Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis.

BACKGROUND: Interleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on creatinine change and the risk of cytomegalovirus (CMV) infection. METHODS: We conducted a systematic review in different databases to identify studies and research work that assessed the effect of IL-2 antibody induction therapy on renal transplant outcomes. Inclusion criteria for our meta-analysis were all studies that compared IL-2 induction therapy with placebo or no induction therapy in standard-risk renal transplant recipients on tacrolimus-based maintenance immunosuppressive therapy. Data collected were the name of the first author, journal title, year of publication, country where the study was conducted, number of patients in the IL-2 induction therapy arm and in the placebo arm, number of patients who had biopsy-proven rejection and graft survival in each arm. A random effects model was used for the meta-analysis. RESULTS: Of the 470 articles found in different databases, 7 were included in the meta-analysis. Forest plot analysis for rate of rejection during the follow-up period post-transplant showed no significant difference between the groups. There was no evidence of heterogenicity between included studies (I 2 = 21.8%, P = 0.27). The overall risk difference was -0.02 [95% confidence interval (CI) -0.05-0.01]. A random effects meta-analysis for patient and graft survival was performed using forest plot analysis and showed no significant effect of IL-2 receptor (IL-2R) antibody induction on patient or graft survival compared with placebo. The overall risk difference was -0.01 (95% CI -0.04-0.01) and 0.00 (95% CI -0.00-0.01), respectively. Three of the included studies showed no effect of basiliximab on creatinine change, two showed no effect on risk of CMV infection and two showed less risk of post-transplant diabetes in the basiliximab group. CONCLUSION: IL-2R antibody induction therapy has no significant effect on the rate of rejection or patient or graft survival in standard-risk renal transplant recipients on tacrolimus-based maintenance immunotherapy. More randomized controlled studies are needed.

Severe co-trimoxazole-induced hypoglycaemia in a patient with microscopic polyangiitis.

A 69-year-old man presented to the emergency department with lower respiratory tract infection and febrile neutropaenia. He was recently discharged following a 50-day hospital stay with newly diagnosed microscopic polyangiitis, complicated by pulmonary haemorrhage and severe renal dysfunction requiring renal replacement therapy, plasma exchange and immunosuppression (cyclophosphamide and methylprednisolone). High risk of pneumocystis pneumonia (PCP) led to an escalation in treatment from prophylactic to therapeutic oral co-trimoxazole, alongside broad-spectrum antibiotics. The patient suffered from severe and protracted hypoglycaemia, complicated by a tonic-clonic seizure 7 days after escalation to therapeutic co-trimoxazole. Endogenous hyperinsulinaemia was confirmed and was attributed to co-trimoxazole use. Hypoglycaemia resolved 48 hours after discontinuation of co-trimoxazole. PCP testing on bronchoalveolar lavage was negative. Owing to the prescription of heavy immunosuppression in patients with vasculitis and the subsequent risk of PCP warranting co-trimoxazole prophylaxis, we believe that the risk of hypoglycaemia should be highlighted.

Exophiala jeanselmei keratitis: case report and review of literature.

PURPOSE: To describe a patient with Exophiala jeanselmei keratitis and to review the prior cases reported in the literature. METHODS: We report one patient with keratitis after remote injury and chronic steroid use and review the six prior reported cases. RESULTS: Culture plates from corneal scraping revealed growth of the dematiaceous fungi, E. jeanselmei, a rare causative organism of ocular infection. The patient underwent therapy with topical and intracameral antifungals and subsequently required a corneal transplant. Biopsy of the donor graft confirmed the diagnosis of E. jeanselmei. This is the first reported case to use intracameral antifungal agents and the first biopsy proven case. Half of reported cases experienced associated trauma, and severity was generally related to delay in diagnosis. CONCLUSIONS: Trauma and chronic topical steroid use contributed to the development of severe keratitis in this patient. Patients on chronic steroids should be monitored closely. Topical, subconjunctival, and intracameral antifungals have all been effective in treating this pathogen. If diagnosed and treated early, E. jeanselmei keratitis can have a good visual outcome.

A cohort study on the rate of progression of diabetic chronic kidney disease in different ethnic groups.

OBJECTIVE: To compare the rate of progression of diabetic chronic kidney disease in different ethnic groups. DESIGN: Prospective longitudinal observational study. PARTICIPANTS: All new patients attending a tertiary renal unit in east London with diabetic chronic kidney disease between 2000 and 2007 and followed up till 2009 were included. Patients presenting with acute end-stage kidney failure were excluded. MAIN OUTCOME MEASURES: The primary outcome was annual decline in the estimated glomerular filtration rate (eGFR) in different ethnic groups. Secondary end points were the number of patients developing end-stage kidney failure and total mortality during the study period. RESULTS: 329 patients (age 60±11.9 years, 208 men) were studied comprising 149 south Asian, 105 White and 75 Black patients. Mean follow-up was 6.0±2.3, 5.0±2.7 and 5.6±2.4 years for White, Black and south Asian patients, respectively. South Asian patients were younger and had a higher baseline eGFR, but both systolic and diastolic blood pressures were higher in Black patients (p<0.05). Baseline proteinuria was highest for the south Asian group followed by the White and Black groups. Adjusted linear regression analysis showed that an annual decline in eGFR was not significantly different between the three groups. The numbers of patients developing end-stage kidney failure and total mortality were also not significantly different between the three groups. ACE or angiotensin receptor blockers use, and glycated haemoglobin were similar at baseline and throughout the study period. CONCLUSIONS: We conclude that ethnicity is not an independent factor in the rate of progression renal failure in patients with diabetic chronic kidney disease.

Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy.

BACKGROUND: Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review. METHODS: In this novel randomized controlled trial, 47 patients with chronic allograft nephropathy, severe renal impairment, and more than or equal to 1 g/24 hr proteinuria were randomized to lisinopril (group A) or other hypotensives (group B) for 1 year. Sodium bicarbonate was given to all patients to treat metabolic acidosis prophylactically (acidosis increases significantly with lisinopril). The annual rate of decline of graft function was measured isotopically (primary outcome) and 24 hr proteinuria, genotyping, radiolabeled polypeptide aprotinin proximal tubular catabolic studies (in group A only) as secondary outcome measurements were undertaken. RESULTS: At baseline, groups were comparable except for greater proteinuria in group A. After 1 year, the rate of decline of graft function and graft survival were comparable in both groups. Proteinuria decreased significantly in group A patients only. Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism, plasma aldosterone, and ammonia excretion. Plasma potassium, bicarbonate, and mean arterial pressures were comparable in both groups. Patients with more than or equal to 30% reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene. CONCLUSIONS: The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year. Lisinopril significantly reduced proteinuria, renal proximal tubular polypeptide catabolism, plasma aldosterone, and ammonia excretion suggesting relative preservation of graft function. Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors.