19., To date, information on the clinical course of COVID-19 among the ESKD population is limited to single-center experiences and/or homogeneous populations.3, 4, 5, 6, 7, 8 We sought to characterize and determine hospitalizations and survival among a diverse ESKD dialysis population with COVID-19 from the United States.

We conducted a retrospective cohort study of patients with ESKD with COVID-19 within Kaiser Permanente Southern California (KPSC). KPSC is an integrated health system comprised of 14 medical centers, more than 200 clinics, and patients at more than 300 dialysis facilities throughout Southern California. The ESKD population is racially/ethnically diverse, reflective of the 4.7 million KPSC membership population. This study was approved by the KPSC Institutional Review Board and exempted from informed consent (IRB #12502). Among patients 18 years and older receiving maintenance hemodialysis or peritoneal dialysis as of March 1, 2020, COVID-19–infected patients with ESKD were identified based on a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction test result and/or clinical documentation of a positive test result between March 1, 2020, and June 30, 2020. The date of the positive test was considered the index date and all patients were followed up for a minimum of 30 days unless a death event occurred or until the end of the observation period (August 10, 2020). Information on demographics, medications, laboratory results, comorbid conditions, hospitalizations, and death within the observation period was extracted from the electronic health records.

Among 7,533 total patients with ESKD, 133 (16 peritoneal dialysis and 117 hemodialysis) patients had COVID-19 diagnosed in our observation period (Fig 1). Mean age was 66 years, with 38% women, 62% Hispanics, 16% Blacks, 11% Asians, and 9% Whites (Table 1). Overall, 76 (57%) patients required hospitalization, with a median hospitalization length of 10 days. There were 30 (23%) patient deaths, with a median survival of 16 days. Patients who died were older (68 vs 64 years) and had more comorbid conditions, including diabetes (93%), heart failure (33%), and ischemic heart disease (57%). Only 2 (7%) deceased patients were receiving an angiotensin-converting enzyme inhibitor compared with 25% among survivors. There appeared to be no differences in mortality by race/ethnicity and socioeconomic status. Inpatient laboratory studies revealed that deceased patients had higher peak lactate dehydrogenase levels compared with survivors.

Figure 1

All patients within the Kaiser Permanente Southern California end-stage kidney disease population who had coronavirus disease 2019 (COVID-19) infection between March 1, 2020, and June 30, 2020. Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Table 1

Characteristics of the KPSC COVID-19 ESKD Population and by Hospitalization and Survival Outcomes

