Prospective nonrandomized study with early steroid withdrawal (Day 5) postrenal transplant in low immunological risk patients: A singlecenter experience at prince sultan military medical city Riyadh.

Steroids remain an essential part of immunosuppressive therapy for renal transplant patients since the start of transplant era. Different immunosuppressive regimens are prescribed so as to minimize the side effects. The purpose of our study is to compare the outcome of early steroid withdrawal with steroid maintenance protocol. It is a prospective nonrandomized study. All patients that received renal transplants from January 2011 to December 2013 were included in the study. Early steroid withdrawal at day 5 was done in low immunological risk patients, and the results were compared with the steroid maintenance group, at one-year, posttransplant. Outcome measures included acute rejection (AR), slow graft function and delayed graft function (SGF and DGF), patient and graft survival, and new-onset diabetes after transplant (NODAT), dyslipidemia, hypertension, and obesity. A total of 249 patients were divided into two groups - 105 patients had early steroid withdrawal and 144 patients were maintained on steroid therapy. Outcome measures were compared one-year posttransplant. There was no significant difference in AR, patient and graft survival, creatinine level, and weight gain. However, a significant difference in systolic and diastolic blood pressure, lipid profile, NODAT, SGF, and DGF was found in the steroid group. Our study shows that early steroid withdrawal is a safe standard of care in low immunological risk patients.

Safety and efficacy of peginterferon-α2a plus ribavirin treatment in renal transplant recipients with chronic hepatitis C.

BACKGROUND & AIMS: Interferon (IFN)-based therapy in chronic hepatitis C virus (HCV)-infected renal transplant (RT) recipients has been associated with a high risk of acute allograft rejection (AAR) and poor efficacy. We assessed the safety and efficacy of PegIFNα-2a and ribavirin (RBV) combination therapy in HCV-infected RT recipients. METHODS: Thirty-two adult RT recipients of >12-month duration, infected with HCV genotypes 1 (62.5%) and 4 (37.5%), and significant fibrosis (Metavir ≥ F2) were recruited in an open-label trial with PegIFNα-2a 135-180 µg/week, plus RBV 200-1200 mg/day for 48 weeks, based on the estimated glomerular filtration rate. Safety assessments were performed weekly for 4 weeks, 2-weekly for 8 weeks, and 6-weekly for 36 weeks. Study end points were sustained virologic response (SVR) or development of AAR. Allograft biopsies were performed for 20% increase in creatinine from pretreatment levels, or optionally at week 12 on surveillance protocol. Renal safety was compared with matched untreated historical controls (n=31). RESULTS: None of the treated patients showed AAR when biopsied for raised creatinine (12.5%) or during surveillance (37.5%), with incremental and sustained creatinine increases occurring in 6.3% of treated patients and 16.1% of untreated controls (p=0.148), by week 72 assessment. Mean pretreatment and end-of-assessment creatinine in treated patients remained similar (106.8 ± 32.0 vs. 113.4 ± 62.8, respectively; p=0.140), while levels increased significantly in the controls (106.6 ± 35.6 vs. 142.5 ± 93.0, respectively; p=0.013). Rapid, early virologic response (EVR) and SVR occurred in 12.5%, 56.3%, and 37.5% of cases, respectively. SVR was similar in both genotypes (p=1.000). PegIFN and RBV dose reductions were required in 34.4% and 78.1%, respectively; discontinuation was required in 12.5%. Binary logistic regression identified only EVR (OR, 20.4; 95% CI: 2.2-192.6; p=0.008) as an independent predictor of SVR. CONCLUSIONS: PegIFN/RBV therapy is not associated with AAR in RT recipients at low risk for rejection but has modest efficacy in the treatment of HCV.

Antibody-mediated rejection: importance of lactate dehydrogenase and neutrophilia in early diagnosis.

We report the importance of elevated serum lactate dehydrogenase (LDH) and neutrophilia (NT) in two renal transplant recipients who developed renal impairment in the early post-operative period. One of our recipients developed oliguria and increased serum creatinine with unexplained elevation of LDH and NT. The biopsy was C4d positive with platelet and fibrin thrombi in the glomerular capillaries and arterioles and interpreted as acute vasculitis or thrombotic form of antibody-mediated rejection (VAMR) with positive donor-specific antibodies (DSA). Despite intensive treatment, this graft was lost. When another patient developed a similar picture, prompt immunoadsorption was started without waiting for a confirmatory biopsy or DSA, and both were later reported as positive. Improvement in renal function was associated with decreasing levels of LDH and NT. Neither of these was elevated in cases of acute cellular rejection (ACR) or antibody mediated rejection (AMR) with isolated tubular injury (TAMR). It may therefore be reasonable to assume that LDH and NT are potential diagnostic and prognostic markers of VAMR.

