eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Nephrotic Syndrome: Treatment & Medication

Author: Jerome C Lane, MD, Assistant Professor of Pediatrics, Northwestern University Medical School; Attending Physician, Department of Pediatrics, Division of Kidney Diseases, Children's Memorial Hospital, Chicago
Contributor Information and Disclosures

Updated: Jun 12, 2009

Treatment

Medical Care

A trial of corticosteroids is the first step in treatment of idiopathic nephrotic syndrome (INS) in which kidney biopsy is not initially indicated. Thus, patients aged 1-8 years with normal kidney function, no macroscopic (gross) hematuria, no symptoms of systemic disease (fever, rash, joint pain, weight loss), normal complement levels, negative antinuclear antibody (ANA) findings, negative viral screens (ie, HIV, hepatitis B and C), and no family history of kidney disease may be considered for steroid treatment prior to kidney biopsy. In select preadolescent patients older than 8 years, empirical steroid treatment can be considered prior to kidney biopsy; however, this should occur only under the care of a pediatric nephrologist experienced with nephrotic syndrome.

Kidney biopsy should be performed prior to any immunosuppressive treatment, including steroids, in patients younger than 1 year or older than 8 years and patients with recurrent gross hematuria, relevant family history of kidney disease, symptoms of systemic disease, positive viral screens, and/or laboratory findings possibly indicative of secondary nephrotic syndrome or INS other than minimal change nephrotic syndrome (MCNS), such as sustained elevation in serum creatinine levels, low C3/C4 levels, positive ANA findings, and positive anti–double-stranded DNA antibody findings. In these cases, histology guides treatment, and steroids may or may not be indicated depending on the underlying etiology.

The treatment of steroid-sensitive INS, steroid-dependent and frequently-relapsing INS, steroid-resistant nephrotic syndrome (SRNS) and FSGS are discussed in detail below. The treatment of mesangiocapillary glomerulonephritis (MPGN), membranous nephropathy (MN), congenital nephrotic syndrome, and secondary nephrotic syndrome (eg, lupus nephritis and vasculitis) are beyond the scope of this article.

