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Sample records for kidney disease gene

  1. Kidney Diseases

    MedlinePlus

    ... Infections Your doctor can do blood and urine tests to check if you have kidney disease. If your kidneys fail, you will need dialysis or a kidney transplant. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  2. Kidney Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  3. Kidney Disease

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Kidney Disease KidsHealth > For Teens > Kidney Disease A A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  4. Kidney Disease

    MedlinePlus

    ... version of this page please turn Javascript on. Kidney Disease What is Kidney Disease? What the Kidneys Do Click for more information You have two ... damaged, wastes can build up in the body. Kidney Function and Aging Kidney function may be reduced ...

  5. Kidney: polycystic kidney disease.

    PubMed

    Paul, Binu M; Vanden Heuvel, Gregory B

    2014-01-01

    Polycystic kidney disease (PKD) is a life-threatening genetic disorder characterized by the presence of fluid-filled cysts primarily in the kidneys. PKD can be inherited as autosomal recessive (ARPKD) or autosomal dominant (ADPKD) traits. Mutations in either the PKD1 or PKD2 genes, which encode polycystin 1 and polycystin 2, are the underlying cause of ADPKD. Progressive cyst formation and renal enlargement lead to renal insufficiency in these patients, which need to be managed by lifelong dialysis or renal transplantation. While characteristic features of PKD are abnormalities in epithelial cell proliferation, fluid secretion, extracellular matrix and differentiation, the molecular mechanisms underlying these events are not understood. Here we review the progress that has been made in defining the function of the polycystins, and how disruption of these functions may be involved in cystogenesis.

  6. Tuberous sclerosis complex and polycystic kidney disease contiguous gene syndrome with Moyamoya disease.

    PubMed

    Lai, Jonathan; Modi, Lopa; Ramai, Daryl; Tortora, Matthew

    2017-04-01

    Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two diseases sharing close genetic loci on chromosome 16. Due to contiguous gene syndrome, also known as contiguous gene deletion syndrome, the proximity of TSC2 and PKD1 genes increases the risk of co-deletion resulting in a shared clinical presentation. Furthermore, Moyamoya disease (MMD) is a rare vaso-occlusive disease in the circle of Willis. We present the first case of TSC2/PKD1 contiguous gene syndrome in a patient with MMD along with detailed histopathologic, radiologic, and cytogenetic analyses. We also highlight the clinical presentation and surgical complications in this case.

  7. Identification of the genes for kidney cancer: opportunity for disease-specific targeted therapeutics.

    PubMed

    Linehan, W Marston; Pinto, Peter A; Srinivasan, Ramaprasad; Merino, Maria; Choyke, Peter; Choyke, Lynda; Coleman, Jonathan; Toro, Jorge; Glenn, Gladys; Vocke, Cathy; Zbar, Bert; Schmidt, Laura S; Bottaro, Donald; Neckers, Len

    2007-01-15

    Recent advances in understanding the kidney cancer gene pathways has provided the foundation for the development of targeted therapeutic approaches for patients with this disease. Kidney cancer is not a single disease; it includes a number of different types of renal cancers, each with different histologic features, a different clinical course, a different response to therapy, and different genes causing the defects. Most of what is known about the genetic basis of kidney cancer has been learned from study of the inherited forms of kidney cancer: von Hippel Lindau (VHL gene), hereditary papillary renal carcinoma (c-Met gene), Birt Hogg Dubé (BHD gene), and hereditary leiomyomatosis renal cell cancer (fumarate hydratase gene). These Mendelian single-gene syndromes provide a unique opportunity to evaluate the effectiveness of agents that target the VHL, c-Met, BHD, and fumarate hydratase pathways.

  8. Kidney disease - resources

    MedlinePlus

    Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Kidney Disease Education Program -- www.nkdep.nih.gov National Kidney Foundation -- www.kidney.org National ...

  9. Acquired Cystic Kidney Disease

    MedlinePlus

    ... They Work Kidney Disease A-Z Acquired Cystic Kidney Disease What is acquired cystic kidney disease? Acquired cystic kidney disease happens when a ... cysts. What are the differences between acquired cystic kidney disease and polycystic kidney disease? Acquired cystic kidney ...

  10. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice.

    PubMed

    Moyer, J H; Lee-Tischler, M J; Kwon, H Y; Schrick, J J; Avner, E D; Sweeney, W E; Godfrey, V L; Cacheiro, N L; Wilkinson, J E; Woychik, R P

    1994-05-27

    A line of transgenic mice was generated that contains an insertional mutation causing a phenotype similar to human autosomal recessive polycystic kidney disease. Homozygotes displayed a complex phenotype that included bilateral polycystic kidneys and an unusual liver lesion. The mutant locus was cloned and characterized through use of the transgene as a molecular marker. Additionally, a candidate polycystic kidney disease (PKD) gene was identified whose structure and expression are directly associated with the mutant locus. A complementary DNA derived from this gene predicted a peptide containing a motif that was originally identified in several genes involved in cell cycle control.

  11. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice

    SciTech Connect

    Moyer, J.H.; Lee-Tischler, M.J.; Kwon, H.Y.; Schrick, J.J. ); Avner, E.D.; Sweeney, W.E. ); Godfrey, V.L.; Cacheiro, N.L.A.; Woychik, R.P. ); Wilkinson, J.E. )

    1994-05-27

    A line of transgenic mice was generated that contains an insertional mutation causing a phenotype similar to human autosomal recessive polycystic kidney disease. Homozygotes displayed a complex phenotype that included bilateral polycystic kidneys and an unusual liver lesion. The mutant locus was cloned and characterized through use of the transgene as a molecular marker. Additionally, a candidate polycystic kidney disease (PKD) gene was identified whose structure and expression are directly associated with the mutant locus. A complementary DNA derived from this gene predicted a peptide containing a motif that was originally identified in several genes involved in cell cycle control.

  12. [Hereditary kidney diseases in children].

    PubMed

    Zhang, Yan-qin; Ding, Jie; Wang, Fang; Zhang, Hong-wen

    2013-04-18

    About 10 to 15 percent of kidney diseases are inherited or related to genetic factors. While, hereditary kidney diseases have no specific clinical manifestations and react poorly to the therapy, as a result, about 30 percent of hospitalized children with chronic renal failure is due to hereditary kidney diseases in our country. Hereditary kidney diseases are related to many genes. Molecular genetic analysis plays an important role in the diagnosis and prenatal diagnosis of hereditary kidney diseases. Our group have made a series of research in hereditary kidney diseases for nearly 30 years. Here we review the research work and the main results in hereditary kidney diseases of our group.

  13. Genetics Home Reference: polycystic kidney disease

    MedlinePlus

    ... Testing Registry: Polycystic kidney disease, adult type Other Diagnosis and Management Resources (3 links) GeneReview: Polycystic Kidney Disease, Autosomal Dominant GeneReview: Polycystic Kidney Disease, Autosomal Recessive ...

  14. Chronic Kidney Diseases

    MedlinePlus

    ... los dientes Video: Getting an X-ray Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  15. Chronic Kidney Diseases

    MedlinePlus

    ... Room? What Happens in the Operating Room? Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases A ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  16. Common variants in Mendelian kidney disease genes and their association with renal function.

    PubMed

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  17. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

    PubMed Central

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

    2013-01-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  18. Polycystic kidney disease

    MedlinePlus

    Cysts - kidneys; Kidney - polycystic; Autosomal dominant polycystic kidney disease; ADPKD ... Polycystic kidney disease (PKD) is passed down through families (inherited). The 2 inherited forms of PKD are autosomal dominant ...

  19. Mutational analysis of PKD1 gene in a Chinese family with autosomal dominant polycystic kidney disease

    PubMed Central

    Liu, Jingyan; Li, Lanrong; Liu, Qingmin

    2015-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease and common renal disease. Mutations of PKD genes are responsible for this disease. We analyzed a large Chinese family with ADPKD using Sanger sequencing to identify the mutation responsible for this disease. The family comprised 27 individuals including 10 ADPKD patients. These ADPKD patients had severe renal disease and most of them died very young. We analyzed 6 survival patients gene and found they all had C10529T mutation in exon 35 of PKD1 gene. We did not found gene mutation in any unaffected relatives or 300 unrelated controls. These findings suggested that the C10529T mutation in PKD1 gene might be the pathogenic mutation responsible for the disease in this family. PMID:26722532

  20. Mutational analysis of PKD1 gene in a Chinese family with autosomal dominant polycystic kidney disease.

    PubMed

    Liu, Jingyan; Li, Lanrong; Liu, Qingmin

    2015-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease and common renal disease. Mutations of PKD genes are responsible for this disease. We analyzed a large Chinese family with ADPKD using Sanger sequencing to identify the mutation responsible for this disease. The family comprised 27 individuals including 10 ADPKD patients. These ADPKD patients had severe renal disease and most of them died very young. We analyzed 6 survival patients gene and found they all had C10529T mutation in exon 35 of PKD1 gene. We did not found gene mutation in any unaffected relatives or 300 unrelated controls. These findings suggested that the C10529T mutation in PKD1 gene might be the pathogenic mutation responsible for the disease in this family.

  1. Polycystic Kidney Disease

    MedlinePlus

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  2. Towards the identification of (a) gene(s) for autosomal dominant medullary cystic kidney disease.

    PubMed

    Scolari, Francesco; Viola, Battista Fabio; Ghiggeri, Gian Marco; Caridi, Gianluca; Amoroso, Antonio; Rampoldi, Luca; Casari, Giorgio

    2003-01-01

    Medullary cystic kidney disease (MCKD) belongs with nephronophthisis (NPH) in a group of inherited tubulo-interstitial nephritis, which has been referred to as the NPH-MCKD complex. Although MCKD and NPH share morphological features, they differ in several respects. The most common variant is recessive juvenile NPH, with onset in childhood and leading to end-stage renal disease (ESRD) within the 2nd decade of life; the most frequent extrarenal involvement is tapeto-retinal degeneration. MCKD is a dominant condition recognized in later life and leading to ESRD at the age of 50 years; hyperuricemia and gout can be associated features. The first sign of MCKD is polyuria; later, the clinical findings relate to renal insufficiency. Originally, NPH and MCKD were considered separate entities. Subsequently, it has been suggested that the two diseases were a single disorder due to the clinico-pathological identity. This unifying conception was later refuted due to the identification of MCKD dominant families. Recently, considerable insight has been gained into the genetics of the NPH-MCKD complex. The majority of juvenile NPH cases are due to deletion of the NPHP1 gene on chromosome 2q13. Genes for infantile and adolescent NPH have been localized respectively to chromosome 9q22-q31 and 3q22. A new locus, NPHP4, has been recently identified on chromosome 1p36. Two genes predisposing to dominant MCKD, MCKD1 and MCKD2, have been localized to chromosome 1q21 and 16p12. Independent confirmation of the locations of MCKD1 and MCKD2 in other MCKD families, with or without hyperuricemia and gout, has been reported. The gene for familial juvenile hyperuricemic nephropathy (FJHN), a phenotype that is very similar to MCKD, was recently mapped to 16p12, in a region overlapping with the MCKD2 locus, raising the question as to whether MCKD2 and FJHN are allelic variants of the same disease entity. The ultimate proof of the allelism between MCKD2 and FJHN will be provided by the

  3. Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease.

    PubMed

    Shin, Youn-Jeong; Jeon, Yeo Jin; Jung, Namhee; Park, Joo-Won; Park, Hae-Young; Jung, Sung-Chul

    2015-10-01

    Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the α-galactosidase A (α-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso‑Gb3) in the plasma of symptomatic patients has also been suggested as a causative molecular event. To elucidate the molecular mechanisms involved in renal fibrosis in Fabry disease, the present analyzed the changes in global gene expression prior to and following Gb3 or lyso‑Gb3 treatment in two types of kidney cell lines, human proximal renal tubular epithelial (HK‑2) and mouse renal glomerular mesangial (SV40 MES 13) cells. Gb3 and lyso‑Gb3 treatment regulated the expression of 199 and 328 genes in each cell type, demonstrating a >2.0‑fold change. The majority of the biological functions of the regulated genes were associated with fibrogenesis or epithelial‑mesenchymal transition (EMT). The gene expression patterns of sphingolipid‑treated HK‑2 cells were distinguishable from the patterns in the SV40 MES 13 cells. Several genes associated with the EMT were selected and evaluated further in kidney cells and in Fabry mouse kidney tissues. In the SV40 MES 13 cells, the DLL1, F8, and HOXA11 genes were downregulated, and FOXP2 was upregulated by treatment with Gb3 or lyso‑Gb3. In the HK‑2 cells, the ADAMTS6, BEST1, IL4, and MYH11 genes were upregulated. Upregulation of the FOXP2, COL15A1, IL4, and MYH11 genes was also observed in the Fabry mouse kidney tissues. The gene expression profiles in kidney cells following the addition of Gb3 or lyso‑Gb3 revealed substrate‑specific and cell‑specific patterns. These findings suggested that Gb3 and lyso‑Gb3 lead to renal

  4. Chronic Kidney Disease

    MedlinePlus

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  5. Both msa genes in Renibacterium salmoninarum are needed for full virulence in bacterial kidney disease

    USGS Publications Warehouse

    Coady, A.M.; Murray, A.L.; Elliott, D.G.; Rhodes, L.D.

    2006-01-01

    Renibacterium salmoninarum, a gram-positive diplococcobacillus that causes bacterial kidney disease among salmon and trout, has two chromosomal loci encoding the major soluble antigen (msa) gene. Because the MSA protein is widely suspected to be an important virulence factor, we used insertion-duplication mutagenesis to generate disruptions of either the msa1 or msa2 gene. Surprisingly, expression of MSA protein in broth cultures appeared unaffected. However, the virulence of either mutant in juvenile Chinook salmon (Oncorhynchus tshawytscha) by intraperitoneal challenge was severely attenuated, suggesting that disruption of the msa1 or msa2 gene affected in vivo expression. Copyright ?? 2006, American Society for Microbiology. All Rights Reserved.

  6. Changes in Pre- and Post-Exercise Gene Expression among Patients with Chronic Kidney Disease and Kidney Transplant Recipients

    PubMed Central

    Coletta, Dawn K.; Campbell, Latoya E.; Weil, Jennifer; Kaplan, Bruce; Clarkson, Marie; Finlayson, Jean; Mandarino, Lawrence J.; Chakkera, Harini A.

    2016-01-01

    Introduction Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown. Methods Study cohort: non-diabetic male/female 4/1, age 52±2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed. Result Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre-and post-transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant. Conclusions Despite an improvement in serum inflammatory markers, no significant differences in glucose

  7. Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel

    PubMed Central

    Al-Hamed, Mohamed H; Kurdi, Wesam; Alsahan, Nada; Alabdullah, Zainab; Abudraz, Rania; Tulbah, Maha; Alnemer, Maha; Khan, Rubina; Al-Jurayb, Haya; Alahmed, Ahmed; Tahir, Asma I; Khalil, Dania; Edwards, Noel; Al Abdulaziz, Basma; Binhumaid, Faisal S; Majid, Salma; Faquih, Tariq; El-Kalioby, Mohamed; Abouelhoda, Mohamed; Altassan, Nada; Monies, Dorota; Meyer, Brian; Sayer, John A; Albaqumi, Mamdouh

    2016-01-01

    Background Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease. Methods To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated. Results In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort. Conclusions In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians. PMID:26862157

  8. Diabetes and Kidney Disease

    MedlinePlus

    ... disease of diabetes, or diabetic nephropathy. How does diabetes cause kidney disease? High blood glucose , also called ... I keep my kidneys healthy if I have diabetes? The best way to slow or prevent diabetes- ...

  9. [Kidney diseases in pregnancy].

    PubMed

    Kolesárova, Eva; Sirotiaková, Jana; Kozárová, Miriam

    2010-01-01

    Knowledge of important morphological, functional and hemodynamic changes occurring in the kidneys during physiological pregnancy is a prerequisite for proper diagnostics and therapy of renal diseases in pregnancy. Kidney diseases may be kidney diseases complicating pregnancy in previously healthy women, or pre-existing or superposed kidney diseases. Knowledge of renal insufficiency management in pregnancy, including haemodialysis treatment and management of pregnancy in patients who have undergone transplantation, is also important.

  10. Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients.

    PubMed

    Annapareddy, Shiva Nagendra Reddy; Elumalai, Ramprasad; Lakkakula, Bhaskar V K S; Ramanathan, Gnanasambandan; Periyasamy, Soundararajan

    2016-01-01

    Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD) in ADPKD. In the present study we investigated six genes coding for endothelin 1 ( EDN1 ) tagging-single nucleotide polymorphisms (tag-SNPs) to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.

  11. Epigenetics of kidney disease.

    PubMed

    Wanner, Nicola; Bechtel-Walz, Wibke

    2017-03-13

    DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

  12. Testing for Kidney Disease

    MedlinePlus

    ... Albumin Children and Kidney Disease Additional Kidney Information Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. September 17, 2014​​ Contact Us Health Information Center Phone: 1-800-860- ...

  13. Kidney Disease Basics

    MedlinePlus

    ... Albumin Children and Kidney Disease Additional Kidney Information Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. March 1, 2012​ Contact Us Health Information Center Phone: 1-800-860- ...

  14. Systems biology of kidney diseases.

    PubMed

    He, John Cijiang; Chuang, Peter Y; Ma'ayan, Avi; Iyengar, Ravi

    2012-01-01

    Kidney diseases manifest in progressive loss of renal function, which ultimately leads to complete kidney failure. The mechanisms underlying the origins and progression of kidney diseases are not fully understood. Multiple factors involved in the pathogenesis of kidney diseases have made the traditional candidate gene approach of limited value toward full understanding of the molecular mechanisms of these diseases. A systems biology approach that integrates computational modeling with large-scale data gathering of the molecular changes could be useful in identifying the multiple interacting genes and their products that drive kidney diseases. Advances in biotechnology now make it possible to gather large data sets to characterize the role of the genome, epigenome, transcriptome, proteome, and metabolome in kidney diseases. When combined with computational analyses, these experimental approaches will provide a comprehensive understanding of the underlying biological processes. Multiscale analysis that connects the molecular interactions and cell biology of different kidney cells to renal physiology and pathology can be utilized to identify modules of biological and clinical importance that are perturbed in disease processes. This integration of experimental approaches and computational modeling is expected to generate new knowledge that can help to identify marker sets to guide the diagnosis, monitor disease progression, and identify new therapeutic targets.

  15. The mouse homologue of the polycystic kidney disease gene (Pkd1) is a single-copy gene

    SciTech Connect

    Olsson, P.G.; Loehning, C.; Frischauf, A.M.

    1996-06-01

    The mouse homologue of the polycystic kidney disease 1 gene (PKD1) was mapped to chromosome 17 using somatic cell hybrid, BXD recombinant inbred strains, and FISH. The gene is located within a previously defined conserved synteny group that includes the mouse homologue of tuberous sclerosis 2 (TSC2) and is linked to the {alpha} globin pseudogene Hba-ps4. Although the human genome contains multiple copies of genes related to PKD1, there is no evidence for more than one copy in the mouse genome. Like their human counterparts, the mouse Tsc2 and Pkd1 genes are arranged in a tail-to-tail orientation with a distance of only 63 bp between the polyadenylation signals of the two genes. 17 refs., 3 figs.

  16. Sulfadiazine for kidney disease

    USGS Publications Warehouse

    Rucker, R.R.; Bernier, A.F.; Whipple, W.J.; Burrows, R.E.

    1951-01-01

    The blueback salmon fingerlings (Oncorhynchus nerka) at the U.S. Fish-Cultural Station at Winthrop, Washington, underwent an infection that was caused by a very short, Gram-positive, nonmotile, rod-shaped bacterium. A further description is impossible at this time, as the organism has not been grown satisfactorily for proper identification. The disease was characterized by white, raised areas of dead tissue mainly in the kidney: for this reason it is referred to as kidney disease. Belding and Merrill (1935) described a disease among the brook, brown, and rainbow trout at a State hatchery in Massachusetts which, from the description, might be the same as kidney disease. J.H. Wales of the California Division of Fish and Game described (unpublished manuscript, 1941) a disease in hatchery trout in California which seems to be identical to kidney disease.

  17. The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination.

    PubMed

    Murcia, N S; Richards, W G; Yoder, B K; Mucenski, M L; Dunlap, J R; Woychik, R P

    2000-06-01

    Analysis of several mutations in the mouse is providing useful insights into the nature of the genes required for the establishment of the left-right axis during early development. Here we describe a new targeted allele of the mouse Tg737 gene, Tg737(Delta)2-3(beta)Gal), which causes defects in left-right asymmetry and other abnormalities during embryogenesis. The Tg737 gene was originally identified based on its association with the mouse Oak Ridge Polycystic Kidney (orpk) insertional mutation, which causes polycystic kidney disease and other defects. Complementation tests between the original orpk mutation and the new targeted knock-out mutation demonstrate that Tg737(Delta)2-3(beta)Gal) behaves as an allele of Tg737. The differences in the phenotype between the two mutations suggest that the orpk mutation is a hypomorphic allele of the Tg737 gene. Unlike the orpk allele, where all homozygotes survive to birth, embryos homozygous for the Tg737(Delta)2-3(beta)Gal) mutation arrest in development at mid-gestation and exhibit neural tube defects, enlargement of the pericardial sac and, most notably, left-right asymmetry defects. At mid-gestation the direction of heart looping is randomized, and at earlier stages in development lefty-2 and nodal, which are normally expressed asymmetrically, exhibit symmetrical expression in the mutant embryos. Additionally, we determined that the ventral node cells in mutant embryos fail to express the central cilium, which is a characteristic and potentially functional feature of these cells. The expression of both Shh and Hnf3(beta) is downregulated in the midline at E8.0, indicating that there are significant alterations in midline development in the Tg737(Delta)2-3(beta)Gal) homozygous embryos. We propose that the failure of ventral node cells to fully mature alters their ability to undergo differentiation as they migrate out of the node to contribute to the developing midline structures. Analysis of this new knockout allele

  18. Medullary cystic kidney disease

    MedlinePlus

    ... to avoid dehydration. As the disease gets worse, kidney failure develops. Treatment may involve taking medicines and diet changes, limiting foods containing phosphorus and potassium. You may need dialysis and a ...

  19. Orphan kidney diseases.

    PubMed

    Soliman, Neveen A

    2012-01-01

    Rare kidney diseases are a unique subset of renal disorders that are often termed 'orphan' as a result of a multitude of reasons: the small number of patients with the consequent lack of well-defined natural history and course of many of these diseases, limited awareness among the medical community, and finally the significant cost of developing novel therapeutics which makes many of these diseases unattractive targets for the pharmaceutical industry. Nevertheless, in the last decade the study and clinical management of rare kidney disease patients has been the focus of many investigative efforts. In recent years we have witnessed an enormous expansion in our knowledge of the genetic nature of a number of rare kidney diseases. Moreover, the investigation of the role of genetic disruption aiming at elucidating the pathogenesis of different and complex renal diseases has helped not only in understanding the disease states, but has also given us fundamental insights into a number of kidney developmental and physiological functions. This article will give an overview of orphan renal diseases with particular emphasis on monogenic kidney diseases. It will also focus on the classification of these diseases while highlighting a prominent example in each category.

  20. Osteoprotegerin and kidney disease.

    PubMed

    Montañez-Barragán, Alejandra; Gómez-Barrera, Isaias; Sanchez-Niño, Maria D; Ucero, Alvaro C; González-Espinoza, Liliana; Ortiz, Alberto

    2014-12-01

    Vascular calcification in chronic kidney disease (CKD) patients is associated to increased mortality. Osteoprotegerin (OPG) is a soluble tumor necrosis factor (TNF) superfamily receptor that inhibits the actions of the cytokines receptor activator of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL) by preventing their binding to signaling receptors in the cell membrane. OPG-deficient mice display vascular calcification while OPG prevented calcification of cultured vascular smooth muscle cells and protected kidney cells from TRAIL-induced death. OPG may be a biomarker in patients with kidney disease. Circulating OPG is increased in predialysis, dialysis and transplant CKD patients and may predict vascular calcification progression and patient survival. By contrast, circulating OPG is decreased in nephrotic syndrome. In addition, free and exosome-bound urinary OPG is increased in human kidney disease. Increased urinary OPG has been associated with lupus nephritis activity. Despite the association of high OPG levels with disease, experimental functional information available suggests that OPG might be protective in kidney disease and in vascular injury in the context of uremia. Thus, tissue injury results in increased OPG, while OPG may protect from tissue injury. Recombinant OPG was safe in phase I randomized controlled trials. Further research is needed to fully define the therapeutic and biomarker potential of OPG in patients with kidney disease.

  1. Downregulation of Nuclear-Encoded Genes of Oxidative Metabolism in Dialyzed Chronic Kidney Disease Patients

    PubMed Central

    Masola, Valentina; Rugiu, Carlo; Fantin, Francesco; Gesualdo, Loreto; Schena, Francesco Paolo; Lupo, Antonio

    2013-01-01

    Background Mitochondria, essential eukaryotic cells organelles defined as the “powerhouse of the cell” because of their ability to produce the vast majority of energy necessary for cellular metabolism, may have a primary role in the oxidative stress-related intracellular machinery associated to chronic kidney disease (CKD). Methods To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in peritoneal dialysis (PD, n = 15) using several bio-molecular methodologies. Results RT-PCR experiments demonstrate that the expression level of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1), two genes primarily involved in mitochondrial biogenesis and functions, were significantly hypo-expressed in peripheral blood mononuclear cells of PD patients compared to healthy subjects (HS, n = 15). Additionally, mRNA levels of several PGC1-α downstream target genes (TFAM, COX6C,COX7C, UQCRH and MCAD) were profoundly down-regulated in PD cells. TFAM protein analysis confirmed gene-expression results. High plasmatic concentration of Malondialdehyde found in PD patients, confirmed the contribution of the oxidative stress to these biological effects. Finally, Nuclear factor erythroid-derived 2-like 2 (NRF2 or NFE2L2), a transcription factor for numerous antioxidant/detoxifying enzymes and one of its target genes, superoxide dismutase-2 mitochondrial (SOD2) were up-regulated in PD compared to HS. Conclusions Our results revealed, for the first time, that CKD-PD patients’ PBMC, through a complex intracellular biochemical machinery, are able to modulate their mitochondrial functions probably in the attempt to reduce oxidative metabolic damage and to turn on a valuable defense cellular strategy against oxidative stress. PMID:24204994

  2. [Pregnancy and kidney diseases].

    PubMed

    Siekierka-Harreis, M; Rump, L C

    2011-10-01

    The prevalence of chronic kidney disease in women of childbearing age reaches approximately 0.2%. Under physiological conditions pregnancy results in important hemodynamic changes on the maternal organism. In the case of chronic kidney disease these adaptations often are only partial. Physiological changes of immune response during pregnancy may contribute to the progress of renal disease. Regardless of the underlying kidney disease, one can assume that the better the glomerular filtration rate and blood pressure are the more favorable the course of pregnancy will be with the chance for a healthy child and stable renal function. To achieve this goal, a close interaction is required between gynecologist, nephrologist, and other specialists in a center with appropriate experience.

  3. microRNAs in Diabetic Kidney Disease.

    PubMed

    Chung, Arthur C K

    2015-01-01

    Diabetes and diabetic kidney diseases have continually exerted a great burden on our society. Although the recent advances in medical research have led to a much better understanding of diabetic kidney diseases, there is still no successful strategy for effective treatments for diabetic kidney diseases. Recently, treatment of diabetic kidney diseases relies either on drugs that reduce the progression of renal injury or on renal replacement therapies, such as dialysis and kidney transplantation. On the other hand, searching for biomarkers for early diagnosis and effective therapy is also urgent. Discovery of microRNAs has opened to a novel field for posttranscriptional regulation of gene expression. Results from cell culture experiments, experimental animal models, and patients under diabetic conditions reveal the critical role of microRNAs during the progression of diabetic kidney diseases. Functional studies demonstrate not only the capability of microRNAs to regulate expression of target genes, but also their therapeutic potential to diabetic kidney diseases. The existence of microRNAs in plasma, serum, and urine suggests their possibility to be biomarkers in diabetic kidney diseases. Thus, identification of the functional role of microRNAs provides an essentially clinical impact in terms of prevention and treatment of progression in diabetic kidney diseases as it enables us to develop novel, specific therapies and diagnostic tools for diabetic kidney diseases.

  4. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... Heart Disease Mineral & Bone Disorder Anemia in Chronic Kidney Disease What is anemia? Anemia is a condition ... they should. How is anemia related to chronic kidney disease? Anemia commonly occurs in people with chronic ...

  5. Chronic Kidney Disease in Kidney Stone Formers

    PubMed Central

    Krambeck, Amy E.; Lieske, John C.

    2011-01-01

    Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

  6. Gene based therapies for kidney regeneration.

    PubMed

    Janssen, Manoe J; Arcolino, Fanny O; Schoor, Perry; Kok, Robbert Jan; Mastrobattista, Enrico

    2016-11-05

    In this review we provide an overview of the expanding molecular toolbox that is available for gene based therapies and how these therapies can be used for a large variety of kidney diseases. Gene based therapies range from restoring gene function in genetic kidney diseases to steering complex molecular pathways in chronic kidney disorders, and can provide a treatment or cure for diseases that otherwise may not be targeted. This approach involves the delivery of recombinant DNA sequences harboring therapeutic genes to improve cell function and thereby promote kidney regeneration. Depending on the therapy, the recombinant DNA will express a gene that directly plays a role in the function of the cell (gene addition), that regulates the expression of an endogenous gene (gene regulation), or that even changes the DNA sequence of endogenous genes (gene editing). Some interventions involve permanent changes in the genome whereas others are only temporary and leave no trace. Efficient and safe delivery are important steps for all gene based therapies and also depend on the mode of action of the therapeutic gene. Here we provide examples on how the different methods can be used to treat various diseases, which technologies are now emerging (such as gene repair through CRISPR/Cas9) and what the opportunities, perspectives, potential and the limitations of these therapies are for the treatment of kidney diseases.

  7. A Novel Mutation of the HNF1B Gene Associated With Hypoplastic Glomerulocystic Kidney Disease and Neonatal Renal Failure

    PubMed Central

    Alvelos, Maria Inês; Rodrigues, Magda; Lobo, Luísa; Medeira, Ana; Sousa, Ana Berta; Simão, Carla; Lemos, Manuel Carlos

    2015-01-01

    Abstract Hepatocyte nuclear factor 1 beta (HNF1B) plays an important role in embryonic development, namely in the kidney, pancreas, liver, genital tract, and gut. Heterozygous germline mutations of HNF1B are associated with the renal cysts and diabetes syndrome (RCAD). Affected individuals may present a variety of renal developmental abnormalities and/or maturity-onset diabetes of the young (MODY). A Portuguese 19-month-old male infant was evaluated due to hypoplastic glomerulocystic kidney disease and renal dysfunction diagnosed in the neonatal period that progressed to stage 5 chronic renal disease during the first year of life. His mother was diagnosed with a solitary hypoplastic microcystic left kidney at age 20, with stage 2 chronic renal disease established at age 35, and presented bicornuate uterus, pancreatic atrophy, and gestational diabetes. DNA sequence analysis of HNF1B revealed a novel germline frameshift insertion (c.110_111insC or c.110dupC) in both the child and the mother. A review of the literature revealed a total of 106 different HNF1B mutations, in 236 mutation-positive families, comprising gross deletions (34%), missense mutations (31%), frameshift deletions or insertions (15%), nonsense mutations (11%), and splice-site mutations (8%). The study of this family with an unusual presentation of hypoplastic glomerulocystic kidney disease with neonatal renal dysfunction identified a previously unreported mutation of the HNF1B gene, thereby expanding the spectrum of known mutations associated with renal developmental disorders. PMID:25700310

  8. Chronic Kidney Disease

    MedlinePlus

    ... factors. It is important to diagnose CKD early. Diagnosis & TestsHow can my doctor tell if I have CKD?There are three simple tests that your doctor might do if he or she suspects you might have chronic kidney disease:Blood pressure testUrine albumin (a test to see ...

