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Background Simkania negevensis is an obligate intracellular bacterium belonging to the family Simkaniaceae in the Chlamydiales order. It is considered an ubiquitous microorganism and aquatic environments may be involved as a source of infection for humans. It was just isolated in samples from domestic water supplies and from mains water supplies, like spa water or swimming pool water, confirming its ability to resist to the common chlorination treatments. Evidence indicates a possible role of the microorganism in respiratory tract infections, in gastroenteric disorders and in the pathogenesis of cardiovascular disease, furthermore it has hypothesized that it could play a role in lung transplant rejection. Prevalence and possible effects in nephrology are unknown. Methods We examined the occurrence of Simkania negevensis in two differents populations, both characterized by a high susceptibility to infectious complications: 105 hemodialysis patients, 105 renal transplant recipients and 105 healthy subjects through the IgG and IgA response to Simkania negevensis in their sera. Serum antibodies to Simkania negevensis were detected by a homemade ELISA performed according to the Kahane’s protocol. Furthermore water samples from hemodialytic circuit were collected, to evaluate Simkania negevensis resistance to usual treatment of disinfection. Results Our results were unexpected, showing a higher seroprevalence of antibodies against Simkania negevensis in the hemodialysis patients, compared to renal transplant patients (IgG 22% vs 9% - IgA 9% vs 3%). S. negevensis was isolated in all water samples analyzed. Conclusions Our study detected for the first time the occurrence of S. negevensis in hemodialysis and in renal transplant patients. Our findings suggest that water used in hemodialysis could be one of the possible sources of S. negevensis infection, without clinical involvement risk for patients.

Background Milk-alkali syndrome is a life-threatening condition defined by the triad of hypercalcaemia, metabolic alkalosis and acute renal failure, and is associated with consumption of calcium and absorbable alkali. Methods We report the case of a patient admitted to a step-down unit of a large hospital in Italy. Results The patient was a 59-year-old woman with hypoparathyroidism and mild chronic kidney insufficiency, treated for a preceding episode of hypocalcaemia with high doses of calcitriol and calcium carbonate, who was also taking hydrochlorothiazide and unreported herbal anthranoid laxatives. The patient was admitted to hospital with severe hypercalcaemia, severe metabolic alkalosis and acute renal insufficiency. The patient was successfully treated with urgent dialysis, loop diuretics and calcitonin administration. Conclusions This case underlines the need for caution when treating patients with impaired calcium metabolism regulation, and suggests that herbal anthranoid laxatives might act as triggers for milk-alkali syndrome. LEARNING POINTS Patients with hypoparathyroidism are more prone to develop milk-alkali syndrome. Patients need careful follow-up and review of their need for calcium supplements. Non-prescription and complementary medicines can aggravate hypercalcaemia.

The oto-renal axis describes the relationship between hearing loss and chronic nephropathy. Several clinical studies have investigated the incidence of hypoacusia in patients affected by chronic renal failure, but the etiopathogenic mechanism is not fully understood. In this context, there is a general agreement that hypoacusia is usually neurosensorial and the cochlea is the main site of lesion. Inner ear and kidney present an interesting similarity in terms of structure and function. In particular, the presence of pericytes and podocytes in inner ear and in glomeruli, respectively, evidence common characteristics of microcirculation. Defects in microcirculation in the inner ear mainly cause an electrolytic imbalance with the consequent impairment of endocochlear potential and sensorial transduction. In kidney, microvessels and podocytes contribute to glomerular stability and function. Microcirculation dysfunction often occurs during the inflammatory status, frequently reported both in chronic nephropathy and in cardiovascular disease. Clinical studies aimed to describe the hypoacusia in nephropathy patients are summarized. Then, in order to speculate the etiopathogenic mechanism of hearing loss in chronic nephropathy, we report the similarities between pericytes and podocytes in inner ear and glomeruli microcirculation in terms of structure and function. Finally, we propose a model in which inflammation plays an important role in oto-renal dysfunction. Our model proposes the inflammation, as an etiopathogenic mechanism of hypoacusia in chronic nephropathy and the defective cross-talk between pericytes/podocytes and vascular endothelium, as the initial event of the degenerative process.

Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20–30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias.

Introduction It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. Materials and Methods We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). Results Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. Conclusion The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

Background: Short-term results of renal transplantation have shown a drastic improvement over time mainly due to changes in immunosuppressive therapy. Non-compliance to therapy is one of the causes of graft loss. Tacrolimus is a cornerstone of immunosuppressive therapy: recently became available Tacrolimus once a day formulation (Advagraf) that could improve the compliance of patients to immunosuppressive therapy. Few are published data about its use in clinical practice. We therefore compared the efficacy and pharmacokinetics of once-daily formulation compared to the classic twice-daily dosing tacrolimus in de novo kidney transplant patients. Methods: Retrospectively evaluation of 30 de novo transplant recipients treated with Advagraf in 2009-2012 (on dose daily of 0.2-0.3 mg/kg) and 30 treated with Prograf (2 doses daily of 0.2 mg /kg). Comparison between the two groups regarding drugs dose, blood level and clinical variables. Result: Both Advagraf and Prograf patients reached the drug target level, even if initially with a higher drug dose for Advagraf. Creatinine levels were initially higher in Advagraf group, no differences are detectable two weeks after transplant. There were no differences between groups for rejection episodes, graft loss and adverse events. Lipid metabolism was significantly better in Advagraf patients. Discussion: Advagraf confirm to offer a similar short-term efficacy compared with the twice a day administration in de novo kidney transplant, with a higher drug dose compared to tacrolimus. The safety profile is comparable with twice-daily administration. Interestingly a better lipid metabolism is present in Advagraf group.

BACKGROUND The progressive deterioration of kidney allograft function leads in most cases to transplant failure. Polymorphisms in genes encoding for inflammatory and apoptosis molecules may be one possible explanation for interindividual differences in kidney transplant outcomes. The objective of our work was to identify the possible effect of interleukin 6 (IL-6), transforming growth factor beta 1 (TGFB1), and Fas on graft function. MATERIAL AND METHODS A case-control study was carried out to assess potential associations between polymorphisms in inflammation- and apoptosis-related genes and the risk for chronic impairment of kidney graft function. The study included 376 cadaveric kidney recipients, 256 of them with stable graft function and 120 who experienced renal deterioration during the follow-up period of 2.6 ± 1.4 years. Genotyping of IL-6/G-174C, TGFB1/L10P, TGFB1/R25P, and Fas/G-670A polymorphisms was performed by PCR-RFLP and direct sequencing. RESULTS Considering the single IL-6, TGFB1, and Fas polymorphisms, we found similar allelic and genotype frequencies between the 2 groups. To test the hypothesis of mutual effects of polymorphisms, multiple logistic regression was performed incorporating data for all the possible dual genotypic associations. The association of IL-6 high producer and Fas low producer genotype resulted in a protective effect against graft dysfunction (OR=0.79; 95% C.I.=0.72-0.86). CONCLUSIONS This study did not find significant associations of apoptosis and inflammation gene polymorphisms with transplanted kidney function in Italian renal transplant recipients. However, our data seem to indicate that the carriage of IL-6 high producer/Fas low producer genotype has a protective effect against graft function loss.

The submission of a drug master file (DMF) is one way of supplying confidential data on a drug substance to licensing authorities by the active ingredients manufacturer (AIM). In the European drug master file (EDMF), three types of active ingredients may be described: new active ingredients, off-patent active ingredients, and pharmacopoeial ingredients. As the EDMF contains some information which should be kept confidential, it should be divided into two sections: an applicant section and a restricted section. Possible advantages and disadvantages of this provision of data are discussed.