Post transplant ureteric stenosis causing allograft hydronephrosis and calyceal rupture: salvage side to side ureteroneocystostomy.

A 26-year-old lady with end stage renal disease who received a cadaveric renal transplant, presented with ureteral stenosis as well as calyceal rupture due to hydronephrosis that was unresponsive to balloon dilation and the allograft was salvaged by a side to side ureteroneocystostomy. The symptoms and renal function improved and patency of the side to side uretroneocystostomy was confirmed post operatively and also at seventeen month follow-up. It may be reasonable to treat post-transplant ureteral stenosis resistant to balloon dilation with this technique. However, long-term follow-up is required to evaluate the efficacy of this treatment.

Post-renal transplant proteinuria: the saudi experience.

We conducted this study to evaluate the risk factors for proteinuria in renal transplant patients. We reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia, transplanted between January 1979 and November 1998. The recipients were grouped according to the presence and magnitude of proteinuria: group I; from zero-0.3 g/L, group II; from 0.4-1.0 g/L, group III; more than one g/L. The records of 340 patients were reviewed in this study. The mean age of the study patients was 39.7 years and the mean duration following transplantation was 82.2 months. There were 209 (61.5%) patients in group I, 92 (27.1%) patients in group II and 39 (11.5%) patients in group III. There was no significant difference among the three groups in terms of mean age, mean duration after transplantation, type of donor (living-related and unrelated, or cadaver), rate of re-transplantation (8.2%), prevalence of hypertension while on dialysis (66.6%), etiology of original renal disease, incidence of acute rejection in the first year, occurrence of diabetes after transplantation (30.6%), or mean serum level of cholesterol (5.9 mmol/L). In comparison to the other groups, group I had significantly more females (44.5 %), more patients with blood pressure within normal limits with or without treatment (56% versus 38% and 17% respectively), lower mean serum creatinine (125 micromol/L versus 149 and 173 micromol/L respectively), higher mean cyclosporine dose (3.28 versus 2.7 and 2.73 mg/kg/day respectively), higher mean prednisolone dose (0.15 mg/kg/day) and less frequency of abnormal electrocardiogram (10% versus 22% and 25% respectively). We conclude that the prevalence of post-transplant proteinuria is high in our study patients. Also, our study suggests that proteinuria may be a marker of renal dysfunction and cardiovascular disease in this group of patients. Further studies are required including allograft histology to delineate better the causes and consequences of post-transplant proteinuria.

Long-term intravenous calcitriol in secondary hyperparathyroidism: the role of technetium-99m-MIBI scintigraphy in predicting the response to treatment.

BACKGROUND: Despite the effectiveness of intravenous calcitriol in suppressing parathyroid hormone secretion in patients with uremic hyperparathyroidism, 50% of the patients remain refractory to this treatment. There are conflicting reports regarding the factors that can predict the response to treatment. Technetium-99m-MIBI scintigraphy was found to be correlated with functional activity of the parathyroid gland. METHODS: We, retrospectively, evaluated 16 chronic hemodialysis patients, who were maintained on i.v. calcitriol for 36 months or longer, and who had MIBI scan either at the start of, or within the first 6 months of starting calcitriol. Nine patients had a positive uptake (+ve group), and 7 patients had a negative uptake (-ve group). All patients had an elevated iPTH (iPTH > 300 pg/ml) at the start of treatment. RESULTS: The percentage reduction of iPTH in the (-ve) and the (+ve) groups was 65% versus 45% at 12 months, and 65% versus 10% at 36 months respectively. In long-term follow-up of 36 months, all the patients in the (-ve) group responded to calcitriol; while 8 of the 9 patients (89%) in the (+ve) group didn't respond. The difference in response between the 2 groups was statistically significant (p<0.001). CONCLUSION: We conclude that MIBI scan is a reliable technique in predicting the response to treatment with i.v. calcitriol in patients with secondary hyperparathyroidism.