Adverse reactions and effects on renal function of COVID-19 vaccines in patients with IgA nephropathy.

BACKGROUND: Although vaccination has been reported to reduce the morbidity and severity of COVID-19 infection in patients with kidney disease, gross hematuria is frequently reported following vaccination in patients with IgA nephropathy. We investigated the frequency of gross hematuria following COVID-19 vaccination and its effect on renal function in IgA nephropathy patients. METHODS: Adverse reactions after two or more COVID-19 vaccine doses were investigated in 295 IgA nephropathy patients attending Osaka Cty general hospital from September 2021 to November 2022. We compared differences in background characteristics and other adverse reactions between groups with and without gross hematuria after vaccination, and examined changes in renal function and proteinuria. RESULTS: Twenty-eight patients (9.5%) had gross hematuria. The median age of patients with and without gross hematuria was 44 (29-48) and 49 (42-61) years, respectively, indicating a significant difference. The percentage of patients with microscopic hematuria before vaccination differed significantly between those with (65.2%) and without (32%) gross hematuria. Adverse reactions, such as fever, chills, headache and arthralgia, were more frequent in patients with gross hematuria. There was no difference in renal functional decline after approximately 1 year between patients with and without gross hematuria. We also found no significant changes in estimated glomerular filtration rate or proteinuria before and after vaccination in the gross hematuria group. However, some patients clearly had worsening of renal function. CONCLUSIONS: While COVID-19 vaccination is beneficial, care is required since it might adversely affect renal function in some patients.

The Relationship of Alcohol Consumption and Drinking Pattern to the Risk of Glomerular Hyperfiltration in Middle-aged Japanese Men: The Kansai Healthcare Study.

BACKGROUND: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals. METHODS: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m2, which was the upper 2.5th percentile value of eGFR in the entire cohort. RESULTS: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1-3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18-4.74) compared with non-drinkers. For those who consumed alcohol on 4-7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1-69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01-2.38), and 1.78 (95% CI, 1.02-3.12), respectively. CONCLUSION: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.

Body Mass Index and the Risk of Persistent Proteinuria in Middle-Aged Men: The Kansai Healthcare Study.

INTRODUCTION: Proteinuria is a risk factor for end-stage renal failure. However, it is not known whether body mass index (BMI) is prospectively associated with the risk of future developing proteinuria, taking into account transient proteinuria. METHODS: We enrolled 9,320 nondiabetic Japanese middle-aged men who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive medications at baseline. "Any proteinuria" was defined as proteinuria detected for the first time during the follow-up period regardless of its frequency. "Persistent proteinuria" was defined as proteinuria that was detected at least twice consecutively at annual examinations and did not return to negative until the end of the follow-up. RESULTS: During the 11-year follow-up period, 1,972 cases of any proteinuria and 151 cases of persistent proteinuria were confirmed. Both lower and higher BMI were associated with the risk of any proteinuria. As for persistent proteinuria, in those with a BMI ≥20 kg/m2, higher BMI was associated with a higher risk of future persistent proteinuria. The association between BMI and the risk of persistent proteinuria was stronger than that between BMI and any proteinuria. In multiple-adjusted model, hazard ratios of persistent proteinuria for BMI <18.0, 18.0-19.9, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, and ≥28.0 kg/m2 were 1.52 (95% confidence interval 0.51-4.49), 1.07 (0.49-2.29), 1.00 (reference), 1.14 (0.64-2.01), 1.89 (1.09-3.27), 2.12 (1.15-3.93), and 3.85 (2.03-7.30), respectively. DISCUSSION/CONCLUSION: In those with a BMI ≥20 kg/m2, higher BMI was associated with a higher risk of future persistent proteinuria and any proteinuria. This relationship was stronger for persistent proteinuria than for any proteinuria.

Serum Gamma-Glutamyltransferase, Daily Alcohol Consumption, and the Risk of Chronic Kidney Disease: The Kansai Healthcare Study.

BACKGROUND: Serum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR). METHODS: We prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ≥1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m2. RESULTS: During the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (≥71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (≤25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (≥58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR. CONCLUSION: In middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease.

