A total of 1056 patients were admitted in this specified period. The mean age of COVID-19 patients hospitalized in our center was 55 ± 15 years, 582 (55,2%) of them were males while 474 (44,8%) of them were females.
427 patients were confirmed by RT-PCR. 104 of the PCR confirmed COVID-19 patients experienced AKI (24,3%). 89 patients who developed AKI with an eGFR of over 60 ml/min/1.73 m2 were included in the final analysis (Figure-1). Patients who were included in our study were older (62,4 ± 14,2 years) than other patients in the general COVID-19 cohort and there was a male predominance (67 males, 75%).
Twenty-nine (32%) of the patients had AKI on admission. 33 of them (37%) developed AKI during the first week of admission and 27 patients (30%) developed AKI starting from the second week of admission. For patients who developed AKI later than hospital admission date, AKI developed on the 6.7th ± 5.4th day of the admission. Initial laboratory values on hospital admission day and in-hospital prognostic indices of all 89 patients can be found in the supplementary document.
Etiologic evaluation
Patients who had AKI on admission
Twenty-nine patients had AKI on admission.
Twelve (41,3%) of these patients had transient pre-renal AKIs as their kidney functions were rescued by relevant fluid resuscitation. Two (6.8%) of the patients had rhabdomyolysis related AKI. Both of these patients also had increasing levels of either ferritin (>750 ng/mL) or D-dimer (>5 mg/L). Six patients (20,6%) had respiratory disruptions (persistent hypoxemia or hypercapnia). These patients were considered to have hypoxemic kidney injury. Four of these patients also had high levels of ferritin (>750 ng/mL) or D-dimer (>5 mg/L) levels. A total of eight patients (27.5%) had hyperferritinemia and/or high D-dimer levels without rhabdomyolysis. AKIs in these patients were attributed to hyper-inflammation. One of the patients in this group developed proteinuria concomitant with AKI, despite normal levels of inflammatory and coagulation markers. COVID severity of the patients who had AKI on admission was mainly moderate and just 7 of them (24%) had severe or critical disease.
Patients who had AKI in the 1st week.
Thirty-three patients experienced AKI during the 1st week.
10 (30,3%) patients had transient pre-renal AKI, which was cured by relevant fluid therapy. Rhabdomyolysis was noted in four patients (12.1%). All of these four patients also had concomitant hyperferritinemia (>750 ng/mL). A total of 13 patients (39.3%) had high ferritin or D-dimer levels without findings of rhabdomyolysis. The kidney injury was attributed to hyper-inflammation in these patients. Three patients (9%) either had hypoxemia or increasing levels of CO2. AKI was attributed to hypoxemia in these patients. AKI in three patients (9%) of this group was related to drug toxicity (contrast agents in two patients and non-steroid anti-inflammatory drug in one patient). When COVID severity of the patients was evaluated, 14 of these 33 patients (42%) were classified as severe or critical.
Patients who had AKI after 1st week:
Twenty-seven patients had AKI after the 1st week of their admission.
One patient (3.7%) had transient pre-renal AKI. Six patients (22.2%) had rhabdomyolysis. All of the patients who had rhabdomyolysis also had either high D-dimer or ferritin levels. Two patients (7.4%) had severely disrupted gas exchange without concomitant high ferritin or D-dimer levels. AKIs in these patients were attributed to hypoxemia. Sixteen patients (59.2%) had very high levels of either ferritin (>750 ng/mL) or D-dimer (>5 mg/L). AKIs in these patients were associated with hyper-inflammation. Two patients (7.4%) had contrast agent induced AKI. Clinical evaluation pointed out to severe or critical illness in 22 of these 27 patients (81%).
Urine analysis:
Urine analysis was available in a total of 35 patients. Hematuria was the most prominent finding, which was seen in 21 of them. Proteinuria was documented in 9 patients and they were all 1+ semiquantitavely. Proteinuria was going along with hematuria in 7 patients while two patients had isolated proteinuria.
Imaging studies
Chest CT to investigate pulmonary involvement was performed in all patients. COVID pneumonia was detected in a total of 82 patients (92.1%).
Kidney imaging (urinary ultrasonography or abdominal CT) was available in 14 patients. Eight of them were reported to be completely normal. Three patients had nephro-urolithiasis, one patient had pelvic ectasia, one had prostatic hypertrophy and one had the findings of cystic kidney diseases. Imaging studies neither yielded obstruction findings nor could explain the AKI etiology.