  9. Chronic Kidney Disease.

    PubMed

    Webster, Angela C; Nagler, Evi V; Morton, Rachael L; Masson, Philip

    2017-03-25

    The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR

  10. FastStats: Kidney Disease

    MedlinePlus

    ... this? Submit What's this? Submit Button NCHS Home Kidney Disease Recommend on Facebook Tweet Share Compartir Data are ... the U.S. Morbidity Number of adults with diagnosed kidney disease: 4.9 million Percent of adults with diagnosed ...

  11. Acupuncture and kidney disease.

    PubMed

    Garcia, Gabriela E; Ma, Sheng-Xing; Feng, Lili

    2005-07-01

    Acupuncture as a complex therapeutic system has been used to treat a variety of diseases and pathological conditions. Although the exact mechanism(s) of acupuncture remains unknown, some evidence suggests a mechanism initially involving signal transduction through connective tissue, with secondary involvement of other systems including the nervous system. Acupuncture has become increasingly popular in the Western countries as a therapy for pain and several chronic disorders difficult to manage with conventional treatments. Acupuncture and acupuncture-like somatic nerve stimulation have been used in different kidney diseases and several complications related to them. The effect of acupuncture techniques in some kidney diseases is reviewed on the basis of clinical reports as well as mechanisms that may possibly explain the beneficial effects mediated by acupressure/acupuncture. The potential effect of acupressure techniques in renal inflammation and whether these effects could be mediated through the newly identified cholinergic anti-inflammatory pathway are discussed.

  12. Restoration of Haemoglobin Level Using Hydrodynamic Gene Therapy with Erythropoietin Does Not Alleviate the Disease Progression in an Anaemic Mouse Model for TGFβ1-Induced Chronic Kidney Disease.

    PubMed

    Pedersen, Lea; Wogensen, Lise; Marcussen, Niels; Cecchi, Claudia R; Dalsgaard, Trine; Dagnæs-Hansen, Frederik

    2015-01-01

    Erythropoietin, Epo, is a 30.4 kDa glycoprotein hormone produced primarily by the fetal liver and the adult kidney. Epo exerts its haematopoietic effects by stimulating the proliferation and differentiation of erythrocytes with subsequent improved tissue oxygenation. Epo receptors are furthermore expressed in non-haematopoietic tissue and today, Epo is recognised as a cytokine with many pleiotropic effects. We hypothesize that hydrodynamic gene therapy with Epo can restore haemoglobin levels in anaemic transgenic mice and that this will attenuate the extracellular matrix accumulation in the kidneys. The experiment is conducted by hydrodynamic gene transfer of a plasmid encoding murine Epo in a transgenic mouse model that overexpresses TGF-β1 locally in the kidneys. This model develops anaemia due to chronic kidney disease characterised by thickening of the glomerular basement membrane, deposition of mesangial matrix and mild interstitial fibrosis. A group of age matched wildtype littermates are treated accordingly. After a single hydrodynamic administration of plasmid DNA containing murine EPO gene, sustained high haemoglobin levels are observed in both transgenic and wildtype mice from 7.5 ± 0.6 mmol/L to 9.4 ± 1.2 mmol/L and 10.7 ± 0.3 mmol/L to 15.5 ± 0.5 mmol/L, respectively. We did not observe any effects in the thickness of glomerular or tubular basement membrane, on the expression of different collagen types in the kidneys or in kidney function after prolonged treatment with Epo. Thus, Epo treatment in this model of chronic kidney disease normalises haemoglobin levels but has no effect on kidney fibrosis or function.

  13. Chronic Kidney Disease (CKD)

    MedlinePlus

    ... upcoming screening events. Kidney Action Day Kidney Action Day Learn about our signature outreach event. About AKF ... support of AKF. Kidney Action Day Kidney Action Day Learn about our signature outreach event. Free health ...

  14. Using Xenopus to study genetic kidney diseases.

    PubMed

    Lienkamp, Soeren S

    2016-03-01

    Modern sequencing technology is revolutionizing our knowledge of inherited kidney disease. However, the molecular role of genes affected by the rapidly rising number of identified mutations is lagging behind. Xenopus is a highly useful, but underutilized model organism with unique properties excellently suited to decipher the molecular mechanisms of kidney development and disease. The embryonic kidney (pronephros) can be manipulated on only one side of the animal and its formation observed directly through the translucent skin. The moderate evolutionary distance between Xenopus and humans is a huge advantage for studying basic principles of kidney development, but still allows us to analyze the function of disease related genes. Optogenetic manipulations and genome editing by CRISPR/Cas are exciting additions to the toolbox for disease modelling and will facilitate the use of Xenopus in translational research. Therefore, the future of Xenopus in kidney research is bright.

  15. [Carnosine, carnosinase and kidney diseases].

    PubMed

    Kiliś-Pstrusińska, Katarzyna

    2012-04-20

     Carnosine (beta-alanyl-L-histidine) is an endogenously synthesized dipeptide which is present in different human tissues, including the kidney. Carnosine is hydrolyzed by the enzyme carnosinase. There are two carnosinase homologues: serum secreted carnosinase and non-specific cytosolic dipeptidase, encoded by the genes CNDP1 and CNDP2 respectively and located on chromosome 18q22.3. Carnosine functions as a radical oxygen species scavenger and as a natural angiotensin converting enzyme inhibitor. Carnosine inhibits advanced glycation end product formation and reduces the synthesis of matrix proteins such as fibronectin and collagen type VI of podocytes and mesangial cells. In experimental studies it was shown that carnosine reduces the level of proinflammatory and profibrotic cytokines. It is suggested that carnosine is a naturally occurring anti-aging substance in human organisms with a beneficial effect on the cardiovascular system. This paper reports the results of studies concerning carnosine's role in kidney diseases, particularly in ischemia/reperfusion induced acute renal failure, diabetic nephropathy, gentamicin-induced nephrotoxicity and also in blood pressure regulation. The correlations between serum carnosine and serum carnosinase activity and polymorphism in the CNDP1 gene are analyzed. The role of CNDP1 gene polymorphism in the development of diabetic nephropathy and non-diabetic chronic kidney disease is discussed. Carnosine is engaged in different metabolic pathways. It has nephroprotective features. Further studies of carnosine metabolism and its biological properties, particularly those concerning the human organism, are required.

  16. Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD)

    PubMed Central

    Ramanathan, Gnanasambandan; Ghosh, Santu; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar V.K.S.

    2016-01-01

    Background & objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. Methods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. Results: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. Interpretation & conclusions: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients. PMID:27748299

  17. At Risk for Kidney Disease?

    MedlinePlus

    ... Albumin Children and Kidney Disease Additional Kidney Information Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. March 5, 2014​ Contact Us Health Information Center Phone: 1-800-860- ...

  18. [Kidney diseases: new issues].

    PubMed

    Ronco, Pierre

    2012-03-01

    Chronic kidney disease (CKD) affects two to four million people in France and most of them are not aware of their disease. CKD is a major, independent risk factor of cardiovascular mortality and morbidity; the cardiovascular risk increases with the severity of renal failure. Evaluation of renal function (GFR) relies on MDRD and CKD-EPI equations. The French CKD-REIN cohort with more than 3000 patients followed for 5 years, will hopefully provide substantial advances in the knowledge of CKD epidemiology, of risk factors and mechanisms of CKD progression and medical practices. Improving CKD screening based on blood pressure, proteinuria (microalbuminuria in diabetic patients) and serum creatinine, is a national duty in high risk patients (with diabetes, hypertension and cardiovascular diseases). A major research goal is to identify new therapeutic targets and biomarkers, in order to treat kidney diseases before the occurrence of renal insufficiency, to halt their progression and to decrease cardiovascular risk. Careful therapeutic education of patients is required to successfully implement established guidelines, appropriate diets and new therapeutic strategies.

  19. Pruritus in Kidney Disease.

    PubMed

    Combs, Sara A; Teixeira, J Pedro; Germain, Michael J

    2015-07-01

    Pruritus is a common and distressing symptom in patients with chronic kidney disease. The most recent epidemiologic data have suggested that approximately 40% of patients with end-stage renal disease experience moderate to severe pruritus and that uremic pruritus (UP) has a major clinical impact, being associated strongly with poor quality of life, impaired sleep, depression, and increased mortality. The pathogenesis of UP remains largely unclear, although several theories on etiologic or contributing factors have been proposed including increased systemic inflammation; abnormal serum parathyroid hormone, calcium, and phosphorus levels; an imbalance in opiate receptors; and a neuropathic process. UP can present somewhat variably, although it tends to affect large, discontinuous, but symmetric, areas of skin and to be most symptomatic at night. A variety of alternative systemic or dermatologic conditions should be considered, especially in patients with asymmetric pruritus or other atypical features. Treatment initially should focus on aggressive skin hydration, patient education on minimizing scratching, and optimization of the aspects of chronic kidney disease care that are most relevant to pruritus, including dialysis adequacy and serum parathyroid hormone, calcium, and phosphorus management. Data for therapy specifically for UP remain limited, although topical therapies, gabapentin, type B ultraviolet light phototherapy, acupuncture, and opioid-receptor modulators all may play a role.

  20. Kidney diseases and tissue engineering.

    PubMed

    Moon, Kyung Hyun; Ko, In Kap; Yoo, James J; Atala, Anthony

    2016-04-15

    Kidney disease is a worldwide public health problem. Renal failure follows several disease stages including acute and chronic kidney symptoms. Acute kidney injury (AKI) may lead to chronic kidney disease (CKD), which can progress to end-stage renal disease (ESRD) with a mortality rate. Current treatment options are limited to dialysis and kidney transplantation; however, problems such as donor organ shortage, graft failure and numerous complications remain a concern. To address this issue, cell-based approaches using tissue engineering (TE) and regenerative medicine (RM) may provide attractive approaches to replace the damaged kidney cells with functional renal specific cells, leading to restoration of normal kidney functions. While development of renal tissue engineering is in a steady state due to the complex composition and highly regulated functionality of the kidney, cell therapy using stem cells and primary kidney cells has demonstrated promising therapeutic outcomes in terms of restoration of renal functions in AKI and CKD. In this review, basic components needed for successful renal kidney engineering are discussed, and recent TE and RM approaches to treatment of specific kidney diseases will be presented.

  1. Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

    PubMed Central

    Sayanthooran, Saravanabavan; Gunerathne, Lishanthe; Abeysekera, Tilak D. J.; Sooriyapathirana, Suneth S.

    2016-01-01

    Objective. To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu) in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase mu 1 (GSTM1), glucose-6-phosphate dehydrogenase (G6PD), fibroblast growth factor-23 (FGF23), and NLR family pyrin domain containing 3 (NLRP3). Methods. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out for the selected populations: CKDu patients (n = 43), chronic kidney disease patients (CKD; n = 14), healthy individuals from a CKDu endemic area (GHI; n = 9), and nonendemic area (KHI; n = 16). Fold changes were quantified relative to KHI. Results. GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI (p = 0.000). GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold (p < 0.05). Upregulation of FGF23 and NLRP3 genes in CKD and CKDu was observed (p < 0.01), with greater fold changes in CKD. Conclusion. Results suggest higher influence of external sources of oxidative stress in CKDu, possibly owing to environmental conditions. PMID:27975059

  2. Kidney Disease: Early Detection and Treatment

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, ...

  3. Macrophage polarization in kidney diseases.

    PubMed

    Tian, Shaojiang; Chen, Shi-You

    Macrophage accumulation associates closely with the degree of renal structural injury and renal dysfunction in human kidney diseases. Depletion of macrophages reduces while adoptive transfer of macrophages worsens inflammation in animal models of the renal injury. However, emerging evidence support that macrophage polarization plays a critical role in the progression of a number of kidney diseases including obstructive nephropathy, ischemia-reperfusion injury, glomerulonephritis, diabetic nephropathy, and other kidney diseases. In this mini-review, we briefly summarize the macrophage infiltration and polarization in these inflammatory and fibrotic kidney diseases, discussing the results mostly from studies in animal models. In view of the critical role of macrophage in the progression of these diseases, manipulating macrophage phenotype may be a potential effective strategy to treat various kidney diseases.

  4. Autosomal Dominant Polycystic Kidney Disease

    MedlinePlus

    ... with available imaging techniques (ultrasound and computerized tomography). Diagnosis of earlier stages of disease in children and young adults was much more difficult. Few treatments were available for chronic kidney disease in general, and there was no specific therapy ...

  5. Polymorphisms in CaSR and CLDN14 Genes Associated with Increased Risk of Kidney Stone Disease in Patients from the Eastern Part of India.

    PubMed

    Guha, Manalee; Bankura, Biswabandhu; Ghosh, Sudakshina; Pattanayak, Arup Kumar; Ghosh, Saurabh; Pal, Dilip Kumar; Puri, Anurag; Kundu, Anup Kumar; Das, Madhusudan

    2015-01-01

    Kidney stone disease (KSD) is a major clinical problem imposing a large burden for both healthcare and economy globally. In India, the prevalence of kidney stone disease is rapidly increasing. This study aimed to evaluate the association between genetic defects in vitamin D receptor (VDR), calcium sensing receptor (CaSR) and claudin 14 (CLDN14) genes and kidney stone disease in patients from eastern India. We enrolled 200 consecutive kidney stone patients (age 18-60 years) (cases) and their corresponding sex and age matched 200 normal individuals (controls). To identify genetic variants responsible for KSD, we performed sequence analysis of VDR, CaSR and CLDN14 genes. Four non-synonymous (rs1801725, rs1042636, rs1801726 and rs2228570), one synonymous (rs219780) and three intronic single nucleotide polymorphisms (SNPs) (rs731236, rs219777 and rs219778) were identified. Genotype and allele frequency analysis of these SNPs revealed that, rs1801725 (Ala986Ser), rs1042636 (Arg990Gly) of CaSR gene and rs219778, rs219780 (Thr229Thr) of CLDN14 gene were significantly associated with KSD. Serum calcium levels were significantly higher in subjects carrying 986Ser allele and calcium excretion was higher in subjects bearing 990Gly allele. In conclusion, rs1801725, rs1042636, rs219778 and rs219780 SNPs were associated with kidney stone risk in patients from the eastern part of India.

  6. Necroinflammation in Kidney Disease.

    PubMed

    Mulay, Shrikant R; Linkermann, Andreas; Anders, Hans-Joachim

    2016-01-01

    The bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury-related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.

  7. Growth Failure in Children with Kidney Disease

    MedlinePlus

    ... Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight ... Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight ...

  8. Medicines and Kidney Disease

    MedlinePlus

    ... Dialysis or Transplant Paying for Kidney Failure Treatment Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. ​​September 17, 2014 ​​ Contact Us Health Information Center Phone: 1-800-860- ...

  9. Glomerulocystic kidney disease

    PubMed Central

    Siroky, Brian J.; Yin, Hong

    2010-01-01

    Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease. PMID:20091054

  10. Pregnancy and chronic kidney disease.

    PubMed

    Davison, John M; Lindheimer, Marshall D

    2011-01-01

    This article reviews the association of chronic renal disease and pregnancy. Included are discussions of guidelines for counseling pregnant women with underlying chronic renal disease who are considering conceiving as well as management of those already pregnant. Specifically highlighted are recent studies that question the validity of using estimated glomerular filtration rate and other formulae and questions of whether we should strive to replace the classic counseling approaches based primarily on serum creatinine levels with guidelines based on chronic kidney disease classification. The article concludes with a review as well as a critique of recent research on the prevalence of preeclampsia in women with underlying chronic renal disease, as well as if women with preeclampsia and underlying kidney disease have accelerated courses toward end-stage renal disease.

  11. Evaluation of Candidate Nephropathy Susceptibility Genes in a Genome-Wide Association Study of African American Diabetic Kidney Disease

    PubMed Central

    Palmer, Nicholette D.; Ng, Maggie C. Y.; Hicks, Pamela J.; Mudgal, Poorva; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.

    2014-01-01

    Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a complex disorder resulting from the combined influence of genetic and environmental factors. This study contains a comprehensive genetic analysis of putative nephropathy loci in 965 African American (AA) cases with T2D-ESKD and 1029 AA population-based controls extending prior findings. Analysis was based on 4,341 directly genotyped and imputed single nucleotide polymorphisms (SNPs) in 22 nephropathy candidate genes. After admixture adjustment and correction for multiple comparisons, 37 SNPs across eight loci were significantly associated (1.6E-05genes is shared across populations of African and European ancestry. PMID:24551085

  12. [Polycystic liver disease without autosomal dominant polycystic kidney disease].

    PubMed

    Peces, R; González, P; Venegas, J L

    2003-01-01

    Polycystic liver disease is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. The natural history and clinical manifestations of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The occurrence of polycystic liver disease independently from polycystic kidney disease has been known for a long time. More recently, a gene for autosomal dominant polycystic liver disease has been identified on chromosome 19p 13.2-13.1. Isolated polycystic liver disease is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis and clinical manifestations. We report here two men with polycystic liver disease no associated with ADPKD. Ultrasound and computed tomography imaging were effective in documenting the underlying lesions non-invasively.

  13. Dietary phosphorus and kidney disease.

    PubMed

    Uribarri, Jaime

    2013-10-01

    High serum phosphate is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Therefore, maintenance of normal serum phosphate levels is a major concern in the clinical care of this population with dietary phosphorus restriction and/or use of oral phosphate binders considered to be the best corrective care. This review discusses (1) evidence for an association between serum phosphate levels and bone and cardiovascular disease (CVD) in CKD patients as well as progression of kidney disease itself; (2) the relationship between serum phosphate and dietary phosphorus intake; and (3) implications from these data for future research. Increasing our understanding of the relationship between altered phosphorus metabolism and disease in CKD patients may clarify the potential role of excess dietary phosphorus as a risk factor for disease in the general population.

  14. Genetic polymorphism of ACE and the angiotensin II type1 receptor genes in children with chronic kidney disease

    PubMed Central

    2011-01-01

    Aim and Methods We investigated the association between polymorphisms of the angiotensin converting enzyme-1 (ACE-1) and angiotensin II type one receptor (AT1RA1166C) genes and the causation of renal disease in 76 advanced chronic kidney disease (CKD) pediatric patients undergoing maintenance hemodialysis (MHD) or conservative treatment (CT). Serum ACE activity and creatine kinase-MB fraction (CK-MB) were measured in all groups. Left ventricular mass index (LVMI) was calculated according to echocardiographic measurements. Seventy healthy controls were also genotyped. Results The differences of D allele and DI genotype of ACE were found significant between MHD group and the controls (p = 0.0001). ACE-activity and LVMI were higher in MHD, while CK-MB was higher in CT patients than in all other groups. The combined genotype DD v/s ID+II comparison validated that DD genotype was a high risk genotype for hypertension .~89% of the DD CKD patients were found hypertensive in comparison to ~ 61% of patients of non DD genotype(p = 0.02). The MHD group showed an increased frequency of the C allele and CC genotype of the AT1RA1166C polymorphism (P = 0.0001). On multiple linear regression analysis, C-allele was independently associated with hypertension (P = 0.04). Conclusion ACE DD and AT1R A/C genotypes implicated possible roles in the hypertensive state and in renal damage among children with ESRD. This result might be useful in planning therapeutic strategies for individual patients. PMID:21859496

  15. Sirtuin and metabolic kidney disease.

    PubMed

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-10-01

    Sirtuin is a nicotinamide adenine dinucleotide-dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti-fibrosis effects, anti-oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule-specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy.

  16. Polymorphism of catalase gene promoter in Romanian patients with diabetic kidney disease and type 1 diabetes.

    PubMed

    Panduru, N M; Moţa, E; Moţa, Maria; Cimponeriu, D; Serafinceanu, C; Cheţa, D M

    2010-01-01

    Hyperglycaemia leads to ROS (Reactive oxygen species) generation, affecting the cells that cannot decrease glucose uptake such as: glomerular epithelial cells, mesangial cells and proximal tubule cells. ROS excess seems to activate important pathogenic pathways of development of diabetic nephropathy. The decrease of CAT activity, one of the most important antioxidant enzymes, following to some genetic defects, may be a risk factor for diabetic nephropathy. The purpose of this study is to investigate the association of 21A/T (rs7943316) polymorphism of CAT gene with advanced diabetic nephropathy in patients with type 1 diabetes in Romania. There have been studied 238 patients with T1D (type 1 diabetes), divided into the group with diabetic nephropathy (DN) (106 patients) and the group without renal affectation (132 patients). The genotyping has been made by using PCR-RFLP technique. The analysis of association has been made by using DeFinetti programme. The value considered significant has been p < 0.05. There has been a deviation from Hardy-Weinberg equilibrium in the group with diabetic nephropathy (p = 0.019), the equilibrium being preserved by the control group (p = 0.771). T allele does not confer a risk for advanced diabetic nephropathy (ORT = 0.757, 95% C.I. = 0.405-1.414; P = 0.381), the result being statistically insignificant even taking into consideration the risk allele A (ORA = 0.793, 95% C.I. = 0.465-1.350; P = 0.392). The results remain concordant too after applying the Cochran -Armitage test. Our data do not suggest an effect of 21A/T (rs7943316) polymorphism in the susceptibility for diabetic nephropathy in Romanian patients with type 1 diabetes. Further studies are necessary in order to demonstrate or exclude the role of CAT gene in diabetic nephropathy in patients with type 1 diabetes.

  17. Hereditary kidney diseases: highlighting the importance of classical Mendelian phenotypes.

    PubMed

    Benoit, Geneviève; Machuca, Eduardo; Heidet, Laurence; Antignac, Corinne

    2010-12-01

    A Mendelian inheritance underlies a nonnegligible proportion of hereditary kidney diseases, suggesting that the encoded proteins are essential for maintenance of the renal function. The identification of genes involved in congenital anomalies of the kidney and in familial forms of nephrotic syndrome significantly increased our understanding of the renal development and kidney filtration barrier physiology. This review will focus on the classical phenotype and clinical heterogeneity observed in the monogenic forms of these disorders. In addition, the role of susceptibility genes in kidney diseases with a complex inheritance will also be discussed.

  18. Diabetes and kidney disease

    MedlinePlus

    Diabetic nephropathy; Nephropathy - diabetic; Diabetic glomerulosclerosis; Kimmelstiel-Wilson disease ... 26696680 . Tong LL, Adler S. Prevention and treatment of diabetic nephropathy. In: Johnson RJ, Feehally J, Floege J, eds. ...

  19. NAFLD and Chronic Kidney Disease.

    PubMed

    Marcuccilli, Morgan; Chonchol, Michel

    2016-04-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases.

  20. [Treatment of autosomal dominant polycystic kidney disease].

    PubMed

    Torra, Roser

    2014-01-21

    Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease. However it lacks a specific treatment. Its prevalence is 1/800 and causes the need for renal replacement therapy in 8-10% of patients on dialysis or kidney transplant. It is caused by mutations in the PKD1 and PKD2 genes, which cause a series of alterations in the polycystic cells, which have become therapeutic targets. There are many molecules that are being tested to counteract the alterations of these therapeutic targets. There are studies in all phases of research, from phase i to phase iv. Some of the molecules being tested are tolvaptan, mTOR inhibitors and, among many other, somatostatin analogues. These drugs are extensively reviewed in this article. Based on the accumulated experience the primary objective of the trials is the slowing of the increase in renal volume. Yet other renal end points such as renal function and hypertension are necessary. It is expected that in the coming years we can have specific, well tolerated, effective and affordable drugs for the treatment of autosomal dominant polycystic kidney disease.

  1. Genetics Home Reference: uromodulin-associated kidney disease

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions uromodulin-associated kidney disease uromodulin- ...

  2. Genetics Home Reference: REN-related kidney disease

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions REN-related kidney disease REN- ...

  3. Macrophage in chronic kidney disease

    PubMed Central

    Flaquer, Maria; Cruzado, Josep M.

    2016-01-01

    Chronic kidney disease (CKD) has become a major health problem worldwide. This review describes the role of macrophages in CKD and highlights the importance of anti-inflammatory M2 macrophage activation in both renal fibrosis and wound healing processes. Furthermore, the mechanisms by which M2 macrophages induce renal repair and regeneration are still under debate and currently demand more attention. The M1/M2 macrophage balance is related to the renal microenvironment and could influence CKD progression. In fact, an inflammatory renal environment and M2 plasticity can be the major hurdles to establishing macrophage cell-based therapies in CKD. M2 macrophage cell-based therapy is promising if the M2 phenotype remains stable and is ‘fixed’ by in vitro manipulation. However, a greater understanding of phenotype polarization is still required. Moreover, better strategies and targets to induce reparative macrophages in vivo should guide future investigations in order to abate kidney diseases. PMID:27994852

  4. Mitochondrial biogenesis in kidney disease.

    PubMed

    Weinberg, Joel M

    2011-03-01

    The transcriptional regulation of mitochondrial biogenesis by normal metabolic adaptation or injury has been clarified over the past decade. Mitochondrial biogenesis and its attendant processes enhance metabolic pathways such as fatty acid oxidation and increase antioxidant defense mechanisms that ameliorate injury from aging, tissue hypoxia, and glucose or fatty acid overload, all of which contribute to the pathogenesis of acute and chronic kidney disease. There has been considerable interest in peroxisome proliferator-activated receptors (PPAR) in the kidney, which affect multiple processes in addition to mitochondrial biogenesis. As yet there is relatively little information focused specifically on mitochondrial biogenesis and its regulation by PPARγ coactivators and their modulators such as SIRT1. The available data indicate that these pathways will be fruitful areas for study in the modification of renal disease.

  5. Sleep disorders in kidney disease.

    PubMed

    De Santo, R M; Perna, A; Di Iorio, B R; Cirillo, M

    2010-03-01

    Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

  6. Transcriptome Analysis of Human Diabetic Kidney Disease

    PubMed Central

    Woroniecka, Karolina I.; Park, Ae Seo Deok; Mohtat, Davoud; Thomas, David B.; Pullman, James M.; Susztak, Katalin

    2011-01-01

    OBJECTIVE Diabetic kidney disease (DKD) is the single leading cause of kidney failure in the U.S., for which a cure has not yet been found. The aim of our study was to provide an unbiased catalog of gene-expression changes in human diabetic kidney biopsy samples. RESEARCH DESIGN AND METHODS Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. DKD samples were significant for their racial diversity and decreased glomerular filtration rate (~25–35 mL/min). Stringent statistical analysis, using the Benjamini-Hochberg corrected two-tailed t test, was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. Two different web-based algorithms were used to define differentially regulated pathways. RESULTS We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli, and 330 probesets were commonly differentially expressed in both compartments. Pathway analysis highlighted the regulation of Ras homolog gene family member A, Cdc42, integrin, integrin-linked kinase, and vascular endothelial growth factor signaling in DKD glomeruli. The tubulointerstitial compartment showed strong enrichment for inflammation-related pathways. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in a different set of DKD samples. CONCLUSIONS Our studies have cataloged gene-expression regulation and identified multiple novel genes and pathways that may play a role in the pathogenesis of DKD or could serve as biomarkers. PMID:21752957

  7. Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities.

    PubMed

    Gorgoglione, Bartolomeo; Wang, Tiehui; Secombes, Christopher J; Holland, Jason W

    2013-07-16

    The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate/inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease.

  8. Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities

    PubMed Central

    2013-01-01

    The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate / inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell / antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease. PMID:23865616

  9. Chromium-induced kidney disease

    SciTech Connect

    Wedeen, R.P. ); Qian, Lifen )

    1991-05-01

    Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of {beta}{sub 2}-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome palters and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chromic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced chromic renal disease cannot be interpreted as evidence of the absence of such injury.

  10. Refining the map and defining flanking markers of the gene for autosomal recessive polycystic kidney disease on chromosome 6p21.1-p12

    SciTech Connect

    Muecher, G.; Wirth, B.; Zerres, K.

    1994-12-01

    Autosomal recessive polycystic kidney disease (ARPKD) is one of the most important hereditary nephropathies in childhood. The reported incidence is 1:6,000 - 1:40,000 live births. We recently mapped the gene for ARPKD to chromosome 6p21-cen by linkage analysis. In a more extensive study, we analyzed two additional microsatellite markers of the region 6p21 in 12 multiplex and 4 simplex ARPKD families, which have previously been published by Zerres et al. (1994). Because of additional typing, more families have become informative for single markers. 12 refs., 2 figs., 2 tabs.

  11. Myeloperoxidase in chronic kidney disease.

    PubMed

    Madhusudhana Rao, A; Anand, Usha; Anand, C V

    2011-01-01

    Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II-V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = -0.85, P < 0.001) and creatinine (r = -0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.

  12. Chronic kidney disease in pregnancy.

    PubMed

    Chinnappa, V; Ankichetty, S; Angle, P; Halpern, S H

    2013-07-01

    Parturients with renal insufficiency or failure present a significant challenge for the anesthesiologist. Impaired renal function compromises fertility and increases both maternal and fetal morbidity and mortality. Close communication amongst medical specialists, including nephrologists, obstetricians, neonatologists and anesthesiologists is required to ensure the safety of mother and child. Pre-existing diseases should be optimized and close surveillance of maternal and fetal condition is required. Kidney function may deteriorate during pregnancy, necessitating early intervention. The goal is to maintain hemodynamic and physiologic stability while the demands of the pregnancy change. Drugs that may adversely affect the fetus, are nephrotoxic or are dependent on renal elimination should be avoided.

