The role of androgen receptor gene in cyclosporine induced gingival overgrowth.

BACKGROUND AND OBJECTIVE: Gingival overgrowth is a prominent side effect of cyclosporine (CsA) therapy in renal transplant patients. Although the exact mechanism by which this drug induces gingival overgrowth is uncertain, marked variations in individual susceptibility to this drug suggest a genetic predisposition. Studies have shown that genetic variation (polymorphism) in the trinucleotide cytosine-adenine- guanine (CAG) sequence in exon 1 of the androgen receptor (AR) gene is related to altered activity of the AR as a transcription factor. However, the relationship between the length of the CAG repeat and gingival overgrowth has not yet been studied. The present study was carried out to determine whether there is an association between CsA-induced gingival overgrowth and the length of the CAG repeats in the AR gene. MATERIAL AND METHODS: Genomic DNA samples were prepared from the blood of 50 renal transplant patients with CsA-induced gingival overgrowth and from the blood of 100 renal transplant patients on CsA with no gingival overgrowth. RESULTS: The difference in allele distribution among the subjects with gingival overgrowth and control samples was statistically significant (p = 0.001). CONCLUSION: The findings suggest a link between CsA7induced gingival overgrowth and a smaller size of CAG repeat in the AR gene.

Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient.

INTRODUCTION: Studies were conducted to investigate changes in the extent of human herpesvirus 8 (HHV-8) shedding and diversity of HHV-8 strains in the mouth of a renal allograft recipient who developed cutaneous post-transplantation Kaposi's sarcoma. METHODS: Matched oral and blood samples were obtained from a Saudi Arabian renal allograft recipient from 3 days before to 38 weeks after transplantation, and from his kidney donor. Polymerase chain reaction (PCR) protocols to amplify selected HHV-8 sub-genomic regions were applied to detect and quantify HHV-8 DNA. Sequence diversity was determined by cloning the PCR products and subjecting them to denaturing gradient gel electrophoresis and to nucleotide sequencing. RESULTS: Before transplantation, the recipient was seropositive for anti-HHV-8 immunoglobulin G, but the donor was seronegative; HHV-8 DNA could be detected in the recipient's blood, whole-mouth saliva (WMS) and buccal exfoliates, and the salivary viral load was estimated as 2.6 million genome-copies/ml. Post-transplantation, the recipient's salivary viral load initially increased to 4.1 million genome-copies/ml, and thereafter declined precipitously, coinciding with an increase in the dosage of valaciclovir given; HHV-8 DNA was detected most often in WMS compared with parotid saliva, and buccal and palatal exfoliates. Carriage of multiple HHV-8 strains was evident in blood and oral samples; whereas before transplantation strains belonging to genotypes A1 and A5 were observed, after transplantation genotype A5 strains became dominant and A2 strains emerged. CONCLUSION: Immunosuppression and antiviral prophylaxis may interact to influence the spectrum of oral HHV-8 strains and the extent of post-transplantation HHV-8 shedding into the mouth.

Successful use of rifampicin in the treatment of tuberculosis in renal transplant patients immunosuppressed with cyclosporine.

Cyclosporine and rifampicin were used simultaneously in 6 renal transplant patients with tuberculosis. The total daily dose of cyclosporine had to be increased 3-5 fold, with the frequency of administration increased from twice to thrice daily. With this regimen, satisfactory cyclosporine levels were attained and there was no adverse affect on graft function.

Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C.

INTRODUCTION: Hepatitis C Viral (HCV) infection is the leading cause of chronic liver disease in end-stage renal disease patients (ESRD). The impact of HCV on patient and graft survival posttransplantation is controversial. The most successful approach is to eliminate the virus while the patient is on dialysis prior to transplantation. The main aim of this pilot study was to assess the efficacy of combined alpha-interferon (alpha-IFN) and ribavirin treatment of HCV hemodialysis (HDx) patients, by comparing the sustained virological response to that obtained by local historical data on treatment with alpha-IFN alone. A secondary aim was to establish the optimal therapeutic dose of ribavirin in this regimen. METHODS: Twenty HCV-HDx patients who were histologically (liver biopsy) and virologically (HCV-PCR)-positive were selected randomly. They received combination therapy with 3 million units (MU) of alpha-IFN and 200 mg of ribavirin three times a week. Initially nine patients were treated for 24 weeks. Later, another 11 patients were randomly selected to give the combination for 48 weeks. RESULTS: Six of the nine patients who were treated for 24 weeks (66%) became HCV-PCR-negative by the end of the treatment period. They continued to have a sustain virologic response at 6 months after the cessation of therapy. Six of the 11 patients (55%) who were treated for 48 weeks became HCV-PCR-negative at the end, and at 6 months after cessation of treatment. Of the first six responders, 4 (66%) maintained a sustained virologic response at 1 year postcessation of therapy. Nine of the 11 patients had genotype 4 and 1. No side effects were reported for a ribavirin dose of 200 mg three times a week. CONCLUSION: This pilot study suggests that combination treatment for 24 weeks and 48 weeks with 3 MU alpha-IFN and 200 mg ribavirin three times a week, elicited a sustained virologic response in HDx patients with HCV infection better than IFN alone with minimal side effects. A prospective, double-blind, controlled study using pegylated INF plus ribavirin is currently underway.

