enalapril and Glomerulonephritis--Membranoproliferative

A 35-year-old renal transplant patient with stable renal function developed an unexplained anaemia. Appropriate investigations proved non-diagnostic. Only when enalapril therapy was stopped did the anaemia reverse and haemoglobin levels returned to pre-treatment levels. An association between angiotensin-converting enzyme inhibitors and anaemia in patients with renal failure is becoming more evident. A literature review of this problem and its possible pathogenesis in patients with renal failure is given.

Topics: Adult; Anemia; Combined Modality Therapy; Drug Therapy, Combination; Enalapril; Glomerulonephritis, Membranoproliferative; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Male; Nephrotic Syndrome; Postoperative Complications

To determine the effect of enalapril, angiotensin-converting-enzyme inhibitor (ACE-I) on progression of renal insufficiency in primary membranoproliferative glomerulonephritis with mild to moderate renal insufficiency.. Thirty patients with histopathologically proved MPGN having hypertension (grade I and II of JNC-VI criteria of hypertension) and mild to moderate impairment of renal function (creatinine clearance varying from 30-80 ml/min, significant albuminuria and serum creatinine 1.2-3.0 mg/dl) were initially treated with diuretics and 3-blockers to bring down BP < 140/90 mm Hg. These patients were then randomly divided into three groups of 10 each, group I--Control; group II--Nifedipine and group III--Enalapril. In group II and III Nifidepine 30 mg/day and in group III Enalapril 10 mg/day respectively were added in addition and treatment was continued for nine months. These patients were followed up monthly for drug efficacy, side effects and any adverse drug reaction.. Out of 30, 28 patients completed the study. At the end of nine months of treatment the patients of control group revealed significant increase in serum creatinine (1.65 +/- 0.38 to 2.17 +/- 0.31 mg/dl), blood urea (34.0 +/- 3.9 to 40.0 +/- 3.1 mg/dl), and 24 hours albuminuria (3.6 +/- 0.6 to 4.2 +/- 0.6 gm) and decrease in creatinine clearance (60.3 +/- 13.3 to 37.5 +/- 11.8 m/min); however, in enalapril group there was decrease in serum creatinine (1.72 +/- 0.45 to 1.24 +/- 0.58 mg/dl), blood urea (34.6 +/- 4.7 to 28.1 +/- 6.7 mg/dl) and 24 hours albuminuria (3.3 +/- 1.0 to 1.6 +/- 1.1 gm) and increase in creatinine clearance (56A +/- 15.8 to 77.1 +/- 23.5 ml/min). The patients on nifedipine showed statistically nonsignificant changes in creatinine clearance, blood urea and serum creatinine; while albuminuria increased from 3.0 +/- 1.3 to 3.9 +/- 0.4 gm/24 hours (p < 0.01). The blood pressure was well controlled in all patients. None of the patient had side effects leading to withdrawal of drugs. No adverse drug reaction was noted.. ACE-I (enalapril) provided protection against the progression of renal insufficiency in patients of MPGN having hypertension with mild to moderate renal impairment. The renoprotective effects of ACE inhibitor (enalapril) is associated with substantial decrease in albuminuria.

Topics: Adult; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Enalapril; Female; Follow-Up Studies; Glomerulonephritis, Membranoproliferative; Humans; Hypertension; Kidney Function Tests; Male; Middle Aged; Nifedipine; Probability; Renal Insufficiency; Severity of Illness Index; Treatment Outcome

The clinical course of a 10-year-old female patient who presented with hematuria, proteinuria, and hypertension is described. Four months after being diagnosed with acute glomerulonephritis, the child was referred to a pediatric nephrologist due to persistent hematuria and unresolved proteinuria. A renal biopsy was performed due to the persistent urinary abnormalities and a family history of renal failure. The renal biopsy demonstrated pathological findings characteristic of membranoproliferative glomerulonephritis type II. The child was treated with an antihypertensive agent and steroids. Despite poor prognostic clinical and pathological features, she has minimal urinary abnormalities, normal renal function, and normal blood pressure on antihypertensive medication six years after the diagnosis of membranoproliferative glomerulonephritis type II.

