Clinical and paraclinical parameters in COVID-19 patients with nephrological disorders

doi:10.21203/rs.3.rs-2009144/v1

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Clinical and paraclinical parameters in COVID-19 patients with nephrological disorders

https://doi.org/10.21203/rs.3.rs-2009144/v1

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Background: In this study, we aimed to examine the relationship between kidney patients’ COVID-19 status and their symptoms, laboratory values, and ICU admission status. We also evaluated the association between COVID-19-positive kidney patients’ age, gender, smoking status, history of underlying diseases and urea and creatinine levels, and their ICU admission status and mortality. Finally, we analyzed the differences in laboratory values in kidney patients with and without a history of diabetes or cardiovascular disease.

Methods: In this cross-sectional study, 253 patients with a history of kidney disease were included. COVID-19 was diagnosed by positive RT-qPCR. Symptoms, laboratory findings, and outcomes were extracted from the patients’ records and statistically investigated.

Results: Fever, chills, myalgia, arthralgia, cough, anorexia, nausea, fatigue, headache, mental status deterioration, and smoking were more common in COVID-19-positive kidney patients compared to COVID-19-negative ones. White blood cells (WBC), platelets, and urea were lower and hemoglobin and hematocrit were higher in the former group. WBC, urea, and blood sugar (BS) levels were higher in kidney patients with a history of cardiovascular disease compared to kidney patients without such a history. Low-density lipoprotein cholesterol (LDL) was lower in the former group. Hemoglobin and hematocrit were lower in diabetic kidney patients compared to non-diabetic kidney patients. BS, triglycerides, and erythrocyte sedimentation rate (ESR) were higher in the former group. History of underlying diseases and abnormal creatinine was associated with increased ICU admission and age ≥ 50, male gender and abnormal creatinine were associated with increased mortality in COVID-19-positive kidney patients.

Conclusions: Smoking cessation should be encouraged in kidney patients. Fever, chills, myalgia, arthralgia, cough, anorexia, nausea, fatigue, headache, and mental status deterioration in kidney patients can indicate COVID-19 infection. Monitoring WBC and platelet counts in COVID-19-positive kidney patients, WBC, urea, and BS in kidney patients with a history of cardiovascular disease, and ESR, triglycerides, and hemoglobin in diabetic kidney patients can prove beneficial in their management. Age, gender, history of underlying diseases, and creatinine levels can be important prognostic markers in COVID-19-positive kidney patients.

COVID-19

kidney disease

cardiovascular disease

diabetes

characteristics

In December 2019, a new type of coronavirus named SARS-CoV-2 emerged in Wuhan, China, and resulted in a pandemic. Most countries including Iran have been affected by this virus (1, 2). The clinical manifestations of this disease range from asymptomatic to severe disease, including lung damage and death, and its primary symptoms include fever, myalgia, fatigue, and dry cough (3–5). Everyone is susceptible to the virus, but the elderly and people with underlying diseases are more prone to adverse outcomes. The elderly experience severe disease, and their mortality rate is high (6–10). Previous studies have shown that the mortality rate is high in COVID-19 patients with a history of underlying diseases (11). For example, it has been seen that patients with a history of heart problems have a poorer prognosis in case of contracting the infection with COVID-19 (12).

According to previous studies, high blood pressure, cardiovascular diseases, diabetes, kidney diseases, and chronic obstructive pulmonary diseases (COPD) are the most common underlying diseases among hospitalized COVID-19 patients. Chronic kidney disease (CKD) is reported among the most prevalent underlying diseases among these patients (13) and has been associated with higher mortality (14). Acute kidney injury (AKI) is also a common complication among these patients (15), as reported in the United States in 28 to 46% of patients admitted with COVID-19, and has been associated with higher mortality, adverse outcomes, and longer stays in the intensive care unit (ICU) (16, 17), and is known as an independent factor in the incidence of mortality in patients with COVID-19 (18).

The characteristics of SARS-CoV-2 are not yet fully known, thus scarce information is at hand about COVID-19 patients with a history of kidney disease. Although some of the previous COVID-19 studies have reported the importance of comorbidities, the role of underlying diseases in the outcome of COVID-19 patients is still elusive. In this study, we aimed to examine the relationship between kidney patients’ COVID-19 status and their clinical symptoms, laboratory values and ICU admission status. We also evaluated the association between COVID-19-positive kidney patients’ age, gender, smoking status, history of underlying diseases and urea and creatinine levels and their ICU admission status and mortality. Finally, we analyzed the differences in laboratory values in kidney patients with and without a history of diabetes or cardiovascular disease.