  13. System analysis of gene mutations and clinical phenotype in Chinese patients with autosomal-dominant polycystic kidney disease

    PubMed Central

    Jin, Meiling; Xie, Yuansheng; Chen, Zhiqiang; Liao, Yujie; Li, Zuoxiang; Hu, Panpan; Qi, Yan; Yin, Zhiwei; Li, Qinggang; Fu, Ping; Chen, Xiangmei

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder mainly caused by mutation in PKD1/PKD2. However, ethnic differences in mutations, the association between mutation genotype/clinical phenotype, and the clinical applicable value of mutation detection are poorly understood. We made systematically analysis of Chinese ADPKD patients based on a next-generation sequencing platform. Among 148 ADPKD patients enrolled, 108 mutations were detected in 127 patients (85.8%). Compared with mutations in Caucasian published previously, the PKD2 mutation detection rate was lower, and patients carrying the PKD2 mutation invariably carried the PKD1 mutation. The definite pathogenic mutation detection rate was lower, whereas the multiple mutations detection rate was higher in Chinese patients. Then, we correlated PKD1/PKD2 mutation data and clinical data: patients with mutation exhibited a more severe phenotype; patients with >1 mutations exhibited a more severe phenotype; patients with pathogenic mutations exhibited a more severe phenotype. Thus, the PKD1/PKD2 mutation status differed by ethnicity, and the PKD1/PKD2 genotype may affect the clinical phenotype of ADPKD. Furthermore, it makes sense to detect PKD1/PKD2 mutation status for early diagnosis and prognosis, perhaps as early as the embryo/zygote stage, to facilitate early clinical intervention and family planning. PMID:27782177

  14. Stem cells in kidney diseases.

    PubMed

    Soler, María José; José Tomas, Ortiz-Pérez

    2012-01-01

    Circulating bone marrow-derived endothelial progenitor cells (EPCs) seem to play a crucial role in both vasculogenesis and vascular homeostasis. Chronic kidney disease is a state of endothelial dysfunction, accelerated progression of atherosclerosis and high cardiovascular risk. As a consequence, cardiovascular disorders are the main cause of death in end-stage renal disease (ESRD). It has been shown that patients with advanced renal failure have decreased number of bone marrow-derived endothelial progenitor cells and impaired EPCs function. Moreover, in kidney transplant patients, renal graft function significantly correlated with EPC number. The reduced number of EPCs in patients with ESRD has been ascribed to the uremia. Therefore, therapies that improve the uremic status in dialysis patients such as nocturnal hemodialysis are associated with restoration of impaired EPCs number and migratory function. In fact, some of the common treatments for patients with chronic kidney disease such as erythropoietin, statins and angiotensin II receptor antagonist increase the number of EPCs. Nowadays, there is growing evidence indicating that, under pathophysiological conditions, stem cells (SCs) derived from bone marrow are able to migrate in the injured kidney, and they seem to play a role in glomerular and tubular regeneration. After acute tubular renal injury, surviving tubular epithelial cells and putative renal stem cells proliferate and differentiate into tubular epithelial cells to promote structural and functional repair. Moreover, bone marrow stem cells, including hematopoietic stem cells and mesenchymal stem cells can also participate in the repair process by proliferation and differentiation into renal lineages. For instance, mesenchymal SCs have been shown to decrease inflammation and enhance renal regeneration. The administration of ex vivo expanded bone marrow-derived mesenchymal SCs have been proved to be beneficial in various experimental models of acute

  15. [Anemia in chronic kidney disease].

    PubMed

    Amador-Medina, Lauro Fabián

    2014-01-01

    Anemia is almost unavoidable in the last stages of chronic kidney disease. It is defined as a condition where hemoglobin concentration is below 2 standard deviations from the mean hemoglobin level of the general population, corrected for age and sex (typically, hemoglobin < 13 g/dL in adults and 12 g/dL in women). Although the cause is multi-factorial, the most known is inadequate erythropoietin production. Anemia has been associated with poor prognosis in patients with several conditions such as cancer, chronic kidney disease and congestive heart failure. Treatment with erythropoiesis-stimulating agents, such as erythropoietin, is a logical strategy that has enabled clinical improvement and reduced transfusion requirements for the patients; however, total correction of anemia with erythropoiesis-stimulating agents has demonstrated an increase in the risk of mortality or cardiovascular complications associated with these agents. In randomized trials, the achievement of normal or nearly normal hemoglobin levels is not associated with improved survival and reduced cardiovascular risk; however the ideal hemoglobin level with the use of erythropoiesis-stimulating agents seems to be problematic. More information is needed in order to obtain definite conclusions; in the meantime, using the lowest possible dose of erythropoietin seems to be the most prudent approach.

  16. Chronic kidney disease in children

    PubMed Central

    Becherucci, Francesca; Roperto, Rosa Maria; Materassi, Marco; Romagnani, Paola

    2016-01-01

    Chronic kidney disease (CKD) is a major health problem worldwide. Although relatively uncommon in children, it can be a devastating illness with many long-term consequences. CKD presents unique features in childhood and may be considered, at least in part, as a stand-alone nosologic entity. Moreover, some typical features of paediatric CKD, such as the disease aetiology or cardiovascular complications, will not only influence the child's health, but also have long-term impact on the life of the adult that they will become. In this review we will focus on the unique issues of paediatric CKD, in terms of aetiology, clinical features and treatment. In addition, we will discuss factors related to CKD that start during childhood and require appropriate treatments in order to optimize health outcomes and transition to nephrologist management in adult life. PMID:27478602

  17. Polycystic kidney disease: an unrecognized emerging infectious disease?

    PubMed Central

    Miller-Hjelle, M. A.; Hjelle, J. T.; Jones, M.; Mayberry, W. R.; Dombrink-Kurtzman, M. A.; Peterson, S. W.; Nowak, D. M.; Darras, F. S.

    1997-01-01

    Polycystic kidney disease (PKD) is one of the most common genetic diseases in humans. We contend that it may be an emerging infectious disease and/or microbial toxicosis in a vulnerable human subpopulation. Use of a differential activation protocol for the Limulus amebocyte lysate (LAL) assay showed bacterial endotoxin and fungal (1-->3)-beta-D-glucans in cyst fluids from human kidneys with PKD. Fatty acid analysis of cyst fluid confirmed the presence of 3-hydroxy fatty acids characteristic of endotoxin. Tissue and cyst fluid from three PKD patients were examined for fungal components. Serologic tests showed Fusarium, Aspergillus, and Candida antigens. IgE, but not IgG, reactive with Fusarium and Candida were also detected in cyst fluid. Fungal DNA was detected in kidney tissue and cyst fluid from these three PKD patients, but not in healthy human kidney tissue. We examine the intertwined nature of the actions of endotoxin and fungal components, sphingolipid biology in PKD, the structure of PKD gene products, infections, and integrity of gut function to establish a mechanistic hypothesis for microbial provocation of human cystic disease. Proof of this hypothesis will require identification of the microbes and microbial components involved and multifaceted studies of PKD cell biology. PMID:9204292

  18. [Recent developments in genetic kidney diseases].

    PubMed

    Liebau, M C; Benzing, T

    2011-05-01

    The improved understanding of genetic kidney diseases has given rise to a more detailed understanding of kidney function within the last decade. Insights into the pathophysiological principles of frequent kidney diseases - partly inherited, partly acquired - have been obtained by the investigation of rare genetic disorders and can now serve as a starting point for the development of novel therapeutic strategies. In this way various clinical multicenter trials, which are based on the observations made in basic science have been established for the very common autosomal dominant polycystic kidney disease. Furthermore, the influence of genetic aspects on frequent kidney diseases, e. g. diabetic nephropathy, is becoming more obvious. This article aims to give an overview over essential recent development in the field of genetic kidney diseases.

  19. Do Kidney Stone Formers Have A Kidney Disease?

    PubMed Central

    Zisman, Anna L.; Evan, Andrew P.; Coe, Fredric L.; Worcester, Elaine M.

    2015-01-01

    Nephrolithiasis is a highly prevalent disorder affecting approximately one in eleven people and is associated with multiple complications including hypertension, cardiovascular disease, and chronic kidney disease. Significant epidemiologic associations with chronic kidney disease and ESRD have been noted and are reviewed herein, but debate persists in the literature as to whether kidney stone formation is a pathogenic process contributing to kidney disease. Corroborating evidence supporting the presence of kidney disease in stone formers includes the variability of renal function by stone type, the positive association of stone size with renal dysfunction, the presence of markers of renal injury in the urine of even asymptomatic stone formers, and direct evidence of renal tissue injury on histopathology. Proposed pathogenic mechanisms include recurrent obstruction and comorbid conditions such as recurrent urinary tract infections and structural abnormalities. Recent work evaluating the renal histopathology of different groups of stone formers adds further granularity, suggesting variability in mechanisms of renal injury by stone type and confirming the pathogenic effects of crystal formation. Genetic abnormalities leading to stone formation including cystinuria and primary hyperoxaluria, among others, contribute to the burden of disease in the stone-forming population. PMID:26376133

  20. Heritability of Measures of Kidney Disease Among Zuni Indians: The Zuni Kidney Project

    PubMed Central

    MacCluer, Jean W.; Scavini, Marina; Shah, Vallabh O.; Cole, Shelley A.; Laston, Sandra L.; Voruganti, V. Saroja; Paine, Susan S.; Eaton, Alfred J.; Comuzzie, Anthony G.; Tentori, Francesca; Pathak, Dorothy R.; Bobelu, Arlene; Bobelu, Jeanette; Ghahate, Donica; Waikaniwa, Mildred; Zager, Philip G.

    2010-01-01

    Background The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. Study Design A community-based participatory research approach was used to recruit family members of individuals with kidney disease. Setting & Participants The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. Predictor Outcomes & Measurements Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was ≥0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. Results Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. Limitations Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. Conclusions Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and

  1. Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

    PubMed Central

    Hashimoto, Hisashi; Miyamoto, Rieko; Watanabe, Naoki; Shiba, Dai; Ozato, Kenjiro; Inoue, Chikako; Kubo, Yuko; Koga, Akihiko; Jindo, Tomoko; Narita, Takanori; Naruse, Kiyoshi; Ohishi, Kazuko; Nogata, Keiko; Shin-I, Tadasu; Asakawa, Shuichi; Shimizu, Nobuyoshi; Miyamoto, Tomotsune; Mochizuki, Toshio; Yokoyama, Takahiko; Hori, Hiroshi; Takeda, Hiroyuki; Kohara, Yuji; Wakamatsu, Yuko

    2009-01-01

    Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients. PMID:19609364

  2. Probiotics and chronic kidney disease.

    PubMed

    Koppe, Laetitia; Mafra, Denise; Fouque, Denis

    2015-11-01

    Probiotics are the focus of a thorough investigation as a natural biotreatment due to their various health-promoting effects and inherent ability to fight specific diseases including chronic kidney disease (CKD). Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Because many of the multifactorial physiological functions of probiotics are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical. The interest in developing new research initiatives on probiotics in CKD have increased over the last decade with the goal of fully exploring their therapeutic potentials. The efficacy of probiotics to decrease uremic toxin production and to improve renal function has been investigated in in vitro models and in various animal and human CKD studies. However to date, the quality of intervention trials investigating this novel CKD therapy is still lacking. This review outlines potential mechanisms of action and efficacy of probiotics as a new CKD management tool, with a particular emphasis on uremic toxin production and inflammation.

  3. The regulation and function of microRNAs in kidney diseases.

    PubMed

    Wei, Qingqing; Mi, Qing-Sheng; Dong, Zheng

    2013-07-01

    MicroRNAs (miRNA) are endogenous short noncoding RNAs, which regulate virtually all major cellular processes by inhibiting target gene expression. In kidneys, miRNAs have been implicated in renal development, homeostasis, and physiological functions. In addition, miRNAs play important roles in the pathogenesis of various renal diseases, including renal carcinoma, diabetic nephropathy, acute kidney injury, hypertensive nephropathy, polycystic kidney disease, and others. Furthermore, miRNAs may have great values as biomarkers in different kidney diseases.

  4. Kidney-specific transposon-mediated gene transfer in vivo.

    PubMed

    Woodard, Lauren E; Cheng, Jizhong; Welch, Richard C; Williams, Felisha M; Luo, Wentian; Gewin, Leslie S; Wilson, Matthew H

    2017-03-20

    Methods enabling kidney-specific gene transfer in adult mice are needed to develop new therapies for kidney disease. We attempted kidney-specific gene transfer following hydrodynamic tail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but found expression primarily in the liver. In order to achieve kidney-specific transgene expression, we tested direct hydrodynamic injection of a DNA solution into the renal pelvis and found that luciferase expression was strong in the kidney and absent from extra-renal tissues. We observed heterogeneous, low-level transfection of the collecting duct, proximal tubule, distal tubule, interstitial cells, and rarely glomerular cells following injection. To assess renal injury, we performed the renal pelvis injections on uninephrectomised mice and found that their blood urea nitrogen was elevated at two days post-transfer but resolved within two weeks. Although luciferase expression quickly decreased following renal pelvis injection, the use of the piggyBac transposon system improved long-term expression. Immunosuppression with cyclophosphamide stabilised luciferase expression, suggesting immune clearance of the transfected cells occurs in immunocompetent animals. Injection of a transposon expressing erythropoietin raised the haematocrit, indicating that the developed injection technique can elicit a biologic effect in vivo. Hydrodynamic renal pelvis injection enables transposon mediated-kidney specific gene transfer in adult mice.

  5. Kidney-specific transposon-mediated gene transfer in vivo

    PubMed Central

    Woodard, Lauren E.; Cheng, Jizhong; Welch, Richard C.; Williams, Felisha M.; Luo, Wentian; Gewin, Leslie S.; Wilson, Matthew H.

    2017-01-01

    Methods enabling kidney-specific gene transfer in adult mice are needed to develop new therapies for kidney disease. We attempted kidney-specific gene transfer following hydrodynamic tail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but found expression primarily in the liver. In order to achieve kidney-specific transgene expression, we tested direct hydrodynamic injection of a DNA solution into the renal pelvis and found that luciferase expression was strong in the kidney and absent from extra-renal tissues. We observed heterogeneous, low-level transfection of the collecting duct, proximal tubule, distal tubule, interstitial cells, and rarely glomerular cells following injection. To assess renal injury, we performed the renal pelvis injections on uninephrectomised mice and found that their blood urea nitrogen was elevated at two days post-transfer but resolved within two weeks. Although luciferase expression quickly decreased following renal pelvis injection, the use of the piggyBac transposon system improved long-term expression. Immunosuppression with cyclophosphamide stabilised luciferase expression, suggesting immune clearance of the transfected cells occurs in immunocompetent animals. Injection of a transposon expressing erythropoietin raised the haematocrit, indicating that the developed injection technique can elicit a biologic effect in vivo. Hydrodynamic renal pelvis injection enables transposon mediated-kidney specific gene transfer in adult mice. PMID:28317878

  6. Niacin and Chronic Kidney Disease.

    PubMed

    Taketani, Yutaka; Masuda, Masashi; Yamanaka-Okumura, Hisami; Tatsumi, Sawako; Segawa, Hiroko; Miyamoto, Ken-ichi; Takeda, Eiji; Yamamoto, Hironori

    2015-01-01

    Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD. Hyperphosphatemia is thought to be a central-risk factor for CKD-MBD. Therefore, managing hyperphosphatemia is crucial to prevent CKD-MBD and CVD. It is difficult to achieve the target serum phosphate level through dietary modifications alone in patients with hyperphosphatemia, because most foods contain phosphate. Thus, phosphate binders such as calcium carbonate are commonly prescribed to CKD patients with hyperphosphatemia, but these have undesirable side effects. Inhibition of intestinal phosphate transport activity has also been investigated as an alternative approach for controlling serum phosphate levels in CKD patients. Nicotinamide, which is the amide of niacin, can inhibit intestinal phosphate transport. Niacin and related compounds have also been developed as drugs for hyperlipidemia conditions, especially hypertriglyceridemia with low high-density lipoprotein. This type of dyslipidemia is frequently observed in CKD patients and is a modifiable risk factor for CVD. Thus, niacin and related compounds may have utility for the treatment of both hyperphosphatemia and dyslipidemia in CKD patients to prevent CVD.

  7. Cerebral Small Vessel Disease and Chronic Kidney Disease

    PubMed Central

    2015-01-01

    Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

  8. Stop chronic kidney disease progression: Time is approaching

    PubMed Central

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-01-01

    Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression. PMID:27152262

  9. Maternal diet programs embryonic kidney gene expression.

    PubMed

    Welham, Simon J M; Riley, Paul R; Wade, Angie; Hubank, Mike; Woolf, Adrian S

    2005-06-16

    Human epidemiological data associating birth weight with adult disease suggest that organogenesis is "programmed" by maternal diet. In rats, protein restriction in pregnancy produces offspring with fewer renal glomeruli and higher systemic blood pressures than controls. We tested the hypothesis that maternal diet alters gene expression in the metanephros, the precursor of the definitive mammalian kidney. We demonstrated that maternal low-protein diet initiated when pregnancy starts and maintained to embryonic day 13, when the metanephros consists of mesenchyme surrounding a once-branched ureteric bud, is sufficient to significantly reduce glomerular numbers in offspring by about 20%. As assessed by representational difference analyses and real-time quantitative polymerase chain reactions, low-protein diet modulated gene expression in embryonic day 13 metanephroi. In particular, levels of prox-1, the ortholog of Drosophila transcription factor prospero, and cofilin-1, a regulator of the actin cytoskeleton, were reduced. During normal metanephrogenesis, prox-1 protein was first detected in mesenchymal cells around the ureteric tree and thereafter in nascent nephron epithelia, whereas cofilin-1 immunolocalized to bud derivatives and condensing mesenchyme. Previously, we reported that low-protein diets increased mesenchymal apoptosis cells when metanephrogenesis began and thereafter reduced numbers of precursor cells. Collectively, these studies prove that the maternal diet programs the embryonic kidney, altering cell turnover and gene expression at a time when nephrons and glomeruli have yet to form. The human implication is that the maternal diet ingested between conception and 5- 6-wk gestation contributes to the variation in glomerular numbers that are known to occur between healthy and hypertensive populations.

  10. Wnt signaling in kidney tubulointerstitium during disease.

    PubMed

    Maarouf, Omar H; Ikeda, Yoichiro; Humphreys, Benjamin D

    2015-02-01

    The evolutionary conserved Wnt signaling transduction pathway plays essential roles in a wide array of biologic processes including embryonic development, branching morphogenesis, proliferation and carcinogenesis. Over the past ten years it has become increasingly clear that Wnt signaling also regulates the response of adult organs to disease processes, including kidney disease. This review will focus on the growing literature implicating important roles for Wnt signaling during disease in two separate kidney compartments: the tubular epithelium and the interstitium.

  11. Why kidneys fail in autosomal dominant polycystic kidney disease.

    PubMed

    Grantham, Jared J; Mulamalla, Sumanth; Swenson-Fields, Katherine I

    2011-08-23

    The weight of evidence gathered from studies in humans with hereditary polycystic kidney disease (PKD)1 and PKD2 disorders, as well as from experimental animal models, indicates that cysts are primarily responsible for the decline in glomerular filtration rate that occurs fairly late in the course of the disease. The processes underlying this decline include anatomic disruption of glomerular filtration and urinary concentration mechanisms on a massive scale, coupled with compression and obstruction by cysts of adjacent nephrons in the cortex, medulla and papilla. Cysts prevent the drainage of urine from upstream tributaries, which leads to tubule atrophy and loss of functioning kidney parenchyma by mechanisms similar to those found in ureteral obstruction. Cyst-derived chemokines, cytokines and growth factors result in a progression to fibrosis that is comparable with the development of other progressive end-stage renal diseases. Treatment of renal cystic disorders early enough to prevent or reduce cyst formation or slow cyst growth, before the secondary changes become widespread, is a reasonable strategy to prolong the useful function of kidneys in patients with autosomal dominant polycystic kidney disease.

  12. [Membranous kidney diseases in adults].

    PubMed

    Sobarzo Toro, Martín; Vilches, Antonio

    2004-01-01

    Membranous nephropathy is the most common histologic phenotype associated with the primary nephrotic syndrome in adults and the second most common etiological diagnosis in over sixteen hundred renal biopsies on native kidneys processed at our institution over a 30 year period. Renal survival at 10 years is about 70%, but the course of the disease is related to a series of factors which have constituted the basis for mathematical models developed to predict the natural history in a given individual. These factors are gender, age, renal function at the time of diagnosis, presence of the nephrotic syndrome, high blood pressure and the degree of structural damage. Although in low risk patients a period of observation and the use of ACE inhibitors is a reasonable option, most nephrologists would elect to use pharmacological treatment to induce remissions of proteinuria and preserve renal function. The use of steroids and cytotoxic agents in alternating monthly cycles over six months is firmly supported by controlled, randomized clinical trials. If patients are resistant to this regimen or clinical considerations indicate it may be inappropriately toxic, the use of cyclosporin over 6 to 12 months is also a good choice, and it has been shown to be useful even in the context of deteriorating renal function. Mycophenolate mofetil and possibly rituximab may be options of last resort before considering the patient resistant to therapy. At all times, treatment of hypertension, non-specific antiproteinuric measures, and preventing complications of the nephrotic state should be top priorities in the overall therapeutic strategy.

  13. Nutrition and chronic kidney disease.

    PubMed

    Fouque, Denis; Pelletier, Solenne; Mafra, Denise; Chauveau, Philippe

    2011-08-01

    The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed patients.

  14. Hypoglycemia, chronic kidney disease, and diabetes mellitus.

    PubMed

    Alsahli, Mazen; Gerich, John E

    2014-11-01

    Hypoglycemia is a major problem associated with substantial morbidity and mortality in patients with diabetes and is often a major barrier to achieving optimal glycemic control. Chronic kidney disease not only is an independent risk factor for hypoglycemia but also augments the risk of hypoglycemia that is already present in people with diabetes. This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetes and chronic kidney disease and reviews therapeutic considerations in this situation. PubMed and MEDLINE were searched for literature published in English from January 1989 to May 2014 for diabetes mellitus, hypoglycemia, chronic kidney disease, and chronic renal insufficiency.

  15. High Blood Pressure and Kidney Disease

    MedlinePlus

    ... Kidney disease is diagnosed with urine and blood tests. Health care providers measure blood pressure with a blood pressure ... the sample to a lab for analysis. A health care provider may order a blood test to estimate how much blood the kidneys filter ...

  16. Obesity and kidney disease: Beyond the hyperfiltration.

    PubMed

    Mascali, A; Franzese, O; Nisticò, S; Campia, U; Lauro, D; Cardillo, C; Di Daniele, N; Tesauro, M

    2016-09-01

    In industrialized countries, overweight and obesity account for approximately 13.8% and 24.9% of the kidney disease observed in men and women, respectively. Moreover, obesity-associated glomerulopathy is now considered as "an emerging epidemic." Kidney function can be negatively impacted by obesity through several mechanisms, either direct or indirect. While it is well established that obesity represents the leading risk factor for type 2 diabetes and hypertension, awareness that obesity is associated with direct kidney damage independently of hypertension and diabetes is still not widespread. In this paper we will discuss the emerging role of adipose tissue, particularly in the visceral depot, in obesity-induced chronic kidney damage.

  17. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids.

    PubMed

    Freedman, Benjamin S; Brooks, Craig R; Lam, Albert Q; Fu, Hongxia; Morizane, Ryuji; Agrawal, Vishesh; Saad, Abdelaziz F; Li, Michelle K; Hughes, Michael R; Werff, Ryan Vander; Peters, Derek T; Lu, Junjie; Baccei, Anna; Siedlecki, Andrew M; Valerius, M Todd; Musunuru, Kiran; McNagny, Kelly M; Steinman, Theodore I; Zhou, Jing; Lerou, Paul H; Bonventre, Joseph V

    2015-10-23

    Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications.

  18. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids

    PubMed Central

    Freedman, Benjamin S.; Brooks, Craig R.; Lam, Albert Q.; Fu, Hongxia; Morizane, Ryuji; Agrawal, Vishesh; Saad, Abdelaziz F.; Li, Michelle K.; Hughes, Michael R.; Werff, Ryan Vander; Peters, Derek T.; Lu, Junjie; Baccei, Anna; Siedlecki, Andrew M.; Valerius, M. Todd; Musunuru, Kiran; McNagny, Kelly M.; Steinman, Theodore I.; Zhou, Jing; Lerou, Paul H.; Bonventre, Joseph V.

    2015-01-01

    Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications. PMID:26493500

  19. Sex hormones in women with kidney disease.

    PubMed

    Ahmed, Sofia B; Ramesh, Sharanya

    2016-11-01

    Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question.

  20. Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

    SciTech Connect

    Chen, Wei-Jen; Huang, Ya-Li; Shiue, Horng-Sheng; Chen, Tzen-Wen; Lin, Yuh-Feng; Huang, Chao-Yuan; Lin, Ying-Chin; Han, Bor-Cheng; Hsueh, Yu-Mei

    2014-09-01

    A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined

  1. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  2. JAK INHIBITION AND PROGRESSIVE KIDNEY DISEASE

    PubMed Central

    Brosius, Frank C.; He, John Cijiang

    2015-01-01

    Purpose of review To review the role of JAK-STAT signaling in the progression of chronic kidney diseases. Recent findings The JAK-STAT pathway transmits signals from extracellular ligands, including many cytokines and chemokines. While these responses are best characterized in lymphoid cells, they also occur in kidney cells such as podocytes, mesangial cells, and tubular cells. JAK-STAT expression and signaling abnormalities occur in humans and animal models of different chronic kidney diseases. Enhanced expression and augmented activity of JAK1, JAK2 and STAT3 promote diabetic nephropathy and their inhibition appears to reduce disease. Activation of JAK-STAT signaling in autosomal dominant polycystic kidney disease may play an important role in cyst growth. Activation of JAK-STAT signaling promotes HIV-associated nephropathy and may also participate in the tubular responses to chronic obstructive uropathy. Based on data from experimental models, inhibition of JAK-STAT signaling, via increased expression of the suppressors of cytokine signaling proteins or pharmacologic inhibition of JAK and STAT proteins, could play a therapeutic role in multiple chronic kidney diseases. Summary Activation of the JAK-STAT pathway appears to play a role in the progression of some chronic kidney diseases. More work is needed to determine the specific role the pathway plays in individual diseases. PMID:25415616

  3. Complement related kidney diseases: Recurrence after transplantation.

    PubMed

    Salvadori, Maurizio; Bertoni, Elisabetta

    2016-12-24

    The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.

  4. Complement related kidney diseases: Recurrence after transplantation

    PubMed Central

    Salvadori, Maurizio; Bertoni, Elisabetta

    2016-01-01

    The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials. PMID:28058212

  5. Kidney Disease Statistics for the United States

    MedlinePlus

    ... kidney diseases, obesity, weight and more Healthy Moments Radio Broadcast Health tips from Dr. Griffin Rodgers, Director ... Research Metabolic Clinical Research Unit Volunteers Healthy Moments Radio Broadcast Expand Healthy Moments Radio Broadcast Archive Broadcasting ...

  6. ACE2 alterations in kidney disease

    PubMed Central

    Soler, María José; Wysocki, Jan; Batlle, Daniel

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1–7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance. PMID:23956234

  7. Vaccination against salmonid bacterial kidney disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial kidney disease (BKD) of salmonid fishes, caused by Renibacterium salmoninarum, has presented challenges for development of effective vaccines, despite several decades of research. The only vaccine against BKD that is commercially licensed is an injectable preparation containing live cells ...

  8. Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo.

    PubMed

    Pereira, Renata C; Delany, Anne M; Khouzam, Nadine M; Bowen, Richard E; Freymiller, Earl G; Salusky, Isidro B; Wesseling-Perry, Katherine

    2015-03-01

    Osteocytes regulate bone turnover and mineralization in chronic kidney disease. As osteocytes are derived from osteoblasts, alterations in osteoblast function may regulate osteoblast maturation, osteocytic transition, bone turnover, and skeletal mineralization. Thus, primary osteoblast-like cells were cultured from bone chips obtained from 24 pediatric ESKD patients. RNA expression in cultured cells was compared with RNA expression in cells from healthy individuals, to RNA expression in the bone core itself, and to parameters of bone histomorphometry. Proliferation and mineralization rates of patient cells were compared with rates in healthy control cells. Associations were observed between bone osteoid accumulation, as assessed by bone histomorphometry, and bone core RNA expression of osterix, matrix gla protein, parathyroid hormone receptor 1, and RANKL. Gene expression of osteoblast markers was increased in cells from ESKD patients and signaling genes including Cyp24A1, Cyp27B1, VDR, and NHERF1 correlated between cells and bone cores. Cells from patients with high turnover renal osteodystrophy proliferated more rapidly and mineralized more slowly than did cells from healthy controls. Thus, primary osteoblasts obtained from patients with ESKD retain changes in gene expression ex vivo that are also observed in bone core specimens. Evaluation of these cells in vitro may provide further insights into the abnormal bone biology that persists, despite current therapies, in patients with ESKD.

  9. Wasting in chronic kidney disease.

    PubMed

    Mak, Robert H; Ikizler, Alp T; Kovesdy, Csaba P; Raj, Dominic S; Stenvinkel, Peter; Kalantar-Zadeh, Kamyar

    2011-03-01

    Wasting/cachexia is prevalent among patients with chronic kidney disease (CKD). It is to be distinguished from malnutrition, which is defined as the consequence of insufficient food intake or an improper diet. Malnutrition is characterized by hunger, which is an adaptive response, whereas anorexia is prevalent in patients with wasting/cachexia. Energy expenditure decreases as a protective mechanism in malnutrition whereas it remains inappropriately high in cachexia/wasting. In malnutrition, fat mass is preferentially lost and lean body mass and muscle mass is preserved. In cachexia/wasting, muscle is wasted and fat is relatively underutilized. Restoring adequate food intake or altering the composition of the diet reverses malnutrition. Nutrition supplementation does not totally reverse cachexia/wasting. The diagnostic criteria of cachexia/protein-energy wasting in CKD are considered. The association of wasting surrogates, such as serum albumin and prealbumin, with mortality is strong making them robust outcome predictors. At the patient level, longevity has consistently been observed in patients with CKD who have more muscle and/or fat, who report better appetite and who eat more. Although inadequate nutritional intake may contribute to wasting or cachexia, recent evidence indicates that other factors, including systemic inflammation, perturbations of appetite-controlling hormones from reduced renal clearance, aberrant neuropeptide signaling, insulin and insulin-like growth factor resistance, and metabolic acidosis, may be important in the pathogenesis of CKD-associated wasting. A number of novel therapeutic approaches, such as ghrelin agonists and melanocortin receptor antagonists are currently at the experimental level and await confirmation by randomized controlled clinical trials in patients with CKD-associated cachexia/wasting syndrome.

  10. Biomarkers in chronic kidney disease, from kidney function to kidney damage

    PubMed Central

    Lopez-Giacoman, Salvador; Madero, Magdalena

    2015-01-01

    Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD. PMID:25664247

  11. Cardiovascular complications of pediatric chronic kidney disease

    PubMed Central

    2006-01-01

    Cardiovascular disease (CVD) mortality is a leading cause of death in adult chronic kidney disease (CKD), with exceptionally high rates in young adults, according to the Task Force on Cardiovascular Disease. Recent data indicate that cardiovascular complications are already present in children with CKD. This review summarizes the current literature on cardiac risk factors, mortality and morbidity in children with CKD. PMID:17120060

  12. [Chronic kidney diseases, metformin and lactic acidosis].

    PubMed

    Borbély, Zoltán

    2016-04-01

    Chronic kidney disease and diabetes mellitus represent a worldwide public health problem. The incidence of these diseases is gradually growing into epidemic proportions. In many cases they occur simultaneously, what leads to increased morbidity and mortality among the affected patients. The majority of the patients treated for diabetes mellitus are unaware of the presence of renal insufficiency. Vascular hypertrophy and diabetic kidney disease in patients with type 2 diabetes are the most common causes of kidney failure in countries with advanced healthcare systems. Metformin is a basic drug used for the treatment of type 2 diabetes mellitus. It is excreted in an unchanged form by the kidneys. When administered to patients with renal insufficiency, sepsis, dehydration or after the parenteral administration of iodinated contrast agents, metformin can cause lactic acidosis, which is also associated with an increased mortality rate.

