Predictors of gross hematuria following SARS-CoV-2 mRNA vaccination in patients with IgA nephropathy.

Background There have been several reports of IgA nephropathy (IgAN) patients with gross hematuria and acute deterioration of urinary findings and kidney function following SARS-CoV-2 mRNA vaccination. Recent case series studies have indicated a possible link between the status of urinary findings at the time of vaccination and the subsequent appearance of gross hematuria. In this study, we aimed to determine whether the status of pre-vaccination urinary findings was associated with post-vaccination gross hematuria in patients already diagnosed with IgAN. Methods Outpatients with IgAN who had been followed up before vaccination were included. We analyzed the association between the remission of pre-vaccination microscopic hematuria (urine sediment <5 red blood cell/high power field) or proteinuria (<0.3 g/gCr) and post-vaccination gross hematuria. Results A total of 417 Japanese patients with IgAN (median age, 51 years; 56% female; estimated glomerular filtration rate (eGFR), 58 mL/min/1.73 m2) were included. The frequency of gross hematuria following vaccination was higher in 20/123 patients (16.3%) with microscopic hematuria than in 5/294 patients (1.7%) without microscopic hematuria prior to vaccination (P <0.001). There was no association between pre-vaccination proteinuria and post-vaccination gross hematuria. After adjusting for potential confounders, such as sex (female), age (<50 years), eGFR (≥60 mL/min/1.73 m2), and histories of tonsillectomy and corticosteroid therapy, pre-vaccination microscopic hematuria was still associated with post-vaccination gross hematuria (OR 8.98, P <0.001). As the severity of pre-vaccination microscopic hematuria increased, the incidence of post-vaccination gross hematuria increased (P <0.001). Conclusions Pre-vaccination microscopic hematuria in patients with IgAN is a major predictor of post-vaccination gross hematuria, regardless of potential confounders including previous treatments for IgAN.

Gross Hematuria Following SARS-CoV-2 Infection in IgA Nephropathy: A Report of 5 Cases.

Gross hematuria after upper respiratory tract infections is a well-known characteristic symptom of immunoglobulin A nephropathy (IgAN). In recent years, there have been several reports of existing or newly diagnosed patients with IgAN susceptible to gross hematuria after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, reports of patients with IgAN and gross hematuria after SARS-CoV-2 infection are extremely rare despite a considerable number of patients with coronavirus disease 2019 (COVID-19) who preferentially present with upper respiratory symptoms. Here, we report the cases of 5 Japanese patients with IgAN who developed gross hematuria associated with SARS-CoV-2 infection. These patients presented with fever and other COVID-19-related symptoms, followed by the appearance of gross hematuria within 2 days, which lasted for 1-7 days. Acute kidney injury occurred after gross hematuria in 1 case. In all cases, microhematuria was identified before gross hematuria associated with SARS-CoV-2 infection, and it persisted after the gross hematuria episode. Because repeated gross hematuria and persistent microhematuria may lead to irreversible kidney injury, the clinical manifestations of patients with IgAN during the COVID-19 pandemic should be carefully monitored.

Persistent SARS-CoV-2 Infection in a Patient with Nephrotic Syndrome under Rituximab Therapy: Successful Treatment with a Combination of Remdesivir and Monoclonal Antibodies.

Rituximab is an effective treatment for frequently relapsing/steroid-dependent nephrotic syndrome, but there is concern about infections caused by humoral immunodeficiency. We herein report a case of prolonged (>7 weeks) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 24-year-old man with minimal-change disease treated with rituximab developed SARS-CoV-2 infection. The clinical response to remdesivir was soon transiently abolished. Treatment with casirivimab and imdevimab (REGEN-COV) monoclonal antibodies in combination with remdesivir resulted in complete clearance of the infection. The REGEN-COV antibody cocktail may improve the outcome of SARS-CoV-2 infection in patients with humoral immunodeficiency.

Long-Term Humoral Response After a Second Dose of SARS-CoV-2 mRNA Vaccine in Japanese Kidney Transplant Recipients.

