Hallmarks of primary hyperoxaluria type 3 are nephrolithiasis and hyperoxaluria. However, little is known about factors influencing stone formation in this disease. We characterized stone events and ...examined associations with urine parameters and kidney function in a primary hyperoxaluria type 3 population.
We retrospectively analyzed clinical, and laboratory data of 70 primary hyperoxaluria type 3 patients enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria Registry.
Kidney stones occurred in 65/70 primary hyperoxaluria type 3 patients (93%). Among the 49 patients with imaging available, the median (IQR) number of stones was 4 (2, 5), with largest stone 7 mm (4, 10) at first imaging. Clinical stone events occurred in 62/70 (89%) with median number of events per patient 3 (2, 6; range 1-49). Age at first stone event was 3 years (0.99, 8.7). Lifetime stone event rate was 0.19 events/year (0.12, 0.38) during follow-up of 10.7 (4.2, 26.3) years. Among 326 total clinical stone events, 139 (42.6%) required surgical intervention. High stone event rates persisted for most patients through the sixth decade of life. Analysis was available for 55 stones: pure calcium oxalate accounted for 69%, with mixed calcium oxalate and phosphate in 22%. Higher calcium oxalate supersaturation was associated with increased lifetime stone event rate after adjusting for age at first event (IRR 95%CI 1.23 1.16, 1.32;
< .001). By the fourth decade, estimated glomerular filtration rate was lower in primary hyperoxaluria type 3 patients than the general population.
Stones impose a lifelong burden on primary hyperoxaluria type 3 patients. Reducing urinary calcium oxalate supersaturation may reduce event frequency and surgical intervention.
Dent disease is an X-linked recessive disorder associated with low molecular weight proteinuria (LMWP), nephrocalcinosis, kidney stones, and kidney failure in the third to fifth decade of life. It ...consists of Dent disease 1 (DD1) (60% of patients) because of pathogenic variants in the CLCN5 gene and Dent disease 2 (DD2) with changes in OCRL.
Retrospective review of 162 patients from 121 different families with genetically confirmed DD1 (82 different pathogenic variants validated using American College of Medical Genetics ACMG guidelines). Clinical and genetic factors were compared using observational statistics.
A total of 110 patients had 51 different truncating (nonsense, frameshifting, large deletions, and canonical splicing) variants, whereas 52 patients had 31 different nontruncating (missense, in-frame, noncanonical splicing, and stop-loss) changes. Sixteen newly described pathogenic variants were found in our cohort. Among patients with truncating variants, lifetime stone events positively correlated with chronic kidney disease (CKD) evolution. Patients with truncating changes also experienced stone events earlier in life and manifested a higher albumin excretion rate than the nontruncating group. Nevertheless, neither age of nephrocalcinosis nor CKD progression varied between the truncating versus nontruncating patients. A large majority of nontruncating changes (26/31; 84%) were clustered in the middle exons that encode the voltage ClC domain whereas truncating changes were spread across the protein. Variants associated with kidney failure were restricted to truncating (11/13 cases), plus a single missense variant previously shown to markedly reduce ClC-5 functional activity that was found in the other 2 individuals.
DD1 manifestations, including the risk of kidney stones and progression to kidney failure, may relate to the degree of residual ClC-5 function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ObjectivesTo compare susceptibility of five different stent platforms with longitudinal stent deformation (LSD) using a clinically relevant bench testing model simulating both short and long ...malapposed lengths.BackgroundRecent data suggest that design modifications to the Promus Element stent which led to the Promus Premier stent has reduced susceptibility to LSD. However, susceptibility to LSD at long malapposed lengths has not been tested. Furthermore, the mechanisms behind susceptibility to LSD are as yet unclear.MethodsThe Omega, Integrity, Multilink 8, Biomatrixand Promus Premier stent platforms were tested. The Omega, Integrity and Multilink 8 platforms were used in place of their drug-eluting equivalents. 3.5 mm stents were deployed in a stepped tube with the distal portion fixed and the proximal test section exposed. The force required to compress stents by a fixed distance at different exposed lengths was compared. Symmetrical and point loading were used.ResultsThe Promus Premier was longitudinally as strong as Multilink and Integrity at a short exposed length (4 mm) but weaker, in between Omega and the other platforms, at longer exposed lengths (12 mm). As previously noted, the Omega (Promus Element) platform was significantly weaker than the other stents and Biomatrix was the strongest stent.ConclusionSusceptibility to LSD varies depending on length of malapposed segment when tested using a clinically relevant model as in this study. The mechanisms behind the susceptibility are likely multifactorial, including connector number, strut thickness, connector alignment and ring orientation but remain to be elucidated.
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