Renal disorders involved in the pathophysiology of urinary excretion of a-1 microglobulin in patients with glomerulopathies.
OBJECTIVE
The protein alpha1-microglobulin (alpha1-microg) is filtered by the glomeruli and fully reabsorbed by the proximal tubules, and tubulointerstitial injury compromises its reabsorption. The aim of this study was to determine which functional, morphological and inflammatory renal disorders associated with tubulointerstitial damage interfere with urinary excretion of alpha1-microg in patients with glomerulopathies.


METHODS
38 patients (33.6 +/- 11.3 years) with primary or secondary glomerulopathies diagnosed by renal biopsies were studied. The urinary fractional excretion of alpha1-microg (FEalpha1-microg), the urinary monocyte chemoattractant protein-1/urinary creatinine (UMCP-1) index and 24-h proteinuria were determined. In the cortex of renal biopsies, the number of macrophages/104 microm2 of glomerular tuft (GT) and tubulointerstitial (TI) areas, the relative interstitial area (RCIA), and the relative interstitial fibrosis area (CIF) were measured. Results are reported as median and range and the Spearman non-parametric test was used to determine the correlations.


RESULTS
FEalpha1-microg was 0.165% (0.008% - 14,790.0%) in patients with glomerulopathies and 0.065% (0.010% - 0.150%) in the control group (p < 0.05; Mann-Whitney U-Test). FEalpha1-microg was correlated with creatinine clearance (r = -0.4396; p = 0.0358), UMCP-1 index (r = 0.5978; p < 0.0001), number of macrophages/TI area (r = 0.5634; p = 0.0034) and RCIA (r = 0.7436; p < 0.0001). However, FEa1-microg was not correlated with proteinuria (r = 0.1465; p = 0.5153) or with CIF (r = 0.0039; p = 0.98).


CONCLUSIONS
renal MCP-1 and the expansion and number of macrophages of the tubulointerstitial area participate in the increase of urinary excretion of alpha1-microg in patients with glomerulopathies. Although proteinuria and interstitial fibrosis have not been associated with this effect, the present study does not exclude some of these disorders in the pathophysiology of urinary excretion of alpha1-microg.
Romão
E A
EA
University of São Paulo, Brazil.
Coimbra
T M
TM
Costa
R S
RS
Vieira Neto
O M
OM
Reis
M A
MA
Rodrigues Júnior
A L
AL
Ribeiro
R A
RA
Ravinal
R C
RC
Dantas
M
M
D000328:Adult; D000510:Alpha-Globulins / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D018932:Chemokine CCL2 / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009391:Nephelometry and Turbidimetry; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology / Q000652:urine*
D000510:Alpha-Globulins; D015415:Biomarkers; D018932:Chemokine CCL2; C016001:alpha-1-microglobulin; D003404:Creatinine