Serum and urinary laminin as markers for diabetic nephropathy

Abstract EN

Background : Abnormalities in glomerular basement membrane and tubular basement membrane metabolism play a major role in the development of diabetic renal damage and dysfunction.

Laminin, a non collagenous glycoprotein component of basement membrane is considered as a valuable indicator of microangiopathic affection occurring in complicated diabetes mellitus.

A raised level of circulating basement membrane protein may indicate connective tissue activity in microangiopathy.

Circulating laminin and type III procollagen peptide showed higher values with the development of diabetic micro angipathy suggesting that progressive changes in diabetic microangiopathy occur with the synthesis of laminin and type III procollagen.

Objective : The aim of the present study is to measure serum and urinary laminin levels by radioimmunoassay in diabetics to assess its value as a marker of diabetic nephropathy .At the same time the parallel immunohistochemical determination of laminin in renal biopsies was carried out in some of the patients aiming to highlight the role of serum and urinary laminin in predicting the occurrence of the early histopathologic changes of diabetic micro angiopathy including diabetic nephropathy.

Results : Serum Laminin was significantly higher in normoalbuminuric diabetic group (1.05 ±0.26 I.U/ml) compared to the control group (0.89 ±0.104 I.U/ml) P<0.05.

Serum Laminin showed highly significant increase in micro and macroalbuminuric diabetic groups (1.29 ±0.316), (1.9 ±0.738) I.U/ml respectively compared to the control group (0.89 ±0.104 I.U/ml).

(P<0.001).

Moreover, urinary laminin levels were significantly higher in normo, micro and macroalbuminuric diabetic groups (0.181 ±0.027), (0.238 ±0.014), (0.248 ±0.028) I.U/ml respectively compared to the control group.

(0.15 ±0.0205 I.U) (P<0.001).

Serum laminin concentration in type 2 diabetic patients was significantly elevated with advanced diabetic nephropathy.There was significant positive correlation between serum laminin and duration of diabetes mellitus (r=0.47),FBG (r=0.70) ,PPBG (r=0.73), HbAl (r=0.061),UAE(R=0.56) ,blood urea (r=0.53) and serum creatinine (r-0.42) .P<0.05 .There was also a significant positive correlation between urinary laminin concentration and duration of diabetes (r=0.42) ,PPBG (r=0.33),serum laminin (r=0.47).P<0.05.

There was no correlation between urinary laminin excretion and HbAl and urinary albumin excretion (P>0.05).Urinary laminin had the highest discriminative power between the three groups of diabetic patients then serum laminin then serum creatinine then urinary albumin excretion.Moreover urinary laminin had the highest discriminative power between the three groups of diabetic patients and the control..

As regard the histopathological part of our work 5 diabetic renal biopsies and 2 non diabetic controls were studied.

H&E stained sections showed 2 cases of early diffuse glomerulosclerosis with hypercellular glomerulus, mild thickening of the glomerular cappillary basement membrane and mild increase in the mesangial matrix .

The remaining 3 cases were diagnosed as advanced diffuse glomerulosclerosis, these cases revealed marked hypertrophy and hypercellularity of the glomeruli together with diffuse thickening of the glomerular capillary basement membrane and Bowman's capsule.

Also, there was a varying degree of increase in the mesangial matrix .PAS stained sections showed strongly easinophilic PAS positive material in the thickened glomerular capillary basement membrane and in the increased - mesangial matrix.

Also diffuse thickening of the tubular basement membrane was detected.

By immunohisto chemical staining, antilaminin antibody highlighted the thickening of the glomerular capillary basement membrane mesangial matrix and Bowman's capsule.

The thickening was more apparent in the 3 advanced diffuse glomerulosclerotic cases than the 2 early case.

Minimal staining with antilaminin antibody was detected in the control cases.

Conclusions : Serum and urinary laminin are early markers of diabetic nephropathy.

The normo and micro albuminuric diabetic patients with raised serum and urinary laminin excretion might have more advanced glomerular and /or tubular lesions who will develop renal functional abnormalities later in the course of the disease .

Long term follow up studies are necessary in order to show the diagnostic relevance of urinary laminin excretion compared with those of albumin and tubular markers and to estimate their future predictive values for the development of clinical diabetic nephoropathy.