  13. Hypermethylation of the CaSR and VDR genes in the parathyroid glands in chronic kidney disease rats with high-phosphate diet.

    PubMed

    Uchiyama, Taketo; Tatsumi, Norifumi; Kamejima, Sahoko; Waku, Tsuyoshi; Ohkido, Ichiro; Yokoyama, Keitaro; Yokoo, Takashi; Okabe, Masataka

    2016-10-01

    Chronic kidney disease (CKD) disrupts mineral homeostasis and its representative pathosis is defined as secondary hyperparathyroidism (SHPT). SHPT occurs during the early course of progressive renal insufficiency, and is associated with mortality and cardiovascular events. SHPT results in reduction of calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) in the parathyroid glands during CKD. However, the precise mechanism of CaSR and VDR reduction is largely unknown. CKD was induced through two-step 5/6 nephrectomy, and then CKD rats and sham-operated rats were maintained for 8 weeks on diets containing 0.7 % phosphorus (normal phosphate) or 1.2 % phosphorus (high phosphate). In gene expression analysis, TaqMan probes were used for quantitative real-time polymerase chain reaction. Finally, CaSR and VDR protein expressions were analyzed using immunohistochemistry. DNA methylation analysis was performed using a restriction digestion and quantitative PCR. CaSR and VDR mRNA were reduced only in CKD rats fed the high-phosphorus diets (CKD HP), then CaSR and VDR immunohistochemical expressions were compatible with gene expression assay. SHPT was then confirmed only in CKD HP rats. Furthermore, sole CKD HP rats showed the hypermethylation in CaSR and VDR genes; however, the percentage methylation of both genes was low. Although CaSR and VDR hypermethylation was demonstrated in PTGs of CKD HP rats, the extent of hypermethylation was insufficient to support the relevance between hypermethylation and down-regulation of gene expression because of the low percentage of methylation. Consequently, our data suggest that mechanisms, other than DNA hypermethylation, were responsible for the reduction in mRNA and protein levels of CaSR and VDR in PTGs of CKD HP rats.

  14. Kidney disease in pregnancy: (Women's Health Series).

    PubMed

    Gyamlani, Geeta; Geraci, Stephen A

    2013-09-01

    Kidney disease and pregnancy may exist in two general settings: acute kidney injury that develops during pregnancy, and chronic kidney disease that predates conception. In the first trimester of pregnancy, acute kidney injury is most often the result of hyperemesis gravidarum, ectopic pregnancy, or miscarriage. In the second and third trimesters, the common causes of acute kidney injury are severe preeclampsia, hemolysis-elevated liver enzymes-low platelets syndrome, acute fatty liver of pregnancy, and thrombotic microangiopathies, which may pose diagnostic challenges to the clinician. Cortical necrosis and obstructive uropathy are other conditions that may lead to acute kidney injury in these trimesters. Early recognition of these disorders is essential to timely treatment that can improve both maternal and fetal outcomes. In women with preexisting kidney disease, pregnancy-related outcomes depend upon the degree of renal impairment, the amount of proteinuria, and the severity of hypertension. Neonatal and maternal outcomes in pregnancies among renal transplant patients are generally good if the mother has normal baseline allograft function. Common renally active drugs and immunosuppressant medications must be prescribed, with special considerations in pregnant patients.

  15. DNA vaccination as a treatment for chronic kidney disease.

    PubMed

    Wang, Yuan Min; Alexander, Stephen I

    2014-01-01

    Chronic kidney disease is one of the major health problems worldwide. DNA vaccination delivers plasmid DNA encoding the target gene to induce both humoral and cellular immune responses. Here, we describe the methods of CD40 DNA vaccine enhanced by dendritic cell (DC) targeting on the development of Heymann nephritis (HN), a rat model of human membranous nephropathy.

  16. Phosphorus Regulation in Chronic Kidney Disease

    PubMed Central

    Suki, Wadi N.; Moore, Linda W.

    2016-01-01

    Serum phosphorus levels stay relatively constant through the influence of multiple factors—such as parathyroid hormone, fibroblast growth factor 23, and vitamin D—on the kidney, bone, and digestive system. Whereas normal serum phosphorus ranges between 3 mg/dL to 4.5 mg/dL, large cross-sectional studies have shown that even people with normal kidney function are sometimes found to have levels ranging between 1.6 mg/dL and 6.2 mg/dL. While this may partially be due to diet and the factors mentioned above, total understanding of these atypical ranges of serum phosphorus remains uncertain. Risks for bone disease are high in people aged 50 and older, and this group comprises a large proportion of people who also have chronic kidney disease. Consuming diets low in calcium and high in phosphorus, especially foods with phosphate additives, further exacerbates bone turnover. Existing bone disease increases the risk for high serum phosphorus, and higher serum phosphorus has been associated with increased adverse events and cardiovascular-related mortality both in people with chronic kidney disease and in those with no evidence of disease. Once kidney function has deteriorated to end-stage disease (Stage 5), maintaining normal serum phosphorus requires dietary restrictions, phosphate-binding medications, and dialysis. Even so, normal serum phosphorus remains elusive in many patients with Stage 5 kidney disease, and researchers are testing novel targets that may inhibit intestinal transport of phosphorus to achieve better phosphate control. Protecting and monitoring bone health should also aid in controlling serum phosphorus as kidney disease advances. PMID:28298956

  17. Phosphorus Regulation in Chronic Kidney Disease.

    PubMed

    Suki, Wadi N; Moore, Linda W

    2016-01-01

    Serum phosphorus levels stay relatively constant through the influence of multiple factors-such as parathyroid hormone, fibroblast growth factor 23, and vitamin D-on the kidney, bone, and digestive system. Whereas normal serum phosphorus ranges between 3 mg/dL to 4.5 mg/dL, large cross-sectional studies have shown that even people with normal kidney function are sometimes found to have levels ranging between 1.6 mg/dL and 6.2 mg/dL. While this may partially be due to diet and the factors mentioned above, total understanding of these atypical ranges of serum phosphorus remains uncertain. Risks for bone disease are high in people aged 50 and older, and this group comprises a large proportion of people who also have chronic kidney disease. Consuming diets low in calcium and high in phosphorus, especially foods with phosphate additives, further exacerbates bone turnover. Existing bone disease increases the risk for high serum phosphorus, and higher serum phosphorus has been associated with increased adverse events and cardiovascular-related mortality both in people with chronic kidney disease and in those with no evidence of disease. Once kidney function has deteriorated to end-stage disease (Stage 5), maintaining normal serum phosphorus requires dietary restrictions, phosphate-binding medications, and dialysis. Even so, normal serum phosphorus remains elusive in many patients with Stage 5 kidney disease, and researchers are testing novel targets that may inhibit intestinal transport of phosphorus to achieve better phosphate control. Protecting and monitoring bone health should also aid in controlling serum phosphorus as kidney disease advances.

  18. Recent developments in epigenetics of acute and chronic kidney diseases.

    PubMed

    Reddy, Marpadga A; Natarajan, Rama

    2015-08-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.

  19. Total Kidney Volume as a Biomarker of Disease Progression in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Tangri, Navdeep; Hougen, Ingrid; Alam, Ahsan; Perrone, Ronald; McFarlane, Phil; Pei, York

    2017-01-01

    Purpose of review: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the formation of kidney cysts and kidney enlargement, which progresses to kidney failure by the fifth to seventh decade of life in a majority of patients. Disease progression is evaluated primarily through serum creatinine and estimated glomerular filtration rate (eGFR) measurements; however, it is known that serum creatinine and eGFR values typically do not change until the fourth or fifth decade of life. Until recently, therapy only existed to target complications of ADPKD. As therapeutic agents continue to be investigated for use in ADPKD, a suitable biomarker of disease progression in place of serum creatinine is needed. Sources of information: This review summarizes recent research regarding the use of total kidney volume as a biomarker in ADPKD, as presented at the Canadian Society of Nephrology symposium held in April 2015. Findings: Measurement of patients’ total kidney volume made using ultrasound (US) or magnetic resonance imaging (MRI) has been shown by the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study to be directly correlated with both increases in cyst volume and change in glomerular filtration rate (GFR). Additional studies have shown total kidney volume to have an association with complications of ADPKD as well. Limitations: Areas for further study continue to exist in comparison of methods of measuring total kidney volume. Implications: We believe that the evidence suggests that total kidney volume may be an appropriate surrogate marker for ADPKD disease progression. PMID:28321323

  20. The expression of immune-regulatory genes in rainbow trout, Oncorhynchus mykiss, during a natural outbreak of proliferative kidney disease (PKD).

    PubMed

    Holland, J W; Gould, C R W; Jones, C S; Noble, L R; Secombes, C J

    2003-01-01

    Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by an apparently abnormal immune response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In order to examine the nature of the immune response at the molecular level, the expression of a range of immune regulatory genes, including cytokines and cyclooxygenase (COX)-2 was examined in naive unexposed fish and in naive fish exposed to parasite-infected water at three points during the course of a natural outbreak of PKD. Since fish with advanced PKD pathology generally exhibit increased susceptibility to secondary infections which is typical of stress/cortisol-mediated immune suppression, a further aim of this work was to examine in vitro the influence of the glucocorticoid cortisol on the bacterial lipopolysaccharide (LPS)-induced expression of the trout cytokine genes studied. Two weeks after the initial sampling, naive exposed fish showed a specific profile of up-regulated tumor necrosis factor (TNF)-alpha2, COX-2 and, to a lesser extent, transforming growth factor (TGF)-beta1 expression. As the disease pathology increased, TNF-alpha2 and COX-2 expression returned to normal levels. Stress levels of cortisol suppressed the LPS inducibility of pro-inflammatory cytokine genes, although TGF-beta1 and TNF-alpha2 appeared to be refractory. These data demonstrate that specific immune responses at the molecular level are affected during PKD infection, with the cortisol suppression of cytokine expression in vitro providing a possible link to PKD-mediated cytokine down-regulation and immune suppression.

  1. Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.

    PubMed

    Linehan, W Marston

    2012-11-01

    Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.

  2. An approach to cystic kidney diseases: the clinician's view.

    PubMed

    Kurschat, Christine E; Müller, Roman-Ulrich; Franke, Mareike; Maintz, David; Schermer, Bernhard; Benzing, Thomas

    2014-12-01

    Advances in molecular genetics have led to the identification of more than 70 different genes involved in the development of cystic kidney diseases. Most of these diseases are rare, and interpreting the resultant plethora of disease-causing mutations requires a methodical and meticulous approach to differential diagnosis. In this Review we discuss a clinical approach to the diagnosis of cystic kidney diseases in adults, for use by nephrologists. This approach is based upon a thorough clinical evaluation, which considers both kidney phenotype and extrarenal manifestations of the underlying disorder, in combination with genetic testing in selected patients. In our view, cystic kidney disease can (in the majority of patients) be reliably classified on the basis of clinical findings. We therefore propose that defining clinical situations to precipitate the initiation of genetic testing is mandatory and cost-effective. New techniques such as next-generation sequencing will facilitate the diagnosis of cystic kidney diseases in the future, increasing diagnostic safety in a subset of patients. In renal tumour syndromes, genetic testing is warranted.

  3. African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.

    PubMed

    Behar, Doron M; Rosset, Saharon; Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Bercovici, Sivan; Kopp, Jeffrey B; Winkler, Cheryl A; Nelson, George W; Wasser, Walter G; Skorecki, Karl

    2010-05-01

    Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.

  4. T cells and autoimmune kidney disease.

    PubMed

    Suárez-Fueyo, Abel; Bradley, Sean J; Klatzmann, David; Tsokos, George C

    2017-03-13

    Glomerulonephritis is traditionally considered to result from the invasion of the kidney by autoantibodies and immune complexes from the circulation or following their formation in situ, and by cells of the innate and the adaptive immune system. The inflammatory response leads to the proliferation and dysfunction of cells of the glomerulus, and invasion of the interstitial space with immune cells, resulting in tubular cell malfunction and fibrosis. T cells are critical drivers of autoimmunity and related organ damage, by supporting B-cell differentiation and antibody production or by directly promoting inflammation and cytotoxicity against kidney resident cells. T cells might become activated by autoantigens in the periphery and become polarized to secrete inflammatory cytokines before entering the kidney where they have the opportunity to expand owing to the presence of costimulatory molecules and activating cytokines. Alternatively, naive T cells could enter the kidney where they become activated after encountering autoantigen and expand locally. As not all individuals with a peripheral autoimmune response to kidney antigens develop glomerulonephritis, the contribution of local kidney factors expressed or produced by kidney cells is probably of crucial importance. Improved understanding of the biochemistry and molecular biology of T cells in patients with glomerulonephritis offers unique opportunities for the recognition of treatment targets for autoimmune kidney disease.

  5. Kidney Disease and Psoriasis. A New Comorbidity?

    PubMed

    González-Parra, E; Daudén, E; Carrascosa, J M; Olveira, A; Botella, R; Bonanad, C; Rivera, R

    2016-12-01

    Psoriasis is a chronic inflammatory disease that has been associated with cardiovascular and metabolic comorbidities, particularly in young patients and patients with more severe forms of the disease. Recent studies have also linked psoriasis to kidney disease, and this would seem only logical, as the kidney is both a target of classic cardiovascular risk factors and susceptible to the toxic effects of some of the traditional drugs used to control psoriasis. In this article, we would like to draw readers' attention to this recently described comorbidity and stress the importance of early detection, as once chronic kidney disease develops, it cannot be reversed. When evaluating patients with psoriasis, particularly when they are candidates for systemic therapy, we believe it is important to order laboratory tests including glomerular filtration rate and a simple urine test to screen for albuminuria (albumin/creatinine ratio).

  6. [Nutritional management of kidney diseases in children].

    PubMed

    Borovik, T E; Kutafina, E K; Tsygin, A N; Sergeeva, T V; Baranov, A A; Namazova-Baranova, L S; Voznesenskaya, T S; Zakharova, I N; Semenova, N N; Zvonkova, N G; Yatsyk, S P

    2016-01-01

    The prevalence of various kidney diseases in children remains high in recent decades. Adequate nutrition management can enhance the effectiveness of drug treatment, slow the frequency of relapses andprevent the progression of the disease. The article is devoted to modern approaches to diet therapy in various kidney diseases in children with the defeat of tubular and glomerular appa ratus. For the first time the therapeutic diets for children with various kidney diseases are presented. Particular attention is paid to diet therapy in nephrotic syndrome (steroid-responsive and steroid-refractory). Dietary approaches with modern formulas for enteral nutrition in cases of steroid therapy complications in children with renal insufficiency (in predialysis stage and on dialysis) are described. Differentiated nutritional approaches for patients with different types of crystalluria are separately presented.

  7. Growth Retardation in Children with Kidney Disease

    PubMed Central

    Zambrano, Maria Jose; Mericq, Veronica

    2013-01-01

    Growth failure is almost inextricably linked with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Growth failure in CKD has been associated with both increased morbidity and mortality. Growth failure in the setting of kidney disease is multifactorial and is related to poor nutritional status as well as comorbidities, such as anemia, bone and mineral disorders, and alterations in hormonal responses, as well as to aspects of treatment such as steroid exposure. This review covers updated management of growth failure in these children including adequate nutrition, treatment of metabolic alterations, and early administration of recombinant human growth hormone (GH). PMID:24187550

  8. [Chronic kidney disease in the elderly patient].

    PubMed

    Mora-Gutiérrez, José María; Slon Roblero, María Fernanda; Castaño Bilbao, Itziar; Izquierdo Bautista, Diana; Arteaga Coloma, Jesús; Martínez Velilla, Nicolás

    2016-05-06

    Chronic kidney disease (CKD) is widely prevalent worldwide, with a special impact on elderly population. Around half of people aged over 75 meet diagnostic criteria for CKD according to the recent 'Kidney disease improving global outcomes' (KDIGO) 2012 clinical practice guideline on the evaluation and management of CKD. However, geriatric patients have characteristics that may not be addressed by general guidelines. Therefore, it is important to know the natural history of the disease, symptoms, and 'red-flags' that could help in the management of these patients. In this review, a complete approach is presented on the pathophysiology, diagnosis, and treatment of CKD in the geriatric population.

  9. Polycystin-1, the product of the polycystic kidney disease 1 gene, co-localizes with desmosomes in MDCK cells.

    PubMed

    Scheffers, M S; van der Bent, P; Prins, F; Spruit, L; Breuning, M H; Litvinov, S V; de Heer, E; Peters, D J

    2000-11-01

    Polycystin-1 is a novel protein predicted to be a large membrane-spanning glycoprotein with an extracellular N-terminus and an intracellular C-terminus, harboring several structural motifs. To study the subcellular localization, antibodies raised against various domains of polycystin-1 and against specific adhesion complex proteins were used for two-color immunofluorescence staining. In Madine Darby canine kidney (MDCK) cells, polycystin-1 was detected in the cytoplasm as well as co-localizing with desmosomes, but not with tight or adherens junctions. Using confocal laser scanning and immunoelectron microscopy we confirmed the desmosomal localization. By performing a calcium switch experiment, we demonstrated the sequential reassembly of tight junctions, subsequently adherens junctions and finally desmosomes. Polycystin-1 only stained the membrane after incorporation of desmoplakin into the desmosomes, suggesting that membrane-bound polycystin-1 may be important for cellular signaling or cell adhesion, but not for the assembly of adhesion complexes.

  10. Overview of Kidney Diseases in Children

    MedlinePlus

    ... Childhood Nephrotic Syndrome Hemolytic Uremic Syndrome in Children Treatment for Kidney Failure in Children Caring for a ... Sponge Kidney Kidney Dysplasia Kidney Failure Choosing a Treatment for Kidney Failure Hemodialysis Peritoneal Dialysis Kidney Transplant ...

  11. Sirtuin 1: A Target for Kidney Diseases

    PubMed Central

    Kong, Lili; Wu, Hao; Zhou, Wenhua; Luo, Manyu; Tan, Yi; Miao, Lining; Cai, Lu

    2015-01-01

    Sirtuin 1 (SIRT1) is an evolutionarily conserved NAD+-dependent histone deacetylase that is necessary for caloric restriction–related lifespan extension. SIRT1, as an intracellular energy sensor, detects the concentration of intracellular NAD+ and uses this information to adapt cellular energy output to cellular energy requirements. Previous studies on SIRT1 have confirmed its beneficial effects on cellular immunity to oxidative stress, reduction of fibrosis, suppression of inflammation, inhibition of apoptosis, regulation of metabolism, induction of autophagy and regulation of blood pressure. All of the above biological processes are involved in the pathogenesis of kidney diseases. Therefore, the activation of SIRT1 may become a therapeutic target to improve the clinical outcome of kidney diseases. In this review, we give an overview of SIRT1 and its molecular targets as well as SIRT1-modulated biological processes, with a particular focus on the role of SIRT1 in kidney diseases. PMID:25587857

  12. Sirtuin 1: A Target for Kidney Diseases.

    PubMed

    Kong, Lili; Wu, Hao; Zhou, Wenhua; Luo, Manyu; Tan, Yi; Miao, Lining; Cai, Lu

    2015-01-12

    Sirtuin 1 (SIRT1) is an evolutionarily conserved NAD(+)-dependent histone deacetylase that is necessary for caloric restriction-related lifespan extension. SIRT1, as an intracellular energy sensor, detects the concentration of intracellular NAD(+) and uses this information to adapt cellular energy output to cellular energy requirements. Previous studies on SIRT1 have confirmed its beneficial effects on cellular immunity to oxidative stress, reduction of fibrosis, suppression of inflammation, inhibition of apoptosis, regulation of metabolism, induction of autophagy and regulation of blood pressure. All of the above biological processes are involved in the pathogenesis of kidney diseases. Therefore, the activation of SIRT1 may become a therapeutic target to improve the clinical outcome of kidney diseases. In this review, we give an overview of SIRT1 and its molecular targets as well as SIRT1-modulated biological processes, with a particular focus on the role of SIRT1 in kidney diseases.

  13. Pregnancy and contraceptive counseling of women with chronic kidney disease and kidney transplants.

    PubMed

    Watnick, Suzanne

    2007-04-01

    Women with kidney disease of childbearing age should expect proactive counseling regarding pregnancy and contraception. Discussions should include the impact of pregnancy on their kidney disease and the impact of kidney disease on maternal and fetal outcomes. However, nephrologists rarely discuss sexual dysfunction, infertility, menstrual irregularities, and contraception with their premenopausal women patients. This review will consider pregnancy-related issues to discuss when counseling women with all stages of chronic kidney disease. Issues related to contraception in women on dialysis, women with functioning kidney transplants, and those with chronic kidney disease will also be reviewed.

  14. Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Grantham, Jared J.

    2010-01-01

    Shortly after being elbowed in the flank during a pickup basketball game, a 35-year-old healthy man has severe, colicky abdominal pain followed by gross hematuria. He is hospitalized, and a renal ultrasound scan reveals bilateral polycystic kidneys and liver cysts, previously unknown to the patient. The blood pressure is 160/100 mm Hg. The serum creatinine concentration is 0.9 mg per deciliter (80 μmol per liter). The pain subsides in 2 days with analgesics, rest, and fluids; the gross hematuria resolves in 4 days, although microscopic hematuria persists. How should his case be further evaluated and managed? PMID:20009161

  15. Kidney Dysplasia

    MedlinePlus

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  16. Dermatoglyphics in kidney diseases: a review.

    PubMed

    Wijerathne, Buddhika T B; Meier, Robert J; Salgado, Sujatha S; Agampodi, Suneth B

    2016-01-01

    Kidney diseases are becoming a major cause of global burden with high mortality and morbidity. The origins of most kidney diseases are known, but for some the exact aetiology is not yet understood. Dermatoglyphics is the scientific study of epidermal ridge patterns and it has been used as a non-invasive diagnostic tool to detect or predict different medical conditions that have foetal origin. However, there have been a limited number of studies that have evaluated a dermatoglyphic relationship in different kidney diseases. The aim of this review was to systematically identify, review and appraise available literature that evaluated an association of different dermatoglyphic variables with kidney diseases. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The PubMed(®) (Medline), POPLINE, Cochrane Library and Trip Database and grey literature sources such as OpenGrey, Google Scholar, and Google were searched to earliest date to 17 April 2014. Of the 36 relevant publications, 15 were included in the review. Of these studies, there are five case reports, seven case series and three comparative studies. Possible association of dermatoglyphics with Wilms tumor (WT) had been evaluated in two comparative studies and one case series that found fewer whorls and a lower mean total ridge count (TRC). Another study evaluated adult polycystic kidney disease (APCD) type III that revealed lower TRC means in all cases. All other case series and case reports describe dermatoglyphics in various kidney disease such as acro-renal-ocular syndrome, potter syndrome, kabuki makeup syndrome, neurofaciodigitorenal syndrome, syndactyly type V, ring chromosome 13 syndrome, trisomy 13 syndrome and sirenomelia. It is evident that whorl pattern frequency and TRC have been used widely to investigate the uncertainty related to the origin of several kidney diseases such as WT and APCD type III. However, small sample sizes

  17. Wait too long to talk about kidney disease and you could be waiting for a kidney.

    MedlinePlus

    ... Home Current Issue Past Issues Public Service Announcement Kidney Disease Past Issues / Summer 2006 Table of Contents ... Javascript on. Wait too long to talk about kidney disease and you could be waiting for a ...

  18. Measurement of renal function in patients with chronic kidney disease

    PubMed Central

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-01-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease. PMID:23802624

  19. Measurement of renal function in patients with chronic kidney disease.

    PubMed

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-10-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.

  20. Treatment of chronic kidney diseases with histone deacetylase inhibitors

    PubMed Central

    Liu, Na; Zhuang, Shougang

    2015-01-01

    Histone deacetylases (HDACs) induce deacetylation of both histone and non-histone proteins and play a critical role in the modulation of physiological and pathological gene expression. Pharmacological inhibition of HDAC has been reported to attenuate progression of renal fibrogenesis in obstructed kidney and reduce cyst formation in polycystic kidney disease. HDAC inhibitors (HDACis) are also able to ameliorate renal lesions in diabetes nephropathy, lupus nephritis, aristolochic acid nephropathy, and transplant nephropathy. The beneficial effects of HDACis are associated with their anti-fibrosis, anti-inflammation, and immunosuppressant effects. In this review, we summarize recent advances on the treatment of various chronic kidney diseases with HDACis in pre-clinical models. PMID:25972812

  1. Early onset polycystic kidney disease: how early is early?

    PubMed

    Birewar, Sonali; Zawada, Edward T

    2003-11-01

    We report a case of a six-month-old infant with autosomal dominant polycystic kidney disease. He was a full term baby with an uneventful pre and postnatal period. He was delivered by uncomplicated vaginal delivery without forceps or fetal distress. His father was recently diagnosed with adult onset autosomal dominant polycystic kidney disease (APKD) with creatinine clearance around 25%-30%. The parents requested renal ultrasound of the baby to screen for APKD. It revealed normal sized and normal shaped kidneys, but with multiple bilateral cysts in the renal cortices, each measuring about 5 mm-7 mm in diameter. Subsequent DNA analysis showed presence of PKD1 gene, present on chromosome 16. His renal function was within normal range. The baby needs to be regularly followed-up for the most common complications of APKD, including hypertension and renal insufficiency.

  2. MicroRNAs and their applications in kidney diseases.

    PubMed

    Badal, Shawn S; Danesh, Farhad R

    2015-05-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that employ classic Watson-Crick base-pairing to identify their target genes, ultimately resulting in destabilization of their target mRNAs and/or inhibition of their translation. The role of miRNAs in a wide range of human diseases, including those afflicting the kidney, has been intensely investigated. However, there is still a vast dearth of knowledge regarding their specific mode of action and therapeutic effects in various kidney diseases. This review discusses the latest efforts to further our understanding of the basic biology of miRNAs, their impact on various kidney diseases and their potential as novel biomarkers and therapeutic agents. We initially provide an overview of miRNA biology and the canonical pathway implicated in their biogenesis. We then discuss commonly employed experimental strategies for miRNA research and highlight some of the newly described state-of-the-art technologies to identify miRNAs and their target genes. Finally, we carefully examine the emerging role of miRNAs in the pathogenesis of various kidney diseases.

  3. Obesity and kidney disease: hidden consequences of the epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan L; Zoccali, Carmine

    2017-02-01

    Obesity is a growing worldwide epidemic. Obesity is one of the strongest risk factors for new-onset chronic kidney disease, and also for nephrolithiasis and for kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

  4. Obesity and Kidney Disease: Hidden Consequences of the Epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan L; Zoccali, Carmine

    2017-03-01

    Obesity is a growing worldwide epidemic. Obesity is one of the strongest risk factors for new-onset chronic kidney disease, and also for nephrolithiasis and for kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

  5. Obesity in kidney disease: A heavyweight opponent

    PubMed Central

    Felizardo, Raphael Jose Ferreira; da Silva, Marina Burgos; Aguiar, Cristhiane Favero; Câmara, Niels Olsen Saraiva

    2014-01-01

    Obesity is an important worldwide challenge that must be faced in most developed and developing countries because of unhealthy nutritional habits. The consequences of obesity and being overweight are observed in different organs, but the kidney is one of the most affected. Excess adipose tissue causes hemodynamic alterations in the kidney that can result in renal disease. However, obesity is also commonly associated with other comorbidities such as chronic inflammation, hypertension and diabetes. This association of several aggravating factors is still a matter of concern in clinical and basic research because the pathophysiologic mechanisms surrounding chronic kidney disease development in obese patients remain unclear. This review will discuss the consequences of obesity in the context of renal injury. PMID:25332896

  6. Statins in chronic kidney disease and kidney transplantation.

    PubMed

    Kassimatis, Theodoros I; Goldsmith, David J A

    2014-10-01

    HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their pleiotropic effects statins have been shown to reduce inflammation, alleviate oxidative stress, modify the immunologic responses, improve endothelial function and suppress platelet aggregation. Patients with chronic kidney disease (CKD) exhibit an enormous increase in CVD rates even from early CKD stages. As considerable differences exist in dyslipidemia characteristics and the pathogenesis of CVD in CKD, statins' CV benefits in CKD patients (including those with a kidney graft) should not be considered unequivocal. Indeed, accumulating clinical evidence suggests that statins exert diverse effects on dialysis and non-dialysis CKD patients. Therefore, it seems that statins improve CV outcomes in non-dialysis patients whereas exert little (if any) benefit in the dialysis population. It has also been proposed that dyslipidemia might play a causative role or even accelerate renal injury. Moreover, ample experimental evidence suggests that statins ameliorate renal damage. However, a high quality randomized controlled trial (RCT) and metaanalyses do not support a beneficial role of statins in renal outcomes in terms of proteinuria reduction or retardation of glomerular filtration rate (GFR) decline.

  7. Cyclic Nucleotide Signaling in Polycystic Kidney Disease

    PubMed Central

    Wang, Xiaofang; Ward, Christopher J.; Harris, Peter C.; Torres, Vicente E.

    2013-01-01

    Increased levels of 3’–5’-cyclic adenosine monophosphate (cAMP) stimulate cell proliferation and fluid secretion in polycystic kidney disease (PKD). Since hydrolytic capacity of phosphodiesterases (PDE) far exceeds maximum rate of synthesis by adenylyl cyclases (AC), cellular levels of cAMP are more sensitive to PDE inhibition than to AC activity changes. We have used enzymatic, western blot, immunohistochemistry, PCR and biochemical assays to study activity and expression of PDE families and isoforms and expression of downstream effectors of cAMP signaling in wildtype and PKD rat and mouse kidneys. The results indicate: 1) Species specific differences in PDE expression; higher PDE activity in kidneys from mice compared to rats; higher contribution of PDE1, relative to PDE4 and PDE3, to total PDE activity of kidney lysate and lower PDE1, PDE3 and PDE4 activities in murine cystic compared to wildtype kidneys. 2) Reduced levels of several PDE1, PDE3 and PDE4 proteins despite mRNA upregulation, possibly due to increased protein degradation. 3) Increased cGMP levels in polycystic kidneys, suggesting in vivo downregulation of PDE1 activity. 4) Additive stimulatory effect of cAMP and cGMP on cystogenesis in vitro. 5) Upregulation of cAMP-dependent protein kinase (PKA) subunits Iα and IIβ, PKare, CREB-1 mRNA, and CREM, ATF-1 and ICER proteins in cystic compared to wildtype kidneys. In summary, the results of this study suggest that alterations in cyclic nucleotide catabolism may render the cystic epithelium particularly susceptible to factors acting on Gs coupled receptors, account at least in part for the upregulation of cyclic nucleotide signaling in PKD, and contribute substantially to the progression of this disease. PMID:19924104

  8. 42 CFR 410.48 - Kidney disease education services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... treatment of cardiovascular disease. (ii) Prevention and treatment of diabetes. (iii) Hypertension... 42 Public Health 2 2010-10-01 2010-10-01 false Kidney disease education services. 410.48 Section... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease...

  9. Kidney Disease in Adenine Phosphoribosyltransferase Deficiency

    PubMed Central

    Runolfsdottir, Hrafnhildur Linnet; Palsson, Runolfur; Sch. Agustsdottir, Inger M.; Indridason, Olafur S.; Edvardsson, Vidar O.

