temocapril-hydrochloride and Glomerulonephritis--IGA

A 70-year-old man with polycystic kidney disease developed nephrotic syndrome, deteriorating to renal insufficiency. Histological examination revealed IgA nephropathy. With treatment of prednisolone, an angiotensin-converting enzyme inhibitor, and an angiotensin II receptor-blocker, his proteinuria markedly decreased and renal function was stabilized. This case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria, for appropriate treatment and prevention of renal failure.

Topics: Aged; Biopsy; Dipyridamole; Glomerulonephritis, IGA; Humans; Kidney; Losartan; Male; Nephrotic Syndrome; Polycystic Kidney, Autosomal Dominant; Prednisolone; Thiazepines

Liver-type fatty acid-binding protein (L-FABP) is a clinical biomarker of tubulointerstitial damage, which plays an essential role in the progression of chronic kidney disease (CKD), including immunoglobin A (IgA) nephropathy. The effect of combination therapy with the angiotensin receptor blocker (ARB) and the angiotensin-converting enzyme inhibitor (ACEI) on CKD has not been elucidated.. Twenty-four normotensive patients with IgA nephropathy were randomly assigned to receive olmesartan 10 mg/day, temocapril 2 mg/day, or combination therapy with both drugs. Urinary levels of L-FABP as well as 8-hydroxydeoxyguanosine (8-OHdG) and protein excretion were measured before and after 3 months of treatment. The chronicity index and activity index were also assessed by histopathologic findings.. Urinary levels of L-FABP and 8-OHdG were higher in patients with IgA nephropathy than in age-matched and sex-matched healthy controls (122.5 +/- 25.5 v 6.4 +/- 3.8 mug/g.creatinine, P < .001; and 22.6 +/- 4.4 v 4.8 +/- 1.4 ng/mg.creatinine, P < .01, respectively). Urinary levels of L-FABP were correlated with those of 8-OHdG (baseline, P = .0001; after 3 months, P = .008) and the severity of proteinuria (baseline, P = .0015; after 3 months, P = .0001). The percent reductions in urinary levels of L-FABP and 8-OHdG, protein excretion, and activity index after 3 months were greater in the combination therapy group, compared with each monotherapy group of olmesartan (P < .05) and temocapril (P < .05).. The data suggest that a combination therapy of ARB plus ACEI has a greater beneficial effect on renal injury compared with monotherapy using ARB or ACEI in normotensive patients with IgA nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Deoxyguanosine; Double-Blind Method; Drug Therapy, Combination; Fatty Acid-Binding Proteins; Female; Glomerulonephritis, IGA; Heart Rate; Humans; Imidazoles; Male; Proteinuria; Tetrazoles; Thiazepines

We are investigating whether aldosterone breakthrough negatively impacts on the antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB).. We examine the role of aldosterone breakthrough in 43 normotensive, proteinuric (0.7 +/- 0.3 g/day) outpatients (aged 41.5 +/- 10.9 years) with immunoglobulin A nephropathy (IgAN) accompanied by stable renal function (creatinine clearance >50 mL/min). The patients were treated with temocapril (1 mg; n = 14), losartan (12.5 mg; n = 16), or a combination therapy (n = 13) for 12 months. We prospectively evaluated blood pressure (BP), urinary protein excretion (UPE), biochemical parameters and the renin-angiotensin-aldosterone system before and after 12 months of treatment.. Although the overall plasma aldosterone concentrations values did not change after any of the treatments administered for 12 months, they eventually increased in 23 (temocapril, seven patients; losartan, eight patients; combination, seven patients) of the 43 patients (53.4%; aldosterone breakthrough), and fell in the remainder (46.6%). Blood pressure and renal function did not differ among the three groups at 12 months. In contrast, UPE was significantly higher in patients with, than without aldosterone breakthrough during temocapril and losartan administration. However, combination therapy induced a more remarkable reduction in UPE regardless of aldosterone breakthrough.. A combination of ACE inhibitors and ARB in normotensive patients with IgAN produces a more profound decrease in proteinuria than either monotherapy. This additive antiproteinuric effect is not dependent on aldosterone breakthrough. Additional larger, prospective, randomized studies will be needed for general acceptance of this strategy.

Topics: Adult; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Heart Failure; Humans; Losartan; Male; Middle Aged; Prospective Studies; Proteinuria; Thiazepines

Tubulointerstitial fibrosis (TIF) is a marker of progression of diabetic and non-diabetic nephropathy, correlating with creatinine clearance (CCr), and functional outcome. Angiotensin-converting-enzyme inhibitors (ACEIs) slow the rate of decline of renal function in proteinuric patients.. To examine whether ACEIs affect TIF, directly or indirectly.. Prospective 3-year follow-up study.. We enrolled 49 patients with IgA nephropathy (IgAN), treating some with ACE inhibitors (n = 26, 1-2 mg/day temocapril or trandolapril) and some with calcium-channel blockers (CCB, n = 23, 2.5-5 mg/day amlodipine). Blood pressure, serum creatinine, and urinalysis were measured monthly, and 24-h endogenous creatinine clearance (CCr) at least once a year.. In the CCB group, TIF was positively correlated with the rate of decline in CCr (dCCr), consistent with previous observations. In the ACEI group, dCCr was lower (0.02 +/- 0.02 vs. 0.06 +/- 0.03), and the TIF-dCCr correlation was absent.. In the absence of post-treatment histological data, it is not possible to say whether ACEIs have an effect on TIF. However, ACEIs appear to slow the progression of renal failure in IgAN, regardless of the degree of TIF at presentation.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Creatinine; Disease Progression; Female; Fibrosis; Glomerulonephritis, IGA; Humans; Indoles; Kidney Tubules; Male; Nephritis, Interstitial; Prospective Studies; Proteinuria; Thiazepines

This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Losartan; Male; Middle Aged; Prospective Studies; Proteinuria; Thiazepines

A 24-year-old Japanese woman with IgA nephropathy was admitted to our hospital due to the development of proteinuria and pretibial edema while on glucocorticoids and an angiotensin-converting-enzyme(ACE) inhibitor. She had been on both medications for more than 2 years. Urinary protein excretion was 2.53 g/day and renal function laboratory data were within the normal range. Plasma aldosterone concentration was high at 248 pg/ml, with normal plasma renin activity. The renal biopsy specimens showed prominent glomerular hypertrophy. Four weeks after the addition of valsartan, an angiotensin II receptor blocker(ARB), urinary protein excretion was remarkably reduced to 0.6 g/day without adversely affecting blood pressure. During the treatment period, proteinuria was maintained at less than 0.6 g/day and renal function remained normal. We propose that glomerular hypertension caused by insufficient suppression of the renin-angiotensin system was an essential factor underlying the increased urinary protein excretion in this patient. Combination therapy of an ARB and an ACE inhibitor appears to have a beneficial effect in patients with IgA nephropathy patients with persistent glomerular hypertension.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Humans; Hypertension, Renal; Renin-Angiotensin System; Tetrazoles; Thiazepines; Treatment Outcome; Valine; Valsartan