Long-term Cyclosporine Research Articles

Pharmacogenomics and lung transplantation: clinical implications

under-immunosuppression, with loss of the graft, and over-immunosuppression, with infection and lymphoproliferative disease as the result. Therefore, considerable effort has been put into the pharmacokinetics (PK) and pharmacodynamics (PD) of the antirejection agents used in organ transplantation. Blood concentration monitoring has permitted the rational use of difficult-to-use agents such as cyclosporine and tacrolimus. The use of complex drug regimens in transplant patients has also been dependent upon monitoring of the PK of the immunosuppressants to adjust for frequent drug–drug interactions. At the same time, blood concentration monitoring alone does not prevent many of the more serious side effects of the immunosuppressants. For example, diminished renal function even in non-renal transplants is a persistent problem, and ultimately affects almost 30% of all patients on long-term cyclosporine or tacrolimus. Therefore, lung transplant patients require the individualization of immunosuppression and freedom from adverse drug effects that is promised by pharmacogenomics. Pharmacogenetic associations now suggest that treatment algorithms for

Renal Function and Tubular Phosphate Handling in Long-Term Cyclosporine- and Tacrolimus-Based Immunosuppression in Kidney Transplantation

The aim of the study was to assess impaired tubular phosphate reabsorption and renal function among patients on cyclosporine- or tacrolimus-based immunosuppression for 2 years after kidney transplantation. Among 60 cadaveric kidney allograft recipients observed for 48 months, 40 received cyclosporine, azathioprine, and prednisone (group A and B). Group C consisted of 20 patients receiving tacrolimus with steroid withdrawal at 3 months after transplantation. Renal function and calcium-phosphate metabolism—iPTH, 25-OHD, 1,25(OH) 2D concentration, phosphate reabsorption (TRP; mmol/L), and tubular maximum phosphate reabsorption per glomerular filtration rate (TmPO 4/GFR; mmol/L)—were assessed at 1, 6, 12, 18, and 24 months (groups A and C) or 24, 30, 36, 42, and 48 months (group B). Renal function after 24 months of observation was significantly better among tacrolimus-treated patients (serum creatinine concentration μmol/L; C: 94.6 ± 16.8 vs A: 110.5 ± 22.1 vs B: 121.1 ± 30.9; P < .05). Among tacrolimus-treated recipients, TRP and TmPO 4/GFR remained within normal values during the whole observation period. In groups A and B, TRP improved during the first year of observation; after 2 years it reached values observed in group C (TRP: A: 0.67 ± 0.1; B: 0.72 ± 0.13; C: 0.76 ± 0.07; P = NS), whereas TmPO 4/GFR remained low in group A after 2 years (A: 0.78 ± 0.19; B: 0.91 ± 0.25; C: 0.94 ± 0.15; P < .05). Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared with cyclosporine-treated recipients. Tacrolimus-based immunosuppression led to better kidney allograft function during 2-year observation.

Long-Term Trends in Allograft Survival

Kidney transplantation has changed dramatically over the past decade. Many advances have occurred that result in shorter hospital stays, decreased acute rejection, less infectious morbidity, and improved long-term allograft survival. Many factors are responsible for the improvement in kidney transplantation, and these factors are discussed in this review. These successes have led to a paradox in the care of the kidney-transplant recipient, however. As the short-term complications are prevented or successfully managed, more patients will develop chronic problems with the function of the allograft.

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.

Intrarenal Blood Oxygenation and Renal Function Measured by Magnetic Resonance Imaging During Long-Term Cyclosporine Treatment

Treatment with cyclosporine (CsA) markedly affects the renin-angiotensin-aldosterone system in parallel with an increase in the net tubular reabsorption or a decrease in secretion. Since tubular reabsorption is closely linked to medullary oxygen consumption, the aim of the present study was to investigate the intrarenal oxygenation and renal function in response to CsA. Six mini Göttingen pigs were treated with CsA (10 mg/kg/d) for 6 months. The intrarenal oxygenation was indirectly measured as R2* obtained with a multiecho gradient-echo magnetic resonance imaging (MRI) sequence. Single-kidney renal blood flow (skRBF) was measured by a velocity-sensitive gradient-echo MRI sequence. Relative single-kidney glomerular filtration rate (rskGFR) was derived from the MRI time-activity curve in response to an intravenous bolus of Gd-DTPA (0.05 mmol/kg). The present study showed that administration of CsA increased the medullary R2* (23.1 Hz vs 19.0 Hz, P = .002), whereas R2* was slightly increased in the renal cortex (13.3 Hz vs 12.3 Hz, P = .012). In parallel, rskGFR increased significantly (47.2 mL/min vs 19.8 mL/min, P = .005) but skRBF was unchanged (197.6 mL/min vs 202.5 mL/min, P > .05). The increased R2* in the renal medulla indicated that CsA augments the tubular reabsorption of water, leading to increased oxygen consumption. The supply of oxygen to the kidney was, however, maintained during treatment with CsA as suggested by an unchanged renal blood flow. The increased tubular reabsorption was compensated for by an elevated glomerular filtration rate.

