Kamel El-Reshaid

Comparison of two immunization schedules with recombinant hepatitis B vaccine and natural immunity acquired by hepatitis B infection in dialysis patien

In a prospective study over a 2-year period we compared two practical dosage schedules to vaccinate dialysis patients against hepatitis B virus (HBV) infection using a yeast-derived recombinant hepatitis B vaccine (Engerix-B). In addition, the natural history of this acquired immunity was compared with that developed through HBV infection in dialysis patients and healthy subjects. Patients on dialysis treatment (haemo or peritoneal) who were tested to be negative for hepatitis B surface antigen (HBsAg), anti-HBs and anti-HB core were allocated at random to receive HB vaccine according to one of the two schedules. The two groups receiving the vaccine were matched for age, sex, mean duration on dialysis and the form of dialysis treatment received. The group of patients who received a four-dose schedule (at 0, 1, 2 and 6 months) of 40 micrograms of HB vaccine each time (group 2) achieved a seroconversion rate of 79% 1 month after the last dose (at month 7) compared with a seroconversion rate of 55% in those who received three doses (at 0, 1 and 6 months) of 40 micrograms each (group 1). Healthy controls who received half the amount of vaccine on a three-dose schedule (group 3) attained 100% seroconversion (p < 0.05). When retested at 24 months, 30% of seroconverters in group 1 had lost their protective immunity, compared with only 6% in group 2 and 15% in group 3. The magnitude of antibody response (total and anti-(a)-specific) was assessed in the vaccinees at 24 months and compared with that of two other control groups, dialysis patients (group 4) and healthy volunteers (group 5), who had acquired immunity from HBV infection. In general, the total and anti-(a)-specific HBs titres in the dialysis patients (groups 1, 2 and 4) were lower than in their corresponding healthy controls (groups 3 and 5), irrespective of whether the protective immunity was acquired by vaccination or HBV infection. However, the anti-HBs titres in dialysis patients who received four doses were significantly higher than in those who received only three doses (p < 0.05), which indicated a better protective immunity in favour of the former regime. The magnitude of antibody response in the vaccinees of groups 2 and 3 compared well with their respective controls, groups 4 and 5, who had acquired their immunity through HBV infection. This implied that the yeast-derived vaccine was sufficiently immunogenic and provided lasting protection in patients and healthy subjects vaccinated by an appropriate dosage schedule.(ABSTRACT TRUNCATED AT 400 WORDS)

Epidemiological profile, mineral metabolic pattern and crystallographic analysis of urolithiasis in Kuwait Urolithiasis in Kuwait

This study was conducted to determine the epidemiological profile of urolithiasis in Kuwaiti patients and the associated metabolic abnormalities favouring stone formation in this patient population. Between 1986 and 1994, a total of 421 Kuwaiti patients were studied in Al-Amiri renal stone laboratory. The mineral composition of stones was determined using a combination of stereoscopic microscopy and infrared spectrophotometry. Mineral metabolic screen (MMS) was available in 306 (72.7%) of those patients. The average annual incidence of new stone formation in Kuwaiti patients was 23.9 per 100,000 population. The incidence was only 6.9 per 100,000 population in those from pediatric age group, 33.4 in adults and 73.6 in the elderly. The frequency of new stone formation was higher among males as compared to females at different age groups. Calcium oxalate (CaO) constituted 72.1% of renal stones encountered in adults as compared to only 52.1% and 40.7% in elderly and pediatric age groups. Eighty four patients had recurrent and/or high stone load. Detailed family history was available in 57 of those 84 patients and was suggestive of strong family aggregation of stone disease in 30 (53%) patients. The proportion of urate stones was 15.4% of all stones formed and constituted a major cause of renal stones in children (24.1%), adults (14.4%) and elderly (12.5%). Cystine stones were found in 10 patients (2.4%). Hyperuricemia was detected in 1/3 of patients from pediatric age group. In adults, 89 (38.4%) of 232 patients had abnormal MMS, of which hyperuricosuria with or without hyperuricemia accounted for 79.8% of those abnormalities. In elderly patients, metabolic disorders were detected in 7 (17.5%) of the 40 patients. In the latter group, all except one, had hyperuricosuria with or without hyperuricemia. Cystinuria, distal renal tubular acidosis (d-RTA) and hyperparathyroidism constituted 6.6% of metabolic abnormalities in the patients studied. Primary abnormalities of upper and lower urinary tract was detected in 6% of adult patients as compared to 47% in children and 30% in the elderly. In conclusion; the incidence rate of new stone former in Kuwait is significantly lower from that reported in Europe and USA. This latter finding and the high familial aggregation of urolithiasis in our area constitute a cogent argument against the role of hot climate in the pathogensis of urolithiasis and are in favour of genetic predisposition. Isolated hyper-uricosuria was detected in 17% of idiopathic CaO stone formers. The latter finding is of practical importance since red-meat is a common food item in our area and restriction of purine-intake may help to decrease the frequency of urate and CaO stone formation in predisposed patients.

