Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies.

Mutations in COL4A3-A5 cause a spectrum of glomerular disorders, including thin basement membrane nephropathy (TBMN) and Alport syndrome (AS). The wide application of next-generation sequencing (NGS) in the last few years has revealed that mutations in these genes are not limited to these clinical entities. In this study, 176 individuals with a clinical diagnosis of inherited kidney disorders underwent an NGS-based analysis to address the underlying cause; those who changed or perfected the clinical diagnosis after molecular analysis were selected. In 5 out of 83 individuals reaching a molecular diagnosis, the genetic result was unexpected: three individuals showed mutations in collagen type IV genes. These patients showed the following clinical pictures: (1) familial focal segmental glomerulosclerosis; (2) end-stage renal disease (ESRD) diagnosed incidentally in a 49-year-old man, with diffuse cortical calcifications on renal imaging; and (3) dysmorphic and asymmetric kidneys with multiple cysts and signs of tubule-interstitial defects. Genetic analysis revealed rare heterozygote/compound heterozygote COL4A4-A5 variants. Our study highlights the key role of NGS in the diagnosis of inherited renal disorders and shows the phenotype variability in patients carrying mutations in collagen type IV genes.

Frailty in kidney transplantation: a review on its evaluation, variation and long-term impact.

The problem of frailty in kidney transplantation is an increasingly discussed topic in the transplant field, partially also generated by the multiple comorbidities by which these patients are affected. The criteria currently used to establish the presence and degree of frailty can be rapidly assessed in clinical practice, even in patients with chronic kidney disease (CKD). The main objectives of this work are: (i) to describe the method of evaluation and the impact that frailty has in patients affected by CKD, (ii) to explore how frailty should be studied in the pre-transplant evaluation, (iii) how frailty changes after a transplant and (iv) the impact frailty has over the long term on the survival of renal transplant patients.

How Vaccinations Changed the Outcome of COVID-19 Infections in Kidney Transplant Patients: Single-Center Experience.

Kidney transplant recipients are a vulnerable population at risk of a life-threatening COVID-19 infection with an incidence of death four-times higher than in the general population. The availability of mRNA COVID-19 vaccines has dramatically changed the fate of this infection also within this fragile population. Transplanted patients have an impaired immunological response also to mRNA vaccines. In March 2021, however, we started a vaccination campaign. These preliminary results show that both the incidence of death and of hospitalization dropped from 13% to 2.4% and from 45% to 12.5% compared to the previous outbreaks reported by our group. In univariate analysis, two variables were associated with an increased risk of hospitalization: older age and dyspnea (p = 0.023, p < 0.0001, respectively). In multivariate analysis, dyspnea (p < 0.0001) and mycophenolate therapy (p = 0.003) were independently associated with the risk of hospitalization. The association was even stronger when the two variables were combined (p < 0.0001). Vaccinations did not reduce the incidence of COVID-19 infections among our transplanted patients, but provided certain protection that was associated with a significantly better outcome for this infection.

Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects.

Renal transplantation (RTx) allows us to obtain the resolution of the uremic status but is not frequently able to solve all the metabolic complications present during end-stage renal disease. Mineral and bone disorders (MBDs) are frequent since the early stages of chronic kidney disease (CKD) and strongly influence the morbidity and mortality of patients with CKD. Some mineral metabolism (MM) alterations can persist in patients with RTx (RTx-p), as well as in the presence of complete renal function recovery. In those patients, anomalies of calcium, phosphorus, parathormone, fibroblast growth factor 23, and vitamin D such as bone and vessels are frequent and related to both pre-RTx and post-RTx specific factors. Many treatments are present for the management of post-RTx MBD. Despite that, the guidelines that can give clear directives in MBD treatment of RTx-p are still missed. For the future, to obtain an ever-greater individualisation of therapy, an increase of the evidence, the specificity of international guidelines, and more uniform management of these anomalies worldwide should be expected. In this review, the major factors related to post-renal transplant MBD (post-RTx-MBD), the main mineral metabolism biochemical anomalies, and the principal treatment for post-RTx MBD will be reported.

[Application of proteomics and metabolomics to study inherited kidney disorders: from big data to precision medicine].

The recent application of proteomics and metabolomics to clinical medicine has demonstrated their potential role in complementing genomics for a better understanding of diseases' patho-physiology. These technologies offer the clear opportunity to identify risk factors, disease-specific or stage-specific biomarkers and to predict therapeutic response. This article is an overview of the recent insights obtained by metabolomic and proteomic studies in inherited kidney disorders. Proteomics studies have allowed the definition of a detailed picture of protein composition, post-translational modifications and interactions in kidney-derived samples, improving our understanding of renal physiology, especially of tubular transport and primary cilium-related functions. Studies on patients' urine samples and experimental models of inherited kidney diseases have provided clues suggesting novel potential pathological mechanisms and biomarkers of disease, for example in polycystic kidney disease. Metabolomic-based studies have been recently applied to assess biological system disturbances caused by specific genetic mutations resulting in inherited kidney disorders. These studies have been mainly carried out on mouse and rat models of cystic and metabolic disorders (such as Fabry disease), and on patients' urine samples. They have provided a significant contribution in understanding disease pathophysiology, promoting the discovery of aberrant biochemical pathways and contributing to the development of targeted therapies.