Back ground: We aimed to represent the effects of SARS Co V -2 on kidney functioning during the COVID-19 pandemic in patients of varied baseline GFR values staged into renal categories of one to five.

Methods: We conducted a single-center, retrospective study using data of patients hospitalized for COVID-19 with acute kidney injuries. Demographic characteristics, clinical findings, laboratory parameters [glomerular filtration rate (GFR), Creatinine, Blood urea nitrogen (BUN)] of pre covid, during covid, post-COVID infection, were reviewed. Predicted changes in the GFR were analyzed. The study’s primary outcome was a predicted decline in GFR observed during the covid infection period compared to pre covid. The secondary outcome was predicted improvement in GFR after resolution of infection or covid -19 tested negative.

Results: The study included one hundred patients (mean age: 57.35+/- 17.5 years). The odds ratio of multivariate logistic regression analysis shows the association of kidney functioning during the pre-covid period with an odds ratio of 1.699 (95% CI- 1.299 to 2.551), during COVID with an odds ratio of 0.5404 (95% CI- 0.3620 to 0.7025), and postcovid with an odds ratio of 0.98 (CI- 0.9646 to 1.000). A decrease in GFR from Pre-COVID to during-COVID was observed with the estimated odds ratio of 1.001 (CI-0.9999 to 1.002, z- value 1.795, p-value-< 0.001). The positive and negative predictive powers were 92.86% and 96.67%, respectively. An association of an improvement in GFR was observed during the post-covid infection period with an odds ratio of 0.999 (CI-0.99-1.002, p-value-0.79). Indeed, the average decrease in GFR was prominent in second renal category patients, and the white race showed a 75% mortality rate, 14% in African Americans, and 11% in other races.

Conclusion: COVID-19 can cause acute ischemic kidney injury. Patients with CKD stage 3A are most affected. Patients who had longer lengths of stay in the hospital had greater severity of acute kidney injury. We found a higher mortality ratio in patients assigned to renal categories 2 and 3.

COVID-19; Ultrasound; Hematuria; Proteinuria; Renal fanconi syndrome

Bacallao-Méndez RA, Roig-Duarte IM, Diez-Martínez N, Smith-González MJ, García-Villar Y, et al. (2022) Renal Morphofunctional Findings in Convalescents of COVID-19. J Clin Nephrol Res 9(1): 1106.

COVID-19: Coronavirus Disease 2019; SARS-Cov-2: Acute Respiratory Syndrome Coronavirus-2; ACE2: Angiotensin Converting Enzyme 2; TMPRSS2: Transmembrane Serine Protease; GFR: Glomerular Filtration Rate; CKD-EPI: Chronic Kidney Disease-Epidemiology Collaboration; Fena: Fractional Excretion of Sodium; FEK: Fractional Excretion of Potassium; FEAU: Fractional Excretion of Uric Acid; PEF: Fractional Excretion of Phosphate; ACR: Albumin/Creatinine Ratio; PCR: Protein/ Creatinine Ratio; ACE: Angiotensin Converting Enzyme; CKD: Chronic Kidney Disease

Dedicatory: To professors Reynaldo Mañalich Comas and Charles Magrans Buch, initiators of Nephrology in Cuba, who died from COVID-19.

The current pandemic of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus (Severe acute respiratory syndrome coronavirus-2) has caused a significant impact on health systems and economies around the world [1]. SARS-CoV-2 is an RNA virus that belongs to the beta coronavirus genus, whose functional receptor in humans is angiotensinconverting enzyme 2 (ACE2) [2,3]. SARS-CoV-2, like other coronaviruses, also requires a transmembrane serine protease (TMPRSS2) for entry into the cell [2]. Another potential route of entry for the virus, demonstrated in vitro, is the CD147 cell receptor [4].

In the kidney, both ACE2 and TMPRSS2 are located in the proximal tubule and collecting ducts, and to a lesser extent in podocytes and mesangial cells [2]. CD147 is also widely expressed in proximal tubules [4]. These characteristics make the kidney an ideal target for direct viral infection. However, other elements may cause or contribute to kidney damage, such as hemodynamic factors, rhabdomyolysis, cytokines release, coagulatory disorders, systemic sepsis, hypoxia, and drug toxicity [5,6].

In the clinical order, kidney damage during COVID-19 is characterized by elevated creatinine levels, variable degrees of hematuria, proteinuria, and disturbances in tubular function, which are distinguished by the appearance of urinary losses of neutral amino acids, low molecular weight proteinuria, hypophosphatemia, and hypouricemia [7,8]. Hypouricemia due to hyperuricosuria seems to be related to the severity of the disease and its progression [8]. However, the progress of these damage markers in convalescent COVID-19 is unknown, so this research is carried out to identify the presence of morphological (ultrasound), urinary and tubular function markers of kidney damage in convalescent COVID-19 and its possible relationship with the clinical condition of patients during infection.

