Glomerular Disease Primer: Therapy for Glomerular Disease
- Blood Pressure Control
- Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)
- Angiotensin Receptor Blockers (ARB)
- Cyclosporine (Neoral, Sandimmune)
- Tacrolimus (FK506, Prograf)
- Cyclophosphamide (Cytoxan)
- Mycophenolate Mofetil (Cellcept)
- Sirolimus (Rapamycin, Rapamune)
Blood Pressure Control
Patients with reduced GFR or proteinuria >1 g/d should have all their blood pressure readings below 140/90. This is the recommendation of the most recent Joint National Commission (JNC 8, http://www.nmhs.net/documents/27JNC8HTNGuidelinesBookBooklet.pdf ). Patients are encouraged to check their blood pressure at home, ideally at the same time each day (e.g. dinner time or bedtime) and record the results.
There is some evidence that restricting protein intake to 0.8 g/kg/d may slow progression of kidney damage. Sodium restriction to <2 g/d will help lower blood pressure and will minimize edema.
Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)
These medicines have generic names ending in –IL (benazapril, captopril, enalapril, fosinopril lisinopril, moexipril, ramipril, quinapril, trandolopril). The medications have four beneficial effects on the kidney: they lower systemic blood pressure, they reduce pressure within the glomerulus, they reduce proteinuria, and they are anti-fibrotic. Higher doses, up to the FDA recommended maximum, are likely to be more effective. The beneficial effects are potentiated by a low sodium diet and by diuretics.
Common adverse reactions: cough, high serum potassium, low blood pressure, fatigue
Angiotensin Receptor Blockers (ARB)
These medicines have generic names endling in –AN (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan). These medications have identical beneficial effects on the kidney compared to the ACE inhibitors.
Common adverse reactions: high serum potassium, low blood pressure, fatigue
These medications are related to cortisol, a steroid produced by the body’s adrenal cortex. High doses are used in kidney disease. The mechanism of action is not well understood, but may include the immunosuppressive effect and also direct effects on glomerular cells, including podocytes. Common agents and regimens include the following: oral prednisone daily or alternate days, intravenous pulse methylprednisolone, and oral pulse dexamethasone
Common adverse reactions: nausea, vomiting, abdominal discomfort, edema, headache, mood swings, anxiety, insomnia, high blood glucose, hypertension, acne, skin atrophy
Serious adverse reactions: adrenal suppression, peptic ulcer, osteoporosis, glaucoma, cataract, psychosis
Cyclosporine (Neoral, Sandimmune)
This is an immunsuppressive medication that alters T lymphocyte function. Cyclosporine also may have direct effects on the glomerulus to reduce proteinuria. A typical course lasts 1 year or longer.
Common adverse reactions: hypertension, hair growth, tremor, numbness and tingling, acne, gum hyperplasia, diarrhea, elevated blood glucose, high serum potassium, low serum magnesium, reduced glomerular filtration rate (typically reversible when the dose is reduced)
Serious adverse reactions: seizures, low white blood count, low platelet count, liver injury, kidney fibrosis, diabetes
Tacrolimus (FK506, Prograf)
This medication has almost identical actions to those of cyclosporine. It has a somewhat different adverse event profile compared to cyclosporine: it is more likely to induce diabetes and less likely to cause hirsutism and gum hyperplasia.
This medication has long been used in cancer chemotherapy, at high doses. Much lower doses are used in glomerular disease, and consequently the medication is better tolerated. The effects on kidney disease are believed to be mediated by suppression of both T and B lymphocytes. Typical regimens include oral cylclophosphamide daily for 12 weeks and intravenous pulse cyclophosphamide monthly or quarterly.
Two adverse events deserve special comment, as they can be prevented by appropriate measures:
- Cyclophosphamide is excreted by the kidney and can damage the bladder cells, causing bloody urine and pain. This can be avoided by drinking extra fluids for at least 4 hours after a dose and emptying the bladder at least hourly for four hours after a dose.
- Cyclophosphamide can cause sterility in males and females. This does not occur before puberty. The highest risk for sterility is after the age of 30, when fertility is declining. Protective measures include hormone administration for men (testosterone) and women (leuprolide) to temporarily suppress gonadal function.
Common adverse reactions (kidney disease doses): bladder inflammation
Serious adverse reactions (kidney disease doses): sterility, hemorrhagic cystitis, low white blood cell counts, immunosuppression (propensity to viral infections in particular), malignancy (not reported with short course)
Mycophenolate Mofetil (Cellcept)
This agent reduces cell proliferation and acts on both T and B lymphocytes; its mechanism of benefit in glomerular disease is unknown.
Common adverse events: diarrhea, nausea, vomiting, abdominal pain, low white blood cells, headache, tremor, acne, insomnia
Serious adverse events: low white blood cells, low platelets, infection, malignancy, gastrointestinal bleeding
Sirolimus (Rapamycin, Rapamune)
This agent reduces cell proliferation and acts on both T and B lymphocytes; it is also an anti-fibrotic agent.
Common adverse events: high serum cholesterol, high serum triglycerides, diarrhea, constipation, nausea, abdominal pain, anemia, tremor, hypertension
Serious adverse events: infection, malignancy, low white blood cells, low platelets