Kaposi's sarcoma in renal transplant recipients.

One hundred and seventeen of 270 (43%) recipients of organs obtained from donors with malignancies had evidence of transmitted cancers. In 9 instances these were removed from renal allografts immediately prior to transplantation. Including these cases there were 45 recipients of organs in which a neoplasm involved the allograft, 6 others in whom adjacent structures were invaded, and another 66 patients who had distant metastases. Precautions to prevent cancer transmission include meticulous preoperative screening of donors, careful examination of all organs at the time of harvesting, biopsy of any suspicious lesions, and routine donor autopsy, if possible.

Influence of sex and chronic haemodialysis treatment on total, free and acyl carnitine concentrations in human serum.

The influence of sex and haemodialysis treatment on serum total, free and acyl carnitine concentrations in healthy controls and chronic renal failure patients has been investigated. Patients on regular haemodialysis treatment generally displayed significantly decreased serum carnitine levels. The mean predialysis serum carnitine levels were not significantly different from the mean healthy control values. However, after dialysis a significant decrease in serum carnitine levels was observed compared to the predialysis and healthy control values. Moreover, serum ratio of acylated to free carnitine was significantly higher after haemodialysis as compared to both healthy controls and predialysis patients. Sex-related changes in serum total, free and acyl carnitine levels and ratios of acylated to free carnitine have been observed in healthy controls and patients on chronic haemodialysis treatment.

Caring for hemodialysis patients in Saudi Arabia. Past, present and future.

There are currently 5706 patients receiving hemodialysis therapy in the Kingdom of Saudi Arabia - a 15 fold increase when compared to 1983. The annual increase in the number of patients on dialysis for 1999 is 696 (10 fold increase when compared to 1983). Besides the massive increase in the number of patients in the last 20 years, we have noticed a marked increase in the mean age of patients (51.3 years in 1999 as compared to 37.9 years in the early 80s). Diabetes mellitus which was an insignificant contributory etiology (4%) in the early 80s is now a major cause (16-25%). Similarly mortality has increased from 4% annually to 11-14% annually. This is largely due to increasing age and prevalence of diabetes mellitus. Within the expired cohort the mean age was 62.3 years compared to 51.3 years of the total dialysis population, and diabetes mellitus was present in 60.5% in those who expired. Moreover, ischemic heart disease was diagnosed in 50% before death. Tuberculosis and Hepatitis C virus incidences, however, have not improved over the years but the degree of rehabilitation has, largely due to better hemoglobin level and due to the technological advances in dialysis delivery. This article describes these changes, their causes and implications.

Does regressed posttransplantation Kaposi's sarcoma recur following reintroduction of immunosuppression?

We report a patient who developed generalized Kaposi's sarcoma (extensive skin and stomach lesions) 24 months after renal transplantation whilst on cyclosporin (CyA) and prednisolone. Kaposi's sarcoma disappeared completely upon withdrawal of CyA. The patient remained with a well-functioning graft and free of Kaposi's sarcoma for 36 months on prednisolone alone. CyA was reintroduced following an episode of acute rejection. Within 8 weeks, Kaposi's sarcoma reappeared on the skin at the same sites as the previously healed lesions. They completely disappeared again upon withdrawal of CyA. Azathioprine was then introduced and Kaposi's sarcoma lesions reappeared 6 months later.

Some of the Lessons Learnt from Renal Transplant Recipients Cared-for at the Riyadh Armed Forces Hospital.

The first-ever renal transplantation in Saudi Arabia was carried out at the Riyadh Armed Forces Hospital in March 1979. Since then, 480 renal transplants have been performed in our institution and we have also followed-up many patients who have been transplanted outside the Kingdom. Over 85% of our patients are on cyclosporin-based immunosuppression and the mean follow-up was 3.4 years. In this paper, we summarize our experiences and findings in the field of renal transplantations.

FK 506 as an alternative in cyclosporin-induced hemolytic uremic syndrome in a kidney transplant recipient.

We describe a patient who received a living related kidney transplant that worked very well initially but developed oliguria and renal failure within 1 week and required dialysis. Clinical and hemological changes, as well as renal biopsy, confirmed the diagnosis of cyclosporin-induced hemolytic uremic syndrome. The patient did not respond to antirejection therapy or plasma exchange but did respond to the withdrawal of cyclosporin A and the commencement of FK 506.

A Prospective Study of Renal Biopsies Performed Over One-year at the Riyadh Armed Forces Hospital.

