The exocyst is a highly conserved eight-subunit protein complex (EXOC1-8) involved in the targeting and docking of exocytic vesicles translocating from the trans-Golgi network to various sites in renal cells. EXOC5 is a central exocyst component because it connects EXOC6, bound to the vesicles exiting the trans-Golgi network via the small GTPase RAB8, to the rest of the exocyst complex at the plasma membrane. In the kidney, the exocyst complex is involved in primary ciliognesis, cystogenesis, and tubulogenesis. The exocyst, and its regulators, have also been found in urinary extracellular vesicles, and may be centrally involved in urocrine signaling and repair following acute kidney injury. The exocyst is centrally involved in the development of other organs, including the eye, ear, and heart. The exocyst is regulated by many different small GTPases of the RHO, RAL, RAB, and ARF families. The small GTPases, and their guanine nucleotide exchange factors and GTPase-activating proteins, likely give the exocyst specificity of function. The recent development of a floxed Exoc5 mouse line will aid researchers in studying the role of the exocyst in multiple cells and organ types by allowing for tissue-specific knockout, in conjunction with Cre-driver mouse lines.

Proximal renal tubular acidosis (RTA) is caused by a defect in bicarbonate (HCO3 -) reabsorption in the kidney proximal convoluted tubule. It usually manifests as normal anion-gap metabolic acidosis due to HCO3 - wastage. In a normal kidney, the thick ascending limb of Henle's loop and more distal nephron segments reclaim all of the HCO3 - not absorbed by the proximal tubule. Bicarbonate wastage seen in type II RTA indicates that the proximal tubular defect is severe enough to overwhelm the capacity for HCO3 - reabsorption beyond the proximal tubule. Proximal RTA can occur as an isolated syndrome or with other impairments in proximal tubular functions under the spectrum of Fanconi syndrome. Fanconi syndrome, which is characterized by a defect in proximal tubular reabsorption of glucose, amino acids, uric acid, phosphate, and HCO3 -, can occur due to inherited or acquired causes. Primary inherited Fanconi syndrome is caused by a mutation in the sodium-phosphate cotransporter (NaPi-II) in the proximal tubule. Recent studies have identified new causes of Fanconi syndrome due to mutations in the EHHADH and the HNF4A genes. Fanconi syndrome can also be one of many manifestations of various inherited systemic diseases, such as cystinosis. Many of the acquired causes of Fanconi syndrome with or without proximal RTA are drug-induced, with the list of causative agents increasing as newer drugs are introduced for clinical use, mainly in the oncology field.

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a wellstudied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic antiinflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.

Dramatic advances in the care of patients with cancer have led to significant improvement in outcomes and survival. However, renal manifestations of the underlying cancer as well as the effects of anti-neoplastic therapies leave patients with significant morbidity and chronic kidney disease risks. The most common renal manifestations associated with cancer include acute kidney injury (AKI) in the setting of multiple myeloma, tumor lysis syndrome, post-hematopoietic stem cell therapy, and AKI associated with chemotherapy. Knowledge of specific risk factors, modification of risk and careful attention to rapid AKI diagnosis are critical for improving outcomes.

Central venous disease (CVD) is difficult to treat and often resistant to treatment. In CVD, hemodialysis vascular access should sometimes be abandoned, or in serious cases, the patient's life may be threatened. Therefore, prevention is ideal. However, as the prevalence of chronic kidney disease (CKD) has increased steadily with population aging, CKD patients with a peripherally inserted central catheter (PICC) are encountered frequently. PICCs can cause CVD, and the basilic vein, which is regarded as the important last option for native arteriovenous fistula (AVF) creation in end-stage renal disease (ESRD) patients, is destroyed frequently after its use as the entry site of PICC. The most well-established risk factors for CVD are a history of central venous catheter (CVC) insertion and its duration of use. Therefore, to reduce the incidence of CVD, catheterization in the central vein (CV) should be minimized, along with its duration of use. In this review, we will first explain the basic territories of the CV and introduce its pathophysiology, clinical features, and advanced treatment options. Finally, we will emphasize prevention of CVD.

Background: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys.
Methods: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy.
Results: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells.
Conclusion: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Background: We investigated the relationship between serum total carbon dioxide (CO2) and bicarbonate ion (HCO3 -) concentrations in pre-dialysis chronic kidney disease (CKD) patients and devised a formula for predicting low bicarbonate (HCO3 - < 24 mmol/L) and high bicarbonate (HCO3 - ≥ 24 mmol/L) using clinical parameters.
Methods: In total, 305 samples of venous blood collected from 207 pre-dialysis patients assessed by CKD stage (G1 + G2, 46; G3, 50; G4, 51; G5, 60) were investigated. The relationship between serum total CO2 and HCO3 - concentrations was analyzed using Pearson's correlation coefficient. An approximation formula was developed using clinical parameters correlated independently with HCO3 - concentration. Diagnostic accuracy of serum total CO2 and the approximation formula was evaluated by receiver operating characteristic curve analysis and a 2 × 2 table.
Results: Serum total CO2 correlated strongly with HCO3 - concentration (r = 0.91; P < 0.001). The following approximation formula was obtained by a multiple linear regression analysis: HCO3 - (mmol/L) = total CO2 - 0.5 × albumin - 0.1 × chloride - 0.01 × (estimated glomerular filtration rate + blood glucose) + 15. The areas under the curves of serum total CO2 and the approximation formula for detection of low bicarbonate and high bicarbonate were 0.981, 0.996, 0.993, and 1.000, respectively. This formula had superior diagnostic accuracy compared with that of serum total CO2 (86.6% vs. 81.3%).
Conclusion: Serum total CO2 correlated strongly with HCO3 - concentration in pre-dialysis CKD patients. An approximation formula including serum total CO2 showed superior diagnostic accuracy for low and high bicarbonate compared with serum total CO2.

