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The present paradigms of selective autophagy in mammalian cells cannot fully explain the specificity and selectivity of autophagic degradation. In this paper, we report that a subset of tripartite motif (TRIM) proteins act as specialized receptors for highly specific autophagy (precision autophagy) of key components of the inflammasome and type I interferon response systems. TRIM20 targets the inflammasome components, including NLRP3, NLRP1, and pro-caspase 1, for autophagic degradation, whereas TRIM21 targets IRF3. TRIM20 and TRIM21 directly bind their respective cargo and recruit autophagic machinery to execute degradation. The autophagic function of TRIM20 is affected by mutations associated with familial Mediterranean fever. These findings broaden the concept of TRIMs acting as autophagic receptor regulators executing precision autophagy of specific cytoplasmic targets. In the case of TRIM20 and TRIM21, precision autophagy controls the hub signaling machineries and key factors, inflammasome and type I interferon, directing cardinal innate immunity response systems in humans.

The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy.

Statement of Problem: Although 1-piece implants are associated with positive clinical outcomes, including improved implant stability, overall survival rate, and marginal bone levels, a few studies have suggested that 1-piece implants have low success rates., Purpose: This prospective multicenter study evaluated the efficacy of 1-piece implants placed in immediate function in private clinic-based and hospital-based settings with a focus on marginal bone level changes and esthetic outcomes over a 3-year follow-up period., Material and Methods: A total of 93 one-piece implants (29 maxillary, 64 mandibular) were placed in 63 participants (25 men and 38 women) at 1 university hospital and 3 private clinics. The implants were restored with interim crowns immediately after placement. Clinical and radiographic evaluations of marginal bone level, implant stability, periimplant mucosa, and plaque and papilla indices were performed at the time of implantation and after 6, 12, 24, and 36 months., Results: The 3-year cumulative implant survival rate was 100%. After implant placement, mean bone levels changed from -0.16 ±1.41 mm at 24 months to 0.40 ±1.46 mm at 36 months. Clinical parameters, including implant stability, periimplant mucosa, and plaque index, remained stable from 3 to 36 months during follow-up. The papilla index score increased over time., Conclusions: Within the limitations of this prospective study, marginal bone level was maintained, soft tissue integration was achieved, and a cumulative survival rate of 100% was obtained for 1-piece implants. The present findings indicate that 1-piece implants are an effective treatment option for immediate function situations., (Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Macroautophagy is a highly evolutionally conserved degradation process by which cytosolic materials (including macromolecules such as proteins and lipids) and damaged organelles are broken down to their basic components. The role of autophagy is not only the elimination of materials, but it also serves as a dynamic recycling system that produces new components and energy for cellular renovation and homeostasis. The association of autophagy with the organ physiology and pathogenesis of various disorders such as neurodegenerative diseases, cancer, infection and inflammatory bowel disease has been revealed in recent years. Autophagy also plays an essential role in cellular homeostasis in kidney and counteracts age-related stress and kidney diseases. Here, we critically review the current evidence regarding autophagy in the kidney, in particular as assessed with tissue- or cell lineage-specific autophagy-deficient mice. Better insight into the mechanisms underlying renoprotective roles of autophagy will pave the way toward novel therapies for kidney diseases., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Recent experimental studies suggest that erythropoietin promotes beneficial myocardial remodeling during left ventricular hypertrophy (LVH); however, such compensatory capacity may be limited due to insufficient erythropoietin production in chronic kidney disease patients. Thus, this study aimed to explore the effect of pre-dialysis erythropoiesis-stimulating agent (ESA) use on the prognostic significance of LVH in dialyzed patients., Methods: This retrospective study included 404 consecutive patients who started dialysis between 2001 and 2009. The interaction of ESA with the association between left ventricular mass index (LVMI) observed at dialysis initiation and all-cause and cardiovascular mortality was analyzed at the end of 2010 using the Cox model., Results: During a median follow-up of 36.5 months, 164 patients died, 31 of them from heart failure. The frequency of pre-dialysis ESA use was 58.7 % and median LVMI was 160.3 g/m(2). Of interest, patients with the lowest tertile of LVMI had worse survival compared with those with each subsequent tertile. LVMI was inversely associated with all-cause mortality [hazard ratio (HR) 0.991, 95 % confidence interval (CI) 0.988-0.995, P = 0.000] after extensive adjustment including ejection fraction, whereas the prognostic value of LVMI for cardiovascular mortality was dependent on pre-dialysis ESA use [adjusted HR 1.010, 95 % CI 0.999-1.020, P = 0.065 for pre-dialysis ESA(+) and 0.978, 95 % CI 0.967-0.989, P = 0.000 for pre-dialysis ESA(-), respectively]., Conclusions: Our results suggest that reverse epidemiology may exist between LVH and mortality and that pre-dialysis ESA use may modify the prognostic significance of LVH observed at dialysis initiation for cardiovascular mortality in dialyzed patients.