Topics: Child; Clinical Chemistry Tests; Diagnosis, Differential; Drug Therapy, Combination; Enalapril; Female; Fluorescent Antibody Technique, Direct; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Hematologic Tests; Humans; Hypertension; Kidney Diseases; Kidney Glomerulus; Methylprednisolone; Prednisone; Treatment Outcome

We examined the effects of KD3-671 (2-propyl-8-oxo-1-[(2'-(H-tetrazole-5-yl)biphenyl-4-yl)methyl]-4,5,6,7-tetrahydrocycloheptimidazole), an angiotensin II type1 receptor antagonist, on an experimental rat model of mesangioproliferative glomerulonephritis, anti-Thy-1 nephritis. Anti-Thy-1 nephritis was induced by intravenous injection of 300 microg/kg of anti-Thy-1.1 monoclonal antibody into rats. KD3-671 (3, 10, 30 mg/kg per day) or enalapril (30 mg/kg per day), an angiotensin II converting enzyme inhibitor, was given p.o. once daily from the day before the antibody injection (the 1st day) to the 15th day after. KD3-671 significantly inhibited an increase in the number of total and proliferating cell nuclear antigen-positive cells and the deposition of alpha-smooth muscle actin and fibronectin in the glomeruli of nephritic rats, but enalapril (30 mg/kg per day) suppressed only the number of total cells and the deposition of alpha-smooth muscle actin in the glomeruli. Moreover, to elucidate the effect of KD3-671 on matrix deposition in the glomeruli, we measured the production of fibronectin in isolated glomeruli obtained from anti-Thy-1 nephritic rats. The glomeruli in anti-Thy-1 nephritic rats produced more fibronectin than that in control rats. KD3-671 (10(-8), 10(-7), 10(-6) M) dose-dependently attenuated fibronectin production in isolated nephritic glomeruli. These findings suggest that KD3-671 may be an effective agent for the treatment of mesangioproliferative glomerulonephritis.

Topics: Actins; Administration, Oral; Angiotensin II Type 1 Receptor Blockers; Animals; Antibodies, Monoclonal; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Fibronectins; Glomerulonephritis, Membranoproliferative; Imidazoles; Isoantibodies; Kidney Glomerulus; Male; Rats; Rats, Sprague-Dawley; Tetrazoles

Overproduction of transforming growth factor-beta (TGF-beta) is a key mediator of extracellular matrix accumulation in fibrotic diseases. We hypothesized that the degree of reduction of pathological TGF-beta expression can be used as a novel index of the antifibrotic potential of angiotensin II (Ang II) blockade in renal disease.. One day after induction of Thy 1.1 glomerulonephritis, rats were treated with increasing doses of the Ang I converting enzyme (ACE) inhibitor enalapril and/or the Ang II receptor blocker losartan in the drinking water. Six days after disease induction the therapeutic effect on glomerular TGF-beta overexpression was evaluated.. Both enalapril and losartan reduced TGF-beta overproduction in a dose-dependent manner, showing a moderate reduction at doses known to control blood pressure in renal forms of hypertension. A maximal reduction in TGF-beta expression of approximately 45% was seen for both drugs starting at 100 mg/liter enalapril and 500 mg/liter losartan, with no further reduction at doses of enalapril up to 1000 mg/liter or losartan up to 2500 mg/liter. Co-treatment with both drugs was not superior to single therapy. Consistent with our hypothesis that reduction in TGF-beta expression is a valid target, other disease measures, including glomerular matrix accumulation, glomerular production and mRNA expression of the matrix protein fibronectin and the protease inhibitor plasminogen-activator-inhibitor type 1 (PAI-1) closely followed TGF-beta expression.. The data suggest that these therapies act through very similar pathways and that, in order to more effectively treat renal fibrosis, these drugs must be combined with other drugs that act by different mechanisms.

