The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

The life expectancy of end-stage renal disease patients undergoing regular hemodialysis (HD) remains significantly lower than in the general population. Reducing excess mortality by improving renal replacement options is an unmet medical need. Online post-dilution hemodiafiltration (HDF) has been promoted as the gold standard, offering improved clinical outcomes, based on numerous observational studies that suggest a reduced mortality risk and lower morbidity with HDF compared with standard HD. However, most randomized controlled trials (RCTs) have failed to demonstrate a significant beneficial effect of HDF on all-cause mortality. The effects on secondary outcomes were often negligible or absent. Unfortunately, these RCTs were characterized by a moderate to high risk of bias. In post-hoc analyses of the largest RCTs and meta-analysis of individual participant data from four RCTs, HDF patients receiving the highest convection volume consistently and dose-dependently saw superior outcomes. However, as these studies were not designed a priori to clarify this issue, and there are no indisputable mechanisms underlying reduced mortality risks, we cannot exclude the possibility that the health status of patients (with vascular access as a proxy) may affect outcomes more than the convective technique itself. There is currently insufficient evidence to support the contention that high-volume HDF confers relevant benefits to patients over standard HD. The conflicting data of published RCTs reduce confidence in the superiority of high-volume convective therapy. Hopefully, ongoing large RCTs (for example, CONVINCE) may supply an indisputable answer to the crucial question of high-volume HDF.

The End-stage Renal Disease Registry Committee of the Korean Society of Nephrology collects data on the dialysis therapy in Korea through an internet-based registry program and reports it annually. In this article, the method and clinical implications of the mortality hazard ratio analyses of various clinical parameters in the 2017 registry report have been described, with the inclusion of data on four additional parameters. The mortality risk based on clinical parameters was analyzed only for hemodialysis patients. The number of registered patients with laboratory data was 13,943 (8,446 male and 5,497 female patients), and death was reported in 3,139 patients. Analysis of the effects of various clinical parameters on mortality was performed using non-linear Cox proportional hazard model with the R statistics program. For all clinical parameters, univariate and adjusted multivariate hazard ratio analyses were performed. Analysis of the mortality hazard ratio showed that low body mass index, low hemoglobin, low serum albumin, low serum phosphorus, and low urea reduction ratio were associated with a significantly increased mortality risk, whereas paradoxically high serum creatinine levels were associated with low mortality risk.

Background: Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives.
Results from several groups, including our own, have reported evidence of a supportive role for mesenchymal stromal cells (MSCs) in functional recovery and prevention of tissue damage in murine models of CKD. Prompted by these data, an open pilot study was conducted to assess the safety and efficacy of a single injection of autologous adipose tissue-derived MSCs (AT-MSCs) for treatment of CKD.
Methods: AT-MSCs were infused intravenously into six CKD patients at a dose of 1 million cells/kg. Patients were stabilized and followed for one year prior to MSC infusion and one year following infusion. Results: No patients presented with adverse effects. Statistically significant improvement in urinary protein excretion was observed in AT-MSCs transplanted patients, from a median of 0.75 g/day (range, 0.15-9.57) at baseline to 0.54 g/day (range, 0.01-2.66) at month 12 (P = 0.046). The glomerular filtration rate was not significantly decreased post-infusion of AT-MSCs.
Conclusion: Findings from this pilot study demonstrate that intravenous infusion of autologous expanded AT-MSCs into CKD patients was not associated with adverse effects and could benefit patients already undergoing standard medical treatment.

Background: P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders.
Methods: We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables.
Results: P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels.
Conclusion: Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.

Background: Severe dehydration decreases renal perfusion. However, it is unclear whether sub-morbid dehydration affects kidney function similarly. Although there have been numerous animal and human studies that have suggested mild dehydration is associated with glomerular hyperfiltration, it has not been confirmed on a large-scale in the general population. Therefore, we aimed to identify the relationship between hydration status and kidney function.
Methods: We reviewed the data of 28,342 adults who participated in the Korea National Health and Nutrition Examination Surveys. Urine specific gravity unit (SGU) was the primary variable that indicated hydration status, and the estimated glomerular filtration rate (eGFR) was used as the primary outcome.
Results: Multivariate linear regression analysis showed urine SGU was positively associated with eGFR, which was J-shaped in the multivariate generalized additive model plot. In the penalized spline curve analysis, the odds ratio for high eGFR was steadily increased. Although increased urine SGU was associated with decreased blood pressure and pulse rate, it had no effect on increased fasting glucose and total cholesterol, suggesting conflicting cardio-metabolic dehydration effects.
Conclusion: Dehydration, presumably sub-morbid in an ambulatory community-dwelling general population, is associated with higher kidney function. The clinical significance of sub-morbid dehydration-associated glomerular hyperfiltration needs further investigation.