Transferrinuria in type 2 diabetes mellitus: An early marker of diabetic nephropathy

Diabetic nephropathy is the commonest cause of end-stage renal failure in the Western world. The incidence of DN rises rapidly over the first 15 to 20 years of diabetes to decline sharply afterwards. The stages of DN progress from normoalbuminuria to microalbuminuria to clinical proteinuria and finally to end-stage renal failure. Several studies proved the applicability of urinary albumin quantification in the early diagnosis of diabetic nephropathy. Several studies of different urinary proteins demonstrated the increased excretion of other high and low molecular mass proteins in different stages of diabetic nephropathy: macromolecular, e.g. transferrin and micromolecular proteins like alpha 1-microalbumin. Elevated urinary transferrin excretion rates have been reported in patients with type 2 diabetes and its complications. Therefore, the aim of the present study was to evaluate the role of transferrin as an early marker for the detection of nephropathy in Egyptian type 2 diabetic patients. Sixty Egyptian type 2 diabetic patients grouped according to the presence or absence of albumin in urine into three groups: group I consisted of 20 normoalbuminuric Egyptian type 2 diabetic patients, group II included 20 microalbuminuric Egyptian type 2 diabetic patients, and group Ill comprised 20 macroalbuminuric Egyptian type 2 diabetic patients. Twenty healthy subjects of matched age and sex were included as a control group. Laboratory investigations included FBG and 2 hours PPBG, HbA[1C] serum albumin, ALT, AST, prothrombin activity, blood urea, serum creatinine and creatinine clearance, and complete urine analysis. Determination of microalbuminuria in fresh urine samples was done using immunoturbidimetry. Estimation of urinary transferrin was done by immuno-nephelometry. Results: Type 2 diabetic patients who had frank proteinuria had a significantly longer duration of diabetes mellitus as compared to micro and norrnoalbuminuric patients. Type 2 diabetic patients with frank proteinuria had significantly higher FBG, PPBG and HbA[1C] levels as compared to normoalbuminuric type 2 diabetic patients and controls. Type 2 diabetic patients with frank proteinuria had significantly higher blood urea and serum creatinine and a significantly lower creatinine clearance as compared to norrnoalbuminuric type 2 diabetic patients and controls. Type 2 diabetic patients with frank proteinuria showed significantly higher urinary albumin and transferrin excretion as compared to normo-and microalbuminuric type 2 diabetic patients and controls. Also, microalbuminuric type 2 diabetic patients had significantly higher urinary albumin and transferrin excretion as compared to normoalbuminuric type 2 diabetic patients and controls. In normoalbuminuric type 2 diabetic patients, a negative correlation was observed between creatinine clearance and transferrinuria. In microalbuminuric type 2 diabetic patients, a strong positive correlation was found between albuminuria and transferrinuria. In type 2 diabetic patients with frank proteinuria, strong positive correlations were obtained between blood urea and serum creatinine and transferrinuria, while a strong negative correlation was observed between creatinine clearance and transferrinuria. However, no significant correlations were found in any of the type 2 diabetic groups between duration of the disease, blood pressure, FBG, PPBG, or HbA[1C] and transferrinuria. Urinary transferrin is a convenient diagnostic parameter of renal impairment in Egyptian type 2 diabetic patients. Transferrinuria could be considered as an early marker of diabetic nephropathy as compared to microalbuminuria

Diabetes mellitus; incidence of proteinuria, micro-albuminuria and transferrinuria

Diabetic nephropathy is a common microvascular complication of diabetes mellitus and reflects serious renal disease specific to diabetes. It is one of the common causes of end stage renal disease. A cross sectional study was carried out to find the incidence of proteinuria, microalbuminuria and transferrinuria in know diabetics of Rawalpindi. One hundred and forty six consecutive diabetics were included in the study [68 men and 78 women] for detection of diabetic nephropathy. Thirty age and sex matched, healthy controls were also included in the study. Urine protein, microalbumin and transferrin concentration were analysed in the 24 hours urine samples submitted by all diabetics and healthy controls. The screening of protein in urine was done by dipstick method using Uristix Ames [UK]. Quantitative urine total protein was estimated by Biuret method; the dipstick negative samples were analysed for microalbuminuria by using Pyrogallol-molybdate test technique and urinary transferrin was estimated by immunoturbidimetry method. The transferrin excretion in diabetic subjects significantly [P<0.01] exceeded that in healthy subject. The 65% of diabetics had an abnormally high urinary transferrin excretion and 40% had high urinary protein excretion [proteinuria: 14%: microalbuminuria: 26%]. It is concluded that microalbuminuria proteinuria and transferrinuria is common in our diabetics reflecting poor metabolic control

Study of urinary transferrin and iron excretion in insulin dependent diabetes mellitus [IDDM] with variable degrees of albuminuria

This study included 60 insulin dependent diabetic male patients in 3 groups according to urinary albumin excretion. Group I with normal albuminuria [urine albumin < 30 mg/day], group II with microalbuminuria [urine albumin 30-300 mg/day] and group III with macroalbuminuria [urine albumin > 300 mg/day]. Each diabetic group included 20 cases and these groups were compared with control group comprised of 20 healthy subjects. The present work was undertaken to study urinary transferrin and iron in diabetic patients with varying amounts of albuminuria. The following were the results of this work: -There was significant increase [P < 0.05] in urinary transferrin and iron in all the studied diabetic groups compared to the normal controls, and this increase occurrs early in the course of the diabetic renal disease. -The iron/transferrin ratio in urine was much higher than that in serum in all the diabetic groups. This means that iron is present in the urine in marked excess than its carrier transferrin. -There was significant positive correlation [P < 0.05] between urinary albumin and urinary transferrin in both the micro and macro albuminuric diabetic groups. -There was significant positive correlation [P < 0.05] between urinary albumin and urinary iron in all the diabetic groups. -There was significant positive correlation [P< 0.05] between urinary iron and urinary transferrin in the macroalbuminuric diabetic group. From this work we can conclude the following: -Transferrin which has the similar molecular size as albumin, its urinary excretion in excess as well as the excess excretion of urinary iron in diabetics may suggest the possibility of development of glomerular disease and nephropathy. -Urinary iron excretion is increased early in the course of diabetic renal disease. The fact that iron is present in the urine in marked excess of transferrin further suggests that either iron is dissociated from transferrin in the tubule fluid with transferrin being reabsorped, or that iron is added to the tubule fluid by means other than filtration without transferrin. This finding suggests that iron could be present in tubule fluid in a form which would catalyze the Haber- Weiss reaction with the formation of free radicals resulting in tubulointerstial injury. -The increase of urinary iron excretion in diabetics may reduce iron stores making the individuals more at risk of developing iron deficiency if there are other causes of iron or blood loss. We recommended detection of urinary transferrin and iron in IDDM patients as their excretion in excess may suggest the possibility of development of glomerular disease and nephropathy which may need further investigations and follow up for proper management of this risky diabetic complication