key: cord-0842573-n7n5o9pz authors: Lebedev, Larissa; Sapojnikov, Marina; Wechsler, Alexander; Varadi, Ronen Levy; Zamir, Doron; Tobar, Ana; Levin-Iaina, Nomy; Fytlovich, Shlomo; Yagil, Yoram title: Minimal Change Disease Following the Pfizer-BioNTech COVID-19 Vaccine date: 2021-04-08 journal: Am J Kidney Dis DOI: 10.1053/j.ajkd.2021.03.010 sha: 6e894300faa04fa69ea94416a4dff9233be68e60 doc_id: 842573 cord_uid: n7n5o9pz We report on the development of minimal change disease (MCD) with nephrotic syndrome (NS) and acute kidney injury (AKI), shortly after first injection of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). A 50-year-old previously healthy male was admitted to our hospital following the appearance of peripheral edema. Ten days earlier, he had received the first injection of the vaccine. Four days after injection, he developed lower leg edema, which rapidly progressed to anasarca. On admission, serum creatinine was 2.31 mg/dL and 24-hr urinary protein excretion was 6.9 grams. As kidney function continued to decline over the next days, empiric treatment was initiated with prednisone 80 mg/day. A kidney biopsy was performed and the findings were consistent with MCD. Ten days later, kidney function began to improve, gradually returning to normal. The clinical triad of MCD, NS and AKI has been previously described under a variety of circumstances, but not following the Pfizer COVID-19 vaccine. The association between the vaccination and MCD is at this time temporal and by exclusion, and by no means firmly established. We await further reports of similar cases to evaluate the true incidence of this possible vaccine side-effect. The global SARS-Cov-2 pandemic has caused extensive morbidity and mortality worldwide during the past year. The advent of novel vaccines appears currently to be altering the course of events in a favorable direction. Along with clear benefits stemming out of vaccination programs in many countries, side-effects of these vaccines remain a concern that must be addressed. Major side-effects appear to be uncommon.. We report on the development of minimal change disease (MCD) with full-blown nephrotic syndrome (NS) and acute kidney injury (AKI) starting a few days after administration of the first injection of the BNT162b2 vaccine (Pfizer-BioNTech COVID-19 vaccine). A 50-year-old previously healthy male was admitted to our medical center following the appearance of peripheral edema. Ten days earlier, he had received the first injection of the Pfizer-BioNTech COVID-19-vaccine. The timeline of clinical events from is shown in Fig. 1 . He initially complained of pain in the injection area. On the 3 rd day after the injection, he developed abdominal pain and diarrhea. One day later, he noticed swelling of the lower extremities, which gradually worsened over the next 6 days. On day 10 after vaccination, he presented to the Emergency Department with anasarca. Laboratory tests 10 months earlier were normal, with serum creatinine 0.78 mg/dL and normal urinalysis. The patient denied use of NSAIDs prior to or after the vaccination. On admission, blood pressure was 170/110 mmHg, heart rate 80 b/min. Physical examination revealed pitting edema in the lower extremities, palms of hands, abdominal wall, and penis. The abdomen was distended. There were rales at both lung bases. Laboratory tests J o u r n a l P r e -p r o o f revealed serum creatinine 2.31 mg/dL, SUN 78 mg/dL, albumin 1.93 g/L, cholesterol 484 mg/dL and triglycerides 166 mg/dL. HBsAg and HCV Ab were negative, C3 and C4 levels were within normal range, and ANCA, anti GBM Ab and ANA were negative. PCR test and serology for COVID-19 (Elecsys Anti-SARS-CoV-2, Cobas, Roche Diagnostics, Mannheim, Germany) were negative. Spike protein subunits S1 and S2 IgG (S1/S2-IgG) antibody titer (Diasorin, Saluggia, Italy) was 38.9 AU/ml. Urinalysis revealed +4 protein; urinary sediment showed 3-5 red blood cells PHPF, some dysmorphic, and fatty casts and oval fat bodies. Twenty four hour urinary collection revealed proteinuria of 6.9 grams/day. Chest X-ray showed bilateral pleural effusions. CT examination without contrast demonstrated kidneys of normal size and no evidence of urinary tract obstruction. During the first few days after admission, kidney function continued to decline, with the serum creatinine increasing to 3.43 mg/dL. Empiric treatment with prednisone 80 mg per day was initiated on day 4 after admission. A percutaneous kidney biopsy was performed the next day. The results are shown in Fig. 2 . Twenty-four glomeruli were detected, one with global sclerosis and the others normal. There was mild congestion in