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.

[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.

Patients' direction, empowerment and quality of life in haemodialysis.

The maintenance of an adequate of quality of life (QoL) represents a critical issue in the management of patients in haemodialysis and is also used to assess the effectiveness of health care programmes. The Consumer Direction Theory of Empowerment (CDTE) implies that greater patient direction in policy formulation and services delivery, together with an increased community integration, endorses a process which leads to a better QOL. The aim of the study was to test a contextualized version of CDTE in an ambulatory for patients in haemodialysis. Sixty-nine patients completed a questionnaire measuring the following variables: Patient direction, family integration, self-efficacy in managing the disease, mental and physical health. The results showed that patient direction and family integration have an indirect effect on QoL, through self-efficacy in managing the disease. The hypotheses were thus confirmed, providing support for the potential of CDTE in the context of health services for haemodialysis patients. Implications for the implementation of health programmes aimed at improving QoL of patients in haemodialysis are discussed, including interventions focused on psychological and contextual factors.

[Renal involvement in monoclonal gammopathy and multiple myeloma]. / Il coinvolgimento renale nelle gammopatie monoclonali e nel mieloma.

Lymphoproliferative disorders often involve the kidney either by direct cell infiltration (lymphoma) or by deposition of paraproteins (monoclonal gammopathy, multiple myeloma, LCDD, amyloidosis). Nowadays the latter phenomenon seems to be the most common as a result of the growing number of elderly people affected by monoclonal gammopathies. The nephrotoxic potential of monoclonal immunoglobulins and amyloidogenic proteins make monoclonal gammopathies clinical entities of considerable interest in nephrology. Renal involvement presents different clinicomorphological patterns depending on the qualitative and quantitative characteristics of the paraproteins. Tubulointerstitial toxicity is frequent, while vascular and glomerular lesions resulting from non-inflammatory reactions due to immunoglobulin deposition are less common. Acute kidney failure may complicate the clinical course; this could be due to tubular obstruction by paraproteins or to hypovolemia induced by chemotherapy in association with diuretics. Early diagnosis of renal involvement will allow prophylactic interventions to prevent renal complications. At the same time, the increased number of therapeutic tools has enabled better management of kidney complications in lymphoproliferative disorders.