    2015-01-01

    Background Adenine phosphoribosyltransferase (APRT) deficiency is a purine metabolism disorder causing kidney stones and chronic kidney disease (CKD). The course of nephrolithiasis and CKD has not been well characterized. The objective of this study was to examine long-term kidney outcomes in patients with APRT deficiency. Study Design An observational cohort study. Setting & Participants All patients enrolled in the APRT Deficiency Registry of the Rare Kidney Stone Consortium. Outcomes Kidney stones, acute kidney injury (AKI), stage of CKD and kidney failure, estimated glomerular filtration rate (eGFR) and changes in eGFR. Measurements Serum creatinine and eGFR calculated using creatinine-based equations. Results Of 53 patients, 30 (57%) were female and median age at diagnosis was 37.0 (range, 0.6–67.9) years. The median duration of follow-up was 10.3 (range, 0.0–31.5) years. At diagnosis, kidney stones had developed in 29 patients (55%) and 20 (38%) had CKD stages 3–5, including 11 patients (21%) with stage 5. At latest follow-up, 33 patients (62%) had had kidney stones; 18 (34%), AKI; and 22 (42%), CKD stage 3–5. Of the 14 (26%) patients with CKD stage 5, 12 had initiated renal replacement therapy. Kidney stones recurred in 18 of 33 patients (55%). The median eGFR slope was −0.38 (range, −21.99 to 1.42) mL/min/1.73 m2 per year in patients receiving treatment with xanthine dehydrogenase inhibitor and −5.74 (range, −75.8 to −0.10) mL/min/1.73 m2 per year in those not treated prior to the development of stage 5 CKD (p=0.001). Limitations Use of observational registry data. Conclusions Progressive CKD and AKI episodes are major features of APRT deficiency, while nephrolithiasis is the most common presentation. Advanced CKD without history of kidney stones is more prevalent than previously reported. Our data suggest that timely therapy may retard CKD progression. PMID:26724837

  10. Pain management in polycystic kidney disease.

    PubMed

    Bajwa, Z H; Gupta, S; Warfield, C A; Steinman, T I

    2001-11-01

    Pain is a common complaint in patients with autosomal-dominant polycystic kidney disease, and a systematic approach is needed to differentiate the etiology of the pain and define an approach to management. A thorough history is the best clue to the multifactorial causes of the pain, superimposed upon an understanding of the complex innervation network that supplies the kidneys. The appropriate use of diagnostic radiology (especially MRI) will assist in differentiating the mechanical low back pain caused by cyst enlargement, cyst rupture and cyst infection. Also, the increased incidence of uric acid nephrolithiasis as a factor in producing renal colic must be considered when evaluating acute pain in the population at risk. MRI is not a good technique to detect renal calculi, a frequent cause of pain in polycystic kidney disease. If stone disease is a possibility, then abdominal CT scan and/or ultrasound should be the method of radiologic investigation. Pain management is generally not approached in a systematic way in clinical practice because most physicians lack training in the principles of pain management. The first impulse to give narcotics for pain relief must be avoided. Since chronic pain cannot be "cured," an approach must include techniques that allow the patient to adapt to chronic pain so as to limit interference with their life style. A detailed stepwise approach for acute and chronic pain strategies for the patient with autosomal dominant polycystic kidney disease is outlined.

  11. Metabolomics in the study of kidney diseases.

    PubMed

    Weiss, Robert H; Kim, Kyoungmi

    2011-10-25

    Metabolomics--the nontargeted measurement of all metabolites produced by the body--is beginning to show promise in both biomarker discovery and, in the form of pharmacometabolomics, in aiding the choice of therapy for patients with specific diseases. In its two basic forms (pattern recognition and metabolite identification), this developing field has been used to discover potential biomarkers in several renal diseases, including acute kidney injury (attributable to a variety of causes), autosomal dominant polycystic kidney disease and kidney cancer. NMR and gas chromatography or liquid chromatography, together with mass spectrometry, are generally used to separate and identify metabolites. Many hurdles need to be overcome in this field, such as achieving consistency in collection of biofluid samples, controlling for batch effects during the analysis and applying the most appropriate statistical analysis to extract the maximum amount of biological information from the data obtained. Pathway and network analyses have both been applied to metabolomic analysis, which vastly extends its clinical relevance and effects. In addition, pharmacometabolomics analyses, in which a metabolomic signature can be associated with a given therapeutic effect, are beginning to appear in the literature, which will lead to personalized therapies. Thus, metabolomics holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in kidney disease.

  12. Women, kidney disease, and pregnancy.

    PubMed

    Smyth, Andrew; Radovic, Milan; Garovic, Vesna D

    2013-09-01

    Several glomerular diseases may occur in women of childbearing age. Pregnancy in such patients should be planned when the disease has been in remission for a minimum of 6 months to minimize maternal and fetal complications. Immunosuppressive agents should be optimized before conception to include those that are safe for pregnancy. The complexity of medical management when caring for these patients calls for a multidisciplinary team approach consisting of a nephrologist, rheumatologist, obstetrician, and pharmacist. This review will address the physiological changes of pregnancy that may affect glomerular disease presentation, activity, and diagnosis; specific glomerular diseases primary and secondary to systemic diseases in the context of pregnancy; fetal and maternal complications and long-term effects; diagnosis and differential diagnosis; and treatment strategies that are considered relatively safe with respect to fetal intrauterine exposure.

  13. Averting the legacy of kidney disease--focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplant, whereas only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  14. Screening for cardiovascular disease before kidney transplantation

    PubMed Central

    Palepu, Sneha; Prasad, G V Ramesh

    2015-01-01

    Pre-kidney transplant cardiac screening has garnered particular attention from guideline committees as an approach to improving post-transplant success. Screening serves two major purposes: To more accurately inform transplant candidates of their risk for a cardiac event before and after the transplant, thereby informing decisions about proceeding with transplantation, and to guide pre-transplant management so that post-transplant success can be maximized. Transplant candidates on dialysis are more likely to be screened for coronary artery disease than those not being considered for transplantation. Thorough history and physical examination taking, resting electrocardiography and echocardiography, exercise stress testing, myocardial perfusion scintigraphy, dobutamine stress echocardiography, cardiac computed tomography, cardiac biomarker measurement, and cardiac magnetic resonance imaging all play contributory roles towards screening for cardiovascular disease before kidney transplantation. In this review, the importance of each of these screening procedures for both coronary artery disease and other forms of cardiac disease are discussed. PMID:26722655

  15. Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease.

    PubMed

    Stenvinkel, Peter; Johnson, Richard J

    2013-11-01

    Most studies on kidney disease have relied on classic experimental studies in mice and rats or clinical studies in humans. From such studies much understanding of the physiology and pathophysiology of kidney disease has been obtained. However, breakthroughs in the prevention and treatment of kidney diseases have been relatively few, and new approaches to fight kidney disease are needed. Here we discuss kidney biomimicry as a new approach to understand kidney disease. Examples are given of how various animals have developed ways to prevent or respond to kidney failure, how to protect themselves from hypoxia or oxidative stress and from the scourge of hyperglycemia. We suggest that investigation of evolutionary biology and comparative physiology might provide new insights for the prevention and treatment of kidney disease.

  16. Chronic kidney Disease and the Aging Population.

    PubMed

    Tonelli, Marcello; Riellae, Miguel

    2014-01-01

    Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics [2]. A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people [3]. Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.

  17. T-Box Genes in the Kidney and Urinary Tract.

    PubMed

    Kispert, A

    2017-01-01

    T-box (Tbx) genes encode an ancient group of transcription factors that play important roles in patterning, specification, proliferation, and differentiation programs in vertebrate organogenesis. This is testified by severe organ malformation syndromes in mice homozygous for engineered null alleles of specific T-box genes and by the large number of human inherited organ-specific diseases that have been linked to mutations in these genes. One of the organ systems that has not been associated with loss of specific T-box gene function in human disease for long is the excretory system. However, this has changed with the finding that mutations in TBX18, a member of a vertebrate-specific subgroup within the Tbx1-subfamily of T-box transcription factor genes, cause congenital anomalies of the kidney and urinary tract, predominantly hydroureter and ureteropelvic junction obstruction. Gene expression analyses, loss-of-function studies, and lineage tracing in the mouse suggest a primary role for this transcription factor in specifying the ureteric mesenchyme in the common anlage of the kidney, the ureter, and the bladder. We review the function of Tbx18 in ureterogenesis and discuss the body of evidence that Tbx18 and other members of the T-box gene family, namely, Tbx1, Tbx2, Tbx3, and Tbx20, play additional roles in development and homeostasis of other components of the excretory system in vertebrates.

  18. Role of Nox2 in diabetic kidney disease

    PubMed Central

    You, Young-Hyun; Okada, Shinichi; Ly, San; Jandeleit-Dahm, Karin; Barit, David; Namikoshi, Tamehachi

    2013-01-01

    NADPH oxidase (Nox) isoforms have been implicated in contributing to diabetic microvascular complications, but the functional role of individual isoforms in diabetic kidney are unclear. Nox2, in particular, is highly expressed in phagocytes and may play a key inflammatory role in diabetic kidney disease. To determine the role of Nox2, we evaluated kidney function and pathology in wild-type (WT; C57BL/6) and Nox2 knockout (KO) mice with type 1 diabetes. Diabetes was induced in male Nox2 KO and WT mice with a multiple low-dose streptozotocin protocol. Groups were studied for kidney disease after 8 and 20 wk of diabetes. Hyperglycemia and body weights were similar in WT and Nox2 KO diabetic mice. All functional and structural features of early and later stage diabetic kidney disease (albuminuria, mesangial matrix, tubulointerstitial disease, and gene expression of matrix and transforming growth factor-β) were similar in both diabetic groups compared with their respective nondiabetic groups, except for reduction of macrophage infiltration and monocyte chemoattractant protein-1 in the diabetic Nox2 KO mice. Systolic blood pressure by telemetry was surprisingly increased in Nox2 KO mice; however, the systolic blood pressure was reduced in the diabetic WT and Nox2 KO mice by tail-cuff. Interestingly, diabetic Nox2 KO mice had marked upregulation of renal Nox4 at both the glomerular and cortical levels. The present results demonstrate that lack of Nox2 does not protect against diabetic kidney disease in type 1 diabetes, despite a reduction in macrophage infiltration. The lack of renoprotection may be due to upregulation of renal Nox4. PMID:23389458

  19. PKHD1, the Polycystic Kidney and Hepatic Disease 1 Gene, Encodes a Novel Large Protein Containing Multiple Immunoglobulin-Like Plexin-Transcription–Factor Domains and Parallel Beta-Helix 1 Repeats

    PubMed Central

    Onuchic, Luiz F.; Furu, Laszlo; Nagasawa, Yasuyuki; Hou, Xiaoying; Eggermann, Thomas; Ren, Zhiyong; Bergmann, Carsten; Senderek, Jan; Esquivel, Ernie; Zeltner, Raoul; Rudnik-Schöneborn, Sabine; Mrug, Michael; Sweeney, William; Avner, Ellis D.; Zerres, Klaus; Guay-Woodford, Lisa M.; Somlo, Stefan; Germino, Gregory G.

    2002-01-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease that presents primarily in infancy and childhood and that is characterized by enlarged kidneys and congenital hepatic fibrosis. We have identified PKHD1, the gene mutated in ARPKD. PKHD1 extends over ⩾469 kb, is primarily expressed in human fetal and adult kidney, and includes a minimum of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest continuous open reading frame encodes a 4,074-amino-acid protein, polyductin, that is predicted to have a single transmembrane (TM)-spanning domain near its carboxyl terminus, immunoglobulin-like plexin-transcription–factor domains, and parallel beta-helix 1 repeats in its amino terminus. Several transcripts encode truncated products that lack the TM and that may be secreted if translated. The PKHD1-gene products are members of a novel class of proteins that share structural features with hepatocyte growth-factor receptor and plexins and that belong to a superfamily of proteins involved in regulation of cell proliferation and of cellular adhesion and repulsion. PMID:11898128

  20. Kidney Disease and Diabetes - What You Need to Know

    MedlinePlus

    ... Issue Past Issues Special Section Kidney Disease and Diabetes: What You Need to Know Past Issues / Winter ... family are at risk for kidney disease or diabetes—conditions that affect millions of Americans. Photo courtesy ...

  1. When Your Child Has a Chronic Kidney Disease

    MedlinePlus

    ... Year-Old When Your Child Has a Chronic Kidney Disease KidsHealth > For Parents > When Your Child Has ... and what parents can do to help. Treating Kidney Diseases Treatment begins with dietary changes and medicines. ...

  2. Autosomal dominant polycystic kidney disease in children

    PubMed Central

    Cadnapaphornchai, Melissa A.

    2015-01-01

    Purpose of review Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting one in 500 individuals. The cardinal manifestation of ADPKD is progressive cystic dilatation of renal tubules with kidney enlargement and progression to end-stage renal disease in approximately half of cases by 60 years of age. Although previously considered a condition of adults, it is clear that children and young adults are subject to the complications of ADPKD. Recent findings It has been increasingly recognized that interventions early in life are necessary in order to confer the best long-term outcome in this common condition. Therefore, it is imperative for pediatricians to recognize the manifestations and complications of this disease. Until recently ADPKD management focused on general principles of chronic kidney disease. However, several recent clinical trials in children and adults with ADPKD have focused on disease-specific therapies. Summary This review will highlight the clinical manifestations, diagnosis, and appropriate management of ADPKD in childhood and will review recent relevant clinical trials in children and adults with this condition. PMID:25635587

  3. Technology innovation for patients with kidney disease.

    PubMed

    Mitsides, Nicos; Keane, David F; Lindley, Elizabeth; Mitra, Sandip

    2014-01-01

    The loss of kidney function is a life-changing event leading to life-long dependence on healthcare. Around 5000 people are diagnosed with kidney failure every year. Historically, technology in renal medicine has been employed for replacement therapies. Recently, a lot of emphasis has been placed on technologies that aid early identification and prevent progression of kidney disease, while at the same time empowering affected individuals to gain control over their chronic illness. There is a shift in diversity of technology development, driven by collaborative innovation initiatives such the National Institute's for Health Research Healthcare Technology Co-operative for Devices for Dignity. This has seen the emergence of the patient as a key figure in designing technologies that are fit for purpose, while business involvement has ensured uptake and sustainability of these developments. An embodiment of this approach is the first successful Small Business Research Initiative in the field of renal medicine in the UK.

  4. Kidney abnormalities in sickle cell disease.

    PubMed

    López Revuelta, K; Ricard Andrés, M P

    2011-01-01

    Patients with sickle cell disease exhibits numerous kidney structural and functional abnormalities, changes that are seen along the entire length of the nephron. Changes are most marked in patients with homozygous sickle cell anemia, but are also seen in those with compound heterozygous states and the sickle cell trait. The renal features of sickle cell disease include some of the most common reasons for referral to nephrologists, such as hematuria, proteinuria, tubular disturbances and chronic kidney disease. Therapy of these conditions requires specialized knowledge of their distinct pathogenic mechanisms. Spanish Haemathology and Hemotherapy Association has recently publicated their Clinical Practice Guidelines of SCD management. Renal chapter is reproduced in this article for Nefrología difussion.

  5. Urinary proteomics for the study of genetic kidney diseases.

    PubMed

    Raimondo, Francesca; Cerra, Davide; Magni, Fulvio; Pitto, Marina

    2016-01-01

    Despite their low prevalence, genetic kidney diseases (GKD) still represent a serious health problem. They often lead to kidney failure and to the consequent need of dialysis or kidney transplant. To date, reliable diagnosis requires laborious genetic tests and/or a renal biopsy. Moreover, only scant and non-specific markers exist for prognostic purposes. Biomarkers assayed in an easily available and low-cost sample, such as urine, would be highly valuable. Urinary proteomics can provide clues related to their development through the identification of differentially expressed proteins codified by the affected genes, or other dis-regulated species, in total or fractionated urine, providing novel mechanistic insights. In this review, the authors summarize and discuss the results of the main proteomic investigations on GKD urine samples and in urinary extracellular vesicles.

  6. 42 CFR 410.48 - Kidney disease education services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Kidney disease education services. 410.48 Section... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease patient education services means face-to-face educational services provided to patients with Stage IV chronic...

  7. 42 CFR 410.48 - Kidney disease education services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Kidney disease education services. 410.48 Section... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease patient education services means face-to-face educational services provided to patients with Stage IV chronic...

  8. 42 CFR 410.48 - Kidney disease education services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Kidney disease education services. 410.48 Section... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease patient education services means face-to-face educational services provided to patients with Stage IV chronic...

  9. 42 CFR 410.48 - Kidney disease education services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Kidney disease education services. 410.48 Section... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease patient education services means face-to-face educational services provided to patients with Stage IV chronic...

  10. Updated management of chronic kidney disease in patients with diabetes.

    PubMed

    Hass, Virginia McCoy

    2014-06-01

    Chronic diseases, including chronic kidney disease (CKD), are the primary threat to global public health in the 21st century. Recently updated guidelines from the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative provide patient care benchmarks that physician assistants can use when caring for patients with diabetes and CKD and developing clinical performance improvement plans.

  11. [Diabetic nephropathy/diabetic kidney disease].

    PubMed

    Boucek, P

    2013-03-01

    Diabetic kidney disease (DKD), which belongs to the triad of diabetic microvascular complications, is currently the main cause of end-stage renal disease in developed countries. DKD usually simultaneously leads to a deteriorated long-term control of glucose metabolism and blood pressure, and to the development of diabetic retinopathy, neuropathy and atherosclerotic complications, which are the main causes of patients' mortality. Screening of the initial stages of DKD is to be based on the detection of increased albumin leak into the urine, microalbuminuria, and the reduction of renal function by means of estimates of glomerular filtration rate based on the serum creatinine level. The main objective of the prophylactic and treatment measures is to prevent the onset of DKD, or at least to stop its transition into an irreversible, progressive stage characterised by a permanent, often nephrotic proteinuria. The basic procedures in the prevention and treatment of DKD are maintaining the optimal metabolic control of diabetes and intensive hypertension treatment based on the inhibition of the renin-angiotensin system. Reaching the stage of progressive renal insufficiency (serum creatinine level approximately > or = 200 micromol/l) is an indication for further follow-up in the nephrology department, which will then take the necessary preparatory measures for dialysis treatment. The optimal method of kidney function replacement for patients with DKD is kidney transplantation, or combined kidney-pancreas transplantation in patients with type 1 diabetes.

  12. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  13. Elevated endothelial HIF-1α contributes to glomerular injury and promotes hypertensive chronic kidney disease

    PubMed Central

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K.; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2016-01-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1alpha is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with RT-PCR profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by Ang II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. PMID:25987665

  14. Histopathology of kidney disease in fish

    USGS Publications Warehouse

    Wood, E.M.; Yasutake, W.T.

    1956-01-01

    Kidney disease is one of the most puzzling fish diseases known to exist in the United States. In less than Io years it has invaded the Pacific Northwest, exacting a heavy toll of hatchery salmon. Its first appearance apparently was in Massachusetts where Belding and Merrill' described a disease similar to that now seen on the Pacific Coast. In I946 it was diagnosed in Washington2 and since that time has been observed in an ever increasing number of hatcheries. There are unpublished reports of the same or similar diseases in both California and Washington in the early I93o's.3 The latest outbreaks occurred in the Federal hatcheries at Berlin, New Hampshire, and Cortland, New York, in brook, brown, and rainbow trout.4 There is evidence to indicate that the disease may be much more widely spread in New York State.5 The disease is especially dangerous since little is known of the origin or source of the causative agent. Indeed, the classification of the diplobacillus associated with kidney disease is still uncertain. Thus, with our present knowledge, it is difficult or impossible to eradicate the malady from an infected hatchery. Histopathologic studies were undertaken to clarify the pathology of the disease and to compare the eastern form with the western form.

  15. Male Sexual Dysfunction and Chronic Kidney Disease

    PubMed Central

    Edey, Matthew M.

    2017-01-01

    Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions. PMID:28382300

  16. Antiphospholipid syndrome and kidney disease.

    PubMed

    Bienaimé, Frank; Legendre, Christophe; Terzi, Fabiola; Canaud, Guillaume

    2017-01-01

    The antiphospholipid syndrome is a common autoimmune disease caused by pathogenic antiphospholipid antibodies, leading to recurrent thrombosis and/or obstetrical complications. Importantly for nephrologists, antiphospholipid antibodies are associated with various renal manifestations including large renal vessel thrombosis, renal artery stenosis, and a constellation of intrarenal lesions that has been termed antiphospholipid nephropathy. This last condition associates various degrees of acute thrombotic microangiopathy, proliferative and fibrotic lesions of the intrarenal vessels, and ischemic modifications of the renal parenchyma. The course of the disease can range from indolent nephropathy to devastating acute renal failure. The pejorative impact of antiphospholipid antibody-related renal complication is well established in the context of systemic lupus erythematous or after renal transplantation. In contrast, the exact significance of isolated antiphospholipid nephropathy remains uncertain. The evidence to guide management of the renal complications of antiphospholipid syndrome is limited. However, the recent recognition of the heterogeneous molecular mechanisms underlying the progression of intrarenal vascular lesions in antiphospholipid syndrome have opened promising tracks for patient monitoring and targeted therapeutic intervention.

  17. Autosomal Dominant Polycystic Kidney Disease: A Path Forward.

    PubMed

    Rangan, Gopala K; Lopez-Vargas, Pamela; Nankivell, Brian J; Tchan, Michel; Tong, Allison; Tunnicliffe, David J; Savige, Judy

    2015-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited cause of renal failure in adults, and is due to loss-of-function mutations in either the PKD1 or PKD2 genes, which encode polycystin-1 and polycystin-2, respectively. These proteins have an essential role in maintaining the geometric structure of the distal collecting duct in the kidney in adult life, and their dysfunction predisposes to renal cyst formation. The typical renal phenotype of ADPKD is the insidious development of hundreds of renal cysts, which form in childhood and grow progressively through life, causing end-stage kidney failure in the fifth decade in about half affected by the mutation. Over the past 2 decades, major advances in genetics and disease pathogenesis have led to well-conducted randomized controlled trials, and observational studies that have resulted in an accumulation of evidence-based data, and raise hope that the lifetime risk of kidney failure due to ADPKD will be progressively curtailed during this century. This review will provide a contemporary summary of the current state of the field in disease pathogenesis and therapeutics, and also briefly highlights the importance of clinical practice guidelines, patient perspectives, patient-reported outcomes, uniform trial reporting, and health-economics in ADPKD.

  18. Ghrelin and cachexia in chronic kidney disease.

    PubMed

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

    2013-04-01

    Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

  19. Polycystic kidney disease in a Chartreux cat.

    PubMed

    Volta, Antonella; Manfredi, Sabrina; Gnudi, Giacomo; Gelati, Aldo; Bertoni, Giorgio

    2010-02-01

    Polycystic kidney disease (PKD) is one of the most common genetic diseases in cats. It has been widely described in Persians and Persian-related cats and sporadically in other breeds. The purpose of the present paper is to describe the first reported case of PKD in a 12-year-old female Chartreux cat. The cat was referred with polyuria and polydipsia and enlarged and irregular kidneys at palpation. Multiple renal cysts and a single liver cyst were identified by ultrasound and the inherited pattern was confirmed by genetic test (polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay). Chartreux cats should be included in the screening programme of PKD, and PKD should be always considered as a possible cause of chronic renal failure in this breed.

  20. Stroke in adult polycystic kidney disease.

    PubMed Central

    Rivera, M.; Gonzalo, A.; Gobernado, J. M.; Orte, L.; Quereda, C.; Ortuño, J.

    1992-01-01

    In order to assess the incidence of acute cerebrovascular events, 142 patients with adult polycystic kidney disease were retrospectively reviewed. Fourteen patients (9.8%) had 19 cerebral attacks. Six patients (4.2%) had intracranial haemorrhage attacks (three ruptured intracranial aneurysms and three cerebral haemorrhages). Ischaemic events occurred in nine patients (five cerebral infarctions and four transient ischaemic attacks). Patients with ischaemic attacks had a better outcome than patients with haemorrhagic events even when transient ischaemic attacks were excluded. Patients with ruptured intracranial aneurysms were younger. Cerebral complications are an important cause of morbidity and mortality in patients with adult polycystic kidney disease. They can prove disabling prior to or after dialysis and transplantation. PMID:1480536

  1. Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease.

    PubMed

    Piccoli, Giorgina B; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M; Pani, Antonello; Veltri, Andrea

    2015-01-01

    The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients.

  2. [Vitamin D and kidney diseases].

    PubMed

    Cavalier, Étienne; Thervet, Éric; Courbebaisse, Marie

    2013-10-01

    Calcitriol and analogs inhibit renin-angiotensin system, which has a pivotal role in glomerular and tubulo-interstitial damages and proteinuria, and inhibit NF-κB activation which is known to play an important role in renal diseases by promoting inflammation and fibrogenesis. Vitamin D presents interesting pleiotropic effects for the CKD patient (reduction of mortality, antiproteinuric effect and anti-inflammatory properties). "Native" vitamin D (cholecalciferol or ergocalciferol) administration in these patients also decrease parathyroid hormone levels. Native vitamin D administration in CKD patients is safe and does not lead to increased risk of vascular calcification, despite the known hypercalcemic and hyperphosphoremic properties of the molecule in its active form. Native vitamin D administration is not associated with an increased risk of renal stones, at pharmacological doses and without important concomitant administration of calcium salts. In the field of renal transplantation, experimental studies show that vitamin D analogs have a protective role against acute rejection but clinical studies remain mainly observational.

  3. Renal diseases as targets of gene therapy.

    PubMed

    Phillips, Brett; Giannoukakis, Nick; Trucco, Massimo

    2008-01-01

    A number of renal pathologies exist that have seen little or no improvement in treatment methods over the past 20 years. These pathologies include acute and chronic kidney diseases as well as posttransplant kidney survival and host rejection. A novel approach to treatment methodology may provide new insight to further progress our understanding of the disease and overall patient outcome. Recent advances in human genomics and gene delivery systems have opened the door to possible cures through the direct modulation of cellular genes. These techniques of gene therapy have not been extensively applied to renal pathologies, but clinical trials on other organ systems and kidney research in animal models hold promise. Techniques have employed viral and nonviral vectors to deliver gene modulating compounds directly into the cell. These vectors have the capability to replace defective alleles, express novel genes, or suppress the expression of pathogenic genes in a wide variety of kidney cell types. Focus has also been placed on ex vivo modification of kidney tissue to promote allograft survival and limit the resulting immune response to the transplanted organ. This could prove a valuable alternative to current immunosuppressive drugs and their deleterious effects on patients. While continued research and clinical trials are needed to identify a robust system of gene delivery, gene therapy techniques have great potential to treat kidney disease at the cellular level and improve patient quality of life.

  4. C-peptide and diabetic kidney disease.

    PubMed

    Brunskill, N J

    2017-01-01

    Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required.

  5. Epigenetics of Progression of Chronic Kidney Disease: Fact or Fantasy?

    PubMed Central

    Wing, Maria R.; Ramezani, Ali; Gill, Harindarpal S.; Devaney, Joseph M.; Raj, Dominic S.

    2013-01-01

    Summary Epigenetic modifications are important in the normal functioning of the cell, from regulating dynamic expression of essential genes and associated proteins to repressing those that are unneeded. Epigenetic changes are essential for development and functioning of the kidney, and aberrant methylation, histone modifications, and expression of microRNA could lead to chronic kidney disease (CKD). Here, epigenetic modifications modulate transforming growth factor β signaling, inflammation, profibrotic genes, and the epithelial-to-mesenchymal transition, promoting renal fibrosis and progression of CKD. Identification of these epigenetic changes is important because they are potentially reversible and may serve as therapeutic targets in the future to prevent subsequent renal fibrosis and CKD. In this review we discuss the different types of epigenetic control, methods to study epigenetic modifications, and how epigenetics promotes progression of CKD. PMID:24011578

  6. World Kidney Day 2016: averting the legacy of kidney disease-focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-04-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  7. The role of urinary peptidomics in kidney disease research.

    PubMed

    Klein, Julie; Bascands, Jean-Loup; Mischak, Harald; Schanstra, Joost P

    2016-03-01

    Urinary peptidomics focuses on endogenous urinary peptide content. Many studies now show the usefulness of this approach for the discovery and validation of biomarkers in kidney diseases that are as varied as chronic kidney disease, acute kidney injury, congenital anomalies of the kidney and the urinary tract, and polycystic kidney disease. Most studies focus on chronic kidney disease and demonstrate that urinary peptidome analysis can substantially contribute to early detection and stratification of patients with chronic kidney disease. A number of multicenter studies are ongoing that aim further validation in a clinical setting and broaden the applicability of urinary peptides. The association of urinary peptides with kidney disease also starts to deliver information on the pathophysiology of kidney disease with emphasis on extracellular matrix remodeling. Bioinformatic peptide centric tools have been developed that allow to model the changes in protease activity involved in kidney disease, based on the urinary peptidome content. A novel application of urinary peptidome analysis is the back-translation of results obtained in humans to animals for animal model validation and improvement of readout in these preclinical models. In conclusion, urinary peptidomics not only contribute to detection and stratification of kidney disease in the clinic, but might also create a new impulse in drug discovery through better insight in the pathophysiology of disease and optimized translatability of animal models.

  8. [Polycystic kidney disease in a patient using lithium chronically].

    PubMed

    Atagün, Murat Ilhan; Oral, Esad Timuçin; Sevinç, Can

    2013-01-01

    Lithium remains to be the gold standard in the treatment of mood disorders. This study presents a case treated with lithium for an extended period with a good response. Following an increase in creatinine levels, further investigation of renal dysfunction revealed polycystic kidney disease. Lithium was used prior to the diagnosis of polycystic kidney disease, resulting in the unique opportunity to examine the effects of lithium on kidneys with polycystic kidney disease. Within this context, this study also discusses the pharmacokinetics of lithium, and its possible relation to cyst formation in polycystic kidney disease.

  9. Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

    PubMed Central

    Merscher-Gomez, Sandra; Guzman, Johanna; Pedigo, Christopher E.; Lehto, Markku; Aguillon-Prada, Robier; Mendez, Armando; Lassenius, Mariann I.; Forsblom, Carol; Yoo, TaeHyun; Villarreal, Rodrigo; Maiguel, Dony; Johnson, Kevin; Goldberg, Ronald; Nair, Viji; Randolph, Ann; Kretzler, Matthias; Nelson, Robert G.; Burke, George W.; Groop, Per-Henrik; Fornoni, Alessia

    2013-01-01

    Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes. PMID:23835338

  10. Rho kinase inhibition in diabetic kidney disease.

    PubMed

    Komers, Radko

    2013-10-01

    Small GTPases of the Rho family and their down-stream effectors Rho associated kinases (ROCKs) are the molecules that converge a spectrum of pathophysiological signals triggered by the diabetic milieu and represent promising molecular targets for nephroprotective treatment in diabetes. The review discusses recent studies exploring the consequences of diabetes-induced Rho-ROCK activation in the kidney and the effects of ROCK inhibition (ROCKi) in experimental diabetic kidney disease (DKD). Studies in models of type 1 and type 2 diabetes have indicated blood pressure-independent nephroprotective actions of ROCKi in DKD. The underlying mechanisms include attenuation of diabetes-induced increases in renal expression of prosclerotic cytokines and extracellular matrix, anti-oxidant effects and protection of mitochondrial function, resulting in slower development of glomerulosclerosis and interstitial fibrosis. The studies have also shown antiproteinuric effects of ROCKi that could be related to reductions in permeability of the glomerular barrier and beneficial effects on podocytes. Glomerular haemodynamic mechanisms might also be involved. Despite remaining questions in this field, such as the effects in podocytes later in the course of DKD, specificity of currently available ROCKi, or the roles of individual ROCK isoforms, recent evidence in experimental diabetes suggests that ROCKi might in future broaden the spectrum of treatments available for patients with DKD. This is supported by the evidence generated in models of non-diabetic kidney disease and in clinical studies in patients with various cardiovascular disorders.