  • Corticosteroid (steroid) treatment (MCNS, INS that does not require initial biopsy)
    • Induction therapy:
      • Exclude active infection or other contraindications prior to steroid therapy.
      • The original ISKDC protocol recommended oral prednisone or prednisolone at 60 mg/m2/d (2 mg/kg/d) daily for 4 weeks.
      • Traditionally, the total daily dose was split into two doses. However, a single daily dose of steroids has equal efficacy to split dosing and fewer side effects.19  
      • Subsequent studies have shown that a longer, 6-week rather than 4-week, period of initial steroid treatment reduces the subsequent rate of relapse. Thus, many centers now prescribe the initial daily steroids for 6 weeks.20
    • Maintenance therapy (following above induction therapy)
      • Original guidelines recommended oral prednisone or prednisolone at 40 mg/m2 (or 1.5 mg/kg) given as a single dose on alternate days for 4 weeks.
      • Subsequent studies demonstrated that a longer alternate day maintenance period of 6 weeks resulted in a lower rate of relapse.20
      • Thus, many centers now recommend daily induction steroid treatment for 6 weeks, followed by alternate day maintenance therapy for another 6 weeks.
      • Following 6 weeks of alternate day treatment, steroids may be stopped or slowly tapered over a variable length of time.
      • Longer duration of alternate-day steroid treatment may further reduce the number of children with subsequent relapses. An assessment of the Cochrane Database concluded that, after the initial daily steroid induction phase, continuation of alternate day steroids for 6 months could reduce the subsequent relapse rate by 33% compared with shorter alternate-day treatment.21 No adverse effects were noted with the longer steroid treatment, although the authors cautioned the adequate randomized controlled trials comparing shorter versus long-term alternate day steroid treatment still needed to be conducted.21
    • Relapse therapy
      • For infrequent relapses, steroids are resumed, although for a shorter duration than treatment during initial presentation
      • Prednisone 2 mg/kg/d(60 mg/m2/d) given as a single morning dose is administered until proteinuria has resolved for at least 2 days.
      • Following remission of proteinuria, prednisone is reduced to 1.5 mg/kg (40 mg/m2) given as a single dose on alternate days for 4 weeks. Steroids may then be stopped or gradually tapered.
  • Other therapy (all patients):
    • Pneumococcal vaccine should be administered to all patients upon presentation, to reduce the risk of bacterial infection and peritonitis.
    • Diuretic therapy may be beneficial, particularly in children with symptomatic edema. The loop diuretics (furosemide) given orally in usual amounts (approximately 1-2 mg/kg/d) are safe and moderately effective; their administration, however, should be handled with care because plasma volume contraction may already be present, and hypovolemic shock has been observed with overly aggressive therapy. Metolazone may be beneficial in combination with furosemide for resistant edema. Patients must be monitored carefully on this regimen. If the child is sent home on diuretic therapy, the family must have clear guidelines about discontinuing therapy when edema is no longer present and careful communication with the family should continue
    • When a patient presents with anasarca and signs of intravascular volume depletion (such as high hematocrit indicative of hemoconcentration), consideration should be given to administration of 25% albumin, although this is controversial. Rapid administration of albumin can result in pulmonary edema. The authors' practice has been to administer 25% albumin at a dose of 1 g/kg body weight given as a continuous infusion over 24 hours. Intravenous albumin may be particularly useful in diuretic resistant edema, and in patients with significant ascites and/or scrotal, penile or labial edema.
    • Antihypertensive therapy should be given when hypertension is present and particularly if it persists, but caution should be exercised. In some patients the hypertension will respond to diuretics. ACE inhibitors or angiotensin II receptor blocker (ARB) agents may also contribute to reducing proteinuria but should be used cautiously in the presence of acute kidney failure or volume depletion because their use can worse kidney function in these settings. Adolescent women must also be counseled regarding use of birth control with chronic ACE inhibitors or ARB due to risk of birth defects, and pregnancy testing should be considered before starting these agents. Calcium channel blockers and beta-blockers may also be used as first-line agents for hypertension.
    • Home monitoring of urine protein and fluid status is an important aspect of management. All patients and parents should be trained to monitor first morning urine proteins at home with urine dipstick. Weight should be checked every morning as well, and a home logbook should be kept recording the patient’s daily weight, urine protein levels, and steroid dose if being treated. Families and patients are instructed to call for any edema, weight gain, or urine protein findings of 2+ or more for more than 2 days. Urine testing at home is also useful in monitoring response (or nonresponse) to steroid treatment.
  • Frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome (SDNS)
    • Frequently relapsing nephrotic syndrome is defined as steroid-sensitive nephrotic syndrome (SSNS) with 2 or more relapses within 6 months or more than 3 relapses within a 12-month period.
    • SDNS is defined a as SSNS with 2 or more consecutive relapses during tapering or within 14 days of stopping steroids.
    • For frequently relapsing nephrotic syndrome and SDNS, the clinical evidence is inadequate to support a preferred method of treatment. Therefore, practitioners must rely on their clinical experience and discuss the potential advantages and disadvantages of each treatment with families and patients.22
    • Alkylating agents (cyclophosphamide [CYP], chlorambucil, nitrogen mustard) offer the benefit of possible sustained remission after a defined course of treatment, although with the risk of infertility and other side effects (see Complications).
      • Calcineurin-inhibitors (eg, cyclosporine [CSA], tacrolimus [TAC]) are useful steroid-sparing agents, but prolonged courses of treatment are needed, nephrotic syndrome tends to recur when treatment is stopped, and nephrotoxic injury may occur.