Patients and Data collection

In this cross-sectional study, 253 patients admitted to Imam Hussein Hospital and Bahar Hospital of Shahroud with a history of kidney disease were included. There was no sampling and all eligible patients entered the study. COVID-19 diagnosis was obtained by reverse-transcription polymerase chain reaction (RT-qPCR) test and CT-scan. Patients with positive results were diagnosed as confirmed cases of COVID-19. Exclusion criteria included patients’ lack of consent for participation or cooperation and patients’ incomplete hospital records.

Patients’ demographic information including age, gender, smoking status, and their history of underlying diseases such as cardiovascular, kidney, liver, respiratory diseases, diabetes and cancer were extracted from their hospital records. The evaluated symptoms included fever, chills, fatigue, anorexia, myalgia, arthralgia, rhinorrhea, sore throat, epistaxis, dry cough, dyspnea, headache, nausea, vomiting, diarrhea, abdominal pain, seizure, and mental status deterioration (Glasgow coma scale < 15). All of the following laboratory values were extracted: Urea, Cr, Na, K, Ca, P, Mg, BS, Alb, Chol, LDL, TG, WBC, Neutr, Lymph, Mono, Hb, MCV, MCH, MCHC, Hct, Plt, Ferritin, ESR, PH, LDH, CPK, SGPT, SGOT, and ALK-P. Patients’ ICU admission status and final outcome (death or recovery) were also recorded.

Statistical analysis

Categorical data were analyzed using Chi-Square test, and continuous data using independent samples t-test in SPSS software (Version 18). Categorical variables were reported as frequencies and percentages. Continuous variables were reported as means and standard deviations. Multivariate regression analysis was performed with 95% confidence intervals to assess the relationship between different variables and ICU admission and mortality in COVID-19-positive kidney patients. P-value ≤ 0.05 was considered statistically significant.

Ethical considerations

All data were used to evaluate the study-related objectives, taking into consideration the confidential principles of patients' information. Informed consent was obtained from all subjects based on the Declaration of Helsinki, and the research has been approved by the Ethics Committee of Shahroud University of Medical Sciences, Shahroud, Iran (Ethics Committee code: IR.SHMU.REC.1398.160).

Out of 253 hospitalized patients with a history of kidney disease, 176 (69%) had confirmed COVID-19 (mean age 56 ± 19 years). Sixty-three percent of COVID-19 patients were male. No significant difference was found in the gender distribution between COVID-19-positive and -negative kidney patients (p = 0.207). The prevalence of smoking was significantly lower in kidney patients without COVID-19 (p = 0.029). There was no significant difference in ICU admission between COVID-19-positive and -negative kidney patients (p = 0.172) (Table 1).

Table 1

Gender, Smoking and ICU admission status of kidney patients by their COVID-19 status
	COVID-19 Status
n (%)	Negative	Positive	P-value
Gender
Male	49 (63)	97 (55)	0.207
Female	28 (36)	79 (44)
Smoker	15 (19)	17 (9)	0.029
ICU Admission	29 (37)	51 (28)	0.172
COVID-19: corona virus disease of 2019, ICU: intensive care unit.

Results of multivariate regression analysis showed that history of underlying diseases (p = 0.001) and abnormal creatinine levels (p = 0.014) were significantly associated with increased ICU admission in COVID-19-positive kidney patients. Age ≥ 50 (p = 0.007), male gender (p = 0.012) and abnormal creatinine levels (p = 0.000) were significantly associated with increased mortality in COVID-19-positive kidney patients (Table 2).

Table 2

Multivariate regression analysis of variables affecting ICU admission and mortality of COVID-19-positive kidney patients
	ICU Admission			Mortality
Variable	OR	95% CI	P value	OR	95% CI	P value
Age ≥ 50 years	1.50	0.62, 3.62	0.362	17.58	2.23, 138.6	0.007
Male gender	1.64	0.88, 3.08	0.117	2.75	1.24, 6.09	0.012
Smoking	1.22	0.52, 2.86	0.641	1.72	0.66, 4.48	0.265
History of underlying diseases	3.67	1.72, 7.80	0.001	1.08	0.48, 2.43	0.851
Abnormal urea	5.55	0.69, 44.22	0.105	1.30	0.14, 11.38	0.812
Abnormal creatinine	2.08	1.15, 3.76	0.014	4.62	2.07, 10.30	< 0.0001
ICU: intensive care unit, OR: odds ratio, CI: confidence interval.
Normal urea = 7–21, normal creatinine = 0.6–1.3, underlying diseases = diabetes, cardiovascular disease, respiratory disease, liver disease, cancer.

