Comparison of renal histopathology in three patients with gross hematuria after SARS-CoV-2 vaccination.

We present three cases of IgA nephropathy with gross hematuria following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination. Case 1 was a 60-year-old woman who has previously experienced transient proteinuria. Case 2 was a 22-year-old woman with no history of urinary abnormality. Finally, case 3 was a 66-year-old woman who has had microscopic hematuria since she was in her 50s. They were all diagnosed as IgA nephropathy with little histological active lesion. Their renal function and proteinuria improved without the use of corticosteroids. There were differences in the findings of vascular endothelial damage based on the time between the appearance of gross hematuria and renal biopsy. Glomerular endocapillary damage could be a part of the mechanism triggered by mRNA vaccination. When a patient presents with gross hematuria following vaccination, a comprehensive approach including renal biopsy should be considered.

Surgical repair of hepatic hydrothorax caused by diaphragmatic fistula.

A 65-year-old woman visited our hospital complaining of dyspnea several days before admission. A chest X-ray showed massive right-sided pleural effusion, which was not observed 1 month previously. Although the patient had never been diagnosed with cirrhosis at regular visits, the patient was diagnosed with primary biliary cholangitis at admission. Hepatic hydrothorax was suspected because pleural effusion was transudative. A diaphragmatic fistula was confirmed and closed by thoracoscopy. Pleural effusion did not reappear after this procedure. Existence of a diaphragmatic defect should be confirmed under direct vision if pleural effusion accumulates acutely or becomes beyond control.

Comparison of the effects of novel vitamin D receptor analog VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder in an experimental model of chronic kidney disease.

When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0.1µg/kg), high-dose paricalcitol (HP, 0.3µg/kg), low-dose VS-105 (LV, 0.2µg/kg), and high-dose VS-105 (HV, 0.6 µg/kg) three times a week for 10 weeks. There were no significant differences in blood pressure or renal function among the five groups. Alhough serum calcium levels were comparable between the LP and LV groups, they were higher in the HP group than in the HV group. Serum phosphate levels were higher in the paricalcitol-treated groups than in the VS-105-treated groups and paticularly higher in the HP group than in the other groups. The urinary excretion of phosphate was greater in the VS-105-treated groups than in the paricalcitol-treated groups. Serum parathyroid hormone (PTH) levels decreased and serum fibroblast growth factor-23 (FGF23) levels were elevated after administering paricalcitol and VS-105; however, serum FGF23 levels were remarkably elevated in the paricalcitol-treated groups. Further biochemical analyses revealed that the calcium content of the aorta was higher in the paricalcitol-treated groups than in the VS-105-treated group. VDR and Klotho expression in the kidney was significantly higher in the VS-105-treated groups than in the paricalcitol-treated groups although both agents increased these expressions. Our data suggest that VS-105 had a lesser effect on CKD-MBD than paricalcitol except in the case of serum PTH levels. The mechanism appears to be associated with the difference in VDR and Klotho expression.

Riser pattern is a predictor of kidney mortality among patients with chronic kidney disease.

BACKGROUND: Hypertension is a crucial risk factor for cardiovascular death and loss of residual kidney function. Absence of the nocturnal decline in blood pressure (BP) predicts cardiovascular events and poor prognosis. However, characteristics of hypertension in moderate-to-severe chronic kidney disease (CKD) have not been fully evaluated. We aimed to assess the circadian variation of BP and kidney survival in CKD patients. METHODS: Patients who were examined by 24-h ambulatory BP monitoring (ABPM) and estimated glomerular filtration rate (eGFR), <45 ml/min/1.73 m(2), were enrolled in the study. The impacts of BP circadian rhythm and brain natriuretic peptide (BNP) on kidney survival were evaluated. RESULTS: A total of 124 patients were enrolled. The average age was 64 ± 14 years, 57% were male, and 43% had diabetes. Forty-five percent of patients had a non-dipper pattern, 35% had a riser pattern, 19% had a dipper pattern, and 1% had an extreme-dipper pattern. The prevalence of diabetes and plasma BNP levels was higher and eGFR was lower in the riser-pattern group than in the non-riser-pattern group. Kidney survival rates were significantly worse in the riser-pattern group than in the non-riser-pattern group (p < 0.05). Moreover, among riser and non-riser pattern groups divided by BNP levels, the riser group with higher BNP level showed the worst kidney survival (p < 0.05). CONCLUSION: The riser pattern is frequently associated with several conditions at higher risk for kidney survival. Patients with a rising pattern and higher BNP levels have a worse kidney prognosis.

