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.

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.

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.

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.

Urine albumin dipstick independently predicts cardiovascular and renal outcomes among rural Thai population: a 14-year retrospective cohort study.

BACKGROUND: Albuminuria is an established risk marker for both cardiovascular and renal outcomes. In this study, we expected to use portable and inexpensive test strips to detect urine albumin level for risk stratification in cardiovascular and renal outcomes among rural Thai community. OBJECTIVE: To evaluate the relationship between urine albumin dipstick and cardiovascular and renal complications in rural Thai population. METHODS: We conducted a retrospective study in 635 rural Thai adults who tested urine albuminuria by using commercial urine albumin dipstick and the Micral-albumin test II strips at baseline. The subjects were divided into normoalbuminuria (albumin < 20 mg/L), microalbuminuria (albumin 20-200 mg/L), or macroalbuminuria (Urine dipstick at least 1+ or albumin > 200 mg/L). We collected data on the incidences of primary composite outcomes including cardiovascular or renal morbidity and mortality. Incident density and cox regression were analyzed to evaluate the association between albuminuria status and primary composite outcome. RESULTS: During an average 14-year follow-up, 102 primary composite events occurred including 59 (13.1%), 32 (20.6%) and 11 (39.3%) among 452, 155, and 28 subjects with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively. Incident densities of primary composite outcome were elevated continually according to the degree of albuminuria (9.36, 17.11 and 38.12 per 1000 person-years). Compared with the subjects without albuminuria, subjects with microalbuminuria and macroalbuminuria at baseline had higher risk for primary composite outcome in univariate model. After multivariate analysis was performed, the effect of macroalbuminuria was only persisted with 3.13-fold risk (adjusted HR 3.13; 95% CI 1.40-6.96, P= 0.005). CONCLUSION: Albuminuria from semi-quantitative methods is an important factor predicting cardiovascular and renal risk among subjects in Thai rural population. Our findings support to also incorporating urine albumin dipstick into assessments of cardiovascular risk in the general population.

Urinary epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors for rapid loss of renal function in type 2 diabetic patients with diabetic kidney disease.

BACKGROUND: Increased monocyte chemoattractant protein-1 (MCP-1) and decreased epidermal growth factor (EGF) are promising biomarkers to predict progressive decline in kidney function in non-diabetic kidney diseases. We aimed to evaluate the performance of urinary EGF, MCP-1 or their ratio in predicting rapid decline of GFR in a cohort of Type 2 diabetic patients (T2DM) with diabetic kidney disease (DKD). METHODS: T2DM patients (n = 83) with DKD at high risk for renal progression were followed up prospectively. The baseline urine values of MCP-1 to creatinine ratio (UMCP-1), EGF to creatinine ratio (UEGF), EGF to MCP-1 ratio (UEGF/MCP-1) and albumin to creatinine ratio (UACR) were measured. The primary outcome was a decline in estimated glomerular filtration rate (GFR) of ≥25% yearly from baseline. RESULTS: During follow-up time of 23 months, patients with rapid decline in estimated GFR of ≥25% yearly from baseline had significantly higher baseline levels of UMCP-1, and UACR and lower UEGF and UEGF/MCP-1 ratio. All renal biomarkers predicted primary outcomes with ROC (95%CI) for UMCP-1=0.73 (0.62-0.84), UEGF=0.68 (0.57-0.80), UEGF/MCP-1=0.74 (0.63-0.85), and UACR =0.84 (0.75-0.93). By univariate analysis, blood pressure, GFR, UACR, UMCP-1, UEGF, and UEGF/MCP-1 were associated with rapid decline GFR. By multivariate analysis, UACR, systolic blood pressure, and UMCP-1 or UEGF/MCP-1 were independently associated with rapid GFR decline. CONCLUSIONS: UMCP-1 or UEGF/MCP-1 ratio were associated with rapid renal progression independent from conventional risk factors in DKD.

Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis.

