Urinary 20-HETE: A prospective Non-Invasive prognostic and diagnostic marker for diabetic kidney disease.

INTRODUCTION: The identification and validation of a non-invasive prognostic marker for early detection of diabetic kidney disease (DKD) can lead to substantial improvement in therapeutic decision-making. OBJECTIVES: The main objective of this study is to assess the potential role of the arachidonic acid (AA) metabolite 20-hydroxyeicosatetraenoic (20-HETE) in predicting the incidence and progression of DKD. METHODS: Healthy patients and patients with diabetes were recruited from the Hamad General Hospital in Qatar, and urinary 20-HETE levels were measured. Data analysis was done using the Statistical Package for Social Sciences (SPSS). RESULTS: Our results show that urinary 20-HETE-to-creatinine (20-HETE/Cr) ratios were significantly elevated in patients with DKD when compared to patients with diabetes who did not exhibit clinical signs of kidney injury (p < 0.001). This correlation was preserved in the multivariate linear regression accounting for age, diabetes, family history of kidney disease, hypertension, dyslipidemia, stroke and metabolic syndrome. Urinary 20-HETE/Cr ratios were also positively correlated with the severity of kidney injury as indicated by albuminuria levels (p < 0.001). A urinary 20-HETE/Cr ratio of 4.6 pmol/mg discriminated between the presence and absence of kidney disease with a sensitivity of 82.2 % and a specificity of 67.1%. More importantly, a 10-unit increase in urinary 20-HETE/Cr ratio was tied to a 10-fold increase in the risk of developing DKD, suggesting a 20-HETE prognostic efficiency. CONCLUSION: Taken together, our results suggest that urinary 20-HETE levels can potentially be used as non-invasive diagnostic and prognostic markers for DKD.

Outcome of sirolimus-based immunosuppression, fifteen years post-live-donor kidney transplantation: Single-center experience.

In a prospective randomized controlled trial, between May 2001 and January 2003, 132 live-donor kidney transplant recipients were randomized to receive sirolimus primary immunosuppression, either in combination with low dose tacrolimus (Tac group) or in combination with mycophenolate mofetil (MMF group). We have previously reported on 2- and 5-year follow-up results, with favorable patient and graft outcomes obtained in both groups. In view of recent published reports of increased risk of inferior outcomes among sirolimus-treated patients, we herein present results of an observational extension of the previously randomized patients 15 years post-transplantation. Mortality rates were 10.8% and 3% in Tac and MMF groups respectively after mean follow-up period of 11.2-11.8 years. Comparable graft survival rates were obtained in both groups ranging from 60% to 62.7%. The (MMF) group continued to have the advantage of remaining on primary plan of immunosuppression (56.7% of patients) as well as to maintain better graft function in terms of serum creatinine level. Herein, we presented longest term published data for sirolimus-based immunosuppression among live-donor kidney transplants with favorable outcome in terms of survival and graft function.

Proteinuria among primarily sirolimus treated live-donor renal transplant recipients' long-term experience.

OBJECTIVES: Recent evidence of a high incidence of proteinuria among de novo sirolimus-based regimens has been reported among renal transplant patients at short-term follow-up. We report on long-term evaluation of proteinuria among patients maintained on such regimen. MATERIALS AND METHODS: Between May 2001 and January 2003, 132 patients received a renal allograft from a living donor and were randomized to 2 groups (steroids/sirolimus/tacrolimus, n=65) and (steroids/sirolimus/mycophenolate mofetil, n=67): Both received basiliximab induction. Retrospective review of those patients was performed, 5 years posttransplant with particular emphasis on the incidence of proteinuria. RESULTS: The 5-year incidence of proteinuria was 29.2% and 38.8% among sirolimus/tacrolimus and sirolimus/mycophenolate mofetil group. Single DR-matched patients (P = .016) and the incidence of acute rejection (P = .039) were associated with significantly higher incidence of proteinuria. Moreover, the presence of mesangial matrix increased (P = .015), and glomerulosclerosis (P = .014), in 1-year protocol biopsies, was found to have a positive predictive value for current and future incidences of proteinuria. Proteinuria was found to be associated with significant inferior graft outcome. Recurrent original kidney disease, de novo glomerulopathy, and acute transplant glomerulopathy were responsible for early cases of nephrotic range proteinuria (first 2 years), while cases presented later were attributed to chronic allograft nephropathy. CONCLUSIONS: Proteinuria has become a recognized, serious event of primarily sirolimus-treated renal transplants patients, which is most probably of glomerular origin. It has been shown that proteinuria exerts a bad prognostic effect upon graft function and subsequent graft survival at 5-year follow-up.

Continuous ambulatory peritoneal dialysis in Egypt: progression despite handicaps.