Autophagy is a highly conserved bulk protein degradation pathway involved in cellular homeostasis. Although emerging evidence indicates involvement of autophagy in various conditions, efforts to clarify the role of autophagy in renal tubules are beginning to be elucidated. In the present study, we examined the hypothesis that autophagy guards against acute kidney injury (AKI) by modulating several deteriorative pathways that lead to tubular cell death using a cisplatin-induced model of AKI. Cisplatin treatment of GFP-LC3 (green fluorescent protein-microtubule-associated protein 1 light chain 3) transgenic mice induced autophagy in kidney proximal tubules in a time-dependent manner. Proximal tubule-specific autophagy-deficient mice exhibited more severe cisplatin-induced AKI than did control mice, as assessed via kidney function and morphologic findings. In addition, cisplatin induced more severe DNA damage and p53 activation, concomitant with an increase in apoptotic cell number, and a massive accumulation of protein aggregates in autophagy-deficient proximal tubules. Cisplatin treatment significantly increased reactive oxygen species-producing damaged mitochondria in immortalized autophagy-deficient proximal tubular cells when compared with autophagy-retrieved control cells. In conclusion, autophagy guards kidney proximal tubules against AKI, possibly by alleviating DNA damage and reactive oxygen species production and by eliminating toxic protein aggregates. Enhancing autophagy may provide a novel therapeutic option to minimize AKI., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

A previously healthy black man presented with acute kidney injury wtih nephrotic syndrome. His serum creatinine and albumin concentrations were 8.0 mg/dL and 0.4 g/dL, respectively. Renal ultrasound demonstrated an enlarged kidney with an extremely high echogenic cortex. Human immunodeficiency virus (HIV) was serologically positive, and kidney biopsy revealed a collapsing variant of focal segmental glomerulosclerosis with interstitial nephritis. He was diagnosed as having HIV-associated nephropathy (HIVAN). Although there have been only a few cases with characteristic HIVAN features in Japan, the number of patients with HIVAN who need dialysis treatment is relatively high globally, and is expected to increase even in Japan. The rapid clinical course of HIVAN, along with its characteristic histology and the direct pathogenesis of HIV on podocytes, is noteworthy. We described this case with reference to some recent findings.

Background: Patients with chronic kidney disease (CKD) still frequently experience cardiovascular events despite recent progress in treatment. We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events., Methods: Patients with advanced stage CKD (stage III-V with or without peritoneal dialysis) were included in this trial if they were considered at high risk for cardiovascular events [past history of cardiovascular diseases, past history of coronary angiography, presence of endothelial dysfunction measured by reactive hyperemia peripheral arterial tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients were randomly assigned to be treated with or without oral nicorandil, 15 mg/day. BNP values and endothelial function (augmentation index, pulse wave velocity, and reactive hyperemia peripheral arterial tonometry) before and 1 month after the initiation of the trial were assessed., Results: Nineteen patients (15 men, 4 women) with a mean age of 61 ± 10 (SD) years were included. The median baseline BNP value was 75.3 (interquartile range, 32.1-138.8) pg/ml, and the BNP level was significantly reduced in the nicorandil group (P < 0.05). Regression analysis demonstrated that only the use of nicorandil is related to a decrease of BNP levels [standardized β coefficient, -75.1 (95% CI, -19.7 to -130.6), P = 0.01]. There were no significant changes in the rest of the parameters in the nicorandil group in comparison to the control group. The change in BNP levels was correlated with changes in the augmentation index (P < 0.01) and central pulse pressure (P = 0.03)., Conclusions: Nicorandil treatment may reduce the level of BNP by reducing the central blood pressure in CKD patients.

