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Abstract
This study was carried out in the Departments of Internal Medicine, Nephrology Unit, Cardiology and Medical Biochemistry, Faculty of Medicine, Zagazig University.
The aim of this work \\as to study the value of urinary glutathione S-tr:lIlsferase as a marker of renal tubular injury in diabetic patients and in pmients exposed to radiocontrast media.
This work included 50 subjects, 40 patients and 10 healthy volunteers to serve as a control group. Patients were classified into the follo\\ing four groups:
1- Ten type-2 diabetic patients with no evidence of renal injury (without nephropathy, GII)
2- Ten type-:? diabetic patients with proteinuria (with nephropathy, Gill)
3- Ten patients with chronic renal impairment (chr __ .;~ GN, G IV).
4- Ten patients exposed to radiocontrast media (coronary angiography, G V).
All patients and the healthy controls \•vere subjected to thorough clinical examination, abdominal ultrasonography, routine biochemical and haematological tests, measurement of albumin excre~ion rate and 24-hours urine protein, and calculated creatinine clearance. Urinary GSTu and GSTpi
were estimated in all subjects (before and after contrast media exposure in GV) by enzyme amplified sensitivity immunoassay.
In the healthy control subjects (GI), the urinary levels of both enzymes (GSTa and GSTpi) were within the normal ”physiological” levels (below 10 ng/ml, and 12 ng/ml respectively).
In the group of type 2- diabetic patients with no sign of renal injury, (GII, without nephropathy), urinary levels of both GST” and GSTpi are significantly higher than that in the controls. They did not correlate neither with serum creatinine nor with the creatinine clearance. This finding may suggest a potential importance of GST-enzymuria as an early indicator of tubular damage in diabetic patients, even before the appearance of microabluminuria.
In type-2 diabetic patients with evidence of nephropathy (GIII), the urinary levels of both GSTa and pi were significantly higher than that in both controls and diabetic patients without nephropathy. In this group, urinary enzyme levels positively correlated with the degree of protein excretion rate. On the other hand, \ve failed to detect any correlation between urinary enzyme levels and serum creatinine in
4- Significantly elevated levels of urinary enzymes (GSTu and GSTpi) were detected in patient with renal impairment (GIV) compared to all other groups. We were able to detect a strong positive correlation between GST iso-enzymes and each of serum creatinine and
proteinuria. Moreover, an inverse correlation was established between urinary enzymes and creatinine clearance.
5- The urinary levels of GSTu and GSTpi before exposure to the contrast did not differ significantly from the physiological levels in the healthy controls. However, urinary levels of both enzymes rose significantly in the first day after exposure to the urograffin. We also detected a significant elevation of serum creatinine in each of the first, second and third days after exposure. Moreover, the changes in the urinary enzyme levels showed a strong positive correlation with the changes in serum creatinine in the days following exposure.
1- In type-2 diabetic patients with no sign of renal injury, increased urinary levels of both GSTa and GSTpi may be used as an early indicator of renal tubular damage in diabetic patients, even before the appearance of 111 icroal bum i nuria.
2- The positive correlation between urinary enzymes and protein suggest that measurement of these enzymes can be a useful diagnostic tool In diabetic nephropathy.
3- It appears that the assay of urinary GST enzymes in the patients with chronic renal impairment might be a highly useful tool in renal
diagnosis since the direct methods such as needle biopsy are relatively complicated and can not be performed on routine basis.
4- This may suggest that a single estimation of urinary GST isoenzymes Illay be sufficient to predict changes in serum creatinine in the following few days after exposure to the contrast media and may identify patients who are at risk of developing contrast-media nephrotoxicity.