The burden of chronic kidney disease in Asia region: a review of the evidence, current challenges, and future directions.

The disease burden of chronic kidney disease (CKD) and its impact on healthcare systems has been poorly studied in Asia, a socioeconomically diverse region with wide variations in availability, access, and quality of CKD care. The high CKD burden in this region is predominantly driven by an increased prevalence of risk factors including diabetes mellitus, hypertension, obesity, and use of traditional medicines and is further aggravated by challenges associated with effective implementation of population-based screening and surveillance systems in early detection and intervention of CKD. The Asian continent mostly comprised of low- and middle-income countries with resource restraints lacks robust population-based CKD registries resulting in a paucity of data on CKD incidence and prevalence, various treatment modalities, uptake of current guidelines, and the overall impact of implementation of developmental programs. There is an urgent need for a collaborative action plan between the healthcare community and governments in this region to detect CKD in its early stages and prevent its complications including kidney failure, cardiovascular disease, and death. Research-based evidence on the impact of early detection, sustainable treatment options, quality of life, delay or avoidance of dialysis, and related cost analysis is the need of the hour. We highlight successful implementation of strategic and policy-sharing programs adopted in a few countries; also, consolidate available region-specific data, quantify estimates of CKD burden and propose strategies with a multidisciplinary approach involving patients, the healthcare community and governmental bodies to combat CKD and its complications.

Neutrophil: Lymphocyte and Platelet: Lymphocyte ratios measured before transplantation and their correlation with new-onset diabetes post-transplantation in renal transplant recipients.

PURPOSE: Our goal was to evaluate the neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios measured before transplantation and their correlation with new-onset diabetes after transplantation (NODAT) in renal transplant recipients. PATIENTS AND METHODS: We conducted our study in 324 adult patients consecutively admitted to Military Hospital 103, Ha Noi, Viet Nam, who received kidney allografts from living donors. These patients were followed-up during the first 2 years post-transplantation for NODAT. We examined the association between NLR and PLR measured prior to transplantation in patients with NODAT: NLR and PLR were calculated based on the results of the complete blood count. The criteria for diagnosis of a fully symptomatic NODAT case were based on the guidelines established by the American Diabetes Association and included fasting venous blood glucose and glycosylated hemoglobin A1c (HbA1c) levels, with or without an oral glucose tolerance test. RESULTS: The overall rate of NODAT during the two years after kidney transplantation was 13.6%. We found mean values of age and body mass index (BMI), and median values of NLR, PLR, high sensitivity C-reactive protein (hs-CRP) levels, and the arteriosclerosis ratio in the NODAT group to be significantly higher than those of the non-NODAT group (all p < 0.05). Furthermore, an adjusted multivariate regression analysis showed that age (area under the curve [AUC] = 0.727, p < 0.001), BMI (AUC = 0.846, p < 0.001), serum hs-CRP levels (AUC = 0.884, p < 0.001), NLR (AUC = 0.888; p < 0.001), and PLR (AUC = 0.818; p < 0.001) had predictive value for NODAT. CONCLUSION: NLR and PLR measured before transplantation were good predictors for NODAT in the first 2 years post-renal transplantation.

Impact and perspective on chronic kidney disease in an Asian developing country: a large-scale survey in North Vietnam.

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 <60 ml/min/1.73 m(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.

Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.

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.

Inhibition of prostasin expression by TGF-beta1 in renal epithelial cells.

BACKGROUND: Prostasin has been shown to be involved in the regulation of sodium handling in the kidney. TGF-beta1 has been demonstrated to suppress alphaENaC expression and sodium uptake. Therefore, we hypothesized that TGF-beta1 may regulate prostasin expression to modulate sodium reabsorption in the kidney. METHODS: To determine if TGF-beta1 has an effect on prostasin expression, we isolated 2.9 kb 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-beta1 on the mRNA and protein abundance of prostasin, and amiloride-sensitive (22)Na uptake was determined. RESULTS: Treatment of M-1 cells with 20 ng/mL of TGF-beta1 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 50 bp region (-410 to -360) containing c-Rel-like sequence in prostasin promoter that is responsible for the TGF-beta1-mediated inhibition, and found that TGF-beta1 increases IkappaBalpha expression in M-1 cells. TGF-beta1 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-beta1 transcriptionally inhibits prostasin expression by the induction of IkappaBalpha and the subsequent inhibition of NF-kappaB/Rel activity in M-1 cells, and also suggest the possibility that TGF-beta1 might inhibit sodium reabsorption through a reduction in prostasin expression and subsequent inhibition of ENaC activity.

Effect of telmisartan on ambulatory blood pressure monitoring, plasma brain natriuretic peptide, and oxidative status of serum albumin in hemodialysis patients.

The effect of telmisartan on ambulatory blood pressure, plasma neurohormonal parameters, and oxidation of serum albumin has not been investigated in hemodialysis (HD) patients. Thirteen hypertensive HD patients were treated with 40 mg telmisartan once daily, and 24-h ambulatory blood pressure monitoring was performed after 0, 4, and 8 weeks of treatment. Plasma renin activity, plasma aldosterone concentration (PAC), brain natriuretic peptide (BNP) level, and serum oxidized albumin level were determined at the same time points. Serum telmisartan concentration was also measured at 4 and 8 weeks. Telmisartan significantly reduced systolic blood pressure and diastolic blood pressure (both awake and sleeping) after 4 weeks, and these pressures showed a further significant decrease after 8 weeks. Plasma levels of aldosterone, BNP, and serum oxidized albumin were markedly decreased after 4 weeks and these lower levels were maintained at 8 weeks. The trough serum telmisartan concentration was not significantly different at 8 weeks compared with 4 weeks. Throughout the treatment period, there were no significant adverse effects. Telmisartan effectively lowers blood pressure and reduces PAC, BNP, and oxidative stress and is safe and well-tolerated by HD patients. A long-term study in a large population is required to determine the influence of telmisartan therapy on cardiovascular mortality and morbidity in HD patients.

Inhibition of prostasin secretion by serine protease inhibitors in the kidney.

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.