SARS-CoV-2 infection in kidney transplant recipients: Experience of the italian marche region.

BACKGROUND: Infection related to Coronavirus-19 (CoV-2) is pandemic affecting more than 4 million people in 187 countries worldwide. By May 10, 2020, it caused more than 280 000 deaths all over the world. Preliminary data reported a high prevalence of CoV-2 infection and mortality due to severe acute respiratory syndrome related CoV-2 (SARS-CoV-2) in kidney-transplanted patients (KTRs). Nevertheless, the outcomes and the best treatments for SARS-CoV-2-affected KTRs remain unclear. METHODS: In this report, we describe the clinical data, the treatments, and the outcomes of 5 KTRs with SARS-CoV-2 admitted to our hospital in Ancona, Marche region, Italy, from March 17 to present. Due to the severity of SARS-CoV-2, immunosuppression with calcineurin inhibitors, antimetabolites, and mTOR-inhibitors were stopped at the admission. All KTRs were treated with low-dose steroids. 4/5 KTRs were treated with hydroxychloroquine. All KTRs received tocilizumab up to one dose. RESULTS: Overall, the incidence of SARS-CoV-2 in KTRs in the Marche region was 0.85%. 3/5 were admitted in ICU and intubated. One developed AKI with the need of CRRT with Cytosorb. At present, two patients died, two patients were discharged, and one is still inpatient in ICU. CONCLUSIONS: The critical evaluation of all cases suggests that the timing of the administration of tocilizumab, an interleukin-6 receptor antagonist, could be associated with a better efficacy when administered in concomitance to the drop of the oxygen saturation. Thus, in SARS-CoV-2-affected KTRs, a close biochemical and clinical monitoring should be set up to allow physicians to hit the virus in the right moment such as a sudden reduction of the oxygen saturation and/or a significant increase in the laboratory values such as D-dimer.

[Diagnosis of Alport syndrome]. / Il percorso diagnostico della sindrome di Alport e della malattia a membrane basali sottili.

Diagnosis of Alport syndrome or Thin basement membrane disease is suggested first of all by the clinical picture, the presence of neurisensorial hypoacusia and/or ocular abnormalities, and the family history which should be as accurate as possible involving the largest number possible of family members to recognize the transmission modalities, i.e. X-linked or autosomal. Renal biopsy remains the main tool to confirm the diagnosis and requires electron microscopy observation and collagen IV alpha chains investigation on renal tissue by means of specific antibodies. Skin biopsy is a useful and less invasive tool in families with X-linked Alport syndrome and can substitute renal biopsy in childhood as well as in patients with contraindication to renal biopsy. Confocal microscopy is mandatory to reduce the risk of false negative results in patients with segmental expression of alpha chains. Genetic analysis is at present indicated for studying subjects at risk for family planning or possible kidney donation but new techniques (Next Generation Sequencing) might increase their use in clinical practice.

m-TOR inhibitors may be useful in the treatment of encapsulating peritoneal sclerosis (EPS).

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of long-term peritoneal dialysis, often occurring after patients have been shifted to haemodialysis or undergone renal transplantation. EPS is still associated with high morbidity and mortality but, although various treatment modalities have been tried, the optimal therapy is still debated. The present paper reports a 16-year-old patient who developed EPS 6 months after shifting to haemodialysis and, following adhesiolysis, was successfully treated with a combination of steroids, tamoxifen and everolimus, this last drug chosen for its antiproliferative effect through mammalian target of rapamycin (mTOR) inhibition and its ability to block vascular endothelial growth factor and neoangiogenesis. EPS progressively improved and the patient successfully underwent renal transplantation 5 years later. The case suggests that, in view of their mechanism of action, mTOR inhibitors should be considered as an immunosuppressive agent after renal transplantation in patients at risk and merit investigation in future trials on this condition.

[Prevention of chronic allograft nephropathy]. / Prevenzione della nefropatia cronica del rene trapiantato.

Chronic allograft nephropathy, characterized by interstitial fibrosis and tubular atrophy, is one of the main causes of allograft failure in the long term. It may be induced by several factors, immunogical or not in nature, which nephrologists must recognize in order to establish the appropriate treatment strategy and prevent progressive loss of graft function. Extensive use of graft biopsy, whether carried out by protocol or suggested by the clinical setting, is recommended for an accurate diagnosis of renal lesions and prompt identification of calcineurin inhibitor-induced toxicity or signs of immunological activity (i.e., subclinical rejection or chronic antibody-mediated rejection) requiring changes of immunosuppressive strategy.

[Kidney transplant: a mere stage of CKD?]. / Il trapianto è uno stato di malattia renale?

At present, renal transplantation is the best treatment for end-stage renal disease but not the cure. The main factors limiting a full recovery after transplantation include the need for lifelong immunosuppressive therapy (which may lead to severe side effects in the long term), and only partial recovery of renal function after grafting. The latter event is not infrequent nowadays due to the increasing age of donors, who frequently die of cerebrovascular accidents and may have subclinical renal vascular lesions despite a GFR >60 mL/min, with increased susceptibility to calcineurin inhibitor toxicity. As a consequence, uremic alterations such as anemia, arterial hypertension and bone disease may persist at various degrees after surgery and affect the patients' outcome in the long term. The outcome of renal transplantation may be improved if, in addition to accurate tuning of immunosuppressive regimens, we take into account the prevention and treatment of all conditions that may impair the clinical course of transplant recipients.