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Background: The prevalence of chronic kidney disease (CKD) in Asia is expected to increase along with increases of hypertension and diabetes. Most cases are not treated and progress to end-stage renal disease (ESRD) with an increased risk for cardiovascular complications. Renal replacement therapies are so expensive that most ESRD patients die without treatment. Thus, countermeasures against early stages of CKD are urgently needed. Nevertheless, basic information for CKD has not been reported in Vietnam. Methods: We conducted a survey of CKD in 8,505 inhabitants aged >40 years in Vietnam. Subjects with abnormal urinary findings were further examined, including serum creatinine levels. In this study, CKD was defined as 2 of estimated creatinine clearance by the Cockcroft-Gault method. Results: We identified 3.1% of subjects as CKD (stages 3–5) with positive findings in urine test. We also found that elderly hypertension and malnutrition were independent risk factors for CKD in this population. Conclusion: We found a significant number of CKD patients in Vietnam. To avoid a CKD pandemic in Asia including Vietnam, we strongly suggest further analyses of risk factors and prognosis of CKD in these populations, and the development of efficient management systems suitable for Asia.

Prostasin has been shown to regulate sodium handling in the kidney. Recently, a serine protease inhibitor, protease nexin-1 (PN-1), was identified as an endogenous inhibitor for prostasin. Therefore, we hypothesized that PN-1 may regulate sodium reabsorption by reducing prostasin activity, and that expression of PN-1 was regulated by transforming growth factor-beta1 (TGF-beta1) or aldosterone, like prostasin. cRNAs for epithelial sodium channel (ENaC), prostasin, and PN-1 were expressed in Xenopus oocytes, and the amiloride-sensitive sodium currents (I(Na)) were measured. The effect of TGF-beta1 and aldosterone on the mRNA and protein abundance of PN-1 and ENaC was detected by real-time polymerase chain reaction and immunoblotting in M-1 cells. Expression of PN-1 substantially decreased prostasin-induced I(Na) by approximately 68% in oocytes. Treatment of M-1 cells with 20 ng/ml TGF-beta1 significantly increased protein expression of PN-1 by 3.8+/-0.5-fold, whereas administration of 10(-6) M aldosterone markedly decreased protein expression of PN-1 to 53.7+/-6.7%. Basolateral, but not apical, application of TGF-beta1 significantly reduced I(eq). To elucidate the involvement of PN-1 in basal ENaC activity, we silenced the expression of PN-1 by using short-interfering RNA. This increased I(eq) by 1.6+/-0.1-fold. Our study indicates that PN-1 could have a natriuretic role by inhibiting prostasin activity and suggests the possibility that aldosterone and TGF-beta reciprocally regulate the expression of PN-1 in renal epithelial cells contributing to salt retention or natriuresis, respectively by an additional mechanism. PN-1 could represent a new factor that contributes to regulation of ENaC activity in the kidney.

Inhibition of prostasin expression by TGF-β1 in renal epithelial cells. Background Prostasin has been shown to be involved in the regulation of sodium handling in the kidney. TGF-β1 has been demonstrated to suppress αENaC expression and sodium uptake. Therefore, we hypothesized that TGF-β1 may regulate prostasin expression to modulate sodium reabsorption in the kidney. Methods To determine if TGF-β1 has an effect on prostasin expression, we isolated 2.9kb of the rat prostasin promoter, and measured its transcriptional activity with a luciferase assay in mouse cortical collecting duct cell line (M-1). The effect of TGF-β1 on the mRNA and protein abundance of prostasin, and amiloride-sensitive 22 Na uptake was determined. Results Treatment of M-1 cells with 20ng/mL of TGF-β1 for 24 hours significantly decreased the promoter activity by 50 ± 1%, and the inhibitory effect was dose dependent over the range of 0.1 to 20 ng/mL. We identified a 50bp region (-410 to -360) containing c-Rel–like sequence in prostasin promoter that is responsible for the TGF-β1–mediated inhibition, and found that TGF-β1 increases IκBα expression in M-1 cells. TGF-β1 reduced endogenous prostasin mRNA and protein expression in M-1 cells by 50 ± 12% and 44 ± 12%, respectively, and the amiloride-sensitive 22 Na uptake by 35.9 ± 4.8%. Conclusion Our findings indicate the possibility that TGF-β1 transcriptionally inhibits prostasin expression by the induction of IκBα and the subsequent inhibition of NF-κB/Rel activity in M-1 cells, and also suggest the possibility that TGF-β1 might inhibit sodium reabsorption through a reduction in prostasin expression and subsequent inhibition of ENaC activity.

