ABSTRACT
Introduction: Chronic kidney disease (CKD) is a major complication of diabetes mellitus and it contributes to increased hospital mortality and morbidity. Microalbumin test is used to identify the first sign of deteriorating kidney function but it is an expensive test. Alternatively, measurement of urine total protein-to-creatinine ratio (TPCR) is a simple and inexpensive method. Objective: To find whether the urine TPCR can predict the presence of microalbuminuria in patients with diabetic nephropathy. Method: A cross sectional study was performed on 216 patients with diabetes mellitus at General Hospital, Ampara over a period of 4 weeks. Urine albumin, urine creatinine and urine total protein were analysed on first voided urine samples and urine albumin to creatinine ratio (ACR) and total-protein-to-creatinine ratio were calculated. Regression analysis and Spearman's rank correlation were used to study the linear relationship between two variables. Results: Among 216 patients, 56 (26.1%) were males and 160 (73.9%) were females. The mean urine total-protein-to-creatinine ratio was 89.3 ± 231.6 mg/g and albumin to creatinine ratio was 43.1±76.3 mg/g. Sixty four (29%) patients were newly detected as having microalbuminuria (n=61; 28%,) or macroalbuminuria (n=3; 1%,). There was a significant correlation between urine total-protein-to-creatinine ratio and urine albumin to creatinine ratio (R2 = 0.824, ACR = [TPCR + 18.421]/ 2.5026) in the total sample (p < 0.001). The total-protein-to-creatinine ratio showed a significant correlation with urine albumin to creatinine ratio in the range of microalbuminuria (30-300 mg/g creatinine) (R2 = 0.798; p < 0.001). The regression equation was ACR = [TPCR 5.0491]/1.2633. Conclusion: The urine total-protein-to-creatinine ratio showed a positive significant correlation with urine albumin to creatinine ratio, which is clinically important to identify early stage of diabetic nephropathy. This can be used in rural areas as it is inexpensive.
Subject(s)
Albumins/analysis , Albuminuria/diagnosis , Creatinine/urine , Diabetic Nephropathies/urine , Renal Insufficiency, Chronic/etiology , Aged , Albuminuria/etiology , Cross-Sectional Studies , Diabetic Nephropathies/complications , Female , Humans , Linear Models , Male , Middle Aged , Predictive Value of Tests , Rural Population , Sri Lanka , Statistics, NonparametricABSTRACT
Activating mutations in the receptor tyrosine kinase KIT, most notably KIT D816V, are commonly observed in patients with systemic mastocytosis. Thus, inhibition of KIT has been a major focus for treatment of this disorder. Here we investigated a novel approach to such inhibition. Utilizing rational drug design, we targeted the switch pocket (SP) of KIT, which regulates its catalytic conformation. Two SP inhibitors thus identified, DP-2976 and DP-4851, were examined for effects on neoplastic mast cell proliferation and mast cell activation. Autophosphorylation of both wild-type and, where also examined, KIT D816V activation was blocked by these compounds in transfected 293T cells, HMC 1.1 and 1.2 human mast cell lines, and in CD34(+)-derived human mast cells activated by stem cell factor (SCF). Both inhibitors induced apoptosis in the neoplastic mast cell lines and reduced survival of primary bone marrow mast cells from patients with mastocytosis. Moreover, the SP inhibitors more selectively blocked SCF potentiation of FcÉRI-mediated degranulation. Overall, SP inhibitors represent an innovative mechanism of KIT inhibition whose dual suppression of KIT D816V neoplastic mast cell proliferation and SCF-enhanced mast cell activation may provide significant therapeutic benefits.