The prevalence of fever, chills, myalgia, arthralgia, cough (p < 0.001), anorexia (p = 0.015), nausea (p = 0.030), fatigue (p = 0.031), headache (p = 0.001) and mental status deterioration (p = 0.044) was significantly higher in COVID-19-positive kidney patients compared to COVID-19-negative ones. No significant difference was found between the two groups in terms of sore throat, rhinorrhea, epistaxis, vomiting, diarrhea, abdominal pain, seizure, and dyspnea (p > 0.05) (Table 3).

Table 3

Clinical symptoms of kidney patients by their COVID-19 status
	COVID-19 Status
n (%)	Negative	Positive	P value
Fever	99 (56)	22 (78)	< 0.001
Chills	15 (19)	88 (50)	< 0.001
Anorexia	31 (40)	100 (56)	0.015
Sore throat	4 (5)	22 (12)	0.078
Rhinorrhea	3 (3)	8 (4)	0.816
Epistaxis	0 (0)	2 (1)	0.348
Myalgia	14 (18)	87 (49)	< 0.001
Arthralgia	12 (6)	74 (29)	< 0.001
Nausea	15 (19)	58 (22)	0.030
Vomiting	10 (12)	36 (20)	0.156
Diarrhea	6 (7)	26 (14)	0.124
Abdominal pain	10 (12)	26 (14)	0.708
Fatigue	21 (27)	73 (41)	0.031
Seizure	0 (0)	1 (0.5)	0.304
Mental status deterioration	13 (7)	12 (15)	0.044
Headache	11 (14)	60 (23)	0.001
Dyspnea	37 (48)	100 (56)	0.198
Cough	23 (29)	99 (56)	< 0.001

WBC count (p = 0.005), platelet count (p = 0.028), and urea (p = 0.005) were significantly lower in COVID-19-positive kidney patients compared to COVID-19-negative ones. Hemoglobin (p = 0.013), hematocrit (p = 0.028), and MCHC (p = 0.033) were significantly higher in COVID-19-positive kidney patients compared to COVID-19-negative ones. No statistically significant difference was noted between the two groups in terms of other laboratory values (p > 0.05) (Table 4).

Table 4

Laboratory values of kidney patients by their COVID-19 status
	COVID-19 Status
Mean ± SD	Negative	Positive	P value
WBC × 10³	8.1 ± 6.5	5.6 ± 4.3	0.005
Neutr%	74.6 ± 13.4	71.7 ± 12.4	0.116
Lymph%	19.8 ± 12.6	22.9 ± 11.7	0.073
Mono%	2.7 ± 1.0	2.9 ± 1.0	0.250
Hb	11.3 ± 2.5	12.3 ± 2.4	0.013
Hct	35.8 ± 7.4	38.1 ± 6.2	0.028
Plt × 10³	237.0 ± 111.9	207.5 ± 84.3	0.028
MCV	88.3 ± 7.3	87.7 ± 6.6	0.540
MCH	28.2 ± 2.6	28.5 ± 2.5	0.383
MCHC	31.9 ± 1.8	32.5 ± 1.8	0.033
Urea	81.3 ± 65.7	56.9 ± 43.5	0.005
Cr	2.2 ± 2.1	1.9 ± 1.7	0.153
Na	136.2 ± 5.9	135.5 ± 4.2	0.314
K	4.3 ± 0.8	4.2 ± 0.6	0.616
Ca	8.8 ± 0.7	9.0 ± 0.7	0.246
P	4.1 ± 1.7	4.0 ± 1.4	0.740
Mg	2.1 ± 0.3	2.1 ± 0.3	0.958
FBS	143.1 ± 68.5	136.5 ± 55.8	0.522
BS	137.1 ± 65.3	144.3 ± 84.0	0.563
TG	134.4 ± 94.4	117.2 ± 74.9	0.324
HDL	34.1 ± 18.7	30.8 ± 16.3	0.628
LDL	78.5 ± 28.9	71.4 ± 25.9	0.252
PH	7.3 ± 0.09	7.3 ± 0.08	0.585
AST	114.6 ± 445.6	36.7 ± 24.4	0.193
ALT	124.1 ± 502.8	35.6 ± 41.3	0.190
ALK-P	273.7 ± 301.9	230.6 ± 158.2	0.184
Ferritin	273.6 ± 209.1	461.8 ± 632.1	0.320
LDH	506.7 ± 450.1	513.7 ± 250.7	0.909
Alb	3.7 ± 0.9	3.5 ± 0.7	0.403
ESR	41.3 ± 33.4	41.2 ± 33.4	0.993

