Crosstalk mechanisms between glomerular endothelial cells and podocytes in renal diseases and kidney transplantation.

The glomerular filtration barrier (GFB), composed of endothelial cells, glomerular basement membrane, and podocytes, is a unique structure for filtering blood while detaining plasma proteins according to size and charge selectivity. Structurally, the fenestrated endothelial cells, which align the capillary loops, are in close proximity to mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and are separated from the endothelial compartment by the glomerular basement membrane. Podocyte-endothelial cell communication or crosstalk is required for the development and maintenance of an efficient filtration process in physiological conditions. In pathological situations, communication also has an essential role in promoting or delaying disease progression. Podocytes and endothelial cells can secrete signaling molecules, which act as crosstalk effectors and, through binding to their target receptors, can trigger bidirectional paracrine or autocrine signal transduction. Moreover, the emerging evidence of extracellular vesicles derived from various cell types engaging in cell communication has also been reported. In this review, we summarize the principal pathways involved in the development and maintenance of the GFB and the progression of kidney disease, particularly in kidney transplantation.

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.

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.

Misidentification of epithelial renal tubular cells as decoy cells in the urinary sediment of a kidney transplant recipient: the importance of adequate clinical information.

The examination of the urinary sediment of a kidney transplant recipient, carried out in blind conditions, showed the presence of a moderate number of cells which were identified as decoy cells. Most frequently these cells are a marker of BK polyomavirus reactivation, which can lead to BK virus nephropathy and graft loss. However, the patient's clinical history, the absence of BK viremia, and the renal biopsy findings excluded this condition. The careful examination of the renal biopsy demonstrated a severe tubular damage with cells resembling those identified in the urine as decoy cells. This paper is the first which demonstrates that damaged renal tubular epithelial cells can be misidentified as decoy cells. In addition, it highlights the importance of supplying adequate clinical information for a correct urinary sediment examination.

Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients.

BACKGROUND: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). METHODS: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV-). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). RESULTS: 25(OH)D levels were lower in COV+ than in controls [19(12-26) vs. 23(17-31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5-0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP- [17(8-25) vs. 20(15-26) ng/mL, p = 0.19] and between D+ and D- [14(6-23) vs. 20(14-26) ng/mL, p = 0.22] and had no significant correlation with disease length. CONCLUSIONS: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.

Bone Effect and Safety of One-Year Denosumab Therapy in a Cohort of Renal Transplanted Patients: An Observational Monocentric Study.

In 32-kidney transplanted patients (KTxps), the safety and the effects on BMD and mineral metabolism (MM) of one-year treatment with denosumab (DB) were studied. Femoral and vertebral BMD and T-score, FRAX score and vertebral fractures (sVF) before (T0) and after 12 months (T12) of treatment were measured. MM, renal parameters, hypocalcemic episodes (HpCa), urinary tract infections (UTI), major graft and KTxps outcomes were monitored. The cohort was composed mainly of females, n = 21. We had 29 KTxps on steroid therapy and 22 KTxps on vitamin D supplementation. At T0, 25 and 7 KTxps had femoral osteoporosis (F-OPS) and osteopenia (F-OPS), respectively. Twenty-three and six KTxps had vertebral osteoporosis (V-OPS) and osteopenia (V-OPS), respectively. Seventeen KTxps had sVF. At T12, T-score increased at femoral and vertebral sites (p = 0.05, p = 0.008). The prevalence of F-OPS and V-OPS reduced from 78% to 69% and from 72% to 50%, respectively. Twenty-five KTxps ameliorated FRAX score and two KTxps had novel sVF. At T12, a slight reduction of Ca was present, without HpCa. Four KTxps had UTI. No graft rejections, loss of graft or deaths were reported. Our preliminary results show a good efficacy and safety of DB in KTxps. Longer and randomized studies involving more KTxps might elucidate the possible primary role of DB in the treatment of bone disorders in KTxps.

Membranous Nephropathy (MN) Recurrence After Renal Transplantation.

Primary membranous nephropathy (MN) is a frequent cause of NS in adults. In native kidneys the disease may progress to ESRD in the long term, in some 40-50% of untreated patients. The identification of the pathogenic role of anti-podocyte autoantibodies and the development of new therapeutic options has achieved an amelioration in the prognosis of this disease. MN may also develop in renal allograft as a recurrent or a de novo disease. Since the de novo MN may have some different pathogenetic and morphologic features compared to recurrent MN, in the present paper we will deal only with the recurrent disease. The true incidence of the recurrent form is difficult to assess. This is mainly due to the variable graft biopsy policies in kidney transplantation, among the different transplant centers. Anti-phospholipase A2 receptor (PLA2R) autoantibodies are detected in 70-80% of patients. The knowledge of anti-PLA2R status before transplant is useful in predicting the risk of recurrence. In addition, the serial survey of the anti-PLA2R titers is important to assess the rate of disease progression and the response to treatment. Currently, there are no established guidelines for prevention and treatment of recurrent MN. Symptomatic therapy may help to reduce the signs and symptoms related to the nephrotic syndrome. Anecdotal cases of response to cyclical therapy with steroids and cyclophosphamide have been published. Promising results have been reported with rituximab in both prophylaxis and treatment of recurrence. However, these results are based on observational data, and prospective controlled trials are still missing.