Effects of Angiotensin-Converting Enzyme Inhibitor, Angiotensin II Receptor Antagonist and Calcium Antagonist on Urinary Podocytes in Patients with IgA Nephropathy

Abstract

The urinary podocyte is postulated to be a marker for estimation of the severity of active glomerular injury and a predictor of disease progression in children with glomerulonephritis. Non-dihydropyridine calcium antagonist, including verapamil, reduce proteinuria to an extent similar to that of the angiotensin-converting enzyme inhibitor (ACEI), including trandolapril, but to a greater extent than other antihypertensives. Angiotensin (Ang) II receptor antagonists, including candesartan cilexetil, show potent and long-term preventive effects against the progression of renal injury. The aim of the present study is to assess whether verapamil, trandolapril and candesartan cilexetil affect proteinuria and urinary podocytes in patients with IgA nephropathy. Thirty-two normotensive patients aged 18-54 years with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (1-3 g/day), and normal renal function (creatinine clearance >80 ml/min) were studied. Twenty patients with diffuse mesangial proliferative glomerulonephritis (non-IgA PGN) and 20 healthy controls were also included in this study. The number of urinary podocytes in patients with advanced IgA nephropathy (n = 16) was significantly higher than that in patients with the disease in the mild stage (n = 16) (p < 0.01) or in patients with non-IgA PGN (p < 0.01). Urinary podocytes were not detected in healthy controls. The 32 patients with IgA nephropathy were randomly divided into four treatment groups: those treated with verapamil (120 mg/day, n = 8); those treated with trandolapril (2 mg/day, n = 8); those treated with candesartan cilexetil (8 mg/day, n = 8), and those given a placebo (n = 8). Treatment continued for 3 months. Antiproteinuric response in the trandolapril group was similar to that in the candesartan cilexetil group (-38 vs. -40%). The action of trandolapril or candesartan cilexetil was greater than that of verapamil (p < 0.01). Reduction in the number of urinary podocytes from baseline was significantly greater in patients treated with trandolapril or candesartan cilexetil than in patients treated with verapamil (p < 0.01). However, there was no difference between patients treated with trandolapril and those treated with candesartan cilexetil. Proteinuria and urinary podocytes were unaffected in the placebo group. These data suggest that urinary podocytes may be a marker of disease activity in adult patients with IgA nephropathy and that trandolapril and candesartan cilexetil are more effective than verapamil in reducing the number of podocytes.

Cumulative Excretion of Urinary Podocytes Reflects Disease Progression in IgA Nephropathy and Scho[Combining Diaeresis]nlein-Henoch Purpura Nephritis

“…These results indicate that u-podo reflect acute glomerular injury, as shown in our previous studies (29,30). Prolonged excretion of u-podo was observed in the cases with disease progression, indicating that acute glomerular injury persisted in such cases.…”

Relationship between Urinary Podocytes and Kidney Diseases

“…Several studies have also indicated that the number of PDX-positive cells in the urine falls after various therapeutic interventions in patients with FSGS, LN, HSP, IgAN, PSGN, and DN. [20][21][22][23][24][25][26] Compared with other markers, PDX proved to be the most reproducible marker for podocyte assessment in the urine of these patients. According to Vogelmann et al, 27 the cells that stained positive for PDX also stained positive for 30-40% of the other podocyte-specific markers.…”

Podocyte Biology and Response to Injury

“…Indeed, studies by Hara and colleagues (123)(124)(125) showed that cells obtained in the urine of patients with various glomerular diseases stained positive for the podocyte marker, podocalyxin. Similar results have been shown in PAN model of podocyte injury in rats (107).…”