Chronic kidney disease (CKD) patients have been disproportionately affected by the Coronavirus Disease 2019 (COVID-19) pandemic^{[1, 2]}. Beyond acute kidney injury (AKI) during acute COVID-19 infection, the long-term effects of SARS-CoV-2 on kidney function of CKD patients remain uncertain^[2]. A compromised immune system, often seen in CKD patients, especially those on dialysis, or recipients of kidney transplants, increases the risk of severe COVID-19^{[3, 4]}. Reduced kidney function is often associated with dysfunction in other organs, which further deteriorates in kidney function^{[5, 6]}. In addition, a novel form of kidney disease termed COVAN (COVID-19 Associated Nephropathy), which includes collapsing glomerulopathy in some cases and tubular damage in others, has been reported during COVID-19^[7]. After hospital discharge, most COVID-19 patients recover within weeks; however, some persons develop long-term damage (lungs, heart, brain, kidneys, or other organs), or present with non-specific symptoms, which is known as long COVID^{[8, 9, 10]}.

Many studies have monitored renal function in patients with COVID-19, primarily focusing on the incidence, prognosis, and outcomes of AKI during infection^{[10,11, 12- 15]}, or examining how preexisting CKD influences COVID-19 severity^[6] and mortality^[12]. In contrast, fewer investigations have explored longitudinal changes in kidney function among individuals with preexisting CKD during and after COVID-19. These studies show inconsistent findings, largely influenced by different follow-up duration, initial kidney function, and the severity of the infection^[16-18]. In clinical nephrology, understanding whether COVID-19 alters CKD progression is essential for patient management, risk stratification, and therapeutic planning.

This multicenter study therefore examined the impact of COVID-19 on kidney function trajectories in CKD patients followed at eight nephrology centers over 36 months.

Baseline characteristics of the study population are summarized in Table 1. At enrollment, the study groups differed in underlying kidney disease, CKD duration, comorbidities frequency, and therapies applied. Baseline GFR was higher in COVID-positive compared to COVID-negative patients due to a significantly lower number of subjects with CKD stage 4 (Table 1), while other demographic differences were not statistically significant.

X±SEM, M(IQR), ° patients number, Statistical analysis: Student’s t-test for comparison of normally distributed variables, Kruskal-Wallis test for comparison of median values, and the chi-square/ Fisher test for comparison of frequency F= female, M= male, GN= chronic glomerulonephritis, Nscl= nephroangiosclerosis, urological causes (prostate adenoma, unilateral nephrectomy) CVD= cardiovascular diseases, COPD= chronic obstructive pulmonary disease, ACEi= angiotensin converting enzyme inhibitor, ARB= angiotensin receptor blocker, active microscopic urinary sediment: erythrocytes and/ or leucocytes > 5/ microscopic field.

To minimize the effect of these imbalances, propensity score matching was performed, yielding 46 well-matched pairs with no significant differences in baseline characteristics. Other markers of kidney injury, including pathological urine sediment and proteinuria, were also balanced between the groups at baseline. Compared to the COVID-positive group, a significantly higher number of COVID -negative patients had proteinuria > 3 g/24 h at the end of the study. Individual values showed that seven COVID -negative and 4 COVID -positive patients with normal proteinuria at the start of the study developed proteinuria values from 0.83 to 2.8 g/24 hours (COVID-positive) and from 0.8 to 3.85 g/24 hours (COVID-negative) until the end of study period (data not shown).

The main characteristics of COVID-19 are shown in Table2. Of the 58 patients, 17 had only a positive PCR test, while the remaining 41 showed varying severity of COVID disease: mild- 22, moderate- 16, and 3 patients experienced severe or critical illness.

