lisinopril and Glomerulonephritis--Membranous

In this prospective study, the effects of an angiotensin-converting enzyme inhibitor [lisinopril (LIS)] and an angiotensin II receptor antagonist [losartan (LOS)] were compared in nephrotic patients with idiopathic membranous nephropathy.. Twenty-seven patients (13 males, mean age +/- SD 51.3 +/- 15.4 years) were treated with LIS (13 patients, six males, mean age 52.1 +/- 15.3 years) or LOS (14 patients, seven males, mean age 50.5 +/- 15.5 years) for 12 months. At baseline and after the treatment period, serum albumin, total cholesterol, estimated glomerular filtration rate (GFR), 24 h proteinuria and mean arterial pressure were determined.. Proteinuria (g/24 h) was significantly reduced in both groups (LIS from 4.82 +/- 1.26 to 1.75 +/- 0.64, p < 0.0001; LOS from 4.55 +/- 1.09 to 2.54 +/- 1.94, p = 0.002) (all results +/- SD). Serum albumin levels (g/dl) increased significantly in both groups (LIS 2.27 +/- 0.41 to 3.17 +/- 0.63, p < 0.0001; LOS 2.93 +/- 0.40 to 3.55 +/- 0.44, p < 0.0001). GFR (ml/min x 1.73 m(2)) did not change significantly in either group (LIS 55 +/- 17 to 56 +/- 17, p = 0.65; LOS 64 +/- 18 to 59 +/- 16, p = 0.13). Total cholesterol (mg/dl) was significantly reduced only in the lisinopril group (LIS 347 +/- 81 to 266 +/- 64, p < 0.0001; LOS 306 +/- 58 to 263 +/- 77, p = 0.138). Mean arterial pressure (mmHg) was reduced in both groups (LIS 107 +/- 12 to 95 +/- 6, p < 0.0001; LOS 104 +/- 10 to 96 +/- 5, p = 0.003). In the comparison between the two groups, serum albumin levels were higher in the losartan group at baseline (p < 0.0001) and after 12 months (p = 0.029). There were no significant differences between the baseline and end-of-study values for the rest of the studied parameters.. Treatment with lisinopril and losartan in nephrotic patients with idiopathic membranous nephropathy results in similar (and significant) effects on renal function, hypoalbuminaemia, proteinuria and blood pressure.

Topics: Adult; Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Hypercholesterolemia; Lisinopril; Losartan; Male; Middle Aged; Nephrotic Syndrome; Prevalence; Prospective Studies; Proteinuria

In this prospective randomized trial, we compared the effects of cyclosporine- and cyclophosphamide-based treatment regimens in patients with idiopathic membranous nephropathy. Twenty-eight patients were randomized to receive treatment with one of the three therapeutic regimens: cyclosporine with methylprednisolone, cyclophosphamide with methylprednisolone or lisinopril (control). Renal function and nephrotic syndrome parameters were determined at baseline and during a 9-month treatment period. At the end of the study period, renal function improved significantly in the cyclophosphamide and deteriorated significantly in the cyclosporine group. Serum albumin levels increased significantly in the cyclosporine and cyclophosphamide group. Total cholesterol levels and proteinuria were significantly reduced in all groups. In the comparison between the groups, serum albumin levels were significantly lower in the control group and there were no differences in the rest of the studied parameters at the end of the study. Six patients from the cyclosporine group (1/10 complete and 5/10 partial), all cyclophosphamide-treated (4/8 complete and 4/8 partial) and all 10 lisinopril-treated patients (10/10 partial) were on remission at the end of the study. In conclusion, cyclosporine-based regimens are not inferior to cyclophosphamide-based regimens. Cyclophosphamide is associated with more complete remissions after 9 months of treatment. Lisinopril is associated with a significant proteinuria reduction and without inducing any complete remissions.

Topics: Cyclophosphamide; Cyclosporine; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Lisinopril; Male; Middle Aged; Nephrotic Syndrome; Prospective Studies

