Supplemented Very Low Protein Diet (sVLPD) in Patients with Advanced Chronic Renal Failure: Clinical and Economic Benefits.

The supplemented very low-protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and postponing the start of the dialysis treatment. However, sVLPD could expose the patient to the risk of malnutrition. This diet is also difficult to implement due to the required intake of large number of keto-analogue/amino acid tablets. In our Center, the Department of Nephrology and Dialysis of Azienda Sanitaria Territoriale n 1, Pesaro-Urbino, of Italy, respecting the guidelines of normal clinical practice, we prescribed sVLPD (0.3 g/prot/day) supplemented with only essential amino acids without the use of ketoanalogues in stage 5 patients and verified its efficacy, safety and clinical and economic effects. Over the 24 months period of observation the progression of chronic kidney disease (CKD) slowed down (mean eGFR 11.6 ± 3.3 vs. 9.3 ± 2.7 mL/min/1.73 m2, p < 0.001) and the start of the dialysis treatment (adjusted HR = 0.361, CI 0.200-0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant vs. non-compliant patients. This led to a substantial cost reduction for the National Health System. This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with essential amino acids could be extensively used to reduce the incidence of dialysis treatments, with a favorable economic impact on the NHS.

ANCA-Associated Glomerulonephritis and Anti-Phospholipid Syndrome in a Patient with SARS-CoV-2 Infection: Just a Coincidence?

Many reports have described a high incidence of acute kidney injury (AKI) among patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to hemodynamic instability. However, other complex processes may be involved, related to the cytokine storm and the activation of innate and adaptive immunity. Here, we describe a patient who developed an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with rapidly progressive glomerulonephritis and lung involvement and an antiphospholipid syndrome soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. After viral pneumonia was excluded by bronchoalveolar lavage, the patient has been treated with rituximab for amelioration of kidney function and resolution of thrombosis without any adverse event. We conclude that COVID-19 may trigger autoimmune diseases including ANCA-associated vasculitis. Thus, this diagnosis should be taken in consideration in COVID-19 patients, especially when they develop AKI with active urinary sediment. In addition, considering the relationship between these 2 diseases, SARS-CoV-2 infection should be excluded in all patients with a new diagnosis ANCA-associated vasculitis before starting immunosuppressive therapy.

[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.

Coronary calcifications in end-stage renal disease patients: a new link between osteoprotegerin, diabetes and body mass index?

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 +/- 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca x P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-beta1 (TGF-beta1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0-7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-beta1, OPG and days with Ca x P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.