A 35-year-old female presented to the emergency room with acute constant right sided flank pain, urge to move, vomiting, and macroscopic hematuria with blood clots for three days. Two weeks earlier, she had been diagnosed with COVID-19, following a transient fever and loss of smell and taste till five days before presentation. At presentation, the patient did not have raised temperature or any urinary tract-, gastrointestinal-, or cardiopulmonary symptoms. Her medical history was unremarkable expect for two episodes of pyelonephritis (side unknown), one during pregnancy, of which she clearly recognized the pain. She did not use any medication.
Vital functions and physical examination showed no abnormalities. Blood tests revealed a serum creatinine level of 65 µmol/L, with an eGFR (MDRD) of 90 ml/min/1.73m^2. Leucocytes were elevated (13.5 x109/L, Table 1). Urine was positive for erythrocytes, leukocytes and nitrites. Ultrasound showed hydronephrosis of the right kidney. Enhanced computed tomography (CT) revealed an obstructive dense mass of 75HU, corresponding with a blood clot, in the proximal right ureter close to the renal pelvis. The right kidney showed severe parenchymal thickening, multiple small calcifications deep in the calyces and extensive hydronephrosis (Fig. 1). In addition, ground glass opacities were observed in the peripheral basal lung area’s; suspect for remnants of the SARS-CoV-2 infection.
Table 1
Test | Range | At first presentation (29-07-2020) | At start of fever (01-08-2020) | 5 days before discharge |
Urea, mmol/L | 2.5–7.5 | 3.7 | 6.1 | |
Creatinine, µmol/L | 50–95 | 65 | 113 | 57 |
estimated GFR (CKD-EPI), ml/min/1.73m^2 | > 83 | 106 | 55 | 116 |
Calcium, mmol/L | 2.15–2.55 | 2.30 | | |
Sodium, mmol/L | 135–145 | 134 | | 134 |
Potassium (plasma), mmol/L | 3.2–4.7 | 3.7 | 4.0 | 4.1 |
Chloride, mmol/L | 97–107 | 102 | | |
ASAT, U/L | < 30 | 23 | 25 | |
ALAT, U/L | < 34 | 9 | 19 | |
LD, U/L | < 248 | 183 | 254 | |
GGT, U/L | < 40 | 11 | 12 | |
Bilirubin, total, µmol/L | 5–19 | 9 | 7 | |
Alkaline Phosphatase, U/L | 40–120 | 66 | 90 | |
Total protein, g/L | 63–83 | 75 | | |
Albumin, g/L | 32–48 | 42 | | |
CK, U/L | 10–145 | 48 | | |
NT-proBNP (ng/l) | < 125 | 93 | | |
Hemoglobin (mmol/L) | 7.2–9.5 | 8.6 | 6.4 | |
Hematocrit (L/L) | 0.36–0.47 | 0.42 | 0.32 | |
Erythrocytes (x10^12/L) | 4.0-5.3 | 5.1 | 3.8 | |
MCV (fL) | 83–100 | 83 | 82 | |
Trombocytes (x10^9/L) | 150–400 | 322 | 119 | |
Leucocytes (x10^9/L) | 4.0–10.0 | 13.5 | 13.9 | |
CRP (mg/L) | < 0.5 | 3 | 246 | 27 |
Glucose (mmol/L) | 3.5-9.0 | 5.6 | | |
Protrombin time (sec) | 9–12 | 10.1 | | |
APTT (sec) | 24–33 | 29 | | |
D-dimer (mg/L) | < 0.5 | 0.49 | | |
Ferritin (ug/L) | 10–100 | 92 | | |
The patient was admitted to the hospital with oral ciprofloxacin, adequate analgesic, ondansetron and nadroparin prophylaxis. Urine culture was collected.
Macroscopic hematuria with clots continued intermittently at the second day of admission and lab parameters showed an increased CRP to 130 mg/L, worsening of the eGFR to 42 ml/min/1.73m^2 and doubling of serum creatinine to 125 µmol/L (Table 1). Therefore, a nephrostomy catheter was introduced and hydration was increased.
Although the renal parameters gradually improved, the patient developed spiking fever. Antibiotic treatment was switched to intravenous cefuroxime with a one-off dose of tobramycin. A thoracic X-ray ruled out a hospital acquired pneumonia and showed minimal basal atelectasis without any other aberrations. Urine culture showed E. coli growth, sensitive to ciprofloxacin and cefuroxime among others.
The spiking fever persisted and the patient developed slight anemia (hemoglobin 6.4 mmol/L). A second abdominal CT at day three showed signs of extending pyelonephritis and resorption of the ureteral blood clod, but no indication for abscesses (Fig. 2). Antibiotic treatment was switched to intravenous ceftriaxone, without subsequent improvement of fever or relief of symptoms. Nevertheless, the renal parameters remained gradually improving and urine production was stable and sufficient.
