Re-examination of renal allograft biopsy blocks for C4d positivity: missed cases of antibody mediated rejection.

INTRODUCTION: C4d immunostaining of renal allograft biopsies is recommended for the diagnosis of antibody-mediated rejection (ABMR), but it was not available to us prior to June 2012. In June 2012, we were able to obtain anti-human C4d polyclonal antibody and decided to retrospectively evaluate archived kidney allograft biopsies at our center for C4d deposition. METHODS: Twenty-four paraffin blocks were available for this study. Immunostaining for C4d was performed using anti-human C4d polyclonal antibody by Immunohistochemistry. The score and pattern of C4d positivity were determined according to the Banff 2007 guidelines. RESULTS: All grafts were from living related donors with negative CDC cross-match. The indications for biopsy were primary, acute and chronic graft dysfunction in 29.2%, 33.3% and 37.5% of patients respectively. Two biopsies revealed extensive necrosis rendering it difficult to interpret the result of C4d staining. Among the remaining 22 biopsies, C4d staining was categorized as negative in 40.9%, minimal in 13.6%, focal in 22.7% and diffuse in 22.7%. The prevalence of C4d positivity among biopsies taken due to primary, chronic and acute graft dysfunction was 71.4%, 44.4% and 12.5% respectively. CONCLUSION: C4d positivity was common in biopsies taken from this group of kidney transplant recipients and its prevalence was particularly high among biopsies taken due to primary graft non-function. This indicates that missed ABMR is an important cause for kidney allograft dysfunction in our setting.

Co-administration of ketoconazole and tacrolimus to kidney transplant recipients: cost minimization and potential metabolic benefits.

To evaluate the effects of the co-administration of tacrolimus and ketoconazole to a group of kidney transplant recipients, we studied 30 kidney transplant recipients with stable kidney function who were maintained on tacrolimus-based immunosuppression. They were prescribed ketoconazole (100 mg/day) with a concomitant reduction in daily tacrolimus dose to maintain its level within the therapeutic range. The study included 19 males and 11 females with a mean age of 36 ± 12 years. All patients were at least three months post-transplant and had tacrolimus trough levels within the therapeutic range of 5-7 ng/mL. Desired tacrolimus trough levels could be achieved in 29/30 patients after the addition of ketoconazole. This resulted in a significant reduction of the median tacrolimus dose from 5 mg/day (range 3-20 mg/day) at baseline to 2 mg/day (range 1-4 mg/day) (P = 0.00). The median reduction in the tacrolimus dose was 63% (range 50-83%). The median monthly tacrolimus cost dropped from 375 US$ per patient (range 225-1440 US$) to 150 US$ per patient (range 120-300 US$). There were no reported adverse drug effects during the study period. After one year of follow-up, there was a small but significant improvement in the estimated glomerular filtration rate (72 ± 18 versus 78 ± 20 mL/min, P = 0.01) and a significant reduction in serum uric acid levels (7.7 ± 1.7 versus 5.9 ± 0.8 mg/dL, P = 0.003). The co-administration of ketoconazole and tacrolimus to kidney trans-plant recipients is safe and significantly reduces the cost of immunosuppression. In addition, this combination appears to have a beneficial effect on kidney function.

Prevalence and Risk Factors of Central Venous Stenosis among Prevalent Hemodialysis Patients, a Single Center Experience.

INTRODUCTION: Central vein stenosis (CVS) is a common complication of central venous catheter (CVC) insertion. In this study we evaluated the prevalence and risk factors of CVS among hemodialysis (HD) patients in a single center in Sudan, using Doppler ultrasound as a screening tool. METHODS: The study included 106 prevalent HD patients. For every patient, we performed Duplex Doppler for the right and left jugular, subclavian and femoral veins. A patient was considered to have hemodynamically significant stenosis if the pre-stenosis to the post-stenosis velocities ratio was ≥ 2.5 or they had complete vein occlusion. RESULTS: Overall, 28.3% of patients had Doppler detected CVS, including 25.5% with hemodynamically significant stenosis and 2.8% with compromised flow. The prevalence of CVS was 68.4% among symptomatic patients compared to 19.5% in asymptomatic patients. The prevalence of CVS among patients with history of 0-1, 2-3 and ≥ 4 central venous catheters was 3.4%, 29.4% and 53.8% respectively (p=0.00). CVS was not more common in patients with history of previous/current jugular or femoral vein catheterization compared to no catheter placement in these veins (28.3% vs 28.6% and 35% vs 26.7% respectively; p >0.1). However, CVS was significantly more common in patients with previous/ current subclavian vein catheterization compared to no catheter placement in this vein (47.8% vs 22.9%, p = 0.02). CONCLUSION: CVS is highly prevalent among studied HD patients, particularly in the presence of suggestive clinical signs. The number of HD catheter placements and subclavian vein utilization for dialysis access impose a significantly higher risk of CVS.