Cyclophosphamide in steroid-dependent nephrotic syndrome.Dec 23, Author: Diuretics are used to reduce edema. Renal biopsy is very helpful to differentiate minimal-change disease and its variants such as IgM nephropathy and C1q nephropathy. Very few bulking vs cutting dieta trials are available to guide treatment for minimal-change disease in adults. Immunosuppressive medications other than steroids are usually reserved for steroid-resistant cyclophosphamide steroid dependent nephrotic syndrome with persistent edema, or for steroid-dependent patients with significant steroid-related adverse effects.
Treatment with Cyclophosphamide for steroid-resistant nephrotic syndrome in children
Dec 23, Author: Diuretics are used to reduce edema. Renal biopsy is very helpful to differentiate minimal-change disease and its variants such as IgM nephropathy and C1q nephropathy. Very few randomized trials are available to guide treatment for minimal-change disease in adults. Immunosuppressive medications other than steroids are usually reserved for steroid-resistant patients with persistent edema, or for steroid-dependent patients with significant steroid-related adverse effects.
Cyclophosphamide may benefit patients who have frequently relapsing steroid-sensitive nephrotic syndrome. Associated complications include bone marrow suppression, hair loss, reduced sperm counts, hemorrhagic cystitis, malignancy, and infertility. Cyclosporine is indicated when relapses occur after cyclophosphamide treatment. Cyclosporine may be preferable in a pubertal male who is at risk of developing cyclophosphamide-induced azoospermia.
Cyclosporine is a highly effective maintenance therapy for patients with steroid-sensitive nephrotic syndrome who are able to stop steroids or take lower doses, but some evidence suggests that although remission is maintained as long as cyclosporine is administered, relapses are frequent when treatment is discontinued. For focal glomerulosclerosis, prednisone, cyclosporine, and cyclophosphamide have all been used in treatment. Corticosteroids should be the first-line agent, with cyclophosphamide or cyclosporine as backup for steroid-resistant cases.
Mycophenolate and rituximab have also been used in treating focal glomerulosclerosis. However, data on the use of these latter two agents are not convincing.
For idiopathic membranous nephropathy, prednisone along with chlorambucil or cyclophosphamide remains important for treatment. Other agents that have been used include cyclosporine, synthetic corticotropin, and rituximab. A Cochrane review of immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome concluded that combination treatment with an alkylating agent and a corticosteroid has both short- and long-term benefits, and that cyclophosphamide is a safer alkylating agent than chlorambucil.
A 6-month course of alternating monthly cycles of corticosteroids and cyclophosphamide is recommended in the KDIGO Clinical Practice Guideline as initial therapy for adult idiopathic membranous nephropathy with nephrotic syndrome, but the benefits of this regimen are not supported by high-quality evidence.
Rituximab has been effective in some cases of nephrotic syndrome that relapse after prednisone treatment or in cases resistant to prednisone treatment. It presumably exerts its benefit by suppressing antibody production. Its adverse effect to cause immunosuppression cannot be ignored. It is presumed to have an anti-inflammatory action.
Its adverse effect profile is similar to steroids, but the most striking disadvantage is its cost. Corticosteroids have anti-inflammatory properties and modify the body's immune response to diverse stimuli. Prednisone is an immunosuppressant used in treatment of autoimmune disorders. This agent may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil PMN activity. It may be administered as a single dose in the morning or as divided doses; once-daily dosing is equally effective and greatly improves compliance.
Cyclophosphamide is a cyclic polypeptide that suppresses some humoral immune activity. It is chemically related to nitrogen mustards. In the liver, this agent is biotransformed by the cytochrome P system to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction.
As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which interferes with growth of normal and neoplastic cells. The mechanism of action of cyclophosphamide in autoimmune diseases is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.
In high doses, cyclophosphamide affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, it affects T cell functions. Cyclophosphamide has been successfully used in conditions that require immunosuppression. It is effective for frequently relapsing steroid-sensitive nephrotic syndrome. Cyclosporine is a cyclic polypeptide that suppresses cell-mediated immune reactions. Tacrolimus Prograf has a similar effect. Rituximab is a chimeric humanized murine monoclonal antibody against CD20 antigen found on the surface of lymphocytes.
Mycophenolate inhibits inosine monophosphate dehydrogenase and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. It inhibits antibody production. Furosemide increases urine output by inhibiting sodium transport in the ascending loop of Henle. The dose must be individualized. Depending on response, administer at increments of mg, no sooner than h after the previous dose, until desired diuresis occurs. Spironolactone is used for management of edema resulting from excessive aldosterone excretion.
It competes with aldosterone for receptor sites in the distal nephron, thus enhancing sodium excretion. ACE inhibitors block conversion of angiotensin I to angiotensin II and prevent secretion of aldosterone from the adrenal cortex. ARBs antagonize the action of angiotensin II at the type 1 receptor, reducing systemic arterial blood pressure and blunting the intrarenal effect of angiotensin II.
Valsartan directly antagonizes type 1 angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.
It does not affect bradykinin and is less likely to be associated with cough and angioedema. Losartan directly antagonizes type 1 angiotensin II receptors. HP Acthar Gel is a synthetic corticotropin that stimulates corticotropin production.
It may induce remission of proteinuria in nephrotic syndrome. Proteinuria in IgA nephropathy. Properties of the glomerular barrier and mechanisms of proteinuria. Renal handling of albumin: Am J Kidney Dis. Glomerular protein sieving and implications for renal failure in Fanconi syndrome.
Hamm LL, Batuman V. Edema in the nephrotic syndrome: J Am Soc Nephrol. Vascular hyperpermeability in nephrotic edema. The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity. N Engl J Med. Status of the coronary arteries in the nephrotic syndrome. Analysis of 20 necropsy patients aged 15 to 35 years to determine if coronary atherosclerosis is accelerated.
Bone histology in patients with nephrotic syndrome and normal renal function. Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function. Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease?. Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: Antiphospholipase A2 receptor autoantibody guided diagnosis and treatment of membranous nephropathy: Clin J Amer Soc Nephrol.
Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe disease. Alloimmune Membranous Nephropathy in Fabry Disease. Nephrotic syndrome after bevacizumab: Membranous nephropathy and cancer: Epidemiologic evidence and determinants of high-risk cancer association. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: J Paediatr Child Health.
Histopathological spectrum of childhood nephrotic syndrome in Indian children. Primary nephrotic syndrome during childhood in Turkey. Kazi JI, Mubarak M. Pattern of glomerulonephritides in adult nephrotic patients--report from SIUT.
J Pak Med Assoc. The changing face of schistosomal glomerulopathy. Nephrotic syndrome in African children: The nephrotic syndrome in the Democratic Republic of Congo. Prevalence of chronic kidney disease in Kinshasa: Changing patterns in the histopathology of idiopathic nephrotic syndrome in children.
Long-term assessment of steroid therapy in childhood nephrosis. Clin J Am Soc Nephrol. Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes.
Urine biomarkers predict the cause of glomerular disease. Cohen EP, Lemann J. The role of the laboratory in evaluation of kidney function. Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin.