Long-term Cyclosporine Therapy Research Articles

P061 CYCLOSPORINE INDUCED KAPOSI SARCOMA IN AN IBD PATIENT: A DOWNWARD SPINDLE

Kaposi Sarcoma is an angioproliferative neoplasm found to be associated with human herpesvirus-8 (HHV8). Although this virus plays a role in the pathogenesis of the disease, in individuals who are human immunodeficiency virus (HIV) negative, it is exceedingly rare. Still, there have been documented cases of individuals developing gastrointestinal Kaposi sarcoma in the setting of immunosuppression, specifically solid organ transplant patients, and less frequently inflammatory bowel disease (IBD). We report a 24-year-old HIV-negative man with a history of ulcerative colitis (UC), psoriasis, atopic dermatitis, and alopecia aereata who was referred to the gastroenterology clinic after experiencing 12 episodes of watery non-bloody diarrhea per day and 20 lb. weight loss over the duration of one-month. Onset of watery diarrhea coincided with starting antibiotics (amoxicillin) for periodontal abscess. Patient reported that since his UC had been well-controlled for several years on cyclosporine prior to his presentation, he attributed the diarrhea and weight loss to antibiotic use. He was initially diagnosed with UC at age 15 and had previously been treated with multiple agents including adalimumab and intermittent prednisone without optimal response. Evaluation showed that he was positive for enteropathic E. coli and norovirus which was thought to be contributing to the diarrhea; he was negative for Giardia, Clostridium difficile, and stool cultures. Given his ongoing symptoms and history of UC, colonoscopy was performed which demonstrated multiple hemorrhagic nodules throughout the colon and terminal ileum. Biopsy results showed vasoformative spindle cell lesions compatible with Kaposi sarcoma that was HHV-8 positive and CMV negative in the terminal ileum and colon. CT chest/abdomen/pelvis demonstrated diffuse lymphadenopathy. He underwent right axillary lymph node biopsy which was consistent with Kaposi sarcoma. His cyclosporine and Truvada were discontinued. Oncology was consulted for further management. Since 1966, there have been only 16 cases of patients documented with IBD developing Kaposi sarcoma secondary to immunosuppressive therapy. Frequently, these patients were on prednisone or biologics with only two patients receiving cyclosporine for a brief period during the course of their therapy. Iatrogenic Kaposi sarcoma has been documented among transplant patients. We report a rare case of an individual with ulcerative colitis developing iatrogenic Kaposi sarcoma in the setting of long-term cyclosporine therapy. (A & B) H&E stained tissue sections of the colon biopsies demonstrates a vasoformative lesion composed of spindle cells with many small, poorly formed, slit-like vascular spaces involving the lamina propria and submucosa. Immunohistochemical stains demonstrate that this lesion is positive for endothelial markers CD31 (C) and CD34 (not pictured) as well as for Human Hepesvirus 8 (HHV-8) (D).

Switching Immunosuppression From Cyclosporine to Tacrolimus in Kidney Transplant Recipients Based on CYP3A5 Genotyping.

Kidney transplant recipients on long-term cyclosporine (CsA) therapy may develop multiple adverse drug events, and immunosuppression conversion from CsA to tacrolimus (Tac) is an option. Genetic variations, especially cytochrome P450 (CYP) 3A5*3, affects Tac dosing. However, little information is available to guide the conversion with regards to patients' pharmacogenomics. We aimed to investigate whether CYP3A5, CYP3A4, and ABCB1 genotyping could contribute to a more precise and individualized initial dosing of Tac at the time of immunosuppressant conversion. Genotypes of 5 candidate genes (CYP3A5*3, CYP3A4*1G, ABCB1C1236T, ABCB1C3435T, and ABCB1G2677T/A) were investigated by polymerase chain reaction and restriction fragment-length polymorphism methods in 46 adult kidney transplant recipients requiring immunosuppressant conversion from CsA to TAC. Associations between these functional genetic polymorphisms and the dose-adjusted trough concentrations of CsA and Tac were evaluated, retrospectively. Based on the linear regression analysis, CYP3A5 expressers (*1/*1 and *1/*3) had lower Tac dose-adjusted trough concentrations on days 7, 14, 21, and 28, and they required 1.40- to 1.75-fold higher daily dose to reach the target concentration compared with nonexpressers (*3/*3) on day 28 [0.07 (0.06-0.09) mg/kg/d versus 0.05 (0.02-0.06) mg/kg/d, P = 0.001]. CYP3A4*1G or ABCB1 genetic polymorphisms had no effect on the Tac dose-adjusted trough concentrations. Our preliminary study supports the use of CYP3A5 genotyping to guide the initial dosing of Tac when converting the immunosuppression therapy from CsA to Tac.

