Influence of irbesartan on the urinary excretion of cytokines in patients with chronic kidney disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD.</p><p><b>METHODS</b>In this randomized perspective clinical trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two groups of patients in a cross-over design. Blood pressure (BP), creatinine clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant.</p><p><b>RESULTS</b>Urinary excretion of cytokines (granulocyte colony stimulating factor (GCSF), intercellular cell adhesion molecule-1 (ICAM-1), interferon γ (IFN-γ), interleukin 1β (IL-1b), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1d (MIP-1d)) in group B (irbesartan 300 mg/d) was significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-γ, IL-1a, IL-11, IL-12p40, MCP-2, MIP-1a), while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1a by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.</p><p><b>CONCLUSION</b>Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cytokines excretion in the urine of CKD patients.</p>

Connective tissue growth factor is associated with the early renal hypertrophy in uninephrectomized diabetic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Renal hypertrophy has been regarded as the early feature of diabetic nephropathy (DN), which may eventually lead to proteinuria and renal fibrosis. However, the exact mechanism of renal hypertrophy is still unclear. The aim of this study was to investigate the possible association of connective tissue growth factor (CTGF) with renal hypertrophy in uninephrectomized diabetic rats.</p><p><b>METHODS</b>Seventy-two Sprague-Dawley (SD) rats were randomly divided into two groups: control group (group C, n = 32) and diabetic nephropathy (group DN, n = 40). Each group was re-divided into 4 subgroups according to the experimental period. The rats were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) after rats had received uninephrectomy. Blood glucose (BG), body weight (BW), 24-h urinary albumin excretion (24hUalb), kidney weight (KW), KW/BW, glomerular tuft area (AG), glomerular tuft volume (VG), proximal tubular area (AT) at each time point, the width of glomerular basement membrane (GBM) and tubular basement membrane (TBM) at week 8 were measured when the rats were sacrificed. Renal expression of CTGF and p27kip1 were detected by immunohistochemical staining. The relationship between CTGF expression and increasing of VG and AT was analyzed.</p><p><b>RESULTS</b>There was a significant increase of 24hUalb, KW, and KW/BW from week 1 onward in diabetic rats compared to those in group C (P < 0.05, respectively), diabetic rats also had a significant increase of AG, VG, and AT from week 1 onward. It was also shown that diabetic rats had a thickening of GBM [(245.7 +/- 103.0) nm vs (121.8 +/- 19.1) nm, P < 0.01] and TBM [(767.7 +/- 331.1) nm vs (293.0 +/- 110.5) nm, P < 0.01] at week 8. There was a weak expression for CTGF and p27kip1 in normal glomeruli and tubuli, while a significant increasing expression of CTGF and p27kip1 was found in glomeruli and tubuli in diabetic kidney from week 1 onward (P < 0.05, respectively), and the extent of CTGF expression was positively correlated with AG (r = 0.92, P < 0.05), VG (r = 0.86, P < 0.05), AT (r = 0.94, P < 0.01) and positively correlated with the expression of p27kip1 (r = 0.96, P < 0.01).</p><p><b>CONCLUSION</b>The expression of CTGF increases in diabetic rat kidney at the early stage, which might be an important mediator of renal hypertrophy through arresting cell cycling.</p>