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.

Intradialytic oral nutrition effects on malnourished hemodialysis patients: a randomized trial.

Oral nutritional supplementation (ONS) is recommended for malnourished hemodialysis patients when their nutritional intake remains inadequate to meet energy and protein requirements. Patients were randomized into two groups: the intradialytic ONS supplements (INTRA-ONS) group (N = 16) and the interdialytic ONS supplements (INTER-ONS) group (N = 16) for a duration of 12 weeks. Malnutrition inflammation score (MIS) and serum albumin levels were assessed. The total MIS decreased significantly in patients from both the INTRA-ONS group (- 6.13, 95% CI - 8.29 to - 3.96) and the INTER-ONS group (- 3.50, 95% CI - 5.56 to - 1.35). A significant difference in the change of MIS was observed between the two groups (- 3.06, 95% CI - 5.94 to - 0.17). No significant differences were observed between the groups concerning serum albumin levels, dietary intake, anthropometric measurements, or body weight. Intradialytic ONS demonstrates similar benefits on nutritional biomarkers but improves the MIS among malnourished ESRD patients compared to interdialytic ONS.Trial registration Thai Clinical Trials Registry (TCTR) identification number is TCTR20220322007: 16/09/2021.

Resistant hypertension: diagnosis, evaluation, and treatment a clinical consensus statement from the Thai hypertension society.

Resistant hypertension (RH) includes hypertensive patients with uncontrolled blood pressure (BP) while receiving ≥3 BP-lowering medications or with controlled BP while receiving ≥4 BP-lowering medications. The exact prevalence of RH is challenging to quantify. However, a reasonable estimate of true RH is around 5% of the hypertensive population. Patients with RH have higher cardiovascular risk as compared with hypertensive patients in general. Standardized office BP measurement, confirmation of medical adherence, search for drug- or substance-induced BP elevation, and ambulatory or home BP monitoring are mandatory to exclude pseudoresistance. Appropriate further investigations, guided by clinical data, should be pursued to exclude possible secondary causes of hypertension. The management of RH includes the intensification of lifestyle interventions and the modification of antihypertensive drug regimens. The essential aspects of lifestyle modification include sodium restriction, body weight control, regular exercise, and healthy sleep. Step-by-step adjustment of the BP-lowering drugs based on the available evidence is proposed. The suitable choice of diuretics according to patients' renal function is presented. Sacubitril/valsartan can be carefully substituted for the prior renin-angiotensin system blockers, especially in those with heart failure with preserved ejection fraction. If BP remains uncontrolled, device therapy such as renal nerve denervation should be considered. Since device-based treatment is an invasive and costly procedure, it should be used only after careful and appropriate case selection. In real-world practice, the management of RH should be individualized depending on each patient's characteristics.

Risk factors associated with mortality among patients on maintenance hemodialysis: The Thailand Renal Replacement Therapy registry.

INTRODUCTION: End-stage kidney disease (ESKD) has been increasing in prevalence across the world, including Thailand, and patients with ESKD on hemodialysis have a high mortality risk. METHODS: A retrospective cohort study was performed across 855 hemodialysis centers in the Thailand Renal Replacement Therapy registry. The database and mortality data were analyzed. RESULTS: A total of 58 952 patients were included. The survival rates at 1, 3, and 5 years were 93.5%, 69.7%, and 41.2%, respectively. On multivariate analysis, factors such as aging, permanent catheter or arteriovenous graft, twice-weekly hemodialysis, low levels of urea reduction ratio, normalized protein catabolic rate, hemoglobin, transferrin saturation, serum albumin, LDL-cholesterol, intact-parathyroid hormone, uric acid, sodium, phosphate, and bicarbonate were significantly related to death. CONCLUSION: Mortality is high in ESKD patients on hemodialysis. Age, type of vascular access, twice-weekly hemodialysis, inadequate dialysis, low protein intake, anemia, abnormal electrolytes, and bone mineral disorders are associated with all-cause mortality.