      • An increased risk of seizures is noted with chlorambucil.12 Additionally, a higher incidence of infections and leukopenia may be seen with chlorambucil compared with CYP.23 Because of these risks, and the need to give nitrogen mustard intravenously, the authors have used cyclophosphamide as the preferred alkylating agent
      • Cyclophosphamide (2–2.5 mg/kg daily) is given orally for 8-12 weeks.
      • Steroids are usually overlapped with initiation of CYP then tapered.
      • An influential study found that a 12 week course of cyclophosphamide was more effective than an 8-week course in producing sustained remission of nephrotic syndrome.24 However, a subsequent randomized trial did not reach this same conclusion,25  and the optimal duration of cyclophosphamide treatment is still unclear at this time.
      • Patients must have weekly CBC counts to monitor for leukopenia.
      • Patients must also maintain adequate hydration and take CYP in the morning (not at bedtime) to limit the risk of hemorrhagic cystitis. Families must be counseled to report gross hematuria, fever, or severe illness.
    • Calcineurin-inhibitors
      • CSA can be used in those children who fail to respond to, or subsequently relapse after, treatment with CYP, or for children whose families object to use of CYP. Because CSA can cause hirsutism and gingival hyperplasia, the authors' practice has been to use TAC instead of CSA, although limited studies are available regarding the effectiveness of TAC compared with CSA.
      • Initial doses of CSA are started at 5–6 mg/kg daily divided every 12 hours, adjusted for trough concentrations of 50–125 ng/mL. Low-dose steroids are continued for a variable length of time; as many as 40% of patients may need to remain on steroids during CSA treatment to maintain remission.12
      • Kidney function and drug levels must be carefully monitored due to the risk of CSA induced nephrotoxicity.
      • Trough levels correlate poorly with area-under-the-curve (AUC) pharmacokinetics and may not represent true exposure to CSA. levels obtained 2 hours after administration (C2) have better correlation with AUC.26
      • TAC trough levels correspond better to AUC than CSA, allowing better determination of dosing and exposure with TAC than with CSA.26
      • TAC is started at a dose of 0.1 mg/kg daily divided every 12 hours and adjusted to keep trough level about 5-10 ng/mL.27 Our practice is to use the lowest possible dose that sustains remission and to aim for a trough level of around 5 ng/mL. As with CSA, continuing low-dose steroids is often necessary to maintain remission, although some patients may eventually be able to discontinue steroid treatment.
      • With CSA and TAC, kidney function and drug levels should be carefully monitored. Consideration should be given to kidney biopsy after prolonged treatment to monitor for calcineurin-inhibitor induced nephrotoxicity and fibrosis.
      • TAC (0.1-0.2 mg/kg/d) or CSA (5-6 mg/kg/d) have similar efficacy in inducing remission in patients with idiopathic SRNS at 6 months and 1 year when combined with alternate-day low-dose corticosteroids and enalapril.28 Relapse was significantly greater in those who received CSA compared with TAC. TAC also decreased blood cholesterol levels to a greater extent and resulted in less incidents of nephrotoxicity that necessitated discontinuance than CSA. Cosmetic adverse effects (eg, hypertrichosis, gum hypertrophy) were significantly more frequent in the CSA group (P <0.001). TAC therapy is a promising alternative to CSA because of the lower relapse risk and lack of cosmetic adverse effects.
    • Levamisole: is an anthelmintic drug that has immune-modulating effects and can be effective in reducing the relapse rate in frequently relapsing nephrotic syndrome. However, it is unavailable in the United States. Side effects include leukopenia, hepatic dysfunction, agranulocytosis, vasculitis, and encephalopathy. Levamisole is prescribed at a dose of 2.5 mg/kg given on alternate days .12
    • Mycophenolate mofetil (MMF): Although small studies have shown MMF to be effective in reducing the number of relapses in frequently relapsing nephrotic syndrome and SDNS, adequate randomized controlled trials still need to be performed. The authors have found MMF to be a useful steroid-sparing agent in stable patients (without excessive edema, need for hospitalizations and without other serious complications) whose families wish to avoid the possible side effects of CYP, CSA, or TAC. However, response to MMF varies and is less reliable than other treatments. MMF is started at a dose of 600 mg/m2 twice daily. CBC counts should be monitored for bone-marrow suppression, and liver function test findings should occasionally be monitored for hepatic toxicity.
  • SRNS and FSGS
    • Adequate randomized controlled trials have not yet been reported to give sufficient evidence to guide treatment of SRNS.29
    • A current, National Institutes of Health (NIH)-sponsored, multicenter, randomized clinical trial has recently concluded enrollment and will compare CSA versus MMF for treatment of FSGS.30
    • The most frequently recommended treatment for FSGS and SRNS is CSA. Approximately 36% of children with SRNS may achieve remission with CSA.29 CSA is dosed as above for FRNS and SDNS. However, higher doses and trough levels may be required to achieve remission in SRNS and FSGS.12 TAC may be effective as well, although studies are limited at this time.30
    • Most studies to date have shown no clear benefit to the use of alkylating agents in FSGS and SRNS.6
    • A controversial treatment involves high-dose, intravenous methylprednisolone tapered over 78 weeks, in combination with alternate day oral prednisone and with the addition of CYP or chlorambucil if remission is not achieved in the first 10 weeks. The authors reported a 52% remission rate in SRNS.31 However, subsequent studies using this protocol have not duplicated the initial success. The risk of steroid toxicity and infection, as well as lack of sufficient evidence for the effectiveness of this protocol, have dampened enthusiasm for this treatment.
    • The use of an ACE inhibitor, such as enalapril, either alone or in combination with an ARB agents, such as losartan, has been shown to reduce proteinuria in FSGS/SDNS and should be considered in all patients, even in the absence of hypertension. Accordingly, ACE inhibitors and ARB agents should be considered as preferred agents in patients with hypertension. ACE inhibitor and ARB treatment may also have a renoprotective effect and slow progression of renal disease by inhibiting pathways of fibrosis.30