  11. Soluble Urokinase Receptor and Chronic Kidney Disease

    PubMed Central

    Hayek, Salim S.; Sever, Sanja; Ko, Yi-An; Trachtman, Howard; Awad, Mosaab; Wadhwani, Shikha; Altintas, Mehmet M.; Wei, Changli; Hotton, Anna L.; French, Audrey L.; Sperling, Laurence S.; Lerakis, Stamatios; Quyyumi, Arshed A.; Reiser, Jochen

    2015-01-01

    BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation

  12. Sexual function in chronic kidney disease.

    PubMed

    Anantharaman, Priya; Schmidt, Rebecca J

    2007-04-01

    Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

  13. 77 FR 28890 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee. Date... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Initial...

  14. 75 FR 3741 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-22

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee. Date... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Initial...

  15. 78 FR 9063 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee. Date... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Initial...

  16. Hypertension in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Chapman, Arlene B.; Stepniakowski, Konrad; Rahbari-Oskoui, Frederic

    2010-01-01

    Hypertension is common and occurs in a majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end stage renal disease. The pathogenesis of hypertension in ADPKD is complex and dependent on many factors that influence each other. Pkd1 and Pkd2 expression levels are highest in the major vessels and are present in the cilia of endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin 1 or 2 expression is associated with abnormal vascular structure and function. Pkd1/Pkd2 deficiency results in reduced nitric oxide (NO) levels, altered endothelial response to shear stress with attenuation in vascular relaxation. 10–20% of ADPKD children demonstrate hypertension and the majority of adults are hypertensive before any loss of kidney function. Cardiac abnormalities such as left ventricular hypertrophy and carotid intimal wall thickening are present prior to the development of hypertension in ADPKD. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased NO production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the RAAS occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to ESRD. Inhibition of the angiotensin aldosterone system is possible with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. However, interventional studies have not yet demonstrated benefit in slowing progression to renal failure in ADPKD. Currently, large multicenter studies are being performed to determine the beneficial effects of RAAS inhibition both early and late in ADPKD. PMID:20219618

  17. Kidney transplantation in patients with Fabry disease.

    PubMed

    Cybulla, Markus; Walter, Kerstin Nanette; Schwarting, Andreas; Divito, Raffaelle; Feriozzi, Sandro; Sunder-Plassmann, Gere

    2009-04-01

    Little is known about the effects of enzyme replacement therapy (ERT) in kidney transplant recipients with Fabry disease. Clinical characteristics of transplant recipients in the Fabry Outcome Survey (FOS) were therefore examined in patients with Fabry disease with or without ERT. Of the 837 European patients in FOS (March 2006), 34 male patients and two female patients had received kidney transplants. Mean age at transplantation was 37.6 +/- 10.9 years, mean time since transplantation was 7.7 +/- 6.4 years, median estimated glomerular filtration rate (eGFR) was 44.4 ml/min/1.73 m(2), and median proteinuria was 296 mg/24 h. Of 27 patients with baseline data, 59% had hypertension, 74% had left ventricular hypertrophy, 22% had cardiac valve disease, 30% had arrhythmia, and 22% had transient ischaemic attacks and 15% stroke. Twenty patients (74%; two female patients, 18 male patients) were receiving ERT with agalsidase alfa. At enrollment or at the start of ERT, median eGFRs were 59 and 35 ml/min/1.73 m(2) (P = 0.05) and median proteinuria levels were 240 and 420 mg/24 h (not significant) in treated and untreated patients respectively. Renal function remained stable in patients receiving ERT. In conclusion, agalsidase alfa is well tolerated in patients with Fabry disease who have undergone renal transplantation.

  18. IgG4-related kidney disease.

    PubMed

    Cornell, Lynn D

    2012-11-01

    IgG4-related kidney disease is a term that refers to any form of renal involvement by IgG4-related disease (IgG4-RD), a recently recognized systemic immune-mediated disease. The most common renal manifestation is IgG4-related tubulointerstitial nephritis (IgG4-TIN), which presents as acute or chronic renal insufficiency, renal mass lesions, or both. On biopsy, IgG4-TIN shows a plasma cell-rich interstitial inflammatory infiltrate with increased IgG4+ plasma cells, along with expansile interstitial fibrosis; tubular basement membrane immune complex deposits are common. IgG4-TIN usually shows a brisk response to immunosuppressive therapy. Glomeruli may be affected by IgG4-RD, usually in the form of membranous glomerulonephritis. Other patterns of glomerular disease include IgA nephropathy, membranoproliferative glomerulonephritis, and endocapillary or mesangioproliferative immune complex glomerulonephritis. IgG4-related plasma cell arteritis has also been observed in the kidney. This review describes the histopathologic and immunophenotypic patterns of renal involvement by IgG4-RD, with associated clinical, radiographic, and serologic features.

  19. Developmental Programming of Hypertension and Kidney Disease

    PubMed Central

    Chong, Euming; Yosypiv, Ihor V.

    2012-01-01

    A growing body of evidence supports the concept that changes in the intrauterine milieu during “sensitive” periods of embryonic development or in infant diet after birth affect the developing individual, resulting in general health alterations later in life. This phenomenon is referred to as “developmental programming” or “developmental origins of health and disease.” The risk of developing late-onset diseases such as hypertension, chronic kidney disease (CKD), obesity or type 2 diabetes is increased in infants born prematurely at <37 weeks of gestation or in low birth weight (LBW) infants weighing <2,500 g at birth. Both genetic and environmental events contribute to the programming of subsequent risks of CKD and hypertension in premature or LBW individuals. A number of observations suggest that susceptibility to subsequent CKD and hypertension in premature or LBW infants is mediated, at least in part, by reduced nephron endowment. The major factors influencing in utero environment that are associated with a low final nephron number include uteroplacental insufficiency, maternal low-protein diet, hyperglycemia, vitamin A deficiency, exposure to or interruption of endogenous glucocorticoids, and ethanol exposure. This paper discusses the effect of premature birth, LBW, intrauterine milieu, and infant feeding on the development of hypertension and renal disease in later life as well as examines the role of the kidney in developmental programming of hypertension and CKD. PMID:23251800

  20. Developmental programming of hypertension and kidney disease.

    PubMed

    Chong, Euming; Yosypiv, Ihor V

    2012-01-01

    A growing body of evidence supports the concept that changes in the intrauterine milieu during "sensitive" periods of embryonic development or in infant diet after birth affect the developing individual, resulting in general health alterations later in life. This phenomenon is referred to as "developmental programming" or "developmental origins of health and disease." The risk of developing late-onset diseases such as hypertension, chronic kidney disease (CKD), obesity or type 2 diabetes is increased in infants born prematurely at <37 weeks of gestation or in low birth weight (LBW) infants weighing <2,500 g at birth. Both genetic and environmental events contribute to the programming of subsequent risks of CKD and hypertension in premature or LBW individuals. A number of observations suggest that susceptibility to subsequent CKD and hypertension in premature or LBW infants is mediated, at least in part, by reduced nephron endowment. The major factors influencing in utero environment that are associated with a low final nephron number include uteroplacental insufficiency, maternal low-protein diet, hyperglycemia, vitamin A deficiency, exposure to or interruption of endogenous glucocorticoids, and ethanol exposure. This paper discusses the effect of premature birth, LBW, intrauterine milieu, and infant feeding on the development of hypertension and renal disease in later life as well as examines the role of the kidney in developmental programming of hypertension and CKD.

  1. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder

    PubMed Central

    Seifert, Michael E.; Hruska, Keith A.

    2015-01-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well, as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This Overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy. PMID:26356179

  2. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  3. Rare inherited kidney diseases: challenges, opportunities, and perspectives.

    PubMed

    Devuyst, Olivier; Knoers, Nine V A M; Remuzzi, Giuseppe; Schaefer, Franz

    2014-05-24

    At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially decrease their quality of life and have a large effect on health-care systems. Since the kidneys regulate essential homoeostatic processes, inherited kidney disorders have multisystem complications, which add to the usual challenges for rare disorders. In this review, we discuss the nature of rare inherited kidney diseases, the challenges they pose, and opportunities from technological advances, which are well suited to target the kidney. Mechanistic insights from rare disorders are relevant for common disorders such as hypertension, kidney stones, cardiovascular disease, and progression of chronic kidney disease.

  4. Averting the legacy of kidney disease: focus on childhood

    PubMed Central

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:28031959

  5. Averting the legacy of kidney disease – focus on childhood

    PubMed Central

    Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group amongst children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help to detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, whilst only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policymakers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:27247150

  6. Averting the legacy of kidney disease - focus on childhood

    PubMed Central

    Ingelfinger, J.R.; Kalantar-Zadeh, K.; Schaefer, F.

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:27096201

  7. Averting the Legacy of Kidney Disease--Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  8. Gonadal dysfunction in chronic kidney disease.

    PubMed

    Palmer, Biff F; Clegg, Deborah J

    2016-09-01

    Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psycho social factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected prior to the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men while the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed towards optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure.

  9. Cardiometabolic syndrome and chronic kidney disease.

    PubMed

    Lastra, Guido; Manrique, Camila; McFarlane, Samy I; Sowers, James R

    2006-06-01

    Chronic kidney disease (CKD) is increasingly recognized as a major risk factor for end-stage renal disease (ESRD), cardiovascular (CV) disease, and CV-related premature death. More than 8 million people in the United States have CKD; therefore, preventive stratiegies should be directed at identifying risk factors for this condition. There is growing evidence implicating the cardiometabolic syndrome, a clustering of CV risk factors that include obesity, insulin resistance, compensatory hyperinsulinemia, dysglycemia, atherogenic dyslipidemia, and hypertension. Factors mediating this relationship include increased glomerular filtration, increased vascular permeability, oxidative and endoplasmic reticulum stress, activation of the renin-angiotensin system, and inappropriate secretion of growth factors. The consequences are microalbuminuria, a marker of inflammation and endothelial dysfunction, renal vascular proliferation, extracellular matrix expansion, and CKD. Prevention of CKD should be directed at controlling all components of the cardiometabolic syndrome, with the ultimate goal of reducing the burden imposed by ESRD.

  10. Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets

    PubMed Central

    Toth-Manikowski, Stephanie; Atta, Mohamed G.

    2015-01-01

    Diabetes is a worldwide epidemic that has led to a rise in diabetic kidney disease (DKD). Over the past two decades, there has been significant clarification of the various pathways implicated in the pathogenesis of DKD. Nonetheless, very little has changed in the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and hypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current understanding of how the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and detail the various therapeutic targets that may one day play a role in quelling this epidemic. PMID:26064987

  11. Vitamin K Status in Chronic Kidney Disease

    PubMed Central

    McCabe, Kristin M.; Adams, Michael A.; Holden, Rachel M.

    2013-01-01

    The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population. PMID:24212088

  12. Baroreflex dysfunction in chronic kidney disease

    PubMed Central

    Kaur, Manpreet; Chandran, Dinu S; Jaryal, Ashok Kumar; Bhowmik, Dipankar; Agarwal, Sanjay Kumar; Deepak, Kishore Kumar

    2016-01-01

    Chronic kidney disease (CKD) patients have high cardiovascular mortality and morbidity. The presence of traditional and CKD related risk factors results in exaggerated vascular calcification in these patients. Vascular calcification is associated with reduced large arterial compliance and thus impaired baroreflex sensitivity (BRS) resulting in augmented blood pressure (BP) variability and hampered BP regulation. Baroreflex plays a vital role in short term regulation of BP. This review discusses the normal baroreflex physiology, methods to assess baroreflex function, its determinants along with the prognostic significance of assessing BRS in CKD patients, available literature on BRS in CKD patients and the probable patho-physiology of baroreflex dysfunction in CKD. PMID:26788464

  13. Keap1 hypomorphism protects against ischemic and obstructive kidney disease

    PubMed Central

    Tan, Roderick J.; Chartoumpekis, Dionysios V.; Rush, Brittney M.; Zhou, Dong; Fu, Haiyan; Kensler, Thomas W.; Liu, Youhua

    2016-01-01

    The Keap1/Nrf2 pathway is a master regulator of antioxidant, anti-inflammatory, and other cytoprotective mechanisms important in protection from kidney disease. For the first time in kidney disease, we describe the use of Keap1 hypomorphic mice, which possess Nrf2 hyperactivation. We exposed these mice and wild type controls to ischemia/reperfusion injury (IRI). The initial tubular injury at 24 hours post-IRI appeared to be unaffected, with the only observed difference being a decrease in inflammatory cytokine expression in the hypomorphs. However, we noted significant improvement in serum creatinine in the hypomorphs at 3 and 10 days after injury, and renal fibrosis was dramatically attenuated at the late timepoint. Assessment of Nrf2-regulated targets (GSTM1, GSTP1, NQO1) revealed higher expression in the hypomorphs at baseline. While injury tended to suppress these genes in wild-type mice, the suppression was attenuated or reversed in Keap1 hypomorphs, suggesting that protection in these mice was mediated by increased Nrf2 transcriptional activity. To assess the generalizability of our findings, we subjected the hypomorphs to unilateral ureteral obstruction (UUO) and again found significant protection and increased expression of Nrf2 targets. Overall, these results support the conclusion that the Nrf2 pathway is protective in a variety of kidney diseases. PMID:27804998

  14. Polycystic kidney disease in four British shorthair cats with successful treatment of bacterial cyst infection.

    PubMed

    Nivy, R; Lyons, L A; Aroch, I; Segev, G

    2015-09-01

    Polycystic kidney disease is the most common inherited disorder in cats. Renal cysts progressively increase in size and number, resulting in a gradual decrease in kidney function. An autosomal dominant mutation in exon 29 of the polycystin-1 gene has been identified, mostly in Persian and Persian-related breeds. This case study describes polycystic kidney disease in four British shorthair cats, of which two had the same genetic mutation reported in Persian and Persian-related cats. This likely reflects introduction of this mutation into the British shorthair breeding line because of previous outcrossing with Persian cats. An infected renal cyst was diagnosed and successfully treated in one of the cats. This is a commonly reported complication in human polycystic kidney disease, and to the authors' knowledge has not previously been reported in cats with polycystic kidney disease.

  15. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management--A KDIGO consensus report.

    PubMed

    Eckardt, Kai-Uwe; Alper, Seth L; Antignac, Corinne; Bleyer, Anthony J; Chauveau, Dominique; Dahan, Karin; Deltas, Constantinos; Hosking, Andrew; Kmoch, Stanislav; Rampoldi, Luca; Wiesener, Michael; Wolf, Matthias T; Devuyst, Olivier

    2015-10-01

    Rare autosomal dominant tubulointerstitial kidney disease is caused by mutations in the genes encoding uromodulin (UMOD), hepatocyte nuclear factor-1β (HNF1B), renin (REN), and mucin-1 (MUC1). Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Juvenile Hyperuricemic Nephropathy (FJHN)', or 'Uromodulin-Associated Kidney Disease (UAKD)' for UMOD-related diseases and 'MCKD type 1' for the disease caused by MUC1 mutations. The multiplicity of these terms, and the fact that cysts are not pathognomonic, creates confusion. Kidney Disease: Improving Global Outcomes (KDIGO) proposes adoption of a new terminology for this group of diseases using the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' (ADTKD) appended by a gene-based subclassification, and suggests diagnostic criteria. Implementation of these recommendations is anticipated to facilitate recognition and characterization of these monogenic diseases. A better understanding of these rare disorders may be relevant for the tubulointerstitial fibrosis component in many forms of chronic kidney disease.

  16. Developments in renal pharmacogenomics and applications in chronic kidney disease

    PubMed Central

    Padullés, Ariadna; Rama, Inés; Llaudó, Inés; Lloberas, Núria

    2014-01-01

    Chronic kidney disease (CKD) has shown an increasing prevalence in the last century. CKD encompasses a poor prognosis related to a remarkable number of comorbidities, and many patients suffer from this disease progression. Once the factors linked with CKD evolution are distinguished, it will be possible to provide and enhance a more intensive treatment to high-risk patients. In this review, we focus on the emerging markers that might be predictive or related to CKD progression physiopathology as well as those related to a different pattern of response to treatment, such as inhibitors of the renin–angiotensin system (including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers; the vitamin D receptor agonist; salt sensitivity hypertension; and progressive kidney-disease markers with identified genetic polymorphisms). Candidate-gene association studies and genome-wide association studies have analyzed the genetic basis for common renal diseases, including CKD and related factors such as diabetes and hypertension. This review will, in brief, consider genotype-based pharmacotherapy, risk prediction, drug target recognition, and personalized treatments, and will mainly focus on findings in CKD patients. An improved understanding will smooth the progress of switching from classical clinical medicine to gene-based medicine. PMID:25206311

  17. Diabetic kidney disease: from physiology to therapeutics

    PubMed Central

    Mora-Fernández, Carmen; Domínguez-Pimentel, Virginia; de Fuentes, Mercedes Muros; Górriz, José L; Martínez-Castelao, Alberto; Navarro-González, Juan F

    2014-01-01

    Diabetic kidney disease (DKD) defines the functional, structural and clinical abnormalities of the kidneys that are caused by diabetes. This complication has become the single most frequent cause of end-stage renal disease. The pathophysiology of DKD comprises the interaction of both genetic and environmental determinants that trigger a complex network of pathophysiological events, which leads to the damage of the glomerular filtration barrier, a highly specialized structure formed by the fenestrated endothelium, the glomerular basement membrane and the epithelial podocytes, that permits a highly selective ultrafiltration of the blood plasma. DKD evolves gradually over years through five progressive stages. Briefly they are: reversible glomerular hyperfiltration, normal glomerular filtration and normoalbuminuria, normal glomerular filtration and microalbuminuria, macroalbuminuria, and renal failure. Approximately 20–40% of diabetic patients develop microalbuminuria within 10–15 years of the diagnosis of diabetes, and about 80–90% of those with microalbuminuria progress to more advanced stages. Thus, after 15–20 years, macroalbuminuria occurs approximately in 20–40% of patients, and around half of them will present renal insufficiency within 5 years. The screening and early diagnosis of DKD is based on the measurement of urinary albumin excretion and the detection of microalbuminuria, the first clinical sign of DKD. The management of DKD is based on the general recommendations in the treatment of patients with diabetes, including optimal glycaemic and blood pressure control, adequate lipid management and abolishing smoking, in addition to the lowering of albuminuria. PMID:24907306

  18. Chronic kidney disease in postmenopausal women.

    PubMed

    Suzuki, Hiromichi; Kondo, Kazuoki

    2012-02-01

    Menopause is derived from the Greek words men (month) and pauses (cessation) and means permanent cessation of menstruation after the loss of ovarian activity. Chronic kidney disease (CKD) has recently been associated with cardiovascular events in several studies. CKD patients have a heavy burden of traditional cardiovascular risk factors in addition to a range of nontraditional risk factors such as inflammation and abnormal metabolism of calcium and phosphate. In this review, the association of CKD and cardiovascular disease (CVD), as well as of osteoporosis in postmenopausal women is discussed. CKD mineral and bone disorder, characterized by disturbances of calcium/phosphate/parathyroid hormone, bone abnormalities and vascular and soft tissue calcification, is highly prevalent in CKD and is a strong, independent predictor of bone fracture, CVD and death. Estrogen has been shown to: (a) decrease the expression of angiotensin type 1 receptors in vasculature and kidneys; (b) reduce the expression and activity of angiotensin-converting enzyme, and (c) cause the release of angiotensinogen substrate from the liver. However, the degree of activation or suppression of the renin-angiotensin-aldosterone system by estrogen has not been clearly established. Clinical data on the effects of estrogen therapy on bone mineral densities are extremely limited in the ESRD population. CVD is the most common cause of death in postmenopausal women with CKD and many contributing factors have been explored. Future research for prevention of CVD in postmenopausal women with CKD would focus on the biology of vascular calcification as well as bone loss.

  19. Central blood pressure and chronic kidney disease

    PubMed Central

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  20. Autosomal dominant polycystic kidney disease diagnosed in utero. Review.

    PubMed

    Nowak, Magdalena; Huras, Hubert; Wiecheć, Marcin; Jach, Robert; Radoń-Pokracka, Małgorzata; Górecka, Joanna

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of most common inherited renal diseases. It is estimated that very early onset ADPKD affects even 2% patients. The purpose of this article is to provide a comprehensive review of genetics, prenatal diagnosis and prognosis in very early onset autosomal dominant polycystic kidney disease.

  1. Schistosomiasis-associated kidney disease: A review

    PubMed Central

    da Silva, Geraldo Bezerra; Duarte, Daniella Bezerra; Barros, Elvino José Guardão; Daher, Elizabeth De Francesco

    2013-01-01

    Schistosomiasis is a parasitic disease caused by organisms from the genus Schistosoma. The disease is endemic in tropical areas, where there are currently millions of people living in areas with transmission risk. Schistosomiasis-associated kidney disease is not frequently described in literature. The disease has a chronic evolution, with variable severity. Glomerulonephritis is described in 10-12% in autopsy studies. Proteinuria is reported in 20% of patients with S. mansoni infection. Schistosomal glomerulopathy generally occur in young patients, male, with hepato-splenomegaly. The glomerular lesion in schistosomiasis has an immunological nature. Antigens from the parasite seem to be related to glomerulopathy and have been found in the sera of humans and animals infected by the S. mansoni. Vesical involvement is common in the infection by S. haematobium, a parasitic disease prevalent in African countries. In the S. haematobium infection, hematuria and dysuria can be observed due to inflammation and ulceration in the bladder mucosa, generaly occuring 3 to 4 months after primary infection. Specific antiparasitic treatment is indicated to all patients infected by Schistosoma. There are 2 drugs available for treatment, praziquantel and oxamniquine. We revise the general aspects of the disease and describe the features of renal involvement in schistosomiasis.

  2. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans.

    PubMed

    Vivante, Asaf; Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hildebrandt, Friedhelm

    2014-04-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) cover a wide range of structural malformations that result from defects in the morphogenesis of the kidney and/or urinary tract. These anomalies account for about 40-50 % of children with chronic kidney disease worldwide. Knowledge from genetically modified mouse models suggests that single gene mutations in renal developmental genes may lead to CAKUT in humans. However, until recently, only a handful of CAKUT-causing genes were reported, most of them in familial syndromic cases. Recent findings suggest that CAKUT may arise from mutations in a multitude of different single gene causes. We focus here on single-gene causes of CAKUT and their developmental origin. Currently, more than 20 monogenic CAKUT-causing genes have been identified. High-throughput sequencing techniques make it likely that additional CAKUT-causing genes will be identified in the near future.

  3. Vaccination against bacterial kidney disease: Chapter 22

    USGS Publications Warehouse

    Elliott, Diane G.; Wiens, Gregory D.; Hammell, K. Larry; Rhodes, Linda D.; Edited by Gudding, Roar; Lillehaug, Atle; Evensen, Øystein

    2014-01-01

    Bacterial kidney disease (BKD) of salmonid fishes, caused by Renibacterium salmoninarum, has been recognized as a serious disease in salmonid fishes since the 1930s. This chapter discusses the occurrence and significance, etiology, and pathogenesis of BKD. It then describes the different vaccination procedures and the effects and side-effects of vaccination. Despite years of research, however, only a single vaccine has been licensed for prevention of BKD, and has demonstrated variable efficacy. Therefore, in addition to a presentation of the current status of BKD vaccination, a discussion of potential future directions for BKD vaccine development is included in the chapter. This discussion is focused on the unique characteristics of R. salmoninarum and its biology, as well as aspects of the salmonid immune system that might be explored specifically to develop more effective vaccines for BKD prevention.

  4. Sleep disorders and chronic kidney disease.

    PubMed

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-05-06

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.

  5. Sleep disorders and chronic kidney disease

    PubMed Central

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-01-01

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD. PMID:27152260

  6. Life cycle analysis of kidney gene expression in male F344 rats.

    PubMed

    Kwekel, Joshua C; Desai, Varsha G; Moland, Carrie L; Vijay, Vikrant; Fuscoe, James C

    2013-01-01

    Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p<0.01) coupled with a fold-change>1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs). Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

  7. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  8. Autosomal dominant polycystic kidney disease: the last 3 years

    PubMed Central

    Torres, Vicente E.; Harris, Peter C.

    2010-01-01

    Autosomal dominant polycystic kidney disease is the most prevalent, potentially lethal monogenic disorder. It has large inter- and intra-familial variability explained to a large extent by its genetic heterogeneity and modifier genes. An increased understanding of its underlying genetic, molecular, and cellular mechanisms and a better appreciation of its progression and systemic manifestations have laid out the foundation for the development of clinical trials and potentially effective therapies. The purpose of this review is to update the core of knowledge in this area with recent publications that have appeared during 2006–2009. PMID:19455193

  9. BEYOND GENETICS: EPIGENETIC CODE IN CHRONIC KIDNEY DISEASE

    PubMed Central

    Dwivedi, Rama S.; Herman, James G.; McCaffrey, Timothy; Raj, Dominic SC

    2013-01-01

    Epigenetics refers to a heritable change in the pattern of gene expression that is mediated by a mechanism specifically not due to alterations in the primary nucleotide sequence. Well known epigenetic mechanisms encompass DNA methylation, chromatin remodeling (histone modifications) and RNA interference. Functionally, epigenetics provides an extra layer of transcriptional control and plays a crucial role in normal physiological development, as well as in pathological conditions. Aberrant DNA methylation is implicated in immune dysfunction, inflammation and insulin resistance. Epigenetic changes may be responsible for “metabolic memory” and development of micro- and macrovascular complications of diabetes. MicroRNAs are critical in the maintenance of glomerular homeostasis and hence RNA interference may be important in the progression of renal disease. Recent studies have shown that epigenetic modifications orchestrate the epithelial-mesenchymal transition and eventually fibrosis of the renal tissue. Oxidative stress, inflammation, hyperhomocysteinemia and uremic toxins could induce epimutations in chronic kidney disease. Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease. Reversible nature of the epigenetic changes gives an unique opportunity to halt or even reverse the disease process through targeted therapeutic strategies. PMID:20881938

  10. Chronic kidney disease and pregnancy: maternal and fetal outcomes.

    PubMed

    Fischer, Michael J

    2007-04-01

    Chronic kidney disease complicates an increasing number of pregnancies, and at least 4% of childbearing-aged women are afflicted by this condition. Although diabetic nephropathy is the most common type of chronic kidney disease found in pregnant women, a variety of other primary and systemic kidney diseases also commonly occur. In the setting of mild maternal primary chronic kidney disease (serum creatinine <1.3 mg/dL) without poorly controlled hypertension, most pregnancies result in live births and maternal kidney function is unaffected. In cases of more moderate and severe maternal primary chronic kidney disease, the incidence of fetal prematurity, low birth weight, and death increase substantially, and the risk of accelerated irreversible decline in maternal kidney function, proteinuria, and hypertensive complications rise dramatically. In addition to kidney function, maternal hypertension and proteinuria portend negative outcomes and are important factors to consider when risk stratifying for fetal and maternal complications. In the setting of diabetic nephropathy and lupus nephropathy, other systemic disease features such as disease activity, the presence of antiphospholipid antibodies, and glycemic control play important roles in determining pregnancy outcomes. Concomitant with advances in obstetrical management and kidney disease treatments, it appears that the historically dismal maternal and fetal outcomes have greatly improved.

  11. Systemic and renal lipids in kidney disease development and progression

    PubMed Central

    Wahl, Patricia; Ducasa, Gloria Michelle

    2015-01-01

    Altered lipid metabolism characterizes proteinuria and chronic kidney diseases. While it is thought that dyslipidemia is a consequence of kidney disease, a large body of clinical and experimental studies support that altered lipid metabolism may contribute to the pathogenesis and progression of kidney disease. In fact, accumulation of renal lipids has been observed in several conditions of genetic and nongenetic origins, linking local fat to the pathogenesis of kidney disease. Statins, which target cholesterol synthesis, have not been proven beneficial to slow the progression of chronic kidney disease. Therefore, other therapeutic strategies to reduce cholesterol accumulation in peripheral organs, such as the kidney, warrant further investigation. Recent advances in the understanding of the biology of high-density lipoprotein (HDL) have revealed that functional HDL, rather than total HDL per se, may protect from both cardiovascular and kidney diseases, strongly supporting a role for altered cholesterol efflux in the pathogenesis of kidney disease. Although the underlying pathophysiological mechanisms responsible for lipid-induced renal damage have yet to be uncovered, several studies suggest novel mechanisms by which cholesterol, free fatty acids, and sphingolipids may affect glomerular and tubular cell function. This review will focus on the clinical and experimental evidence supporting a causative role of lipids in the pathogenesis of proteinuria and kidney disease, with a primary focus on podocytes. PMID:26697982

  12. 75 FR 2147 - National Institute of Diabetes and Digestive and Kidney Diseases, Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... Committee: National Diabetes and Digestive and Kidney Diseases Advisory Council. Date: February 24, 2010... of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Blvd., Room 715, MSC 5452, Bethesda, MD... Kidney Diseases Advisory Council; Diabetes, Endocrinology, and Metabolic Diseases Subcommittee....

  13. Regulatory T cells in kidney disease and transplantation.

    PubMed

    Hu, Min; Wang, Yuan Min; Wang, Yiping; Zhang, Geoff Y; Zheng, Guoping; Yi, Shounan; O'Connell, Philip J; Harris, David C H; Alexander, Stephen I

    2016-09-01

    Regulatory T cells (Tregs) have been shown to be important in maintaining immune homeostasis and preventing autoimmune disease, including autoimmune kidney disease. It is also likely that they play a role in limiting kidney transplant rejection and potentially in promoting transplant tolerance. Although other subsets of Tregs exist, the most potent and well-defined Tregs are the Foxp3 expressing CD4(+) Tregs derived from the thymus or generated peripherally. These CD4(+)Foxp3(+) Tregs limit autoimmune renal disease in animal models, especially chronic kidney disease, and kidney transplantation. Furthermore, other subsets of Tregs, including CD8 Tregs, may play a role in immunosuppression in kidney disease. The development and protective mechanisms of Tregs in kidney disease and kidney transplantation involve multiple mechanisms of suppression. Here we review the development and function of CD4(+)Foxp3(+) Tregs. We discuss the specific application of Tregs as a therapeutic strategy to prevent kidney disease and to limit kidney transplant rejection and detail clinical trials in this area of transplantation.