Topics: Angiotensin II; Animals; Blood Pressure; Body Weight; Eating; Enalapril; Fibronectins; Fibrosis; Glomerulonephritis, Membranoproliferative; Kidney; Losartan; Male; Plasminogen Activator Inhibitor 1; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta

Loin pain-hematuria (LPH) syndrome is a poorly understood disorder in which the patients, mainly young women, experience unexplained severe chronic unilateral or bilateral flank pain associated with gross and/or microscopic hematuria. By contrast, thin glomerular basement membrane (GBM) disease is generally thought to be a benign disorder, affecting males and females equally, in which the major manifestation is asymptomatic microscopic hematuria. Herein we describe seven patients (6 females, 1 male) in whom thin GBM appeared to be the cause of the LPH syndrome. The gross hematuria in these patients could be attributed to thin GBM disease because the renal biopsy demonstrated red cells in renal tubules (indicating glomerular hematuria) and the only glomerular abnormality present with thin GBM. In addition, the other causes of gross hematuria were excluded by appropriate testing. The flank pain in these patients might also have been the result of their thin GBM disease. This is suggested by renal biopsy findings of multiple renal tubules filled with red cells, apparently occluding the tubules. We suggest that occlusion of a relatively small fraction of renal tubules could cause renal pain if back-leak of glomerular filtrate occurred that was of sufficient magnitude to expand renal parenchymal volume and stretch the renal capsule. Preliminary observations suggest that treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril importantly reduces the frequency and severity of the episodes of gross hematuria and flank pain in most patients. ACE inhibition might decrease glomerular hemorrhage in patients with think GBM by decreasing glomerular hydrostatic pressure. We conclude that (1) Thin GBM disease can be the cause of gross hematuria, apparently as a result of rupture of thin GBM. (2) Rupture of thin GBM resulting in hemorrhage into renal tubules may be the cause of the flank pain and gross hematuria in some patients with the LPH syndrome.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Enalapril; Female; Glomerulonephritis, Membranoproliferative; Hematuria; Humans; Male; Middle Aged; Retrospective Studies

Ten patients (6 men, 4 women, age range 35-64 years) with glomerulopathies were studied. Diagnoses were membranoproliferative glomerulonephritis (GN; n = 4), membranous GN (n = 3), focal and diffuse glomerulosclerosis (n = 2), and poststreptococcal GN (n = 1). These were confirmed by renal biopsy in 8 of the 10 patients. All patients had reduced function (creatinine clearance 15-55 ml/min); proteinuria ranged from 1.0 to 10.4 g/day. Three normotensive patients received enalapril 10 mg once daily. Seven hypertensives received enalapril 10-40 mg once daily to control blood pressure (BP). Concomitant diuretic therapy (furosemide/bumetanide) was administered to 6 patients. There were visits every 14 days for a mean of 15.9 months (range 9-26 months). Diet was monitored, and BP was significantly controlled in the hypertensive patients but not altered in the normotensives. Serum creatinine, blood urea nitrogen, creatinine clearance, and 24-hour urinary protein improved and did not deteriorate progressively. Serum potassium did not change significantly. No adverse clinical events were noted. Enalapril therapy may improve the prognosis for GN over time by maintaining glomerular filtration rate and decreasing proteinuria.

Topics: Adult; Chronic Disease; Creatinine; Enalapril; Female; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Hypertension; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Proteinuria; Time Factors

The aim of the study was to evaluate the long term antihypertensive effect of nicardipine in hypertensive patients with chronic renal disease. Eight patients (creatinine clearance ranging from 51 to 78 ml/min/1.73 m2) received nicardipine (20 mg t.i.d.). Four weeks later, patients with diastolic blood pressure greater than or equal to 90 mmHg in recumbent position, were given enalapril (10 mg/day) as well. Blood pressure control was achieved in 3 patients treated with nicardipine alone and in 5 patients on a combined nicardipine-enalapril regimen, and it was maintained throughout the whole trial period (52 weeks). In two cases serum creatinine rose from 2.3 to 3.3 and from 1.4 to 2.2 respectively. However, the slope of the creatinine ratio, plotted against time, showed a significant reduction in renal function loss as compared to expected values. In conclusion, nicardipine, alone or in combination with enalapril, is an effective and well tolerated drug for use in treatment of hypertension secondary to chronic renal disease.

Topics: Adult; Drug Evaluation; Drug Therapy, Combination; Enalapril; Female; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Hypertension, Renal; Male; Middle Aged; Nicardipine; Polyarteritis Nodosa