Conversion From Cyclosporine Microemulsion to Tacrolimus-Based Immunoprophylaxis Improves Cholesterol Profile in Heart Transplant Recipients With Treated but Persistent Dyslipidemia: The Canadian Multicentre Randomized Trial of Tacrolimus vs Cyclosporine Microemulsion

Tacrolimus improves lipid profile in renal and liver transplant recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported. One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion-treated heart transplant recipients with low-density lipoprotein cholesterol >2.5 mmol/liter and/or a total cholesterol/high-density lipoprotein cholesterol ratio >4 were recruited for the study. Complete lipid profile was assessed before (baseline) and after 6 months of treatment with either cyclosporine microemulsion maintenance (n=64) or tacrolimus conversion (n=65). At 6 months, tacrolimus-converted patients exhibited a greater decrease in total cholesterol (from 5.51 +/- 0.16 to 4.88 +/- 1.22 mmol/liter [tacrolimus], vs 5.61 +/- 1.36 to 5.38 +/- 0.87 mmol/liter [cyclosporine]; p = 0.0078). This decrease in cholesterol was caused largely by a decrease in low-density lipoprotein cholesterol (-0.41 +/- 0.54 [tacrolimus] vs -0.13 +/- 0.55 [cyclosporine]; p=0.0018). There were no changes in high-density lipoprotein cholesterol and triglyceride levels, but apolipoprotein B therapy was reduced in tacrolimus-converted vs cyclosporine-maintained patients (p=0.0003). By 6 months, 23.7% of tacrolimus- vs 6.7% of cyclosporine-treated patients met the target lipid levels for high-risk patients (p=0.0094). Conversion from cyclosporine to tacrolimus resulted in decreases in blood urea nitrogen, creatinine, and uric acid without any changes in glucose, HbA(1C), and insulin levels. Conversion from cyclosporine microemulsion- to tacrolimus-based immunoprophylaxis resulted in decreased cholesterol, apolipoprotein B, urea, creatinine, and uric acid without any clinically evident perturbation of glucose metabolism in stable heart transplant recipients with treated but persistent mild dyslipidemia.

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.

Cyclosporine treatment of anal furunculosis in 26 dogs

To evaluate the effect of cyclosporine on anal furunculosis lesions in 26 dogs. Lesions were graded as mild in 11 dogs, moderate in eight and severe in seven. Each dog was treated with approximately 4 mg/kg cyclosporine orally every 12 hours until the lesions resolved or showed no further improvement. Residual lesions were resected surgically. Eighteen dogs (69 per cent) experienced complete resolution, seven (27 per cent) improved but had residual lesions and one (4 per cent) showed no improvement. The mean duration of treatment until resolution or no further improvement was 8.8 weeks (range four to 24 weeks). Nine dogs (35 per cent) experienced recurrence. Six were from the group that had shown complete resolution and three were from the group that had surgery. Fifteen dogs (58 per cent) developed side effects to cyclosporine, although none required treatment to be discontinued. Mean duration of follow-up was 6.8 months (range one to 20 months). Cyclosporine was effective at resolving or reducing anal furunculosis lesions in 25 of 26 dogs (96 per cent). However, residual or recurrent lesions remain a potential problem, and surgical resection or long-term cyclosporine treatment may be necessary in some dogs.

