BACKGROUND Autosomal dominant tubulointerstitial kidney disease(ADTKD)is a progressive chronic disease that is inherited in an autosomal dominant fashion.Symptoms include hyperuricemia,gout,interstitial nephritis,rena...BACKGROUND Autosomal dominant tubulointerstitial kidney disease(ADTKD)is a progressive chronic disease that is inherited in an autosomal dominant fashion.Symptoms include hyperuricemia,gout,interstitial nephritis,renal cysts,and progressive renal damage that can lead to end-stage renal disease.Mutations in the uromodulin gene(UMOD)characterize the ADTKD-UMOD clinical subtype of this disease.To date,>100 UMOD mutations have been identified.Early diagnosis of ADTKD-UMOD is important to treat the disease,slow down disease progression,and facilitate the identification of potentially affected family members.CASE SUMMARY We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD(c.554G>T;p.Arg185Leu).The patient had hyperuricemia,gout,and chronic kidney disease.The same mutation was detected in his daughter,aunt and cousin.CONCLUSION A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation(c.554G>T,p.Arg185Leu).展开更多
Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors.Crystallization inhibitors include citrate,magnesium,zinc,and organic compounds such as glycosam...Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors.Crystallization inhibitors include citrate,magnesium,zinc,and organic compounds such as glycosaminoglycans.In the urine,there are various proteins,such as uromodulin(Tamm-Horsfall protein),calgranulin,osteopontin,bikunin,and nephrocalcin,that are present in the stone matrix.The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis.Proteins are the most abundant component of kidney stone matrix,and their presence may reflect the process of stone formation.Many recent studies have explored the proteomics of urinary stones.Among the stone matrix proteins,the most frequently identified were uromodulin,S100 proteins(calgranulins A and B),osteopontin,and several other proteins typically engaged in inflammation and immune response.The normal level and structure of these macromolecules may constitute protection against calcium salt formation.Paradoxically,most of them may act as both promoters and inhibitors depending on circumstances.Many of these proteins have other functions in modulating oxidative stress,immune function,and inflammation that could also influence stone formation.Yet,the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.展开更多
文摘BACKGROUND Autosomal dominant tubulointerstitial kidney disease(ADTKD)is a progressive chronic disease that is inherited in an autosomal dominant fashion.Symptoms include hyperuricemia,gout,interstitial nephritis,renal cysts,and progressive renal damage that can lead to end-stage renal disease.Mutations in the uromodulin gene(UMOD)characterize the ADTKD-UMOD clinical subtype of this disease.To date,>100 UMOD mutations have been identified.Early diagnosis of ADTKD-UMOD is important to treat the disease,slow down disease progression,and facilitate the identification of potentially affected family members.CASE SUMMARY We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD(c.554G>T;p.Arg185Leu).The patient had hyperuricemia,gout,and chronic kidney disease.The same mutation was detected in his daughter,aunt and cousin.CONCLUSION A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation(c.554G>T,p.Arg185Leu).
文摘Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors.Crystallization inhibitors include citrate,magnesium,zinc,and organic compounds such as glycosaminoglycans.In the urine,there are various proteins,such as uromodulin(Tamm-Horsfall protein),calgranulin,osteopontin,bikunin,and nephrocalcin,that are present in the stone matrix.The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis.Proteins are the most abundant component of kidney stone matrix,and their presence may reflect the process of stone formation.Many recent studies have explored the proteomics of urinary stones.Among the stone matrix proteins,the most frequently identified were uromodulin,S100 proteins(calgranulins A and B),osteopontin,and several other proteins typically engaged in inflammation and immune response.The normal level and structure of these macromolecules may constitute protection against calcium salt formation.Paradoxically,most of them may act as both promoters and inhibitors depending on circumstances.Many of these proteins have other functions in modulating oxidative stress,immune function,and inflammation that could also influence stone formation.Yet,the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.