Focus on five patients treated with cyclosporine up to 62 months

Background: Cyclosporine is a validated treatment for moderate to severe psoriasis. Long-term cyclosporine administration may induce toxic effects. The duration of treatment usually ranges from 10 to 16 weeks. However, some patients may take cyclosporine for a longer time. Aim: The objective of the present study is to evaluate the dose, efficacy and safety in long-term cyclosporine therapy. Patients and methods: We studied the hospital records of patients with psoriasis treated with cyclosporine between 1 January 2009, and 30 April 2015. We decided to focus on patients who, for different reasons, have continued cyclosporine for more than 2 years. Results: Five patients (2.69%) had been assuming cyclosporine for up to 62 months and had achieved a substantial response with no toxic effects. All of them were concerned about recurrence and all patients had personal reasons to prefer Cyclosporine over other drugs, including: familiar history of neurodegenerative disease, desire for motherhood, easy availability on prescription, systemic scleroderma, belenophobia. Conclusion: Cyclosporine is an acceptable monotherapy for psoriasis in selected patients. The prompt discontinuation of treatment usually results in resolution of any eventual toxicity.

Sweet spot for cyclophosphamide: a balancing act

Severe aplastic anaemia is a rare but life-threatening disorder for which allogeneic haemopoietic stem-cell transplant (HSCT) is a potential cure. In patients younger than 35 years and up to 50 years of age without substantial comorbidities with HLA-matched sibling donor, upfront HSCT is the recommended treatment. Healthy patients without a HLA-matched sibling donor are offered HSCT as a second-line treatment after failure of immunosuppressive therapy. 1 Marsh JC Ball SE Cavenagh J et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009; 147: 43-70 Crossref PubMed Scopus (419) Google Scholar Although 60–70% of patients respond to immunosuppressive therapy, blood counts return to normal only in a third of patients, and another third need long-term cyclosporin therapy and the risk of relapse of aplastic anaemia and clonal evolution to myelodysplastic syndromes occurs in a further third of patients. HSCT, however, offers an opportunity for longlasting haematological response and minimises the risk of relapse and reduces the likelihood of clonal evolution. Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1–2 dose de-escalation studyCyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti-thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies. Full-Text PDF

Efficacy of oral glucocorticoid and cyclosporine in a case of rituximab-refractory type B insulin resistance syndrome.

We describe a case of type B insulin resistance syndrome associated with systemic lupus erythematosus (SLE) that was refractory to rituximab and successfully treated with a combination of oral glucocorticoids and cyclosporine. Prior to treatment, insulin resistance was severe, and application of a hyperinsulinemic euglycemic clamp was not possible despite the continuous intravenous infusion of insulin at a maximum rate of 9.0 mU/kg/min. The addition of cyclosporine to oral glucocorticoid therapy resulted in remission of insulin resistance. The combination of oral prednisolone and cyclosporine might be effective in treating type B insulin resistance syndrome, particularly in rituximab-resistant cases. However, nephrotoxicity is a particular concern for patients receiving long-term cyclosporine therapy.

Long-Term Evolution of Cytophagic Histiocytic Panniculitis

Cytophagic histiocytic panniculitis is a disorder manifested by multiple subcutaneous nodules, characterized by lobular panniculitis, and occasionally accompanied by severe systemic manifestations, which require an aggressive medical approach. Several case reports with a good response to immunosuppressive therapy in the acute phase can be found in the literature. Nevertheless, the long-term evolution of this entity has not been described yet, nor have precise recommendations regarding the most adequate posology and duration of therapy. We report the result of switching from a long-term cyclosporine therapy to tacrolimus in a patient with a severe form of cytophagic histiocytic panniculitis.

Alopecia areata presenting in 2 kidney-pancreas transplant recipients taking cyclosporine

Alopecia areata (AA) is an autoimmune disease of uncertain pathogenesis, typically treated with immunomodulators. We report the paradoxical development of AA in two kidney-pancreas transplant recipients receiving immunosuppressive therapy, which included cyclosporine. Review of the literature revealed only 7 other cases of AA occurring in solid organ transplant recipients; all occurred during long-term cyclosporine therapy. The development of AA in this population highlights the complexity of this immunologic disease.