Surgical Care

No routine surgical care is indicated for this condition. Occasionally, a patient with nephrotic syndrome either presents with or develops clinical signs of an acute surgical abdomen, which is frequently due to peritonitis. The diagnosis can usually be made clinically and confirmed by bacteriologic examination of the peritoneal fluid aspirate. The organism most often responsible for the peritonitis is pneumococcus; however, enteric bacteria may also cause peritonitis. Treatment is medical.

Consultations

In most instances, nephrotic syndrome is a chronic problem that requires understanding of the pathophysiology and knowledge of treatment options. For these reasons, consultation with a pediatric nephrologist is appropriate for all patients with nephrotic syndrome. Referral to a pediatric nephrologist is mandatory for all children with nephrotic syndrome whose symptoms fail to respond to initial therapy (complete remission of proteinuria); in most of these patients, a percutaneous renal biopsy is indicated, and an alternative treatment plan may be desirable.

Diet

A sodium restricted diet should be maintained while a patient is edematous and until proteinuria remits. Thereafter, a normal diet can be followed. During severe edema, careful and modest fluid restriction may be appropriate but the patient must be monitored closely for excessive intravascular volume depletion. Protein restriction is not indicated, except in cases of acute or chronic kidney failure when severe azotemia is present and, even then, protein restriction should be done carefully as to avoid impaired somatic growth.

Activity

A normal activity plan is recommended. Because viral respiratory illnesses are often associated with relapses of nephrotic syndrome, keeping children with INS away from those who have obvious respiratory tract infections may be beneficial. However, children should not be kept out of school and should have as normal a routine as possible.

Medication

Prednisone is the first-line therapy for children with nephrotic syndrome (NS). Other immunosuppressive medications may be useful in those whose symptoms fail to respond to standard corticosteroid therapy or in those who have frequent relapses.

Glucocorticoids

All glucocorticoids are effective; however, prednisone or prednisolone is used most commonly. Their specific mode of action in nephrotic syndrome is unknown.


