Crystalline composition and etiologic factors of kidney stone in Thailand : update 2007.

Objective: The etiology of kidney stone is multifactorial including environmental, behavioral and genetic. Insights about predisposing causes and mineral composition are mandatory for better management of kidney stone disease. The present hospital-based study aims to explore the mineral constituents and etiologic risks of kidney stones in Thai patients from the four geographic regions of the country. Method: Two hundred and fifty six kidney stone patients from four geographic regions of Thailand, including the northeastern (n=103), the northern (n=81), the central (n=47) and the southern (n=25) were recruited in this study. Of these, 144 patients completed the food frequency questionnaire to assess the kidney stone risk. Mineral composition of stones were analyzed by Fourier transformed infrared spectrometry. Results: Kidney stone frequently affected peoples aged 40-49 years. Only 31.9 % of patients had a positive family history of renal stone. Calcium oxalate (CaOx) stone was the most prevalent type (73.8 %). Uric acid (UA) stone was found in 16.0 % commonly affected peoples aged 60-70 years. Mixed stones, notably CaOx mixed with calcium phosphate (CaP), were more prevalent than pure stones. The food frequency questionnaire data showed that 59.7 % of stone patients consumed less than two liters of water per day. Low intakes of fruits and vegetables were notably present. In contrast, high consumption of rice was observed in over 65 % of stone patients. Conclusion: CaOx mixed with CaP was the most prevalent stone type. UA stone was more likely to occur in the elderly. Kidney stone patients were found to consume less-than-adequate amounts of water, food high in carbohydrates, along with low consumtion of fruits and vegetables. These dietary habits might be risk factors in stone development among the Thai population.

Study of cyclosporine level at 2 hours after administration in preoperative kidney transplant recipients for prediction of postoperative optimal cyclosporine dose.

OBJECTIVE: Absorption profiling of cyclosporine is a current concept of drug monitoring. A single blood concentration measurement 2 hours after cyclosporine administration (C2) has been shown to be a good predictor of drug exposure and clinical outcome. The recommendation states that achieving the recommended target level of 1700 +/- 340 ng/ml within 3-5 days after renal transplantation is associated with a lower rate of acute rejection and nephrotoxicity. The high variation of pharmacokinetic profile and short limited time during early post-transplantation period make it hard to adjust the cyclosporine dose that can reach that target level on time. The present study was designed to be a method to predict the optimal pre-transplant CsA dose. MATERIAL AND METHOD: Eleven living-related kidney transplant recipients were recruited to receive cyclosporine and were monitored for C2 concentration during the 2 weeks before operation by the designed method. The pre-transplant empirical dose of 3.5 mg/kg/dose every 12 hours were assigned to all patients. The first predicted dose was estimated by using C2 concentration of 1,700 ng/mL. The first predicted dose was prescribed to the patients. The second predicted dose was estimated by using C2 concentration of the first predicted dose. All patients received the average of the first and the second predicted doses of cyclosporine within 12-24 hrs before transplantation and until the 3rd day after transplantation. RESULTS: Nine out of 11 patients (81.81%) reached the target C2 level on the 3rd day after transplantation without any serious side effect and complications. The most common side effect was nausea and a flushing sensation that usually abated with a later dose after transplantation. CONCLUSION: The early postoperative optimal cyclosporine dose can be effectively predicted by pre-transplant C2 measurement as conducted in the present study.

Accuracy of using 30-minute post-dialysis BUN to determine equilibrated Kt/V.

