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Long-term treatment with proton pump inhibitors (PPI) is becoming more prevalent. Although they are well tolerated in the short term, serious concerns about long-term use have arisen. Recent data suggest that the latter is associated with an increased risk for osteoporotic fracture (especially vertebral), Clostridium difficile infection and rebound acid hypersecretion after treatment discontinuation. Acute interstitial nephritis is rare but may progress to chronic renal failure. An increased risk of community-acquired pneumonia has not been established in the general population and seems limited to the most vulnerable patients. Consistent data are still missing to correctly assess the risk of iron deficiency, vitamin B12 deficiency or hypomagnesaemia and the risk of digestive malignant diseases, despite the pathophysiological basis that exists concerning gastric malignancy. Many drug interactions can occur on long-term treatment, including some that imply the cytochrome P450 enzymes. Finally, the risk-benefit balance for a chronic PPI use in children seems unfavorable in most cases., (Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

The recent 90-year anniversary of the Battle of the Somme presents an opportunity to examine the public health response to the trench diseases, new conditions which arose in the trenches of World War I. Throughout history, there have been two views of epidemic disease: the configurationist and contagionist perspectives. Most doctors responding to the trench diseases, 'contingent-contagionists', combined these two conceptions of disease. Because of the difficulty of finding a causative organism and the absence of effective treatment, the majority view became that these conditions were a product of the trench environment. Configurationism, with its emphasis on environmental and social determinants, seemed to provide the most obvious approaches for tackling the trench diseases. The diseases were effectively controlled using the tools of public health science: sanitary discipline and a battery of measures, such as improving trench construction, improving the diet, providing protective kit, regular bathing and treating lice infestation. The response demonstrates the triumph of public health science over new medical technologies. It also illustrates the importance of considering all the many determinants of health and of close surveillance, discipline and partnership working to counter ill-health. Although technology, training, doctrine and health beliefs change over time, the interaction between disease and environment remains the core challenge to public health practitioners.

Around the 90-year anniversary of the Battle of the Somme, it is important to remember the international effort that went into responding to the new diseases, which appeared during the First World War, such as trench nephritis. This condition arose among soldiers in spring 1915, characterized by breathlessness, swelling of the face or legs, headache, sore throat, and the presence of albumin and renal casts in urine. It was speedily investigated by the military-medical authorities. There was debate over whether it was new condition or streptococcal nephritis, and the experts agreed that it was a new condition. The major etiologies proposed were infection, exposure, and diet (including poisons). Research pointed to the origin of the disease as being infective rather than toxic, but no definite cause was discovered. A number of labels were given to the disease, including war nephritis. However, trench nephritis was the one used most widely. Trench nephritis was a serious problem for the Allies, leading to 35 000 casualties in the British and 2000 in the American forces. There were also hundreds of deaths. The condition was treated in line with pre-war regimens designed for acute nephritis. No significant preventative methods were implemented for trench nephritis, as there was no consensus regarding causation. The medical response to trench nephritis was largely ineffective, with medical commentators recognizing that there had been a lack of medical progress.

BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condition remains poorly understood. Increasing prevalence has been correlated with newer immunosuppressive agents and the decline in acute rejection rates in recent years. The clinical manifestation varies from the asymptomatic state of viremia and nephritis to clinical renal dysfunction. The diagnosis of this infection is based on the combination of the presence of urinary decoy cells, virus in the urine/blood, and typical renal histological findings of interstitial nephritis. Routine post-transplant screening for BK viremia and viruria prior to the occurrence of nephritis and the reduction in immunosuppressive therapy for subjects with viremia appear to be attractive approaches. The treatment of BKV nephritis (BKVN) consists of reduction in immunosuppressive therapy and antiviral therapy with cidofovir or leflunomide or a combination of both. Approximately 30-60% of subjects with BKVN experienced irreversible graft failure. However, in recent years, the combinations of early detection, prompt diagnosis, and appropriate reduction in immunosuppressive therapy have been associated with better outcome. The pathogenesis of BK virus infection in renal transplant recipients needs to be explored. The source of BKV infection (donor as opposed to recipient), the role of host humoral, and cellular immunity to BKV, and the role of alloimmune activation in renal graft to the occurrence of nephritis are discussed in this review.