	All ESKD Patients With COVID-19	Severity				Mortality
		No Hospitalization After COVID-19		Hospitalized After COVID-19		Alive		Died During Follow-up After COVID-19		P
	N = 133	N	N = 57 (42.9%)	N	N = 76 (57.1%)	N	N = 103 (77.4%)	N	N = 30 (22.6%)
Age, y	66.0 [52.0-74.0]		63 [50.0-74.0]		66.0 [54.0-75.0]		64.0 [50.0-74.0]		68.0 [61.0-80.0]	0.02
Female sex	51 (38.3%)		24 (42.1%)		27 (35.5%)		41 (39.8%)		10 (33.3%)	0.52
Race										0.34
White/Caucasian	12 (9%)		5 (8.8%)		7 (9.2%)		8 (7.8%)		4 (13.3%)
Black	21 (15.8%)		8 (14%)		13 (17.1%)		17 (16.5%)		4 (13.3%)
Hispanic	83 (62.4%)		38 (66.7%)		45 (59.2%)		66 (64.1%)		17 (56.7%)
Asian Pacific Islander	14 (10.5%)		6 (10.5%)		8 (10.5%)		11 (10.7%)		3 (10%)
Other	3 (2.3%)		0 (0%)		3 (3.9%)		1 (1%)		2 (6.7%)
Household income, $	56,100 [44,018-67,024]		56,407 [43,809-66,264]		55,793 [44,701-67,217]		55,782 [43,442-70,416]		57,179 [45,236-63,942]	0.87
Weight, lbs	180.1 [152.5-214.5]		173.6 [141.2-200.4]		182.9 [158.8-219.8]		174.2 [152.1-212.5]		185.5 [158.5-219.1]	0.49
Body mass index, kg/m2	28.4 [25.0-32.6]		27.9 [23.8-32.4]		29.0 [25.2-33.0]		28.3 [24.8-32.6]		29.1 [25.1-33.4]	0.68
Baseline BP, mm Hg
Systolic BP	135.0 [118.0-156.0]		138.0 [121.0-157.0]		133.0 [111.0-155.0]		132.0 [114.0-154.0]		143.0 [118.0-158.0]	0.21
Diastolic BP	67.0 [59.0-78.0]		67.0 [60.0-78.0]		65.5 [59.0-77.0]		66.0 [59.0-77.0]		68.0 [60.0-80.0]	0.55
Primary cause of ESKD										0.40
Diabetes	93 (69.9%)		37 (64.9%)		56 (73.7%)		68 (66%)		25 (83.3%)
Hypertension	19 (14.3%)		11 (19.3%)		8 (10.5%)		17 (16.5%)		2 (6.7%)
Glomerulonephritis	10 (7.5%)		5 (8.8%)		5 (6.6%)		9 (8.7%)		1 (3.3%)
Polycystic kidney disease	2 (1.5%)		1 (1.8%)		1 (1.3%)		2 (1.9%)		0 (0%)
Other	9 (6.8%)		3 (5.3%)		6 (7.9%)		7 (6.8%)		2 (6.7%)
History of transplant										0.18
Kidney	4 (3%)		2 (3.5%)		2 (2.6%)		3 (2.9%)		1 (3.3%)
Other organs	1 (0.8%)		0 (0%)		1 (1.3%)		0 (0%)		1 (3.3%)
Modality										0.36
Peritoneal dialysis	16 (12.0%)		5 (8.8%)		11 (14.5%)		14 (13.6%)		2 (6.7%)
Hemodialysis	117 (88.0%)		52 (91.2%)		65 (85.5%)		89 (86.4%)		28 (93.3%)
ESKD duration, y	3.5 [1.9-5.8]		3.0 [1.4-6.1]		4.0 [2.2-5.7]		3.1 [1.5-5.7]		4.6 [3.1-6.4]	0.05
Comorbid conditions
Congestive heart failure	34 (25.6%)		14 (24.6%)		20 (26.3%)		24 (23.3%)		10 (33.3%)	0.27
Ischemic heart disease/coronary artery disease	54 (40.6%)		19 (33.3%)		35 (46.1%)		37 (35.9%)		17 (56.7%)	0.04
Hypertension	129 (97%)		55 (96.5%)		74 (97.4%)		99 (96.1%)		30 (100%)	0.27
Diabetes mellitus	103 (77.4%)		38 (66.7%)		65 (85.5%)		75 (72.8%)		28 (93.3%)	0.02
Peripheral vascular disease	8 (6%)		1 (1.8%)		7 (9.2%)		4 (3.9%)		4 (13.3%)	0.06
Cerebrovascular disease	8 (6%)		2 (3.5%)		6 (7.9%)		5 (4.9%)		3 (10%)	0.30
Liver disease	22 (16.5%)		13 (22.8%)		9 (11.8%)		17 (16.5%)		5 (16.7%)	0.90
Chronic obstructive pulmonary disease	13 (9.8%)		6 (10.5%)		7 (9.2%)		11 (10.7%)		2 (6.7%)	0.51
Asthma	17 (12.8%)		8 (14.0%)		9 (11.8%)		13 (12.6%)		4 (13.3%)	0.92