A prospective cohort descriptive observational exploratory study was carried out in 92 convalescent adults of COVID-19, diagnosed by a real-time polymerase chain reaction in the nasopharyngeal swab, admitted to the Hospital “Dr. Salvador Allende,” in Havana, Cuba, between March 13-June 20, 2020.

The data used in the study were collected from a structured interview (general characteristics and clinical elements of interest), the physical examination, the report of ultrasound study, and the report of laboratory tests.

The variables used were: age, sex, skin color, clinical condition during admission (asymptomatic, mild symptomatic, severe [admitted to intensive care unit], critical [with mechanical ventilation]), weight, height, toxic habits (smoking, alcoholism), comorbidities, medications, oxygen saturation, kidney’s ultrasound findings; in the direct urine examination, the variables used were: hematuria, leukocyturia, bacteriuria, casts, crystalluria, glucosuria, and dibasic aminoaciduria; while in the biochemical measurements the variables were: plasma and urinary concentrations of sodium, potassium, phosphorus, uric acid, and creatinine, in addition to plasma bicarbonate and urinary pH.

After signing their informed consent, the patients attended the Institute of Nephrology “Dr. Abelardo Buch López,” in Havana, Cuba, on two occasions, six months and a year after the diagnosis. On their visits, patients were fasting and subjected to a medical interview to obtain the data to complete the form designed for the research purpose. Patients also had a physical assessment conducted (including weight and height measurement), and a measure of oxygen saturation was taken at rest. In addition, a 10 ml venous blood sample and a urine sample were taken, and a renal ultrasound was performed (the latter only at six months).

Oxygen saturation was measured with an Oxy 9800 pulse oximeter from Combiomed. Renal ultrasound was performed on a Philips machine, Affiniti 70G model with color-Doppler effect. The urine was examined for red blood cells, leukocytes, bacteria, and glucose with Roche Combur10 Test® M dipstick; a microscopic study was done if cells or bacteria were found. Electrolytic measurements were made on a Radiometer ABL 800 Flex gas analyzer. Biochemical measurements in urine and blood were performed in a Spinreact spectrophotometric autoanalyzer, model 200E. Urinary pH was measured with a Crison GLP 21+ equipment.

The body mass index was calculated, and the patients were divided into the following categories: <18.5 kg/m2 (malnourished), 18.5-24.9 (normal weight), 25-29.9 (overweight), and ≥30 (obese) [9]. The Glomerular Filtration Rate (GFR) (estimated by the CKD-EPI equation from serum creatinine), the fractional excretion of sodium (FENa), potassium (FEK), uric acid (FEUA), and phosphate (FEP) were also calculated. In addition to albumin/creatinine ratio (ACR) and protein/creatinine ratio (PCR) [10,11].

The following values were considered normal: resting oxygen saturation greater than 95%, serum sodium concentrations between 135 and 145 mEq/l, potassium between 3.5 and 5.5 mEq/l, phosphorus from 2.5 to 4.5 mg/dl (0.8 to 1.45 mmol/l), bicarbonate from 22 to 28 mEq/l, uric acid in men from 2.5 to 7 mg/dl (148.71-416.4 µmol/l) and in women from 2.5 to 6 mg/ dl ( 148.71-356.9 µmol/l), and creatinine levels below 1.18 mg/ dl (104.3 µmol/l). Increased FENa was considered if greater than 2%, increased FEK, if greater than 17%, increased FEUA if greater than 10% with plasma uric acid concentrations lower than 2.5 mg/dl (148.71 µmol/l) (hypouricemia) or greater than 15% in subjects without hypouricemia, increased FEP, if greater than 20%, ACR increased if equal or greater than to 30 mg/g and PCR increased if equal or greater than 0.2 g/g.

Ethical considerations

The study was approved by the Research Ethics Committee of the Institute of Nephrology “Dr. Abelardo Buch López.” The research was designed and developed following the principles of the Declaration of Helsinki. All participants gave their written informed consent to take part in the study. In addition, patients with any abnormality were guaranteed adequate clinical followup. It was agreed not to release the information individually but as part of the work.

Statistics

The data were processed with the SPSS statistical software version 22.0. Frequency distribution analysis was performed. Summary measures were calculated for qualitative variables such as proportion and percentage and measures of central tendency and dispersion for quantitative variables such as the mean and standard deviation. To assess the association between the clinical condition of the patients and the presence of urinary disorders and tubular function tests, association analyzes were performed using contingency tables and the Chi-square test of independence. A significance level α = 0.05 was set for this hypothesis test.