Anti-oxidative effect of AST-120 on kidney injury after myocardial infarction.

BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is a crucial risk factor for cardiovascular disease (CVD), and combined CKD and CVD further increases morbidity and mortality. Here, we investigated effects of AST-120 on oxidative stress and kidney injury using a model of myocardial infarction (MI) in rats. EXPERIMENTAL APPROACH: At 10 weeks, male spontaneously hypertensive rats (SHR) were divided into three groups: SHR (n = 6), MI (n = 8) and MI + AST-120 (n = 8). AST-120 administration was started at 11 weeks after MI. At 18 weeks, the rats were killed, and blood and urine, mRNA expression and renal histological analyses were performed. Echocardiography was performed before and after MI. KEY RESULTS: At 18 weeks, the BP was significantly lower in the MI and MI+AST-120 groups than in the SHR group. Elevated levels of indoxyl sulfate (IS), one of the uremic toxins, in serum and urine were reduced by AST-120 treatment, compared with the MI group. Markers of oxidative stress in urine and serum biomarkers of kidney injury were decreased in the MI+AST-120 group compared with the other two groups. Renal expression of mRNAs for kidney injury related-markers were decreased in the MI+AST-120 group, compared with the MI group. In vitro data also supported the influence of IS on kidney injury. Immunohistological analysis showed that intrarenal oxidative stress was reduced by AST-120 administration. CONCLUSIONS AND IMPLICATIONS: Serum IS was increased after MI and treatment with AST-120 may have protective effects on kidney injury after MI by suppressing oxidative stress.

The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus.

PURPOSE: Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes. METHODS: At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS + OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks. RESULTS: At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition. CONCLUSION: Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.

Anti-oxidative effect of the ß-blocker carvedilol on diabetic nephropathy in non-obese type 2 diabetic rats.

Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The ß-blocker carvedilol has been proven to have an anti-oxidant property. The aim of the present study was to elucidate the effects of carvedilol on diabetic nephropathy. At 20 weeks of age, male Spontaneously Diabetic Torii (SDT) rats were divided into three groups based on treatment: (i) an INS group (administered insulin); (ii) a CAR group (administered 10 mg/kg per day, p.o., carvedilol); and (iii) a diabetic (DM) group (administered vehicle). Rats were treated for a period of 10 weeks and were killed at 30 weeks of age. Urinary albumin excretion, renal histomorphology, and oxidative stress were evaluated. Urinary albumin excretion was significantly lower in the CAR than DM group (42.82 ± 3.94 vs 76.62 ± 13.74 mg/day respectively; P < 0.05). The mesangial index was lower in the CAR group than in the DM group. Urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), the number of 8-OHdG-positive cells in glomeruli, and the mRNA expression of NADPH oxidase p22phox and p47phox were also lower in the CAR than DM group. However, haemoglobin A1c (HbA1c) and blood pressure levels were comparable between the two groups. The results suggest that carvedilol could prevent the progression of diabetic nephropathy by suppressing oxidative stress.

Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy.

BACKGROUND: Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. METHODS: This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. RESULTS: Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. CONCLUSIONS: Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

22-Oxacalcitriol attenuates bone loss in nonobese type 2 diabetes.

Active vitamin D is a major therapeutic agent for bone disease. Although some studies have reported that vitamin D ameliorates bone disease related to diabetes, the mechanism remains unclear. Our study investigated the effect of the vitamin D receptor activator 22-oxacalcitriol (OCT) on bone disease in a rat model of diabetes. OCT was administered at a dose of 0.2µg/kg three times per week for 10weeks. We performed blood and urine analyses, single energy X-ray absorptiometry, micro-computed tomography, bone histomorphometry, and oxidative stress assessment in rats at 30weeks of age. OCT did not affect hemoglobin A1c or serum calcium levels. Bone mineral density (BMD), bone volume in the cortical and trabecular bones, and bone turnover were decreased in rats with diabetes. OCT treatment increased BMD and bone formation and tended to increase bone volume in the trabecular bone, but did not change bone volume in the cortical bone or bone resorption. The urinary oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells in bone were increased in rats with diabetes, and OCT treatment suppressed these increases. Our data suggest that OCT attenuated bone loss in a rat model of diabetes. This attenuation may be partially mediated by improved bone formation resulting from the antioxidative effect of OCT.