Effects of long-term cyclosporin therapy on gingiva of rats: analysis by stereological and biochemical estimation

Cyclosporin A (CsA) is used as an immunosuppressive agent and its prominent side effect is the induction of gingival overgrowth, which remains a significant problem. The risk factors appraised include the duration of treatment. However, there are no stereological and biochemical studies exploring the effects of long-term CsA therapy on gingival tissue. The purpose of the present study was to investigate the level of TGF-beta1 in saliva and describe the densities of fibroblasts and collagen fibers in the gingival tissue of rats treated with CsA for long periods. Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg of body weight of CsA. At the end of the experimental periods, saliva was collected for the determination of TGF-beta1 levels. After histological processing, the oral epithelium and the connective tissue area were measured as well as the volume densities of fibroblasts (Vf) and collagen fibers (Vcf). After 60 and 120 days of CsA treatment, there was a significant increase in Vf and Vcf as well as a significant increase in TGF-beta1 levels. After 180 and 240 days, reduction in the gingival overgrowth associated with significant decreases in the level of TGF-beta1, and also decreased Vf and Vcf, were observed. The data presented here suggest that after long-term therapy, a decrease in TGF-beta1 levels occurs, which might contribute to an increase in the proteolytic activity of fibroblasts in the gingiva, favoring the normality of extracellular matrix synthesis.

Experience with cyclosporine in heart transplantation

The introduction of cyclosporine as an immunosuppressant in early 1980s dramatically improved the outcome of organ transplantation. The adverse effects of nephrotoxicity and increased incidence of lymphomas were recognized with high doses of cyclosporine during the early part of that decade. This led to lower doses of cyclosporine and combination with prednisolone and azathioprine as the basis of immunosuppression in transplantation. During the second half of the 1990s, the microemulsion formulation of cyclosporine was introduced that gave superior and predictable drug absorption profiles. Therapeutic drug monitoring is considered as a tool to optimize transplantation results and minimize side effects. The nephrotoxicity associated with long-term cyclosporine therapy is recognized; we are learning to take measures to minimize it. As we enter the third decade of cyclosporine use, cyclosporine-based immunosuppressive protocols remain the most popular method in heart transplantation. Newer agents in combination with cyclosporine as the core immunosuppressant are being explored.

"Striped" pattern of medullary ray fibrosis in allograft biopsies from kidney transplant recipients maintained on tacrolimus.

A striped pattern of fibrosis has been described in the kidneys of patients undergoing long-term cyclosporine or tacrolimus therapy. This lesion is frequently misconstrued as being specific for drug toxicity. We performed clinicopathologic correlation on 18 patients with striped fibrosis identified by reviewing 61 biopsies from kidney transplant recipients maintained with tacrolimus. Acute rejection was identified in 14 of 18 patients, chronic rejection in 9 of 18 patients, potential diabetic microvascular injury in 8 of 18, and pre-existing donor disease in 2 of 18. In only one patient could striped fibrosis be ascribed primarily to tacrolimus. Striped fibrosis could also be demonstrated in 6 of 10 late allograft biopsy specimens from patients maintained with only azathioprine, and 8 of 10 native biopsies from patients with advanced diabetes mellitus. Multiple insults contribute to the pathogenesis of striped fibrosis in the kidney. This lesion can be attributed entirely to chronic drug toxicity in only a minority of allografts.

Cholesterol feeding accentuates the cyclosporine-induced elevation of renal plasminogen activator inhibitor type 1

