Management of Primary Hyperoxaluria Type 1 in Italy

Abstract

Primary hyperoxaluria type 1 is a rare genetic disease; the onset of symptoms ranges from childhood to the sixth decade of life and the disease may go unrecognized for several years. There is an urgent need for drugs able to inhibit the liver production of oxalate and to prevent the disease progression; lumasiran, an innovative molecule based on RNAi interference, is one of the most promising drugs. A group of leading Italian experts on this disease met to respond to some unmet medical needs (early diagnosis, availability of genetic tests and dosage of plasma oxalate, timing of liver transplantation, need for etiologic treatment), based on the analysis of the main scientific evidence and their personal experience. Children showing the characteristic symptoms of the disease usually undergo a metabolic screening and obtain an early diagnosis, while the experience is very limited in adults and the diagnosis difficult. It is therefore essential to increase the knowledge around this disease and the importance of metabolic and genetic screening to define a checklist of shared clinical and laboratory criteria and to establish a multidisciplinary management of potential patients. Oxalate is the cause of the disease: it is crucial to reduce both oxaluria and oxalemia through appropriate therapeutic strategies, able to prevent and/or reduce renal and systemic complications of primary type 1 hyperoxaluria. Lumasiran allows to significantly reduce the levels of oxalate both in blood and in urine, halting the course of the disease and preventing serious renal and systemic complications, if the therapy is started at an early stage of the disease.

Keywords: primary hyperoxaluria type 1, hyperoxalemia, hyperoxaluria, lumasiran

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Introduzione

L’iperossaluria primitiva tipo 1 (PH1) è una malattia genetica autosomica recessiva ultra-rara, con una prevalenza stimata di 1-3 casi per milione di popolazione e un’incidenza di circa 1 caso ogni 120.000 nati in Europa, ed è responsabile dell’1-2% dei casi di insufficienza renale terminale (ESKD) pediatrici [12].

La PH1 è causata da mutazioni nel gene AGXT che codifica per l’enzima epatico L-alanina-gliossilato amino transferasi (AGT), il quale catalizza la conversione di gliossilato a glicina. Si tratta quindi di un difetto metabolico epatico. Quando l’attività della AGT è assente, il gliossilato viene trasformato in ossalato, la cui iperproduzione determina aumento dei livelli ematici di ossalato ed iperossaluria aumentando il rischio di nefrolitiasi (figura 1) [2].

 

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Recurrent Kidney Stones in a patient with Malabsorption Syndrome

Abstract

Enteric hyperoxaluria is one of the most frequent complications of bariatric surgery. In this setting the prevalence of kidney stones is increased. Currently the treatment of enteric hyperoxaluria is based not only on the reduction of urinary oxalate but even controlling other lithogenic risk factors, like urinary volume and urinary citrate levels.

This case report suggests a possible benefit using magnesium citrate in addition to calcium supplementation, in the treatment of hyperoxaluria caused by enteric malabsorption.

 

Keywords: kidney stones, hyperoxaluria, magnesium citrate

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INTRODUZIONE

L’ossalato è un prodotto di scarto del metabolismo, generato da una varietà di precursori. Approssimativamente il 50-60% di esso è prodotto endogenamente, la restante quota proviene dall’intake dietetico (1).

 

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Nephrocalcinosis in children

Abstract

Nephrocalcinosis (NC) is a renal disease characterized by  deposition of calcium salts into the renal medulla. There are several causes, organic, iatrogenic, hereditary and sometimes related to extrarenal diseases. We studied 34 children affected by  NC, 21 M and 13 F (average age at diagnosis 7.8 months), with the aim of analyzing the associated diseases, clinical manifestations, metabolic abnormalities, growth and renal function at onset and after follow-up. At onset 70% of patients were asymptomatic and diagnosis was occasional. Renal function was normal in 33 patients. The most frequent clinical symptoms were: failure to thrive (9%), abdominal pain (6%), proteinuria/hematuria (7%). The associated diseases  were: tubulopathies (8 pcs – tubular acidosis, Dent, Bartter and Lowe Syndromes), medullary sponge kidney, policalicosis (3 pcs ), Short bowel Syndrome (3 pcs), hyperparathyroidism, hypothyroidism (2 pcs), thalassemia (1pc), tyrosinemia (1 pc.). We recognized two forms of hypervitaminosis D. In a pc NC would be correlated with prematurity, another one with lipid necrosis. Among the metabolic abnormalities, observed in 25% of pcs, hyperoxaluria is the most frequent (47%), hypercalciuria (20%), hypercalcemia (15%). In some cases we found endocrine non pathogenic alterations: hypovitaminosis D (2 pcs) and hypoparathyroidism (6 pcs). During follow-up  the growth was normal in 87% of cases and glomerular function was stable in 90% of pcs; IRC developed in 3 cases. From our analysis, it appears that the treatment of the underlying condition of NC is associated with catch-up growth and stabilization of renal function in most patients, but not with the reduction of the degree of the NC.

Keywords: nephrocalcinosis, tubulopathies, hyperoxaluria, ultrasound, growth, renal function

Sorry, this entry is only available in Italian. For the sake of viewer convenience, the content is shown below in the alternative language. You may click the link to switch the active language.

INTRODUZIONE

La nefrocalcinosi (NC) è un quadro morfologico renale caratterizzato da aumentato deposito di calcio a livello del parenchima renale, più spesso a carico della midollare o della giunzione cortico-midollare, con accumuli di materiale cristallino all’apice delle piramidi renali che possono coinvolgere le cellule tubulari, l’interstizio o il lume tubulare (1). Le cause possono essere associate a: iperparatiroidismo, iper- ed ipotiroidismo, acidosi tubulare distale, iperossaluria ; S. di Bartter, S. di Dent, S. di Lowe, Rene a spugna midollare, M. di Wilson, tirosinemia, fibrosi cistica, anemia mediterranea, S. di Cushing, anemia falciforme, Ipomagnesiemia familiare con ipercalciuria; patologie iatrogene (diuretici, intossicazione da Vitamina D, Nutrizione parenterale , amfotericina B, Sindrome da intestino corto);  necrosi corticale renale e miscellanea di altre patologie che non sempre riguardano il rene. 

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