Obesity	51 (38.3%)		20 (35.1%)		31 (40.8%)		38 (36.9%)		13 (43.3%)	0.52
Smoking										0.77
Never	83 (62.4%)		33 (57.9%)		50 (65.8%)		62 (60.2%)		21 (70%)
Current	1 (0.8%)		0 (0%)		1 (1.3%)		1 (1.0%)		0 (0%)
Former	44 (33.1%)		22 (38.6%)		22 (28.9%)		36 (35%)		8 (26.7%)
Elixhauser comorbidity score										0.39
1-3	9 (6.8%)		2 (3.5%)		7 (9.2%)		8 (7.8%)		1 (3.3%)
≥4	124 (93.2%)		55 (96.5%)		69 (90.8%)		95 (92.2%)		29 (96.7%)
Drugs taken within 1 y before admissions
Antiplatelets/nonsteroidal inflammatory agents	17 (12.8%)		6 (10.5%)		11 (14.5%)		14 (13.6%)		3 (10%)	0.60
Antiarrhythmic	3 (2.3%)		2 (3.5%)		1 (1.3%)		2 (1.9%)		1 (3.3%)	0.65
Calcium channel blockers	68 (51.1%)		29 (50.9%)		39 (51.3%)		56 (54.4%)		12 (40%)	0.17
Lipid-lowering agents	91 (68.4%)		36 (63.2%)		55 (72.4%)		69 (67%)		22 (73.3%)	0.51
β-Blockers	84 (63.2%)		35 (61.4%)		49 (64.5%)		62 (60.2%)		22 (73.3%)	0.19
Angiotensin-converting enzyme inhibitors	28 (21.1%)		15 (26.3%)		13 (17.1%)		26 (25.2%)		2 (6.7%)	0.03
Angiotensin receptor blockers	34 (25.6%)		15 (26.3%)		19 (25.0%)		26 (25.2%)		8 (26.7%)	0.88
Diuretics	3 (2.3%)		2 (3.5%)		1 (1.3%)		3 (2.9%)		0 (0%)	0.34
Insulin	45 (33.8%)		14 (24.6%)		31 (40.8%)		32 (31.1%)		13 (43.3%)	0.21
Oral hypoglycemics	21 (15.8%)		8 (14%)		13 (17.1%)		15 (14.6%)		6 (20%)	0.47
Laboratory values
Hemoglobin, g/dL	10.8 [9.7-11.7]	57	10.5 [9.4-11.6]	76	11.1 [9.9-11.7]	103	10.8 [9.6-11.8]	30	10.7 [9.8-11.4]	0.18
Albumin, g/dL	3.3 [2.8-3.7]	57	3.2 [2.6-3.7]	74	3.3 [2.9-3.7]	101	3.2 [2.8-3.7]	30	3.3 [2.9-3.7]	0.72
Hemoglobin A1c, %	6.0 [5.3-7.2]	54	6.0 [5.2-7.0]	76	6.1 [5.3-7.3]	100	5.9 [5.3-7.1]	30	6.5 [5.3-7.3]	0.48
Total cholesterol, mg/dL	131.5 [102.5-155.5]	57	131.0 [106.0-161.0]	75	132.0 [100.0-154.0]	102	139.0 [107.0-161.0]	30	117.5 [90.0-146.0]	0.01
High-density lipoprotein cholesterol, mg/dL	38.5 [31.0-47.0]	57	39.0 [33.0-47.0]	75	38.0 [30.0-46.0]	102	39.5 [32.0-47.0]	30	34.5 [30.0-44.0]	0.09
Low-density lipoprotein cholesterol, mg/dL	61.5 [44.5-87.0]	57	61.0 [46.0-85.0]	75	62.0 [44.0-88.0]	102	62.0 [46.0-91.0]	30	56.5 [40.0-79.0]	0.09
Inpatient laboratory valuesa
Triglycerides, mg/dL	266.0 [189.0-363.0]			25	266.0 [189.0-363.0]	16	257.0 [182.0-360.5]	9	316.0 [189.0-390.0]	0.90
D-Dimer, mcg/mL	2.4 [1.8-4.4]			43	2.4 [1.8-4.4]	28	2.3 [1.8-4.2]	15	2.5 [2.0-4.4]	0.70
Fibrinogen, mg/dL	649.0 [501.0-762.0]			23	649.0 [501.0-762.0]	14	638.5 [546.0-768.0]	9	653.0 [486.0-689.0]	0.61
C-Reactive protein, mg/L	180.0 [99.4-315.8]			53	180.0 [99.4-315.8]	37	186.1 [98.7-285.4]	16	177.9 [116.5-319.2]	0.55
Lactate dehydrogenase, U/L	363.0 [243.5-481.0]			52	363.0 [243.5-481.0]	38	304.5 [241.0-473.0]	14	426.5 [353.0-523.0]	0.04
Creatine kinase, U/L	177.0 [85.0-304.0]			33	177.0 [85.0-304.0]	23	142.0 [80.0-304.0]	10	243.0 [107.0-340.0]	0.24
Lymphocyte count, 103 × cells/mL	1.3 [0.6-1.7]			58	1.3 [0.6-1.7]	39	1.3 [0.7-1.7]	19	1.3 [0.4-1.7]	0.41

