Cyclosporine hypertension with

Taylor DO, Barr ML, Radovancevic B, Renlund DG, Mentzer RM Jr, Smart FW, Tolman DE, Frazier OH, Young JB, VanVeldhuisen P. A randomized, multicenter comparison of tacrohmus and cyclosporine immunosuppressive regimens in cardiac transplantation decreased hyperlipidemia and hypertension with tacrohmus. J Heart Lung Transplant 1999 18(4) 336-45. 

For patients with severe nephrotic syndrome who did not respond to cytotoxic therapy, cyclosporine may offer some benefits however, the risk for cyclosporine nephrotoxicity is of concern, especially during long-term therapy. A 12-month course of cyclosporine (mean dose of 3.8 mg/kg per day) was found to reduce proteinuria as well as the rate of renal deterioration. In a recent study of 41 patients who received cyclosporine, many with concurrent steroid and ACE inhibitor therapy, the median treatment time to complete remission was 225 days among the 34% of patients who attained complete remission. At present, the beneficial effects of cyclosporine are not well substantiated and the optimal duration of treatment is also not known. For many patients, hypertension may be exacerbated and the serum creatinine concentration may be increased due to nephrotoxicity. When the renal function declines, the dose of cyclosporine should be reduced. In addition, proteinuria may recur when the cyclosporine treatment is stopped. 

P. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation decreased hyperlipidemia and hypertension with tacrolimus. J Heart Lung Transplant 1999 18 336-345. 

Cyclosporine is a cyclic polypeptide immunosuppressant typically used to prevent organ rejection in transplant patients. Its use is restricted to patients with fulminant or refractory symptoms in patients with active IBD. Significant toxicides associated with cyclosporine are nephrotoxicity, risk of infection, seizures, hypertension, and liver function test abnormalities.1,13,14... 

Methotrexate has been used successfully with cyclosporine, either concurrently34 or in rotation. Rotational therapy is particularly effective since it minimizes the serious adverse effects of both agents hepatotoxidty from methotrexate and hypertension and nephrotoxicity from cyclosporine. Having an overlapping treatment period may not be necessary and patients have been successfully switched after a 1-week washout period.21,35 This is a very useful combination of systemic agents in the longterm management of this chronic disease. 

Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated Ever function tests. 

Hypersensitivity to polyoxyethylated castor oil (injection only see Warnings and Administration and Dosage), cyclosporine, or any component of the products Gengraf and Neoral in psoriasis or RA patients with abnormal renal function, uncontrolled hypertension, or malignancies Gengraf and A/eora/concomitantly with PUVA or DVB, methotrexate or other immunosuppressive agents, coal tar or radiation therapy in psoriasis patients. 

Elderly Patients at least 65 years of age are more likely to develop systolic hypertension on therapy, and more likely to show serum creatinine rises greater than or equal to 50% above the baseline after 3 to 4 months of therapy. Monitor elderly patients with particular care, because decreases in renal function also occur with age. If patients are not properly monitored and dosages are not properly adjusted, cyclosporine therapy can cause structural kidney damage and persistent renal dysfunction. 

While calcium antagonists can be effective agents in treating cyclosporine-associated hypertension, use care because interference with cyclosporine metabolism may require a dosage adjustment. 

A 47-year-old man recently received a heart transplant and is being discharged home with oral medications, including cyclosporine. The physician also prescribed diltiazem, a calcium channel blocker used for the treatment of hypertension. Since he did not have hypertension, the patient wondered why this additional drug was being prescribed. 

Compared with previously available therapy, the adverse effects associated with cyclosporine are much less severe but still worthy of concern. Nephrotoxicity, which can occur in up to 75% of patients, ranges from severe tubular necrosis to chronic interstitial nephropathy. This effect is generally reversible with dosage reduction. Vasoconstriction appears to be an important aspect of cyclosporine-induced nephrotoxicity. Hypertension occurs in 25% of the patients and more frequently in patients with some degree of renal dysfunction the concomitant use of antihypertensive drugs may prove useful. Hyperglycemia, hyperlipidemia, transient liver dysfunction, and unwanted hair growth are also observed. 

The introduction of cyclosporin, a peptide derived from a fungus, revolutionised immunosuppressive therapy, and was one of the major influences in the improvement of early graft survival in transplant surgery when introduced in the 1980s. The main action is a relatively selective inhibition of IL-2 production and consequently a decreased proliferation of T cells. A major advantage of cyclosporin is that it does not cause myelosuppression in therapeutic doses. The major side effect is nephrotoxicity, which occurs in about 20% of patients, and about 50% of patients develop moderate hypertension. The other major side effect is hepatotoxicity with cholestasis and hyperbilirubinaemia. 

Cyclosporine has significant nephrotoxicity, and its toxicity can be increased by drug interactions with diltiazem, potassium-sparing diuretics, and other drugs inhibiting CYP3A. Serum creatinine should be closely monitored. Other toxicities include hypertension, hyperkalemia, hepatotoxicity, gingival hyperplasia, and hirsutism. 

Calcium channel blockers are considered the drug of first choice for the treatment of posttransplant I hypertension since they increase renal blood flow. Nifedipine, isradipine and amlopidine show little interac-l tion with cyclosporine-A. Diltiazem and verapamil elevate cyclosporine-A levels. I... 

Adverse Effects. The primary problem associated with cyclosporine is nephrotoxicity, which can range from mild, asymptomatic cases to severe kidney dysfunction, which requires discontinuation of the drug.33,46 Hypertension is also a common adverse effect, especially when cyclosporine is used for prolonged periods.58 Other problems include neurotoxicity, gingival hyperplasia, hair growth (hirsutism), and increased infections. These problems, however, tend to... 

Hypertension is associated with increased TXA2 and decreased PGE2 and PGI2 synthesis in some animal models, eg, the Goldblatt kidney model. It is not known whether these changes are primary contributing factors or secondary responses. Similarly, increased TXA2 formation has been reported in cyclosporine-induced nephrotoxicity, but no causal relationship has been established. 

Toxicities are numerous and frequently include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, and hirsutism. A significant increase in the incidence of cholelithiasis has been observed in children treated with cyclosporine after heart transplantation. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) has been documented in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because it induces TGF-3, which promotes tumor invasion and metastasis. 

Cyclosporine A Cyclosporine was used for the first time by G. Routhier et al. (1980) and by G.J. M. Alexander et al. (1984) with encouraging results, yet with nephrotoxic side effects. In subsequent studies, the clinical picture and laboratory parameters as well as histological findings also showed significant improvement. However, an imptairment of renal function and the occurrence of hypertension have to be anticipated. (180, 189, 288)... 

Rodier M, Ribstein J, Parer-Richard C, Mimran A. Renal changes associated with cyclosporine in recent type I diabetes mellitus. Hypertension 1991 18 334-340. 

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