COVID-19: corona virus disease of 2019, SD: standard deviation, WBC: white blood cells, neutr: neutrophils, lymph: lymphocytes, mono: monocytes, Hb: hemoglobin, Hct: hematocrit, Plt: platelets, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, Cr: creatinine, FBS: fasting blood sugar, BS: blood sugar, TG: triglycerides, HDL: high density lipoprotein, LDL: low density lipoprotein, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALK-P: alkaline phosphatase, LDH: lactate dehydrogenase, ESR: erythrocyte sedimentation rate.

WBC count (p = 0.016), Urea (p = 0.016), and blood sugar levels (p = 0.017) were significantly higher in kidney patients with a history of cardiovascular disease compared to kidney patients without such a history. LDL (p = 0.039) and MCHC (p = 0.020) were lower in patients who had cardiovascular disease. No statistically significant difference was noted between the two groups in terms of other laboratory values (p > 0.05) (Table 5).

Table 5

Laboratory values of kidney patients by their cardiovascular disease status
	Cardiovascular disease Status
Mean ± SD	Negative	Positive	P value
WBC × 10³	5.6 ± 4.3	7.2 ± 5.8	0.016
Neutr%	71.5 ± 13.6	73.8 ± 11.7	0.174
Lymph%	23.0 ± 12.9	20.9 ± 11.1	0.171
Mono%	2.8 ± 1.1	2.8 ± 0.9	0.969
Hb	12.1 ± 2.5	12.1 ± 2.4	0.754
Hct	37.2 ± 6.3	37.6 ± 6.9	0.691
Plt × 10³	209.8 ± 95.1	219.1 ± 93.6	0.444
MCV	87.5 ± 6.1	88.2 ± 7.5	0.415
MCH	28.5 ± 2.2	28.3 ± 2.8	0.458
MCHC	32.6 ± 1.6	32.0 ± 2.0	0.020
Urea	56.1 ± 43.5	72.1 ± 58.5	0.016
Cr	1.9 ± 2.1	2.0 ± 1.6	0.802
Na	136.0 ± 4.9	135.2 ± 4.7	0.208
K	4.3 ± 0.8	4.2 ± 0.6	0.616
Ca	8.8 ± 0.7	9.0 ± 0.7	0.246
P	4.1 ± 1.7	4.0 ± 1.4	0.740
Mg	2.1 ± 0.3	2.1 ± 0.3	0.357
FBS	143.1 ± 68.5	136.5 ± 55.8	0.522
BS	128.9 ± 68.1	155.3 ± 86.1	0.017
TG	119.5 ± 92.1	121.6 ± 67.4	0.876
HDL	34.1 ± 18.7	30.8 ± 16.3	0.628
LDL	78.9 ± 30.3	68.7 ± 22.9	0.039
PH	7.3 ± 0.07	7.3 ± 0.09	0.779
AST	39.6 ± 28.8	76.5 ± 323.8	0.240
ALT	41.6 ± 51.6	76.7 ± 365.2	0.322
ALK-P	228.6 ± 177.4	266.4 ± 254.8	0.217
Ferritin	450.7 ± 664.7	370.8 ± 424.5	0.635
LDH	555.8 ± 281.8	471.3 ± 323.0	0.096
Alb	3.5 ± 0.8	3.5 ± 0.6	0.967
ESR	41.0 ± 33.2	41.9 ± 33.7	0.851

Hemoglobin and hematocrit (p = 0.016) were lower in diabetic kidney patients compared to non-diabetic kidney patients. Blood sugar (p = 0.000), triglyceride levels (p = 0.036), and ESR (p = 0.016) were higher in diabetic kidney patients. No statistically significant difference was noted between the two groups in terms of other laboratory values (p > 0.05) (Table 6).

