Somnuek Domrongkitchaiporn

Risk Factors for Development of Decreased Kidney Function in a Southeast Asian Population: A 12-Year Cohort Study

End-stage kidney disease has become an increasing burden in all regions of the world. However, limited epidemiologic data on chronic kidney disease in Southeast Asian populations are available. Therefore, a cohort study over a period of 12 yr (1985 to 1997) in 3499 employees of the Electric Generation Authority of Thailand, aged 35 to 55 yr, was conducted to determine the prevalence of decreased kidney function and risk factors associated with future development of decreased kidney function. The prevalence of decreased kidney function (GFR <60 ml/min) increased from 1.7% (95% confidence interval [CI], 1.3 to 2.1) in 1985 to 6.8% (95% CI, 5.7 to 7.9) in 1997, and the prevalence of elevated serum creatinine was 6.1% (95% CI, 5.3 to 6.9) and 16.9% (95% CI, 15.3 to 18.5) in 1985 and 1997 surveys, respectively. The adjusted odds ratio for future development of decreased kidney function was 2.57 (1.0 to 6.81) for systolic hypertension (>159 mmHg), 1.82 (1.12 to 2.98) for hyperuricemia (>6.29 mg/dl), 1.68 (1.02 to 2.77) for elevated body mass index (>24.9 kg/m(2)) compared with subjects with systolic BP <140 mmHg, serum uric acid <4.5 mg/dl, and body mass index 20.8 to 22.8 kg/m(2). The rising prevalence of decreased kidney function in this population resulted mainly from the increasing prevalence of the risk factors in the population. Screening to detect decreased kidney function and early intervention to modify the associated risk factors should be considered in otherwise healthy individuals. Future studies are also necessary to determine whether implementation of these measures results in a reduction of ESRD incidence in the population.

Ceftriaxone Compared with Sodium Penicillin G for Treatment of Severe Leptospirosis

A prospective, open-label, randomized trial at Khon Kaen Hospital (Thailand) was conducted from July 2000 through December 2001 to compare the clinical efficacies of ceftriaxone and sodium penicillin G for the treatment of severe leptospirosis. A total of 173 patients with severe leptospirosis were randomly assigned to be treated with either intravenous ceftriaxone (1 g daily for 7 days; n=87) or intravenous sodium penicillin G (1.5 million U every 6 h for 7 days; n=86). The primary outcome was time to fever resolution. Survival analysis demonstrated that the median duration of fever was 3 days for both groups. Ten patients (5 in each group) died of leptospirosis infection. There were no statistically significant differences in the duration of organ dysfunction. Ceftriaxone and sodium penicillin G were equally effective for the treatment of severe leptospirosis. Once-daily administration and the extended spectrum of ceftriaxone against bacteria provide additional benefits over intravenous penicillin.

Prognostic factors of death in leptospirosis: a prospective cohort study in Khon Kaen, Thailand

OBJECTIVES To determine the prognostic factors of death in leptospirosis. METHODS A prospective cohort study was conducted. One hundred and twenty one patients with clinically compatible leptospirosis, serologically confirmed, were recruited in this study. Clinical presentations and biochemical parameters on admission were selected as input variables for survival analysis. Multivariable Cox regression model was used to identify the prognostic factors of death. RESULTS Most patients were male (94.2%), with the mean +/-SD age of 38+/-13.4 years; 77.4% of them were farmers. Among the 121 patients, 1206 patient-days were observed. Seventeen patients died. Overall mortality rate was 1.4 per 100 patient-days (95% confidence interval [CI]: 0.9-2.3). The causes of death included: a) pulmonary hemorrhage in eight (47.1%) patients; b) complicated acute renal failure in three (17.6%) patients; c) multiple organ failure in three (17.6%) patients; d) acute respiratory distress syndrome in two (11.8%) patients, and e) irreversible shock in one (5.9%) patient. Four independent risk factors associated with the mortality were identified, including hypotension (relative risk [RR], 10.3; 95% CI, 1.3-83.2; P<0.05); oliguria (RR, 8.8; 95% CI, 2.4-31.8; P<0.01); hyperkalemia (RR, 5.9; 95% CI, 1.7-21; P<0.01), and presence of pulmonary rales (RR, 5.2; 95% CI, 1.4-19.9; P<0.05). CONCLUSION The presence of oliguria, hyperkalemia, pulmonary rales, or hypotension on admission in patients with leptospirosis indicated high risk of death. Intensive care and early intervention should be provided for patients who present with these risk factors.

Abnormalities in Bone Mineral Density and Bone Histology in Thalassemia

This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF‐I was reduced and may modulate the reduction of bone mass.

