Lupus Nephritis


Table 2: Recommended Therapeutic Drug Monitoring in Patients with Lupus Nephritis Receiving Commonly Used Immunosuppressive Therapies


Drug Azathioprine Dosage 1–2 mg/kg/day


Dose Adjustment ↓ 25 % if eGFR 10–30 ml/min; ↓ 50 % if eGFR <10 ml/min


Mycophenolate mofetil


Cyclophosphamide


1–3 g/day in two Maximum 1 g/day if divided doses eGFR <25 ml/min


1–2 mg/kg/day ↓ 25 % if eGFR


in a single dose 25–50 ml/min; with breakfast;


force fluids, urge <25 ml/min;


frequent voiding ↓ 25 % if serum Bili 3–5 mg/dl


or transaminases greater than three times ULN


Methotrexate


7.5–15 mg/week ↓ 50 % if eGFR in one to three 10–50 ml/min; avoid doses


Myelosuppression, hepatic fibrosis, pneumonitis


use if eGFR <10 ml/min; avoid use in hepatic


dysfunction (serum Bili 3–5 mg/dl or transaminases greater than three times ULN)


Cyclosporine A


100–400 mg/day Avoid in impaired in two doses at renal function 12-hour intervals


Renal insufficiency, anemia, hypertension


CBC, SCr, uric acid, SCr every two weeks until dose AST or ALT, SAlb,


is stable, then monthly; CBC,


ALP, blood pressure potassium, AST or ALT, SAlb, and ALP every one to three months; drug levels only with doses >3 mg/kg/day


Tacrolimus


1–3 mg/day in two doses at


12-hour intervals Leflunomide


Cautious use in liver Renal insufficiency, neurotoxicity, SCr, potassium, AST or renal insufficiency malignancy, infections, hyperkalemia


or ALT, glucose, blood pressure


100 mg/day in a Avoid in hepatic single dose for


three days, then 3–5 mg/dl or Rituximab


10–20 mg/day transaminases greater than three times ULN) None


1,000 mg on day 1 and 15


Myelosuppression, dysfunction (serum Bili hepatotoxicity, fetal toxicity


CBC, SCr, AST or ALT, SAlb, ALP


Baseline tests every week for the first three to four weeks,


then every one to three months; monitor drug trough levels


CBC, AST or ALT, SAlb, and ALP monthly for six months, then every one to three months; monthly monitoring if MTX co-administered


Infections, HBV reactivation (rare) CBC, SCr, AST or ALT, CBC with platelets


HBV serology (high-risk patients), TST


ALP = alkaline phosphatase; ALT = alanine transaminase; AST = aspartate transaminase; Bili = bilirubin; CBC = complete blood cell count; CxR = chest x-ray; eGFR = estimated glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; MTX = methotrexate; SAlb = serum albumin; SCr = serum creatinine; TST = tuberculin skin testing; ULN = upper limit of normal; WBC = white blood cell count.


nephritis has been demonstrated,56,57 further studies are needed to


determine whether monitoring MPA levels can improve the efficacy of MMF in patients with SLE. Similarly, cyclosporine concentrations can be measured in whole blood, but this is rarely needed in treating autoimmune diseases unless cyclosporine is administered in doses higher than 3 mg/kg/day.


Infections, attributed predominantly to corticosteroids and cytotoxic drugs, contribute to significant morbidity and mortality in patients with lupus nephritis.2,3


Strategies to reduce infections include the following: 120


judicious use of glucocorticoids; simple hygiene measures and education aimed at both patients and physicians; adherence to recommended immunizations; and consideration for antimicrobial prophylaxis in patients with increased prevalence of certain infections, patients who receive heavy doses of immunosuppressive agents, or those undergoing procedures associated with transient bacteremia.


Cardiovascular events represent another major source of morbidity in patients with lupus nephritis, as a result of the pathophysiology of the disease itself, including protracted nephrotic syndrome, hypertension,


US NEPHROLOGY CxR, HBV/HCV ↓ 30–50 % if eGFR


Toxicities Requiring Monitoring Baseline Evaluation Laboratory Monitoring Myelosuppression, hepatotoxicity, CBC, platelets, SCr, CBC with platelets every two lymphoproliferative diseases, malignancies


and AST or ALT


Myelosuppression, hematotoxicity, CBC, platelet, infection, malignancies


Myelosuppression, hemorrhagic cystitis, myeloproliferative disease, malignancies


SCr, and AST or ALT two weeks with changes in dosage; baseline tests every one to three months


CBC, platelet, SCr, CBC with differential every one AST or ALT, urinalysis to two weeks, with changes in dosage and then every one to three months; keep WBC >4,000/mm3 with dose


adjustment; urinalysis, AST or ALT every three months;


urinalysis every 6–12 months following treatment cessation CBC with platelets, AST, SAlb,


serology in high-risk and SCr every one to patients, AST or ALT, three months SAlb, ALP, SCr


weeks with changes in dosage; baseline tests every one to three months


CBC with platelets every one to


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84