°= patient number, AKI+dialysis= Acute deterioration of kidney function requiring dialysis

Hospitalization was required in 20 of 58 patients (only one with asymptomatic COVID-19 was hospitalized), with durations from 4 to 25 days. Six hospitalized patients had AKI episodes, during which one to three hemodialysis sessions were performed, but none in asymptomatic group. After recovery from acute infection, renal function recovered to previous values in 29 out of 58 patients, but hemodialysis treatment was initiated in one patient a month later. During COVID, not a single patient had fungal pneumonia. Pneumonia was found in 43/ 58 patients by chest computerized tomography (CT) scan, and three patients had an iodine-contrast CT angiography scan due to suspected pulmonary embolism. Majority of patients were treated with non-nephrotoxic antibiotics, oxygen, corticosteroids, low molecular weight heparin, and less frequently, tocilizumab was administered. Two patients had recurrent COVID-19 more than twice. Until January 2024 new co-morbidities developed in 15.5% patients: hypertension (two patients), cardiovascular disorders (atrial fibrillation, thrombophlebitis) (two patients), diabetes mellitus type 2 (three patients), neurological disorders and prostate neoplasm (one patient each). In addition, nine of 17 patients with asymptomatic, seven of 19 patients with mild, eleven with moderate and two patients with severe and critical COVID had progression of CKD. Compared to the COVID-positive group, in the control COVID negative group, no patient had AKI or transitor dialysis or needed iodine contrast for diagnostic purposes. Nevertheless, there was no difference in the use of iodinated contrast between studied groups: three patients COVID positive vs no one patient COVID negative, p = 0.2442.

Patients outcome and changes in kidney function over the 36-month follow-up are shown in Table 3.

* median value, ° = patients number, Statistical analysis: Kruskal-Wallis test for comparison of median values, and the Fisher test for comparison of frequency

A similar number of patients continued nephrological follow-ups in their institutions, but one patient died due to surgical complications, and two initiated chronic hemodialysis treatment. Patients with prior SARS-CoV-2 infection experienced a significantly greater median annual decline in eGFR compared to those without COVID-19 (−4.00 vs. −1.50 ml/min/1.73 m², P = 0.005). The difference persisted after matching, confirming the robustness of this finding. Importantly, kidney function worsened not only in patients with symptomatic COVID-19 but also in those who had been asymptomatic at the time of infection, suggesting that even subclinical infection may contribute to long-term renal decline. In addition, a rapid decrease in eGFR was found in 30 (51.7%) COVID positive and 12 (22.2%) COVID negative patients, which was a significantly different (χ² = 11.3, P = 0.0008). This difference remained significant when stratifying by CKD stage and presence of comorbidities, highlighting the independent contribution of COVID-19 to kidney disease progression. At the end of the study six COVID-positive and 11 COVID-negative patients with mild and rapid eGFR decline progressed to stage 5 non-dialysis-dependent CKD, but this difference was not statistically significant.

Risk factor analysis for CKD progression is summarized in Table 4. Univariate linear regression identified COVID-19 status, baseline eGFR, and presence of comorbidities as significant predictors of kidney function decline.

In multivariate analysis, only COVID-19 status and baseline eGFR remained independently associated with the rate of progression. Using the threshold of −4 ml/min/1.73 m²/year, COVID-19 infection conferred a 3.7-fold higher risk of rapid progression (CI 1.67 – 8.18, p< 0.001: Hosmer–Lemeshow P = 0.71; c-statistic = 0.71), even after adjustment for age, sex, CKD stage, and comorbidities. The risk factor for rapid GFR decline identified by logistic regression analysis was COVID-19 infection independently conferred 3.7-fold higher odds of rapid progression.

In this multicenter cohort of patients with CKD followed for three years, we found that SARS-CoV-2 infection was independently associated with accelerated decline in kidney function. Patients with prior COVID-19 experienced a steeper annual loss of eGFR compared to those without infection, and more than half met the definition of rapid progression. Importantly, kidney function decline was observed not only among patients with symptomatic COVID-19 but also in those with asymptomatic infection, suggesting that even mild or subclinical disease may have long-term renal consequences.

