Successful use of kidneys from deceased donors with acute renal failure.

BACKGROUND: Kidneys from deceased donors with acute renal failure are not widely used. OBJECTIVE: To compare outcomes for recipients of kidneys from donors with acute renal failure at organ recovery with outcomes for recipients of kidneys from donors with normal serum levels of creatinine. METHODS: Records of deceased donors and recipients of their organs at the Saudi Center for Organ Transplantation from 2003 to 2005 were reviewed. A total of 33 donors (donating 65 kidneys to 65 recipients) with elevated serum levels of creatinine (>1.7 mg/dL) and 94 donors (donating 188 kidneys to 188 recipients) with normal (<1.1 mg/dL) serum levels of creatinine at organ recovery and their respective recipients were compared. Both groups had normal creatinine levels at admission. RESULTS: Recipients in both groups had similar renal function at discharge and follow-up. Delayed graft function occurred more often (P= .009) in the recipients of kidneys from donors with acute renal failure (47.7%) than in recipients of kidneys from donors with normal creatinine levels (29.8%). Elevation of serum level of creatinine at organ recovery did not correlate significantly with kidney function at discharge or last follow-up or with graft survival. CONCLUSIONS: Survival of patients or grafts at 1, 2, and 3 years did not differ significantly between the recipients in the 2 groups. Only the frequency of delayed graft function differed between the 2 groups.

Can renal scan findings predict biopsy-proven allograft rejection?

OBJECTIVES: To assess the usefulness of isotopic renogram in diagnosing acute renal graft rejection. MATERIALS AND METHODS: Degree of perfusion and allograft uptake of tracer were correlated with the clinical and biopsy diagnoses in 15 postrenal transplant patients with varying degrees of renal impairment. Renographic findings and perfusion calculations were done by a blinded observer. RESULTS: A strong correlation was found between renal histology and renal scan findings in 13 of 15 patients. Sensitivity and specificity of renal scanning in diagnosing acute rejection were 85% and 50% respectively (using renal biopsy findings as the gold standard). CONCLUSION: Our results demonstrate a strong correlation between blinded perfusion assessment and biopsy-proven acute rejection. We conclude, therefore, that single renal flow scan with DTPA (noninvasive/nonnephrotoxic) allows a physician to tailor therapy for acute renal graft dysfunction. We suggest that in cases with a renographic diagnosis of AR, the patient should receive standard antirejection therapy. Renal biopsy should be reserved for those instances when the renographic findings are not definitive and those when the patient fails to respond to a standard methylprednisolone therapy.

A model for scoring and grading willingness of a potential living related donor.

There are few examples in the literature of objective measures for the assessment of donor willingness. The author describes the scoring system in use at his own renal transplant unit which has brought objectivity to the process of determining the willingness of living related donors. In this system, a total score to determine the degree of willingness or unwillingness is calculated based on responses to a series of questions. The author believes that with minor modifications this system could be implemented by transplant units in different countries and cultures to screen out donors who are acting under duress.

A proposed Saudi approach to the ethical utilization of living unrelated kidney donation.

We outline a proposal for the use of living unrelated kidney donors for transplantation. This proposal, although recommended by the Saudi National Committee on Renal Transplantation, is still under discussion and has not been implemented yet. We feel that this proposal is ethical with airtight safeguards against commercialization and for the protection of the well-being of the donor with assurance that he or she has not been coerced into donation.

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.

Posttransplant complications encountered in renal transplantation in the Middle East.

This paper discusses the commonly seen complications encountered in Middle Eastern transplant recipients, including posttransplant Kaposi's sarcoma, tuberculosis, infective diarrhea, and pregnancy.

Pregnancies in renal transplant recipients--with a focus on the maternal issues.