BACKGROUND: Despite the well-known advantages of continuous ambulatory peritoneal dialysis (CAPD), it continues to be grossly underutilized in many developing countries. However, some developing countries, such as Mexico, use the modality very effectively. In view of this, we started the first CAPD program in Egypt. METHODS: Since its start in 1997, our program has treated 33 patients. Straight double-cuffed Tenckhoff catheters were surgically placed in all patients. Twin-bag systems were used. All patients underwent monthly clinical and biochemical assessment and measurement of Kt/V urea. Peritonitis and exit-site infection rates were monitored. RESULTS: Most treated patients were adult and female. Mean age was 31.7 years and mean follow-up duration was 18 months. Peritonitis rate was 1 episode /21.3 months and was easily managed in most patients. Staphylococcus aureus was the most commonly isolated organism (24%) but 49% of cases were culture negative. There were no exit-site infections. Mean weekly Kt/V urea was 1.78 +/- 0.23. CONCLUSION: We report the successful development of a small CAPD program in Egypt, made possible by well-established financial support, a motivated team of doctors and nurses, and good patient selection and training.

Long-term efficacy and safety of a calcineurin inhibitor-free regimen in live-donor renal transplant recipients.

Calcineurin inhibitor (CNI) nephrotoxicity is a major concern after renal transplantation. To investigate the safety and efficacy of a CNI-free immunosuppressive regimen, 132 live-donor renal transplant recipients were included in a prospective, randomized controlled trial. All patients received induction therapy with basiliximab and steroids. The patients were randomized to a maintenance immunosuppression regimen that included steroids, sirolimus, and either low-dose tacrolimus or mycophenolate mofetil (MMF). Over a mean follow-up period of approximately 5 yr, patient and graft survival did not significantly differ between the two maintenance regimens. Patient survival was 93.8% and 98.5% in the tacrolimus/sirolimus and MMF/sirolimus groups, respectively, and graft survival was 83% and 88%, respectively. However, the MMF/sirolimus group had significantly better renal function, calculated by Cockcroft-Gault, from the second year post-transplant until the last follow-up. In addition, this group was less likely to require a change in their primary immunosuppression regimen than the tacrolimus/sirolimus group (20.8% versus 53.8%, P = 0.001). The safety profile was similar between groups. In summary, after long-term follow-up, a CNI-free maintenance regimen consisting of sirolimus, MMF, and steroids was both safe and efficacious among low to moderate immunologic risk renal transplant recipients.

Long-term evaluation of single bolus high dose ATG induction therapy for prophylaxis of rejection in live donor kidney transplantation.

BACKGROUND/AIMS: The long-term evaluation of single bolus high dose antithymocyte globulin (ATG) induction therapy has not been adequately studied. We aimed to evaluate its long-term effects in the living related donor kidney transplantation. METHODS: Eighty adult recipients with their first kidney allograft were randomized into two equal treatment groups, one group received intraoperative single bolus rabbit ATG in a dose of 9 mg/kg and the second group served as a control. All patients were maintained on triple immunosuppressive therapy (steroids, calcineurin inhibitor and antiproliferative agent). We followed them thoroughly for minimum of 5 years. RESULTS: ATG significantly reduced the proportion of patients who experienced acute rejection episodes in the first year (9/40) when compared to the control group (26/40) and in 5 years (11/40) when compared to (30/40) in controls. The cumulative steroid dose used throughout the study was significantly lower in the ATG group. The overall incidence of posttransplant complications was comparable among the two treatment groups. There was no significant difference in patient and graft survival: 5 year survival was 100% and 85% for the ATG group, and 95% and 92.5% in the control group, respectively. CONCLUSION: Although routine single bolus ATG induction significantly reduces the incidence of acute rejection, its long-term beneficial effects on graft function and patient and graft survival are not evident.

Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation.

UNLABELLED: 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.

A prospective, randomized study of coadministration of ketoconazole and cyclosporine a in kidney transplant recipients: ten-year follow-up.

BACKGROUND: In a prospective, randomized study, we previously proved the safety and financial benefits of the coadministration of ketoconazole (keto) and cyclosporine A (CsA) in patients. We report the 10-year follow-up of these patients and the controls. PATIENTS AND METHODS: In January 1992, 100 living-related kidney transplant recipients were randomized into two groups: Group 1 (51 patients) received 100 mg/day keto, and group 2 (49 patients) did not receive keto (control). Both groups were evaluated regarding graft function, CsA dose and levels, liver function tests, serum calcium and phosphorus, bone mineral density, and histopathologic assessment. RESULTS: Follow-up for 10 years showed that CsA dose reduction was maximum after 1 month (76.5%) and decreased gradually after 10 years (64.6%). Acute rejection was diagnosed in 22% and 27% in the keto and control groups, respectively (P =0.27). In the control group, the acute rejection episodes were more frequent with poorer response to treatment. Chronic allograft nephropathy was statistically significantly less in the keto group. Hepatotoxicity and metabolic complications were similar in both groups. The annual cost saving of CsA was 60% after 1 year and 50% at the end of the study. CONCLUSIONS: We conclude that the long-term use of keto for CsA dose reduction in kidney transplant recipients is safe, tolerable, and cost-sparing and is associated with stable graft function.