COVID-19–Associated Prerenal Acute Kidney Injury: Hemodynamic Instability and Renal Hypoperfusion

1. Introduction

Prerenal acute kidney injury (AKI) is a functional, reversible renal dysfunction caused by reduced renal perfusion without structural kidney damage [1]. COVID-19 has been associated with AKI, with regional incidence ranging from 5–15% in Asia, 20–35% in Europe, and 36–46% in North America, and with higher risk in older adults, patients with chronic kidney disease, diabetes, cardiovascular disease, and those admitted to the ICU [2]. The incidence of AKI among hospitalized patients ranges from 0.5% to 25%, with substantially higher rates in intensive care units [3]. Renal involvement often presents as hematuria and proteinuria and is associated with worse outcomes [4]. Mechanistically, prerenal AKI arises from hemodynamic instability, hypovolemia, hypoxia, cardiovascular complications, RAAS dysregulation, and systemic inflammation [5]. Cytokine profiling shows elevated IL-6, IL-1β, TNF-α, IFN-γ, and chemokines, contributing to endothelial dysfunction and renal hypoperfusion [6].

Early detection using urine sodium, urine osmolality, and fractional excretion of sodium (<1%) is essential [7]. Prompt fluid resuscitation, oxygen therapy, and avoidance of nephrotoxic agents can restore renal function and prevent progression to intrinsic AKI [8]. This case demonstrated that COVID-19 caused prerenal AKI in a patient without pre-existing kidney disease. Early markers, including low FeNa (<1%) and high urine osmolality, helped distinguish prerenal from intrinsic AKI. Prompt fluid resuscitation, oxygen therapy, and supportive care resulted in rapid recovery without the need for renal replacement therapy. Hemodynamic instability, hypovolemia, hypoxia, and systemic inflammation were key contributors. These findings highlighted COVID-19 multisystem effects and underscored the importance of vigilant renal monitoring in hospitalized patients.

2. Case Presentation

In December 2022, a 60-year-old male presented to the emergency department with a three-day history of dry cough and progressively worsening dyspnea, accompanied by a two-day history of generalized weakness, dizziness, and malaise. He denied any prior use of nephrotoxic medications, as well as any history of sepsis, heart failure, shock, cirrhosis, or bilateral renal artery stenosis. The patient was a non-smoker, did not consume alcohol, and was unaware of his family’s medical or medication history. Five days before admission, he had traveled outside the town using public transportation without wearing a face mask. He reported no previous history of COVID-19 infection or chronic kidney disease. On arrival, he reported two days of oliguria, cold intolerance, dehydration, and fever; seven days prior, he had been in his usual state of health. Initial vital signs were as follows: temperature 38.8 °C, heart rate 102 beats/min, respiratory rate 20 breaths/min, blood pressure 144/97 mmHg, and oxygen saturation 87% on room air. Anthropometric measurements revealed a weight of 79 kg, height of 1.75 m, and a body mass index of 25.8 kg/m².

Laboratory investigations on admission revealed a blood urea nitrogen level of 51 mg/dL, plasma creatinine of 2.7 mg/dL, fasting blood glucose of 117 mg/dL, serum potassium of 7.1 mEq/L, serum sodium of 140 mEq/L, serum phosphate of 2.6 mg/dL, hemoglobin of 12.7 g/dL, and a white blood cell count of 18,750 cells/mm³ with polymorphonuclear leukocytosis (70% neutrophils; 1,850/µL). Liver enzymes were elevated, with aspartate aminotransferase of 61 U/L and alanine aminotransferase of 79 U/L.

The estimated glomerular filtration rate (eGFR), calculated using the below formula:

$$\mathrm{C}\mathrm{o}\mathrm{c}\mathrm{k}\mathrm{c}\mathrm{r}\mathrm{o}\mathrm{f}\mathrm{t}-\mathrm{G}\mathrm{a}\mathrm{u}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{q}\mathrm{u}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}={\displaystyle \frac{\left(140-age\right)xweight\left(kg\right)}{72\mathrm{x}\mathrm{s}\mathrm{e}\mathrm{r}\mathrm{u}\mathrm{m}\mathrm{c}\mathrm{r}\mathrm{e}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{n}\mathrm{i}\mathrm{n}\mathrm{e}(\mathrm{m}\mathrm{g}/\mathrm{d}\mathrm{L})}}$$

$$\mathrm{C}\mathrm{o}\mathrm{c}\mathrm{k}\mathrm{c}\mathrm{r}\mathrm{o}\mathrm{f}\mathrm{t}-\mathrm{G}\mathrm{a}\mathrm{u}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{q}\mathrm{u}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}={\displaystyle \frac{\left(140-60\right)x79\mathrm{k}\mathrm{g}}{72\mathrm{x}2.7\frac{\mathrm{m}\mathrm{E}\mathrm{q}}{\mathrm{L}}}}={\displaystyle \frac{6320}{194.4}}=32.5\mathrm{m}\mathrm{L}/\mathrm{m}\mathrm{i}\mathrm{n}$$