One hundred and thirteen pregnancies in 73 women who received a renal transplant were studied. The duration between the transplant operation and the conception averaged 19.9 months with a range of I month to 72 months. The mean age was 28 years. The majority (50 recipients had one pregnancy each, but two women had 5 children each and one had seven children). Only 12 (11.5%) out of the 113 pregnancies ended up with spontaneous abortions. The maternal medical problems encountered were reversible rejection in 11%, hypertension in 43%, UTI in 17% and gestational diabetes in 21%. It was noted that there was high incidence of preterm delivery in 64% of the pregnancies Caesarian section was required in 72% % of the cases. In conclusion we observed a high prevalence of successful pregnancies with no adverse effect on the allograft function and excellent fetal outcome (which is described in a separate paper focusing on the fetal outcome).

Pregnancies in renal transplant recipients--with a focus on babies.

We studied 113 pregnancies in 72 renal transplant recipients. The mean duration between the transplant operation and the first pregnancies was 19.9 months (1-72). This paper focuses on the findings in babies and their outcome. The male babies were 34% of the total. 28% of the babies were delivered vaginally and 72% by Caesarian section. It was noted that there was high incidence of preterm delivery in 64% of the pregnancies. The birth weights were also less than that observed in the general population. 84% was under 50th percentile for weight with 19% being under the 10th percentile. (Saudi growth chart, KACST) The mean hospital stay was 18 days (2-44). The Apgar score was less than 7 in only 10% of the cases and 10 in 50.9%. The incidence of congenital defects was low and no different than the general population (we encountered only 4 cases with minor defects). Despite exposure to cyclosporine throughout the pregnancy and having reduced Nephron mass by virtue of their low birth weight we could not find any glomerular or tubular defects, hypertension or prorienuria in 41 children with a mean age of 52 months. We advised against breast feeding in view of the presence of cyclosporine in the mothers' milk.

important social factors that affect organ transplantation in Islamic countries.

Social attitudes and beliefs have direct and strong impact on people's acceptance of organ donation and brain death, and therefore affect the entire practice of organ transplantation. The views differ from one society to another, and they at least partially explain regional variations in the world with respect to success of organ transplantation. Social attitudes and ethics in Islamic countries are closely intertwined with Islamic tradition, teachings and heritage. These positions are strongly adhered to in many Islamic countries, and by Moslems who live in countries that are not predominantly Islamic. We feel that transplant physicians and transplant coordinators should be aware of these factors when dealing with potential donors and recipients. Decision-making can be facilitated if these issues are considered prior to consulting with a donor's family and if an appropriate compassionate explanation of need for transplantation and basis of brain death diagnosis is provided based on a knowledge of underlying social constraints. Such steps can make the donation process smoother for both health care workers and the family.

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.

The need for guidelines for the practice of hemodialysis in the kingdom of saudi arabia: a questionnaire survey.

Hemodialysis remains the most widely used form of renal replacement therapy world-wide. In view of the large number of patients who are on maintenance hemodialysis in Saudi Arabia, it was felt to have some sort of guidelines to standardize dialysis delivery in the Kingdom. We performed a survey on various aspects of dialysis delivery. A detailed questionnaire was sent to 120 hemodialysis centers in the Kingdom and response was obtained from 55 (45.8%). The questionnaire consisted of questions for which answer on the present situation and ideal recommendation were sought. With these data, it is hoped to have proper guidelines that can be laid down to assist the practicing nephrologists in the Kingdom in optimizing dialysis delivery.

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.

Effect of lithium on cyclosporin induced nephrotoxicity in rats.