BACKGROUND: Tubulointerstitial injury is important to predict the progression of lupus nephritis (LN). Urine neutrophil gelatinase-associated lipocalin (NGAL) has been reported to detect worsening LN disease activity. Thus, urine NGAL may predict renal outcomes among lupus patients. METHODS: We conducted a prospective multi-center study among active LN patients with biopsy-proven. All patients provided urine samples for NGAL measurement by ELISA collected from all patients at baseline and at 6-month follow-up after induction therapy. RESULTS: In all, 68 active LN patients were enrolled (mean age 31.7 ± 10.0 years, median UPCR 4.8 g/g creatinine level with interquartile range (IQR) 2.5 to 6.9 and mean estimated glomerular filtration rate (GFR) 89.6 ± 33.7 mL/min/1.73 m2). At baseline measurement, median urinary NGAL in complete response, partial response and nonresponse groups was 10.86 (IQR; 6.16, 22.4), 19.91 (IQR; 9.05, 41.91) and 65.5 (IQR; 18.3, 103) ng/mL, respectively (p = 0.006). Urinary NGAL (ng/mL) correlated positively with proteinuria and blood pressure, and correlated negatively with serum complement C3 level and estimated GFR. Based on ROC analysis, urinary NGAL (AUC; 0.724, 95%CI 0.491-0.957) outperformed conventional biomarkers (serum creatinine, urine protein, and GFR) in differentiating complete and partial response groups from the nonresponse group. The urine NGAL cut-off value in the ROC curve, 28.08 ng/mL, discriminated nonresponse with 72.7% sensitivity and 68.4% specificity. CONCLUSION: Urine NGAL at baseline performed better than conventional markers in predicting a clinical response to treatment of active LN except serum complement C3 level. It may have the potential to predict poor response after induction therapy.

Electrolyte disturbances and risk factors of acute kidney injury patients receiving dialysis in exertional heat stroke.

BACKGROUND: Exertional heat stroke (EHS) is a life-threatening illness and leads to multi-organ dysfunction including acute kidney injury (AKI). The clinical significance of abnormal electrolytes and renal outcomes in ESH patients has been poorly documented. We aim to exhibit the electrolyte abnormalities, renal outcomes and risk factors of patients with AKI receiving dialysis in EHS. METHODS: A retrospective cohort study in EHS patients between 2003 and 2014 were conducted. Clinical and laboratory outcomes including serum and urine electrolytes, AKI and dialysis were assessed on admission, during hospitalization and at the time of their discharge from the hospital. A logistic regression analysis was performed for risk factors of acute dialysis. RESULTS: All 66 subjects with mean age 22.1 ± 4.3 years were included. On admission, the common electrolyte disturbances were hypokalemia (71.2 %), hypophosphatemia (59.1 %), hyponatremia (53.0 %), hypocalcemia (51.5 %), and hypomagnesemia (34.9 %). Electrolytes depletion was confirmed as renal loss (potassium loss; 54.2 %, phosphate loss; 86.7 %, sodium loss; 64.7 % and magnesium loss; 83.3 %). During hospitalization ranging from 2 to 209 days, 90.9 % patients suffered from AKI with 16.7 % receiving acute dialysis, and 3 % patients died. At discharge, AKI and electrolyte abnormalities had dramatically improved. The prognosis factors for AKI receiving dialysis were identified as neurological status, renal function and serum muscle enzyme at time of admission. CONCLUSION: The study suggests that hypoelectrolytemia and AKI are frequently observed in patients with EHS. Neurological impairment, impaired renal function, and increased serum muscle enzyme should be considered risk factors of acute dialysis.

BIOPSY-PROVEN BK VIRUS NEPHROPATHY WITHOUT DETECTABLE BK VIREMIA IN A ONE-YEAR POST-KIDNEY TRANSPLANT RECIPIENT.

BK virus nephropathy (BKVN) is an important clinical problem in kidney transplant (KT) recipients. The sequence of disease is usually viruria, viremia and then nephropathy. Diagnosis of BK virus (BKV) infection includes checking BKV DNA in the urine, in the plasma and histology on renal biopsy. This last method is used to diagnose BKVN. We describe a KT patient with BKVN without detectable BK viremia. A 62-year-old female with hypertensive nephropathy underwent renal transplant from a living relative donor in December 2011. Fourteen months after transplantation, her serum creatinine(SCr) rose up from 1.2 to 1.6 mg/dl with biopsy-proven acute antibody-mediated and cellular rejection. After pulse methylprednisolone, plasmapheresis and intravenous immunoglobulin, her SCr decreased to baseline but she subsequently developed cytomegalovirus infection with pancytopenia and transaminitis. The SCr rose to 1.9 mg/dl despite ganciclovir treatment. Renal ultrasound and antegrade pyelogram showed partial obstruction of the proximal ureter with moderate hydronephrosis. A quantitative polymerase chain reaction (PCR) assay for BKV DNA was negative (less than 10 copies/ml). A renal biopsy was performed and the pathology revealed viral cytopathic changes in the tubular epithelium with interstitial inflammation. The renal biopsy also showed BKV nucleic acid sequences by in-situ hybridization confirming BKVN. Immunosuppression regimen was changed to cyclosporine, low-dose prednisolone and leflunomide. A temporary percutaneous nephrostomy was performed. Her renal function improved within one week. The diagnosis of BKVN should be considered in a KT recipient with a rising SCr with or without BK viremia and should be made by renal biopsy.