Prednisone (Deltasone, Orasone)

Delta1-derivative of naturally occurring adrenocortical steroids. Suppresses key components of immune system.

Adult

Pediatric

2 mg/kg/d (60 mg/m2/d) PO given as a single daily dose in the morning for 6 wk, not to exceed 60 mg/d, followed by 1.5 mg/kg (40 mg/m2) as single dose every other morning for an additional 6 wk, then discontinue or gradually taper
For relapses, 2 mg/kg/d (60 mg/m2/d) PO given as a single daily dose in the morning, not to exceed 60 mg/d, until urine protein negative for 2 d; followed by 1.5 mg/kg (40 mg/m2) as single dose every other morning for 4 wk, may then be discontinued or gradually tapered

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids

Documented hypersensitivity; active bacterial, viral, fungal, or any other infection; once antibacterial or antifungal therapy has been initiated and patient begins to respond, administration of prednisone may begin

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Severity of adverse effects are related directly to total daily dosage, duration of therapy, and mode of administration (qd or qod); assess benefit-to-risk ratio periodically during treatment; virtually all patients treated as recommended develop increased appetite and cushingoid changes (eg, moon facies, truncal obesity, hirsutism), but these changes disappear after therapy is discontinued or reduced significantly in amount
Prolonged daily treatment can interfere with linear growth; increased susceptibility to infections during intensive therapy; may mask usual evidence of infections
Other possible adverse effects include hypertension, hyperglycemia, hypercalciuria, hypokalemia, nephrolithiasis, osteomalacia, and CNS manifestations (eg, behavioral changes, rarely psychosis)


Prednisolone (Delta-Cortef, Pediapred, Prelone)

Delta1-derivative of the naturally occurring adrenocortical steroids. Suppresses key components of immune system.

Adult

Pediatric

2 mg/kg/d (60 mg/m2/d) PO given as a single daily dose in the morning for 6 wk, not to exceed 60 mg/d, followed by 1.5 mg/kg (40 mg/m2) as single dose every other morning for an additional 6 wk, then discontinue or gradually taper
For relapses, 2 mg/kg/d (60 mg/m2/d) PO given as a single daily dose in the morning until urine protein negative for 2 days; not to exceed 60 mg/d; followed by 1.5 mg/kg (40 mg/m2) as single dose every other morning for 4 wk, may then be discontinued or gradually tapered

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids

Documented hypersensitivity; active bacterial, viral, fungal, or any other infection; once antibacterial or antifungal therapy has been initiated and patient begins to respond, administration of prednisone may begin

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Severity of adverse effects are related directly to total daily dosage, duration of therapy, and mode of administration (qd or qod); assess benefit-to-risk ratio periodically during treatment; virtually all patients treated as recommended develop increased appetite and cushingoid changes (eg, moon facies, truncal obesity, hirsutism), but these changes disappear after therapy is discontinued or reduced significantly in amount
Prolonged daily treatment can interfere with linear growth; increased susceptibility to infections during intensive therapy may occur; may mask usual evidence of infections
Other possible adverse effects include hypertension, hyperglycemia, hypercalciuria, hypokalemia, nephrolithiasis, osteomalacia, and CNS manifestations (eg, behavioral changes, rarely psychosis)

Diuretics

Promotes excretion of water and electrolytes by the kidneys. These agents are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.


Furosemide (Lasix)

Used when symptomatic edema occurs. Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.

Adult

Pediatric

1-2 mg/kg/d PO. IV administration at similar doses may be given but only with caution and one should consider simultaneous administration of salt-poor albumin to protect the vascular space.

Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication

Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, CO2, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter


Metolazone (Zaroxolyn)

Increases excretion of sodium, water, potassium and hydrogen ions by inhibiting reabsorption of sodium in distal tubules. Metolazone may be used to augment diuretic response during treatment with furosemide.

