Reducing agalsidase beta infusion time in Fabry patients: low incidence of antibody formation and infusion-associated reactions in an Italian multicenter study.

BACKGROUND: Fabry disease is a rare progressive X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A. Agalsidase beta is a recombinant enzyme replacement therapy authorized in Europe at a standard dose of 1.0 mg/kg intravenously every other week at an initial infusion rate of ≤ 0.25 mg/min until patient tolerance is established, after which the infusion rate may be increased gradually. However, specific practical guidance regarding the progressive reduction in infusion time is lacking. This study investigated a new and specific protocol for reducing agalsidase beta infusion time in which a stable dosage of 15 mg/h is infused for the first four months, and the infusion rate is increased progressively from 15 to 35 mg/h for the subsequent four infusions. The shortest infusion time is reached after six months and maintained thereafter. The incidence of infusion-associated reactions (IARs) and the development of anti-drug antibodies were analyzed, and the disease burden and the clinical evolution of the disease at 12 months were evaluated. RESULTS: Twenty-five of the 31 patients were naïve to enzyme or chaperone treatment at baseline and six patients had been switched from agalsidase alfa. The reduced infusion time protocol was well tolerated. Only one patient exhibited an IAR, with mild symptoms that resolved with low-dose steroids. Six patients globally seroconverted during treatment (4 with a classic phenotype and 2 with late-onset disease). All but three patients were seronegative at month 12. All patients were stable at the study's end (FAbry STabilization indEX value < 20%); reducing infusion time did not negatively impact clinical outcomes in any patient. The perceived medical assessment showed that the quality of life of all patients improved. CONCLUSIONS: The study demonstrates that reducing agalsidase beta infusion time is possible and safe from both an immunogenic and clinical point of view. The use of a low infusion rate in the first months when the probability of onset of the development of antibodies is higher contributed to very limited seroconversion to antibody-positive status.

[New Perspectives in Post-Surgical Acute Kidney Injury During Sepsis].

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. Sepsis is a common complication in patients undergoing surgery and is a major risk factor for the development of acute kidney injury (SA-AKI). Prevention of AKI in surgery patients is largely based on identification of high baseline risk, monitoring, and reduction of nephrotoxic insults. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches.

[Discovering uncommon nephropathies: a case of acute kidney damage from malaria].

Malaria is one of the most common infectious diseases in the world with a high prevalence in developing countries. Renal impairment occurs in 40% of Plasmodium falciparum infections; glomeruli, tubules or interstitium can be involved with different pathophysiological mechanisms. We describe a case of severe acute renal failure caused by P. falciparum malaria in a young woman from the Ivory Coast. Renal biopsy revealed severe and widespread acute tubular necrosis and the presence of blackish pigment granules in the glomerular and peritubular capillaries, negative for iron histochemical staining; in electron microscopy we found rounded-oval-shaped structures containing cytoplasmic organelles, electrondensic granules and cellular debris, likely of infectious origin, within monocyte-macrophages located in the tubular lumen. Specific Antigen for P. falciparum and malarial parasite in blood were positive, with very rare trophozoites and gametocytes compatible with Plasmodium falciparum. Steroid therapy and specific antiparasitic therapy were set up with progressive functional improvement until complete recovery. This case highlights the importance of paying maximum attention to low incidence pathologies in our country, considering the continuous migratory movements of these years that can cause an increase in these diseases; anamnestic data are essential for a timely diagnosis which can contribute to a rapid remission avoiding severe complications.

Renal Thrombotic Microangiopathy in Concurrent COVID-19 Vaccination and Infection.

We report on the development of nephrotic proteinuria and microhematuria, with histological features of renal thrombotic microangiopathy (TMA), following the first dose of BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) and COVID-19 diagnosis. A 35-year-old previously healthy man was admitted at our hospital due to the onset of foamy urine. Previously, 40 days earlier, he had received the first injection of the vaccine, and 33 days earlier, the RT-PCR for SARS-CoV-2 tested positive. Laboratory tests showed nephrotic proteinuria (7.9 gr/day), microhematuria, serum creatinine 0.91 mg/dL. Kidney biopsy revealed ultrastructural evidence of severe endothelial cell injury suggestive of a starting phase of TMA. After high-dose steroid treatment administration, complete remission of proteinuria was achieved in a few weeks. The association of COVID-19 with renal TMA has been previously described only in patients with acute renal injury. Besides, the correlation with COVID-19 vaccine has not been reported so far. The close temporal proximity (7 days) between the two events opens the question whether the histological findings should be ascribed to COVID-19 itself or to vaccine injection.

[Resilience in COVID-19 times: general considerations on the recovery of a 93-year-old patient on haemodialysis treatment].

We report the case of a 93-year-old woman on haemodialysis treatment for more than 30 months and with multiple comorbidities who recovered from a Covid-19 infection without any significant clinical problems. The patient has shown a delay in viral clearance with swab test negativization (confirmed) after 33 days; after testing positive again, she has resulted persistently negative, (confirmed after 49 days). After the first negative swab, IgG and IgM antibodies have been found; these have remained persistently positive after a month. As well as highlighting an unexpected resilience in an extremely fragile context, the analysis of this case draws attention to patients' management and, potentially, to the need to arrange dialysis treatments in isolation for some time after their "laboratory recovery".

[Dyslipidemia in Kidney transplant recipients]. / Dislipidemia post-trapianto.

The kidney transplant recipients' population shows pronounced alterations of the lipidic profile, with hypercholesterolemia (total cholesterol, LDL, VLDL), normal HDL and hypertriglyceridemia. Multiple factors contribute to the development of dyslipidemia, towards these, immunosuppressive therapy plays an important role. The impact on cardiovascular outcomes is less well defined than in general population. This work is a revaluation of the clinical approach to dyslipidemia in kidney transplant based on the more recent Guide Lines and literature. The use of statins in an adult transplanted population (eventually associated with ezetimibe) is safe and is a good compromise in terms of a cost/benefit analysis. Other hypolipidemic drugs are not usually suggested for the high incidence of side effects. Lifestyle changes are taking more and more relevance, and in the pediatric population is the only therapeutic act suggested.

[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.

[Post-transplant recurrence of glomerulonephritis: a complex clinical case]. / Recidiva di glomerulonefrite post-trapianto: un caso clinico complesso.

Lupus nephritis (LN) seldom recurs in a grafted kidney. By contrast, primary membranoproliferative glomerulonephritis (MPGN), which has been included, along with hemolytic uremic syndrome and age-related maculopathy, among the complement dysregulation diseases, has a high recurrence rate and is considered a contraindication to living-donor kidney transplant because of the poor prognosis. We report the case of a young girl with LN-related chronic renal failure who underwent a living donor transplant from her mother. After four months she had a recurrence that did not match the criteria for LN. Graft biopsies and revision of the clinical course pointed to type II MPGN on the basis of a lack of ARA criteria, persistent isolated low C3 levels, and response to plasma therapy. If confirmed by genetic analysis, the patient might benefit from treatment with the monoclonal antibody against the C5-C9 complex, eculizumab.