Background: The mortality rate due to COVID-19 in kidney transplant recipients (KTRs) is 16.8 to 32%. Vaccination against COVID-19 is expected to contribute to the prevention of infection, severe disease, and mortality; however, it has been reported that the humoral response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in KTRs is poor. Vaccination strategies against COVID-19 vary from country to country, and in Japan, the third dose is given 6 months after the second dose. Few studies have evaluated long-term humoral responses after the second dose of SARS-CoV-2 mRNA vaccine. In addition, the superiority of BNT162b2 vaccine and mRNA-1,273 vaccine in KTRs regarding humoral response is controversial. Methods: Ninety-four KTRs were administered a second dose of the BNT162b2 or mRNA-1,273 vaccines, and anti-spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 antibody levels were measured 5 months (149.2 ± 45.5 days) later. The cutoff value of anti-S antibodies was defined ≥50 AU/ml and 1.4 Index for anti-N antibodies. The primary outcome was the rate of seropositivity, and factors associated with an appropriate humoral response were assessed by univariate and multivariate analysis. Results: Of 94 KTRs, only 45 (47.9%) patients were positive for anti-S antibodies. The median anti-S SARS-CoV-2 IgG antibody titers was 35.3 (Interquartile range 3.8 to 159.7). Anti-N SARS-CoV-2 IgG antibodies in all patients were < 1.4 Index. Response to SARS-CoV-2 mRNA vaccines were 43.2 and 65% for BNT162b2 and mRNA-1,273, respectively (p = 0.152). In comparison with high-dose, low-dose of mycophenolic acid was a robust factor associated with an adequate humoral response. Conclusion: The long-term humoral response after a second dose of SARS-CoV-2 mRNA vaccine in Japanese KTRs was poor. In comparison with high-dose, low-dose mycophenolic acid was related to an appropriate humoral response. Five months is too long to wait for a 3rd dose after 2nd dose of SARS-CoV-2 vaccine in KTRs. In this cohort, there was no statistical difference in humoral response to the BNT162b2 and mRNA-1,273 vaccines. Additional large observational studies and meta-analyses are needed to clarify the factors related to an appropriate humoral immune response to COVID-19 vaccination.

Chronic kidney disease and clinical outcomes in patients with COVID-19 in Japan.

BACKGROUND: Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to the severity of various infectious diseases. However, the association between on-admission kidney dysfunction and the clinical outcome in COVID-19 patients is unclear. METHODS: This study was a multicenter retrospective observational cohort study of COVID-19 patients, diagnosed by polymerase chain reaction. We retrospectively analyzed 500 COVID-19 patients (mean age: 51 ± 19 years) admitted to eight hospitals in Japan. Kidney dysfunction was defined as a reduced estimated glomerular filtration rate (< 60 mL/min/1.73 m2) or proteinuria (≥ 1 + dipstick proteinuria) on admission. The primary composite outcome included in-hospital death, extracorporeal membrane oxygenation, mechanical ventilation (invasive and noninvasive methods), and intensive care unit (ICU) admission. RESULTS: Overall, 171 (34.2%) patients presented with on-admission kidney dysfunction, and the primary composite outcome was observed in 60 (12.0%) patients. Patients with kidney dysfunction showed higher rates of in-hospital death (12.3 vs. 1.2%), mechanical ventilation (13.5 vs. 4.0%), and ICU admission (18.1 vs. 5.2%) than those without it. Categorical and multivariate regression analyses revealed that kidney dysfunction was substantially associated with the primary composite outcome. Thus, on-admission kidney dysfunction was common in COVID-19 patients. Furthermore, it correlated significantly and positively with COVID-19 severity and mortality. CONCLUSIONS: On-admission kidney dysfunction was associated with disease severity and poor short-term prognosis in patients with COVID-19. Thus, on-admission kidney dysfunction has the potential to stratify risks in COVID-19 patients.

Gross hematuria after SARS-CoV-2 vaccination: questionnaire survey in Japan.

BACKGROUND: Recent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination. METHODS: We conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination. RESULTS: In the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction. CONCLUSION: This study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.

Correction: Proteinuria changes in kidney disease patients with clinical remission during the COVID-19 pandemic.

[This corrects the article DOI: 10.1371/journal.pone.0250581.].

Proteinuria changes in kidney disease patients with clinical remission during the COVID-19 pandemic.

BACKGROUNDS: Data on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce. METHODS: This study retrospectively analyzed clinical variables in patients with stage G1-G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June-July 2020) were compared to those one year before the pandemic (term 0, June-July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure. RESULTS: This study included 325 patients with stage G1-G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92-624) and 203 (84-508) mg/day [median (25th-75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p<0.001), with no marked difference in body weight, blood pressure, protein intake or urinary salt excretion. In multivariable analyses, incomplete remission of proteinuria in term 0 (odds ratio [OR] = 2.70, p = <0.001), RAASi use (OR = 2.09, p = 0.02) and decreased urinary salt excretion in term 1 vs. term 0 (OR = 1.94, p = 0.002) were identified as independent variables associated with reduced UPE in term 1 vs. term 0. No significant interactions between the variables were observed. CONCLUSION: In kidney disease patients receiving standard medical care from nephrologists, the UPE after the emergency declaration in relation to the COVID-19 pandemic was lower than before the declaration. The UPE reduction may be associated with reduced dietary salt intake during the pandemic in patients treated with RAASi for insufficient control of proteinuria. Our results support the current proposal to continue therapeutic approaches to these patients, which involve RAASi therapy along with optimizing dietary habits, even while dealing with the COVID-19 pandemic.