Benefits of Allopurinol Treatment on Blood Pressure and Renal Function in Patients with Early Stage of Chronic Kidney Disease.

BACKGROUND: Hyperuricemia has been associated with increased risk of endothelial dysfunction, cardiovascular, and renal disease. Allopurinol is a potent xanthine oxidase inhibitor used in hyperuricemic patients. It has been shown to decrease cardiovascular disease and hypertension. However, studies have reported conflicting evidence on its effects on blood pressure (BP) and estimated glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients. OBJECTIVE: To demonstrate the effect of allopurinol on BP and estimated GFR in CKD patients. MATERIAL AND METHOD: Patients with CKD stage II-III were screened for possible study enrollment. All patients received allopurinol 50 mg once daily for 12 weeks. The main outcomes were to observe the changes of BP and GFR after given treatment. RESULTS: Forty-four patients were eligible with mean age of 70.14 ± 8.50 years and mean estimated GFR of 43.22 ± 14.44 mL/ min/1.73 m². Serum uric acid decreased significantly from 8.11 ± 2.68 to 7.05 ± 2.38 mg/dL (p = 0.012) at the end of the study. Allopurinol had also statistically significant lower systolic BP (137.72 ± 14.72 to 131.34 ± 12.10 mmHg, p = 0.019) and diastolic BP (79.63 ± 11.56 to 75.43 ± 9.80 mmHg, p = 0.037) at 12 weeks when compared to baseline. There was significant increased in GFR after treatment (43.22 ± 14.44 vs. 45.34 ± 16.09, mL/min/1.73 m², p = 0.029). No serious adverse effects were noted in any of the treated subjects. Two patients (4.5%) in the treatment group had minor skin reaction. CONCLUSION: The study results confirmed that 12 weeks of allopurinol treatment affects the values of serum uric acid, BP and GFR in early stage of CKD patients who already received standard antihypertensive agents without any significant serious adverse effects.

Efficacy of High vs. Conventional Ergocalciferol Dose for Increasing 25-Hydroxyvitamin D and Suppressing Parathyroid Hormone Levels in Stage III-IV CKD with Vitamin D Deficiency/Insufficiency: A Randomized Controlled Trial.

BACKGROUND: Vitamin D deficiency/insufficiency is common in chronic kidney disease (CKD) patients and it contributes to secondary hyperparathyroidism, which occurs early in CKD. It is not clear whether the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommended doses of ergocalciferol are adequate for correction of vitamin D insufficiency and hyperparathyroidism. OBJECTIVE: To evaluate the parathyroid hormone (PTH)-lowering effect, safety, and tolerability of high-dose ergocalciferol compared with conventional-dose ergocalciferol in CKD subjects. MATERIAL AND METHOD: We enrolled CKD stage III-IV patients who had 25-hydroxyvitamin D (25-OH-D) level <30 ng/mL. The patients were randomized into two groups, control group treated with ergocalciferol as recommended by K/DOQI guidelines, and treatment group treated with double dosage of ergocalciferol from the recommendation. We compared serum 25-OH-D, intact-PTH, phosphate, calcium, and bone biomarker levels, during the 8-week intervention. RESULTS: Sixty-eight patients were included (34 controls and 34 treatments). Baseline characteristics of both groups were similar except calcium level 9.12 ± 0.56 mg/dL in control group and 9.44 ± 0.38 mg/dL in treatment group (p = 0.009), but not clinically significant. At the end of the 8-week, the mean 25-OH-D level significantly increased from 20.99 ± 6.68 to 33.41 ± 8.92 ng/mL in the treatment group (p = 0.001) and increased from 20.84 ± 7.21 to 23.42 ± 7.89 ng/mL in the control group (p = 0.026). There was also a significantly greater increase of 25-OH-D levels in the treatment group. Additionally, PTH levels significantly decreased from 90.75 ± 67.12 to 76.40 ± 45.97 at 8 weeks (p = 0.024) in the treatment group, and there was no change in the control group (97.14 ± 83.52 vs. 101.13 ± 95.03 pg/mL, p = 0.546). Serum calcium, phosphate, and adverse effects did not significantly change in either group throughout the study. CONCLUSION: In addition to improving vitamin D levels, oral high-dose ergocalciferol was safe and had a beneficial effect in decreasing PTH in patients with stage III-IV of CKD.