  14. Burden of chronic kidney disease: North Africa

    PubMed Central

    Barsoum, Rashad S

    2013-01-01

    North Africa (NAF) is composed of six countries located in the African Sahara, namely the Western Sahara, Morocco, Algeria, Tunisia, Libya, and Egypt. Common features between these countries include similar climate, ecology, population genetics, and the socioeconomic environment. This commonality reflects on the chronic kidney disease (CKD) profile in these countries. While there are some estimates on the epidemiology of end-stage kidney disease, that of earlier stages is unknown. Several national screening programs are currently addressing this issue, such as the EGIPT-CKD project in Egypt and the MAREMAR study in Morocco. Preliminary results from the former suggest a prevalence of proteinuria in 10.6% of the relatives of patients on regular dialysis treatment. Despite the lack of reliable registries, it was possible to gather information on the etiology of CKD by direct contact with leading nephrologists in those countries. It turns out that glomerulonephritis (GN) accounts for 9–20%, diabetes 11–18%, hypertensive nephrosclerosis 10–35%, chronic interstitial nephritis 7–17%, and polycystic disease 2–3%. Compared to two decades earlier, diabetes has become more common at the expense of GN, proliferative GN, and amyloidosis regressed in favor of IgA and membranous nephropathies in Tunisian adults. Conventional schistosomal nephropathies are regressing in favor of hepatitis C viral (HCV) nephropathy in Egyptians. Focal segmental glomerulosclerosis is increasing at the expense of proliferative GNs in the region at large. Access to regular dialysis has been optimized during the past decade, with favorable outcomes despite the high incidence of HCV infection, tuberculosis, and protein-calorie malnutrition. Kidney transplantation is available in all NAF countries except the Western Sahara. About 650 transplants are performed annually from live donors, the majority in Egypt, where data from the largest center in Mansoura display a 10-year graft survival of 62

  15. Management of hyperkalaemia in chronic kidney disease.

    PubMed

    Kovesdy, Csaba P

    2014-11-01

    Hyperkalaemia is common in patients with chronic kidney disease (CKD), in part because of the effects of kidney dysfunction on potassium homeostasis and in part because of the cluster of comorbidities (and their associated treatments) that occur in patients with CKD. Owing to its electrophysiological effects, severe hyperkalaemia represents a medical emergency that usually requires prompt intervention, whereas the prevention of hazardous hyperkalaemic episodes in at-risk patients requires measures aimed at the long-term normalization of potassium homeostasis. The options for effective and safe medical interventions to restore chronic potassium balance are few, and long-term management of hyperkalaemia is primarily limited to the correction of modifiable exacerbating factors. This situation can result in a difficult trade-off in patients with CKD, because drugs that are beneficial to these patients (for example, renin-angiotensin-aldosterone-system antagonists) are often the most prominent cause of their hyperkalaemia. Maintaining the use of these beneficial medications while implementing various strategies to control potassium balance is desirable; however, discontinuation rates remain high. The emergence of new medications that specifically target hyperkalaemia could lead to a therapeutic paradigm shift, emphasizing preventive management over ad hoc treatment of incidentally discovered elevations in serum potassium levels.

  16. [Treatment of hypertension in chronic kidney disease].

    PubMed

    Palomo-Piñón, Silvia; Rosas-Peralta, Martín; Paniagua-Sierra, José Ramón

    2016-01-01

    Systemic arterial hypertension (SAH) is a progressive cardiovascular syndrome caused by complex and interrelated causes. The early markers of this syndrome are often present even before the blood pressure (BP) elevation; therefore, SAH cannot only be classified by the BP elevation threshold, which sometimes is discreet. Its progression is strongly associated with structural and functional cardiovascular abnormalities, which lead to end-organ damage (heart, kidney, brain, blood vessels and other organs), and cause premature morbidity and death. In this sense, the BP is only a biomarker of this cardiovascular syndrome, which is why it is more useful to consider individual BP patterns of the ill patient rather than a single BP threshold. The study and treatment of hypertension in chronic kidney disease (CKD) has made some progresses, especially in patients requiring dialysis. The use of non-invasive technology to register the BP has reconfigured health care of patients in regards to the diagnosis, circadian pattern, clinical surveillance, pharmacological prescription, prognosis, and risk of cardiovascular events (as well as mortality). The opportunity in the diagnosis and treatment means a delay in the onset of complications and, also, of dialysis. The blockade of the renin-aldotensin-aldosterone system (RAAS), a regular monitoring of the dry weight of the population in dialysis, and non-pharmacological interventions to modify lifestyle are the maneuvers with greater impact on the morbidity and mortality of patients.

  17. Neprilysin inhibition in chronic kidney disease

    PubMed Central

    Judge, Parminder; Haynes, Richard; Landray, Martin J.; Baigent, Colin

    2015-01-01

    Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin–angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population. PMID:25140014

  18. Neprilysin inhibition in chronic kidney disease.

    PubMed

    Judge, Parminder; Haynes, Richard; Landray, Martin J; Baigent, Colin

    2015-05-01

    Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin-angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population.

  19. Integrative Biology of Diabetic Kidney Disease

    PubMed Central

    Harder, Jennifer L.; Hodgin, Jeffrey B.; Kretzler, Matthias

    2015-01-01

    Background The leading cause of end-stage renal disease in the US is diabetic kidney disease (DKD). Despite significant efforts to improve outcomes in DKD, the impact on disease progression has been disappointing. This has prompted clinicians and researchers to search for alternative approaches to identify persons at risk, and to search for more effective therapies to halt progression of DKD. The identification of novel therapies is critically dependent on a more comprehensive understanding of the pathophysiology of DKD, specifically at the molecular level. A more expansive and exploratory view of DKD is needed to complement more traditional research approaches that have focused on single molecules. Summary In recent years, sophisticated research methodologies have emerged within systems biology that should allow for a more comprehensive disease definition of DKD. Systems biology provides an interdisciplinary approach to describe complex interactions within biological systems, including how these interactions influence systems' functions and behaviors. Computational modeling of large, system-wide, quantitative data sets is used to generate molecular interaction pathways, such as metabolic and cell signaling networks. Key Messages Importantly, the interpretation of data generated by systems biology tools requires integration with enhanced clinical research data and validation using model systems. Such an integrative biological approach has already generated novel insights into pathways and molecules involved in DKD. In this review, we highlight recent examples of how combining systems biology with traditional clinical and model research efforts results in an integrative biology approach that significantly adds to the understanding of the complex pathophysiology of DKD. PMID:26929927

  20. A computer-aided diagnostic system for kidney disease

    PubMed Central

    Jahantigh, Farzad Firouzi; Malmir, Behnam; Avilaq, Behzad Aslani

    2017-01-01

    Background Disease diagnosis is complicated since patients may demonstrate similar symptoms but physician may diagnose different diseases. There are a few number of investigations aimed to create a fuzzy expert system, as a computer aided system for disease diagnosis. Methods In this research, a cross-sectional descriptive study conducted in a kidney clinic in Tehran, Iran in 2012. Medical diagnosis fuzzy rules applied, and a set of symptoms related to the set of considered diseases defined. The input case to be diagnosed defined by assigning a fuzzy value to each symptom and then three physicians asked about each suspected diseases. Then comments of those three physicians summarized for each disease. The fuzzy inference applied to obtain a decision fuzzy set for each disease, and crisp decision values attained to determine the certainty of existence for each disease. Results Results indicated that, in the diagnosis of seven cases of kidney disease by examining 21 indicators using fuzzy expert system, kidney stone disease with 63% certainty was the most probable, renal tubular was at the lowest level with 15%, and other kidney diseases were at the other levels. The most remarkable finding of this study was that results of kidney disease diagnosis (e.g., kidney stone) via fuzzy expert system were fully compatible with those of kidney physicians. Conclusion The proposed fuzzy expert system is a valid, reliable, and flexible instrument to diagnose several typical input cases. The developed system decreases the effort of initial physical checking and manual feeding of input symptoms. PMID:28392995

  1. Chronic Kidney Disease: Highlights for the General Pediatrician

    PubMed Central

    Quigley, Raymond

    2012-01-01

    Chronic kidney disease in the pediatric population has been increasing. Early detection and treatment can slow down the progression of kidney disease and help prevent the development of end stage renal disease. In addition, as the kidney function declines, there are many pathophysiologic interactions with other organ systems that need to be monitored and treated. In particular, because of impaired vitamin D metabolism, calcium and phosphorus homeostasis is dysregulated and results in secondary bone disease. Anemia is common due to a number of factors including impaired erythropoietin production. Growth is often impacted by chronic kidney disease but can be improved by proper treatment. Complications of chronic kidney disease can be minimized by proper monitoring and treatment of these parameters. The general pediatrician plays a critical role in this process. PMID:22829845

  2. Genetic heterogeneity of autosomal dominant polycystic kidney disease in Argentina.

    PubMed Central

    Iglesias, D M; Martín, R S; Fraga, A; Virginillo, M; Kornblihtt, A R; Arrizurieta, E; Viribay, M; San Millán, J L; Herrera, M; Bernath, V

    1997-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder with genetic heterogeneity. Up to three loci are involved in this disease, PKD1 on chromosome 16p13.3, PKD2 on 4q21, and a third locus of unknown location. Here we report the existence of locus heterogeneity for this disease in the Argentinian population by performing linkage analysis on 12 families of Caucasian origin. Eleven families showed linkage to PKD 1 and one family showed linkage to PKD2. Two recombinants in the latter family placed the locus PKD2 proximal to D4S1563, in agreement with data recently published on the cloning of this gene. Analysis of clinical data suggests a milder ADPKD phenotype for the PKD2 family. PMID:9350815

  3. Increased risk of cardiovascular complications in chronic kidney disease: a possible role of leptin.

    PubMed

    Korolczuk, Agnieszka; Dudka, Jaroslaw

    2014-01-01

    Leptin is a small peptide hormone (16 kDa), a product of the obesity gene (Ob), and is mainly synthesized and secreted by adipocytes. It is removed from the blood by the kidneys. The kidney is not only a site of leptin clearance, but also a target organ for its action in different pathophysiological states. Several studies have documented a strong relationship between chronic kidney disease (CKD) and accelerated cardiovascular disease (CVD) defined as a cardiorenal syndrome. Patients with stage 3 and 4 CKD develop cardiovascular complications and are at increased risk of death from CVD. Renal dysfunction promotes several mechanisms responsible for exacerbation of cardiovascular disease. These include activation of the renin-angiotensin system, oxidative stress, elevated asymmetric dimethylarginine (ADMA), low-grade inflammation with increased circulating cytokines, and dyslipidemia. Recently, it has been observed that plasma leptin level is elevated in patients with cardiorenal syndrome. In obesity, hyperleptinemia combined with selective leptin resistance appear to have a critical role in the development and progression of kidney disease, CVD and metabolic syndrome. This has clinical implications for the treatment of obesity-related hypertension and kidney disease. In this paper the role of leptin in chronic kidney disease and accelerated cardiovascular disease is out lined. The link between hyperleptinemia and development and progression of morphologic changes that effect kidney in obese patients is also discussed.

  4. Chronic kidney disease - different role for HDL?

    PubMed

    Jacek, Rysz; Anna, Gluba; Danilo, Fliser; Timo, Speer; Andrzej, Wiecek

    2014-01-01

    Chronic kidney disease (CKD) is an emerging health hazard, connected to very high cardiovascular mortality due to accelerated atherosclerosis. Increased cardiovascular risk cannot be explained only by traditional risk factors. Patients with renal dysfunction have significant disturbances in lipoprotein metabolism and HDL in these patients becomes dysfunctional. It has been documented that in patients with CKD lower plasma level of HDL cholesterol and reduced ability of HDL to bind to ABCA1 are seen, which result in slowing down the reverse cholesterol transport and disturbances in HDL maturation due to decreased lecithin cholesterol ester transfer protein. Studies demonstrated that HDL of CKD patients loses its vasoprotective, antioxidative and anti-inflammatory properties and turns into a noxious particle which promotes endothelial dysfunction via stimulating superoxide production and limiting NO bioavailability. Alterations of HDL at the 'molecular and functional level' are also seen in renal transplant recipients even in those with excellent graft function.

  5. [Iron therapy in chronic kidney disease].

    PubMed

    Graczyk, Maciej; Kohmann, Anna

    Iron deficiency is one of the main causes of anemia in patients with chronic kidney disease, and iron supplements along the erythropoietin constitute the basis of its therapy. Among hemodialysis patients a preferred method of iron supplementation is an intravenous route, but the route of administration of iron to patients with nondialysis CKD raises a lot of controversy. Treatment with oral iron is cheap, does not require vascular access, but of lower efficacy due to insufficient absorption and frequent occurrence of side effects from the gastrointestinal, with discontinuation of therapy. Intravenous iron though effective is associated with the risk of allergic reactions, oxidative stress and the risk of iron overload. Modern oral medications may constitute an alternative to intravenous iron.

  6. HIV and kidney diseases: 35 years of history and consequences.

    PubMed

    Campos, Pedro; Ortiz, Alberto; Soto, Karina

    2016-12-01

    Kidney diseases in human immunodeficiency virus (HIV)-infected patients are often misdiagnosed. Despite reductions in morbidity and mortality owing to widespread use of highly effective combination antiretroviral therapy (cART), acute kidney injury (AKI) and chronic kidney disease (CKD) are still more common in these patients than in the general population, and are associated with poor health outcomes. HIV-associated nephropathy and HIV immune complex kidney diseases are the more recognizable HIV-related kidney diseases. However, a broad spectrum of kidney disorders related or not directly related with HIV infection can be observed, including cART-induced AKI, CKD, proximal tubular dysfunction, crystalluria and urolithiasis, among others. This review summarizes the major epidemiologic studies of kidney diseases in HIV-infected patients, discusses novel approaches that may potentially limit nephrotoxicity such as the use of tenofovir alafenamide, and outlines current screening measures for early diagnosis of kidney dysfunction or tubular damage, and for accurate detection of increased risk for acute or chronic kidney diseases.

  7. HIV and kidney diseases: 35 years of history and consequences

    PubMed Central

    Campos, Pedro; Ortiz, Alberto

    2016-01-01

    Kidney diseases in human immunodeficiency virus (HIV)-infected patients are often misdiagnosed. Despite reductions in morbidity and mortality owing to widespread use of highly effective combination antiretroviral therapy (cART), acute kidney injury (AKI) and chronic kidney disease (CKD) are still more common in these patients than in the general population, and are associated with poor health outcomes. HIV-associated nephropathy and HIV immune complex kidney diseases are the more recognizable HIV-related kidney diseases. However, a broad spectrum of kidney disorders related or not directly related with HIV infection can be observed, including cART-induced AKI, CKD, proximal tubular dysfunction, crystalluria and urolithiasis, among others. This review summarizes the major epidemiologic studies of kidney diseases in HIV-infected patients, discusses novel approaches that may potentially limit nephrotoxicity such as the use of tenofovir alafenamide, and outlines current screening measures for early diagnosis of kidney dysfunction or tubular damage, and for accurate detection of increased risk for acute or chronic kidney diseases. PMID:27994853

  8. Mechanisms and management of hypertension in autosomal dominant polycystic kidney disease.

    PubMed

    Rahbari-Oskoui, Frederic; Williams, Olubunmi; Chapman, Arlene

    2014-12-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease, characterized by progressive cyst growth and renal enlargement, resulting in renal failure. Hypertension is common and occurs early, prior to loss of kidney function. Whether hypertension in ADPKD is a primary vasculopathy secondary to mutations in the polycystin genes or secondary to activation of the renin-angiotensin-aldosterone system by cyst expansion and intrarenal ischemia is unclear. Dysregulation of the primary cilium causing endothelial and vascular smooth muscle cell dysfunction is a component of ADPKD. In this article, we review the epidemiology, pathophysiology and clinical characteristics of hypertension in ADPKD and give specific recommendations for its treatment.

  9. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

    PubMed

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

    2016-11-01

    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine.

  10. Recurrence of diabetic kidney disease in a type 1 diabetic patient after kidney transplantation.

    PubMed

    Nyumura, Izumi; Honda, Kazuho; Babazono, Tetsuya; Horita, Shigeru; Murakami, Toru; Fuchinoue, Shohei; Uchigata, Yasuko

    2015-07-01

    Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control.

  11. Increases in kidney volume in autosomal dominant polycystic kidney disease can be detected within 6 months.

    PubMed

    Kistler, Andreas D; Poster, Diane; Krauer, Fabienne; Weishaupt, Dominik; Raina, Shagun; Senn, Oliver; Binet, Isabelle; Spanaus, Katharina; Wüthrich, Rudolf P; Serra, Andreas L

    2009-01-01

    Kidney volume growth is considered the best surrogate marker predicting the decline of renal function in autosomal dominant polycystic kidney disease. To assess the therapeutic benefit of new drugs more rapidly, changes in kidney volume need to be determined over a short time interval. Here we measured renal volume changes by manual segmentation volumetry applied to magnetic resonance imaging scans obtained with an optimized T1-weighted acquisition protocol without gadolinium-based contrast agents. One hundred young patients with autosomal dominant polycystic kidney disease and preserved renal function had a significant increase in total kidney volume by 2.71+/-4.82% in 6 months. Volume measurements were highly reproducible and accurate, as indicated by correlation coefficients of 1.000 for intra-observer and 0.996 for inter-observer agreement, with acceptable within-subject standard deviations. The change in renal volume correlated with baseline total kidney volume in all age subgroups. Total kidney volume positively correlated with male gender, hypertension, albuminuria and a history of macrohematuria but negatively with creatinine clearance. Albuminuria was associated with accelerated volume progression. Our study shows that increases in kidney volume can be reliably measured over a 6 month period in early autosomal dominant polycystic kidney disease using unenhanced magnetic resonance imaging sequences.

  12. Hormones and arterial stiffness in patients with chronic kidney disease.

    PubMed

    Gungor, Ozkan; Kircelli, Fatih; Voroneanu, Luminita; Covic, Adrian; Ok, Ercan

    2013-01-01

    Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population.

  13. Gut microbiota in chronic kidney disease.

    PubMed

    Cigarran Guldris, Secundino; González Parra, Emilio; Cases Amenós, Aleix

    The intestinal microflora maintains a symbiotic relationship with the host under normal conditions, but its imbalance has recently been associated with several diseases. In chronic kidney disease (CKD), dysbiotic intestinal microflora has been reported with an increase in pathogenic flora compared to symbiotic flora. An enhanced permeability of the intestinal barrier, allowing the passage of endotoxins and other bacterial products to the blood, has also been shown in CKD. By fermenting undigested products that reach the colon, the intestinal microflora produce indoles, phenols and amines, among others, that are absorbed by the host, accumulate in CKD and have harmful effects on the body. These gut-derived uraemic toxins and the increased permeability of the intestinal barrier in CKD have been associated with increased inflammation and oxidative stress and have been involved in various CKD-related complications, including cardiovascular disease, anaemia, mineral metabolism disorders or the progression of CKD. The use of prebiotics, probiotics or synbiotics, among other approaches, could improve the dysbiosis and/or the increased permeability of the intestinal barrier in CKD. This article describes the situation of the intestinal microflora in CKD, the alteration of the intestinal barrier and its clinical consequences, the harmful effects of intestinal flora-derived uraemic toxins, and possible therapeutic options to improve this dysbiosis and reduce CKD-related complications.

  14. Inflammation and cachexia in chronic kidney disease.

    PubMed

    Cheung, Wai W; Paik, Kyung Hoon; Mak, Robert H

    2010-04-01

    Chronic inflammation is associated with cachexia and increased mortality risk in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Inflammation suppresses appetite and causes the loss of protein stores. In CKD patients, increased serum levels of pro-inflammatory cytokines may be caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions. Cachexia is brought about by the synergistic combination of a dramatic decrease in appetite and an increase in the catabolism of fat and lean body mass. Pro-inflammatory cytokines act on the central nervous system to alter appetite and energy metabolism and to provide a signal-through the nuclear factor-kappaB and ATP-ubiquitin-dependent proteolytic pathways-that causes muscle wasting. Further research into the molecular pathways leading to inflammation and cachexia may lead to novel therapeutic therapies for this devastating and potentially fatal complication of chronic disease.

  15. The podocyte in diabetic kidney disease.

    PubMed

    Stitt-Cavanagh, Erin; MacLeod, Laura; Kennedy, Chris

    2009-10-14

    Approaching epidemic levels, diabetic kidney disease (DKD) is now the leading cause of end-stage renal disease (ESRD). Microalbuminuria is an early clinical marker of DKD that results from damage to the glomerular filtration barrier at the level of the highly differentiated glomerular podocyte cells. Injury to these epithelial cells, podocytopathies, includes cellular hypertrophy, foot process effacement, detachment from the glomerular basement membrane, and apoptosis. Here we review the role of a number of recently identified factors that contribute to podocytopathies in DKD. These factors include members of the renin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE) types 1 and 2, prorenin and its receptor, reactive oxygen species (ROS), prostanoids, peroxisome proliferator-activated receptors (PPAR), advanced glycation end-products (AGEs) and their receptors (RAGE), adiponectin, and microRNAs. As the number of therapeutic options that slow, but do not halt, the progression of DKD to ESRD remains limited, a more comprehensive understanding of the signaling events that contribute to this increasingly prevalent disease may identify novel avenues for treatment and prevention.

  16. [Chronic kidney disease : What is currently available for treatment?

    PubMed

    Fleig, S; Patecki, M; Schmitt, R

    2016-12-01

    Chronic kidney disease is common in the general population with an estimated prevalence of roughly 2 million in Germany. Typically, chronic kidney disease is progressive and in the terminal stage the patients require dialysis or kidney transplantation. In many cases the disease remains silent for a long time but early stages are already associated with increasing morbidity and mortality. Therefore early detection is very important. In recent years several new concepts have been introduced that might help to slow the progression of chronic kidney disease or improve the accompanying risks. Here, we want to provide a nephrologist's perspective on the current guidelines for the treatment and prevention of chronic kidney disease. We summarize which diagnostic approaches are useful for general practitioners and we take a pragmatic look at the existing opportunities for combating renal functional decline. We also shed light on established measures to minimize the risk of comorbidities.

  17. Disease resistance and immune-relevant gene expression in golden mandarin fish, Siniperca scherzeri Steindachner, infected with infectious spleen and kidney necrosis virus-like agent.

    PubMed

    Shin, G W; White, S L; Dahms, H U; Jeong, H D; Kim, J H

    2014-12-01

    Infectious spleen and kidney necrosis virus (ISKNV), family Iridoviridae, genus Megalocytivirus, may cause high mortality rates such as those seen in mandarin fish, Siniperca chuatsi. ISKNV has attracted much attention due to the possible environmental threat and economic losses it poses on both cultured and wild populations. We have investigated the pathogenicity of ISKNV-like agent Megalocytivirus, isolated from infected pearl gourami, in golden mandarin fish, Siniperca scherzeri - a member of the Percichthyidae family - and in another Percichthyidae species, S. chuatsi. Fish were challenged with four different doses of ISKNV-like agent Megalocytivirus (1, 10, 100 or 1000 μg per fish) over a 30-day period, and cumulative fish mortalities were calculated for each group. No significant mortality was observed for fish challenged with the lowest dose (1 μg per fish) relative to a control group. However, all other challenged groups showed 100% mortality over a 30-day period in proportion to the challenge dose. Quantitative real-time PCR was performed to measure mRNA expression levels for six immune-related genes in golden mandarin fish following ISKNV-like agent challenge. mRNA expression levels for IRF1, Mx, viperin and interleukin 8 significantly increased, while mRNA levels for IRF2 and IRF7 remained constant or declined during the challenge period.

  18. Extracellular vesicles in diagnosis and therapy of kidney diseases.

    PubMed

    Zhang, Wei; Zhou, Xiangjun; Zhang, Hao; Yao, Qisheng; Liu, Yutao; Dong, Zheng

    2016-11-01

    Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may also mediate the cross talk between kidneys and other organs under physiological and pathological conditions. EVs have been implicated in the pathogenesis of both acute kidney injury and chronic kidney diseases, including renal fibrosis, end-stage renal disease, glomerular diseases, and diabetic nephropathy. The release of EVs with specific molecular contents into urine and plasma may be useful biomarkers for kidney disease. In addition, EVs produced by cultured cells may have therapeutic effects for these diseases. However, the role of EVs in kidney diseases is largely unclear, and the mechanism underlying EV production and secretion remains elusive. In this review, we introduce the basics of EVs and then analyze the present information about the involvement, diagnostic value, and therapeutic potential of EVs in major kidney diseases.

  19. Hypertension in children with autosomal dominant polycystic kidney disease (ADPKD).

    PubMed

    Cadnapaphornchai, Melissa A

    2013-02-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting 1 in 1000 individuals. Previously termed "adult polycystic kidney disease", ADPKD is now known to have important clinical manifestations beginning early in life and even in utero. Hypertension is an important risk factor for progressive renal and cardiovascular disease in children with ADPKD and may signify irremediable organ injury. The purpose of this article is to review current knowledge and treatment strategies in hypertension associated with pediatric ADPKD.

  20. Histone deacetylases in kidney development: implications for disease and therapy.

    PubMed

    Chen, Shaowei; El-Dahr, Samir S

    2013-05-01

    Histone deacetylases (HDACs) are an evolutionarily conserved group of enzymes that regulate a broad range of biological processes through removal of acetyl groups from histones as well as non-histone proteins. Recent studies using a variety of pharmacological inhibitors and genetic models of HDACs have revealed a central role of HDACs in control of kidney development. These findings provide new insights into the epigenetic mechanisms underlying congenital anomalies of the kidney and urinary tract (CAKUT) and implicate the potential of HDACs as therapeutic targets in kidney diseases, such as cystic kidney diseases and renal cell cancers. Determining the specific functions of individual HDAC members would be an important task of future research.

  1. Hereditary hypophosphatemias: new genes in the bone-kidney axis.

    PubMed

    Negri, Armando L

    2007-08-01

    Hypophosphatemia due to isolated renal phosphate wasting is a genetically heterogeneous disease. Two new genes linked to two different forms of hereditary hypophosphatemias have recently been described. Autosomal recessive form of hypophosphatemic rickets was mapped to chromosome 4q21 and identified homozygous mutations in dentin matrix protein 1 (DMP1) gene, which encodes a non-collagenous bone matrix protein. Intact plasma levels of the phosphaturic protein FGF23 (fibroblast growth factor 23) were clearly elevated in some of the affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels, and suggesting that DMP1 may regulate FGF23 expression. Hereditary hypophosphatemic rickets with hypercalciuria is another rare disorder of autosomal recessive inheritance. Affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. The disease was mapped to a 1.6 Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaPi-IIc. This was the first demonstration that NaPi-IIc has a key role in the regulation of phosphate homeostasis. Thus, DMP1 and NaPi-IIc add two new members to the bone-kidney axis proposed since it was discovered that the first phosphatonin, FGF23, was of osteoblastic/osteocyte origin. This provides a mechanism for the skeleton to communicate with the kidney to coordinate the mineralization of extracelular matrix and the renal handling of phosphate.

  2. Nutraceutical for Autosomal Dominant Polycystic Kidney Disease Therapy.

    PubMed

    Yuajit, Chaowalit; Chatsudthipong, Varanuj

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder caused by mutations of either PKD1 or PKD2 gene. Cyst formation initiates from a combination of abnormal cell proliferation along with enhanced fluid secretion. ADPKD is characterized by the progressive enlargement of cysts which destroy the renal parenchymal cells, resulting in renal failure. Currently, there is no effective treatment for this disease. Interestingly, several relevant therapeutic effects of herbal medicine relevant to pathogenic process of ADPKD have urged the researchers to search for potential candidate herb as nutraceutical for ADPKD therapy. Up to now, several natural compounds, such as triptolide, curcumin, ginkolide B, and steviol (stevia extract) have been shown to be able to retard cyst progression in ADPKD. The detailed mechanism of these compounds showed that triptolide enhanced calcium restoration, curcumin inhibited ERK & p-STAT3 pathways, ginkolide B inhibited Ras/MAPK pathway, and steviol activated AMPK, which inhibited CFTR channel and mTOR pathway in cell and mouse models of PKD. In addition, they are currently inpreclinical and clinical studies, respectively. This review focuses on the pathophysiology of ADPKD and the recent therapeutic approaches, especially a potential use of nutraceutical for the treatment of autosomal dominant polycystic kidney disease.

  3. 78 FR 28859 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... and Kidney Diseases Initial Review Group; Diabetes, Endocrinology and Metabolic Diseases B... Committee: National Institute of Diabetes and Digestive and Kidney Diseases Initial Review Group;...

  4. 76 FR 3147 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Fellowships in Digestive Diseases and Nutrition. Date: February... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Lactation and...

  5. 77 FR 34395 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Medication Adherence among Children with CKD: Ancillary Studies... Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research,...

  6. 76 FR 34717 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis... of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Islet Autoantibodies Ancillary... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, GUDMAP Project Cooperative Grants....

  7. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    ClinicalTrials.gov

    2017-03-21

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  8. Con: Phosphate binders in chronic kidney disease

    PubMed Central

    Kestenbaum, Bryan

    2016-01-01

    Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or ‘pragmatic’ designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications. PMID:26681747

  9. Con: Phosphate binders in chronic kidney disease.

    PubMed

    Kestenbaum, Bryan

    2016-02-01

    Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or 'pragmatic' designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications.

  10. Building the chronic kidney disease management team.

    PubMed

    Spry, Leslie

    2008-01-01

    The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing.

  11. ACE and ACE2 in kidney disease

    PubMed Central

    Mizuiri, Sonoo; Ohashi, Yasushi

    2015-01-01

    Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang II are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang I and the catabolism of Ang II to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang II-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2. PMID:25664248

  12. Chronic kidney disease and fragility fracture.

    PubMed

    Kazama, Junichiro James

    2017-03-01

    Osteoporosis is defined simply as "a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Thus, any bone lesion that causes fragility fracture is osteoporosis, which has quite heterogeneous backgrounds. Chronic kidney disease-related bone and mineral disease (CKD-MBD) is defined as "a systemic disorder of mineral and bone metabolism due to CKD, which is manifested by abnormalities in bone and mineral metabolism and/or extra-skeletal calcification". Although CKD-MBD is one of the possible causes of osteoporosis, we do not have evidences that CKD-MBD is the only or crucial determinant of bone mechanical strength in CKD patients. The risk of hip fracture is considerably high in CKD patients. Drugs that intervene in systemic mineral metabolism, indeed, lead to the improvement on bone histology in CKD patients. However, it remains unclear whether the intervention in systemic mineral metabolism also improves bone strength, today. Thus, the use of drugs that directly act on bone and the introduction of fracture liaison concept are promising strategies for fragility fracture prevention among CKD patients, as well as treatment for CKD-MBD.