Adult

Pediatric

Children: 0.2-0.4 mg/kg/d PO divided q12-24h
Dose generally limited to 2.5-5 mg total cumulative daily dose

May decrease effect of anticoagulants, sulfonylureas, and gout treatments; anticholinergics and amphotericin B may increase toxicity; effects may decrease when used concurrently with bile acid sequestrants, NSAIDs, or methenamine; when administered concurrently, increases toxicity of anesthetics, diazoxide, digitoxin, lithium, loop diuretics, antineoplastics, allopurinol, calcium salts, vitamin D, and nondepolarizing muscle relaxants

Documented hypersensitivity; hepatic coma or anuria

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hepatic or renal disease, diabetes mellitus, gout, or lupus erythematosus

Plasma protein

These agents are used to supplement diuresis in patients with edema. Increases oncotic pressure to urge a fluid shift from interstitial tissues.


Albumin (Albuminar, Buminate)

Raises oncotic pressure, and thus supplements the diuretic effect of furosemide.

Adult

Pediatric

1 g/kg of 25% concentration (ie, 25 g/100 mL) IV given as a continuous infusion over 24 h; administer with furosemide

Documented hypersensitivity; anemia; heart failure; respiratory distress; pulmonary edema

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Rapid infusion may cause hypotension; caution in renal or hepatic dysfunction due to protein load; may cause hemolysis or acute renal failure when dilute with sterile water; caution with increased intravascular volume. May cause pulmonary edema or congestive heart failure if administered too quickly, or in patients with severe intravascular volume expansion.

Immunosuppressive agents

These drugs may be used for frequently relapses (despite corticosteroid therapy) or to attempt steroid-sparing therapy.


Cyclophosphamide (Cytoxan)

Cyclic polypeptide that suppresses some humoral activity. Chemically related to nitrogen mustards. Activated in the liver 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 may interfere with growth of normal and neoplastic cells.
Biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. Interaction of phosphoramide mustard with DNA considered cytotoxic.
When used in autoimmune diseases, mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.
In high doses, affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, affects T cell functions.
Successfully has been used in conditions that require immunosuppression. Highly effective for frequently relapsing steroid-sensitive nephrotic syndrome; half of the children enter a prolonged remission. Researchers have formulated various protocols for different renal pathological lesions.

Adult

Pediatric

Frequently-relapsing and steroid-dependent nephrotic syndrome: 2-2.5 mg/kg PO daily for 8-12 wk

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity

Documented hypersensitivity; severely depressed bone marrow function

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; administer in morning (not before bedtime) to maintain hydration and decrease risk of hemorrhagic cystitis


Cyclosporine (Sandimmune, Neoral)

An 11-amino acid cyclic peptide and natural product of fungi. Acts on T-cell replication and activity.
Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested.
Binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin 2 and the subsequent recruitment of activated T cells.
Has about 30% bioavailability but marked interindividual variability. Specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that drug be present during first 24 h of antigenic exposure.
Suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for various organs.

Adult

Pediatric

5-6 mg/kg/d PO divided q12h; target trough level ranges between 50-125 ng/mL

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin; methylprednisolone and cyclosporine mutually inhibit one another resulting in increased plasma levels of each drug

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, and serum bilirubin levels and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO


Tacrolimus (Prograf)

Immunomodulator produced by the bacteria Streptomyces tsukubaensis. Mechanisms of action similar to cyclosporine. Primarily used in transplants but used in Behçet disease to treat uveitis.

Adult

Pediatric

0.1 mg/kg/d PO divided q12h; adjust dose to maintain trough level about 5 ng/mL

Caution with drugs associated with renal dysfunction, including aminoglycoside, amphotericin B, cisplatin, and others (can enhance nephrotoxicity); concentrations may be increased in presence of diltiazem, nicardipine, nifedipine, verapamil, clotrimazole, fluconazole, itraconazole, ketoconazole, clarithromycin, erythromycin, troleandomycin, cisapride, metoclopramide, bromocriptine, cimetidine, cyclosporine, danazol, methylprednisolone, and protease inhibitors; concentrations may decrease when administered with carbamazepine, phenobarbital, phenytoin, rifabutin, and rifampin