Sodium thiosulfate delays the progression of coronary artery calcification in haemodialysis patients

BACKGROUND Coronary artery calcification (CAC) is prevalent among haemodialysis patients and predicts cardiovascular mortality. In addition to modifying traditional cardiovascular risk factors, therapy aimed at lowering serum phosphate and calcium-phosphate product has been advocated. Sodium thiosulfate, through its chelating property, removes calcium from precipitated minerals decreasing calcification burden in calcific uraemic arteriolopathy and soft tissue calcification. The effect of sodium thiosulfate on CAC in haemodialysis patients has never been studied. METHODS Eighty-seven stable chronic haemodialysis patients underwent multi-row spiral computed tomography and bone mineral density (BMD) measurement. Patients with a CAC score >or=300 were included to receive intravenous sodium thiosulfate infusion twice weekly post-haemodialysis for 4 months. CAC and BMD were re-evaluated at the end of the treatment course. RESULTS Progression of CAC occurred in 25% and 63% of the patients in the treatment and control group, respectively (P = 0.03). CAC score was unchanged in the treatment group but increased significantly in the control group. BMD of the total hip declined significantly in the treatment group. In multivariate analysis adjusted for factors that influenced CAC progression, therapy with sodium thiosulfate was an independent protective factor (odds ratio = 0.05, P = 0.04). Major side effects were persistent anorexia and metabolic acidosis. CONCLUSIONS The effect of sodium thiosulfate in delaying the progression of CAC is encouraging and will require a larger study. Determination of the safe therapeutic window is necessary in order to avoid bone demineralization.

Risk of calcium oxalate nephrolithiasis after calcium or combined calcium and calcitriol supplementation in postmenopausal women

Abstract: Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n= 28) or 750 mg of calcium carbonate plus 0.5 mg calcitriol (n= 25) daily. Mean ± SEM for age was 65.3 ± 1.1 years, body weight 53.5 ± 1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius’s index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90 ± 0.43 mmol/day; after treatment 3.58 ± 0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87 ± 0.41 mmol/day; after treatment, 4.08 ± 0.57 mmol/day; p<0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17 ± 0.39; after treatment, 1.36 ± 0.28) or after calcium plus calcitriol (baseline, 1.09 ± 0.17; after treatment, 1.09 ± 0.19). However, after treatments, 12 subjects (23%) – 6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement – had high AP(CaOx) values (greater than the upper limit of 95% CI for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21 ± 0.74 for urinary calcium, 1.01 ± 0.19 for urinary oxalate, and 2.23 ± 0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis.

Indices of Iron status in continuous ambulatory peritoneal dialysis patients

Data for iron-status indices in continuous ambulatory peritoneal dialysis patients are limited. The reliability of commonly used indices for the diagnosis of iron-deficiency anemia in peritoneal dialysis patients is still unknown. To study diagnostic values of iron-status indices, including serum ferritin, transferrin saturation, reticulocyte hemoglobin content, and bone marrow-stainable iron, 21 stable anemic peritoneal dialysis patients who have been treated with erythropoietin and oral iron supplementation for more than 3 months were enrolled in this study. The mean age was 51.4 +/- 2.9 years; dialysis duration, 28.7 +/- 5.1 months; initial hemoglobin, 8.4 +/- 0.2 g/dL; erythropoietin dosage, 71 +/- 2 micro/kg/wk; serum albumin, 3.5 +/- 0.1 g/dL; intact parathyroid hormone (PTH), 233 +/- 44 ng/mL; serum ferritin, 643 +/- 135 ng/mL; transferrin saturation, 33.93% +/- 3.9%; and reticulocyte hemoglobin content, 31.6 +/- 4 pg. Bone marrow aspiration was performed in all patients to determine marrow iron content and exclude hematological disorders. All patients were treated with 1, 000 mg of intravenous ferric saccharate infusion in two divided doses more than 1 week apart. Patients who responded to the iron infusion within 3 months by increasing serum hemoglobin of greater than 1 gm/dL more than baseline were defined as being functional iron deficient before the intravenous iron infusion. Serum ferritin, transferrin saturation, and reticulocyte hemoglobin content were followed serially after iron infusion. Fifteen patients (71.4%) responded to the iron administration, indicating iron deficiency. Nine of 13 (69%) patients with the presence of bone marrow-stainable iron still responded to intravenous iron supplementation, suggesting functional iron deficiency. Absence of bone marrow-stainable iron was not a sensitive marker for the diagnosis of iron deficiency, 25% sensitivity. No single value of iron-status indices that can definitely exclude iron-deficiency anemia in peritoneal dialysis patients was found. Therefore, failure to increase hemoglobin concentration after intravenous iron administration should be shown before excluding iron-deficiency anemia as a cause of poor erythropoietic response to erythropoietin therapy.

