Use of CFTR Modulators for Cystic Fibrosis in a Patient with Liver Transplant and ESRD on Hemodialysis.

Cystic fibrosis is an autosomal recessive disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most recent therapeutic approach to cystic fibrosis aims to correct structural and functional abnormalities of CFTR protein. CFTR modulators including ivacaftor-tezacaftor-elexacaftor are used in patients with F508del mutation, with clinical improvement. To date, there are no experiences of CFTR modulator therapy in cystic fibrosis patients with organ transplantation and severe renal impairment. We report the case of a patient diagnosed with cystic fibrosis with F508del mutation, who underwent liver transplantation at the age of 19 and started hemodialysis at the age of 24 due to end-stage renal disease secondary to membranous glomerulonephritis. She was treated with Kaftrio (ivacaftor-tezacaftor-elexacaftor) with clinical benefits on appetite, improvement of body mass index, and reduction of pulmonary exacerbations. A reduction of dosage to 75% of the standard dose was required due to alterations of the liver function. Conclusions. Use of CFTR modulators in patient with cystic fibrosis, liver transplant and end-stage renal disease could be considered safe but a clinical and laboratoristic monitoring of hepatic function is needed.

[Acute kidney injury in severely burned patient: prevention and treatment].

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF). The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena.

Efficacy of SARS-CoV-2 Vaccination in Dialysis Patients: Epidemiological Analysis and Evaluation of the Clinical Progress.

This study investigated the impact of the fourth COVID-19 pandemic wave on dialysis patients of Romagna territory, assessing the associations of vaccination status with infection risk, clinical severity and mortality. From November 2021 to February 2022, an epidemiological search was conducted on 829 patients under dialysis treatment for at least one month. The data were then analyzed with reference to the general population of the same area. A temporal comparison was also carried out with the previous pandemic waves (from March 2020 to October 2021). The epidemiological evolution over time in the dialysis population and in Romagna citizens replicated the global trend, as the peak of the fourth wave corresponded to the time of maximum diffusion of omicron variant (B.1.1.529). Of 771 prevalent dialysis patients at the beginning of the study, 109 (14.1%) contracted SARS-CoV-2 infection during the 4-month observation period. Vaccine adherence in the dialysis population of the reference area was above 95%. Compared to fully or partially vaccinated subjects, the unvaccinated ones showed a significantly higher proportion of infections (12.5% vs. 27.0% p = 0.0341), a more frequent need for hospitalization (22.2% vs. 50.0%) and a 3.3-fold increased mortality risk. These findings confirm the effectiveness of COVID-19 vaccines in keeping infectious risk under control and ameliorating clinical outcomes in immunocompromised patients.

Too bad to be true: pseudo-AKI due to traumatic bladder rupture.

Acute Kidney Injury (AKI) is described as a rapid decline in Glomerular Filtration Rate (GFR), reflected by an increase in serum creatinine (SCr) and/or contraction of diuresis. The traditional paradigm considers pre-renal, renal and post-renal causes of AKI. However, there are some settings in which an elevated SCr does not reflect a real decline in GFR. Here we describe the case of a pseudo-AKI, consequence of a massive intraperitoneal urinary leakage due to a traumatic bladder rupture. Besides the pathophysiological considerations, we want to raise awareness about this condition, especially in relation to patients presenting with oliguria, hematuria, apparent AKI, abdominal pain and ascites, particularly after trauma; we do this not only to prevent late diagnosis complications, but also to avoid costly and risky overtreatment.

COVID-19 incidence and mortality in non-dialysis chronic kidney disease patients.

Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.

[Metformin-associated lactic acidosis]. / Incidenza di acidosi lattica in corso di terapia con metformina. 15 mesi di osservazione.

INTRODUCTION: Metformin is the first choice drug in type II diabetes. This drug has a renal excretion and its use requires caution in a setting of glomerular filtration rate reduction; an accumulation can be associated with a lactic acidosis, complication burden with a high rate mortality. METHODS: In a user base of 390.000 people we reviewed all the cases of metformin-associated lactic acidosis treated at the First Aid in a 15 months period; we considered the patients characteristics, their risk factors and the outcome. RESULTS: We observed 11 cases (incidence 60/year/100.000 patients). 10 had an acute renal failure due to dehydration. None had absolute contraindications to metformin, but most of the patients had at least one risk factor for acute kidney injury. 10 patients had been treated with hemodialysis. The total mortality rate was 36%. CONCLUSIONS: In our experience we found a higher incidence compared to literature, probably because of the widespread use of this drug in more and more fragile patients. We confirm the need of a strict adherence to prescription with a specific attention, not only to renal function, but also to the concomitant presence of risk factors (age over 80, use of Ace-inhibitors, angiotensin receptor blockers and diuretics). We draw the attention to the importance of acute clinical events and we reaffirm the need of an adequate education of the patient and his relatives for a better management of the acute event.

Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy.

BACKGROUND: In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT). METHODS: This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals. RESULTS: The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group. CONCLUSIONS: Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study.

BACKGROUND: We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-alpha-galactosidase A (rh-alpha-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population. METHODS: Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-alpha-Gal A, agalsidase beta, 1 mg/kg of body weight every 2 weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18 months. RESULTS: Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2 months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients. CONCLUSION: Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1 mg/kg every 2 weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population.