Long-term cyclosporine (CsA) therapy is accompanied by the occurrence of hypercholesterolemia and renal interstitial fibrosis. The present study investigates the effect of dietary cholesterol on CsA-induced lipid disturbances in the rat and on CsA nephrotoxicity. Since plasminogen activator inhibitor type 1 (PAI-1) is a major inhibitor of matrix degradation and elevated plasma PAI-1 levels are reported to be associated with increased low-density lipoprotein (LDL) cholesterol, PAI-1 was examined in the kidneys of rats fed a sodium-deficient diet, with or without cholesterol. After nine weeks, both diet groups were subdivided into a CsA-treated group and a vehicle-treated group. Although cholesterol feeding significantly aggravated CsA-induced renal function impairment, CsA-induced histological lesions were comparable in both diet groups. Cholesterol feeding significantly decreased high-density lipoprotein (HDL) cholesterol irrespective of the treatment, while CsA treatment significantly elevated serum triglycerides irrespective of the diet. Cholesterol feeding alone did not increase the number of infiltrating cells in the renal interstitium. In contrast, in both diet groups CsA treatment caused a significant influx of macrophages, while combined treatment with CsA and cholesterol additionally elevated the number of T-helper cells in the cortex. In all rats, PAI-1 immunostaining was found mainly in intracellular vesicles (lysosomes) in proximal tubules, which stained most intensely in fibrotic areas of kidneys from CsA-treated rats. Cholesterol feeding enhanced the CsA-induced elevation of renal PAI-1 immunostaining to a significant level. These results show that, although serum creatinine, PAI-1 staining and T cell influx were significantly increased in the cholesterol-fed CsA-treated group compared to the other groups, renal CsA-induced histological lesions were not influenced by cholesterol feeding after short-term (3 weeks) CsA administration. To what extent the more pronounced proximal tubular PAI-1 (inhibitor of matrix degradation) immunostaining in fibrotic areas in the cortex of cholesterol-fed CsA-treated rats contributes to the progression of CsA-induced renal fibrosis remains to be determined.

Long-term cyclosporin therapy not acceptable in psoriasis

Long-term cyclosporin therapy not acceptable in psoriasis

Long-term cyclosporine therapy for pediatric nephrotic syndrome

Cyclosporine (CsA) is effective in treating steroid-dependent (SDNS) and steroid-resistant (SRNS) nephrotic syndrome (NS) in children, but because of the potential for chronic nephrotoxicity, its long-term use is controversial. This study reports the results of long-term CsA treatment in 22 children with idiopathic NS. Indications for treatment included SDNS (N = 7) and SRNS (N = 15) children. Pre-CsA histology showed minimal change disease in three patients, immunoglobulin M nephropathy (IgM) in 14 patients, and focal segmental glomerulosclerosis (FSGS) in five patients. All patients had normal initial serum creatinine values. CsA was added to prednisone at 6.3 +/- 0.4 mg/kg per day (mean +/- SE) and adjusted to maintain whole blood trough HPLC levels of 70 to 120 ng/mL for a period of 6 to 53 months (mean, 22 months). Analysis by clinical course revealed that 13 of 15 patients with SRNS (87%) entered remission after a mean duration of CsA treatment of 58 days, whereas seven of seven patients with SDNS were able to be weaned off of daily prednisone therapy. Histologic analysis showed that all five patients with FSGS and 13 of 14 patients with IgM nephropathy either entered remission or were weaned off of daily steroids. Ten of the 22 patients (45%) with complete remission required CsA plus low-dose alternate-day prednisone to maintain remission. Hypertension was seen in eight of 22 patients (36%). No patient had a significant increase in serum creatinine concentration. Renal biopsies performed in 12 patients after 12 to 41 months (mean, 21 months) of CsA therapy showed no nephrotoxicity or disease progression in ten patients. Progression of the previous interstitial fibrosis and tubular atrophy was noted in two patients, suggesting a 17% incidence of CsA nephrotoxicity. This analysis of the long-term risks and benefits of CsA for childhood NS has identified two important findings: (1) combined CsA and alternate-day steroids can be highly effective in inducing complete remission in patients with SRNS and biopsy-proven IgM nephropathy, and (2) long-term use of CsA in moderate doses with closely monitored levels can result in a relatively low incidence of nephrotoxicity.

Vascularized Allogeneic Nerve Transplantation with Cyclosporine Immunosuppression

Allogenic grafts have many advantages over autogenous grafts. An experimental rat model using the great saphenous nerve was developed to study the reconstruction of long peripheral nerve defects with vascularized allogeneic nerve grafts, and the effects of cyclosporine therapy on graft survival were assessed. In animals receiving short-term immunosuppression, the number of regenerated axons increased steadily during the treatment, but rejection began immediately after cyclosporine was discontinued. As the tissues transplanted with the nerves underwent necrosis, the grafts showed demyelination. In contrast, in animals receiving long-term cyclosporine therapy, nerve regeneration assessed in terms of the myelinated axon count was excellent until at least 12 weeks postoperatively but was less active than in vascularized autografts or conventional allografts. These results indicate that the short-term immunosuppressive therapy with cyclosporine cannot produce immunological tolerance of vascularized nerve allografts. In addition, even when administration of cyclosporine was prolonged, nerve regeneration did not exceed that in autografts.