A comparative study of efficacy and safety of the lyophilized powder alpha-erythropoietin and the liquid form alpha-erythropoietin for hemoglobin maintenance in patients with hemodialysis treatment.

BACKGROUND: Insufficient production oferythropoietin (EPO) is the primary cause ofanemia in patients with chronic kidney disease (CKD). The EPO treatment is an established treatment for renal anemia. The study investigated the therapeutic outcome between lyophilized powder and liquid form of EPO alpha by intravenous (IV) administration in hemoglobin maintenance of anemic treatment for CKD patients receiving hemodialysis. MATERIAL AND METHOD: Forty patients were randomly assigned to either lyophilized powder of EPO alpha (treatment, n = 21) or liquidform of EPO alpha (control, n = 19) for 12 weeks by lVadministration. The hemoglobin was maintained within the target range of 10. 0 to 12.0 g/dL by adjusting the dosage of EPO. The clinical and biochemical profiles including transferrin saturation andferritin were measured. Adverse events were documented. RESULTS: The mean hemoglobin ofboth groups at baseline was 11.2±0.6 g/dL. Mean hemoglobin and mean hematocrit levels at baseline, and follow-up data of both groups were not statistically different. The mean weekly dosage of EPO in the treatment and control groups had no statistical significance within the same group and between groups as well. Stable hemoglobin levels were maintained without EPO dosage adjustment in the majority ofpatients in both groups (treatment group, 90.5%, control group, 94.7%). During the 12-week study period, no serious side effect was detected CONCLUSION: The present study demonstrated that the lyophilizedpowder ofEPO alpha was effective and safe as the standard liquid form of EPO alpha when it was administered by IV route in hemoglobin maintenance of anemia treatment.

Short-term administration of an angiotensin II receptor blocker in patients with long-term hemodialysis patients improves insulin resistance.

BACKGROUND: Insulin resistance is commonly observed in uremic patients. Angiotensin II receptor blockers (ARB) are reported to act as insulin sensitizers in the animal model of hypertension and hypertensive patients. The authors investigated the effects of valsartan on insulin resistance and glucose metabolism in patients with long-term hemodialysis in the prospective, randomized controlled study. MATERIAL AND METHOD: Thirty-three hemodialysis patients were randomized into two treatment groups, valsartan 80 to 320 mg/day (n = 18) or non-renin-angiotensin-aldosterone-system blocking antihypertensive agents (control, n = 15), treated for 12 weeks. Insulin resistance determined by homeostasis model assessment (HOMA-IR), fasting plasma glucose (FPG), fasting plasma insulin, and blood pressure monitoring were measured during the study. RESULTS: At baseline, metabolic profiles did not significantly differ between the treatment and the control groups. After 12 weeks of treatment, the valsartan group significantly improved HOMA-IR from 2.6 +/- 0.9 to 2.3 +/- 0.7 (p = 0.041) and significantly decreased FPG from 90.1 +/- 15.1 to 84.8 +/- 13.2 mg/dL (p = 0.008). In contrast, the control group was not associated with any significant changes in HOMA-IR, FPG, and fasting insulin levels. At the end of 12-week treatment, HOMA-IR, FPG, and fasting insulin levels were not significantly different between the two groups. CONCLUSION: These results indicate that the antihypertensive action of valsartan improves glucose metabolism by improving the peripheral insulin sensitivity in subjects with long-term dialysis.

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.

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.

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.

Obesity and its relation to chronic kidney disease: a population-based, cross-sectional study of a Thai army population and relatives.