eGFR 32.5 mL/min, indicated moderately reduced renal function consistent with stage II acute kidney injury. Metabolic acidosis was evident, with a decreased serum bicarbonate level of 18.0 mEq/L (reference range 22–29 mEq/L). Urinalysis showed a urine sodium level of 18 mmol/L (reference range 20–40 mmol/L), urine osmolality of 650 mOsm/kg (reference range 50–1000 mOsm/kg), and urine creatinine of 2.3 mg/dL, resulting in a fractional excretion of sodium (FeNa) of 0.16%, calculated as:

$$\mathrm{F}\mathrm{e}\mathrm{N}\mathrm{a}={\displaystyle \frac{\mathrm{U}\mathrm{r}\mathrm{i}\mathrm{n}\mathrm{e}\mathrm{s}\mathrm{o}\mathrm{d}\mathrm{i}\mathrm{u}\mathrm{m}\mathrm{x}\mathrm{P}\mathrm{l}\mathrm{a}\mathrm{s}\mathrm{m}\mathrm{a}\mathrm{c}\mathrm{r}\mathrm{e}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{n}\mathrm{i}\mathrm{n}\mathrm{e}}{\mathrm{P}\mathrm{l}\mathrm{a}\mathrm{s}\mathrm{m}\mathrm{a}\mathrm{s}\mathrm{o}\mathrm{d}\mathrm{i}\mathrm{u}\mathrm{m}\mathrm{x}\mathrm{U}\mathrm{r}\mathrm{i}\mathrm{n}\mathrm{e}\mathrm{c}\mathrm{r}\mathrm{e}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{n}\mathrm{i}\mathrm{n}\mathrm{e}}}x100$$

$$\mathrm{F}\mathrm{e}\mathrm{N}\mathrm{a}={\displaystyle \frac{18\frac{\mathrm{m}\mathrm{m}\mathrm{o}\mathrm{l}}{\mathrm{L}}x2.7\frac{\mathrm{m}\mathrm{g}}{\mathrm{d}\mathrm{L}}}{140\frac{\mathrm{m}\mathrm{E}\mathrm{q}}{\mathrm{L}}x2.3\frac{\mathrm{m}\mathrm{g}}{\mathrm{d}\mathrm{L}}}}x100=0.16\mathrm{\%}$$

These findings shown high urine osmolality, low urine sodium, and FeNa <1% were consistent with prerenal acute kidney injury. Urine microscopy and culture revealed mixed bacterial growth, most likely due to sample contamination, and were not indicative of a true urinary tract infection. In contrast, acute tubular necrosis typically presents with low urine osmolality, elevated urine sodium, and FeNa >2%.

Renal ultrasonography demonstrated normal kidney size with preserved parenchymal architecture, while Doppler imaging showed reduced renal blood flow with low resistance. Chest radiography revealed multifocal, patchy airspace opacities consistent with atypical pneumonia or viral infection, suggestive of COVID-19. Electrocardiography showed a QT interval of 421 milliseconds. COVID-19 infection was confirmed by reverse transcription polymerase chain reaction testing within 30 hours of admission, after which the patient was transferred to the critical care unit. The final diagnosis was stage II (moderate) prerenal acute kidney injury secondary to COVID-19 infection.

The patient received supplemental oxygen via nasal cannula at 3 L/min. Fluid resuscitation was initiated with a 1 L bolus of Ringer’s lactate, followed by maintenance fluids at 200 mL/hour, adjusted according to his hemodynamic status and urine output. He remained anuric during the first 24 hours; however, urine output increased to 800 mL over the subsequent 12 hours, indicating improved renal perfusion. Furosemide 40 mg intravenously was administered twice daily for three days to support diuresis and facilitate renal recovery. Low-molecular-weight heparin, 5,000 IU every 12 hours, was given for thromboprophylaxis. Empiric intravenous ceftriaxone 1 g daily was administered for three days to prevent secondary bacterial infection, and acetaminophen 500 mg was given as needed for fever control.

During hospitalization, the patient developed hypokalemia, with a serum potassium level of 3.1 mEq/L, which was corrected with intravenous potassium chloride supplementation, followed by oral potassium replacement once oral intake was tolerated. Serum electrolytes were monitored closely, and potassium levels normalized without complications. Renal function was closely monitored, with the estimated glomerular filtration rate calculated using the Cockcroft–Gault equation, which improved from 32.5 mL/min on admission to 61 mL/min/1.73 m² prior to discharge. The patient did not require renal replacement therapy. After two consecutive negative RT-PCR tests for COVID-19, he was discharged with instructions for monthly outpatient follow-up.