Table 6

Laboratory values of kidney patients by their diabetes status
	Diabetes Status
Mean ± SD	Negative	Positive	P value
WBC × 10³	6.1 ± 5.2	6.6 ± 5.1	0.491
Neutr%	72.2 ± 13.2	73.1 ± 12.2	0.617
Lymph%	22.4 ± 12.5	21.4 ± 11.5	0.532
Mono%	2.8 ± 1.1	2.9 ± 0.9	0.275
Hb	12.4 ± 2.4	11.5 ± 2.4	0.016
Hct	38.3 ± 6.4	36.2 ± 6.7	0.016
Plt × 10³	204.3 ± 89.8	227.7 ± 98.9	0.056
MCV	87.8 ± 6.9	87.9 ± 6.7	0.931
MCH	28.5 ± 2.6	28.3 ± 2.3	0.565
MCHC	32.4 ± 1.8	32.2 ± 1.9	0.403
Urea	61.9 ± 52.2	66.5 ± 51.1	0.491
Cr	2.0 ± 2.0	2.0 ± 1.7	0.871
Na	135.8 ± 4.2	135.4 ± 5.6	0.566
K	4.3 ± 0.8	4.2 ± 0.6	0.616
Ca	8.8 ± 0.7	9.0 ± 0.7	0.246
P	4.1 ± 1.7	4.0 ± 1.4	0.908
Mg	2.1 ± 0.3	2.1 ± 0.3	0.301
FBS	143.1 ± 68.5	136.5 ± 55.8	0.522
BS	117.5 ± 55.3	171.8 ± 91.6	< 0.0001
TG	107.4 ± 79.1	136.6 ± 76.7	0.036
HDL	34.1 ± 18.7	30.8 ± 16.3	0.628
LDL	72.2 ± 24.8	73.7 ± 28.9	0.767
PH	7.3 ± 0.08	7.3 ± 0.09	0.585
AST	65.7 ± 286.9	49.1 ± 132.8	0.609
ALT	65.6 ± 296.8	51.7 ± 214.9	0.705
ALK-P	240.0 ± 174.4	258.8 ± 271.5	0.543
Ferritin	509.0 ± 703.3	333.8 ± 399.0	0.298
LDH	524.8 ± 281.6	494.1 ± 338.6	0.553
Alb	3.5 ± 0.8	3.6 ± 0.7	0.509
ESR	36.4 ± 30.8	48.0 ± 35.6	0.016

In this cross-sectional study, we identified several symptoms and laboratory values strongly related to COVID-19 infection or a history of diabetes or cardiovascular disease. We also found that history of underlying diseases and creatinine levels were associated with ICU admission, and that age, gender and creatinine levels were associated with mortality in COVID-19-positive kidney patients.

Results of a study by Nikonejad et al. (19) showed that men were significantly more likely to be infected with SARS-CoV-2 than women. There was no significant relationship between gender and COVID-19 infection in hospitalized patients with a history of kidney disease in our study. This contradicts the results of previous studies (16) and may be due to the smaller sample size of our study. As in a systematic review conducted by Figliozzi et al., male gender has been found to increase the risk of death (20). Our results showed that male gender was associated with increased mortality in COVID-19-positive kidney patients (p = 0.012). According to Cai et al., men may be more susceptible to COVID-19 than women since men smoke more (21). We observed a significant relationship between smoking and COVID-19 in kidney patients (p = 0.029), i.e. smoking can make kidney patients more susceptible to COVID-19 infection. Gaol et al. stated that smoking was associated with higher expression of ACE2 in the epithelial cells of the respiratory tract, thereby predisposing a person to COVID-19 infection (22). However, smoking was not associated with ICU admission or mortality in COVID-19-positive kidney patients in our study.

Previous studies have reported that elderly COVID-19 patients are more susceptible to adverse outcomes. The elderly experience severe disease, and their mortality rate is high, and the age of a person is considered to be the most effective predictor of a patient's death (6–9, 20). In agreement with these studies, our results showed a significant association between age ≥ 50 and mortality in COVID-19-positive kidney patients (p = 0.007). This finding is consistent with a study that identified aging as a contributing factor to mortality in COVID-19 patients with AKI (23). The mechanism of the effect of age on the outcome of the disease is not fully understood, but it is possible that factors such as reduced immunity and reduced pro-inflammatory responses can be effective, and also due to the greater number of co-morbidities in the elderly and the absence or reduction of the symptoms of the Covid-19 disease in older people and the reduction of naïve T cells, which reduces the individual's response against new infectious agents, older people are at greater risk for the Covid-19 virus (24–26).