Effect of intradialytic weight resistance training exercise in sarcopenic hemodialysis patients: A randomized controlled trial.

BACKGROUND: Sarcopenia has a high prevalence in end-stage kidney disease (ESKD). However, there is limited evidence of resistance exercise in these patients. OBJECTIVE: The study investigated the effects of resistance exercise on muscle mass, strength, and physical functioning. METHOD: Fifty-three patients were randomly assigned to resistance training exercise (n = 26) and standard exercise (n = 27) groups. All of the patients were diagnosed with sarcopenia by the Asian Working Group for Sarcopenia 2019 criteria. RESULTS: After 12 weeks, an improvement in leg muscle strength was significantly greater in the resistant exercise group compared with standard exercise (12.19 vs. 2.83 kg, p < 0.001). Appendicular skeletal muscle mass had a mean difference (1.01 vs. 1.02 kg/m2 , p = 0.96). Physical performance status had a mean difference (-2.3 vs. -18 s, p = 0.42). There were no serious adverse events. CONCLUSION: Over a 12-week follow-up, resistance exercise improved muscle strength in sarcopenic ESKD patients. Muscle mass and physical performance showed no significant change, but there is still a trend demonstrating to improve.

Safety and Efficacy of Long-Term Voclosporin Treatment for Lupus Nephritis in the Phase 3 AURORA 2 Clinical Trial.

OBJECTIVE: AURORA 2 evaluated the long-term safety, tolerability, and efficacy of voclosporin compared to placebo in patients with lupus nephritis (LN) receiving an additional two years of treatment following completion of the one-year AURORA 1 study. METHODS: Enrolled patients continued their double-blinded treatment of voclosporin or placebo randomly assigned in AURORA 1, in combination with mycophenolate mofetil and low-dose glucocorticoids. The primary objective was safety assessed with adverse events (AEs) and biochemical and hematological assessments. Efficacy was measured by renal response. RESULTS: A total of 216 patients enrolled in AURORA 2. Treatment was well tolerated with 86.1% completing the study and no unexpected safety signals. AEs occurred in 86% and 80% of patients in the voclosporin and control groups, respectively, with an AE profile similar to that seen in AURORA 1, albeit with reduced frequency. Investigator reported AEs of both glomerular filtration rate (GFR) decrease and hypertension occurred more frequently in the voclosporin than the control group (10.3% vs 5.0%, and 8.6% vs 7.0%, respectively). Mean corrected estimated GFR (eGFR) was within the normal range and stable in both treatment groups. eGFR slope over the two-year period was -0.2 mL/min/1.73 m2 (95% confidence interval [CI] -3.0 to 2.7) in the voclosporin group and -5.4 mL/min/1.73 m2 (95% CI -8.4 to -2.3) in the control group. Improved proteinuria persisted across three years of treatment, leading to more frequent complete renal responses in patients treated with voclosporin (50.9% vs 39.0%; odds ratio 1.74; 95% CI 1.00-3.03). CONCLUSION: Data demonstrate the safety and efficacy of long-term voclosporin treatment over three years of follow-up in patients with LN.

Effects of febuxostat on markers of endothelial dysfunction and renal progression in patients with chronic kidney disease.

Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury among patients with CKD remains limited. A total of 84 patients with CKD stages III-IV with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) group for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle brachial index (ABI) and serum uric acid were measured at baseline and at the end of study. Febuxostat administration significantly reduced the serum uric acid concentration among patients with CKD when compared with control [- 3.40 (95% CI - 4.19 to - 2.62) vs. - 0.35 (95% CI - 0.76 to 0.06) mg/dL; P < 0.001, respectively). No significant difference in the changes in serum ADMA, hs-CRP, eGFR and albuminuria was identified between the two groups. Subgroup analysis among patients with decreased serum uric acid after febuxostat, the estimated GFR change between the febuxostat and the control group showed significant difference at 8 weeks (2.01 (95% CI 0.31 to 3.7) vs. 0.04 (95% CI - 1.52 to 1.61) mL/min/1.73 m2; P = 0.030, respectively). Adverse events specific to febuxostat were not observed. Febuxostat effectively reduced serum uric acid in the CKD population without improving endothelial dysfunction. It was able to preserve renal function in the subgroup of patients with CKD and lower serum uric acid level after treatment.Trial registration: Thai Clinical Trials, TCTR20210224005: 24/022021 http://www.thaiclinicaltrials.org/show/TCTR20210224005 .

Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

OBJECTIVE: To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). METHODS: A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26. RESULTS: A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7-95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9-75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5-10%) and severe infections (10% vs. 4.8-5.0%) were reported with 240 mg BI 655064. CONCLUSION: The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.

Effect of pioglitazone on serum FGF23 levels among patients with diabetic kidney disease: a randomized controlled trial.

AIM: Elevated fibroblast growth factor-23 (FGF23) is an established marker of cardiovascular disease among patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Recently, circulating FGF23 positively correlated with insulin resistance level among patients with CKD. Pioglitazone improves insulin sensitivity and it may have potential for treating CKD-related FGF23 overactivity. METHODS: A randomized, open-label, controlled trial was performed among patients with T2DM and CKD. Eligible participants were randomly assigned to either oral 15 mg/day of pioglitazone (N = 22) or control group (N = 24) for 16 weeks. Serum FGF23 and homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were measured. RESULTS: Forty-six patients completed the trial. After 16 weeks of treatment, significant decreases in serum intact FGF23 level (median change - 49.01 (IQR, - 103.51 to - 24.53) vs. 1.07 (IQR, - 22.4-39.53) pg/mL, P = 0.01) and HOMA-IR (mean change - 1.41 (95% CI, - 2.24 to - 0.57) vs. - 0.05 (95% CI, - 1.00-0.89), P = 0.031) were observed in the pioglitazone group compared with the control group. HemoglobinA1C also significantly decreased in the pioglitazone group compared with the control group. No difference was found in the changes of serum phosphorus, calcium and serum intact parathyroid hormone between the two groups. Changes of FGF23 were positively associated with changes of HOMA-IR (R = 0.47) and insulin levels (R = 0.47). No serious adverse event was reported during the study. CONCLUSION: This study confirmed that pioglitazone effectively reduced serum FGF23 levels and related to improved insulin sensitivity among patients with T2DM and CKD. CLINICAL TRIAL REGISTRATION: TCTR20210316009.

Prediction of cardiovascular outcome by estimated glomerular filtration rate among high-risk patients: a Thai nationwide cohort study.

BACKGROUND: Decline of estimated glomerular filtration rate (eGFR) is associated with increased cardiovascular (CV) morbidity and mortality, but the predictive value of different eGFR on CV outcomes is limited in Southeast Asian populations. AIMS: We aimed to stratify CV outcomes according to renal function among Thai patients with high atherosclerosis risk. METHODS: We performed a secondary analysis in a 5-year national cohort entitled "CORE-Thailand study." Subjects were classified in 6 groups according to baseline kidney function: group I, eGFR ≥ 90; group II, eGFR 60-89; group IIIa, eGFR 45-59; group IIIb, eGFR 30-44; group IV, eGFR 15-29; group V, eGFR < 15 ml/min/1.73 m2 or receiving renal replacement therapy. The primary outcome was 4-point major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, CV mortality, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: A total of 6376 subjects (3467 men and 2909 women) were categorized in 6 groups. After adjusting covariates in the Cox proportional hazards model, compared to group I, subjects in groups II-V had a 1.65-fold, 2.17-fold, 2.67-fold, 4.24-fold, and 4.87-fold risk for 4-point MACE, respectively, with statistical significance at P < 0.05 in all groups. Kaplan-Meier analysis illustrated stepwise lower survivals from 4-point MACE following the groups with lower baseline eGFR (log-rank test with P < 0.001). All secondary outcomes showed similar trends as the primary outcome, except nonfatal stroke. CONCLUSION: Lower baseline kidney function was independently associated with increased risk of CV events and all-cause mortality in Thai populations at high CV risk.