A prospective study of renal structure and function in psoriasis patients treated with cyclosporin

The impact of long-term cyclosporin therapy on kidney structure and function was evaluated in psoriasis patients with normal baseline renal function. Patients received cyclosporin at an average dose 3.9 mg/kg/day for up to three years and underwent serial kidney biopsies and measurements of iothalamate clearance and serum creatinine concentration. Kidney biopsy specimens (assessed on a scale of 0 to 4 where 0 = normal and 4 = severe) from 19 cyclosporin-treated patients as compared to 38 age-matched transplant donors showed increased interstitial fibrosis (1.9 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) and tubular atrophy (1.6 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) at one year. Eleven patients had a second biopsy after an additional two years of cyclosporin treatment demonstrating additional interstitial fibrosis (1.8 +/- 0.2 to 2.4 +/- 0.3, P = 0.002) and tubular atrophy (1.4 +/- 0.2 to 1.9 +/- 0.2, P = 0.053), and the onset of cyclosporin-associated arteriolopathy (0 to 0.5 +/- 0.2, P = 0.02). Quantitative digital morphometric analysis of trichrome-stained specimens also showed increased interstitial fibrosis (22.5 +/- 1.5 to 32.0 +/- 2.0% of interstitial area, P = 0.0008). Iothalamate clearance declined at an average rate of -3.1 ml/min/1.73 m2 per year (95% CI -5.8, -0.3) during the period of cyclosporin treatment. The slope of reciprocal serum creatinine declined by -0.06 dl/mg per year (95% CI -0.08, -0.04). Chronic cyclosporin treatment of otherwise healthy psoriasis patients is associated with progressive renal structural injury and reduced glomerular filtration rate.

Long-term efficacy and safety of cyclosporine in renal-transplant recipients.

The safety of long-term immunosuppression with cyclosporine in renal-transplant recipients is not well understood. This drug may cause a progressive toxic nephropathy, but it also preserves renal function because it prevents rejection. To determine the effect of cyclosporine on renal function and graft rejection, we conducted a retrospective analysis of data on 1663 renal-transplant recipients at six centers. The rate of graft survival was 78 percent (median follow-up, 36 months). Grafts were was lost in 279 patients (17 percent), mostly because of acute rejection (68 patients) or chronic graft dysfunction that was unresponsive to a reduction in the dose of cyclosporine (125 patients); 92 patients died with functioning grafts. The median change in the serum creatinine concentration in all patients after transplantation was less than 0.001 mg per deciliter per month (< 0.09 mumol per liter per month). Patients who had episodes of rejection had decreased rates of long-term graft function and survival. Eight percent of patients with functioning grafts at one year had first episodes of rejection more than one year after transplantation. These late first rejections were associated with noncompliance with therapy (in 34 percent), blood cyclosporine concentrations that were marginally lower than those of patients who had no episodes of rejection, and a low rate of successful reversal of rejection (77 percent, vs. 97 percent in patients with rejection during the first year; P < 0.001). The majority of renal-transplant patients tolerate long-term cyclosporine therapy without evidence of progressive toxic nephropathy. Graft failure is most often due to rejection.

Renal Biopsy Specimens From Patients With Rheumatoid Arthritis and Apparently Normal Renal Function After Therapy With Cyclosporine

Renal biopsies were performed in 14 patients with severe rheumatoid arthritis who had no evidence of compromised renal function after completion of treatment with low-dose cyclosporine (< or = 5 mg/kg/d). Mean serum creatinine at the time of biopsy was 0.84 mg/dL (range, 0.59 to 1.23 mg/dL). In the 13 patients who had received 6 months of cyclosporine therapy, mild glomerular expansion was noted in two biopsy specimens, obsolescent glomeruli (range, 5% to 20%) in five, and glomerular amyloid deposits in one. Five biopsy specimens had mild and three had mild to moderate interstitial fibrosis. Moderate interstitial fibrosis with a striped pattern was attributed to cyclosporine in the 14th patient. The results of a second biopsy performed in one patient after a further 18 months of therapy were unchanged. Although the renal biopsy changes were minimal in 13 patients and pathologic features characteristic of cyclosporine nephropathy were absent from all but one biopsy, a greater frequency of adverse effects due to cyclosporine could not be excluded. In the absence of clinical data, long-term cyclosporine therapy must be administered with caution to patients with rheumatoid arthritis, who commonly have underlying renal damage, and the value of renal biopsies in predicting and preventing end-stage renal failure remains to be determined.

