Methods: One hundred and fifty hard-working agricultural farmers from high-prevalence area for CKDu (Madawachchiya) were screened three times for proteinuria; 66 proteinuric and 21 non-proteinuric were identified as the baseline classification. Selected individuals were analysed further for creatinine, protein and cystatin C in urine and creatinine, cystatin C in serum. Urine protein-to-creatinine ratio (UP/UC) was calculated.
Results: Based on creatinine and cystatin C cut-off levels in serum, individuals were classified as high or normal. Diagnosis of two functional markers (creatinine and cystatin C) were evaluated using receiver operating characteristic (ROC) curve and in terms of sensitivity and specificity using UP/UC as the baseline. Creatinine and cystatin C-based eGFR (estimated Glomerular filtration rate) levels were calculated, and Pearson's correlation coefficient was determined between different eGFR measurements using UP/UC. Mean (SD) UP/UC ratio, serum creatinine, and serum cystatin C levels of the proteinuric subjects were 129.0 (18.4) mg/mmol, 1.35 (0.39) mg/dL, 1.69 (0.58) mg/L. For non-proteniuric individuals, the results were found to be 14.4 (2.28), 1.22 (0.40) mg/dL, 0.82 (0.25) mg/L. The ROC analysis showed excellent accuracy in using cystatin C for identifying proteinuric patients than creatinine area under the curve (AUC): 0.9675, P < 0.001). Cut-off points were identified as 1.015 mg/dL for serum creatinine and 0.930mg/L for cystatin C. Furthermore, cystatin C based Hoek formula showed the better correlation (0.635, P < 0.001) with UP/UC compared with creatinine based modification of diet in renal disease (MDRD) formula.
Conclusion: The study showed elevated serum cystatin C in patients with persisting proteinuria compared with non-responding serum creatinine. Moreover, cystatin C-based eGFR equations were more accurate to determine the kidney function than serum creatinine in proteinuric patients who are vulnerable for CKDu in high-prevalence areas.
METHODS: Predialysis CKD patients were included in this cross-sectional study. Patient demographics, medical/medication histories, and laboratory parameters (serum 25-hydroxyvitamin D (25(OH)D), creatinine, phosphate (P), calcium, albumin, and intact-PTH (i-PTH)) were collected and compared among patients with various CKD stages. The association between 25(OH)D and these parameters was determined by multiple linear regression.
RESULTS: A total of 196 patients with mean ± SD eGFR of 26.4 ± 11.2 mL/min/1.73 m2 was included. Vitamin D deficiency (25(OH)D concentration < 15 ng/mL) and insufficiency (25(OH)D concentration 16 - 30 ng/mL) was found in 29.1% and 57.7% of the patients, respectively. Mean ± SD serum 25(OH)D was 20.8 ± 9.3 ng/mL. Female patients had lower vitamin D concentrations than males (16.9 ng/mL vs. 23.9 ng/mL; p < 0.001). Vitamin D levels were also higher in Chinese (22.3 ng/mL) than Malay (17.3 ng/mL) and Indian (13.1 ng/mL) patients (p < 0.05). Nonadjusted analyses showed higher i-PTH concentration in vitamin D deficient patients (p < 0.05).
CONCLUSION: Despite being a sun-rich country all year round, the majority (86.8%) of predialysis CKD patients in Singapore have suboptimal vitamin D status. Lower vitamin D concentrations were found in females and in those with darker skin tone. Vitamin D deficient patients also tended to have higher i-PTH levels.
METHODS: This is a prospective observational study on patients with SIRS. Plasma creatinine (pCr) and NGAL were measured on ICU admission. Patients were classified according to the occurrence of AKI and sepsis.
RESULTS: Of 225 patients recruited, 129 (57%) had sepsis of whom 67 (52%) also had AKI. 96 patients (43%) had non-infectious SIRS, of whom 20 (21%) also had AKI. NGAL concentrations were higher in AKI patients within both the sepsis and non-infectious SIRS cohorts (both P
RESEARCH DESIGN AND METHODS: NIDDM patients of Chinese, Indian, and Malay origin attending a diabetic clinic in Kuala Lumpur, Malaysia, were matched for age, sex, diabetes duration, and glycemic control (n = 34 in each group). Urinary albumin-to-creatinine ratio was measured in an early morning urine sample. Biochemical measurements included markers of the acute-phase response: serum sialic acid, triglyceride, and (lowered) HDL cholesterol.
RESULTS: The frequency of microalbuminuria did not differ among the Chinese, Indian, and Malay patients (44, 41, and 47%, respectively). In Chinese patients, those with microalbuminuria had evidence of an augmented acute-phase response, with higher serum sialic acid and triglyceride and lower HDL cholesterol levels; and urinary albumin-to-creatinine ratio was correlated with serum sialic acid and triglyceride. The acute-phase response markers were not different in Indians, with microalbuminuria being high in even the normoalbuminuric Indians; only the mean arterial blood pressure was correlated with urinary albumin-to-creatinine ratio in the Indians. Malay NIDDM subjects had an association of microalbuminuria with acute-phase markers, but this was weaker than in the Chinese subjects.
CONCLUSIONS: Microalbuminuria is associated with an acute-phase response in Chinese NIDDM patients in Malaysia, as previously found in Caucasian NIDDM subjects. Elevated urinary albumin excretion has different correlates in other racial groups, such as those originating from the Indian subcontinent. The acute-phase response may have an etiological role in microalbuminuria.
METHODOLOGY/PRINCIPLE FINDINGS: The D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.
CONCLUSIONS/SIGNIFICANCE: This study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell's viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.