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Should kidneys pay the price ▸

Calcineurin inhibitor (cyclosporin or tacrolimus) therapy has significantly improved survival among patients who have received organ transplantation. However, these drugs which form a key component of immunosuppressive regimens have been implicated in the development of chronic renal failure. Ojo et al used a population based cohort of 69 321 subjects in the Scientific Registry of Transplant Recipients (SRTR) to determine the incidence of chronic renal failure in those receiving non-renal (heart, lung, liver, and intestine) transplantation. During a median follow up of 36 months, 16.5% developed chronic renal failure (defined as a glomerular filtration rate of ⩽29 ml/min per 1.73 m2 of body surface area). The cumulative incidence of chronic renal failure at five years was highest in those with intestinal transplantation (21%) followed by liver transplantation (18%), and the risk increased with increasing age, female sex, hepatitis C, hypertension, diabetes, and postoperative acute renal failure. In those undergoing liver transplantation, the risk was higher with cyclosporin than that with tacrolimus. The occurrence of chronic renal failure was associated with more than a fourfold risk of death.

This study highlights the magnitude of a problem that is primarily related to the immunosuppressive regimen. Late reduction in the dose of calcineurin inhibitors appears to have limited benefit in improving renal function. Therefore, attention should be focused on measures to reduce the risk of chronic renal impairment, including investigations to identify novel immunosuppressive strategies.

Multidetector colonography: shows promise but needs to do better ▸

Computed tomographic colonography (CTC) could become a less invasive alternative to colonoscopy for both colorectal cancer screening and investigation of symptomatic patients but has yet to prove its superiority over colonoscopy. Hoping that newer CT scanners might perform better, the authors have prospectively evaluated the performance of multidetector CTC (MDCTC) and colonoscopy in detecting lesions of 6 mm or larger. A total of 148 patients (median age 60 years) with symptoms (49%) or undergoing surveillance of polyps or cancer underwent MDCTC immediately prior to colonoscopy. Each segment of bowel was scored separately during each procedure for quality of bowel preparation, and lesions were carefully documented. Patients with an abnormal MDCTC but a normal colonoscopy immediately underwent a second “back to back” colonoscopy to serve as the gold standard. Colonoscopy was complete in 91% (135/148) of patients, failures being mainly the result of pain. In contrast, MDCTC was complete in only 76% (p<0.01), mostly because of poor colonic distension, almost always in the sigmoid, and associated with diverticulosis in half of these cases. Suboptimal bowel preparation also contributed. Overall detection rates of 81% (MDCTC) and 87% (colonoscopy) were similar but colonoscopy was more sensitive for detection of polyps of 6–9 mm (p = 0.008). Colonoscopy missed polyps in two patients and missed a lipoma and a diverticular abscess, both seen on MDCTC. However, MDCTC missed 13 lesions (poor distension/preparation in six, four flat lesions, one near the anal verge, and two that were seen but misinterpreted). There were also five false positive results with MDCTC. Reassuringly, both techniques detected all 11 carcinomas and there was no overall difference in detection of adenomas of any size but, just as with colonoscopy, the sigmoid colon also vexes radiologists and the faster data acquisition and better spatial resolution of MDCTC does not overcome this. Perhaps combining MDCTC with flexible sigmoidoscopy may be the way forward.

PPIs as a risk factor for pseudomembranous colitis ▸

Clostridium difficile is the main cause of diarrhoea in hospital inpatients, and reports have increased 10-fold in the past decade (from 822 to 8376, data on file at CDSC). It has been implicated in antibiotic associated colitis since the 1970s (

), particularly with cephalosporins. As almost all strains isolated from elderly patients now have innate resistance to cephalosporins (

), these represent one of the principal risk factors. However, the role of gastric antisecretory drugs is unclear, even though acid suppression increases the risk of Salmonella or Campylobacter infection. The current report from Plymouth examined 207 patients found to be toxin positive in 1999. Six were excluded because of coexistent inflammatory bowel disease and 31 sets of notes were unobtainable; hence 170 patients were matched with controls for age, sex, month of admission, admitting consultant, and diagnostic code. Proton pump inhibitor (PPI) use in the preceding two months was associated with double the risk of C difficile diarrhoea (odds ratio (OR) 2.5 (95% confidence interval (CI) 1.5–4.2)). This was almost identical to the risk of prior antibiotic use (OR 2.8 (95% CI 1.5–5.2)). When antibiotics and PPIs were coprescribed, the risk increased fivefold (OR 5.4 (95% CI 2.2–13.2)). The risk was even higher when PPIs were coprescribed with cytotoxic chemotherapy (OR 19.8 (95% CI 3.0–130.7)) and highest of all when PPIs and chemotherapy and antibiotics had been used together (OR 43.2 (95% CI 5.7–330.4)).

The hypothesis that reduction in gastric acid is a predisposing factor is biologically plausible. Even though spores are relatively resistant to acid, vegetative cells are highly susceptible and hypochlorhydria is more common in the elderly who represent the most susceptible group. This study is credible because there was a summation and (in the case of chemotherapy) multiplication of risk when factors were combined. An earlier study that did not find an association between PPIs and C difficile (

) did not match controls as closely as the present study. Consequently, we should be conscious of the potential risks of inhibiting acid barrier function, especially when antibiotics or chemotherapy are coprescribed.