A Randomized Controlled Trial of Cyclosporine Withdrawal in Renal-Transplant Recipients: 15-Year Results

In renal transplantation, the immunosuppressive efficacy of cyclosporine is counterbalanced by its nephrotoxicity. Although cyclosporine improves short-term graft survival, its long-term effects are unclear. Recipients of first cadaver renal transplants were randomized into three groups between 1983 and 1986: azathioprine and prednisolone alone (AP, n = 158), long term cyclosporine alone (Cy, n = 166), and short-term cyclosporine followed by azathioprine and prednisolone (CyAP, n = 165). All groups received methylprednisolone induction. There were no significant differences in patient survival at 15 years (48 vs. 56 vs. 51%, P = 0.14), and 15-year graft survival (censored for death) in those patients in the CyAP group (47 vs. 44 vs. 59%, P = 0.06) was not significantly different statistically. When deaths or graft losses before 12 months were censored, the differences in 15-year graft survival between the groups were significant (58%, 51%, 70%, P = 0.01). The CyAP group also had lower mean serum creatinine at all time points beyond 3 months posttransplant out to 10 years (143 vs. 169 vs. 131 micromoles/L, P = 0.04). Per protocol analysis, after censoring patients at change in therapy, increased the observed differences in 15-year graft survival between the groups (54 vs. 38 vs. 65%, P = 0.01). Survival and function of first cadaveric kidney transplants is improved by use of short-term cyclosporine followed by azathioprine and prednisolone. Long-term cyclosporine use reduces long-term graft survival.

Long-term cyclosporin A exposure suppresses cathepsin-B and -L activity in gingival fibroblasts.

Gingival overgrowth is a common side-effect following administration of cyclosporin A. We reported previously that lysosomal protease cathepsin-L activity, but not cathepsin-B, was significantly suppressed by short-term cyclosporin A exposure in human gingival fibroblasts. Although this suppression may lead to decreased degradation of gingival connective tissue, a net increase in matrix proteins, and gingival overgrowth, the effects of cyclosporin A need to be more elucidated, considering the long-term use for patients following organ transplantation. The aim of the present study was to evaluate the effects of clinically relevant doses of cyclosporin A on cultured human gingival fibroblasts. We evaluated the effects of long-term cyclosporin A exposure on cell proliferation, mRNA expression of various proteases and both cathepsin-B and -L activity in human gingival fibroblasts. Human gingival fibroblasts were isolated from three donors' healthy gingiva and cultured from five to eight passages with or without 200 ng/ml of cyclosporin A. Proliferative activity of cyclosporin A-treated cells was examined using MTT assay. Total RNA and cellular proteins were collected for semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and for measurement of the cathepsin-B and -L activity. Long-term cyclosporin A exposure had no effects on cell proliferation. Accumulation of cathepsin-B, -H and -L mRNA was markedly suppressed by long-term cyclosporin A exposure, whereas accumulation of another lysosomal enzyme N-acetyl-beta-D-glucosaminidase mRNA, which is involved in remodeling of gingival epithelium, was not apparently impaired in cyclosporin A-treated cells. Accumulation of matrix metalloprotease-1 (MMP-1) and tissue inhibitor of matrix metalloprotease-1 (TIMP-1) mRNA, which are involved in remodeling of extracellular matrix, also was not impaired. In addition, we demonstrated that long-term cyclosporin A exposure significantly suppressed not only the activity of the active form of cathepsin-(B + L) compared to the activity in non-treated cells (p = 0.0458), but also the activity of the active form of cathepsin-B (p < 0.0001) in human gingival fibroblasts. The decreased ability of protein degradation by not only cathepsin-L but also cathepsin-B is, at least, one of the several factors developing the cyclosporin A-induced gingival overgrowth.

THE EFFICACY, SAFETY, AND FEASIBILITY OF LONG-TERM TWO-HOUR CYCLOSPORINE LEVEL MONITORING IN AFRICAN AMERICAN RENAL TRANSPLANT PATIENTS

