Nabil Hassan

Effect of Angiotensin II Receptor Blocker on Plasma Levels of TGF-β1 and Interstitial Fibrosis in Hypertensive Kidney Transplant Patients

Background/Aim: Transforming growth factor-β1 (TGF-β1) is involved in the pathogenesis of chronic allograft nephropathy after kidney transplantation. The aim of the study was to evaluate the effect of the angiotensin receptor blocker losartan on TGF-β1 plasma levels and proteinuria in hypertensive transplant recipients. Methods: A total of 162 transplant recipients were included in the study. The patients were randomized into 3 groups: group 1 received losartan; group II received an angiotensin-converting enzyme inhibitor (captopril), and group III received a calcium channel blocker (amlodipine). All the parameters were recorded at the time of therapy initiation and at 1, 4 and 12 weeks and 12 months thereafter. Graft biopsy before the start and at the end of the study was done to evaluate histopathological progression. Results: Blood pressure was controlled in the 3 groups; however, the need for other antihypertensive agents was significant in groups I and II. Treatment with losartan significantly decreased the plasma level of TGF-β1, 24-hour urinary protein and serum uric acid (p < 0.05). No significant changes were seen in the hemoglobin or serum potassium levels. The rate of histopathological progression was significantly lower in the losartan group. No patient was discharged from the study due to side effects. Conclusions: After transplantation all drugs were able to control blood pressure with good safety and tolerability. The study demonstrates that ARB significantly decreases the plasma levels of TGF-β1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.

Echocardiographic changes and risk factors for left ventricular hypertrophy in children and adolescents after renal transplantation

Abstract:  Long‐term consequences of cardiac alteration in children with chronic renal failure and after renal transplantation are largely unknown. In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular hypertrophy (LVH) or left ventricular dilatation. The correction of uremic state by renal transplantation leads to normalization of left ventricular contractility, regression of LVH and improvement of cavity volume and so dialysis patients with uremic cardiomyopathy would benefit from renal transplantation. We studied 73 patients, aged 17 yr or less, who underwent renal transplantation in our center. This cross‐sectional study was performed 4.6 yr (median) after transplantation. Of the total, 48 were males and 25 were females. Transthoracic echocardiographic examination was performed for all cases. The effects of clinical, demographic, biochemical and therapeutic data on echocardiographic parameters were assessed. Multivariate analysis was used to assess the relation between the risk factors and the left ventricular muscle mass index. The most common echocardiographic abnormalities were the LVH (47.9%), left atrial enlargement (31.5%) and left ventricular dilatation and systolic dysfunction (13.7% for each). The pretransplant dialysis, arteriovenous fistula, acute rejection, cumulative steroid dose per square meter surface area, post‐transplant hypertension, anemia and graft dysfunction were significant risk factors for LVH by univariate analysis. The significant factors by multivariate analysis were pretransplant dialysis, post‐transplant hypertension and anemia. From this study we may conclude that LVH is a common problem among renal transplant children and adolescents. Early transplantation, control of hypertension and correction of anemia may be beneficial regarding left ventricular function and structure.

Effect of Donor/Recipient Body Weight Mismatch on Patient and Graft Outcome in Living-Donor Kidney Transplantation

Background/Aims: There have been conflicting reports showing that kidneys from small donors may be at risk for graft loss if they are transplanted into large recipients. The aim of this work was to examine the donor/recipient body weight ratio (D/RBWR) on patient and graft outcome. Methods: During the period from January 1990 to January 2002, 856 kidney transplants were performed. Of these, 776 kidney transplant recipients were selected after exclusion of pediatric, second transplant patients and those with a body mass index of ≧35. All patients achieved a minimum follow-up of 1-year. According to D/RBWR, patients were divided into 3 groups: low (≤0.9), medium (0.91–1.2) and high (≧1.2). Data were collected on graft function, acute and chronic rejection, post-transplant complications, and 1- and 5-year graft and patient survival. Results: There was a statistically significant increase in the incidence of chronic rejection, post-transplant hypertension and diabetes mellitus in the low group. The incidence and frequency of acute rejection episodes were nearly the same in the 3 groups. Graft function, estimated by serum creatinine at 1 year, was significantly lower in the low group. The 5-year graft and patient survival was 71, 80, 88 and 81, 85 and 92%, in the low, medium and high groups, respectively. Conclusions: We conclude that a low D/RBWR may contribute to inferior long-term renal allograft survival. The hyperfiltration hypothesis due to low nephron mass in the low D/RBWR group may explain these findings.

