Amgad E. El-Agroudy

Weight gain after renal transplantation is a risk factor for patient and graft outcome.

Background. The present study aimed to evaluate the effect of weight gain after transplantation on patient and graft outcome. Methods. Patients receiving kidney transplants between April 1986 and April 2001 were divided according to their body mass index (BMI) at 6 months after transplantation into group I, BMI less than 25 (normal weight); group II, BMI greater than or equal to 25 and less than 30 (overweight); and group III, BMI greater than or equal to 30 (obese) after exclusion of pediatric patients (aged ≤18 years), second transplant recipients, those with a history of cardiovascular disease, and those with a BMI less than 25 and greater than 18.5 kg/m2. Six hundred fifty kidney transplant recipients were selected for this retrospective study. Results. There was a statistically significant increase in the incidence of posttransplant hypertension, diabetes mellitus, and ischemic heart disease in the obese group. The incidence and frequency of acute rejection episodes were similar in the three groups. A trend toward decreased graft and patient survival, which reached significance at 5 years and 10 years, was observed in the obese group. Conclusions. BMI has a strong association with outcomes after renal transplantation independent of most of the known risk factors for patient and graft survival.

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.

Preventing Bone Loss in Renal Transplant Recipients with Vitamin D

Very rapid bone loss, osteopenia, and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation. Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss. Forty adult men who were recent renal transplant recipients were enrolled onto the study. Patients were randomized into two groups: group 1 received daily alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every patient in both groups received daily 500-mg calcium carbonate supplements. Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period. Bone mineral density was increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm, respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the same sites in the control group (P < 0.05). Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group (P = 0.003). Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol. Use of alfacalcidol early after transplantation is safe and well tolerated.

Comparison of Sirolimus with Low‐Dose Tacrolimus Versus Sirolimus‐based Calcineurin Inhibitor‐Free Regimen in Live Donor Renal Transplantation

Between May 2001 and January 2003, 132 live donor renal allotransplant recipients were included in a prospective, randomized controlled trial where they were divided into two groups. All patients received steroids and basiliximab induction therapy. For maintenance immunosuppression, tacrolimus and sirolimus were used in group A. In group B, mycophenolate mofetil (MMF) and sirolimus were utilized. Patients were followed up for a minimum of 24 months. One‐year patient and graft survival rates were not significantly different between group A (96.9%, 92.3%) and group B (100%, 98.4%), respectively. However, the incidence of biopsy‐proven acute rejection was less in group B but the difference was not statistically significant (13.5% vs. 18.5% in group A). Statistically significant better renal function was encountered among group B patients at two years post‐transplantation as measured by serum creatinine (1.25 vs. 1.43 mg/dl; P = 0.017) and calculated glomerular filtration rate (GFR) (94.9 vs. 79.6 ml/min; P = 0.005). One year protocol biopsies showed insignificant differences relative to chronic allograft damage index (CADI) between either group (Group A: 2.41 vs. Group B: 2.69; P = 0.436). Conclusion: Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen. The long term impact of this observation on graft survival and function needs longer follow up.

Treatment of osteopenia and osteoporosis in renal transplant children and adolescents

Abstract:  Successful renal transplantation corrects many of the metabolic abnormalities associated with the development of renal osteodystrophy, but despite a well‐functioning graft osteopenia, growth failure, spontaneous fractures, and avascular necrosis remain prevalent in adult and pediatric kidney recipients. A paucity of information exists regarding the effects of different therapies to prevent and treat bone loss in the renal transplant recipients. We constructed a design to study the effect of different modalities of treatment on bone mass in our renal transplant children. Among 93 patients who underwent renal transplantation at the age of 17 yr or less and were subjected to dual‐energy X‐ray absorptiometry (DEXA), we blindly randomized 60 patients who had osteopenia or osteoporosis (T‐score = −1 by DEXA) in a prospective study. Their mean age at time of transplantation was 13.4 ± 4.3 yr. The mean duration after transplantation was 48 ± 34 months. The patients were classified randomly into four groups. Each group consisted of 15 patients: group 1 was the control group, group 2 received oral alfacalcidol 0.25 μg daily, group 3 received oral alendronate 5 mg daily, and group 4 received 200 IU/day nasal spray calcitonin. Parameters of bone turnover, calcium metabolism, and DEXA were measured before and after 12 months of treatment duration. The characteristics of all groups were comparable at the beginning of the study. At the lumber spine, bone mass density decreased from −2.4 to −2.8 in group 1, increased from −2.3 to −0.5 in group 2, from −2.3 to −1.9 in group 3, and from −2.3 to −1.0 in group 4. The four groups had similar patient profiles, serum creatinine, intact parathyroid hormone, osteocalcin, and deoxypyridinoline. This study confirmed the value of alfacalcidol and antiresorptive agents in the treatment of osteopenia and osteoporosis in young renal transplant recipients .These therapies were safe, tolerable, simple to administer and potentially applicable to other renal transplant patients.

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.

Long-term follow-up of living kidney donors: a longitudinal study

To analyse retrospectively the general health status and renal and cardiovascular consequences of living‐related kidney donation, as the long‐term effects of unilateral nephrectomy for kidney donation are of particular interest with the currently increasing practice of living‐donor transplantation.

A Prospective Randomized Study for the Treatment of Bone Loss with Vitamin D During Kidney Transplantion in Children and Adolescents

The effect of treatment with alfacalcidol on post‐transplantation bone loss in children and adolescents was investigated.

Living-donor kidney retransplantation: risk factors and outcome

Authors from Mansoura in Egypt present a study of risk factors and outcome from living‐donor renal re‐transplantation. This is sometimes avoided as being unlikely to have a good outcome, but it is shown here to be the treatment of choice in patients who have lost the primary graft.

Coadministration of ketoconazole to cyclosporin-treated kidney transplant recipients : a prospective randomized study

In this work, 100 living related donor kidney transplant recipients under cyclosporin (CsA) therapy were randomly distributed to two groups. Group 1 were administered ketoconazole, with group 2 serving as the control. Ketoconazole was given orally, 100 mg/day, while the dose of CsA was adjusted for a CsA whole blood trough level of 100-150 ng/ml. Patients and controls were assessed regularly in an outpatient clinic for 12 months and compared statistically for CsA dose, graft and liver functions, cholesterol, blood sugar, CsA nephrotoxicity, acute rejection episodes, chronic rejection and fungal skin infections. Statistical analysis showed a significant reduction in the CsA dose in the ketoconazole-treated group (73-76%), along with significantly lower alanine aminotransferase, aspartate aminotransferase, bilirubin, and serum creatinine values. CsA chronic nephrotoxicity and chronic rejections were also significantly lower in the ketoconazole-treated group, as was fungal skin infection (6.6 vs 63.2%). From this study, we conclude that addition of a low dose of ketoconazole to CsA-treated kidney transplant recipients not only saves costs, but may also have a favorable effect on graft function, chronic CsA nephrotoxicity, chronic rejection and fungal skin infection.