Furthermore, the patient noted a decrease in vision of the right eye at day four. Fundoscopy showed diffuse retinal capillary micro-bleeding in the right eye, characteristic for a thrombotic venous occlusion (Fig. 3). Beta-blocker eye droplets were prescribed. The prophylactic dosage of nadroparin was not increased to a therapeutic dosage after consulting the vascular specialists. Follow up through fundoscopy every other day showed no further changes during the admission.
At day six, a third abdominal CT was performed and was compatible with an ongoing pyelonephritis. There were multiple hypodense areas. As a renal abscess could not be ruled out, an attempt for drainage of the suspected presumed abnormality was performed. However, the drainage revealed solely swollen hydrous kidney parenchyma without purulence.
As fever-spikes up to 40,4 degrees Celsius lingered through admission, another real-time reverse transcription PCR for SARS-COV-2 from a throat swab sample was performed at day seven, with a negative result.
Due to diarrhea with mucus admixture, PCRs of campylobacter coli/jejuni, salmonella, shigella and yersinia enterocolitica were performed, all with a negative result. The diarrhea ceased spontaneously within five days.
Sudden and recurrent symmetrical paresthesia and severe lower back pain during consecutive nights were indications to perform a cerebral and spinal MRI at day eight, which did not show any abnormalities. In addition, also in respect to the ocular vascular occlusion, a carotid and vertebral artery duplex analysis was performed at day eight, without any aberrations.
Although antibiotic treatment for sepsis was adequate, the clinical condition of the patient did not improve thus far. An urgent multidisciplinary meeting with the departments of urology, infectious disease, microbiology, neurology, and ophthalmology did not result in an added diagnosis or full explanation of the woman's symptoms. Analysis for the persistent fever was continued by extensive determination of systemic and (auto-)immunogenic disorders (Table 2), but no indications were found. The International Normalized Ratio (1.1) and the activated partial thromboplastin time (25, range 24–33 seconds) were not aberrant. The anemia remained stable throughout admission, with a minimum hemoglobin level of 6.0 mmol/L. All blood, urine and drainage fluid culture analyses resulted in growth of E.coli with sensitivity for ciprofloxacin, cefuroxime and ceftriaxone.
Table 2
Systemic and (auto)immunogenic parameters
Test | Reference range | Result |
IgG4, g/l | 0.08–1.4 | 0.34 |
ANCA anti-PR3 | 0.0–3.0 | 0.3 |
ANCA anti-MPO | 0.0–5.0 | 0.2 |
ANA | 0.0-1.5 | < 0.5 |
Anti-dsDNA, U/ml | 0.0–15.0 | 0.7 |
Cardiolipin IgM, U/ml | 0–40 | 9.4 |
Cardiolipin IgG, U/ml | 0–40 | 30.0 |
Beta-2-glycoprotein I IgM, U/ml | 0–10 | < 0.01 |
Beta-2-glycoprotein I IgG, U/ml | 0–10 | 1.3 |
lupus anticoagulant | | undetectable |
CH-50, % | 68–133 | 122 |
C1q (subfactor C1), IE/ml | 81–128 | 129 |
C3 (determined with anti-C3c), g/L | 0.9–1.8 | 1.54 |
C4, mg/L | 150–400 | 180 |
DAT IgG | neg | neg |
DAT C3b/3d | neg | neg |
DAT Titer | | 1:1 |
JAN2 V617F mutation | | undetectable |
The symptoms of fever and flank pain slowly decreased at the 10th day of admission and the catheter was removed. The fever disappeared two days later. The patient further recuperated till acceptable condition to discharge at day 17 with oral ciprofloxacin treatment for another 10 days.
Follow-up
The patient returned to the ER one week later due to complains of the nephrostomy and was advised to hydrate and continue analgesics. There were no indications for a (recurrent) infection.
Three weeks after discharge, an antegrade pyelography revealed effective and easy passage of fluid to the bladder. Two months later, a micturating cystourethrogram (MCUG) did not show any signs of urinary reflux or anatomical deviations. Thereafter, the nephrostomy was successfully removed.
At four months after discharge, a CT-scan for follow-up showed clear decrease of volume of the right kidney compared to the CT at admission (Fig. 4). At the site of the preceded pyelonephritis, an irregular aspect of the surface of the interpolar region and inferior pole and decreased density suggested scarring of the renal cortex. The previous multiple small concrements were observed as unchanged. By multidisciplinary consultation, a one-year follow-up was chosen for monitoring blood pressure, serum creatinine/eGFR and urinal protein level.
Follow-up of the eye through repetitive fundoscopy showed gradual improvement of the quantity and sizes of the retinal bleeding sites. However, remnant bleedings in the peripheral retina were still visible at three months after discharge.