Fecal microbiota transplantation for severe clostridium difficile infection after left ventricular assist device implantation: a case control study and concise review on the local and regional therapies.

BACKGROUND: We report herein a case of fecal microbiota transplantation (FMT) used for severe Clostridium difficile infection for a 65-year-old Lebanese man who underwent left ventricular assist device implantation. To the best of our knowledge this is the first case report from Lebanon and the region presenting such technique. CASE PRESENTATION: The patient experienced diarrhea and rectal bleeding and was diagnosed of pseudomembranous colitis (PMC). His condition failed to improve on maximal pharmacological therapy. Protocolectomy, an invasive operation consisting in resection of the entire colon and rectum seemed to be the last resort before the patient responded to FMT given through gastroscopy. CONCLUSION: Despite the increasing experience with FMT for C. difficile infection, published evidence in severe related cases from this region is very limited. Hence, we promote adjunctive FMT, an effective noninvasive method, to be considered as a promising early treatment option in severe C. difficile infection.

Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis.

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²-3×10⁻¹°), with heterogeneity detected only at the PSMB9/TAP1 locus (I²â€Š= 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻4). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²8). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity.

BACKGROUND: Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years' detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. METHODS: Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents' consanguinity were recorded when feasible. RESULTS: The mean age at renal biopsy was 36.76 ± 20 years (range 1-84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). CONCLUSIONS: Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population.

The cardiorenal syndrome in diabetes mellitus.

The cardiorenal syndrome in patients with diabetes mellitus represents a systemic condition that affects both the cardiovascular and renal systems. Diabetes is a well established risk factor for cardiovascular disease (CVD), and a significant proportion of diabetic patients go on to develop clinically significant nephropathy. In the diabetic state the kidney is involved by progressive sclerosis/fibrosis and proteinuria, due most likely to overactivity of the transforming growth factor-beta system and, to some extent, the vascular endothelial growth factor system, respectively. The pathogenesis of CVD in diabetes is multifactorial, involving hemodynamic forces, humoral/metabolic factors, and oxidative stress. Additionally, it has been suggested that endothelial dysfunction may lead to simultaneous development and progression of renal and cardiac pathology in diabetes. The risk of microvascular complications can be reduced by intensive glycemic control in patients with type 1 and type 2 diabetes mellitus whereas benefit to the cardiovascular system is less clear. However, intensified intervention involving other CVD risk factors like hypertension and dyslepidemia and interception of the rennin-angiotensin-aldosterone system in patients with type 2 diabetes have been shown to be associated with significant reduction in the risk for renal disease progression that was paralleled by a significant reduction in cardiovascular disease burden.

Characterization of a large Lebanese family segregating IgA nephropathy.

BACKGROUND: Familial aggregation of IgA nephropathy (IgAN) suggests that genetic factors contribute to the development of this trait. Because clinical manifestations in IgAN families are often limited to episodic haematuria, large kindreds tractable to linkage analysis have been difficult to identify. METHODS: We identified a large Lebanese-Druze kindred ascertained via an index case with biopsy-documented IgAN. We performed systematic screening of 38 family members and tested linkage to reported IgAN loci. RESULTS: Screening of this family identified 16 affected individuals, including 2 individuals with biopsy-documented IgAN and 14 with chronic renal failure or abnormal urinalyses on at least three separate occasions. This kindred spanned five generations and contained five consanguineous unions. Multigenerational inheritance suggested that autosomal dominant inheritance was most likely. Phenotypic manifestations among affected individuals varied from isolated haematuria to advanced renal failure necessitating transplantation; one instance of IgAN recurrence after transplantation was also documented. Older age was associated with greater severity of disease and higher incidence of renal failure. Parametric and non-parametric analyses with 33 microsatellite markers did not reveal any evidence of linkage to reported IgAN loci on chromosomes 6q22-23, 2q36 and 4q22-31. CONCLUSIONS: We describe one of the largest multigenerational IgAN kindreds reported to date. The high incidence of renal failure among older generations suggests a significant risk of progression to renal failure. We found no evidence of linkage to known loci, suggesting that familial IgAN encompasses multiple subtypes that will require distinction based on genetic or biomarker data.