Use of Nandrolone Decanoate as an Adjuvant for Erythropoietin Dose Reduction in Treating Anemia in Patients on Hemodialysis

Background/Aims: Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. Methods: This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. Results: A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. Conclusion: Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.

Effect of Spontaneous Closure of Arteriovenous Fistula Access on Cardiac Structure and Function in Renal Transplant Patients

Background/Aim: The effect of spontaneous closure of arteriovenous fistula (AVF) used for hemodialysis on the heart is not adequately studied. The aim of this study was to assess the effect of spontaneous AVF closure in the early period after renal transplantation on the patient’s outcome. Methods: Seventeen patients (13 males, 4 females) who had their AVF thrombosed within the first month after transplantation were retrospectively compared to another well-matched and persistent AVF group of patients comprising of 34 patients (27 males, 7 females). Echocardiographic assessment was done before transplantation and at 1 year after transplantation. Results: In the thrombosed fistula group, there was a trend towards lower values of left ventricular end-systolic andend-diastolic diameters as well as end-systolic and end-diastolic volumes of the left ventricle, but it did not reach statistical significance. The persistent AVF group had significantly higher estimates for cardiac output and cardiac index (p < 0.05). Both groups were comparable for left ventricular mass, left ventricular mass index, and left ventricular systolic and diastolic functions. There was no difference regarding patient and graft survival in both groups. Conclusion: Spontaneous AVF thrombosis did not offer a cardiac beneficial effect and routine fistula closure is not warranted.

Parenteral Iron Therapy in Treatment of Anemia in End-Stage Renal Disease Patients: A Comparative Study between Iron Saccharate and Gluconate

Background: Anemia in hemodialysis patients is a complex syndrome. The impetus of this study was to assess the safety and efficacy of iron saccharate complex (ISC) and sodium ferric gluconate complex (SFGC) in treating anemia in hemodialysis patients. Methods: Forty-eight adult anemic patients of both genders (33 males and 15 females) who had an adequate level of both hemodialysis and nutrition status and received neither EPO nor parenteral iron therapy during the preceding 6 months were randomized to 2 groups. The first group comprised 22 patients who were treated with parenteral ISC, 100 mg twice weekly for 2 months and once weekly thereafter. The second group included 26 patients who received SFGC, 62.5 mg twice weekly for 2 months and once weekly thereafter. The patients were followed up for 6 months. Results: This head-to-head study showed that iron stores were adequately repleted by the use of both drugs. Repletion of iron stores was associated with a significant rise in both hemoglobin and hematocrit in both groups at the end of the follow-up period in comparison to their initial values at the start of the study (p < 0.001). Both parenteral iron therapy preparations were tolerated without a statistical difference between both groups. Conclusion: This head-to-head study confirmed that both parenteral iron preparations are effective for adequate repletion of iron stores and constituted a step forward in the management of anemic hemodialysis patients without noticeable adverse effects related to the administration of both iron preparations.

Characteristics of Long-Term Live-Donor Renal Allograft Survivors

Background/Aims: Despite the high rate of rejection, allograft failure and patient mortality in the early years of renal allotransplantation, some patients have done-remarkably well. We report here on 62 renal transplant recipients out of 144 patients (43%) who had functioning grafts for more than 15 years (range 15–24 years). Materials: Demographic and follow-up data for patients fulfilling the criteria were reviewed. These patients include 43 males and 19 females, with a mean age at transplantation of 27.5 ± 6.6 years (range 9–43 years), and mean donor age of 30 ± 8.6 years. The donor source was 8 parents, 49 siblings and 5 unrelated. The main causes of end-stage renal disease were chronic pyelonephritis and chronic glomerulonephritis. Twenty-nine patients were treated with cyclosporine (CsA) while 33 patients were primarily immunosuppressed by steroids and azathioprine. Results: Acute rejection episodes occurred in 40 patients (64.3%), out of them 19 patients experienced two or more acute rejection episodes. Univariate analysis showed that recipient and donor age, HLA-DR matching, pre- and post-transplant hypertension, ATN, delayed diuresis and chronic allograft nephropathy are significant risk factors; while recipient age, delayed diuresis and post-transplant hypertension were still significant by multivariate analysis. Conclusions: We concluded that renal transplantation, even in its earliest years and despite the numerous complications, has provided 15 or more years of near-normal life to patients with end-stage renal disease. Certain characteristics of long-term renal allograft survivors include young donor/recipient pairs, good DR matching with less pre- and post-transplantation prevalence of hypertension.