The Effect of Intravenous Mannitol Combined With Normal Saline in Preventing Cisplatin-Induced Nephrotoxicity: A Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Nephrotoxicity is a major dose-limiting toxicity among patients with cancer who were treated with cisplatin. Although no standard approach is available to prevent cisplatin-induced nephrotoxicity, administering intravenous isotonic saline is recommended. Additionally, mannitol combined with hydration has been evaluated, but none of them have been established. Our study aimed to determine the efficacy of mannitol combined hydration to prevent cisplatin-induced nephrotoxicity. PATIENTS AND METHODS: This study was a phase II, randomized, placebo-controlled design. All patients with solid cancers who were treated with cisplatin (n = 48) were randomly assigned to receive either placebo (n = 25) or 20 g of mannitol (n = 23) after completing 2 L of prehydration and receiving cisplatin. Serum creatinine, blood urea nitrogen, electrolyte, and glomerular filtration rate (GFR) were measured at baseline and days 2 and 7. Moreover, GFR was calculated based on the 24-hour urine creatinine clearance rate to assess renal function at baseline and 48 hours after receiving cisplatin. Severity of nausea and vomiting was evaluated using Common Terminology Criteria for Adverse Events. RESULTS: No difference was found regarding baseline characteristics between the two groups. Seven of 23 patients (37.4%) in the mannitol group and 10 of 25 patients (40%) in the placebo group increased serum creatinine level ≥ 0.3 mg/dL at 48 hours after intervention (P value = .48). Patients receiving mannitol exhibited significantly lower incidence of 24-hour urine GFR below 60 mL/min/1.73 m than those in the placebo group (13.6% v 48.0% in the placebo group; P value = .012). Univariate analysis showed the greatest benefit for administering mannitol among patients receiving cisplatin > 80 mg/m2, or patients receiving concomitant radiation. CONCLUSION: Mannitol combined with hydration significantly prevented cisplatin-induced nephrotoxicity. Additionally, mannitol should be particularly considered among patients with cancer, treated with cisplatin > 80 mg/m2, or patients receiving concomitant radiation.

Association of body mass index with kidney function and mortality in high cardiovascular risk population: A nationwide prospective cohort study.

BACKGROUND: There is increasing awareness of the impact of obesity and underweight on cardiovascular (CV) disease, chronic kidney disease (CKD) and mortality. Abnormal body mass index (BMI) might be associated with worse clinical outcomes, including CKD progression, but limited evidence exists among Asian patients with high CV risk. OBJECTIVE: To investigate the association of BMI with progressive loss of kidney function and all-cause mortality in Thai patients with high CV risk. METHODS: In a national cohort of 5887 high CV risk subjects, we assessed the association of high BMI with the composite renal outcome (estimated glomerular filtration rate [eGFR] decline over 40%, eGFR less than 15 mL/min/1.73 m2 , doubling of serum creatinine, initiation of dialysis and death related to renal causes) and with all-cause mortality in Cox proportional hazards models. RESULTS: A total of 5887 participants (3217 male and 2670 female) with high CV risk were enrolled. Participants were classified into five groups by their baseline BMI; <20 kg/m2 (n = 482), 20-24.9 kg/m2 (n = 2437), 25-29.9 kg/m2 (n = 2140), 30-34.9 kg/m2 (n = 665) and 35 kg/m2 (n = 163), respectively. On multivariate analysis of Cox proportional hazards models, adjusted for other covariates, baseline BMI ≥35 kg/m2 was an independent predictor of loss of kidney function (HR 1.60, 95% CI 1.04-2.40) and all-cause mortality (HR 2.68, 95% CI 1.50-4.80). Baseline BMI <20 kg/m2 was an independent predictor of all-cause mortality as well (adjusted HR 2.26, 95% CI 1.50-3.42). CONCLUSION: In the high CV risk Thai population, a BMI of 35 kg/m2 or more is associated with loss of kidney function and mortality. On the other hand, a BMI less than 20 kg/m2 is also associated with all-cause mortality.

