Bone impairment in primary hyperoxaluria: a review

Abstract

Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria (PH). Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains, and specific oxalate osteopathy on X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction corresponding to an invasion of bone surface by macrophages. The objective of this manuscript is therefore to provide an overview of bone impairment in PH, by reviewing the current literature on bone and dental symptoms as well as imaging techniques used for assessing bone disease.

Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

“…A long-recognized clinical observation is the overlap of phenotypic features that at times leads to difficulty delineating ARPKD from ADPKD in pediatric patients[3,5,16]. Data now reveal that the pathophysiology of the two diseases have significant overlap.…”

“…ARPKD (OMIM 263200) belongs to a group of congenital hepatorenal fibrocystic diseases characterized by dual renal and hepatic involvement[1-5]. ARPKD has an incidence estimated at 1/20000 to 1/40000 with a wide spectrum of phenotypic expression[2,4-6].…”

“…ARPKD has an incidence estimated at 1/20000 to 1/40000 with a wide spectrum of phenotypic expression[2,4-6]. ARPKD occurs as the result of a mutations in a single gene, polycystic kidney and hepatic disease 1 ( PKHD1 )[7,8]; encodes a protein called fibrocystin or polyductin (FPC)[9,10]; and is commonly diagnosed in utero through early childhood[2,3,5]. …”

“…Recent investigations at the cellular and molecular level provide compelling rationale for this clinical observation as ARPKD and ADPKD share many common pathophysiological features[2,5,16]. Such studies reveal: (1) PKHD1, PKD1 and PKD2 proteins are expressed in multimeric “cystoprotein” complexes at specific locations within epithelial cells[5,17-19]; (2) complex interactions between all three genes and their protein products occur at a molecular and cellular level[15,20-23]; (3) cyst formation not only requires a PKD mutation but also requires simultaneous cell proliferation; (4) cyst development in both ARPKD and ADPKD begins in utero [24-26]; and (5) clinical manifestations of both disorders are seen in newborns, children, and adolescents[3,5,27-30]. These findings suggest that therapeutic interventions at an early stage of disease may provide the best opportunity for beneficial long-term clinical outcomes for patients with PKD[3,5,31].…”

Bone impairment in oxalosis: An ultrastructural bone analysis

“…Patients with PH1 -and less frequently patients with PH2 -can present with severe impaired renal function, and thus systemic oxalosis and bone damage [2]. From a clinical point of view, they can experience severe bone pain, pathological fractures and bone deformations [10]. Although regarded as the reference standard for bone evaluation, iliac crest bone biopsy is an invasive procedure that cannot be recommended for routine follow-up [11].…”