Browsing by Author "Gatua, Wilfred Kimani"

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    Evaluation of Urinary Tubular Enzymes as Screening Markers of Renal Dysfunction in Patients Suffering from Diabetes Mellitus Type 2
    (Kenyatta University, 2010-04) Gatua, Wilfred Kimani
    Diabetes mellitus is a global disorder and complications resulting from the disease are the third leading cause of death in the world. A survey by the National Diabetes Data Group estimates the prevalence of diabetes in the world population at 6.6%. One of the principle complications of diabetes mellitus is diabetic nephropathy and renal function tests are important indicators in diabetic patients needed to identify the early structural and functional changes in diabetic nephropathy. Diabetes mellitus type 2 patients show elevated levels of albumin in urine and assessment of renal injury based on the concentrations of blood urea nitrogen (BUN), serum creatinine (S.Cr) or urinary micro protein (U.MP) that are commonly used are usually insensitive since these parameters could be within normal ranges despite considerable impairment of the renal function because of the great reserve capacity of the kidney. More sensitive urinary biomarkers, which could be used to detect nephrotoxicity at early stages on various parts of the nephron, are being investigated. Animal studies have identified enzymes as potential urinary biomarkers of renal injury. These biomarkers include the high molecular weight albumin for evaluating glomerular integrity, the brush border enzymes alkaline phosphatase (V.ALP) and gamma glutamyl transferase (U.y- GT), lysosomal enzyme N-acetyl-~-D-glucosaminidase (D.NAG), and cytoplasmic enzyme lactate dehydrogenase (V.LDH) for indicating proximal tubular injury. The present study investigated early signs of renal injury due to diabetes mellitus type 2 by measuring urinary indicators of nephrotoxicity. The study subjects comprised 251 patients with diabetes mellitus type 2 (mean age 54.2yrs) and 73 healthy normal individuals recruited as control group (mean age 40.9 yrs). The diabetic group was further subdivided into those with normoproteinuria, microproteinuria and diabetics with renal failure. Glomerular function was studied by determining the urinary levels of micro protein U.MP), serum urea and creatinine while proximal tubular structural integrity was studied by determining the activities of the enzymes U.ALP, U.NAG, U.y-GT, and U.LpH. Compared with normal healthy individuals, diabetic patients with normoproteihuria.excreted significantly high levels ofU.ALP, U.LDH, U.y-GT, and U.NAG (p<0.05). Patients with renal impairment excreted high levels of the enzymes and urinary micro protein compared to healthy individuals and diabetic patients without renal failure. In conclusion, the present study confirms that diabetes mellitus leads to nephrotoxicity; that urinary excretion of V.ALP, U.LDH, U. y-GT, and V.NAG could be useful biomarkers for proximal tubular injury. These results suggest that site-specific urinary biochemical markers provide valuable information about early renal proximal tubular insult that ultimately may precede glomerular permeability in subjects with diabetes mellitus.
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    Relationship between Arterial and Venous Biochemistry and Acid-Base Values in Patients with Diabetic Ketoacidosis and Chronic Kidney Disease
    (Kenyatta University, 2024-06) Gatua, Wilfred Kimani
    Two of the complications of diabetes mellitus include diabetic ketoacidosis (DKA) and chronic kidney disease (CKD) and both conditions may lead to metabolic acidosis. In DKA there is excessive oxidation of fatty acids with subsequent accumulation of acetoacetate and β-hydroxybutyric acid while in patients with kidney dysfunction, the renal tubules lose the ability to regenerate bicarbonates effectively with resultant reduction of bicarbonate in blood. Clinical management of metabolic acidosis requires frequent arterial blood gas analysis (BGA) to determine the levels of acid-base parameters. Other biochemistry parameters tested to monitor the progress of management include: liver function tests, kidney function tests and pancreatic function tests. Arterial puncture is a painful and traumatic procedure which may lead to the formation of hematomas and sepsis and requires special skills to perform. There is therefore the need to substitute arterial blood with venous blood which is easy to obtain and is less painful to patients and has less complications. However, venous blood as a substitute for arterial blood has not been evaluated in the country to ascertain the level of relationship and agreement with arterial blood. The objective of this study was to evaluate levels of acid-base and routine biochemistry parameters in both arterial and venous blood in patients with diabetic ketoacidosis and chronic kidney disease and also determine the relationship and agreement between the two types of blood samples. A cross-sectional study composed of 200 patients with CKD and 150 patients sampled at Kenyatta National Hospital were uesd. Arterial and venous blood were collected from each study subject, and acid-base parameters, liver, kidney, and pancreatic function tests were carried out. Laboratory methods included measurements of acid-base parameters using RapidLab 348 blood gas analyzer. Biolis Clinical Chemistry Autoanalyser was used for the measurements of biochemistry parameters. The data generated was tested for its normality using Kolmogorov-Smirnov test. The results were expressed as mean ± SD and t-test used for statistical comparison of two means for two data sets. For relationships between measured arterial and venous blood parameters, correlation coefficient, simple and multiple linear regressions was used. For agreement between measured arterial and venous blood parameters, Bland-Altman bias plot was used. The key findings of this study were that patients with DKA and CKD have significant variations in the levels of both acid-base and biochemistry parameters. The generated bootstrapped simple linear regression equations between the measured arterial and venous blood analytes demonstrated strong correlations and agreements. This study therefore validates the use of venous blood for the measurement of blood gas and biochemistry parameters in the management and monitoring of acid-base metabolic disorders in patients with chronic kidney disease and diabetic ketoacidosis. This will hopefully minimize the need for arterial sampling which is hazardous and traumatic to the patients.