Using a metagenome library constructed from a bacterial associated with a marine sponge Hyrtios erecta, we identified a novel esterase that belongs to the SGNH hydrolase superfamily of esterases. The substrate specificity of EstHE1 was determined using p-nitrophenyl (pNP) ester (C2: acetate, C4: butylate, C6: caproate, C12: laurate, C16: palmitate). EstHE1 exhibited activity against C2 (5.6 U/mg), C4 (5.1 U/mg), and C6 (2.8 U/mg) substrates. The optimal temperature for EstHE1 esterase activity of the pNP acetate substrate was 40 degrees C, and EstHE1 retained 60% of its enzymatic activity in the 30-50 degrees C range. This esterase showed moderate thermostability, retaining 58% of its activity even after preincubation for 12 h at 40 degrees C. EstHE1 also maintained activity in high concentrations of NaCl, indicating that this esterase is salt-tolerant. Thus, EstHE1 has the thermal stability and salt tolerance necessary for use as an industrial enzyme.

Purpose: Elevation of the plasma level of B-type natriuretic peptide (BNP) is commonly seen in patients with chronic kidney disease (CKD), but its significance remains unclarified. We conducted a prospective study to evaluate the role of plasma BNP level as a predictive marker of renal outcome., Methods: 237 patients with CKD stage 3, 4 not on dialysis were prospectively enrolled as a hospital cohort from August 2004 to December 2008. Combined renal endpoint was doubling of baseline serum creatinine or end-stage renal disease requiring dialysis. Endpoint free renal survival was calculated by Kaplan Meier analysis and compared by the log-rank test. We used Cox proportional hazards analysis to determine the independent predictor for renal outcome among the clinical data at the time of referral to a nephrologist. ROC analysis was used to determine the best cut-off value of plasma BNP level to predict the renal outcome., Results: The mean follow-up period was 2.5 +/- 1.1 years. Median age was 65 years. Of the subjects, 65.8% were men and 37.9% had diabetes mellitus. Median serum creatinine level was 2.7 mg/dL. Plasma BNP level was significantly higher among 147 patients who reached the combined renal endpoint compared with 90 patients who did not (116.0 pg/mL vs 54.5 pg/mL, p<0.001). After adjustment with other established predictive factors of renal outcome, plasma BNP level was selected to be the strongest predictive marker for renal endpoint (Hazard ratio 1.173, 95%CI 1.000-1.376). The optimal cut-off value of plasma BNP level suggested by ROC analysis was 69.5 pg/mL. Patients with a plasma BNP level above the cut-off point revealed a significantly poor renal outcome compared with those with a plasma BNP level below the cut-off point., Conclusions: The present study suggests that the plasma BNP level might be a predictive marker for renal outcome and a guide for management of cardio-renal interaction.

Left ventricular hypertrophy (LVH), which is a strong predictor of mortality in patients with endstage renal disease, is present in over 70% of patients commencing dialysis. However, only a few studies on LVH are available in patients before the start of dialysis treatment. The purpose of this study was to evaluate the prevalence and clinical correlates of LVH in patients with advanced stages of chronic kidney disease(CKD). We performed a cross sectional study of 90 patients who had renal diseases but no history of either cardiovascular diseases or arrhythmia. Circulating levels of human atrial natriuretic peptide (hANP) were also measured. LVH was present in 40.0% of the study population. The prevalence of LVH tended to increase with progression of renal decline: 22.7% in stage 3, 43.6% in stage 4, and 48.3% in stage 5 (creatinine clearance >10 mL/min) (p = 0.15). Univariate analyses revealed that hANP and albumin were significantly different between the groups with and without LVH. Stepwise logistic regression analysis showed that hANP and albumin were selected as the independent risk factors. These findings suggest that strict control of body fluid and nutrition could prevent the progression of LVH, and as a result, could attenuate the risk of cardiovascular events in CKD.