The influences of larger physical constitutions including obesity on the amount of urine protein excretion in primary glomerulonephritis: research of the Japan Renal Biopsy Registry.

BACKGROUND: This study aimed to describe the influences of larger physical constitutions including obesity on the amount of urine protein excretion (AUPE) in primary glomerulonephritis. The distinct effects on the AUPE in various types of glomerulonephritis were evaluated. METHODS: Using the database of the Japan Renal Biopsy Registry (J-RBR) from 2007 to 2010, 4060 cases with primary glomerulonephritis including MCNS, FSGS, MN, MPGN, IgAN, and non-IgA were reviewed. The AUPEs were compared between high and low Body Mass Index (BMI) groups, and larger and smaller body surface area (BSA) groups using the indexes of BMI 25.0 kg/m(2) and BSA 1.73 m(2) in all cases and in each histological group. Multivariable analysis was performed to evaluate the predominant contributors to the AUPE. RESULTS: The larger physical constitution groups (BMI ≥25.0 kg/m(2) or BSA ≥1.73 m(2)) had significantly higher AUPEs in all cases with primary glomerulonephritis. When compared in each histological group, the mean AUPEs were significantly higher in the larger physical constitution groups, excluding the FSGS and non-IgA groups. Multiple regression analysis revealed that the significant contributors to the AUPE were BMI and BSA in MCNS and MN, whereas BMI and BSA were not significant and mean blood pressure and serum creatinine were significant in FSGS and non-IgA. CONCLUSION: Larger physical constitutions including obesity had a significant impact on the increase in the AUPE in primary glomerulonephritis, especially in MCNS and MN. However, FSGS and non-IgA were distinct for having blood pressure and renal dysfunction as possibly the major causes of proteinuria.

Dietary phosphorus restriction by a standard low-protein diet decreased serum fibroblast growth factor 23 levels in patients with early and advanced stage chronic kidney disease.

BACKGROUND: Elevated serum fibroblast growth factor 23 (FGF23) levels are associated with mortality, cardiovascular disease, and disease progression in patients with chronic kidney disease (CKD). Although recent studies demonstrated that FGF23 levels decreased in response to dietary restriction of phosphorus and/or use of phosphate binders, research on the effects of a standard low-protein diet is lacking. METHODS: The effects of a standard low-protein diet on serum FGF23, intact parathyroid hormone, and 1,25-dihydroxyvitamin D levels were investigated in patients with early (n = 15) and advanced (n = 20) CKD. RESULTS: Serum FGF23 levels decreased in both groups. Changes in FGF23 levels correlated with changes in 24 h urinary phosphorus excretion in the advanced CKD group. Decreased serum intact parathyroid hormone levels were observed only in the advanced CKD group and increased serum 1,25-dihydroxyvitamin D levels only in the early CKD group. CONCLUSIONS: These findings suggest that consuming standard low-protein diet decreased serum FGF23 levels in patients with CKD. Serum FGF23 levels may therefore be a useful marker to monitor the effects of a low-protein diet in early and advanced stage CKD.

[A case of hypomagnesemia linked to refractory hypokalemia and hypocalcemia with short bowel syndrome].

We report a case of a 59-year old Japanese woman with short bowel syndrome, whose hypokalemia and hypocalcemia were successfully treated with magnesium (Mg) supplementation. Two years previously, she underwent Mile's operation for advanced rectal cancer, which could have been the cause of subsequent extensive resection of the small intestine by strangulation. After serial resection, she gradually developed chronic diarrhea and anorexia. Three weeks before admission, she developed general fatigue and tetany, and was hospitalized at another hospital. On admission, her serum K and Ca were 2.5 mEq/L and 4.3 mg/dL, respectively, hence regular fluid therapy containing potassium (K) and calcium (Ca) was provided following admission. However, her hypokalemia and hypocalcemia persisted, and she also displayed renal dysfunction and thereafter was transferred to our department for further evaluation and treatment. Since the laboratory tests revealed severe hypomagnesemia (0.4 mg/dL), we started intravenous Mg supplementation together with fluid therapy containing K and Ca. After the combination therapy, her clinical symptoms and electrolyte disorders were remarkably improved within a week. As Mg is essential for PTH secretion in response to hypocalcemia and to inhibit the K channel activity that controls urinary K excretion, hypomagnesemia can cause hypocalcemia and hypokalemia, which is refractory to repletion therapy unless Mg is administered. Therefore, for patients who present with signs of Mg deficiency, early and accurate diagnosis of Mg deficiency should be made and corrected.