Comparison of the Efficacy of Two Injectable Forms of Vitamin D3 and Oral One-Alpha in Treatment of Secondary Hyperparathyroidism in Patients on Maintenance Hemodialysis

In the present study, we compared the efficacy of two intravenous forms of vitamin D3[Calcijex: 1,25(OH)2D3 and One-Alpha: 1(OH)D3] and that of oral One-Alpha in the treatment of secondary hyperparathyroidism in patients receiving maintenance hemodialysis. Twenty patients were assigned to 1 of 2 treatment groups (A and B) which were matched for age, sex, and duration of maintenance hemodialysis. None of the patients included had chronic liver disease or had received drugs known to interfere with hepatic enzymes. All patients had received a stable dose of oral calcium and One-Alpha for a minimum period of 1 year, which maintained corrected serum calcium at the upper limit of the normal range. At the start of the study, oral One-Alpha was replaced by Calcijex in group A and injectable One-Alpha in group B. Treatment was maintained for 3 months (phase I). Subsequently, injectable vitamin D3 was discontinued and all patients received their previous dose of oral One-Alpha for a period of 1 month. Finally, oral One-Alpha was discontinued again and the injectable forms of vitamin D3 were crossed over in the 2 treatment groups for another 3 months (phase II). The results showed that the serum concentrations of 1,25(OH)2D3, measured 48 h after intravenous injection of One-Alpha, were not different from that produced by an equivalent dose of Calcijex in the same group of patients. Furthermore, overall analysis of intact parathyroid levels during the cross-over, using ANOVA with repeated responses, indicated that the two analogues were equipotent as regards suppression of PTH secretion. In our study, treatment with intravenous vitamin D3 led to significant suppression of PTH secretion. These results were achieved by a lower drug dosage of vitamin D3 and at lower trough blood levels of 1,25(OH)2D3 as compared to those of oral One-Alpha. Our findings are in favor of the early use of either forms of injectable vitamin D3 in the treatment of secondary hyperparathyroidism.

Combination of Immunosuppressive Agents in Treatment of Steroid-Resistant Minimal Change Disease and Primary Focal Segmental Glomerulosclerosis

Background. Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. Methods. Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. Results. With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. Conclusion. Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.

Glomerulopathy in Kuwait: the spectrum over the past 7 years.

There are few studies that examine, prospectively, the epidemiological profile of glomerulopathy (GP) and its clinicopathological correlation. All patients referred to Al-Amiri renal center in Kuwait from 01 1st, 1995 to 12 31st, 2001 were screened for GP. Detailed clinical data were collected and serological markers were done. Renal biopsy was performed whenever indicated. During those 7 years, a total of 584 patients were diagnosed, on histological basis, to have GP, 315 of whom were Kuwaiti nationals. During the same period of the study, 26 patients presented with bilateral small kidneys, history of proteinuria >2 g/day and lacked systemic manifestations of autoimmune disease. Furthermore, 164 patients with clinical manifestations of diabetic glomerulosclerosis were not subjected to kidney biopsy. Hence, the calculated annual incidence rate of GP in Kuwaiti nationals was 34.5 per 100,000 population (PTP). The calculated rate of diabetic glomerulosclerosis was 13.4 PTP and that of non-diabetic 21.1 PTP. The calculated incidence rates of GP increased with age and were twice as high in males compared to females. Vasculitis was more common in elderly males while SLE nephritis was a disease of adults, 88.7% of whom were females. In the subgroup of primary GP, focal segmental glomerulosclerosis was the most common histological lesion accounting for 18.0% of the total biopsies in Kuwaiti patients, yet only 36.8% of those who fulfilled the criteria of primary type. Minimal change disease was the second primary GP (13.0%), followed by immunoglobulin A deposition disease (7.9%) and membranous glomerulonephritis (5%). Autoimmune diseases such as systemic lupus erythematosus (SLE) and vasculitis were common. Interestingly, only 44 of 72 (61.1%) of patients with SLE and 11 of the 62 (17.7%) of patients with vasculitis presented with rapidly progressive glomerulonephritis. On the other hand, 10 of 58 (17.2%) patients with nephroangiosclerosis presented with renal failure and protein excretion >2 g/day simulating primary GP. Furthermore, only 21 of 40 (52.5%) patients with IgA nephropathy presented with “benign disease”. Prospective studies are essential to ascertain the actual incidence and etiology of GP. The loose clinicopathological correlation in GP dictates an aggressive diagnostic approach in its study and management.

Treatment of children with steroid refractory idiopathic nephrotic syndrome: the Kuwaiti experience.

