Clinical exome sequencing is a powerful tool in the diagnostic flow of monogenic kidney diseases: an Italian experience.

Background: A considerable minority of patients on waiting lists for kidney transplantation either have no diagnosis (and fall into the subset of undiagnosed cases) because kidney biopsy was not performed or histological findings were non-specific, or do not fall into any well-defined clinical category. Some of these patients might be affected by a previously unrecognised monogenic disease.

Methods: Through a multidisciplinary cooperative effort, we built an analytical pipeline to identify patients with chronic kidney disease (CKD) with a clinical suspicion of a monogenic condition or without a well-defined diagnosis.

Detection of Angiotensin II type I-receptor antibodies in transplant glomerulopathy.

Background: Transplant glomerulopathy (TG) is an important cause of late graft loss. The role of angiotensin type 1-receptor antibodies (AT R-Ab) in TG is not known.

Methods: All the TG cases (N = 137) between January 2007 and December 2014 (N = 1410) were analyzed.

Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

Background: Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.

Methods: To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls.

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection.

Background: Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies.

Methods: RNA extracted from archival formalin-fixed, paraffin-embedded renal biopsies was used for gene expression profiling.

Different regulatory and cytotoxic CD4+ T lymphocyte profiles in renal transplants with antibody-mediated chronic rejection or long-term good graft function.

Comparative analysis of the different subsets of CD4(+) T-lymphocytes may provide hints on the immunologic mechanisms operating in the long-term fate of a kidney transplant. We analyzed peripheral regulatory CD4(+) T cells (Tregs) and CD4(+) cytotoxic T lymphocytes (CTLs) in antibody-mediated chronic rejection (AMCR), in middle-term kidney transplants (2-4 years, MTKT) with good graft function and rejection-free history, in long-term kidney transplants (>15 years, LTKT) and in normal healthy subjects (NHS). Transplant groups with good prognosis (MTKT and LTKT) displayed a significant lower amount of CD4(+)CD25(high) T lymphocytes than NHS, with a trend of a higher percentage in AMCR than in MTKT and LTKT.

Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy.

In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements.

A case of successful pregnancy in a woman with Friedreich ataxia.

We report on a 34-year-old woman with advanced FA who achieved a successful pregnancy. The neurological and cardiological features of the disease remained unchanged during and after pregnancy. Because of a slight respiratory impairment, which appeared at the 6th month, cesarean section was performed at the 34th week.