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"Kashihara, Naoki"
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Gross hematuria after SARS-CoV-2 vaccination: questionnaire survey in Japan
2022
BackgroundRecent 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.MethodsWe 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.ResultsIn 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.ConclusionThis 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.
Journal Article
Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia
by
Kondo, Megumi
,
Kidokoro, Kengo
,
Kashihara, Naoki
in
Albumin
,
Angiotensin II
,
Angiotensin-converting enzyme inhibitors
2021
Serum zinc (Zn) levels tend to be low in chronic kidney disease (CKD) patients. This cohort study was conducted to investigate the relationship between zinc deficiency and CKD progression. Patients were classified into two groups based on Zn levels < 60 μg/dl (low-Zn group, n = 160) and ≥ 60 μg/dl (high-Zn group, n = 152). The primary outcome was defined as end-stage kidney disease (ESKD) or death and was examined over a 1-year observation period. Overall, the mean Zn level was 59.6 μg/dl and the median eGFR was 20.3 ml/min/1.73 m 2 . The incidence of the primary outcome was higher in the low-Zn group ( p <0.001). Various Cox proportional hazards models adjusted for baseline characteristics showed higher risks of the primary outcome in the low-Zn group than in the high-Zn group. Competing risks analysis showed that low Zn levels were associated with ESKD but not with death. Moreover, in propensity score-matched analysis, the low-Zn group showed a higher risk of the primary outcome [adjusted hazard ratio 1.81 (95% confidence interval 1.02, 3.24)]. Furthermore, an interaction was observed between Zn and serum albumin levels (interaction p = 0.026). The results of this study indicate that zinc deficiency is a risk factor for CKD progression.
Journal Article
The renoprotective effect of esaxerenone independent of blood pressure lowering: a post hoc mediation analysis of the ESAX-DN trial
by
Kashihara, Naoki
,
Shikata, Kenichi
,
Nangaku, Masaomi
in
Aldosterone
,
Angiotensin Receptor Antagonists - pharmacology
,
Angiotensin Receptor Antagonists - therapeutic use
2023
Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are recommended as first-line drugs for hypertension with diabetic nephropathy owing to their renoprotective effect; however, their effect beyond lowering blood pressure (BP) has not been confirmed. Recent studies have shown that aldosterone plays a key role in causing renal injury; therefore, it is likely that mineralocorticoid receptor (MR) blockers inhibit aldosterone-induced renal damage in different ways from ACE inhibitors and ARBs. Therefore, we investigated the mechanism of the effect of an MR blocker on reducing the urinary albumin-to-creatinine ratio (UACR) using data from a randomized, double-blind, placebo-controlled phase 3 study (ESAX-DN) of a new nonsteroidal MR blocker, esaxerenone. This post hoc analysis used a novel statistical method to quantitatively estimate the effect of esaxerenone on UACR reduction mediated, or not mediated, by changes in systolic BP (SBP) and/or estimated glomerular filtration rate (eGFR). The proportion of the mediated effect by SBP changes to the total effect on UACR reduction was 9.8–10.7%; the UACR was reduced to 0.903–0.911 times the baseline at the end of treatment through the SBP-related pathway and to 0.422–0.426 times the baseline through the non-SBP-related pathway. Even considering both SBP and eGFR simultaneously, the proportion of the mediated effect was 21.9–28.1%. These results confirm that esaxerenone has a direct UACR-lowering effect independent of BP lowering and that its magnitude is much larger than that of the BP-dependent effect. Thus, esaxerenone could be a UACR-reducing treatment option for patients with diabetic nephropathy.
Journal Article
eGFR slope as a surrogate endpoint for clinical study in early stage of chronic kidney disease: from The Japan Chronic Kidney Disease Database
by
Nagasu, Hajime
,
Kanda, Eiichiro
,
Kashihara, Naoki
in
Clinical trials
,
Dialysis
,
End-stage renal disease
2023
BackgroundIn clinical trials targeting early chronic kidney disease (CKD), eGFR slope has been proposed as a surrogate endpoint for predicting end-stage kidney disease (ESKD). However, it is unclear whether the eGFR slope serves as a surrogate endpoint for predicting long-term prognosis in Japanese early CKD populations.MethodsThe data source was the J-CKD-Database, which contains real-world data on patients with CKD in Japan. eGFR slope was calculated from the eGFR of each period, 1-year (1-year slope), 2-year (2-year slope), and 3-year (3-year slope), for participants with a baseline eGFR ≥ 30 ml/min/1.73 m2. The outcome was ESKD (defined as dialysis initiation or incidence of CKD stage G5). The relationship between eGFR slope and the sub-distribution hazard ratio (SHR) of ESKD with death as a competing event was investigated using a Fine-Gray proportional hazard regression model.ResultsThe number of participants and mean observation periods were 7768/877 ± 491 days for 1-year slope, 6778/706 ± 346 days for 2-year slope, and 5219/495 ± 215 days for 3-year slope. As the eGFR slope decreased, a tendency toward a lower risk of ESKD was observed. Compared with the 1-year slope, there was a smaller variation in the slope values for the 2-year or 3-year slope and a greater decrease in the SHR; therefore, a calculation period of 2 or 3 years for the eGFR slope was considered appropriate.ConclusionEven in Japanese patients with early stage CKD, a slower eGFR slope calculated from eGFR values over 2–3 years was associated with a decreased risk of ESKD.