Psychoactive drugs provide essential intervention in the care of transplant recipients, yet little is known of their interaction with immunosuppressants such as cyclosporin (CSA). Lithium (Li) is an invaluable drug for the treatment of manic disorders in organ transplant patients. As both these drugs are known to produce renal toxicity, the concomitant use of CSA and Li may be potentially harmful. The present study was undertaken to investigate the effect of CSA and Li chloride individually and in combination on renal structure and function of rats. Male Sprague-Dawley rats were divided into the following eight groups of seven animals each: group I, control (vehicle only); group 2, Li (2 mEq/ kg i.p.) alone; group 3, CSA 12.5 mg/kg (subcutaneous); group 4, CSA 25 mg/kg; group 5, CSA 50 mg/kg; group 6, CSA 12.5 mg/kg + Li; group 7, CSA 25 mg/kg + Li; and group 8, CSA 50 mg/kg + Li. The drugs were given once a day for seven days; Li being administered 30 min before CSA. Twenty four hours after the last dose of drugs the animals were sacrificed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Li levels. The left kidney was analyzed for malondialdehyde (MDA) and conjugated dienes (CD) levels and right kidney was used for histopathological studies. Our results showed that Li alone did not produce any significant renal toxicity, whereas CSA dose dependently caused structural and functional changes in kidneys. However, significantly higher structural and functional impairment was observed in the animals treated with Li plus CSA as compared to CSA alone treated animals. Several fold increase in blood Li level was also noticed in the rats concomitantly treated with CSA and Li. A significant increase in MDA and CD in the rats treated with CSA plus Li suggests the role of oxidative stress in drug induced nephrotoxicity. These findings clearly demonstrate that even non toxic doses of Li may significantly exacerbate CSA induced nephrotoxicity in rats. The enhanced nephrotoxicity following concomitant use of these drugs may be attributed to significant increase in the bioavailability of Li and enhanced oxidative stress. Further clinical studies are warranted to investigate the interaction of these nephrotoxic drugs in human subjects.

Total plasma clearance of 51Cr-EDTA: variation with age and sex in normal adults.

Although inulin clearance measured during constant infusion is still considered the reference method, single-injection of 51Cr-EDTA with subsequent plasma sampling has become the most popular technique for the routine assessment of glomerular filtration rate. Despite the fact that the technique has been in use for 30 years, there are only a few reports of normal values calculated directly from 51Cr-EDTA data and normal ranges have generally been produced by conversions of inulin data. The aim of this study was to measure the variation in total plasma clearance, calculated directly from 51Cr-EDTA measurements, in normal males and females, of Saudi Arabian origin, over a wide range. Altogether, 201 potential kidney donors aged 16-60 years were studied. No statistically significant association of total plasma clearance with age or sex could be demonstrated; however, predictive equations suggesting a small decline in total plasma clearance with age were developed. The figures presented suggest that the reduction in total plasma clearance of 51Cr-EDTA with age is relatively shallow up to the age of at least 60 years and that normal ranges produced by conversion of inulin data may overestimate the decline with age.

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 spectrum of glomerulonephritis in saudi arabia: the results of the saudi registry.

Only few studies regarding glomerulonephritis, with relatively small numbers of patients, have so far been published from different centers in Saudi Arabia, and have reported conflicting results regarding the patterns, even in the same city. The possible reasons for these differences include the small number of patients in the different studies, differences in the indications for renal biopsies, referral bias, geographical differences, and, sometimes, the non-availability of the necessary diagnostic facilities in the reporting centers. In order to overcome these problems, a registry for glomerulonephropathy was attempted in Saudi Arabia. Six large referral hospitals from different regions of Saudi Arabia participated in this registry. Biopsy reports and clinical information of 1294 renal biopsies were obtained. There were 782 renal biopsies due to glomerulonephritis (GN) accounting for 77.2% of the total biopsies. Five hundred eighty seven (72.6%) were primary glomerulonephritidis. Focal and segmental glomerulosclerosis (FSGS) (21.3%) and membrano-proliferative glomerulonephritis (MPGN) (20.7%) were the most common types found in the primary glomerulonephritidis. Membranous glomerulonephritis (MGN) was present in only 10.6% of the cases. IgA nephropathy was found in 6.5% of the cases. Of the secondary glomerulo-nephritides, systemic lupus erythematosus (SLE) was the most common indication for biopsy (57.0%) and amyloidosis was found in only 3.2% of the biopsies. In conclusion, FSGS and MPGN were the most common forms of primary glomerulonephritis in adult patients in Saudi Arabia. MGN was not as common as in the western world. SLE was the commonest cause of secondary GN. Amyloidosis was not as common as in other Arab countries. There is a need for more centers from Saudi Arabia to join this national GN registry. Similar registries can be established in different Arab countries, which all would, hopefully, lead to a Pan-Arab GN registry.