Efficacy and safety of evocalcet in Japanese peritoneal dialysis patients The article “Efficacy and safety of evocalcet in Japanese peritoneal dialysis patients.

The cortical rim sign in graft renal infarction

Impact of acute kidney injury at the onset of idiopathic nephrotic syndrome in Japanese children

Histopathological and proteomic analyses identify integrin-β1 as a potential mediator of phlebosclerosis in uremic patients Abstract Background Patients with uremia have an excessive mortality from cardiovascular disease (CVD). Arterial remodeling is mainly responsible for uremia-induced CVD and has been well studied, yet venous remodeling is poorly understood. Here we investigate the histopathology and proteomic profiles of venous remodeling in uremic patients. Methods Forearm cephalic veins were isolated from nine uremic patients during surgeries for arteriovenous fistula, and from nine healthy controls when applying surgical debridement. Hematoxylin–eosin, Masson’s trichrome, von Kossa, and immunohistochemistry (IHC) against proliferating cell nuclear antigen were stained for histopathology. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was executed to explore the proteome of the veins. The core regulatory protein was validated by western blot, IHC, and immunofluorescence. Results Phlebosclerosis, characterized by intimal rarefaction and medial thickening with disordered proliferation of vascular smooth muscle cells (VSMCs), was the prominent pathological manifestation of peripheral veins in uremic patients, while inflammatory cell infiltration, atherosclerosis or calcification were not obviously detected. iTRAQ analysis showed that 350 proteins were significantly changed in phlebosclerosis of uremic patients compared with healthy controls, of which integrin-β1 (ITGβ1) exhibited the strongest regulatory ability by intermolecular interaction network analysis. The enhanced ITGβ1 expression was mainly co-expressed with the disordered proliferation of VSMCs while a little with vascular endothelial cells in the forearm cephalic veins of uremic patients. Conclusions Phlebosclerosis is the prominent pathological manifestation in peripheral veins of uremic patients. This pathological alteration mainly attributes to the disordered proliferation of VSMCs, which is potentially mediated by ITGβ1.

Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease Abstract Background Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. Methods Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. Results MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45–5.17] vs. 4.2 [3.45–8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1–27.49] vs. 24.9 [16.23–39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8–26.4] vs. 26.78 [18.22–35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09–1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09–9.87]; p = 0.035). Conclusions Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

Increased heart rate is associated with intrarenal renin–angiotensin system activation in chronic kidney disease patients Abstract Background A higher heart rate is one of the risk factors for heart failure and cardiovascular disease. Activation of the intrarenal renin–angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. However, the association between heart rate and intrarenal RAS activation is unclear. Methods We investigated the relationship between heart rate and urinary angiotensinogen (U-AGT) excretion, a surrogate marker for intrarenal RAS activity, in ten subjects without chronic kidney disease (CKD) and 72 CKD patients who were not taking medications that influence heart rate and RAS blockers (age 50.0 ± 17.4 years, 27 men and 45 women, serum creatinine (sCr) 1.85 ± 2.71 mg/dL, blood pressure 120.5 ± 15.8/72.9 ± 10.1 mmHg, heart rate 67.3 ± 8.9 /min, urinary protein excretion 1.27 ± 2.63 g/day, and U-AGT excretion 747.4 ± 2714.6 µg/day). Results As heart rate is influenced by behavior and emotion, we divided it into daytime and nighttime. Heart rate had a significant positive association with sCr levels during daytime and nighttime in CKD patients but not in non-CKD subjects. Moreover, although heart rate was not associated with U-AGT excretion levels in non-CKD subjects, it was associated with U-AGT excretion levels during daytime (r = 0.23 and p = 0.047) and nighttime (r = 0.45 and p < 0.01) in CKD patients. Multiple linear regression analysis revealed that heart rate had a significant positive association with the U-AGT excretion levels during nighttime, but not daytime, after adjustments for age, sex, body mass index, and sCr (β = 0.31 and p = 0.034). Conclusion Heart rate is associated with U-AGT excretion levels, especially during the nighttime, in CKD patients.

