Altered transcapillary escape of albumin and microalbuminuria reflects two different pathogenetic mechanisms

We studied the following in normo- and microalbuminuric
hypertensive type 2 diabetic patients: 1) transcapillary
escape rate of albumin (TERalb) and 2)
expression of mRNA slit diaphragm and podocyte proteins
in renal biopsies. Normoalbuminuric subjects had
renal cancer, and kidney biopsy was performed during
surgery. TERalb was evaluated by clearance of 125Ialbumin.
Real-time PCR of mRNA slit diaphragm was
measured in kidney specimens. Albumin excretion rate
(AER) was by definition lower in normoalbuminuric
subjects than in microalbuminuric subjects with typical
diabetic glomerulopathy (group 1), in microalbuminuric
subjects with normal or near-normal glomerular structure
(group 2), and in microalbuminuric subjects with
atypical diabetic nephropathy (group 3). This classification
was based on light microscopy analysis of renal
tissue. TERalb (%/h) was similar in normoalbuminuric
and microalbuminuric group 1, 2, and 3 diabetic patients
(medians: 14.1 vs. 14.4 vs. 15.7 vs. 14.9, respectively)
(ANOVA, NS). mRNA expression of slit diaphragm proteins
CD2AP, FAT, Actn 4, NPHS1, and NPHS2 was
higher in normoalbuminuric patients than in microalbuminuric
patients (groups 1, 2, and 3) (ANOVA, P <
0.001). All diabetic patients had greater carotid artery
intimal thickness than normal control subjects using
ultrasound technique (ANOVA, P < 0.01). In conclusion,
the present study suggests that microalbuminuria identifies
a subgroup of hypertensive type 2 diabetic patients
who have altered mRNA expression of slit
diaphragm and podocyte proteins, even before glomerular
structure shows abnormalities using light microscopy
analysis. On the contrary, altered TERalb and
increased carotid artery intimal thickness are shown by
all hypertensive type 2 diabetic patients, both with
normal and altered patterns of AER. Diabetes 54:
228–233, 2005