P203 Aims: (1) Evaluate the impact of two-hour cyclosporine level (C2) monitoring in stable, maintenance-phase African American cadaveric renal transplant patients. (2) Establish the safety of the two-hour cyclosporine target range 800-1200 ng/ml in African American cadaveric renal transplant recipients. Methods: Study subjects were African Americans stable in maintenance-phase immunosuppression at least one year after their first cadaveric renal transplant. All patients were on triple immunosuppression consisting of low-dose prednisone, mycophenolate mofetil or azathioprine, and cyclosporine (Neoral). At study entry, cyclosporine monitoring was switched from the routine 12-hour trough levels to two-hour (C2) levels and all subsequent dose adjustments were based on the C2 level. C2 levels were measured by the fluorescence polarization immunoassay (Tdx) 2 hours after an oral dose. If the baseline level was outside the target C2 range of 800-1200 ng/ml, dose adjustments were made and serial C2 levels were obtained until the target level was reached. Follow-up C2 and serum creatinine levels were obtained every 3 months thereafter. C2 levels, cyclosporine (Neoral) dose and serum creatinine at baseline and at 6 months were tested for statistical significance (paired t test). Acute rejections were diagnosed by histological examination in cases warranted by clinical suspicion. Results: Of the 26 subjects recruited, 6 month follow-up data were available in 15 patients. A substantial number of patients were lost to follow-up due to poor compliance or other economic reasons. There were 10 males and 5 females, age 52.7 ± 5.7 years, 63.1 ± 41.9 months post-transplant. Co-morbidities at baseline included diabetes mellitus (33%), hyperlipidemia (86.6%) and hypertension (100%). Switching to C2 monitoring resulted in a decrease of cyclosporine dose in 8 patients due to high initial C2 levels (53.3%). The change in C2 level, cyclosporine dose, and serum creatinine at baseline and 6 months were as follows:FigureThere were no episodes of acute rejection. Renal function remained stable or improved in nearly all patients during the study period of 6 months. Conclusions: Cyclosporine monitoring based on two-hour levels with a target range of 800-1200 ng/ml appears safe in African American renal transplant recipients and may allow a decrease of cyclosporine dose in a substantial number of patients. Further investigation is needed to see if such dose reduction may result in reduced long-term cyclosporine toxicity.

Effects of long-term cyclosporin therapy on the periodontium of rats.

The treatment of cyclosporin A triggers an early bone loss and gingival overgrowth. There is a lack of studies exploring the effects of long-term cyclosporin A therapy on alveolar bone homeostasis and gingival tissue. The purpose of this study was to evaluate the effects of long-term therapy with cyclosporin A on the gingival tissue and on the alveolar bone metabolism in rats. Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg body weight of cyclosporin A. At the end of experimental periods, animals were killed and the serum calcium (Ca(2+)) and alkaline phosphatase levels were measured in all groups. After histological processing, the oral epithelium and the connective tissue, as well as volume densities of alveolar bone (V(b)) and multinucleated osteoclasts (V(o)), were assessed at the region of the lower first molars. Significant increases in the serum alkaline phosphatase were observed in those groups that received cyclosporin A therapy. After 60 and 120 days of the treatment with cyclosporin A, evident gingival overgrowth associated with a significant increase of epithelium and connective tissue was observed, as well as a decrease of the densities of bone and an increase of densities of osteoclasts. After 180 and 240 days of the treatment, there was a reduction of the gingival overgrowth associated with significant decreases of epithelium and connective tissue, as well as an increase of bone densities and a decrease of osteoclasts. Within the limits of this experimental study, it can be concluded that the deleterious periodontal effects of cyclosporin A administration may be time-related side-effects.

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.

The role of the protocol biopsies in renal allograft recipients

Subclinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy. In a prospective study 32 low-risk patients were randomized to either a reduced CsA dose (5 mg/kg/d) and daclizumab (group A, n = 16) for 7 months posttransplant with subsequent CsA tapering/withdrawal, or to a normal CsA dose (10 mg/kg/day) without daclizumab (group B, n = 16). Both groups received MMF and prednisone. Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx. The number of rejection episodes was the primary endpoint. The secondary endpoints were: renal function, histological parameters related to CsA, and serum levels of TGF-β and PDGF-BB. A low incidence of clinically suspected rejection episodes was observed (19% in group A and 12.4% in group B; P = NS). Although protocol biopsies showed 12 subclinical rejection episodes (six in group A, six in group B), serum creatinine levels were not different between the examined groups at 3 months. However, at 12 months, there was a statistically improved mean creatinine level in group A patients (1.2 mg/dL ± 0.5 in group A vs 1.54 mg/dL in group B; P < .05). Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies (with no differences between groups, or between 3 and 12 months in both groups). Serum TGF-β and PDGF-BB did not differ between the groups. Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocols. Immunosuppressive regimens with low CsA doses followed by the drug's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.

Severe resistant subacute prurigo successfully controlled by long-term cyclosporin

The case of a 50-year-old woman with an intensely pruritic subacute prurigo resistant to multiple therapeutic regimens is described. Therapy with cyclosporin was started, achieving complete control of the disease, demonstrating a good safety profile during long-term treatment. This is the first report on the successful use of cyclosporin for subacute prurigo.

