ramipril and Glomerulosclerosis--Focal-Segmental

Clinical studies have shown that hyperglycemia can induce early-stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial-mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)-induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF-β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co-treatment of STZ-induced DN rats showed that glomerulosclerosis in early-stage DN was reversible (P < .05 compared with that in STZ-induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Disease Progression; Drug Therapy, Combination; Glomerulosclerosis, Focal Segmental; Kidney; Male; Ramipril; Rats; Rats, Sprague-Dawley; Resveratrol; rho-Associated Kinases; rhoA GTP-Binding Protein; Severity of Illness Index; Signal Transduction; Streptozocin

Topics: Adolescent; Adrenal Cortex Hormones; Antihypertensive Agents; Fibrillins; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Humans; Losartan; Male; Marfan Syndrome; Microfilament Proteins; Ramipril

Recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation with nephrotic syndrome is a serious problem with a high risk of graft loss. The therapeutic role of renin-angiotensin-system (RAS) blockers in recurrent FSGS is not clear. We present the safety and efficacy of an intensified triple RAS blockade with an ACE-inhibitor, an AT 1 receptor blocker and the direct renin inhibitor aliskiren in a 29-year-old renal transplant recipient with biopsy proven recurrence of FSGS and relapsing severe nephrotic syndrome. We subsequently used full dose ramipril, candesartan and aliskiren under a close monitoring of kidney function and electrolytes and examined the effect on proteinuria, clinical course and tolerability over 12 months. We found a significant and sustained antiproteinuric effect under triple RAS blockade. RAS blockade was generally well tolerated. This can offer a new therapeutic approach in selected hypertensive patients with recurrent FSGS.

Topics: Adult; Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Benzimidazoles; Biphenyl Compounds; Drug Therapy, Combination; Female; Fumarates; Glomerulosclerosis, Focal Segmental; Humans; Hypertension, Renal; Kidney Transplantation; Nephrotic Syndrome; Plasma Exchange; Proteinuria; Ramipril; Recurrence; Renin; Renin-Angiotensin System; Rituximab; Tetrazoles

Collapsing glomerulopathy (CG), a variant of idiopathic focal segmental glomerulosclerosis (FSGS), can occur in both human immunodeficiency virus (HIV)-positive and HIV-negative patients. Idiopathic membranous glomerulonephritis (MGN) has been reported to coexist with FSGS, but rarely with CG. We report 3 HIV-negative patients (2 men, 1 woman) who developed nephrotic syndrome secondary to MGN complicated by CG, with relatively rapid disease progression despite aggressive therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Disease Progression; Female; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; HIV Seronegativity; Humans; Immunosuppressive Agents; Kidney; Male; Nephrotic Syndrome; Ramipril; Renal Replacement Therapy; Retrospective Studies