Effect of Concomitant Administration of Cyclosporine and Ketoconazole in Children with Focal Segmental Glomerulosclerosis

Background: Focal segmental glomerulonephritis (FSGS) is now the most common primary glomerulonephritis that leads to end-stage renal disease in both adults and children. Cyclosporine (CsA) is a well-known and effective immunosuppressive agent that has become a cornerstone of immunotherapy in solid organ transplantation and it has been used in the treatment of FSGS for over 15 years. The deliberate use of ketoconazole (keto) to reduce the need for CsA is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in children with nephrotic syndrome (NS). Methods: This study included 116 children (below 18 years of age) with primary FSGS who were steroid resistant or dependent and received CsA therapy. Among them, 88 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of CsA dose by one third, while 28 patients received CsA alone (non-keto group). Mean (±SD) age was 6.17 ± 4.68 years and male to female ratio was 1.9:1. The great majority of the study population received the drugs for 1–2 years. The characteristics of both groups were comparable. Results: Co-administration of keto significantly reduced mean doses of CsA by 46% at 1 year with overall net cost savings of 36%. It also significantly improved the response to CsA therapy and decreased the frequency of renal impairment. No significant side effects for keto were observed. Conclusion: Co-administration of keto and CsA in idiopathic FSGS children is safe. This combination not only reduces the costs but also may improve the response to CsA and stabilize the renal function.

Effect of donor and recipient variables on the long-term live-donor renal allograft survival in children

Abstract Objective: We aimed to analyse donor and recipient predictors of graft survival in children who received live-donor renal grafts. Patients and methods: The study comprised 273 children who received live-donor renal transplants at our center between March 1976 and October 2010. The follow-up ranged from 6 months to 25 years. Donor variables included donor age, gender, donor/recipient body weight ratio (DR BWR), ABO blood groups, human leukocyte antigen, and DR mismatching. Donor-specific problems, e.g., ischemia time during surgery and number of renal arteries, were included. Recipient variables included recipient age, sex, original kidney disease, ischemia time, acute tubular necrosis (ATN) after transplantation, immunosuppression, number of acute rejection episodes, re-transplantation, and development of hypertension. Results: Independent variables with a sustained effect on the 5- and 10-year graft survival on multivariate analysis were: ATN after transplant, number of acute rejections, hypertension, and DR BWR. At the last follow-up, 185 patients (67.8%) had a functioning graft, while 82 (30.0%) had graft failure. Only six patients (0.02%) were lost to follow-up. Conclusion: Donor and recipient variables that affect short- and long-term graft survival in children with a live-donor renal allograft are DR BWR, number of acute rejections, ATN and hypertension after transplant. Considering these variables provides a better outcome.

Co-Administration of Cyclosporine and Ketoconazole in Children with Minimal Change Nephrotic Syndrome

Background/Aims: The use of cyclosporine A (CsA) in the treatment of idiopathic nephrotic syndrome was firstly reported in 1986. On the other hand, many studies have documented the benefit of ketoconazole (keto) administration in renal and cardiac transplant adults treated with CsA, but this co-administration has not been reported in children with minimal change disease (MCD). Thus, deliberate use of keto to reduce the need for cyclosporine is not new, but it is particularly relevant because of the high cost of cyclosporine. Methods: This study included 46 children with MCD who were steroid resistant or dependent and received CsA. Among them, 31 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of the CsA dose by one third while 15 patients received CsA alone (non-keto group). Results: The mean (±SD) duration of CsA treatment was 25.7 ± 13.7 months. The characteristics of both groups were comparable. Co-administration of keto significantly improved the response to CsA therapy (from 60 to 94%) and decreased the frequency of renal impairment (from 27 to 3%). Hepatic function remained within the normal range in both groups. Co-administration of keto significantly reduced mean doses of CsA with overall net cost savings of about 34%. Conclusion: From this study, we may conclude that co-administration of low dose ketoconazole to cyclosporine in children with idiopathic MCD is safe. This combination significantly reduces CsA cost and, moreover, keto may improve the response to cyclosporine and may have a favorable effect on the kidney function.