Electrolyte and acid/base disturbances
Hypochloremia and hyponatremia were the most common electrolyte abnormalities. 65 of the 89 patients (73%) had hypochloremia and 50 (56.1%) of the patients had hyponatremia. Hypernatremia and hyperchloremia was seen in 22 (24.7%) and 18 (20.2%) of the patients respectively. Among potassium abnormalities, hyperkalemia developed in 35 (39.3%) of the patients, while hypokalemia was seen in 16 (17.9%) of them. Calcium disturbances were observed less frequently. Hypocalcemia was seen in 16 patients (17.9%) and hypercalcemia was detected in 3 patients (3.3%). Among patients for whom phosphorus levels were evaluated (79 patients); 22 had hypophosphatemia (27.8%) and 20 patients (25.3%) had hyperphosphatemia. In patients who had their magnesium levels checked (83 patients) 6 (6.7%) had hypomagnesemia and 21(25.3%) had hypermagnesemia. Acidosis (respiratory and/or metabolic) developed in 23 (25.8%) of the patients and respiratory alkalosis was seen in 38 (42.6%) of them.
Treatment modalities
Although there is no specific validated treatment for COVID-19 yet, some antiviral therapies were applied in accordance with the ministry of health (MoH) treatment guidelines. These include different combinations of hydroxychloroquine, favipiravir and lopinavir. Anti IL-6 receptor antibody tocilizumab or steroids were used in patients who had high inflammatory response. Low-molecular-weight heparin were prescribed for all patients in line with the MoH guidelines [10]. Continuous renal replacement therapy (CRRT) in ICU setting was performed with Prismaflex® system in a citrate anti-coagulated circuit, aiming a blood flow of around 20 mL/kg/hour.
Comparison between the groups formed according to the AKI timing
Patients of the three groups (AKI on admission, AKI in the 1st week, AKI after the 1st week) were in similar age and had similar baseline mean arterial pressure, creatinine and hemoglobin levels. Co-morbidities such as diabetes, hypertension, malignancies and ischemic heart diseases/heart failure were also similar between three groups. CRP and D-dimer levels on admission didn’t differ between the groups. Patients who had AKI on admission day had higher initial uric acid levels. All initial laboratory values of the patients can be found in table-1.
Duration of hospital stay, intensive care unit (ICU) requirement and mortality was higher when AKI developed later in the disease course, especially after 7th day. Patients who develop later AKIs had lower serum albumin levels as well as lower arterial O2 pressure and lower oxygen saturation levels. Pre-dominant stage of AKI was stage 1; however, stage 2 & 3 AKIs, which have worse prognosis tend to increase with AKIs that occurred later (table-2). AKI related prognostic indices of the patients can be found in table-2.
While there were no significant differences between the initial inflammatory markers of the three groups, comparison of changes put forth significant differences. Nadir lymphocyte counts were significantly lower while peak CRP and peak D-dimer levels were significantly higher for patients who developed AKI later in the disease course (Table-3). Although it couldn’t reach the statistical significance, peak ferritin levels were also higher for patients who developed AKI later.
Sodium, chlorine and potassium abnormalities were more common in patients who developed AKI later (Table-3).
Treatment modalities were not different between the groups (Table-4). RRT had to be performed in 6 patients who developed AKI later (2 among the 1st week AKIs and 4 among the AKIs developed after the 1st week) but none of the patients who had AKI on admission needed RRT. Anti IL-6 receptor antibody tocilizumab use was significantly more frequent for patients who developed AKI after 7th day. Pulmonary involvement (i.e. COVID pneumonia) was similar between the groups and there was not a statistically significant difference for secondary bacterial infections (Table-2).
Comparison between survivors and non-survivors
Duration of hospital stay was not different for survivors and non-survivors. Those who died were older. Patients who survived and who didn’t had similar rates of diabetes or hypertension, while concomitant malignancies were more frequent in patients who died (Table-5).
AKI had 24.7% mortality in our patients who had eGFRs above 60 ml/min/1.73 m2. AKI developed later in non-survivors and it lasted longer. Non-survivors had significantly higher initial CRP, LDH, ferritin and D-dimer levels while their hemoglobin and lymphocyte counts were significantly lower (Table-5).
Patients who died had lower serum albumin levels than those who survived. Hematuria or proteinuria (p=0.001; OR:2.4; 95% CI: 1.4 – 3.8 and p=0.015; OR:4.34; 95% CI:1.3 – 14.3 respectively) were more common in patients who died.
Among electrolyte disturbances hyponatremia and hypochloremia were similar between survivors and non-survivors. On the other hand, hypernatremia (p=0.000, OR: 6.5; 95% CI: 3.0 – 13.9) and hyperchloremia (p=0.002, OR:3.8; 95%CI: 1.7 – 8.4) were more common in patients who died. Comparison of other electrolytes can be found in table-5.
Patients who died had more secondary bacterial infections (OR: 3.5 ; 95%CI: 1.9 – 6.4). However, ferritin levels, as a marker of inflammation, were similar in patients who had secondary bacterial infections and in those who hadn’t (n=24; 1120 ±691 vs n=62; 976 ± 109; p=0.548). Urea-to-creatinine ratios checked both on the day of AKI and on the day of worst kidney function, were higher in patients who died (p=0,02 and p=0,000 respectively).