Le iperossalurie

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Pubblicato il 10 novembre 2016

The Hyperoxalurias

Le iperossalurie

The Hyperoxalurias

Martino Marangella¹, Michele Petrarulo², Francesca Bermond³, Cristina Marcuccio³, Corrado Vitale³

(1) Fondazione Scientifica Mauriziana ONLUSS.C.
(2) Laboratorio Centrale A.O. Ordine Mauriziano
(3) Nefrologia e Dialisi. A.O. Ordine Mauriziano, Torino

Corrispondenza a: Martino Marangella; corso De Nicola 26. 10129 Torino; Tel: +39 0113049977; E-mail: mmarangella@alice.it

Abstract

L’ossalato (Ox), un end-product metabolico, deriva la sua importanza dalla scarsa solubilità del sale di calcio nei liquidi biologici. Circa il 70% dei calcoli renali contiene Ox e l’iperossaluria (HOx), definita come escrezione urinaria >0.5 mmol/die, è causa di nefrolitiasi/nefrocalcinosi. Può essere classificata come: dietetica (DX), enterica (EH), primitiva (PH).

La DH è spesso associata a basso intake di calcio. Infatti l’assorbimento frazionale di Ox, in genere < 10%, aumenta fino ad oltre il 20% con calcio dietetico inferiore a 200 mg/die.

La EH consegue alla riduzione del calcio intestinale saponificato dagli acidi grassi non assorbiti. Ox forma complessi più solubili e determina HOx. Un meccanismo analogo opera nelle HOx conseguenti a chirurgia bariatrica.

Le PH sono le forme più severe. Tre tipi sono stati fin qui descritti, tutti a trasmissione autosomica recessiva. PH1 consegue a mutazioni di AGXT che codifica per alanina-gliossilato aminotransferasi epatica, PH2 a mutazioni di GR/HPR che codifica per gliossilato reduttasi e PH3 a mutazioni di HOGA1 che codifica per 4-idrossi-1-ossoglutarato aldolasi. La PH è causata dall’accumulo di gliossilato poi ossidato ad Ox. Le diverse PH hanno diversa severità anche se clinicamente non sono sempre distinguibili. Vengono identificate con indagine biochimica e genetica e, per la PH1, sono state stabilite buone correlazioni genotipo/fenotipo. Grazie alla diagnosi precoce, cruciale per la prevenzione della progressione verso l’IRC e per la scelta di una corretta strategia di trapianto, la prognosi dei pazienti con PH è drammaticamente migliorata negli ultimi anni, con buone prospettive derivanti da nuovi strumenti terapeutici.

Abstract

Oxalate (Ox) is an end-product of metabolism, important for poor solubility of its calcium salt in biological fluids. Ox can therefore be found in about 70% of urinary calculi. Hyperoxaluria (HOx) defined as Ox exceeding 0.5 mmol)/day, may cause nephrolithiasis/nephrocalcinosis and may be classified as dietary (DH), enteric (EH) or primary (PH).

Fractional intestinal absorption of Ox is less than 10%, but increases to over 20% at calcium intakes below 200 mg/day. DH is often related to low-calcium diets.

EH is caused by non-absorbed fatty acids which bind to calcium and lower its concentration in the intestinal lumen. Ox forms more soluble complexes with other cations and results in HOx. Similar mechanisms may cause HOx following bariatric surgery.

PHs are the most severe causes of HOx. Three types have so far been described, all being autosomic recessive. PH1 is due to mutations of AGXT gene encoding liver alanine-glyoxylate aminotransferase, PH2 is caused by mutations of GR-HPR gene encoding glyoxylate reductase and PH3 by mutations of HOGA1 encoding for hydroxyl-oxoglutarate aldolase. HOx results from deficient detoxification from glyoxylate, which is oxidized to Ox. The three PHs have different severity, though not always clinically distinguishable. They are identified through genetics and, in PH1, good genotype/phenotype correlations have been established. Thanks to early biochemical and genetic diagnosis, which are crucial to either prevent progression to ESRF or choose adequate transplantation strategies, the outlook of PH patients has dramatically improved in the last decades and will furtherly do in view of new therapeutic strategies.

Tabella 1. Valori normali di ossaluria in relazione all’età

Fasce d’età	Ossaluria (µmol/mmol Cr)
0-6 mesi	325-360
7-24 mesi	132-174
2-5 anni	98-101
5-15 anni	70-82
< 16 anni	< 50

Tabella 3. Metabolismo ed handling renale dell’Ox

Parametro	Unità di Misura	Media ± DS/Range
Plasma	µmol/L	1.61 ± 0.46
Urine	mmol/24 ore	0.27 ± 0.16
Clearance renale	mL/min	126 ± 42
Clearance frazionale	%	108 ± 46
Assorbimento intestinale	14C-Ox (%)	14.4 ± 1.4
Produzione endogena	mmol (%)	15-20 (40-50%)
Catabolismo dell’acido ascorbico	mmol (%)	10-12 (40%)
Dieta	mmol (%)	3-6 (10-20

Tabella 4. Differenti caratteristiche cliniche e biochimiche nelle PH

Variabile	PH1	PH2	PH3	NON MUT	P
Età di presentazione	5.2	7.4	2.6	11.5	<0.01
Nefrocalcinosi (%)	49	5	1	5	<0.0001
uOx (mmol/1.73 m2)	1.8	1.7	1.1	1.2	<0.0001
uGlicolato (mg/g uCr)	102	28	18	33	<0.0001
uGlycerato (mg/g uCr)	3.0	785	1.0	7.0	<0.0001

Modificata da ref. 14.

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Contenuti articolo

release 1
pubblicata il 10 novembre 2016
Da

Martino Marangella¹, Michele Petrarulo², Francesca Bermond³, Cristina Marcuccio³, Corrado Vitale³

(1) Fondazione Scientifica Mauriziana ONLUSS.C.
(2) Laboratorio Centrale A.O. Ordine Mauriziano
(3) Nefrologia e Dialisi. A.O. Ordine Mauriziano, Torino

Corrispondenza a: Martino Marangella; corso De Nicola 26. 10129 Torino; Tel: +39 0113049977; E-mail: mmarangella@alice.it

Parole chiave: Iperossaluria, Nefrocalcinosi, nefrolitiasi, Ossalosi, Trapianto fegato rene

Key words: Hyperosaluria, Liver kidney transplantation, Nephrocalcinosis, nephrolithiasis, Oxalosis

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