In the present study, fever (78%), dyspnea (56%), anorexia (56%), and cough (56%) were the most common clinical manifestations among 176 COVID-19-positive kidney patients. Fatigue (41%), myalgia (49%), and chills (50%) were also observed in many patients. Epistaxis (1%) and seizure were very rare among these patients. Headache (23%) and arthralgia (29%) were reported in some patients while mental status deterioration (7%) and rhinorrhea (4%) were reported in a few cases. The results indicate that a significant relationship exists between COVID-19 and cough, myalgia, arthralgia, fever, chills (p < 0.001), anorexia (p = 0.015), nausea (p = 0.030), fatigue (p = 0.031), headache (p = 0.001) and mental status deterioration (p = 0.044).

Contrary to the results reported by Zheng et al., the frequency of dyspnea in the present study was the same between COVID-19-positive and -negative kidney patients (p = 0.198) (27). This could be due to the fact that COVID-19 patients in our study may not have had a severe disease involving large portions of the lungs. Zheng et al. also found that there was a significant relationship between dyspnea and COVID-19 severity (27).

A previous study reported a significant increase in creatinine levels in COVID-19-positive cardiovascular patients compared to COVID-19-negative ones. No significant relationship was observed between creatinine levels and COVID-19 in kidney patients in the present study (p = 0.153) (28). Our results indicated that abnormal creatinine levels were strongly associated with increased ICU admission (p = 0.014) and mortality (p = 0.000) in COVID-19-positive kidney patients. This result is consistent with another study that found high creatinine levels to be associated with higher in-hospital mortality as well as greater need for mechanical ventilation and intensive care (16). They also found that higher levels of creatinine due to the abnormality created in the coagulation pathway make it difficult to treat and make the disease of COVID-19 more severe.

The present study showed that the mean WBC count of COVID-19-positive kidney patients was significantly lower than COVID-19-negative ones (p = 0.005). This is in line with the results of previous studies (21, 29, 30). In their case report, Wang et al. evaluated the laboratory values and clinical course of two COVID-19 patients with a history of chronic kidney disease (31). One of the patients had increased WBC and neutrophil counts. This is while in another study that examined patients with severe and non-severe conditions of COVID-19, both groups experienced an increase in leukocytes and a significant increase was seen in the severe group (32). However, the results of the present study do not indicate a significant relationship between neutrophil count and COVID-19 infection. Tian et al. observed a significant decrease in lymphocyte counts of COVID-19 patients with different underlying diseases (21). However, in the kidney patients in the present study, no significant association was found between lymphocyte count and COVID-19.

Tian et al. evaluated the laboratory parameters of 14 COVID-19 patients with a history of underlying diseases (21). AST and LDH levels were increased in one of these patients who had a history of renal disease. The rise of these two parameters was also a common finding in patients with a history of other underlying diseases such as heart disease, diabetes, lymphoma, and malignancies. Mardani et al. studied 200 patients with suspected COVID-19 and reported that AST, ALT, and LDH levels were significantly higher in patients with a positive PCR test for COVID-19 compared to those with a negative PCR test (30). In the present study, no significant relationship was observed between COVID-19 and ALT, AST, and LDH levels in kidney patients. Such discrepancies can be due to the small sample size of our study. Also, liver function tests are not always abnormal in COVID-19 patients, and the abnormal ALT and AST levels found in some patients can be attributed to treatment-induced injury or underlying liver disease (33).

Wu et al. found that increased LDH is related to COVID-19 severity (34), we also know that in the COVID-19 infection, LDH secretion indicates lung damage and cell membrane necrosis stimulates its secretion (35). And according to a study, in ICU patients, this enzyme had a higher level than non -ICU patients, so it can be considered as a bio-marker for predicting the disease prognosis (36). These results are reinforced by a study that even found the LDH level to be associated with the pneumonia intensity in the CT scan, thus it can be concluded that the patients in our study may have had less severe COVID-19 (37).

Tian et al. also observed a decrease in hematocrit of most COVID-19 patients, including patients with a history of renal impairment. Normal to low hemoglobin was reported in most patients (16). In contrast, in the present study, hematocrit (p = 0.028), hemoglobin (p = 0.013), and MCHC (p = 0.033) were reported significantly higher in COVID-19-positive kidney patients compared to COVID-19-negative ones.