3. Discussion

AKI is a common complication of COVID-19, with incidence varying by region: 5–29% in China [9], 37–57% in the US [10], and 56% in Brazil [11], with a substantial proportion reaching stage 3. COVID-19–positive patients are more likely to develop severe AKI and require renal replacement therapy (RRT), with rates of up to 19% in the US and 47% in Brazil [12]. According to KDIGO, AKI is defined as an increase in serum creatinine of ≥0.3 mg/dL within 48 hours, a rise to ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/h for 6 hours [12]. Severity is staged as follows: Stage 1 – SCr 1.5–1.9× baseline or ≥0.3 mg/dL rise; Stage 2 – SCr 2.0–2.9× baseline; Stage 3 – SCr ≥3× baseline, ≥4.0 mg/dL, or requirement of RRT [12].

Prerenal AKI, the most frequent type in COVID-19, results from reduced renal perfusion without structural kidney injury [13]. In this patient, laboratory findings included low urine sodium (<20 mEq/L), high urine osmolality (>500 mOsm/kg), and a FeNa <1%, typically with bland urine sediment. In contrast, intrinsic AKI is characterized by low urine osmolality (<350 mOsm/kg), high FeNa (>2%), and casts indicative of tubular or glomerular injury, while postrenal AKI is identified via imaging to rule out obstruction.

Case comparisons illustrate the spectrum of COVID-19–associated AKI. Li et al. (2021) reported immune-mediated IgA vasculitis/nephropathy with rash, hematuria, proteinuria, and biopsy-confirmed IgA deposition [15], which required immunomodulatory therapy. In contrast, the present patient had prerenal/ATN-type AKI without immune-complex deposition, was managed supportively with hemoperfusion, and achieved rapid renal recovery. Onoriode Kesiena et al. (2022) described collapsing glomerulopathy in a patient with advanced CKD, nephrotic-range proteinuria, and irreversible renal failure [16], contrasting with this patient’s fully reversible AKI. Taghizadieh et al. (2020) [17] and Sise et al. (2020) [18] reported severe AKI in older patients with multiple comorbidities, requiring CRRT and prolonged ICU care, whereas this young, previously healthy patient recovered quickly with intermittent dialysis. Ghobadi et al. (2020) [19] reported moderate prerenal AKI in an older patient who recovered rapidly without dialysis, consistent with the present case.

The pathophysiology of COVID-19–associated prerenal AKI involves multiple mechanisms, including SARS-CoV-2–induced RAAS dysregulation [20], renal vasoconstriction, hypovolemia from fever or fluid loss, systemic hypotension, cytokine-mediated inflammation, endothelial dysfunction, hypoxia from pneumonia or ARDS, hypercoagulability, and the effects of perfusion-limiting medications such as diuretics, vasopressors, or nephrotoxins [21,22].

Prompt management focuses on hemodynamic optimization, fluid resuscitation, oxygenation, and avoidance of nephrotoxic agents [23]. In this patient, supportive care included ICU transfer, a 1 L bolus of lactated Ringer’s, maintenance fluids at 200 mL/hour, and close cardiopulmonary and metabolic monitoring. With timely intervention, prerenal AKI can resolve completely, whereas delayed or inadequate treatment may lead to acute tubular necrosis or other complications [24].

4. Limitations

This case report has several limitations. It involved a single patient, limiting generalizability to broader populations with COVID-19–associated prerenal AKI. Long-term renal outcomes were not assessed, and detailed cytokine or inflammatory profiling (e.g., IL-6, TNF-α) was unavailable. Hemodynamic monitoring was not performed, and fluid resuscitation followed empirical protocols without age- or comorbidity-specific guidance. Advanced kidney injury biomarkers (e.g., NGAL, KIM-1) were not measured, and comparative imaging or laboratory data were limited. Incomplete information on family history and prior medications may have affected interpretation of AKI susceptibility, and the patient’s lack of comorbidities reduces applicability to more critically ill patients.

5. Conclusion

This case highlighted that COVID-19 precipitated prerenal acute kidney injury in a patient without pre-existing renal disease. Early recognition using biochemical markers, including low fractional excretion of sodium and high urine osmolality, enabled prompt diagnosis and differentiation from intrinsic AKI. Timely interventions such as judicious fluid resuscitation, oxygen therapy, and supportive care facilitated rapid renal recovery without the need for renal replacement therapy. The report emphasized the multifactorial pathophysiology of COVID-19–associated prerenal AKI, including hemodynamic instability, hypovolemia, hypoxia, systemic inflammation, and RAAS imbalance, underscoring the importance of vigilant renal monitoring in hospitalized COVID-19 patients. Early and tailored management resulted in a favorable outcome, even in the context of severe infection.