Declines in eGFR after COVID-19 have been reported in several studies, although findings vary depending on follow-up duration, severity of infection, and criteria used to define renal outcomes. Some investigations examined changes only within infected cohorts^[26], while others compared infected and non-infected patients^[14]. Few, however, specifically analyzed kidney function trajectories in CKD populations across extended follow-up periods after COVID-19^{[16, 18]}. Our study contributes to this evidence base by using a matched case–control design in CKD patients and by evaluating eGFR slope as a continuous marker of progression, which provides a sensitive estimate of decline and is particularly useful in studies with modest sample sizes. Similar to our findings, Lu et al. reported an annual eGFR decline of −2.12 ml/min/1.73 m² in COVID-positive patients compared with −1.12 ml/ min/1.73 m² in COVID-negative patients over 24 months^[27], while Basha et al. demonstrated a 3.7-fold higher risk of rapid progression and increased mortality in infected CKD patients during 15 months of follow-up^[28].

In our analysis, both COVID-19 status and baseline eGFR independently predicted the magnitude of decline. Although the explained variance was modest (adjusted R² = 0.054), the model was statistically robust, without evidence of autocorrelation or multi-collinearity. COVID-19 conferred a 3.7-fold higher odds of rapid progression, reinforcing the hypothesis that viral infection accelerates renal function decline, even in patients with previously stable CKD. Several mechanisms may underlie this association. While only a minority of our patients experienced AKI during acute illness, COVID-19 is known to cause tubular injury, endothelial dysfunction, persistent inflammation, and microvascular damage. These processes may trigger subclinical injury that manifests as progressive renal decline over time, as supported by reports of SARS-CoV-2 tropism for renal tissue, persistence of histologic abnormalities months after infection, and experimental data in animal models^{[14, 29, 30]}.

Although COVID-19 status and baseline eGFR was selected as only independent predictors of kidney function decline, the influence of some other factors cannot be ruled out. Contrast agent use was comparable between groups, and pairs from the two groups of participants were matched in terms of key variables. Nevertheless, AKI and hospitalization of COVID-19 group could contribute to kidney function deterioration. On the other side, rapid decline was also observed among COVID-negative patients, most likely reflecting their older age, higher prevalence of nephroangiosclerosis, and greater burden of cardiovascular and pulmonary comorbidities. Indirect pandemic-related effects such as delays in routine care, social isolation, or psychosocial stress may also have played a role, as suggested by other reports^{[31, 32,33]}.

Despite these differences, the number of patients progressing to dialysis-dependent ESRD during follow-up remained low and did not differ between groups. This may reflect the relatively short observation period or the limitations of eGFR estimation in advanced CKD stages. Even so, our findings emphasize the need for intensified renal monitoring in CKD patients after COVID-19, regardless of infection severity or presence of long COVID symptoms. Early identification of rapid progressors, combined with strict management of hypertension and proteinuria, may help delay progression to ESRD.

The strengths of our study include its multicenter design, use of a carefully matched control group, and analysis based on propensity score adjustment. These features increase confidence that COVID-19 itself contributed to faster CKD progression. Equally important is the observation that asymptomatic infections were not benign, underscoring the need for vigilance across the entire CKD population. Clinically, these findings highlight the importance of intensified monitoring after COVID-19 in CKD patients, including regular eGFR assessments and timely management of risk factors such as hypertension and proteinuria. Early identification of rapid progressors may allow for more aggressive interventions to delay progression to end-stage kidney disease. From a public health perspective, our data underscore the need for prioritizing CKD patients in vaccination and post-infection follow-up strategies.

Several limitations should be acknowledged. The retrospective design prevents definitive causal inference, and residual confounding cannot be excluded despite matching and adjustment. The sample size, though multicentric, remains modest, and generalizability may be limited to similar populations. Furthermore, we did not evaluate inflammatory biomarkers or direct measures of viral injury, which might provide mechanistic insights.

In conclusion, our study demonstrates that SARS-CoV-2 infection accelerates CKD progression, even in asymptomatic cases, and that both infection status and baseline eGFR independently predict renal decline. These findings call for heightened clinical vigilance and suggest that lessons from COVID-19 should inform preparedness strategies for future viral outbreaks.