Optimal immunosuppression post cardiac transplantation: clinical outcomes of long-term cyclosporine monotherapy in a large patient population

Background: Optimal long-term immunosuppressive therapy after cardiac transplantation has not been established. Prolonged exposure to multiple immunosuppressive agents carries the potential for adverse effects: susceptibility to infection and malignancy and the catabolic effects of corticosteroids. A therapeutic regimen to minimize exposure to these drugs would therefore be beneficial.

Long-term use of cyclosporine in cardiac transplantation: the Pitié experience

WITH the introduction of new immunosuppressive drugs, the place that calcineurin inhibitors currently occupy in the treatment of cardiac transplant recipients will be questioned. The introduction of cyclosporine after cardiac transplantation to prevent acute rejection has been associated with a dramatic improvement in short-term survival. However, little is known about long-term outcome in heart transplant recipients. None of the centers has reported its experience with the use of calcineurin inhibitors in patients transplanted 15 years ago. The Registry of the International Society for Heart and Lung Transplantation has provided no data regarding long-term morbidity. Knowledge of long-term advantages and disadvantages of the current immunosuppressive regimens is necessary to develop new drugs. In the present study we describe complications associated with long-term cyclosporine treatment of heart transplant recipients.

Long-term low-dose cyclosporin effective in ITP

Long-term low-dose cyclosporin effective in ITP

Effect of long-term cyclosporine administration on muscle flap hemodynamics.

Long-term use of cyclosporine A (CsA) is associated with deleterious effects such as nephrotoxicity and hypertension as a result of its toxicity on microvasculature. These effects raise the possibility that long-term CsA use harms the microvasculature of the skeletal muscle tissue. An experimental study was conducted to investigate the effect of chronic systemic cyclosporine administration on the microvasculature of the cremaster flap model in the rat. Thirty male Sprague-Dawley rats were divided into five groups of 6 animals each. The control group received no treatment. The four CsA treatment groups received a daily subcutaneous injection of 2 mg per kilogram, 4 mg per kilogram, 8 mg per kilogram, and 16 mg per kilogram of cyclosporine for 6 weeks before surgery. The effect of long-term CsA administration on cremaster flap microcirculation was evaluated in vivo using an intravital microscopy system. Hemodynamic parameters of the cremaster muscle flap such as vessel diameter, red blood cell velocity, capillary density, leukocyte-endothelial interaction, and microvascular permeability were measured. There was no significant (p > 0.05) difference in vessel diameter in all groups. There was a significant increase in the number of adherent leukocytes in the 8-mg and 16-mg CsA group compared with the control (12 +/- 4.8 leukocytes per 100 microm and 12 +/- 4.5 leukocytes per 100 microm vs. 6 +/- 4.3 leukocytes per 100 microm; p < 0.05). Microvascular permeability indices increased significantly at 0 and 30 minutes after fluorescent isothiocyanate-albumin injection in the 8-mg and 16-mg CsA groups compared with the control (0 minutes: 0.6 +/- 0.2% and 0.5 +/- 0.1% vs. 0.4 +/- 0.05%; 30 minutes: 0.8 +/- 0.2% and 0.7 +/- 0.1% vs. 0.5 +/- 0.04%; p < 0.05). Histologically, the cremaster muscle flaps in all cyclosporine groups showed evidence of interstitial inflammation and venous vasculitis. In the 8-mg and 16-mg CsA groups there was also focal muscle injury. The toxic effect of CsA on the microvascular tree of a muscle flap was demonstrated by the increased permeability index in vivo, and the moderate venulitis and focal muscle injury histologically. Systemic CsA administration seems to have minimal impact on the viability of the muscle flaps, which was confirmed by preserved capillary function and muscle flap perfusion. These data suggest that there is a minimal risk in undertaking a pedicled muscle flap transfer procedure using a CsA immunosuppressive protocol.

Adverse effects with long-term cyclosporin for severe psoriasis.

The use of cyclosporin A (CSA) for the treatment of severe psoriasis is well established. However its use is limited by its adverse effects, especially nephrotoxicity. We reviewed 28 patients treated with CSA for severe psoriasis over an 11-year period. All patients were on long-term CSA treatment (median duration 55.5 months). Twenty patients developed renal impairment which required discontinuation of treatment in seven. Twelve patients' renal function stabilized on dose reduction and one improved. Sixteen patients developed hypertension. For this small group of patients with severe psoriasis, recalcitrant to other treatments, CSA afforded better quality of life which they otherwise could not enjoy. Although this comes at a cost with the development of renal impairment we feel that such patients can be continued on CSA provided that they are under the combined care of a dermatologist and a nephrologist.