the glomerular capillaries and no thickening of the glomerular basement membrane. The interstitium was notable for small lymphocytic infiltrates. There was extensive acute tubular injury, with beginning of calcifications in the medulla. Immunofluorescence revealed linear membranous and mesangial albumin, IgG trace, mesangial IgM +1, vascular C3 +1, and tubular IgG trace. Two glomeruli were examined by electron microscopy. The glomerular basement membrane thickness ranged 360-550 nm with diffuse flattening of the podocyte foot processes over ~90% of the glomerular volume. There were no electron dense deposits but there were foci of microvillous transformation. These findings were consistent with minimal change disease with acute tubular injury. Steroid therapy was continued and treatment for hypertension was initiated. The clinical course showed a further rise in creatinine levels to a maximum of 6.6 mg/dL. Five days after initiation of corticosteroid therapy, urine output increased, there was a short polyuric phase with loss of 7 kg in body weight, and peripheral edema gradually disappeared. In parallel, kidney function began to improve and serum creatinine gradually declined to 1.25 mg/dL. The patient was discharged after 17 days in hospital with continued steroid treatment. One week later, serum creatinine was 0.97 mg/dl/, plasma albumin 3.2 gm/L and Albumin Creatinine Ratio (ACR) 155 mg/g. The clinical triad of MCD, NS and AKI has been previously described under a variety of circumstances 1;2 , including at least two cases following the influenza vaccine 3;4 . To the best of our knowledge, such occurrence has not been previously reported following the Pfizer-BioNTech or other COVID-19 vaccines. The clinical appearance of MCD in our case, with NS and severe AKI, is somewhat atypical. Usually, the major presenting clinical features in MCD are related to NS, with overt peripheral edema, massive proteinuria with hypoalbuminemia and no major disturbance in glomerular filtration rate 4 . AKI has been described, however, as a complication of NS 2 , including in the setting of MCD 1 . The explanation for the occurrence of AKI in our case may be found in the results of the kidney biopsy, demonstrating extensive acute tubular injury. This is indeed atypical for MCD in which the pathological hallmark is absence of visible alterations by light microscopy. The inevitable question that arises is whether the appearance of MCD with NS and AKI is coincidental to or causally related to the vaccination. The association between COVID-19 vaccination and the appearance of this triad, as described in this report, can only be based on Further studies, however, are needed to continue exploring the early immune response to the vaccine, particularly in relation to side effects, a task beyond the scope of the current report. In addition to anaphylaxis, an uncommon life-threatening side effect of the COVID-19 J o u r n a l P r e -p r o o f vaccination, our case report raises the possibility of another major side effect, which at this time cannot be conclusively attributed to the COVID-19 vaccine. Of significance is that this side effect is treatable with corticosteroids, with prompt and apparently complete resolution. We suggest, therefore, that patients who develop NS and AKI within the days to weeks following COVID-19 vaccination, should undergo a kidney biopsy. If MCD is confirmed, prompt initiation of treatment with oral corticosteroids, such as prednisone ~1 mg/kg over several weeks, should be considered as it appeared to be helpful in our patient. Figures Fig.1 : Timeline of clinical events from time of vaccination and until the kidney biopsy was performed. Acute Kidney Injury Associated with Minimal Change Nephrotic Syndrome in an Elderly Patient Successfully Treated with both Fluid Management and Specific Therapy Based on Kidney Biopsy Findings The nephrotic syndrome and its complications Minimal change disease following influenza vaccination and acute renal failure: just a coincidence? Minimal change nephrotic syndrome in a 65-year-old patient following influenza vaccination Minimal Change Disease Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteriapoliomyelitis-vaccination Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus Adaptive immunity to SARS-CoV-2 and COVID-19 The authors wish to acknowledge Prof. Eli Magen for consulting on immunological issues during the discussions that led to drafting of this manuscript. The authors declare that they have obtained consent from the patient reported in this article for publication of the information about him that appears within this Case Report.