Journal Article
Efficacy and safety of esaxerenone (CS-3150) in Japanese patients with type 2 diabetes and macroalbuminuria: a multicenter, single-arm, open-label phase III study
2021
BackgroundEsaxerenone has potential renoprotective effects and reduces the urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease and overt nephropathy. We investigated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes (T2D) and macroalbuminuria (UACR ≥ 300 mg/g creatinine).MethodsWe conducted a multicenter, single-arm, open-label phase III study in 56 patients with T2D and UACR ≥ 300 mg/g creatinine with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and treated with a renin–angiotensin system inhibitor. Patients received esaxerenone for 28 weeks at 1.25 mg/day initially with titration to 2.5 mg/day based on serum potassium (K+) monitoring. Efficacy was evaluated as the change in UACR from baseline to week 28. Safety endpoints included adverse events (AEs), incidence of serum K+ increase, and change in eGFR from baseline.ResultsUACR decreased by 54.6% (95% CI 46.9%, 61.3%) on average from baseline (544.1 mg/g creatinine) to the end of treatment (246.8 mg/g creatinine); 51.8% of patients showed improvement to early nephropathy. AE incidence was 69.6%. Three patients (5.4%) had serum K+ levels ≥ 6.0 mEq/L or ≥ 5.5 mEq/L on two consecutive occasions. Hyperkalemia in two patients was transient and resolved during the treatment period. One patient discontinued following two consecutive serum K+ values ≥ 5.5 mEq/L. The maximum change from baseline in eGFR was − 8.3 mL/min/1.73 m2 at week 24.ConclusionsEsaxerenone reduced UACR in Japanese patients with T2D and UACR ≥ 300 mg/g creatinine; more than half experienced a transition from UACR ≥ 300 mg/g creatinine to UACR < 300 mg/g creatinine.Clinical trial registrationJapicCTI-173696
Journal Article
Correction: Proteinuria changes in kidney disease patients with clinical remission during the COVID-19 pandemic
2021
[This corrects the article DOI: 10.1371/journal.pone.0250581.].[This corrects the article DOI: 10.1371/journal.pone.0250581.].
Journal Article
New-onset and relapse of nephrotic syndrome following COVID-19 vaccination: a questionnaire survey in Japan
by
Narita, Ichiei
,
Isaka, Yoshitaka
,
Maruyama, Shoichi
in
Coronaviruses
,
COVID-19
,
COVID-19 vaccines
2022
BackgroundRecent clinical reports indicate a correlation between new-onset and relapse of nephrotic syndrome (NS) following coronavirus 2019 (COVID-19) vaccination in patients with glomerular diseases. However, there are no reports of a nationwide survey on NS following COVID-19 vaccination in Japan.MethodsWe conducted a web-based survey of council members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between COVID-19 vaccination and new-onset and relapse of NS.ResultsFollowing COVID-19 vaccination, 27 patients (male: 15, 55.6%) with new-onset (n = 6) and relapse (n = 21) of NS were reported. Of them, 12 (44.4%) patients were diagnosed with minimal change disease at the occurrence of NS. Five patients developed a slight increase in serum creatinine levels; however, none progressed to severe renal dysfunction.ConclusionOur findings clarify the clinical features of new-onset and relapse of NS following COVID-19 vaccination. Although there was no obvious progression to severe renal dysfunction, clinicians and pathologists should be aware that NS is a potential adverse effect of the vaccines.
Journal Article
New measures against chronic kidney diseases in Japan since 2018
2019
Since 2008, the Japanese government has started measures against chronic kidney disease (CKD), and steady changes have been achieved, including a decrease in the age-adjusted rate of new dialysis introduction. However, the total number of dialysis patients has not declined because of the progression of aging. Therefore, the Japanese government has started more concrete measures since 2018. It aims to prevent CKD exacerbation mainly by early referrals to nephrologists using “criteria for referral from a primary care physician to a kidney specialist/specialized medical institution”. In addition, key performance indicators are set to reduce the number of new dialysis patients from 39,000 in 2016 to ≤ 35,000 by 2028. We hope that you can refer to this measure all over the world and proceed with CKD measures. This report has been originally notified from the Ministry of Health, Labor and Welfare in Japanese. This is the English version of it.
Journal Article
Proteinuria changes in kidney disease patients with clinical remission during the COVID-19 pandemic
by
Yokoo, Takashi
,
Sasaki, Takaya
,
Tsuboi, Nobuo
in
Adult
,
Aged
,
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
2021
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.
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.
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.
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.
Journal Article