AIM: Obesity represents a significant problem in patients with cardiovascular disease and chronic kidney disease (CKD). The aim of the present study was to investigate the association between body mass index (BMI) and CKD in Thai individuals. METHODS: Participants underwent general health screening. Overweight, weight at risk, obese I and obese II were defined as having a BMI ≥23 kg/m(2), 23-24.9 kg/m(2) , 25-29.9 kg/m(2) and ≥30 kg/m(2), respectively. Waist circumference ≥ 90 cm for men and > 80 cm for women were represented by abdominal obesity. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2). An estimate of the GFR was obtained by the four-variable Modification of Diet in Renal Disease (MDRD) equation. RESULTS: The study population had 12 348 males and 3009 females. The survey population had a 7.5% prevalence of CKD. There was also a significant graded relationship between the degrees of overweight with the prevalence of CKD. Mean BMI were 25.36 ± 3.29 kg/m(2) for CKD subjects and 24.04 ± 3.13 kg/m(2) for non-CKD subjects (P < 0.001). Prevalence of overweight and abdominal obesity in the participants with CKD were found to be higher than in those without CKD (overweight, 77.6% vs. 61.6%, P < 0.001; abdominal obesity, 35.7% vs. 25.3%, P < 0.001). In a multivariate logistic regression analysis, weight at risk (adjusted odds ratio 1.29; 95% CI 1.07-1.54), obese I (adjusted odds ratio 1.58; 95% CI 1.33-1.87) and obese II (adjusted odds ratio 1.65; 95% CI 1.24-2.19) were associated with CKD. CONCLUSION: Our data showed that overweight and obesity were associated with CKD in Thai members of the army population and their relatives undergoing a general health screening, independently of age, gender, blood pressure, serum lipid, uric acid and glucose levels.

Vitamin D insufficiency and deficiency with stages of chronic kidney disease in an Asian population.

BACKGROUND: Vitamin D insufficiency is associated with proteinuria and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined the significance of vitamin D insufficiency as a contributing factor for the development of ESRD in the Asian chronic kidney disease (CKD) population. METHODS: Authors examined the relationship between vitamin D status and the staging of CKD using data from an outpatient clinic-based screening in 2,895 Thai CKD patients. Serum levels of 25-hydroxyvitamin D were analyzed according to CKD stages. Vitamin D deficiency and insufficiency were defined as a serum 25-hydroxyvitamin D concentration < 10 ng/mL and 10-30 ng/mL, respectively. RESULTS: The mean (SD) 25-hydroxyvitamin D levels were significantly lower according to severity of renal impairment (CKD stage 3a: 27.84 ± 14.03 ng/mL, CKD stage 3b: 25.86 ± 11.14 ng/mL, CKD stage 4: 24.09 ± 11.65 and CKD stage 5: 20.82 ± 9.86 ng/mL, p<0.001). The prevalence of vitamin D deficiency/insufficiency was from CKD stage 3a, 3b, 4 to 5, 66.6%, 70.9%, 74.6%, and 84.7% (p<0.001). The odds ratio (95% CI) of vitamin D insufficiency/deficiency (serum 25-hydroxyvitamin D ≤ 30 ng/mL) and vitamin D deficiency (serum 25-hydroxyvitamin D < 10 ng/mL) for developing ESRD, after adjustment for age, gender, hemoglobin, serum albumin, calcium, phosphate and alkaline phosphatase were 2.19 (95% CI 1.07 to 4.48) and 16.76 (95% CI 4.89 to 57.49), respectively. CONCLUSION: This study demonstrates that 25-hydroxyvitamin D insufficiency and deficiency are more common and associated with the level of kidney function in the Thai CKD population especially advanced stage of CKD.

Apolipoprotein E genetic polymorphisms and the development of nephropathy in type 2 diabetes.

BACKGROUND: Apolipoprotein E (ApoE) polymorphisms have been proposed as the risk factor for the development of diabetic nephropathy (DN). A number of studies have investigated the association between the ApoE isoforms and DN. However the findings remain inconclusive. OBJECTIVE: To determine the association between the ApoE polymorphisms and DN. MATERIAL AND METHOD: Two hundred thirty patients with type 2 diabetes were divided into two groups, patients with clinically diagnosed DN and normoalbuminuric patients. ApoE genotypes were determined by RT-PCR analysis. Student's t-test, ANOVA test, Chi-square test, odds ratio, and logistic regression was performed. RESULTS: The frequency of ApoE4 genotype was significantly lower in DN patients (8.7%) than in normoalbuminuric patients (21.7%). Logistical regression analysis showed that subjects with ApoE4 genotype (adjusted OR = 0.43; 95% CI: 0.19-0.99) were less likely to have DN than subjects with ApoE3 genotype. Furthermore, when analyzed only in patients with overt DN vs. patients with normoalbuminuria, the frequency of e4 allele was decreased in overt DN (2.8% vs. 21.7%, adjusted OR = 0.13; 95% CI: 0.03-0.57) and the frequency of e2 allele was increased (25.4% vs. 13.0%, adjusted OR = 2.34; 95% CI: 1.02- 5.38). CONCLUSION: ApoE4 genotype is associated with protection from type 2 DN, and subjects with e2 allele have increased risk of developing type 2 overt DN.