Renin-angiotensin-aldosterone system (RAAS) blockade provides renoprotective effects in chronic kidney disease (CKD); yet progressive renal function loss remains common. Dietary sodium restriction potentiates the renoprotective effects of RAAS blockade. Vitamin D receptor activator (VDRA) treatment reduces proteinuria, inflammation and fibrosis, but whether these effects depend on sodium intake has not been studied. We hypothesized that the renoprotective effects of VDRA treatment, with or without RAAS blockade, are modulated by sodium intake.. Six weeks after the induction of adriamycin nephrosis in Wistar rats, i.e. with established proteinuria, animals were treated with the VDRA paricalcitol, lisinopril, the combination, or vehicle; each treatment was given during either a high- (2% NaCl) or a low-sodium (0.05% NaCl) diet for 6 weeks. We assessed proteinuria, blood pressure, renal macrophage accumulation and renal expression of the pre-fibrotic marker alpha-smooth muscle actin (α-SMA) at the end of the treatment.. Both paricalcitol and lisinopril individually, as well as in combination, reduced proteinuria and glomerular and interstitial inflammation during a low-sodium diet, but not during a high-sodium diet. All interventions also reduced focal glomerulosclerosis and interstitial expression of α-SMA during the low-sodium diet, while similar trends were observed during the high-sodium diet. The renoprotective effects of paricalcitol were not accompanied by blood pressure reduction. As proteinuria was already abolished by lisinopril during the low-sodium diet, the addition of paricalcitol had no further effect on proteinuria or downstream inflammatory or pre-fibrotic changes.. The renoprotective effects of the VDRA paricalcitol are blood pressure independent but do depend on dietary sodium status. The combination of RAAS blockade, dietary sodium restriction and VDRA may be a promising intervention to further retard renal function loss in CKD.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bone Density Conservation Agents; Diet, Sodium-Restricted; Ergocalciferols; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Kidney; Lisinopril; Male; Peptidyl-Dipeptidase A; Proteinuria; Rats; Rats, Wistar; Receptors, Calcitriol; Renin-Angiotensin System; Sodium Chloride, Dietary; Sodium, Dietary

A 32-year-old male patient was admitted at our department presenting microhematuria and full nephrotic syndrome in April 1995. A percutaneous kidney biopsy showed a stage I-lI membranous nephropathy and an eight-week course with oral prednisone was initiated without response. Then, oral cyclosporine A (3.5 mg/kg/day) was given and after 5 weeks of treatment, remission of the nephrotic syndrome was observed but creatinine raised to 1.6 mg/dl, normalizing after reducing the dose of cyclosporine A. We discuss the settings, prognostic and therapeutic alternatives for idiopathic membranous nephropathy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcineurin Inhibitors; Calcium Channel Blockers; Creatinine; Cyclosporine; Drug Therapy, Combination; Glomerulonephritis, Membranous; Humans; Hypercholesterolemia; Hypertension; Hypolipidemic Agents; Immunosuppressive Agents; Kidney Diseases; Lisinopril; Lovastatin; Male; Nephrotic Syndrome; Prednisone; Recurrence; Verapamil

In several models of renal disease progression, angiotensin-converting enzyme (ACE) inhibitors reduced proteinuria and limited glomerulosclerosis, which suggested that reduction of renal angiotensin II (Ang II) activity is crucial for the preservation of glomerular structure and function. However, it cannot be ruled out that other hormonal systems, including inhibition of the bradykinin breakdown, also play a role. We compared the effects of chronic treatment with the ACE inhibitor lisinopril with those of a specific Ang II receptor antagonist, L-158,809, on proteinuria and renal injury in passive Heymann nephritis (PHN), a model of immune renal disease that closely resembles human membranous nephropathy, with long-lasting proteinuria followed by tubulointerstitial damage and glomerulosclerosis. Passive Heymann nephritis was induced with 0.5 mL/100 g of rabbit anti-Fx1A antibody in 24 male Sprague-Dawley rats. The animals were divided into three groups of eight rats each, and were given the following in the drinking water on a daily basis: lisinopril (40 mg/L), L-158,809 (50 mg/L), or no therapy. Treatment started at day 7 (proteinuria was already present) and lasted 12 months. Eight normal rats were used as controls. Untreated PHN rats developed hypertension, while rats with PHN given lisinopril or L-158,809 all had systolic blood pressure values even lower than those of normal rats. Urinary protein excretion progressively increased with time in untreated PHN rats, who developed tubulointerstitial damage and glomerulosclerosis. Both lisinopril and L-158,809 exhibited a potent antiproteinuric effect and preserved glomerular and tubular structural integrity at a similar extent. Renal gene expression of transforming growth factor-beta and extracellular matrix proteins was also effectively reduced by the two treatments. These results indicate that ACE inhibitors and Ang II receptor antagonists are equally effective in preventing renal injury in PHN and suggest that the renoprotective effects of ACE inhibitors in this model are solely due to inhibition of Ang II.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Chronic Disease; Extracellular Matrix Proteins; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Imidazoles; Kidney; Lisinopril; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Renal Plasma Flow; Tetrazoles; Transforming Growth Factor beta