BACKGROUND: The equilibrated Kt/V (eKt/V), a clinical index of hemodialysis adequacy, can be calculated by several means. The commonly used methods are second generation of natural logarithm by Daugirdas and rate adjustment methods. However these two methods used immediate post-dialysis blood urea nitrogen (BUN) (C0). The authors investigated the accuracy of 30-minute post-dialysis BUN (C30), equilibrated BUN at the end of urea rebound time, to determine the eKt/V MATERIAL AND METHOD: We measured 7 values of eKt/V in 30 hemodialysis sessions by using the 5 following methods: 1). Empirical method (Emp) 2). Smye method (Sm) 3). Daugirdas method using C0 and C30 (Dau0, Dau30) 4). Rate adjustment method using C0 and C30 (Rate0, Rate30) 5). Double Pool urea kinetic model (DP), and compared with the gold standard values calculated by the modified Direct Dialysate Quantitative method (mDDQ). RESULTS: All patients had adequate hemodialysis with eKt/V (mDDQ) = 1.80 + 0.22. Compared with mDDQ, the median of absolute difference of eKt/V were Rate30 (0.10); Dau30 (0.11), Rate0 (0.11), Sm (0.11); Emp (0.13); DP (0.15); Dau0 (0.35) while the correlation coefficient (r2) were 0.926, 0.948, 0.785, 0.629, 0.551, 0.833,and 0.806 respectively. CONCLUSION: By using 30-minute post-dialysis BUN to calculate, the values of eKt/V by Daugirdas and rate adjustment methods were associated with better accuracy and correlation than immediate post-dialysis BUN. In the demand of the accurate eKt/V measurement, the Dau30 and Rate30 may be the suitable method to determine the eKt/V in clinical hemodialysis.

Alleviation of renal and pulmonary injury by immunomodulation in leptospirosis: hamster model.

OBJECTIVE: Severe leptospirosis manifestations include acute renal failure, caused by acute interstitial nephritis and pulmonary hemorrohage. Spirochete invasion and toxicity of outer membrane cause robust inflammatory host responses. These responses lead to the generation of cytokines, chemokines, and inflammatory cell infiltrations which result in severe organ dysfunctions. The immunomodulation by the modulation of host immune response may alleviate the renal and pulmonary injury. The authors determined whether the current immunosuppressive agents could alleviate the inflammation and minimize the organ injury in hamster model. MATERIAL AND METHOD: The animal experiments were conducted with the approval of The Ethical Research Committee of Chulalongkorn University Hospital. The leptospira interrogan serovar pyrogenese was isolated from a wild rat. The spirochete was grown in Fletcher's semisolid media and after subcultures were transferred to the Fletcher's liquid media. An amount of 0.5 ml of the spirochete culture media containing 1 x 10(8) leptospires/ml was intraperitoneally injected to golden Syrian hamsters (Mesocrietus auratus), age 4-6 weeks, weighing 60-80 grams. The hamsters were randomed into 5 groups (n = 4 in each group) namely, 1) Normal group (Control group), 2) Leptospira group, 3) CsA group (leptospira with cyclosporine feeding, 100 mg/kg/ day), 4) Rapa group (leptospira with rapamicin feeding, 0.6 mg/kg/day), and 5) Irra group (leptospira with irradiation). Cyclosporine and rapamicin were started at day 0 after the spirochete injection. Gamma ray dose 200 cGy was irradiated to the hamster 3 days before the spirochete inoculation. The animals were autopsied or euthanized if expired or at day 5 post inoculation. The blood samples for BUN, and creatinine were drawn before the inoculation and at autopsy or euthanasia. RESULTS: The inoculation of L Interrogan 0.5 ml (1 x 10(8) leptospires/ml) without immunomodulation cause mortality of all animals at day 4 or day 5 post inoculation. The blood chemistry showed acute severe azotemia. The autopsy findings revealed severe interstitial nephritis and severe pulmonary hemorrhage. The hamsters in the Rapa group had only minimal pulmonary hemorrhage and minimal focal interstitial inflammation of kidney. There were cytoadherance of inflammatory cells to the endothelial cells in lungs and kidneys without the intrusion into the interstitium. The blood chemistry in Rapa group showed mild elevation of BUN and Cr. The immunomodulation by cyclosporine and irradiation did not alleviate the disease. On the contrary, cyclosporine and irradiation caused more severe histopathology. CONCLUSION: The immunomodulation by rapamicin in leptospirosis in hamsters could alleviate the kidney and pulmonary injuries. The up-regulation of IL-2 in peripheral blood lymphocytes did not result in the kidney and pulmonary injuries.

Citrate attenuates tubulointerstitial fibrosis in 5/6 nephrectomized rats by decreasing transforming growth factor-beta1.