The study’s first phase (six months after infection) included 92 patients, and the second phase (one year after infection) included 85 patients. The difference was two patients who did not participate in the second phase and five who had difficulties collecting urine samples.

When analyzing the characteristics of the patients (Table 1),

it stands out slightly higher participation of females and the predominance of subjects between 40 and 59 years of age, who constituted little more than 60% of the cases. Individuals with black and mestizo skin color were over 50% of the patients (51.1% in the first phase and 51.8% in the second). Nearly half of the subjects were asymptomatic during the infection (46.7% in the first phase and 49.4% in the second), while under 20% were severe or critical. Four required mechanical ventilation, one of them non-invasively (without orotracheal intubation).

No patient had a GFR lower than 45 ml/min/1.73 m2 BS, which means all the patients had a normal renal function or were in stages 1-3a of Chronic Kidney Disease (CKD). It stands out a lower frequency of stage 2 patients in the second phase with an increase in subjects without CKD and patients in stages 1 and 3a. Overweight and obese individuals constituted 63% and 60% of the first and second phases, respectively.

Smoking was present in just under 30% of the patients in both phases, and five subjects were alcoholics. The most common comorbidities reported were hypertension (first phase-48.9%, second phase-50.6%), and diabetes mellitus (first phase-16.3%, second phase-15.3%). Two patients (participants in both phases) had a diagnosis of CKD (stage 2), and another two were infected with HIV. The most commonly used medications regularly were diuretics and angiotensin-converting enzyme inhibitors. Hydrochlorothiazide (17 patients), and Enalapril (16 patients), were the most widely used individual drugs.

All patients examined had normal levels of oxygen saturation at rest. The most common findings in renal ultrasound (Table 2),

were: cysts and microcysts (9.8% of kidneys and 7.6% of patients), nephrolithiasis (9.8% of kidneys and 6.5% of patients), the irregular surface (8.7% of kidneys and 6.5% of patients) and the double excretory system (7.6% of kidneys and 5.4% of patients). Renal perfusion was preserved in all cases, and no thrombi were evident in the renal vessels.

The urine study (Table 3),

revealed the presence of microscopic hematuria in 12% of patients studied in the first phase and 17.6% of those in the second. Leukocyturia and bacteriuria were identified in less than 5% of the samples examined. In the microscopic study of the urine, it was found that 2.2% of hematuria identified in the first phase was dysmorphic, while it was 3.5% of the second phase. In addition, casts (hyaline) and crystals (calcium oxalate) were found in two cases. There was insufficient evidence to suggest a relationship between the presence of urinary sediment alterations and the clinical condition of the subjects during admission due to the infection (p> 0.05).

The mean plasma concentrations of sodium, potassium, phosphorus, bicarbonate, and uric acid (Table 4) in both phases were within the limits of normality. However, the means of sodium concentrations in the upper limit of normality were remarkable in both phases (144.5 mEq/L and 145.0 mEq/L, respectively). No patient had a plasma sodium concentration greater than 150 mEq/L or uric acid less than 2.5 mg/dl (148.71 µmol/l) (hypouricemia). Mean plasma creatinine was 1.03 mg/ dl (91 µmol/l) at six months and 0.99 mg/dl (87.5 µmol/l) at one year, below the upper limit of normality.

The urinary concentrations (Table 4),

of the different analytes correspond with the plasma concentrations (they do not have exact normality values). The average urinary pH, expression of the concentration of free hydrogen ions, of 5.75 and 5.79, in the first and second phases, respectively, was expected for subjects with a typical western diet.

Fractional excretions of solutes, expression of tubular function, (Table 5),

were increased in less than 5% of patients in both phases; FENa was the highest in both phases and corresponded to patients receiving diuretics. The case with increased FEK was also using diuretics. Of those patients with increased FEAU, one used aspirin (in low doses), another was diabetic, and the other was HIV positive. Increased FEP occurred in the same three patients in both phases; one of them had diabetes, and the three had a history of alcoholism. There was insufficient evidence to suggest a relationship between the increased fractional excretions of solutes and the clinical condition of subjects during admission due to the infection (p> 0.05). No patient had normoglycemic glycosuria, and the same patient had a positive Brand’s test (expression of dibasic aminoaciduria) in both phases.

The ACR was increased in 12.0% of patients in the first phase and 15.3% of those in the second (Table 5), while the increased PCR decreased from 16.3% in the first phase to 8.2% in the second. The persistence of increased PCR in the second phase was related to the clinical condition of subjects during admission for the acute infection (p-0.01). In other words, the increased PCR persisted longer as the patients presented worse clinical conditions. The evaluation of patients with normal ACR and increased PCR shows a notable decrease from 7.6% in the first phase to 1.2% in the second (it should be clarified that no patient with increased PCR in the first phase stopped participating in the second).