Cathepsin L and dynamin-biomarkers of proteinuric renal disease
Background Chronic kidney disease (CKD) is a major public health problem. It is important to be able to identify those individuals at high risk of CKD progression in order to implement strategies to delay progression to end stage renal disease. Hence, early more sensitive biomarkers are required. Recently, promising new biomarkers have been identified for monitoring CKD progression. Objectives To determine whether Dynamin and Cathepsin L can be used as biomarkers for proteinuric chronic kidney disease (CKD). To compare the levels of Dynamin and Cathepsin L in serum and urine of participants with proteinuric kidney disease to those of normal controls. To determine if the levels of Cathepsin L and Dynamin correlates with the degree of proteinuria. Methods A prospective study of 37 patients with proteinuric kidney disease versus a healthy control group of 40 individuals, where the serum and urine levels of Cathepsin L and Dynamin were determined using an Enzyme Linked immunosorbent assay and the levels compared between the two groups. Data Analysis v The sample size was determined from previous similar studies, with assistance of a statistician. Sample size was calculated by comparing the means of the groups where the average value for sample 1= 1.0 (standard deviation=0.5); average value sample 2= 1.5 (standard deviation=0.5; alpha= 5% and beta= 20%. A sample size of 20 was initially selected for the kidney disease group and 20 for the Control group (to give a 1:1 ratio). The numbers were there after doubled to increase sample size in order to improve the statistics. An independent sample t-test was used to assess whether the mean serum Dynamin, urine Dynamin, serum Cathepsin L and urine Cathepsin L differed for the control group compared with kidney disease group. Pearson’s correlation analysis was used to measure the strength of the relationship between variables. Statistical significance was p<0.05. Results There was a significant increase in the level of urine Cathepsin L in the renal disease group 10.44±11.47 pg/ml compared with the control group 2.91±2.88 pg/ml; p= 0.000. There was no difference in the levels of serum Cathepsin L between the renal disease and the control groups (p= 0.23). There were no significant differences in the levels of Dynamin in the serum and urine of patients with proteinuric renal disease and controls (p-values 0.11 and 0.13 respectively). Although serum Cathepsin L (r = -0.22, p-value = 0.19), urine Cathepsin (r = -0.07, p-value = 0.68), and urine Dynamin (r = -0.04, p-value = 0.83) are negatively related to the degree of proteinuria, the correlation is not significant; all the p-values were greater than 0.05. Serum Dynamin (r = 0.12, p-value = 0.49) had a positive correlation to the degree of proteinuria but vi the correlation was not significant at the 5% significance level. Thus, there is no correlation between Cathepsin L and Dynamin levels with the degree of proteinuria. Discussion Podocyte dysfunction is a key element in understanding the progression of CKD resulting in proteinuria. In this study, levels of Cathepsin L and Dynamin were determined in participants with proteinuric renal disease and compared with healthy controls. Cathepsin L levels were elevated in the urine of the renal disease group, in keeping with the notion that Cathepsin L proteolysis plays a critical role in the various forms of proteinuria. There was negative correlation between the levels of proteinuria and Dynamin in the serum; however the correlation was not significant statistically. Conclusion Cathepsin L could potentially serve as a biomarker of proteinuric kidney disease.
A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment for the degree of Master of Medicine in Internal Medicine Johannesburg 2016