Documented hypersensitivity (including hypersensitivity reactions to tacrolimus or HCO-60 [polyoxyl 60 hydrogenated castor oil])

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Insulin-dependent diabetes reported in 20% of patients using tacrolimus for transplants, which is reversible in 15% after 1 year and in 50% after 2 years; increased risk for African American and Hispanic patients; nephrotoxicity, neurotoxicity, hyperglycemia, hyperkalemia, tremor, headache, and increased risk of lymphomas and other malignancies (especially skin tumors) may occur; anaphylaxis, hypertension, myocardial hypertrophy, gastrointestinal abnormalities, arthralgias, cramps, asthma, and bronchitis have been reported with its use


Mycophenolate mofetil (CellCept)

Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

In combination with either acyclovir or ganciclovir may result in higher levels for both interacting drugs due to competition for renal tubular excretion; aluminum/magnesium present in some antacids, and cholestyramine containing products may decrease absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates and azathioprine may increase toxicity; may decrease levonorgestrel AUC; may decrease live virus vaccine immune response; when administered in combination with theophylline may increase free fraction levels of theophylline; may reduce blood levels hormones contained in oral contraceptives and could reduce effectiveness

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk for infection (monitor blood count); severe renal impairment (CrCl <25 mL/min) may have increased adverse effects due to increased free MPA; caution in active peptic ulcer disease; incidence of malignancies and lymphoma consistent with that reported for other immunosuppressants (0.9%); commonly causes constipation, nausea, diarrhea, urinary tract infection, and nasopharyngitis; rare reports include interstitial lung disorders, colitis, pancreatitis, intestinal perforation, GI hemorrhage, gastric ulcers, duodenal ulcers, and ileus; do not chew, crush, or cut Myfortic tab; women of childbearing potential must have a negative serum or urine pregnancy test must be completed within one week of beginning MMF and must receive contraceptive counseling and use effective contraception; continue contraception for 6 wk following discontinuing

More on Nephrotic Syndrome

Overview: Nephrotic Syndrome
Differential Diagnoses & Workup: Nephrotic Syndrome
Treatment & Medication: Nephrotic Syndrome
Follow-up: Nephrotic Syndrome
References
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Further Reading

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Keywords

nephrotic syndrome, NS, nephrosis, lipoid nephrosis, primary nephrotic syndrome, primary NS, PNS, idiopathic nephrotic syndrome, idiopathic NS, INS, secondary nephrotic syndrome, secondary NS, minimal change nephrotic syndrome, MCNS, minimal lesion nephrotic syndrome, MLNS, nil disease, steroid-sensitive nephrotic syndrome, SSNS, steroid-resistant nephrotic syndrome, SRNS, steroid-dependent nephrotic syndrome, SDNS, mesangial proliferative glomerulonephritis, MPN, immunoglobulin M nephropathy, focal segmental glomerulosclerosis, FSGS, membranoproliferative or mesangiocapillary glomerulonephritis, MPGN, hypocomplementemic glomerulonephritis, membranous glomerulonephritis, MGN, congenital nephrotic syndrome, Henoch-Schönlein purpura, HSP, systemic lupus erythematosus, diabetes mellitus, syphilis, HIV, hepatitis B, hepatitis C, Wilms tumor, Denys-Drash syndrome, Frasier syndrome

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Contributor Information and Disclosures

Author

Jerome C Lane, MD, Assistant Professor of Pediatrics, Northwestern University Medical School; Attending Physician, Department of Pediatrics, Division of Kidney Diseases, Children's Memorial Hospital, Chicago
Disclosure: Nothing to disclose.

Medical Editor

Laurence Finberg, MD, Clinical Professor, Department of Pediatrics, University of California at San Francisco and Stanford University
Laurence Finberg, MD is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Adrian Spitzer, MD, Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director of NIH Training Program, Children's Hospital at Montefiore Medical Center
Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

 
 
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