BACKGROUND: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. METHODS: A prospective cohort study of 9,116 middle-aged nondiabetic -Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1-23.0 g ethanol/day), moderate drinkers (23.1-46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. RESULTS: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11-1.70), 1.58 (95% CI 1.28-1.95), 2.27 (95% CI 1.86-2.77), and 3.12 (95% CI 2.56-3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46-0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. CONCLUSIONS: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.

The Association Between Metabolically Healthy Obesity and the Risk of Proteinuria: The Kansai Healthcare Study.

BACKGROUND: Metabolically healthy obesity seems to be a unique phenotype for the risk of cardiometabolic diseases. However, it is not known whether this phenotype is associated with the risk of proteinuria. METHODS: Study subjects were 9,185 non-diabetic Japanese male workers aged 40-55 years who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive or lipid-lowering medications at baseline. Obesity was defined as body mass index ≥25.0 kg/m2. Metabolic health was defined as the presence of no Adult Treatment Panel III components of the metabolic syndrome criteria, excluding waist circumference, and metabolic unhealth was defined as the presence of one or more metabolic syndrome components, excluding waist circumference. "Consecutive proteinuria" was considered positive if proteinuria was detected twice consecutively as 1+ or higher on urine dipstick at annual examinations to exclude chance proteinuria as much as possible. RESULTS: During the 81,660 person-years follow-up period, we confirmed 390 cases of consecutive proteinuria. Compared with metabolically healthy non-obesity, metabolically healthy obesity was not associated with the risk of consecutive proteinuria (multiple-adjusted hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.37-1.99), but metabolically unhealthy non-obesity with ≥2 metabolic syndrome components (HR 1.77; 95% CI, 1.30-2.42), metabolically unhealthy obesity with one component (HR 1.71; 95% CI, 1.12-2.61), and metabolically unhealthy obesity with ≥2 metabolic syndrome components (HR 2.77; 95% CI, 2.01-3.82) were associated with an increased risk of consecutive proteinuria. CONCLUSIONS: Metabolically healthy obesity did not increase the risk of consecutive proteinuria in Japanese middle-aged men.

Blood pressure components and the risk for proteinuria in Japanese men: The Kansai Healthcare Study.

BACKGROUND: We examined prospectively which of the four blood pressure (BP) components (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean arterial pressure [MAP]) was best in predicting the risk of proteinuria. METHODS: This prospective study included 9341 non-diabetic Japanese middle-aged men who had no proteinuria and an estimated glomerular filtration rate ≥60 mL/min/1.73 m2 and were not taking antihypertensive medications at entry. Persistent proteinuria was defined if proteinuria was detected two or more times consecutively and persistently at the annual examination until the end of follow-up. We calculated the difference in values of Akaike's information criterion (ΔAIC) in comparison of the BP components-added model to the model without them in a Cox proportional hazards model. RESULTS: During the 84,587 person-years follow-up period, we confirmed 151 cases of persistent proteinuria. In multiple-adjusted models that included a single BP component, the hazard ratios for persistent proteinuria for the highest quartile of SBP, PP, and MAP were 3.11 (95% confidence interval [CI], 1.79-5.39), 1.87 (95% CI, 1.18-2.94), and 2.21 (95% CI, 1.33-3.69) compared with the lowest quartile of SBP, PP, and MAP, respectively. The hazard ratio for the highest quartile of DBP was 2.69 (95% CI, 1.65-4.38) compared with the second quartile of DBP. Of all models that included a single BP component, those that included SBP alone or DBP alone had the highest values of ΔAIC (14.0 and 13.1, respectively) in predicting the risk of persistent proteinuria. CONCLUSIONS: Of all BP components, SBP and DBP were best in predicting the risk of persistent proteinuria in middle-aged Japanese men.

Relationship Between Alcohol Drinking Pattern and Risk of Proteinuria: The Kansai Healthcare Study.

BACKGROUND: Moderate alcohol consumption has been reported to be associated with a decreased risk of cardiometabolic diseases. Whether drinking pattern is associated with the risk of proteinuria is unknown. METHODS: Study subjects were 9154 non-diabetic Japanese men aged 40-55 years, with an estimated glomerular filtration rate ≥60 mL/min/1.73 m(2), no proteinuria, and no use of antihypertensive medications at entry. Data on alcohol consumption were obtained by questionnaire. We defined "consecutive proteinuria" as proteinuria detected twice consecutively as 1+ or higher on urine dipstick at annual examinations. RESULTS: During the 81 147 person-years follow-up period, 385 subjects developed consecutive proteinuria. For subjects who reported drinking 4-7 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was significantly associated with a decreased risk of consecutive proteinuria (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.36-0.80) compared with non-drinkers. However, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with an increased risk of consecutive proteinuria (HR 1.78; 95% CI, 1.01-3.14). For subjects who reported drinking 1-3 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was associated with a decreased risk of consecutive proteinuria (HR 0.76; 95% CI, 0.51-1.12), and alcohol consumption of ≥69.1 g ethanol/drinking day was associated with an increased risk of consecutive proteinuria (HR 1.58; 95% CI, 0.72-3.46), but these associations did not reach statistical significance. CONCLUSIONS: Men with frequent alcohol consumption of 0.1-23.0 g ethanol/drinking day had the lowest risk of consecutive proteinuria, while those with frequent alcohol consumption of ≥69.1 g ethanol/drinking day had an increased risk of consecutive proteinuria.

Diastereoselective [2+2] photocycloaddition of chiral cyclic enones with olefins in aqueous media using surfactants.

We conducted diastereodifferentiating [2+2] photocycloadditions of cyclo-hexenones modified with a chiral 8-(p-methoxy phenyl)menthyl auxiliary with olefins in water. Although the photoreaction didn't proceed at all in pure water owing to very low solubility, the use of surfactants [sodium dodecyl sulfate (SDS) or dodecylamine hydrochloride (DAH)] and additive (organic solvent) enabled the reactions to progress with moderate to high conversions and yields. Furthermore, we synthesized a new menthol derivative substrate containing a (p-octyloxy)phenyl group for enhancing hydrophobicity, and elucidated that this new substrate was found to be a suitable chiral auxiliary in this asymmetric photoreaction in aqueous system. The additive effect of organic molecules on the yield and diastereoselectivity of the photo-adducts is also discussed.

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung.

A 76-year-old man with lung cancer and multiple metastases was admitted for purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma of the lung had been diagnosed 6 months earlier. Two anti-cancer drug regimens had no effect. At admission, his survival with his malignancy was estimated to be several months. Renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme-linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by indirect immunofluorescence. He was diagnosed with ANCA-negative pauci-immune CrGN. Although steroids were initiated, the patient died of renal failure and intestinal bleeding 2 weeks later. It was later found that cancer cells were positive for interleukin (IL)-6 and that serum IL-6 levels were significantly elevated, concomitantly with increased IL-8, granulocyte-colony stimulating factor and transforming growth factor-ß levels. Some kinds of lung cancer are known to produce IL-6 that activate neutrophils and are related to ANCA-associated CrGN. It appears that IL-6 can activate neutrophils in the pathogenesis of ANCA-negative pauci-immune CrGN with lung cancer. Therapy that blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms in such cases.

Tonsillectomy has beneficial effects on remission and progression of IgA nephropathy independent of steroid therapy.