Data on the treatment and outcome of Kuwaiti children with steroid refractory idiopathic glomerulonephritis (SRIGN), i.e. nephrotic syndrome who failed an eight-week course of prednisone, were collected retrospectively from the records of children attending the two renal centers of Kuwait between January 1, 1990 to December 31, 1996. During those seven years, a total of 34 Kuwaiti children were diagnosed to have SRIGN. Histologically, 22 (65%) of those patients had minimal change, 5 (15%) focal segmental GN, 2 (6%) non-IgA mesangioproliferative GN and one membranous GN. Twenty-two patients had manifested frequent relapses, six were steroid-dependent and six were steroid-resistant. Treatment options were in the following order: (a) small maintenance-dose of corticosteroids (< 0.5 mg/kg/alternate days); (b) cyclophosphamide and or chlorambucil for a single eight week-course or eight then 12 week courses (c) cyclosporin A for three months. The response to therapy was as follows: nine children were cured with low-dose corticosteroids; 17 with chlorambucil and/or cyclophosphamide; and five with cyclosporin A. At the end of study, only three children failed such drug therapy, two of who had focal segmental glomerulosclerosis.

Endocrine Abnormalities in Patients with Amyloidosis

This study was conducted to examine systematically the endocrine function in 10 patients diagnosed to have renal amyloidosis. Basal and dynamic endocrine tests (GnRh, TRH, and ACTH stimulation tests as well as modified glucose tolerance test) were performed in all patients. Eight patients had advanced renal disease (creatinine clearance < 10 mL/min). Hypofunction of the thyroid gland was present in 5 out of those 8 patients, and thyroid biopsy confirmed amyloid deposition. Of those 5 patients, pituitary and adrenal defects were present in 2. In conclusion, endocrine abnormalities were evident at a later stage of renal amyloidosis. Hypothyroidism was present in all patients who manifested endocrine defects and should be considered as an early sign of endocrine involvement with the disease.

Chronic Renal Disease in Kuwaiti Nationals: A Prospective Study During the Past 4 Years

Our study is a prospective one conducted at Al-Amiri Hospital and including all new cases of chronic renal disease (CRD) seen at the capital area of Kuwait between 1 January 1999 and 30 December 2003. Diagnosis of CRD was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. A total of 271 cases of chronic renal failure (CRF) were diagnosed, of whom 143 were women. The median age was 40 years (range, 5 to 80 years; mean ± SD: 40 ± 14). The most common cause of CRF was glomerulonephritis (32%), of which systemic lupus erythematosis and vasculitis constituted 5% and 4%, respectively. Diabetic glomerulosclerosis was the second leading cause of CRD (24%), followed by tubulointerstitial disease (11%) and nephroangiosclerosis (10%). Less frequent causes included renovascular/ischemic disease (6%), obstructive nephropathy (3%), and adult polycystic kidney disease (3%). One hundred and seven patients had 121 incidents of acute deterioration of underlying renal disease. This was mostly due to drugs (22%), infection (21%), and volume depletion (13%). Antiinflammatory drugs were the most common drugs (63%) responsible for the acute decline in renal function. By the end of the study, 18 (7%) patients died, 55 (20%) required maintenance dialysis, and 40 (15%) had received a kidney allograft. Diabetic patients did not differ from nondiabetic with regard mortality, although had more renal replacement therapy (p = .002). Using the Cox regression model, analysis of the relative risk factors likely to contribute to mortality, viz. age, gender, original kidney disease, fitness for transplantation, and mode of presentation, did not show significant factors except for less hazard to death in those diagnosed early with CRD (i.e., on routine testing; relative risk 0.06, p = .01). In conclusion, our study indicates that early diagnosis and management of CRD can improve the patients quality of life and decrease the cost of frequent hospitalization, morbidity, and even mortality associated with end-stage renal disease.

Progressive ischemic gangrene in dialysis patients: a clinicopathological correlation

The syndrome of progressive ischemic gangrene (PIG) of the extremities was examined over 3.5 years in patients undergoing maintenance dialysis (MD) in Kuwait and was compared to that in a similar age group (> 40 years) in the general population. The incidence of PIG in MD patients was 15.4/1000 person years of observation (PYO) versus 0.086/1000 PYO in the general population. Patients with diabetes mellitus were found to be at particular risk. PIG developed in 41.4/1000 PYO of diabetic patients who received MD, compared to 7.1/1000 in nondiabetic patients on MD and 0.14/1000 in diabetics without renal disease. The clinical, biochemical, radiological, and histological findings in the 8 patients who developed PIG while on maintenance dialysis (MD) are presented. Two patients had severe hyperparathyroidism and their histological findings were consistent with systemic calciphylaxis. Histological examination, in the remaining patients, showed severe calcified atherosclerosis. Intimal hypertrophy was common especially in patients with long duration on dialysis. The three lesions produced a variable degree of luminal narrowing and were associated with arterial thrombosis. None of the patients showed evidence of iron deposition even in those with systemic calciphylaxis and excessive iron stores. Our study indicated a high incidence of PIG in patients undergoing MD, especially in those with diabetes mellitus. These findings constitute a cogent argument in favor of early parathyroidectomy in selected cases and concern with long-term consequences of atherosclerosis in this patient population.

Rituximab in treatment of idiopathic glomerulopathy

The aim of our study was to assess the role of rituximab (Mabthera) in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD) group, 31 of the 32 patients had complete remission (CR) and were off any immunosuppressive therapy and one of the previous non-responders (NR) did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months). Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS), while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab. The drug is effective and safe for treatment of patients refractory to the conventional agents.