Peter A Andrews

Recent developments: Renal transplantation

Since the first successful transplant of a kidney from one twin to another in 1954, renal transplantation has moved from being at the cutting edge to being a mature technology. Registry data show that the current survival rates for grafts from cadavers are around 88% and 60% at one and 10 years after transplantation, respectively, while comparable rates for grafts from living donors are in excess of 95% and 70% (fig ​(fig11).1,3 These rates have shown steady improvements over the past 10 years, with the one year survival rates for grafts from cadavers and living donors improving by around 5% in that time.1,3 One year patient survival after transplantation is steady at 95%, with 87% alive at five years. In the medium term (one to three years) after transplantation, clinical outcomes are now so good that it is difficult to improve the survival of the patients or the grafts. Rejection rates have fallen over the years, and rejection is now an uncommon cause of early loss of a graft.

Tumor necrosis factor α blockade with infliximab for refractory uveitis and scleritis

Abstract Objective To assess the efficacy and safety of the anti–tumor necrosis factor α agent infliximab in treatment-resistant uveitis and scleritis. Design Retrospective, noncomparative interventional case series. Participants Seven patients with noninfectious ocular inflammatory disease that was refractory to alternative immunosuppression. These included one patient with idiopathic retinal vasculitis and panuveitis, one patient with intermediate uveitis, one patient with chronic juvenile anterior uveitis, three patients with scleritis, and one patient with scleritis and peripheral ulcerative keratitis. Four patients had an underlying systemic disease that was in remission in three cases. Intervention Infusions of infliximab, 200 mg, were given at 4-week to 8-week intervals, depending on the clinical response. Main outcome measures Clinical response, including symptoms, visual acuity, degree of scleral vascular engorgement, corneal thinning, anterior chamber activity, and posterior segment inflammation, reduction in concomitant immunosuppression, and adverse effects. Results The mean patient age was 47 years (range, 24–78), and four patients were female. The mean number of infliximab infusions was seven (range, 2–19), and the mean follow-up period was 12 months (range, 4–22 months). Six patients experienced a clinical improvement, with five achieving remission and significant reduction in immunosuppression. One patient showed an initial response but developed a delayed hypersensitivity response that precluded further treatment. No other adverse effects occurred. Conclusions Infliximab seems to be an effective and safe treatment for noninfectious uveitis and scleritis and may be indicated as rescue therapy for relapses of ocular inflammation or as maintenance therapy when conventional immunosuppression has failed. Further investigation of infliximab for treatment-resistant scleritis and uveitis is warranted.

Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.

Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (>95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with omeprazole is more effective in achieving H pylori eradication than is triple therapy plus famotidine. Use of 20 mg omeprazole twice daily rather than 40 mg famotidine with a 12 day, low dose triple therapy enhances eradication to over 97% whether the H pylori is metronidazole sensitive or resistant.

Safety and efficacy of TNFα blockade in relapsing vasculitis

Blockade of tumour necrosis factor alpha (TNFα) using infliximab, a chimeric monoclonal antibody against TNFα, is an effective treatment in rheumatoid arthritis and Crohns disease.1, 2 Sifikakis reported success using infliximab in sight threatening Behcets disease.3 A preliminary study has also reported clinical improvements in the primary systemic vasculitis, Wegeners granulomatosis, with the soluble TNFα receptor etanercept.4 The benefit of lenercept, a soluble p55 TNFα receptor fusion protein, on digital vasculitis in rheumatoid arthritis has also …

Helicobacter pylori Eradication with Doxycycline—Metronidazole—Bismuth Subcitrate Triple Therapy

Triple therapy containing tetracycline HCl is currently among the most efficient combination therapies for eradication of Helicobacter pylori. Substitution of doxycycline for tetracycline HCl offers advantages of less frequent dosing and extrarenal excretion. In this study patients with duodenal ulcer or non-ulcer dyspepsia positive for H. pylori were randomized to either doxycycline or tetracycline HCl triple therapy in conjunction with bismuth subcitrate and metronidazole. Of the 34 patients taking doxycycline, only 22 (65%) achieved H. pylori eradication at the 4-week rebiopsy, compared with 36 of 39 (92%) taking tetracycline HCl (p = 0.004). We conclude that doxycycline-containing triple therapy is less effective for H. pylori eradication and offers no clinical advantage over tetracycline HCl-containing triple therapy.

Cytomegalovirus infection and abdominal pain with mycophenolate mofetil: is there a link?