Ankle-brachial index predicts renal outcomes and all-cause mortality in high cardiovascular risk population: a nationwide prospective cohort study in CORE project.

BACKGROUND: Low ankle-brachial index (ABI) related ischemic events are common among individuals with chronic kidney disease (CKD). It is also associated with an increased risk of rapid renal function decline. The presence of peripheral artery disease (PAD) with low ABI among patients with high cardiovascular (CV) risk increases limb loss and mortality. AIMS: To estimate the association between abnormal ABI and renal endpoints and all-cause mortality. METHODS: A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. The subjects were divided into 3 groups based on ABI at baseline > 1.3, 0.91-1.3, and ≤ 0.9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine and initiation of dialysis. The secondary outcome was all-cause mortality. Cox regression analysis and Kaplan-Meier curve were performed. RESULTS: A total of 5543 subjects (3005 men and 2538 women) were included. Cox proportional hazards model showed a significant relationship of low ABI (ABI ≤ 0.9) and primary composite outcome and all-cause mortality. Compared with the normal ABI group (ABI 0.91-1.3), subjects with low ABI at baseline significantly had 1.42-fold (95% CI 1.02-1.97) and 2.03-fold (95% CI 1.32-3.13) risk for the primary composite outcome and all-cause mortality, respectively, after adjusting for variable factors. CONCLUSION: Our study suggested that PAD independently predicts the incidence of renal progression and all-cause mortality among Thai patients with high CV risk.

Cardio-ankle vascular index with renal progression and mortality in high atherosclerosis risk: a prospective cohort study in CORE-Thailand.

BACKGROUND: Increased arterial stiffness is linked to markers of endothelial dysfunction and vasculopathy such as albuminuria, vascular calcification, left ventricular hypertrophy and cardiovascular (CV) diseases. Studies of arterial stiffness on renal progression are limited. OBJECTIVE: The study aimed to evaluate the association between high cardio-ankle vascular index (CAVI) and renal endpoint and all-cause mortality in a Thai population with high atherosclerosis risk. METHODS: A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. Subjects were divided into 3 groups with mean CAVI < 8, 8-8.9, and ≥ 9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine, initiation of dialysis and death related to renal causes. The secondary outcomes were all-cause mortality, CV mortality and eGFR decline. RESULTS: A total of 4898 subjects (2743 men and 2155 women) were enrolled. Cox proportional hazards model showed a significant relationship of high CAVI (CAVI ≥ 9) and primary composite outcome. Subjects with high CAVI at baseline had a 1.45-fold (95% CI 1.13-1.84) significant risk for the primary composite outcome and 1.72-fold (95% CI 1.12-2.63) risk for all-cause mortality, compared with normal CAVI (CAVI < 8). After stepwise multivariate analysis, the high CAVI group was only positively associated with primary composite outcome. Kaplan-Meier curve of the primary composite outcome and all-cause mortality demonstrated the worst survival in the high CAVI group (log-rank test with P < 0.05). CONCLUSION: In a Thai cohort with high atherosclerosis risk, increased arterial stiffness was a risk factor for worsening renal function, including end-stage renal disease and initiation of dialysis.

Efficacy of high versus conventional dose of ergocalciferol supplementation on serum 25-hydroxyvitamin D and interleukin-6 levels among hemodialysis patients with vitamin D deficiency: A multicenter, randomized, controlled study.

Long-term dialysis involves a chronic inflammatory state and produces a high prevalence of vitamin D deficiency. A clinical trial was conducted in hemodialysis with serum 25-hydroxyvitamin D (25[OH]D) level <30 ng/ml. The conventional-group (N = 35) and the high-dose group (N = 35) were treated with ergocalciferol according to the K/DOQI guidelines and double dosage of ergocalciferol from the recommendation for 8 weeks, respectively. The main outcomes were measured by serum 25[OH]D and interleukin-6 (IL-6). At the end of 8 weeks, a statistically significant greater increase was observed of mean serum 25[OH]D levels and a decrease of mean parathyroid hormone levels in the high-dose group compared with the conventional-dose group. The high dose group had the higher achievement of vitamin D sufficiency than the conventional-dose group (97.4% vs. 76.4%, p = 0.012). No significant difference was found in mean changes of serum IL-6 level in both groups, except subgroup patients with vitamin D deficiency or serum 25[OH]D <20 ng/ml, high dose treatment suppressed serum IL-6 level (-2.67 pg/ml [IQR -6.56 to -0.17], p = 0.039). No differences were observed between the two groups in adverse events. Oral high-dose ergocalciferol supplementation has achieved higher vitamin D sufficiency than standard dose in end stage renal disease patients on dialysis.

Effect of senna glycoside on serum potassium levels among patients on maintenance hemodialysis: A randomized controlled trial.

BACKGROUND: Hyperkalemia is common among end-stage renal disease (ESRD) patients, and consequently contributes to an increased risk of cardiac arrhythmia. Senna glycoside may decrease colonic transit time and potassium colonic reabsorption. METHODS: Patients on hemodialysis were randomized to receive either oral senna glycoside (n = 37) or control (n = 36) for 8 weeks. The primary outcomes were predialysis serum potassium and prevalence of hyperkalemia. RESULTS: At the end of the study, significantly reduced serum potassium concentrations were observed in the senna glycoside compared with the control (-0.32 [95%CI -0.43, -0.04] vs. -0.02 [95%CI -0.12, 0.05] mEq/L, p < 0.001, respectively). The prevalence of hyperkalemia during the study occurred at 13.8% in the control and 5.4% in the senna glycoside (p = 0.309). No serious adverse events were observed. CONCLUSION: Among patients with ESRD on hemodialysis, senna glycoside significantly decreases serum potassium level. Senna glycoside is a safe and possibly effective alternative treatment for hyperkalemia in ESRD.

Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial.

INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients with diabetic kidney disease (DKD). METHODS: This study employed a multicenter, prospective, randomized, placebo-controlled design. A total of 201 participants were enrolled and randomly assigned to one of two groups, one received treatment with 50 mg gemigliptin daily along with standard care for diabetes mellitus for 6 months. The changes in the coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (eGFR), vascular calcification level, and tubular renal injury marker expression were evaluated at baseline and 6 months. RESULTS: In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in the CAC score, CAVI, eGFR, and level of proteinuria over the 6 months of the study did not significantly differ between the gemigliptin and control groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the gemigliptin treatment group compared with the control group. No serious adverse events were observed during the study. CONCLUSION: Our study showed that gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; however, gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. A larger study with a longer follow-up is essential to verify these beneficial effects. Clinical Trials. This trial is registered with ClinicalTrials.Gov Identifier NCT04705506.

Efficacy of Lactulose versus Senna Plus Ispaghula Husk Among Patients with Pre-Dialysis Chronic Kidney Disease and Constipation: A Randomized Controlled Trial.