Yuan et al. showed that there might be a meaningful rise in ferritin levels of COVID-19 patients due to hemophagocytosis (38). Unlike this study, no significant relationship was found between ferritin and COVID-19 in the present study (p = 0.320). A study by Bozkurt et al. showed that increased ferritin levels can be related to COVID-19 severity. Thus it can be concluded that the patients in our study may have had less severe COVID-19 (39).

Mardani et al. evaluated the specificity and sensitivity of laboratory parameters for COVID-19 diagnosis in the general population and reported that urea can be a promising factor for predicting the presence of COVID-19 (30). Hassanein et al. (40) showed that increased urea in COVID-19 patients could be a predictor of acute renal failure. The severity of the disease is also related to the abnormalities seen in the results of the patient's urine test (41). However, in the present study, the mean urea level was lower in COVID-19-positive kidney patients (p = 0.005) compared to COBID-19 negative ones and urea levels were not associated with ICU admission or mortality in COVID-19-positive kidney patients. In a study conducted on 178 COVID-19 patients, five patients (2.8%) had an increased blood urea nitrogen (BUN), and out of 83 COVID-19 patients without a history of kidney disease, 45 patients had abnormal urinalyses and poorer prognoses. It was concluded that urine tests are better at assessing possible kidney damage in COVID-19 patients than blood biochemistry tests such as urea (42).

Results of the present study show no significant relationship between COVID-19 and ICU admission in kidney patients (p = 0.172). This is in line with previous studies conducted on patients with other underlying diseases. Choi et al. reported that there was no relationship between COVID-19 and ICU admission in patients with a history of other respiratory diseases like asthma (43). However, contrary to Choi’s study, Beltramo et al. found that COVID-19 patients with a history of respiratory disease were more likely to be admitted to ICU (4). Also, a study by Cheng et al. showed that COVID-19 patients with renal failure were more likely to be admitted to the ICU and intubated. In this study, renal failure was also identified as a risk factor for in-hospital death (14).

Zaki et al. found an association between the severity and mortality of COVID-19 and various underlying diseases including hypertension, diabetes, stroke, cancer, kidney disease, and hypercholesterolemia (44). They concluded that cancer patients were more likely to develop COVID-19 than people without a history of cancer and that COVID-19-positive cancer patients had a poorer prognosis. Miyashita et al. evaluated the clinical course of COVID-19 patients with a history of cancer. They observed that the mortality rate was higher in COVID-19-positive cancer patients younger than 50 years (45). The need for intubation was significantly higher in COVID-19-positive cancer patients aged 66 to 80 years. Based on our results, history of underlying diseases including cancer, diabetes, cardiovascular disease, respiratory disease and liver disease was associated with increased ICU admission in COVID-19-positive kidney patients (p = 0.001), but not with increased mortality.

Forty-three percent of kidney patients in our study were diabetic. Li et al. reported a significant association between ICU admission and a history of diabetes in COVID-19 patients and found that patients with newly diagnosed diabetes were more likely to be admitted to the ICU (46). They also found that diabetic patients had higher rates of COVID-related complications such as acute renal failure, cardiac failure, respiratory failure, and coagulopathies. In our study, hemoglobin and hematocrit were lower in diabetic kidney patients compared to non-diabetic kidney patients (p = 0.016). This finding could be due to a reduction in erythropoietin production in diabetic patients because of microvascular complications and renal damage (30). Diabetes will also predispose patients to systemic inflammation that can induce anemia of chronic disease (30). Therefore, anemia in diabetic kidney patients should be addressed. Diabetic kidney patients in our study had higher ESR (p = 0.016), which according to Guo et al. is associated with a lower glomerular filtration rate in these patients (31). Diabetic kidney patients in our study also had higher triglyceride levels (p = 0.036). Gong et al. found that high TG level was an independent risk factor for the development of diabetic kidney disease (32). Control of triglyceride levels can delay the progression of kidney disease in diabetic patients (33).