OBJECTIVE: Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD) in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study examines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human. MATERIAL AND METHOD: Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups. Renal function, renal histopathology, renal alpha-Smooth muscle actin (SMA), and renal transforming growth factor (TGF)-beta1 were determined immediately and at the 8th week after operation. RESULTS: Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups were 2.39 +/- 0.25 and 2.35 +/- 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups (p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis score, increased alpha-SMA positive cells, and renal tissue TGF- beta1 when compared with the sham groups. The 5/ 6cit group, when compared with the 5/6tap group, had higher GFR (2.51 +/- 0.22 vs 1.17 +/- 0.33 mL/kg/min; p < 0.05), lower fibrosis score (1.83 +/- 0.88 vs 3.0 +/- 0.4, p < 0.001), lower alpha-SMA activity (159 +/- 2.9 vs 187 +/- 12.3 cells per 1000 interstitial cells, p < 0.05), and lower renal TGF-beta1 levels (1771.3 +/- 239.5 vs 4716.9 +/- 871.2 pg/mg protein, p < 0.005). CONCLUSION: As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-beta1 levels and additionally by attenuating the increased myofibroblast activity.

Pharmacokinetics of sirolimus in Thai healthy volunteers.

Sirolimus, a novel immunosuppressive drug, has been used in kidney transplant recipients to minimize calcineurine inhibitor (CNI) and steroid toxicities. Likewise CNI, Sirolimus's pharmacokinetics have both inter and intra-individual pharmacokinetic variations. Due to ethnic differences, the recommended oral loading dose of 6 mg and oral maintenance dose of 2 mg per day for Caucasian patients and oral loading dose of 10 mg and oral maintenance dose of 5 mg per day for African-American patients may not be appropriate for Asian recipients. We, therefore conducted the pharmacokinetic study of sirolimus in Thai population, aimed to delineate the appropriate sirolimus dose for further clinical use. The study was performed in 12 healthy Thai volunteers. After an over night fasting, a single oral dose of 6 mg sirolimus was given. The complete pharmacokinetic study was done by UVhigh performance liquid chromatography (HPLC-UV) to measure the whole blood sirolimus level at 0.5 hour after the dose (C0.5) and then C1, C1.5, C2, C2.5, C3, C4, C6, C8, C12, and C24 hours. A complete area under the concentration time curve from 0-24 hours (AUC(0-24 hr)) was calculated by using the trapezoidal rule. The mean (+/- SD) time to maximal concentration (Tmax) was 1.45 +/- 0.5 hr (range 1-3 hrs). The maximal (Cm) and minimal plasma concentration (Ctroug) for sirolimus were 25.3 +/- 6.1 ng/ml (range 18.10 - 40 ng/ml) and 4.47 +/- 0.57 ng/ml (range 2.90 - 7.20) ng/ml respectively. The AUC(0-24 hr) were 187.9 +/- 48.2 ng * hr/ml (range 151.3 - 294.8 ng * hr/ml). Sirolimus level at 4 hr post-dose had the best of correlation with AUC(0-24 hr) (Pearson correlation = 0.76, p < 0.007). One volunteer had a very high sirolimus level. This subject's pharmacokinetic data showed AUC(0-24 hr) of 256 ng * hr/ml and Cmax of 40 ng/ml. In conclusion, the oral loading dose of 6 mg of sirolimus in Thai volunteers did not achieve the recommended therapeutic level (5-10 ng/ml) in most subjects. There are differences in pharmacokinetics of sirolimus between Thais and Caucasians.

Etiologies of glomerular diseases in Thailand: a renal biopsy study of 506 cases.

BACKGROUND: The nationwide renal registry has not yet been organized in Thailand, and the literature contains no registry of renal pathologic finding across the Southeast Asian (SEA) countries in the modern era when electron microscopy (EM) is routinely available. OBJECTIVE: The aim of the present study was to examine the prevalence of renal pathology in Thai population. MATERIAL AND METHOD: The authors reviewed the case file and renal biopsy specimens of King Chulalongkorn University Hospital to identify all adult native renal biopsy specimens received from January 2001 to December 2004, investigating prevalence and clinical and histological data. Biopsy of renal graft and in cases of trauma and tumors the authors excluded. Most of the biopsy specimens obtained The authorsre analyzed using light microscopy (LM), immunofluorescense (IF), and EM. Final diagnosis was made for each patient based on clinicopathologic correlations. RESULTS: A total of 506 native renal biopsies were processed during this period, 69.8% were female and 30.2% were male. Their age average was 37 +/- 14.2 (13-80) years. The most common indications for renal biopsy were nephrotic syndrome and SLE (36.8%, 34.5%, respectively), followed by asymptomatic hematuria/proteinuria in 10.9% of patients. Secondary glomerular diseases were dominant against primary diseases in all but elderly age group (>50 years), particularly LN. Among primary glomerular diseases, the prevalence of IgAN, focal segmental glomerulosclerosis, and membranous nephropathy were 31.0%, 24.9%, and 13.1%, respectively. The provisional clinical diagnosis was correct in three fourths (73.2%) of the SLE cases. Postbiopsy complications occurred in 3.3% (17/506). Gross hematuria was seen in 2.3% (12/506), and perinephric hemptoma in 0.79%. Three of them required blood transfusion but none of them died and required an invasive procedure for resolution. The major complications were 2 folds less than regular prevalence (0.6% compared to 1.3%). CONCLUSION: Although the data was collected from single center where EM is routinely performed, the authors believe that IgAN is the commonest primary GN in SEA countries. The authors are looking forward to seeing the nationwide registry data in Thailand and other SEA countries.

