ramipril and Nephritis--Interstitial

Angiotensin-converting enzyme (ACE) inhibitors are the drugs of choice for the treatment of hypertension in patients with non-diabetic nephropathies. However, not every trial has reported better results with ACE inhibitors (ACE-I) than with other drugs. This study investigates whether the acute and chronic effects of ACE inhibition on renal and glomerular haemodynamics are similar in glomerular and interstitial nephropathies.. We studied 20 hypertensive patients, on their usual diet, with mild-to-moderate chronic renal failure secondary to non-diabetic nephropathy. After a three-week wash out period, we determined plasma clearances of para-amino-hippurate and inulin before, and after acute oral administration of either enalapril or ramipril. This same test was carried out after one and two years of treatment with the same drug.. Acute ACE inhibition causes a decrease of renal perfusion, glomerular filtration and pressure with an increase of afferent resistances. Long-term ACE inhibition is associated only with a decrease in renal perfusion, with a non-significant tendency to higher filtration fraction and lower afferent resistances. All the renal haemodynamic modifications mentioned above are present only in patients with glomerular diseases.. Renal and glomerular haemodynamic responses are not similar after acute and chronic ACE inhibition. Only patients with glomerular diseases show acute or long-term responses to ACE inhibition.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypertension, Renal; Inulin; Kidney Failure, Chronic; Kidney Function Tests; Kidney Glomerulus; Male; Middle Aged; Nephritis, Interstitial; p-Aminohippuric Acid; Ramipril; Renal Circulation

Autoimmune pancreatitis is a rare form of pancreatitis characterized by responsiveness to steroid therapy and an often relapsing disease course. The mainstay of therapy is oral corticotherapy. Associations of interstitial nephritis with various autoimmune disorders have been described. We hereby report the case of a 69-year-old Caucasian man with a 2-year history of autoimmune pancreatitis, who presented with impairment of kidney function, proteinuria, and hypertension. Renal histopathology showed severe diffuse interstitial nephritis. With oral prednisone and ACE inhibitor therapy, complete recovery of kidney function was not achieved and proteinuria persisted. Therefore, mycophenolate mofetil was initiated. After 8 weeks, serum creatinine decreased, and a nearly complete and sustained resolution of proteinuria was seen, while tapering oral steroid doses. With autoreactive T cells playing a major role in the pathogenesis of both diseases, a common etiology of pancreatitis and interstitial nephritis can be assumed, and the beneficial effects of an inhibitor of lymphocyte proliferation, such as mycophenolate mofetil, can be explained. We infer from our case that mycophenolate mofetil can be effective in the control of simultaneous autoimmune pancreatitis and interstitial nephritis.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Autoimmune Diseases; Cortisone; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephritis, Interstitial; Pancreatitis; Prednisolone; Ramipril

Osteopontin (OPN) mediates progressive renal injury in various renal diseases by attracting macrophages, and its expression is regulated by the renin-angiotensin system (RAS). We studied the association between OPN expression and tubulointerstitial injury, and investigated the effect of ramipril on OPN expression in an animal model of non-insulin-dependent diabetes mellitus (NIDDM): Otsuka Long-Evans Tokushima Fatty (OLETF) rats.. Control (Long-Evans Tokushima Otsuka, LETO) and diabetic (OLETF) rats were treated with ramipril (3 mg/kg in drinking water) or vehicle for nine months, starting at 20 weeks of age. Systolic blood pressure, body weight, urinary protein excretion and oral glucose tolerance tests (OGTT) were monitored periodically. Renal function, histology (glomerulosclerosis, tubulointerstitial fibrosis, and ED-1-positive cells as a measure of macrophage infiltration), and expressions of OPN and transforming growth factor-beta1 (TGF-beta1) were evaluated at the end of the study.. Compared with the LETO rats, OLETF rats showed declines in creatinine clearance rate, increases in urinary protein excretion and systolic blood pressure, and development of glomerulosclerosis, tubulointerstitial fibrosis, and inflammatory cell infiltration (all P < 0.05). Blocking angiotensin II with ramipril significantly improved all of these parameters (all P < 0.01). At the molecular level, expressions of OPN and TGF-beta1 were up-regulated in the OLETF rats, and were markedly suppressed following ramipril treatment. The sites of strong OPN mRNA and protein expressions were localized to areas of renal injury. Of note, the expression of OPN mRNA was strongly correlated with the number of ED-1-positive cells (r = 0.560, P = 0.01) and the tubulointerstitial fibrosis score (r = 0.500, P < 0.05).. Up-regulation of OPN expression may play a role in tubulointerstitial injury associated with diabetic nephropathy, and blockade of the RAS by ramipril may confer renoprotection by decreasing OPN expression in non-insulin-dependent diabetic nephropathy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Administration Schedule; Ectodysplasins; Kidney; Macrophages; Male; Membrane Proteins; Nephritis, Interstitial; Osteopontin; Ramipril; Rats; Rats, Inbred OLETF; Rats, Long-Evans; RNA, Messenger; Sialoglycoproteins; Transforming Growth Factor beta; Transforming Growth Factor beta1

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Glucose; Blood Pressure; Creatinine; Cystatin C; Cystatins; Diabetic Nephropathies; Female; Glomerulonephritis; Glycation End Products, Advanced; Homocysteine; Humans; Lipofuscin; Lysine; Male; Malondialdehyde; Middle Aged; Nephritis, Interstitial; Oxidative Stress; Polycystic Kidney Diseases; Ramipril; Severity of Illness Index; Statistics as Topic; Treatment Outcome

Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule and has been shown to play a role in glomerular and tubulointerstitial injury in several kidney disease models.. The present study examined whether OPN expression is involved in the progression of renal disease following subtotal (5/6) nephrectomy (STNx) in rats and whether angiotensin II (Ang II) mediates the up-regulation of renal OPN expression and macrophage accumulation in this model by administering valsartan, an Ang II type I (AT1) receptor antagonist, or ramipril, an angiotensin-converting enzyme (ACE) inhibitor.. In normal and sham-operated rat kidneys, OPN was expressed in a few tubules (<5%) and was absent in glomeruli. Following STNx (weeks 2 to 16), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli [2 to 12 cells/glomerular cross section (gcs)] and tubular epithelial cells (20 to 75% OPN+). The up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histologic damage, including tubulitis and tubulointerstitial fibrosis (all P < 0.001). Treatment with either valsartan or ramipril completely abrogated the up-regulation of OPN mRNA and protein expression in glomeruli and tubules. The reduction in OPN expression was associated with a significant inhibition of macrophage accumulation and progressive renal injury (P < 0.001).. An up-regulation of OPN expression may play a role in progressive renal injury following STNx. Inhibition of OPN expression may be one of the mechanisms by which Ang II blockade attenuated renal injury after renal ablation.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Blotting, Northern; Disease Models, Animal; Gene Expression; In Situ Hybridization; Kidney; Macrophages; Male; Nephrectomy; Nephritis, Interstitial; Osteopontin; Ramipril; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sialoglycoproteins; Tetrazoles; Valine; Valsartan