BACKGROUND: Indication of tonsillectomy in IgA nephropathy is controversial. The purpose of this study was to examine the efficacy of tonsillectomy on remission and progression of IgA nephropathy. METHODS: We conducted a single-center 7-year historical cohort study in 200 patients with biopsy-proven IgA nephropathy. Study outcomes were clinical remission defined as disappearance of urine abnormalities at two consecutive visits, glomerular filtration rate (GFR) decline defined as 30% GFR decrease from baseline and GFR slope during the follow-up. RESULTS: Seventy of the 200 patients received tonsillectomy. Tonsillectomy was associated with increased incidence of clinical remission (P+0.01, log-rank test) and decreased incidence of GFR decline (P=0.01, log-rank test). After adjustment for age and gender, hazard ratios in tonsillectomy were 3.90 (95% confidence interval 2.46-6.18) for clinical remission and 0.14 (0.02-1.03) for GFR decline. After further adjustment for laboratory (baseline mean arterial pressure, GFR, 24-h proteinuria and hematuria score), histological (mesangial score, segmental sclerosis or adhesion, endocapillary proliferation and interstitial fibrosis) or treatment variables (steroid and renin-angiotensin system inhibitors), similar results were obtained in each model. Even after exclusion of 69 steroid-treated patients, results did not change. GFR slopes in tonsillectomy and non-tonsillectomy groups were 0.60±3.65 and -1.64±2.59 mL/min/1.73 m2/year, respectively. In the multiple regression model, tonsillectomy prevented GFR decline during the follow-up period (regression coefficient 2.00, P=0.01). CONCLUSION: Tonsillectomy was associated with a favorable renal outcome of IgA nephropathy in terms of clinical remission and delayed renal deterioration even in non-steroid-treated patients.

Relationship between urinary angiotensinogen and salt sensitivity of blood pressure in patients with IgA nephropathy.

We demonstrated previously that the blood pressure of patients with IgA nephropathy becomes salt sensitive as renal damage progresses. We also showed that increased urinary angiotensinogen levels in such patients closely correlate with augmented renal tissue angiotensinogen gene expression and angiotensin II levels. Here, we investigated the relationship between urinary angiotensinogen and salt sensitivity of blood pressure in patients with IgA nephropathy. Forty-one patients with IgA nephropathy consumed an ordinary salt diet (12 g/d of NaCl) for 1 week and a low-salt diet (5 g/d of NaCl) for 1 week in random order. The salt-sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linking 2 data points obtained during consumption of each diet. The urinary angiotensinogen:creatinine ratio was significantly higher in patients who consumed the ordinary salt diet compared with the low-salt diet (17.5 µg/g [range: 7.3 to 35.6 µg/g] versus 7.9 µg/g [range: 3.1 to 14.2 µg/g] of creatinine, respectively; P<0.001). The sodium sensitivity index in our patients positively correlated with the glomerulosclerosis score (r=0.43; P=0.008) and changes in logarithmic urinary angiotensinogen:creatinine ratio (r=0.37; P=0.017) but not with changes in urinary protein excretion (r=0.18; P=0.49). In contrast, changes in sodium intake did not alter the urinary angiotensinogen:creatinine ratio in patients with Ménière disease and normal renal function (n=9). These data suggest that the inappropriate augmentation of intrarenal angiotensinogen induced by salt and associated renal damage contribute to the development of salt-sensitive hypertension in patients with IgA nephropathy.

Endovascular repair of sealed rupture of a thoracic inflammatory aneurysm that developed after corticosteroid therapy.

A 53-year-old man was admitted to our hospital with thoracic back pain and weight loss. Computed tomography revealed inflammatory aortic aneurysm (IAA) of the descending aorta. Sealed rupture of the aneurysm occurred while the patient was under corticosteroid therapy. Endovascular aneurysm repair (EAR) was performed without postoperative complications. Periaortic fibrosis was remarkably decreased three months later while the patient was under prednisolone (20 mg) administration. We believe that EAR could become a practical alternative to open surgical repair. The possibility of an aneurysm rupturing during corticosteroid therapy for IAA should be considered.

Development of various arrhythmias and conduction disturbances following corticosteroid therapy for systemic lupus erythematosus with antiphospholipid syndrome.

A 45-year-old Chinese woman with active systemic lupus erythematosus, lupus anticoagulant positive, was admitted to our hospital. Electrocardiography on admission was normal. Though anti-Sjögren's syndrome A (anti SS-A/Ro) antibodies were negative and ultrasound cardiographic findings were normal, she developed various arrhythmias/conduction disturbances shortly after starting corticosteroid. Nearly all were resolved with continuous corticosteroid and aspirin therapy before discharge. Vasculitis, the presence of antiphospholipid antibodies, and platelet aggregation due to corticosteroid were possible mechanisms underlying the arrhythmias/conduction disturbances.