The prevalence and risk factors of osteoporosis in Thai renal-transplant patients.

OBJECTIVES: To determine the prevalence and risk factors of osteoporosis after renal transplantation in Thai patients. MATERIAL AND METHOD: A single-center cross-sectional study of bone mineral density was conducted in 102 Thai renal allograft recipients. Correlations were made between the clinical parameters and the occurrences of osteoporosis. RESULTS: The prevalence of osteoporosis was 24.5%, 9.8% and 26.4% at lumbar vertebrae, hip region, and any sites, respectively. Binary logistic regression analysis revealed that cumulative dosage of steroids was significantly correlated with osteoporosis of the lumbar spine (p = 0.023, adjusted OR = 1.005), while body mass index (p = 0.005, adjusted OR = 0.738) and age (p = 0.052, adjusted OR = 1.077) were correlated with osteoporosis of the hip region. CONCLUSION: Osteoporosis is common in Thai renal allograft recipients, particularly of the lumbar vertebrae. Cumulative dosage of steroids is the most important risk factor of low BMD of the lumbar vertebrae.

Comparison of different culture methods on bacterial recovery in hemodialysis fluids.

To examine the culture method that could provide the highest bacterial recovery, 143 reverse osmosis water samples used in hemodialysis were collected for comparison of the media (Tryptic Soy Agar, TSA vs Reasoner's 2A Agar, R2A), the temperature (20 degrees C vs 37 degrees C), the duration of incubation (48-hour vs 7-day), and the culture technique (membrane filtration vs spread plate methods). The European Best Practice Guideline method, R2A at 20 degrees Cfor 7-day incubation provided higher bacterial recovery than the Association for the Advancement of Medical Instrumentation (AAMI) method, TSA at 37 degrees C for 48-hour incubation. The membrane filtration method gave better yield than the spread plate method. As such, the European Best Practice Guideline method in combination with the membrane filtration technique would be the culture method of choice for hemodialysis fluids.

The effects of potassium and magnesium supplementations on urinary risk factors of renal stone patients.

The effects of potassium and magnesium supplementation on urinary risk factors for renal stone disease were studied in 61 renal stone patients. The subjects were divided into four groups and supplemented for a period of one month with potassium chloride (KCl, Group 1), potassium sodium citrate (K Na citrate, Group 2), magnesium glycine (Mg glycine, Group 3) and potassium magnesium citrate (K Mg citrate, Group 4) with a daily dose of 42 mEq potassium, 21 mEq magnesium or sodium and 63 mEq citrate, accordingly. The results showed that serum potassium and magnesium of all four groups normalized after the supplementation. Though urinary potassium significantly increased in all three groups supplemented with elemental potassium containing solutions [i.e. KCl (p < 0.001), K Na citrate (p < 0.001) and K Mg citrate (p < 0.001)] only K Na citrate and K Mg citrate, caused a significant increase in urinary pH and citrate but decrease in calcium. Supplementation with Mg glycine in Group 3 although caused a significant increase in urinary magnesium, its effects on urinary pH, citrate and calcium, however, were similar to KCl, in that they caused a significant decrease in urinary pH without any change in urinary citrate or calcium. Supplementation with K Mg citrate in Group 4 seems to have given the best results, as far as lowering stone risk factors in that it caused an increase in urinary pH, potassium and citrate and decreased calcium excretions similar to K Na citrate in Group 2. In addition, K Mg citrate also caused the enrichment of urine with magnesium, another inhibitor of calcium-containing stones. Although the four supplements had no effect on urinary saturation of calcium oxalate salt, their effects on the saturations of brushite (CaHPO4 x 2H2O), octacalcium phosphate (Ca8H2 (PO4)6 x 5H2O) and uric acid were clearly associated with changes in urinary pH. Therefore, in Group 1 and 3, subjects having a decrease in urinary pH, also experienced a significant increase in uric acid saturation. Though the saturation of brushite and octacalcium phosphate in Group 2 and 4 and the sodium acid urate in Group 2 were significantly increased, these urinary risk factors could be overcome, however, by the concomitant increase in urinary citrate. The present results demonstrate that for those stone vulnerable subjects having a high risk of potassium and magnesium depletion, to obtain the best therapeutic results, they should be provided supplementations of both potassium and magnesium together and also in the forms that would result in the delivery of an alkali loading effect.

