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.

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.

Hypercholesterolemia in renal transplantation.

OBJECTIVES: We conducted this study to evaluate the prevalence, and risk factors of hypercholesterolemia (HC) in renal transplant population. METHODS: We reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia transplanted between 1979 and November 1998. The patients were grouped according to the measurement of serum cholesterol level; group I (normal): below or equal 5.2 mmol/L, group II (mild HC): from 5.3-6.0 mmol/L, group III (moderate HC): from 6.1-8.0 mmol/L group IV (severe HC): above 8.0 mmol/L. RESULTS: There were 1096 patients' records included in the study. According to the level of measured serum cholesterol, there were 421 (38.4%) patients is group I, 256 (23.3%) patients in group II, 363 (33.1%) patients in group III and 57 (5.2%) patients group IV. We found no significant difference between the study groups in terms of gender (60% males, 40% females), mean duration of transplantation (66.9 months), between those transplanted before 1990 and those transplanted after 1990, donor type, prevalence of hypertension (85%), history of hypertension on dialysis, original kidney disease, frequency of rejections in the first year (28%), mean serum creatinine (220 mumol/L), cyclosporine mean dose (3.2 mg/kg/day) mean prednisone dose (0.15 mg/kg/day), number of patients on azathioprine (65%), the mean proteinuria (0.6 G/L) or number of antihypertensives. In comparison with the group with normal serum cholesterol level, the group with severe hypercholesterolemia had significantly higher mean age (40.6 versus 37.4 years), higher mean weight (72 versus 65.8 kg), rate of retransplantation (8.8% versus 3.1%), higher frequency of diabetics (35% versus 20%) and higher frequency of abnormal electrocardiogram (18.2% versus 5.2%). CONCLUSION: That hypercholesterolemia is a significant problem in the renal transplant population in Saudi Arabia. Risk factors for the development of hypercholesterolemia are mainly related to weight, age, diabetes and retransplantation.

Diabetes and renal transplantation: saudi experience.

We conducted this study to evaluate the prevalence and risk factors of diabetes mellitus (DM) in our renal transplant population. We retrospectively reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia, transplanted between 1979 and November 1998. The recipients were grouped according to the diagnosis of diabetes; group I: diabetes developed before transplantation (BTDM), group II: diabetes developed only after transplantation (ATDM) and group III: did not have diabetes (NDM). There were 1112 patients' records included in the study. The mean age was 38.2 years and the mean duration of transplantation was 66.9 months. There were 113(10.2%) patients in BTDM group, 134 (12.1%) patients in the ATDM group and 865 (77.8%) patients in the NDM group. There was no significant difference in the prevalence of hypertension among the study groups. In comparison to the other groups, the BTDM group had significantly more males (78.8%), more patients who were transplanted after 1990 (pre-cyclosporin era), more patients with grafts from living non-related donors (46%), higher incidence of acute rejection episodes (39%), higher mean serum creatinine and more patients treated with azathioprine (71%). The ATDM group had significantly higher mean age (46.4 years), higher mean duration of transplantation (91.5 months), higher rate of retransplantation (8.2%), higher mean serum cholesterol level (6.0mmol/L) and more frequently abnormal electrocardiogram (24.6%) than the other two groups. The ATDM group had comparable mean weight (70.2 kg) to the BTDM group but significantly higher than the NDM group (66.1kg). The NDM group had significantly higher mean dose of cyclosporine (3.3 mg/kg/day) and higher mean dose of prednisone (0.16 mg/kg/day) than the other groups. The only independent risk factor for developing DM after transplantation was advancing age. The currently used low-dose steroid therapy was not significantly associated with development of DM after renal transplantation. Nevertheless DM is an important co-morbid condition in the transplant population and is associated with increased risk for cardiovascular and cerebrovascular events.

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.

The diagnosis of segmental transplant renal artery stenosis by captopril renography.

The captopril renogram test has been shown to be a sensitive test for the diagnosis of renal artery stenosis in native and transplanted kidneys. Most reports have involved only stenosis of the main renal artery. Although segmental renal artery stenosis has been diagnosed successfully in native kidneys, it is not clear whether the captopril renogram test can diagnose segmental renal artery stenosis in a transplanted kidney. The authors report two cases of successful identification, by the captopril renogram test, of functionally significant stenosis in an intrarenal branch of a single transplant renal artery.

Hypertension in renal transplantation: saudi arabian experience.

To evaluate the prevalence, etiologic factors and therapy of hypertension in actively followed up transplant population in Saudi Arabia; we retrospectively reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia. These subjects were transplanted between January 1979 and November 1998. The patients were grouped according to the measurement of blood pressure; group 1 (considered normo-tensive): blood pressure below 140/90 mmHg, group2: blood pressure between 140-159/90-99, group 3: blood pressure 160-179/100-109 group 4: equal to or above 180/110. There were 1115 patients' records included in the study. The mean duration of transplantation was 66.9 +/- 50.1 months. According to the level of measured blood pressure, there were 641 (57.5%) patients in the normotensive group (group 1), 404 (36.3%) patients in the mildly hypertensive group (group 2) 64 (5.7%) patients in the moderately severe hypertension group (group 3) and only six (0.5%) patients in the severe hypertension group (group 4). The estimated prevalence of hypertension in this study was almost 85%. We found no significant difference in the prevalence of hypertension in terms of gender, year of transplantation, duration of transplantation, type of donor, number of previous transplants, diagnosis of renal artery stenosis, etiology of kidney disease, diagnosis of diabetes after transplantation, diagnosis of cerebrovascular accidents, or mean dose of prednisolone and cyclosporine. There was a statistically significant association between increased level of blood pressure and old age (above 50 years), original disease associated with hypertension, history of hypertension on dialysis, acute rejection (once or more), presence of protienuria (more than 0.3 mg/day), abnormality of ECG, or serum creatinine above 300 micromol/L. We conclude that hypertension is highly prevalent in the renal transplant population in Saudi Arabia. Risk factors for the development of hypertension or its complication should be more aggressively approached in order to protect the patients and their grafts alike.

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.

Reversible acute renal failure due to oral acyclovar.

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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.

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.

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.