Incidence and risk factors of contrast-induced nephropathy after transcatheter arterial chemoembolization in hepatocellular carcinoma Abstract Background Transcatheter arterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate incidence and risk factors of contrast-induced nephropathy (CIN) after TACE in patients with HCC. Methods In this single-center retrospective study, we examined 461 consecutive TACE sessions in 260 patients between January 2003 and October 2015. CIN was defined as an increase in serum creatinine levels by ≥ 0.5 mg/dl or ≥ 25% from baseline within 72 h after TACE. We calculated incidence rate of CIN and tried to identify its risk factors by logistic regression analysis. Results Twenty-one cases of CIN (5%) were observed in 461 TACE sessions. One patient required subsequent hemodialysis transiently. In univariate analysis, tumor size > 5 cm [odds ratio (OR) 5.76, 95% confidence interval (CI) 2.34–14.14, p < 0.001], chronic kidney disease (OR 2.54, 95% CI 1.05–6.14, p = 0.04), serum hemoglobin level [OR 0.79 (per 1 g/dl increase), 95% CI 0.64–0.98, p = 0.03] and serum albumin level [OR 0.44 (per 1 g/dl increase), 95% CI 0.19–1.02, p = 0.05] were associated with the development of CIN. Stepwise logistic regression methods showed that tumor size > 5 cm (OR 7.81, 95% CI 2.99–20.46, p < 0.001) and serum albumin [OR 0.29 (per 1 g/dl increase), 95% CI 0.11–0.75, p = 0.01] were risk factors of CIN. Conclusions In this study, HCC tumor size and lower serum albumin level were independent predictors of CIN after TACE.

Relative hypophosphatemia early after transplantation is a predictor of good kidney graft function Abstract Background Phosphate level is a potent independent risk factor for cardiovascular disease and mortality in patients with chronic kidney disease. The association between hypophosphatemia and kidney function in kidney transplant patients is uncertain. Methods In total, 90 kidney transplant recipients were divided into two groups: one group of patients with hypophosphatemia and the other group without hypophosphatemia. The recipients with hypophosphatemia were identified as having less than or equal to the lowest quartile of serum phosphate levels at 1-, 3-, and 12-month post-transplant. The cumulative kidney survival rates were calculated for each group using the Kaplan–Meier method, and the adjusted hazard ratio (HR) was calculated using the Cox regression model. Results The mean age of patients was 47 years and the median follow-up period was 58 months. During the follow-up period, the following results were demonstrated in 90 transplant patients: graft loss (n = 6), mortality (n = 3). According to the Kaplan–Meier analysis results, the patients with hypophosphatemia demonstrated a significantly lower risk of 30% decline in eGFR compared to those without hypophosphatemia at 1- and 3-month post-transplant, but not at 12-month post-transplant. After adjusting for confounding factors, hypophosphatemia at 1- and 3-month post-transplant was an independent predictor of good kidney survival (HR 0.31, 95% CI 0.10–0.82 and HR 0.31, 95% CI 0.07–0.92, respectively). Conclusions Our findings suggest that hypophosphatemia during the first 3 months after kidney transplantation was associated with better kidney survival.

Clinical characteristics of HNF1B -related disorders in a Japanese population Abstract Background Hepatocyte nuclear factor 1β (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype–phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. Methods We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. Results Most cases had morphological abnormalities in the renal–urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m2; p = 0.0091). Conclusion We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.

Clinical and histological features and therapeutic strategies for IgA nephropathy Abstract Chronic glomerulonephritis is the second most common reason, after diabetic nephropathy, for initiation of dialysis in Japan and IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis. In the half century since IgAN was initially reported, our understanding of the long-term prognosis, clinical and histological features, pathogenesis of onset and progression, risk factors for progression, and appropriate treatment under different clinical and histological conditions, has steadily increased. Strong experimental and clinical evidence, the Clinical Practice Guidelines for IgA Nephropathy in Japan, the Oxford Classification, and the Kidney Disease Improving Global Outcomes guidelines have all contributed to the appropriate treatment of IgAN. Several intensive therapies, such as tonsillectomy, steroid therapy, and their combinations, can result in clinical remission, and prevent the progression to end stage renal disease (ESRD). However, some IgAN patients still progress to ESRD even when treated with intensive therapies. In this review, we discuss the clinical and histological features of IgAN, focusing primarily on our previous reports, and our opinions on therapeutic strategies for IgAN.