Mycophenolate mofetil (MMF) is an immunosuppressive agent that exerts relatively selective antiproliferative effects on T and B lymphocytes. Efficacy has been demonstrated in large-scale randomised studies, but the use of MMF is complicated by gastrointestinal upset and is associated with an increased incidence of tissue-invasive cytomegalovirus (CMV) disease.The gastrointestinal tract is a well recognised site for invasive CMV disease, and it has therefore been hypothesised that the abdominal pain commonly seen with MMF is related to CMV infection. This has only been tested in a single small uncontrolled study, where abdominal pain was associated with the presence of CMV on endoscopic biopsy. In contrast, the toxicity profile in 85 patients with psoriasis who had received relatively high dosages of mycophenolic acid, the active moiety of MMF, for up to 13 years showed that the incidence of gastrointestinal upset fell dramatically over time.We can find little evidence that CMV disease explains the gastrointestinal adverse event profile associated with MMF, and instead support the contention that high local concentrations of MMF have a direct toxic effect on cells of the small intestine. We do not recommend any changes to current policy on CMV prophylaxis in patients receiving MMF, although we recognise that some severe gastrointestinal adverse effects may be CMV-associated. The use of trough plasma concentration monitoring, divided doses and a gradually increasing dosage schedule may be of value in limiting toxicity.

Oxygenating mouthguard alleviates hypoxia during gastroscopy.

A randomized study was carried out to determine the effect of oxygen (3 liters/min) via a novel oxygenating mouthguard (Oxyguard) on arterial oxygenation in 242 intravenously sedated patients undergoing gastroscopy. In another group of 21 patients, a randomized crossover study of arterial oxygen saturation using either the standard mouthguard or the oxygenating mouthguard (3 liters/min) was conducted. Significant O2 desaturation (pulse oximeter reading less than 90%) occurred in 25% of patients on room air but only 3% of those on oxygen (p less than 0.001). Severe desaturation (reading less than 85%) occurred in 5% of patients on room air but was prevented by the oxygenating mouthguard. Minimum oxygen saturation levels were significantly higher in patients on oxygen (90.5 +/- 0.3%) than on air (86.5 +/- 0.5%; p less than 0.001). In the crossover group, O2 saturation was uniformly higher in the recordings of all patients using the oxygenating mouthguard. In conclusion, administration of oxygen via the oxygenating mouthguard alleviates hypoxemia during gastroscopy and prevents severe oxygen desaturation. However, hypoxemia may occur even during use of supplemental oxygen. Hence, monitoring of arterial oxygenation is recommended.

Review: Renal dysfunction as a marker of increased vascular risk

Minimisation of risk factors for the development of vascular disease has made a major contribution to the decline in vascular morbidity and mortality reported over the last decade. Recent evidence has highlighted that elevation of serum creatinine is a strong marker of increased vascular risk, with a predictive value as high as the development of diabetes. As serum creatinine is easily measured — albeit often misinterpreted — this provides another easily applied clinical tool for the stratification of cardiovascular risk and the targeting of preventative medicine in primary and secondary care.

A painful skin rash in a patient with Stage V chronic kidney disease

This case highlights the importance of early identification of skin lesions in patients with Stage V CKD, whether on dialysis or not. It illustrates the relevant differential diagnosis and the investigations required to establish a diagnosis. Most importantly, it illustrates that calciphylaxis may occur in a pre-dialysis patient with normal levels of calcium and phosphate and minimal elevation of PTH levels, a combination that is poorly recognized in the literature. Although the management of calciphylaxis is largely supportive, with little evidence of benefit from medical or surgical therapy, it is likely that outcome will be improved by earlier diagnosis. An International Calciphylaxis Registry has been established to increase knowledge and data collection in this condition, to create a tissue bank comprising of blood, tissue and DNA from patients with calciphylaxis and to support future research. This may be accessed at http://www.calciphylaxis.org.uk/.

Early identification and management of chronic kidney disease in adults in primary and secondary care: a commentary on NICE Guideline No 73, Sept 2008

Chronic kidney disease (CKD) is common, but more than 30% of people with CKD are referred late, leading to increased morbidity and mortality. An updated classification of CKD, using estimated glomerular filtration rate (eGFR) allows the severity of CKD to be determined and when it is appropriate to refer to a consultant nephrolo gist. New approaches to the measurement of protein excretion are stressed with particular reference to using urine albumin:creatinine ratio or urine protein:creatinine ratio. Annual measurement of serum creatinine in atrisk patients is clearly outlined as are the indications for renal ultrasound examination. Two algorithms for the management of newly detected abnormal eGFR and for the management of CKD, Stages 3 ‐5, are not in the NICE Guideline No 73 document but reflect the author’s clinical experience of working in this area, with the aim of simplifying these two important topics. The safe use of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin blocking agents in the everyday clinical work place is outlined. The management of CKD due to diabetic nephropathy and hypertension is an important part of diabetes man agement and this review of NICE Guideline No 73 on the early identification and management of CKD in adults in both primary and secondary care settings will further enable the better care of type 1 and type 2 diabetic subjects with renal impairment. Br J Diabetes Vasc Dis 2008; 8: 257 ‐262