Urinary Saturations in Children with or without Renal Lithiasis.

INTRODUCTION: In lithogenesis, for a stone to form it is necessary that the urine is supersaturated with respect to the salt that will constitute the future stone. The objective was to analyze the urinary saturations of Calcium Oxalate (CaOxa), brushite (calcium phosphate), struvite (ammonium-magnesium phosphate) and uric acid (UA) in children with and without lithiasis. Correlate them with the different parameters involved in the lithiasic process. And compare saturations in children with or without overweight. MATERIAL AND METHODS: We examined 108 healthy children and 53 patients diagnosed with lithiasis. In 24-h urine, the different biochemical parameters involved in lithiasis and the saturation levels of CaOxa, brushite, struvite and UA. RESULTS: We studied 108 healthy children with a mean age of 9.5 ± 3.9 years. Renal lithiasis was diagnosed in 53 patients with an average age of 10.5 ± 5.8 years. Children with lithiasis had higher saturation values of CaOxa (4.86 ± 2.71 vs. 3.15 ± 1.99, p < 0.01) and brushite (1.58 ± 1.23 vs. 0.86 ± 0.81, p < 0.001) compared to non-lithiasic children. UA saturation was higher in children with body mass index greater than 22 (5.25 ± 3.52 vs. 3.84 ± 3.5, p < 0.04). Finally, urinary pH, ammonium concentration and uricosuria influenced UA saturation. that the urinary pH regression coefficient in the uric acid saturation regression analysis was -4.5. CONCLUSIONS: The mean values of calcium oxalate and brushite saturations were higher in children with lithiasis. Uric acid saturation was elevated in overweight children. Finally, urinary pH greatly influenced uric acid saturation.

Urinary Saturations in Children with or without Renal Lithiasis

Introduction: In lithogenesis, for a stone to form it is necessary that the urine is supersaturated with respect to the salt that will constitute the future stone. The objective was to analyze the urinary saturations of Calcium Oxalate (CaOxa), brushite (calcium phosphate), struvite (ammonium-magnesium phosphate) and uric acid (UA) in children with and without lithiasis. Correlate them with the different parameters involved in the lithiasic process. And compare saturations in children with or without overweight. Material and Methods: We examined 108 healthy children and 53 patients diagnosed with lithiasis. In 24-h urine, the different biochemical parameters involved in lithiasis and the saturation levels of CaOxa, brushite, struvite and UA. Results: We studied 108 healthy children with a mean age of 9.5 ± 3.9 years. Renal lithiasis was diagnosed in 53 patients with an average age of 10.5 ± 5.8 years. Children with lithiasis had higher saturation values of CaOxa (4.86 ± 2.71 vs. 3.15 ± 1.99, p < 0.01) and brushite (1.58 ± 1.23 vs. 0.86 ± 0.81, p < 0.001) compared to non-lithiasic children. UA saturation was higher in children with body mass index greater than 22 (5.25 ± 3.52 vs. 3.84 ± 3.5, p < 0.04). Finally, urinary pH, ammonium concentration and uricosuria influenced UA saturation. that the urinary pH regression coefficient in the uric acid saturation regression analysis was –4.5. Conclusions: The mean values of calcium oxalate and brushite saturations were higher in children with lithiasis. Uric acid saturation was elevated in overweight children. Finally, urinary pH greatly influenced uric acid saturation (AU)

Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) almost invariably progresses to end-stage renal disease. Although more than 50 monogenic causes of SRNS have been described, a large proportion of SRNS remains unexplained. Recently, it was discovered that mutations of NUP93 and NUP205, encoding 2 proteins of the inner ring subunit of the nuclear pore complex (NPC), cause SRNS. Here, we describe mutations in genes encoding 4 components of the outer rings of the NPC, namely NUP107, NUP85, NUP133, and NUP160, in 13 families with SRNS. Using coimmunoprecipitation experiments, we showed that certain pathogenic alleles weakened the interaction between neighboring NPC subunits. We demonstrated that morpholino knockdown of nup107, nup85, or nup133 in Xenopus disrupted glomerulogenesis. Re-expression of WT mRNA, but not of mRNA reflecting mutations from SRNS patients, mitigated this phenotype. We furthermore found that CRISPR/Cas9 knockout of NUP107, NUP85, or NUP133 in podocytes activated Cdc42, an important effector of SRNS pathogenesis. CRISPR/Cas9 knockout of nup107 or nup85 in zebrafish caused developmental anomalies and early lethality. In contrast, an in-frame mutation of nup107 did not affect survival, thus mimicking the allelic effects seen in humans. In conclusion, we discovered here that mutations in 4 genes encoding components of the outer ring subunits of the NPC cause SRNS and thereby provide further evidence that specific hypomorphic mutations in these essential genes cause a distinct, organ-specific phenotype.