Immune response of intradermal hepatitis B vaccination at lower dose versus intramuscular vaccination at double standard dose in predialytic chronic renal failure patients.

The immune responses to hepatitis B vaccine were studied in 2 groups of predialytic chronic renal failure patients who had negative results of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti HBc). In the intradermal group, vaccine at the dose of 0.1 ml, 2 microg, was intradermally administered at 5 positions. In the intramuscular group, the vaccine at the dose of 1.0 ml, 20 microg, was intramuscularly given at 2 positions and, thus, was a double standard dose. Both groups received 4 vaccinations at month 0, 1, 2, and 6 (M0, M1, M2, and M6). The results showed that there were no significant differences in the results of seroconversion rates, defined as having anti HBs levels above 10 mIU/ml, between the intradermal (ID) and intramuscular (IM) groups at M1, M2, M6, and M7. In patients with positive seroconversion results at M7, the numbers of patients in the good and excellent subgroups, having HBs Ab levels ranged 10-999 and above 1,000 mIU/ml respectively, showed no difference between both routes. The body weight and seroconversion rates at M2 and M6 were the factors which had a positive influence on the seroconversion rates of intradermal hepatitis B vaccination. In conclusion, intradermal hepatitis B vaccination at a lower dose could provide comparable satisfactory immune response with the intramuscular route at double the standard dose.

Magnesium and zinc status in survivors of sudden unexplained death syndrome in northeast Thailand.

Sudden Unexplained Death Syndrome (SUDS) is a major health problem in rural residents of Northeast Thailand. The cause of death in SUDS is suspected to be cardiovascular abnormalities. As magnesium (Mg) and zinc (Zn) deficiency contribute significantly to several cardiovascular diseases, we investigated the Mg- and Zn-status of patients with sudden respiratory distress and cardiac arrest who had survived resuscitation attempts or a near-SUDS episode (N-SUDS). The following subjects were enrolled: 12 N-SUDS inhabitants of rural Northeast Thailand (rural group 1, R1), 13 rural villagers with no past history of N-SUDS (rural group 2, R2), 15 urban Northeasterners (urban group 1, U1); 13 Bangkokians (urban group 2, U2). All subjects were free of structural heart disease. Magnesium and zinc were assessed by atomic absorption spectrophotometry of samples of plasma, red blood cells (RBC), white blood cells (WBC), and 24-hour urine. The mean levels of magnesium in the RBC, WBC, and 24-hour urine of N-SUDS patients (R1) were significantly lower than those of the urban groups (U1 and U2), while the plasma levels did not show any differences. When comparing the Zn-status of R1 with that of the urban groups (U1 and U2), the plasma, RBC, and WBC levels were found to be significantly lower in R1 (except for the RBC-Zn of the U1 group), while the 24-hour urine levels was higher. Although the magnesium and zinc parameters were not significantly different between the rural groups R1 and R2, the prevalence of hypomagnesuria (<2.2 mmol/day), hypozincemia (<9.7 micromol/l), and hyperzincuria (>10.7 micromol/day) was higher in the R1 group. These findings suggest that the homeostasis of both magnesium and zinc is altered in N-SUDS patients. Similar alterations, to a lesser degree, were observed in those people living in the same rural environment (R2).