Fifty percent of patients in our study had a history of cardiovascular disease. Inciardi et al. reported a significant relationship between history of cardiac disease and the need for ICU admission and mortality in COVID-19 patients (28). In our study, WBC count and urea were higher in kidney patients with a history of cardiovascular disease compared to kidney patients without such a history regardless of their COVID-19 status (p = 0.016). Hsu et al. showed that WBC count predicts one-year mortality related to cardiovascular disease and infection in kidney patients under hemodialysis (34). Smith et al. showed that, in older cardiovascular patients, serum urea was a powerful predictor of post-discharge mortality (35). Based on these findings, monitoring WBC and urea levels can be beneficial in kidney patients with a history of cardiovascular disease. LDL levels were lower in kidney patients with a history of cardiovascular disease in our study (p = 0.039). This might be due to the consumption of lipid-lowering medication such as statins in cardiovascular patients. Blood sugar levels were also higher in kidney patients with a history of cardiovascular disease (p = 0.017). High blood glucose is associated with an increased risk of all-cause and cardiovascular mortality (36). Therefore, controlling blood glucose levels in kidney patients with a history of cardiovascular disease is very important.

Strategies to educate kidney patients on the adverse effects of smoking and the possible increased risk of COVID-19 associated with it should be implemented to promote smoking cessation and prevent harmful consequences. Kidney patients should be monitored closely for fever, chills, myalgia, arthralgia, cough, anorexia, nausea, fatigue, headache and mental status deterioration as such symptoms can indicate a co-existent COVID-19 infection. Monitoring WBC and platelet counts in kidney patients with COVID-19, WBC count, urea, and blood sugar in kidney patients with a history of cardiovascular disease, and ESR, TG and Hb in diabetic kidney patients can prove beneficial in the long-term management of kidney patients, as changes in these values could possibly affect patients’ clinical course. Age, gender, history of underlying diseases and creatinine levels can be important prognostic markers in COVID-19-positive kidney patients. The level of the patient's biomarkers can be very helpful in diagnosing the disease process and its severity and can be used as a factor in guiding the treatment process and the need for special care. Knowing the clinical characteristics of the Covid-19 infection can help to reduce mortality and better understand the pathogenesis of this virus, and therefore we need more research in this field. Our study was performed on hospitalized patients. Therefore, patients with milder forms of COVID-19 that did not require hospital admission were not included in this study. More extensive studies with larger sample sizes are required to further investigate the effects of COVID-19, diabetes, and cardiovascular disease on clinical course and outcome of kidney patients. More information on these topics can help healthcare workers to implement the best treatment strategies for these patients and improve their outcome and quality of life.

ICU

intensive care unit

RT-PCR

reverse-transcription polymerase chain reaction

SARS-COV-2

severe acute respiratory syndrome coronavirus 2

COVID-19

coronavirus disease of 2019

GCS

Glasgow coma scale

computed tomography

COPD

chronic obstructive pulmonary disease

AKI

acute kidney injury

WBC

white blood cells

neutr

neutrophils

lymph

lymphocytes

mono

monocytes

hemoglobin

Hct

hematocrit

Plt

platelets

MCV

mean corpuscular volume

MCH

mean corpuscular hemoglobin

MCHC

mean corpuscular hemoglobin concentration

creatinine

FBS

fasting blood sugar

blood sugar

triglycerides

HDL

high-density lipoprotein

LDL

low-density lipoprotein

AST

aspartate aminotransferase

ALT

alanine aminotransferase

ALK-P

alkaline phosphatase

LDH

lactate dehydrogenase

ESR

erythrocyte sedimentation rate.

Acknowledgement

This research has been conducted at Shahroud University of Medical Sciences (project code: 98126). The research has received no fund.

Data availability statement

Data are available from the corresponding authors upon reasonable request.

Conflict of interest

The authors declare no conflict of interest.

Ethical Consideration

Informed consent were obtained from all subjects in accordance with the Declaration of Helsinki, and the research has been approved by the Ethics Committee of Shahroud University of Medical Sciences, Shahroud, Iran (Ethics Committee code: IR.SHMU.REC.1398.160).

Funding

This study was financially supported by Shahroud University of Medical Sciences.

Author Contributions Statement

H. A., V. K., and P. R. G. wrote the main manuscript text, B. K., Y. N. A., and P. J. D. revised the first draft, and A. F. and S. T. prepared all tables. All authors reviewed the final manuscript.

Consent to publish/consent for publication

Not applicable

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Clinical and paraclinical parameters in COVID-19 patients with nephrological disorders

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Abstract

Introduction

Materials And Methods

Patients and Data collection

Statistical analysis

Ethical considerations

Results

Discussion

Conclusion

Abbreviations

Declarations

References

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