Background: Previous randomized controlled trials of revascularization for atherosclerotic renal artery stenosis (ARAS) were not successful. We investigated the effects of percutaneous transluminal angioplasty with stent insertion (PTA/S) on kidney function and blood pressure (BP) control in patients with ARAS.
Methods: From 2000 to 2017, 47 subjects who underwent PTA/S for ARAS were identified. A high-risk group was defined, composed of patients having one or more of the following clinical presentations: pulmonary edema, refractory hypertension, and rapid deterioration of kidney function. Subjects who met the criteria of 'kidney function improvement' or 'hypertension improvement' after PTA/S were classified as responders.
Results: Twenty-one (44.7%) subjects were classified into the high-risk group. Two subjects (8.0%) in the low-risk group (n = 25) and 5 subjects (27.8%) in the high-risk group (n = 18) showed improvement in kidney function after PTA/S (P = 0.110). In patients with rapid decline of kidney function, estimated glomerular filtration rate improved from 28 (interquartile range [IQR], 10-45) mL/min/1.73 ㎡ to 41 (IQR, 16-67) mL/min/1.73 ㎡ at 4 months after PTA/S, although the difference was not significant (P = 0.084). Regarding BP control, 9 (36.0%) and 14 (77.8%) subjects showed improvement after PTA/S in the low- (n = 25) and high-risk (n = 18) groups, respectively (P = 0.007). In patients with refractory hypertension, the systolic BP dropped from 157 (IQR, 150-164) mmHg to 140 (IQR, 131- 148) mmHg at 4 months after PTA/S (P = 0.005). Twenty-five subjects were defined as responders and comprised a significant proportion of the high-risk group (P = 0.004).
Conclusion: PTA/S might improve BP control and kidney function in patients with ARAS presenting with highrisk clinical features. The optimal application of PTA/S should be based on individual assessment of the clinical significance of renal artery stenosis.

Background: Yersinia pseudotuberculosis is known to cause fever, gastroenteritis, or acute kidney injury (AKI). There have been several Y. pseudotuberculosis infection outbreaks to date associated with ingestion of contaminated food or unsterile water. While this disease was considered to have practically been eradicated with the improvement in public health, we encountered several cases of AKI associated with Yersinia infection.
Methods: We retrospectively collected data from medical records of patients with suspected Y. pseudotuberculosis infection who visited Seoul National University Children's Hospital in 2017.
Results: There were nine suspected cases of Yersinia infection (six males and three females; age range 2.99- 12.18 years). Among them, five cases occurred in May, and seven patients were residing in the metropolitan Seoul area. Three patients had history of drinking mountain water. Every patient first presented with fever for a median of 13 days, followed by gastrointestinal symptoms and oliguria. Imaging studies revealed mesenteric lymphadenitis, terminal ileum wall thickening, and increased renal parenchymal echogenicity. Creatinine levels increased to 5.72 ± 2.18 mg/dL. Urinalysis revealed sterile pyuria, proteinuria, and glycosuria. Oliguria continued for 4 to 17 days, and two patients required dialysis; however, all of them recovered from AKI. Mucocutaneous manifestations developed later. In the diagnostic work-up, Yersinia was isolated from the stool culture in one patient. Anti-Yersinia immunoglobulin (Ig) A and IgG were positive in 6 patients.
Conclusion: Y. pseudotuberculosis infection is an infrequent cause of interstitial nephritis presenting with AKI. When a patient presents with fever, gastroenteritis, and AKI not resolving despite hydration, the clinician should suspect Y. pseudotuberculosis infection.

Background: Few data showed the optimal blood pressure (BP) in noncritically ill patients with acute kidney injury (AKI) relative to mortality or severe AKI. We therefore sought to analyze the data that exist for the ideal target range for BP in noncritically ill patients with AKI.
Methods: We performed a retrospective cohort study involving 1,612 hospitalized patients who were diagnosed with AKI using the Kidney Disease: Improving Global Outcomes definition based on serum creatinine measurements for a period of 1 year. The average systolic BP (SBP) was categorized into 10-mmHg increments (within 48 hours after the development of AKI). The primary outcome was a composite of severe AKI or 90-day mortality.
Results: The composite outcome rate in patients was 18.7% (302/1,612). The relationship between BP and the composite outcome followed a U-shaped curve, with an increased event rate observed at both low and high BP values. The average SBP after AKI predicted the composite outcome after adjusting for baseline variables (reference SBP: 120-129 mmHg; < 100 mmHg: hazard ratio [HR] 1.84, P = 0.015; 100-109 mmHg: HR 1.56, P = 0.038; 110-119 mmHg: HR 1.15, P = 0.483; 130-139 mmHg: HR 1.51, P = 0.045; ≥ 140 mmHg: HR 1.73, P = 0.005).
Conclusion: Among noncritically ill patients with AKI, a U-shaped curve association was observed between the average SBP within 48 hours after AKI and the composite primary outcome of this study, with the lowest event rate for SBP ranging from approximately 110 to 129 mmHg.