Shuhei Watanabe

Newly Developed Rat Model of Chronic Kidney Disease–Mineral Bone Disorder

Aim: Chronic kidney disease–mineral bone disorder (CKD–MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD–MBD in a newly developed CKD rat model. Methods: We used male Sprague–Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed. Results: At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats. Conclusions: We suggest that our new CKD rat model using SDT rats represents a useful CKD–MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

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

ABSTRACT 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 m2, 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.

Distal renal tubular acidosis without renal impairment after use of tenofovir: a case report

BackgroundTenofovir, one of antiretroviral medication to treat human immunodeficiency virus (HIV) infection, is known to cause proximal renal tubular acidosis such as Fanconi syndrome, but cases of distal renal tubular acidosis had never been reported.Case presentationA 20-year-old man with HIV infection developed nausea and vomiting without diarrhea after starting antiretroviral therapy. Arterial blood gas revealed non-anion-gap metabolic acidosis and urine test showed positive urine anion gap. Tenofovir, one of antiretroviral medicine the patient received, was considered to be the cause of this acidosis and all antiretroviral drugs were discontinued. Symptoms disappeared promptly without recurrence of symptoms after resuming antiretroviral medications without tenofovir.ConclusionDistal renal tubular acidosis caused by tenofovir, without renal impairment is very rare. Since causes of nausea and vomiting among HIV/AIDS patients are very diverse, awareness of this phenomenon is useful in diagnosing and managing the problem.

Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction.

A Case of Fibrillary Glomerulonephritis with Fibril Deposition in the Arteriolar Wall and a Family History of Renal Disease

Herein, we report a case of fibrillary glomerulonephritis (FGN). FGN usually shows non-amyloidal fibrils in the mesangium and glomerular capillary walls on electron microscopy. Inherited cases of FGN have been reported in only 3 families, and the suspected genetic form was autosomal dominant. In the present case, the deposition of microfibrils in the arteriolar wall as well as the glomerulus is unique. Our patient’s father died of nephrotic syndrome, and his elder brother had a biopsy-proven glomerulopathy. The histological findings of the brothers are similar to mesangial proliferative glomerulonephritis and resemble each other. Therefore, our case is presumed to be familial FGN. Additionally, herein, we review the literature and reconsider the histological and clinical characters of FGN.

Relationship Between Type of Hypertension and Renal Arteriolosclerosis in Chronic Glomerular Disease.

Background/Aims: Hypertension (HT) is a common complication in patients with chronic kidney disease (CKD). However, the relationship between circadian rhythm disorder of blood pressure (BP) and intra-renal damage remains unclear. Methods: Ninety patients with chronic glomerular disease (CGD) were included in the present study. On the basis of the clinic BP (CBP) and 24 h-ambulatory BP (ABP) measurements, the patients were divided into the following groups; normotension (NT), white coat HT (WHT), masked HT (MHT), and sustained HT (SHT). For renal histopathological assessment, we evaluated each biopsy specimen for sclerotic glomeruli (SG), interstitial fibrosis (IF), intimal thickening of intra-lobular arteries (ILA), and arteriolar hyalinosis (AH). Results: The prevalence of NT, WHT, MHT and SHT was 60.0%, 3.3%, 23.3%, and 13.4%, respectively. Compared with circadian BP pattern, all-day HT was most prevalent in the SHT group, whereas nighttime HT was most prevalent in the MHT group. The results of histological analysis showed that the SHT group had more severe SG and IF and the MHT group had more severe IF compared to the NT group. As for renal arteriolosclerosis, the MHT and SHT groups had more severe AH compared with the NT group, whereas ILA was comparable among all four groups. Furthermore, multivariate analysis revealed that ILA was significantly correlated only with age, whereas AH was significantly correlated with age and HT based on ABP, but not HT based on CBP. Conclusions: Our findings suggest that renal AH was severe not only in the SHT group, but also in the MHT group. Careful ABP monitoring should be recommended in patients with CGD.