Note: Values expressed as median [interquartile range] or number (percent).

Abbreviations: BP, blood pressure; COVID-19, coronavirus disease 2019; ESKD, end-stage kidney disease; KPSC, Kaiser Permanente Southern California.

The highest levels during the hospitalization were used to capture patients who may have met criteria for cytokine storm syndrome.

We describe the clinical course of all 133 patients with ESKD with COVID-19 diagnosed within a large integrated health system. Most (57%) required hospitalization. The 23% mortality in our ESKD cohort is significantly greater than the 1.3% within KPSC, 1.8% in California, and the 3% to 4% mortality reported from the Centers for Disease Control and Prevention and the World Health Organization for people with COVID-19 diagnosed. The dialysis population is more likely to be identified with COVID-19 given the frequency of screening and care they receive at health facilities because they have a low threshold for screening and testing. Tests were routinely performed based on clinical presentation (fever and symptoms) or history of exposure. Beginning early March 2020, individual dialysis units throughout California instituted strict policies and procedures to screen for SARS CoV-2 infection to protect patients and personnel throughout these dialysis centers.

Among our COVID-19–infected ESKD population, there appeared to be a greater proportion of Hispanics (62% vs 38%) and lesser proportion of Blacks (16% vs 23%) and non-Hispanic Whites (9% vs 28%) compared with the overall KPSC ESKD population. The 12% of peritoneal dialysis patients with COVID-19 was lower than the 20% of the prevalent home dialysis/peritoneal dialysis population at KPSC. We observed no apparent differences in survival based on race/ethnicity or socioeconomic status. Patients who died were older and had more comorbid conditions; specifically, heart failure, ischemic heart disease, and diabetes. Our findings are comparable to a French National ESKD cohort with an overall 21% mortality. Previous observations among hospitalized patients with ESKD with COVID-19 have observed mortality rates ≥30% reported in relatively homogeneous populations.,

Strengths of our study include our observation period of 30 or more days to fully capture the clinical course of patients with ESKD. Information was drawn from a single integrated system that tracks this population using a comprehensive internal registry and thus was able to reliably capture all hospitalizations and deaths. Limitations include the fact that we cannot fully determine that deaths were due to COVID-19 or whether patients opted for palliative care/hospice. The reported death rate, although high, is an aggregate over a 3-month period. It does not reflect changing rates of mortality, which may occur with the evolving care of COVID-19, including more aggressive oxygenation support, screening and monitoring for cytokine storm syndrome, and earlier use of steroids, immunosuppression, prophylactic anticoagulation, and expanded remdesivir use to include patients with ESKD.

Although the overall COVID-19 rates were low among the ESKD population, we observed high mortality among patients with ESKD with COVID-19. Although cardiovascular disease and diabetes were higher among deceased patients, there were no differences in race/ethnicity and socioeconomic status compared with survivors.