A prospective study of all native kidney biopsies performed over one year at the Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia was conducted. During this period, 52 kidney biopsies were performed of which, 49 had adequate tissue. All biopsies were processed for light microscopy, immunofluorescence and electron microscopy. The indications for biopsy included the nephrotic syndrome (n=28; 53.8%), asymptomatic proteinuria (n=12; 21.2%), acute nephritic presentation (n=7; 13.5%) and asymptomatic hematuria (n=7; 13.5%). Primary glomerulonephritis (GN), excluding IgA nephropathy (IgAN) was seen in 34 of the 49 patients (77.6%). Focal and segmental glomerulosclerosis and mesangial proliferative GN were the most common histological diagnoses (31% and 20.4% respectively). Surprisingly, we found a high prevalence of IgA nephropathy (IgAN) of 14.5% in comparison with other studies. The prevalence of mesangiocapillary glomerulonephritis (MCGN) was low (2%) and can only be explained as incidental. The study patients were followed-up for an average of 26.3 weeks. At the end of the observation period, 50% has unchanged course, 37.5% had improved their renal function and protein excretion, and 12.5% had deteriorated. The prognosis of different GN groups and renal survival rate cannot be assessed or calculated in this study because of the relatively short duration of follow-up. Our study further emphasizes the need for a national GN registry and long-term follow-up, in order to recognize the common patterns of GN, their natural histories, the appropriate line of management, and to try and arrest their progression to end-stage renal disease.

Development of systemic lupus erythematosus in a male patient after 14 years on hemodialysis.

We report a 38-year-old man who developed systemic lupus erythematosus (SLE) 14 years after commencing regular hemodialysis. When he was initially diagnosed as having end-stage renal disease (ESRD) secondary to chronic glomerulonephritis, he did not have any clinical or serological criteria to suspect SLE. He did not receive, at any stage, any of the drugs known to cause SLE. He showed remarkable improvement after treatment with steroids and cyclophosphamide.

Renal parenchymal malacoplakia and megalocytic interstitial nephritis: clinical and histological features. Report of two cases and review of the literature.

We report 2 cases of acute renal failure caused by rare and closely related inflammatory conditions, i.e. renal parenchymal malacoplakia and megalocytic interstitial nephritis. We have discussed the clinical presentation, natural progression of the disease, the short- and longterm prognosis of the kidney, the histological appearances, the radiological features and the medical therapy together with a review of the literature.

Effect of Ramadan fasting on Moslem kidney transplant recipients.

This study was carried out to find out whether Ramadan fasting would affect the renal function in kidney transplant recipients with normal or impaired graft function. Twenty-three transplant recipients, 17 with a normal function and 6 with an impaired but stable function with plasma creatinine levels not exceeding 300 mmol/l, were included in this study. The mean posttransplant period was 2.0 (range 0.6-6.3) years. Urinary and serum biochemical parameters, ciclosporin A level, and hematocrit were checked weekly, during Ramadan as well as 1 week before and after. Statistical analysis showed no significant changes in all parameters before, during, and after Ramadan. In conclusion, our findings indicate that fasting during the month of Ramadan does not seem to be associated with any significant adverse effects in kidney transplant recipients with normal or impaired graft function and suggest that it is safe for those patients to fast during Ramadan after 1 year of renal transplantation.

Hepatitis C associated chronic liver disease in renal transplant recipients.

Infection with Hepatitis C Virus (HCV) is emerging as a major cause of morbidity and mortality in renal transplant recipients. We studied three hundred and forty stable renal transplant recipients on follow-up in our transplant clinic. Anti-HCV, tested by second generation ELISA, was positive in 185 patients (54%) of whom 52 (28%) had evidence of chronic liver disease. Six of the study patients were positive for anti-HCV and hepatitis B surface antigen. Twenty-three patients consented to undergo liver biopsy of whom eight had normal histology or fatty changes. Five patients had chronic non-specific hepatitis; four each had chronic lobular and chronic active hepatitis (CAH) and two had CAH with cirrhosis. All 15 patients with significant abnormalities on liver histology had elevated serum transaminase levels. Repeat liver biopsies were performed in seven patients after a mean period of 23.8 months following the first biopsy which showed worsening of the disease in four while three retained the same pattern. These results suggest that the prevalence of anti-HCV in our renal transplant recipients is high and that these patients have a high prevalence of chronic liver disease associated with major changes on liver histology. It is therefore recommended that caution is exercised while considering transplantation in patients who are anti-HCV positive.

Progression of hepatitis C infection in a renal transplant recipient: a case report.

We present a patient with hepatitis C virus (HCV) infection who developed chronic active hepatitis (CAH) after renal transplantation. Alpha-interferon (a-IF) therapy was administered in view of deteriorating liver biochemistry. Liver histology at this stage showed features suggestive of chronic active hepatitis (CAH). The patient had stable graft function. Therapy with a-IF resulted in noticeable biochemical response within two weeks of commencement. An episode of steroid resistant renal allograft rejection occurred after 10 weeks of a-IF therapy which responded well to anti-lymphocyte globulin. Since then, the CAH has gradually progressed on to the development of cirrhotic changes and hepato-cellular carcinoma after 10 years following transplantation. Our case indicates that liver disease in anti-HCV positive patients can follow a serious course following renal transplantation.