Background: BK virus nephritis (BKVN) has emerged as an important cause of renal transplant failure. Quantified analysis of its timing and clinical course is generally lacking. We have thus quantified the timing, risk factors, evolution of renal function, and transplant graft outcome in renal transplant recipients with BKVN from our center., Methods: A total of 41 cases of BKVN were diagnosed in 1001 renal and renal/pancreas transplant recipients. There were 2 groups: group I (N= 16), with diagnosis based on renal biopsy alone from January 1996 to August 2001, and group II (N= 25), with diagnosis based on quantitative blood BKV-PCR and biopsy from September 2001 to December 2003. The demographics, the clinical course, immunosuppressive therapy, renal function, and graft outcome were quantified. Donor, recipient, and transplant risk variables were studied using a univariate analysis. Actuarial graft survival was calculated. An immunosuppressive scale created to evaluate the degree of immunosuppression in these patients and its reduction after the diagnosis of BKVN., Results: The median time from transplant to BKVN diagnosis was 318 days (range 48-1356). The actuarial graft survival in patients with BKVN at 6 months, 1, 3, and 5 years was 97%, 90%, 58%, and 47%. The corresponding values for those without BKVN were 94%, 92%, 83%, and 76%, respectively, P < 0.001. Graft loss occurred in 46% of patients. The rate of decline of renal function in group II (N= 25) patients in the 4 months preceding BKVN was rapid (4.8 mL/min/month) and this declined to 0.7 mL/min/month at 3 months' post-BKVN diagnosis, P= 0.004. In those who recovered, the time to stabilization of renal function was a median of 112 days. The immunosuppressive scale score was 7 units at the time of diagnosis of BKVN and decreased to 3.5 units at 3 months' post-BKVN. Reduction in the dose of calcineurin inhibitors but not the overall reduction in dose of immunosuppression correlated with recovery of renal function in these patients., Conclusion: BKVN is a relatively late complication of renal transplantation. Despite reduction in immunosuppression, graft loss occurred in 46% of patients. There was a steep decline in renal function in months preceding the diagnosis of BKVN, and reduction in calcineurin inhibitor dose, but not overall immunosuppression, correlated with stabilization of renal function.

Background: The prevalence of increased oxidative stress and acute-phase inflammation in patients with chronic kidney disease (CKD) has not been thoroughly investigated., Methods: Biomarkers of oxidative stress and acute-phase inflammation were measured in a cohort of 60 patients with stage 3-5 CKD compared to a healthy subject cohort. Levels of oxidative stress and inflammation were also compared to estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula., Results: All biomarkers of oxidative stress (plasma protein carbonyl group content, plasma free F2-isoprostane content, plasma protein reduced thiol content) and all markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6)] differed significantly between CKD patients and healthy subjects. There was no significant relationship between estimated GFR and any oxidative stress or inflammation biomarker. CRP levels were higher in patients with known coronary vascular disease (CVD) and in patients not taking angiotensin II inhibitors. Plasma IL-6 levels were significantly higher in patients with known coronary vascular disease and lower in patients taking statins. Biomarkers of oxidative stress were significantly higher in patients with diabetes and hypercholesterolemia., Conclusion: There is evidence of increased oxidative stress and acute-phase inflammation in patients with stage 3-5 chronic kidney disease compared to healthy subjects that does not closely correlate with estimates of GFR. Among CKD patients, inflammatory biomarkers correlate with known CVD and inversely correlate with the use of angiotensin II inhibitors and statins. A further increase in oxidative stress was noted in diabetic and hypercholesterolemic patients. Inflammation and oxidative stress may contribute to cardiovascular risk in CKD patients.

Background: Outbreaks of nephritis have been rare since the 1970s. From December, 1997, to July, 1998, 253 cases of acute nephritis were identified in Nova Serrana, Brazil. Seven patients required dialysis, and three patients died. We did a case-control study to investigate the cause of the outbreak., Methods: Using a matched cluster design, we examined seven recent patients, their family members (n=23), and members of neighbourhood-matched control households (n=22). We subsequently interviewed 50 patients and 50 matched controls about exposure to various dairy products. We also cultured dairy foods and took udder-swab and milk samples from cows., Findings: Throat cultures indicated that nephritis was associated with group C Streptococcus equi subspecies zooepidemicus, a cause of bovine mastitis. S. zooepidemicus was detected in four of seven case households (six of 30 people) and no control households (p=0.09). Patients were more likely than matched controls to have consumed a locally produced cheese called queijo fresco (matched odds ratio 2.1, p=0.05). The nephritis attack rate was 4.5 per 1000 in Nova Serrana but 18 per 1000 in the village Quilombo do Gaia (p=0.003). The largest supplier of unpasteurized queijo fresco was a farm in Quilombo do Gaia. S. zooepidemicus was not detected in food samples or in swabs collected from cows in August, 1998, although mastitis was evident among cows on the suspected farm. Throat cultures of the two women who prepared cheese on this farm yielded the outbreak strain of S. zooepidemicus. After the cheese was removed from the distribution system, no further cases were reported., Interpretation: A large outbreak of glomerulonephritis was attributed to S. zooepidemicus in unpasteurised cheese. This outbreak highlights the dangers of consuming unpasteurized dairy products and need for global efforts to promote food safety.