Renal function in patients receiving long-term cyclosporine therapy.

The site at which the vasomotor effects of cyclosporine are associated with acute nephrotoxicity appears to be the afferent arteriole. Proposed mechanisms mediating these effects include sympathetic nerve stimulation, disruption of the balance between vasodilating and vasoconstricting prostaglandins, hypersensitivity to vasoactive peptides, and endothelin release. These mechanisms mediate cyclosporine-associated intrarenal vasoconstriction, yet the causal relationship between these changes and the obliterative vasculopathy seen in association with chronic progressive renal allograft dysfunction is uncertain. Histologic findings seen in chronic progressive renal dysfunction are nonspecific and cannot be correlated solely with cyclosporine use. Retrospective studies analyzing both aggregate serial serum creatinine and reciprocal creatinine determinations did not report a pattern of progressive attrition consequent to toxic nephropathy. Prospective studies with serial GFR determinations with various reference substances found no progressive deterioration in allograft function. Both the retrospective and prospective studies indicate that the attrition of renal allograft function associated with cyclosporine use reflect the chronic effects of immunologic injury. Renal function in extrarenal transplant recipients immunosuppressed with cyclosporine can be characterized by an initial decline in native renal function followed by subsequent stabilization beyond the first 6 months. There does not appear to be an inordinate rate of progression to ESRD.

Post-transplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile

Abstract The benefits of long-term cyclosporin (CyA) therapy are not yet established and must be weighed against its toxicity. We studied cardiovascular risk factors in 25 patients who received a kidney transplant between 1985 and 1989 and in whom CyA was discontinued. The protocol for discontinuing CyA involved starting azathioprine (Aza) and then weaning CyA over 6 weeks without changing the prednisone dose. Parameters collected from the patients' charts 3 months before (pre) and 3 months after conversion (post) and at the most current follow-up (cur) included serum creatinine, cholesterol, blood pressure, and anti-hypertensive medication. The severity of the hypertension was graded, based on a hypertension index reflecting the nature and dose of the anti-hypertensive medication. Of the 25 patients in whom CyA was discontinued, 2 experienced a rejection episode during conversion and were switched back to CyA; 1 patient had a rejection episode after conversion but remained on Aza. Converted patients demonstrated improved renal function (1/Cr pre 0.69 ± 0.20, post 0.84 ± 0.23, P < 0.05), lower serum cholesterol levels (pre 6.8 ± 1.0, post 5.8 ± 1.2, P < 0.05), lower meanarterialpressure(prelll ± 14, postl02 ± 8, P < 0.05) and a lower hypertension index (pre 2.45 ± 2.77, cur 1.62 ± 1.70, P<0.05). Although conversion may carry some risk of acute rejection, it improves graft function and the cardiovascular risk profile significantly.

Post-transplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile.

The benefits of long-term cyclosporin (CyA) therapy are not yet established and must be weighed against its toxicity. We studied cardiovascular risk factors in 25 patients who received a kidney transplant between 1985 and 1989 and in whom CyA was discontinued. The protocol for discontinuing CyA involved starting azathioprine (Aza) and then weaning CyA over 6 weeks without changing the prednisone dose. Parameters collected from the patients' charts 3 months before (pre) and 3 months after conversion (post) and at the most current follow-up (cur) included serum creatinine, cholesterol, blood pressure, and anti-hypertensive medication. The severity of the hypertension was graded, based on a hypertension index reflecting the nature and dose of the anti-hypertensive medication. Of the 25 patients in whom CyA was discontinued, 2 experienced a rejection episode during conversion and were switched back to CyA; 1 patient had a rejection episode after conversion but remained on Aza. Converted patients demonstrated improved renal function (1/Cr pre 0.69 +/- 0.20, post 0.84 +/- 0.23, P < 0.05), lower serum cholesterol levels (pre 6.8 +/- 1.0, post 5.8 +/- 1.2, P < 0.05), lower mean arterial pressure (pre 111 +/- 14, post 102 +/- 8, P < 0.05) and a lower hypertension index (pre 2.45 +/- 2.77, cur 1.62 +/- 1.70, P < 0.05). Although conversion may carry some risk of acute rejection, it improves graft function and the cardiovascular risk profile significantly.