Mineral metabolism and outcomes in chronic kidney disease stage 2–4 patients

BackgroundMarked hyperphosphatemia, hyperparathyroidism and 25-hydroxyvitamin D deficiency are associated with mortality in dialysis patients. Such data in chronic kidney disease stage 2–4 population are limited. It has been suggested that high-normal serum phosphate predicts worse renal and patient outcomes. The data regarding parathyroid hormone and outcomes in this population is limited. The present study examined mineral metabolism and its association with the development of end-stage renal disease and mortality in stage 2–4 chronic kidney disease patients.MethodsThis is a prospective cohort study that included 466 non-dialysis chronic kidney disease stage 2–4 patients. Mineral parameters were obtained at the time of enrollment and the patients were followed prospectively for 25 (1–44) months or until they reached the endpoints of end-stage renal disease or mortality.ResultsHyperparathyroidism and 25-hydroxyvitamin D deficiency began to occur in the early stages of chronic kidney disease, whereas significant hyperphosphatemia only developed in the later stages. High-normal and mildly elevated serum phosphate (>4.2 mg/dL) predicted the composite outcome of end-stage renal disease or mortality after adjustments for cardiovascular risk factors, chronic kidney disease stage and other mineral parameters. Parathyroid hormone levels above the upper limit of normal (>65 pg/mL) predicted the future development of end-stage renal disease and the composite outcome of end-stage renal disease or mortality after adjustments. 25-hydroxyvitamin D deficiency (<15 ng/mL) was also associated with worse outcomes.ConclusionsIn chronic kidney disease, hyperparathyroidism developed prior to significant hyperphosphatemia confirming the presence phosphate retention early in the course of chronic kidney disease. High-normal serum phosphate and mildly elevated parathyroid hormone levels predicted worse renal and patient outcomes. This data emphasizes the need for early intervention in the care of chronic kidney disease stage 2–4 patients.

Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with calcium or combined calcium and estrogen

BACKGROUND Recent studies showed that postmenopausal women lost less bone mass when supplemented with calcium or estrogen therapy. However, the safety of the treatments in terms of the risk of calcium oxalate stone formation is unknown. We therefore conducted this study to determine the alteration in calcium oxalate supersaturation after calcium supplement or after combined calcium and estrogen therapy in postmenopausal osteoporotic women. METHODS Fifty-six postmenopausal women were enrolled in this study. All subjects were more than 10 years postmenopausal with vertebral or femoral osteoporosis by bone mineral density criteria. They were randomly allocated to receive either 625 mg of calcium carbonate (250 mg of elemental calcium) at the end of a meal three times a day (group A, n=26) or calcium carbonate in the same manner plus 0.625 mg/day of conjugated equine estrogen and 5 mg medrogestone acetate from day 1-12 each month (group B, n=30). The age (mean +/- S.E.M.) was 66.3 +/- 1.2 and 65.1 +/- 1.1 years, weight 54.1 +/- 1.2 and 55.3 +/- 2.1 kg, in group A and group B, respectively. Urine specimens (24-h) were collected at baseline and 3 months after treatment for the determination of calcium oxalate saturation by using Tiseliuss index (AP(CaOx)) and calcium/citrate ratio. RESULTS After 3 months of treatment, there was no significant alteration from baseline for urinary excretion of calcium, citrate and oxalate. Urinary phosphate excretion was significantly reduced (6.3 +/- 0.7 vs. 5.1 +/- 0.7 mmol/day for group A and 8.2 +/- 0.9 vs. 5.8 +/- 0.7 mmol/day for group B, P<0.05), whereas net alkaline absorption was significantly elevated (10.1 +/- 3.6 vs. 20.1 +/- 4.4 meq/day for group A and 4.8 +/- 3.2 vs. 19.9 +/- 3.6 meq/day for group B, P<0.05). Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from the corresponding values after treatment in both groups; calcium/citrate: 10.1 +/- 3.1 vs. 10.1 +/- 2.5 for group A and 9.3 +/- 1.8 vs. 11.9 +/- 2.5 for group B and AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/- 0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively. CONCLUSIONS Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.

Dialysis dose and risk factors for death among ESRD patients treated with twice-weekly hemodialysis: a prospective cohort study.

Background/Aims: We aimed to define the dosing and risk factors for death in patients undergoing twice-weekly hemodialysis. Methods: A prospective multi-center cohort study was conducted with one-year observation. Patients treated with twice- or thrice-weekly hemodialysis were identified. Death and first admission were the outcomes. spKt/V was a factor of interest. Results: We enrolled 504 twice-weekly and 169 thrice-weekly hemodialysis patients. The mean weekly values of spKt/V in the two groups were 3.4 and 5.1. The one-year survival rate and times to hospitalization were similar in both groups. The hazard ratios for death in higher spKt/V quartile was not associated with lower mortality, p = 0.70. The four significant predictors for death were serum albumin, HR = 2.6, current smoking, HR = 19.3, age, HR = 1.1, and the Index of Coexistent Disease [ICED], HR = 1.9. Conclusion: The effect of spKt/V on short-term mortality was not obvious in twice-weekly dialysis patients. Attention should be paid to patients who smoke, have hypoalbuminemia, are elderly, or have a high ICED.