BACKGROUND: Constipation is a common problem among patients with advanced chronic kidney disease (CKD), leading to a loss of quality of life. Pharmacologic treatments are in common use, but whether lactulose and senna plus ispaghula husk is effecive to treat constipation among patients with pre-dialysis CKD remains unknown. OBJECTIVE: The aim of the study was to compare efficacy of lactulose and senna plus ispaghula husk to treat constipation among patients with pre-dialysis CKD. METHODS: A study was conducted among patients with pre-dialysis CKD receiving a diagnosis of constipation by ROME IV criteria. All subjects were randomly assigned to receive either lactulose or senna plus ispaghula husk daily for 14 days. After a 7-day washout period, the patients were switched to the other substance for another 14 days. Primary outcome was complete spontaneous bowel movement (CSBM) weekly, assessed using a stool diary after each laxative. Secondary outcome measure was the change of stool appearance using the Bristol stool form scale (BSFS). RESULTS: A total of 22 patients underwent randomization. Baseline CSBM and BSFS were 3.4 ± 1.4 and 2.3 ± 1.2 time/week, respectively. At the end of the study, the mean CSBM weekly increased in the lactulose group (mean difference 1.3 ± 1.6, P < 0.001) and the senna plus ispaghula husk group (mean difference 2.1 ± 2.1, P < 0.001) from baseline. Comparing CSBM between lactulose and senna plus ispaghula husk exhibited no significant difference (95% CI -1.2 to 0.06; P = 0.276). BSFS was significantly changed after using ispaghula husk with senna, the mean ± SD of BSFS changed to 1.7 ± 1.8 (p = 0.001) and after use lactulose, the mean ± SD of BSFS changed to 1.6 ± 1.8 (p = 0.001). No significant BSFS change was observed between groups regarding stool appearance. No serious adverse event in either group was found. CONCLUSION: Lactulose and senna plus ispaghula husk were similar in efficacy to treat constipation among patients with pre-dialysis CKD. TRIAL REGISTRATION: Thai Clinical Trials number is TCTR20200818006. Retrospectively Registered 18 August 2020.

Hyperuricemia and Impaired Renal Function: A Prospective Cohort Study.

BACKGROUND: Related studies have demonstrated a relationship of elevated serum uric levels with a decline in kidney function. However, limited evidence exists in a Southeast Asian community-based population. OBJECTIVE: The study aimed to examine the relationship between serum uric acid levels and impaired renal function. METHODS: A prospective cohort study was conducted in the Thai army health checkup population between July 1, 2006 and December 31, 2012. Inclusion criteria included age older than 20 years and baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73 m2. Cox regression analysis was used to evaluate the association between incidence of impaired renal function and baseline serum uric acid quartiles. Impaired renal function was defined as eGFR <60 mL/min/1.73 m2 over 3 months. RESULTS: A total of 9,534 participants (7,474 men and 2,060 women) were enrolled. Cox regression analysis revealed a significant association of serum uric acid level with impaired renal function in the whole population as the unadjusted hazard ratio (HR) (95% CI) of impaired renal function in second, third, and fourth quartiles were 2.1 (1.39, 3.17), 2.39 (1.6, 3.59), and 3.94 (2.71, 5.74), respectively, when compared with serum uric acid in the first quartile, respectively. After adjusting in 2 models, the HR still significantly persisted with similar magnitudes in all quartiles. Higher incidences of impaired renal function were observed among males than among females in all quartiles. Kaplan-Meier curve showed better renal survival rate in the lower quartile groups. Linear regression analysis showed that eGFR negatively correlated with serum uric acid (r = -0.213, p < 0.001). CONCLUSION: Our study suggests that an independent association exists of serum uric acid levels with the incidence of impaired renal function and renal progression in the Southeast Asian community-based population.

Effect of Oral carnosine supplementation on urinary TGF-ß in diabetic nephropathy: a randomized controlled trial.

BACKGROUND: Activation of the transforming growth factor beta (TGF-ß) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-ß synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-ß levels among patients with diabetic nephropathy. METHODS: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-ß level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-ß. RESULTS: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-ß and renal function measurements. Urinary TGF-ß significantly decreased with carnosine supplement (- 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects. CONCLUSIONS: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-ß level that serves as a marker of renal injury in diabetic nephropathy. TRIAL REGISTRATION: Thai Clinical Trials, TCTR20200724002 . Retrospectively Registered 24 July 2020.