A serine protease, prostasin, has been shown to stimulate the activity of amiloride-sensitive sodium channels (ENaC). Prostasin is a glycosylphosphatidylinositol-anchored protein that is found free in physiologic fluids and tissue culture medium, but the mechanism by which prostasin is secreted from the cells has not been elucidated. The current studies found that serine protease inhibitor aprotinin blocked the secretion of prostasin in a mouse cortical collecting duct (CCD) cell line (M-1 cells). A synthetic serine protease inhibitor, nafamostat mesilate (NM), which is commonly used for the treatment of pancreatitis and disseminated intravascular coagulation in Japan, also inhibited the secretion of prostasin in M-1 cells. Continuous infusion of NM into rats resulted in a substantial decrease in urinary prostasin and urinary sodium excretion. p-guanidinobenzoic acid and 6-amidino-2-naphtol, catalytically inactive metabolites of NM, had no effect on prostasin secretion both in M-1 cells and in rats. These findings suggest that a serine protease-sensitive mechanism is involved in the secretion of prostasin in vitro as well as in vivo. Potassium secretion in the CCD is tightly linked to sodium reabsorption through EnaC; therefore, NM-induced decrease in prostasin secretion and subsequent inhibition of ENaC activity could account for the side effects of hyponatremia and/or hyperkalemia that are found sometimes in patients treated with NM. The results indicate an important role for prostasin in sodium reabsorption in the kidney under pathophysiologic conditions.

To date, 11 loss of function mutations in the human urate transporter 1 (hURAT1) gene have been identified in subjects with idiopathic renal hypouricemia. In the present studies we investigated the clinical features and the mutations in the hURAT1 gene in seven families with presecretory reabsorption defect-type renal hypouricemia and in one family with the postsecretory reabsorption defect type. Twelve affected subjects and 26 family members were investigated. Mutations were analyzed by PCR and the direct sequencing method. Urate-transporting activities of wild-type and mutant hURAT1 were determined by [14C]urate uptake in Xenopus oocytes. Mutational analysis revealed three previously reported mutations (G774A, A1145T, and 1639–1643 del-GTCCT) and a novel mutation (T1253G) in families with the presecretory reabsorption defect type. Neither mutations in the coding region of hURAT1 gene nor significant segregation patterns of the hURAT1 locus were detected in the postsecretory reabsorption defect type. All hURAT1 mutants had significantly reduced urate-transporting activities compared with wild type (P < 0.05; n = 12), suggesting that T1253G is a loss of function mutation, and hURAT1 is responsible for the presecretory reabsorption defect-type familial renal hypouricemia. Future studies are needed to identify a responsible gene for the postsecretory reabsorption defect-type familial renal hypouricemia.

Currently, the Asian region is showing marked population growth and economic progress. In developing countries in Asia, rapid demands for dialysis therapy which have the same standard as those delivered in developed countries have arisen. The end stage renal disease (ESRD) patients have been increasing in these countries, but every country has its own barriers to promote better dialysis due to several reasons as the financial, educational, historical matters and so on. However, they have overcome these problems step by step. The Japanese Society for Dialysis Therapy (JSDT) has started to make efforts to promote exchanges in the region, and increase the standard of dialysis therapy in each country. Based on the information obtained in this symposium, the committee is planning to prepare effective programs for young physicians and paramedics in developing countries. This report is the Review Article by the Committee of International Communication for Academic Research of JSDT. The presentation associated this article was opened at the 61st Annual Meeting of the Japanese Society for Dialysis Therapy held on June 26, 2015 (FRI), Yokohama City, Japan.