  13. Neurological complications in chronic kidney disease

    PubMed Central

    Arnold, Ria; Issar, Tushar; Krishnan, Arun V

    2016-01-01

    Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. These complications can potentially affect both the central and peripheral nervous systems. Common neurological complications in CKD include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic neuropathies. These conditions have significant impact not only on patient morbidity but also on mortality risk through a variety of mechanisms. Understanding the pathophysiological mechanisms of these conditions can provide insights into effective management strategies for neurological complications. This review describes clinical management of neurological complications in CKD with reference to the contributing physiological and pathological derangements. Stroke, cognitive dysfunction and dementia share several pathological mechanisms that may contribute to vascular impairment and neurodegeneration. Cognitive dysfunction and dementia may be differentiated from encephalopathy which has similar contributing factors but presents in an acute and rapidly progressive manner and may be accompanied by tremor and asterixis. Recent evidence suggests that dietary potassium restriction may be a useful preventative measure for peripheral neuropathy. Management of painful neuropathic symptoms can be achieved by pharmacological means with careful dosing and side effect considerations for reduced renal function. Patients with autonomic neuropathy may respond to sildenafil for impotence. Neurological complications often become clinically apparent at end-stage disease, however early detection and management of these conditions in mild CKD may reduce their impact at later stages. PMID:27867500

  14. Impact of Lifestyle Modification on Diabetic Kidney Disease.

    PubMed

    Onyenwenyi, Chijoke; Ricardo, Ana C

    2015-09-01

    Kidney disease is common in patients with type 1 and type 2 diabetes mellitus and is associated with adverse health outcomes, including progression to end-stage renal disease. In the general population, adherence to a healthy lifestyle is known to reduce the risk of cardiovascular events and death. Among individuals with diabetic kidney disease, modifications in lifestyle factors, including diet, physical activity, smoking habits, and body mass index, represent a promising cost-effective therapeutic adjunct to pharmacologic treatment of kidney disease incidence and progression.

  15. Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy.

    PubMed

    Alam, Ahsan; Dahl, Neera K; Lipschutz, Joshua H; Rossetti, Sandro; Smith, Patricia; Sapir, Daniel; Weinstein, Jordan; McFarlane, Philip; Bichet, Daniel G

    2015-10-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials.

  16. Sex differences in kidney gene expression during the life cycle of F344 rats

    PubMed Central

    2013-01-01

    Background The kidney functions in key physiological processes to filter blood and regulate blood pressure via key molecular transporters and ion channels. Sex-specific differences have been observed in renal disease incidence and progression, as well as acute kidney injury in response to certain drugs. Although advances have been made in characterizing the molecular components involved in various kidney functions, the molecular mechanisms responsible for sex differences are not well understood. We hypothesized that the basal expression levels of genes involved in various kidney functions throughout the life cycle will influence sex-specific susceptibilities to adverse renal events. Methods Whole genome microarray gene expression analysis was performed on kidney samples collected from untreated male and female Fischer 344 (F344) rats at eight age groups between 2 and 104 weeks of age. Results A combined filtering approach using statistical (ANOVA or pairwise t test, FDR 0.05) and fold-change criteria (>1.5 relative fold change) was used to identify 7,447 unique differentially expressed genes (DEGs). Principal component analysis (PCA) of the 7,447 DEGs revealed sex-related differences in mRNA expression at early (2 weeks), middle (8, 15, and 21 weeks), and late (104 weeks) ages in the rat life cycle. Functional analysis (Ingenuity Pathway Analysis) of these sex-different genes indicated over-representation of specific pathways and networks including renal tubule injury, drug metabolism, and immune cell and inflammatory responses. The mRNAs that code for the qualified urinary protein kidney biomarkers KIM-1, Clu, Tff3, and Lcn2 were also observed to show sex differences. Conclusions These data represent one of the most comprehensive in-life time course studies to be published, assessing sex differences in global gene expression in the F344 rat kidney. PCA and Venn analyses reveal specific periods of sexually dimorphic gene expression which are associated with

  17. MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease.

    PubMed

    Ha, Tai-You

    2011-12-01

    MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases.

  18. MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease

    PubMed Central

    2011-01-01

    MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases. PMID:22346770

  19. Therapeutic potential of endothelin receptor antagonism in kidney disease.

    PubMed

    Czopek, Alicja; Moorhouse, Rebecca; Webb, David J; Dhaun, Neeraj

    2016-03-01

    Our growing understanding of the role of the endothelin (ET) system in renal physiology and pathophysiology is from emerging studies of renal disease in animal models and humans. ET receptor antagonists reduce blood pressure and proteinuria in chronic kidney disease and cause regression of renal injury in animals. However, the therapeutic potential of ET receptor antagonism has not been fully explored and clinical studies have been largely limited to patients with diabetic nephropathy. There remains a need for more work in nondiabetic chronic kidney disease, end-stage renal disease (patients requiring maintenance dialysis and those with a functioning kidney transplant), ischemia reperfusion injury, and sickle cell disease. The current review summarizes the most recent advances in both preclinical and clinical studies of ET receptor antagonists in the field of kidney disease.

  20. Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

    PubMed Central

    Weiner, Daniel E.; Dad, Taimur

    2015-01-01

    Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

  1. The spectrum of polycystic kidney disease in children.

    PubMed

    Dell, Katherine MacRae

    2011-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are important inherited kidney diseases with distinct clinical features and genetics. Although these diseases have classically been considered "adult" (ADPKD) or "infantile/pediatric" (ARPKD), it is now clear that both diseases can present in children and adults. ADPKD and ARPKD also share important pathophysiologic features, including cilia dysfunction. ADPKD is a systemic disease involving cysts in the kidneys and abdominal organs as well as abnormalities in the heart and vasculature. Although it typically presents in adults, ADPKD has been diagnosed in fetuses, infants, children, and adolescents. The majority of children diagnosed with ADPKD are asymptomatic. Those with symptoms typically present with hypertension or gross hematuria. Routine screening for renal cysts in asymptomatic children who have a parent with ADPKD is generally not recommended. ARPKD is a disorder confined to the kidneys (polycystic kidneys) and liver (a developmental biliary lesion called congenital hepatic fibrosis). Although most children with ARPKD present in infancy with large, echogenic kidneys, a subset present later in childhood and even adulthood, primarily with complications related to the liver disease. As more patients with ARPKD survive to adulthood, these liver complications are likely to become more prevalent.

  2. Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

    PubMed

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2015-07-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by angiotensin II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease.

  3. Resistant Hypertension in Nondialysis Chronic Kidney Disease

    PubMed Central

    Stanzione, Giovanna; Conte, Giuseppe

    2013-01-01

    Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the target of less than 140/90 mmHg in the general population and 130/80 mmHg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic or as BP that reaches the target by means of four or more drugs. In CKD, RH is a common condition due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. Before defining the hypertensive patient as resistant it is mandatory to exclude the so-called “pseudoresistance.” This condition, which refers to the apparent failure to reach BP target in spite of an appropriate antihypertensive treatment, is mainly caused by white coat hypertension that is prevalent (30%) in CKD patients. Recently we have demonstrated that “true” RH represents an independent risk factor for renal and cardiovascular outcomes in CKD patients. PMID:23710342

  4. Exaggerated natriuresis in adult polycystic kidney disease.

    PubMed

    Danielsen, H; Nielsen, A H; Pedersen, E B; Herlevsen, P; Kornerup, H J; Posborg, V

    1986-01-01

    Angiotensin II (AII), aldosterone (Aldo) arginine vasopressin (AVP) in plasma, serum osmolality (Sosm), and renal sodium excretion (UNaV) were studied before and after infusion of hypertonic sodium chloride solution in 20 patients with adult polycystic kidney disease (PKD) with normal or moderately reduced creatinine clearance (Ccr) and in 10 healthy control subjects. UNaV increased after sodium loading in all, significantly more in the PKD patients. AII and Aldo were normal before sodium loading and suppressed after saline in PKD patients and controls. The increase in VNaV correlated with Aldo in patients but not in controls. AVP before loading was increased in hypertensive PKD patients with reduced Ccr, but not in normotensive patients with normal Ccr. After hypertonic saline, Sosm increased to the same degree both in PKD and control subjects, but AVP increased more in those with PKD. The exaggerated natriuresis of PKD is probably not explained by a change in the activity of the renin-angiotensin-aldosterone system. The enhanced response of AVP to osmotic stimuli in PKD may be a compensatory reaction to a reduced renal tubular effect of AVP.

  5. Contextual Poverty, Nutrition and Chronic Kidney Disease

    PubMed Central

    Gutiérrez, Orlando M.

    2014-01-01

    Nutrition plays an important role in chronic kidney disease (CKD) outcomes. One of the strongest factors that impacts nutrition is socioeconomic status as evidenced by the large body of epidemiologic data showing that income and education are directly associated with diet quality. Apart from individual-level markers of socioeconomic status such as income and education, contextual factors such as availability of and transportation to food outlets that provide healthy food options and the density of fast food restaurants within particular regions markedly impact the ability of individuals to comply with nutrition recommendations. This is particularly true for nutrition guidelines most specific to individuals with CKD such as the consumption of protein, saturated fat, sodium and phosphorus, all of which have been shown to impact CKD health and are influenced by the availability of healthy food options within individual neighborhood food environments. Because of the strong association of contextual poverty with the diet quality, any serious attempt to improve the diet of CKD patients must include a discussion of the environmental barriers that each individual faces in trying to access healthy foods and health care providers should take account of these barriers when tailoring specific recommendations. PMID:25573510

  6. The role of phosphate in kidney disease.

    PubMed

    Vervloet, Marc G; Sezer, Siren; Massy, Ziad A; Johansson, Lina; Cozzolino, Mario; Fouque, Denis

    2017-01-01

    The importance of phosphate homeostasis in chronic kidney disease (CKD) has been recognized for decades, but novel insights - which are frequently relevant to everyday clinical practice - continue to emerge. Epidemiological data consistently indicate an association between hyperphosphataemia and poor clinical outcomes. Moreover, compelling evidence suggests direct toxicity of increased phosphate concentrations. Importantly, serum phosphate concentration has a circadian rhythm that must be considered when interpreting patient phosphate levels. Detailed understanding of dietary sources of phosphate, including food additives, can enable phosphate restriction without risking protein malnutrition. Dietary counselling provides an often underestimated opportunity to target the increasing exposure to dietary phosphate of both the general population and patients with CKD. In patients with secondary hyperparathyroidism, bone can be an important source of serum phosphate, and adequate appreciation of this fact should impact treatment. Dietary and pharmotherapeutic interventions are efficacious strategies to lower phosphate intake and serum concentration. However, strong evidence that targeting serum phosphate improves patient outcomes is currently lacking. Future studies are, therefore, required to investigate the effects of modern dietary and pharmacological interventions on clinically meaningful end points.

  7. Sugar-sweetened soda consumption, hyperuricemia, and kidney disease.

    PubMed

    Bomback, Andrew S; Derebail, Vimal K; Shoham, David A; Anderson, Cheryl A; Steffen, Lyn M; Rosamond, Wayne D; Kshirsagar, Abhijit V

    2010-04-01

    The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead to elevations in uric acid levels. Here we determined whether soda drinking is associated with hyperuricemia and, as a potential consequence, reduced kidney function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities Study completed a dietary questionnaire and had measurements of their serum creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds ratios from logistic regressions for binary outcome of hyperuricemia and chronic kidney disease (eGFR less than 60 ml/min per 1.73 m(2)) were evaluated. Compared to participants who drank less, consumption of over one soda per day was associated with increased odds of prevalent hyperuricemia and chronic kidney disease. The odds ratio for chronic kidney disease significantly increased to 2.59 among participants who drank more than one soda per day and had a serum uric acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than one soda per day was not associated with hyperuricemia or chronic kidney disease. Neither preexistent hyperuricemia nor development of hyperuricemia modified the lack of association between soda drinking and incident chronic kidney disease. Thus our study shows that high consumption of sugar-sweetened soda was associated with prevalent but not incident hyperuricemia and chronic kidney disease.

  8. Hypoxia: The Force that Drives Chronic Kidney Disease

    PubMed Central

    Fu, Qiangwei; Colgan, Sean P; Shelley, Carl Simon

    2016-01-01

    In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the β2-integrin family of adhesion molecules. This induction likely maintains the long-term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy. PMID:26847481

  9. Parkinson's disease: gene therapies.

    PubMed

    Coune, Philippe G; Schneider, Bernard L; Aebischer, Patrick

    2012-04-01

    With the recent development of effective gene delivery systems, gene therapy for the central nervous system is finding novel applications. Here, we review existing viral vectors and discuss gene therapy strategies that have been proposed for Parkinson's disease. To date, most of the clinical trials were based on viral vectors to deliver therapeutic transgenes to neurons within the basal ganglia. Initial trials used genes to relieve the major motor symptoms caused by nigrostriatal degeneration. Although these new genetic approaches still need to prove more effective than existing symptomatic treatments, there is a need for disease-modifying strategies. The investigation of the genetic factors implicated in Parkinson's disease is providing precious insights in disease pathology that, combined with innovative gene delivery systems, will hopefully offer novel opportunities for gene therapy interventions to slow down, or even halt disease progression.

  10. Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre-existing chronic kidney disease.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Hashimoto, Yasunobu; Yoshida, Kazuhiko; Tanabe, Kazunari

    2014-06-01

    We compared kidney functional recovery between patients with pre-existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre-existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: -6.8%, group 2: -18%, group 3: -7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: -0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre-existing chronic kidney

  11. Obesity and kidney disease: Hidden consequences of the epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan L; Zoccali, Carmine

    2017-03-01

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risks of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a series of complex pathophysiologic changes occur that lead to the development of Chronic Kidney Disease. These include on the one hand effects mediated by the downstream consequences of obesity (such as diabetes mellitus and hypertension), but also direct effects of adipose tissue, via humoral factors such as leptin, adiponectin, resistin and visfatin). In obese individuals a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight, leading to glomerulomegaly and accompanied by deposition of adipose tissue in the glomerulus and the gradual development of focal segmental glomerulosclerosis. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. In addition to the development of Chronic Kidney Disease, obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. Interventions to stem the tide of obesity are thus extremely important for preventing the development and progression of Chronic Kidney Disease and other disorders of the kidneys. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

  12. Obesity and kidney disease: Hidden consequences of the epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan; Zoccali, Carmine

    2017-03-01

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

  13. Obesity and kidney disease: hidden consequences of the epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan L; Zoccali, Carmine

    2017-02-01

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

  14. Obesity and Kidney Disease: Hidden Consequences of the Epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan L; Zoccali, Carmine

    2017-02-08

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

  15. Obesity and Kidney Disease: Hidden Consequences of the Epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan L; Zoccali, Carmine

    2017-01-01

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

  16. Obesity and Kidney Disease: Hidden Consequences of the Epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan; Zoccali, Carmine; World Kidney Day Steering Committee, /

    2017-03-01

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes mellitus, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

  17. A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats.

    PubMed

    Islam, Mohammad Ariful; Kim, Sanghwa; Firdous, Jannatul; Lee, Ah-Young; Hong, Seong-Ho; Seo, Min Kyeong; Park, Tae-Eun; Yun, Cheol-Heui; Choi, Yun-Jaie; Chae, Chanhee; Cho, Chong-Su; Cho, Myung-Haing

    2016-09-01

    Aside from kidney transplantation - a procedure which is exceedingly dependent on donor-match and availability leading to excessive costs - there are currently no permanent treatments available which reverse kidney injury and failure. However, kidney-specific targeted gene therapy has outstanding potential to treat kidney-related dysfunction. Herein we report a novel kidney-specific targeted gene delivery system developed through the conjugation of chitobionic acid (CBA) to a polysorbitol gene transporter (PSGT) synthesized from sorbitol diacrylate and low molecular weight polyethylenimine (PEI) carrying hepatocyte growth factor (HGF) gene to alleviate unilateral ureteral obstruction (UUO) in rats. CBA-PSGT performed exceptionally well for targeted delivery of HGF to kidney tissues compared to its non-targeted counterparts (P < 0.001) after systemic tail-vein injection and significantly reduced the UUO symptoms, returning the UUO rats to a normal health status. The kidney-targeted CBA-PSGT-delivered HGF also strikingly reduced various pathologic and molecular markers in vivo such as the level of collagens (type I and II), blood urea nitrogen (BUN), creatinine, and the expressions of ICAM-1, TIMP-1 and α-SMA which play a critical role in obstructive kidney functions. Therefore, CBA-PSGT should be further investigated because of its potential to alleviate UUO and kidney-related diseases using high affinity kidney targeting.

  18. Estimating risks of de novo kidney diseases after living kidney donation.

    PubMed

    Steiner, R W; Ix, J H; Rifkin, D E; Gert, B

    2014-03-01

    De novo post donation renal diseases, such as glomerulonephritis or diabetic nephropathy, are infrequent and distinct from the loss of GFR at donation that all living kidney donors experience. Medical findings that increase risks of disease (e.g. microscopic hematuria,borderline hemoglobin A1C) often prompt donor refusal by centers. These risk factors are part of more comprehensive risks of low GFR and end-stage renal disease (ESRD) from kidney diseases in the general population that are equally relevant. Such data profile the ages of onset, rates of progression, prevalence and severity of loss of GFR from generically characterized kidney diseases. Kidney diseases typically begin in middle age and take decades to reach ESRD, at a median age of 64. Diabetes produces about half of yearly ESRD and even more lifetime near-ESRD. Such data predict that (1) 10- to 15-year studies will not capture the lifetime risks of post donation ESRD; (2)normal young donors are at demonstrably higher risk than normal older candidates; (3) low-normal predonation GFRs become risk factors for ESRD when kidney diseases arise and (4) donor nephrectomy always increases individual risk. Such population-based risk data apply to all donor candidates and should be used to make acceptance standards and counseling more uniform and defensible.

  19. APOL1 variants and kidney disease. There is no such thing as a free lunch.

    PubMed

    Kronenberg, Florian

    2011-03-01

    A recent study by Genovese et al. unraveled the findings of the intensively discussed gene region around MYH9 and its association with non-diabetic chronic kidney disease in African-Americans. First, it is not the genetic variation in MYH9 but in the neighbouring APOL1 that causes the strong association with disease in African-Americans and second, the study showed strong evidence for a positive selection against vulnerability for Trypanosoma brucei rhodesiense infection but at the price of a higher susceptibility of non-diabetic chronic kidney disease. This overview reviews the findings and the possible impact of the study mentioned above as well as of related studies.

  20. 78 FR 19275 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases, including consideration of personnel qualifications and performance, and the competence..., National Institute of Diabetes and Digestive, and Kidney Diseases, National Institute of Health, Building...

  1. 75 FR 5602 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Hormones in Postmenopausal Women Ancillary Studies. Date... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Training Grants in Digestive...

  2. For Kids with Kidney Disease, Race May Play Role in Outcomes

    MedlinePlus

    ... gov/news/fullstory_162794.html For Kids With Kidney Disease, Race May Play Role in Outcomes Risk of ... chronic kidney failure. All had been treated for kidney disease with either dialysis or transplants between 1995 and ...

  3. 77 FR 53208 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases, including consideration of personnel qualifications and performance, and the competence..., National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Building...

  4. 75 FR 65365 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Genetics of Nephropathy Ancillary Studies. Date: November 15... Digestive and Kidney Diseases Special Emphasis Panel, Consortium for Radiologic Imaging Studies...

  5. 75 FR 9231 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Metabolic Dysfunction Collaborative Interdisciplinary Science... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; CAMUS Trial. Date: April 2, 2010....

  6. 75 FR 9911 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-04

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Seeding Team Science in Diabetes Endocrinology and Metabolic... of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

  7. 78 FR 58325 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Bariatric Surgery-- Related Ancillary Studies (R01s). Date... Digestive and Kidney Diseases Special Emphasis Panel, Regulatory Mechanisms in Intestinal Motility...

  8. 76 FR 11499 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... Intramural Research, National Institute of Diabetes and Digestive, and Kidney Diseases, NIH, Bethesda, MD... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases, including consideration of personnel qualifications and performance, and the...

  9. Pregnancy across the spectrum of chronic kidney disease.

    PubMed

    Hladunewich, Michelle A; Melamad, Nir; Bramham, Kate

    2016-05-01

    Management of the pregnant woman with chronic kidney disease is difficult for both nephrologists and obstetricians. Prepregnancy counselling with respect to risk stratification, optimization of maternal health prior to pregnancy, as well as management of the many potential pregnancy-associated complications in this complex patient population remains challenging due to the paucity of large, well-designed clinical studies. Furthermore, the heterogeneity of disease and the relative infrequency of pregnancy, particularly in more advanced stages of chronic kidney disease, leaves many clinicians feeling ill prepared to manage these pregnancies. As such, counselling is imprecise and management varies substantially across centers. All pregnancies in women with chronic kidney disease can benefit from a collaborative multidisciplinary approach with a team that consists of nephrologists experienced in the management of kidney disease in pregnancy, maternal-fetal medicine specialists, high-risk pregnancy nursing staff, dieticians, and pharmacists. Further access to skilled neonatologists and neonatal intensive care unit support is essential given the risks for preterm delivery in this patient population. The goal of this paper is to highlight some of the data that currently exist in the literature, provide management strategies for the practicing nephrologist at all stages of chronic kidney disease, and explore some of the knowledge gaps where future multinational collaborative research efforts should concentrate to improve pregnancy outcomes in women with kidney disease across the globe.

  10. Dietary protein intake and kidney disease in Western diet.

    PubMed

    Pecoits-Filho, Roberto

    2007-01-01

    Components of the diet related to changes in eating habits that characterize the modern Western world are important factors in the increasingly high prevalence of chronic disease, including obesity, diabetes, hypertension and as a consequence, chronic kidney disease. The healthy diets recommended for the general population to promote longevity (such as the Mediterranean diet), are defined based on epidemiological and intervention studies and are usually characterized by a relatively higher amount of protein than the usual Western diet. Unfortunately, very few clinical studies focused on diet-based strategies of prevention of kidney disorders. Furthermore, this review will propose that the concept that protein restricted diets decrease the risk of developing kidney disease in the general population is not supported by the scientific literature. Indeed, preliminary studies showing a positive effect of relatively high protein diets on risk factors for chronic kidney disease (particularly on obesity, hypertension and diabetes) point to the need for future studies addressing diets that could prevent the increasingly high prevalence of kidney disease in the Western world. On the other hand, there is a potential role for protein restriction in patients with established kidney disease, particularly in patients with significant decrease in glomerular filtration rate. The exact protective action of protein restriction in patients with established renal disease needs further analysis, taking into account the more broad effects of protein restriction (lower phosphate, acidosis, uric acid) and a more current definition of malnutrition.

  11. The role of heat shock proteins in kidney disease

    PubMed Central

    2016-01-01

    Abstract Heat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases. PMID:28191532

  12. When Your Child Has a Chronic Kidney Disease

    MedlinePlus

    ... slushy beverages or ice cubes to suck on. Sodium Some kids with kidney disease, particularly those with ... pressure, may need to restrict their intake of sodium, which is found in table salt and many ...

  13. [Related reproductive issues on male autosomal dominant polycystic kidney disease].

    PubMed

    Cai, Hong-cai; Shang, Xue-jun; Huang, Yu-feng

    2015-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a most common inherited renal disease, about 50% with a family history, although the exact etiology not yet clear. To date, ADPKD, a multisystem disorder without effective preventive and therapeutic means, has been shown to be detrimental to human health. Recent studies show that severe oligoasthenozoospermia, necrospermia, immotile sperm, azoospermia, epididymal cyst, seminal vesicle cyst, and ejaculatory duct cyst found in male ADPKD patients may lead to male infertility, though the specific mechanisms remain unknown. Structural anomaly of spermatozoa, defect of polycystin, mutation of PKD genes, and micro-deletion of the AZF gene could be the reasons for the higher incidence of abnormal semen quality in male ADPKD patients. Assisted reproductive techniques can increase the chances of pregnancy, whereas the health of the offspring should be taken into consideration. This article presents an overview of reproductive issues concerning infertile male ADPKD patients from the perspective of the morbidity, pathophysiological mechanism, diagnosis, and management of the disease.

  14. A Soft Computing Approach to Kidney Diseases Evaluation.

    PubMed

    Neves, José; Martins, M Rosário; Vilhena, João; Neves, João; Gomes, Sabino; Abelha, António; Machado, José; Vicente, Henrique

    2015-10-01

    Kidney renal failure means that one's kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient's history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis. The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the

  15. Whole exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies

    PubMed Central

    Gee, Heon Yung; Otto, Edgar A.; Hurd, Toby W.; Ashraf, Shazia; Chaki, Moumita; Cluckey, Andrew; Vega-Warner, Virginia; Saisawat, Pawaree; Diaz, Katrina A.; Fang, Humphrey; Kohl, Stefan; Allen, Susan J.; Airik, Rannar; Zhou, Weibin; Ramaswami, Gokul; Janssen, Sabine; Fu, Clementine; Innis, Jamie L.; Weber, Stefanie; Vester, Udo; Davis, Erica E.; Katsanis, Nicholas; Fathy, Hanan M.; Jeck, Nikola; Klaus, Gunther; Nayir, Ahmet; Rahim, Khawla A.; Attrach, Ibrahim Al; Hassoun, Ibrahim Al; Ozturk, Savas; Drozdz, Dorota; Helmchen, Udo; O’Toole, John F.; Attanasio, Massimo; Nürnberg, Gudrun; Nürnberg, Peter; Washburn, Joseph; MacDonald, James; James, Jeffrey W.; Levy, Shawn; Hildebrandt, Friedhelm

    2013-01-01

    Rare single-gene disorders cause chronic disease. However, half of the 6,000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical management and potentially treatment. Rare diseases comprise the majority of chronic kidney disease (CKD) in children but are notoriously difficult to diagnose. Whole exome resequencing facilitates identification of recessive disease genes. However, its utility is impeded by the large number of genetic variants detected. We here overcome this limitation by combining homozygosity mapping with whole exome resequencing in 10 sib pairs with a nephronophthisis-related ciliopathy, which represents the most frequent genetic cause of CKD in the first three decades of life. In 7 of 10 sib-ships with a histologic or ultrasonographic diagnosis of nephronophthisis-related ciliopathy we detect the causative gene. In six sib-ships we identify mutations of known nephronophthisis-related ciliopathy genes, while in two additional sib-ships we found mutations in the known CKD-causing genes SLC4A1 and AGXT as phenocopies of nephronophthisis-related ciliopathy. Thus whole exome resequencing establishes an efficient, non-invasive approach towards early detection and causation-based diagnosis of rare kidney diseases. This approach can be extended to other rare recessive disorders, thereby providing accurate diagnosis and facilitating the study of disease mechanisms. PMID:24257694

  16. [Horseshoe kidney, stone disease and prostate cancer: a case presentation].

    PubMed

    Hermida Pérez, J A; Bermejo Hernández, A; Hernández Guerra, J S; Sobenes Gutierrez, R J

    2013-01-01

    The horseshoe kidney is the most common congenital renal fusion anomalies. It occurs in 0.25% of the population, or 1 in every 400 people. It is more frequent in males (ratio 2:1). The most observed complication of horseshoe kidney is stone disease, although there may be others such as, abdominal pain, urinary infections, haematuria, hydronephrosis, trauma and tumours (most commonly associated with hypernephroma and Wilms tumour). We describe a case of a male patient with horseshoe kidney, stone disease and adenocarcinoma of the prostate. One carrier of this condition who suffered a transitional cell carcinoma of the prostate was found in a review of the literature.

  17. The Renal Connexome and Possible Roles of Connexins in Kidney Diseases.

    PubMed

    Sala, Gabriele; Badalamenti, Salvatore; Ponticelli, Claudio

    2016-04-01

    Connexins are membrane-spanning proteins that allow for the formation of cell-to-cell channels and cell-to-extracellular space hemichannels. Many connexin subtypes are expressed in kidney cells. Some mutations in connexin genes have been linked to various human pathologies, including cardiovascular, neurodegenerative, lung, and skin diseases, but the exact role of connexins in kidney disease remains unclear. Some hypotheses about a connection between genetic mutations, endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) in kidney pathology have been explored. The potential relationship of kidney disease to abnormal production of connexin proteins, mutations in their genes together with ER stress, or the UPR is still a matter of debate. In this scenario, it is tantalizing to speculate about a possible role of connexins in the setting of kidney pathologies that are thought to be caused by a deregulated podocyte protein expression, the so-called podocytopathies. In this article, we give examples of the roles of connexins in kidney (patho)physiology and propose avenues for further research concerning connexins, ER stress, and UPR in podocytopathies that may ultimately help refine drug treatment.

  18. Pharmacological management of acute kidney injury and chronic kidney disease in neonates.

    PubMed

    Jetton, Jennifer G; Sorenson, Mark

    2017-04-01

    Both acute kidney injury (AKI) and chronic kidney disease (CKD) are seen more frequently in the neonatal intensive care unit (NICU) as advances in supportive care improve the survival of critically ill infants as well as those with severe, congenital kidney and urinary tract anomalies. Many aspects of the infant's care, including fluid balance, electrolyte and mineral homeostasis, acid-base balance, and growth and nutrition require close monitoring by and collaboration among neonatologists, nephrologists, dieticians, and pharmacologists. This educational review summarizes the therapies widely used for neonates with AKI and CKD. Use of these therapies is extrapolated from data in older children and adults or based on clinical experience and case series. There is a critical need for more research on the use of therapies in infants with kidney disease as well as for the development of drug delivery systems and preparations scaled more appropriately for these small patients.

  19. Genetic loci influencing kidney function and chronic kidney disease in man

    PubMed Central

    Chambers, John C; Zhang, Weihua; Lord, Graham M; van der Harst, Pim; Lawlor, Debbie A; Sehmi, Joban S; Gale, Daniel P; Wass, Mark N; Ahmadi, Kourosh R; Bakker, Stephan JL; Beckmann, Jacqui; Bilo, Henk JG; Bochud, Murielle; Brown, Morris J; Caulfield, Mark J; Connell, John M C; Cook, Terence; Cotlarciuc, Ioana; Smith, George Davey; de Silva, Ranil; Deng, Guohong; Devuyst, Olivier; Dikkeschei, Lambert D.; Dimkovic, Nada; Dockrell, Mark; Dominiczak, Anna; Ebrahim, Shah; Eggermann, Thomas; Farrall, Martin; Ferrucci, Luigi; Floege, Jurgen; Forouhi, Nita G; Gansevoort, Ron T; Han, Xijin; Hedblad, Bo; van der Heide, Jaap J Homan; Hepkema, Bouke G; Hernandez-Fuentes, Maria; Hypponen, Elina; Johnson, Toby; de Jong, Paul E; Kleefstra, Nanne; Lagou, Vasiliki; Lapsley, Marta; Li, Yun; Loos, Ruth J F; Luan, Jian'an; Luttropp, Karin; Maréchal, Céline; Melander, Olle; Munroe, Patricia B; Nordfors, Louise; Parsa, Afshin; Penninx, Brenda W.; Perucha, Esperanza; Pouta, Anneli; Prokopenko, Inga; Roderick, Paul J; Ruokonen, Aimo; Samani, Nilesh; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Seelen, Marc AJ; Shuldiner, Alan R; Sjögren, Marketa; Smit, Johannes H.; Snieder, Harold; Soranzo, Nicole; Spector, Timothy D; Stenvinkel, Peter; Sternberg, Michael JE; Swaminathan, Ramasamyiyer; Tanaka, Toshiko; Ubink-Veltmaat, Lielith J.; Uda, Manuela; Vollenweider, Peter; Wallace, Chris; Waterworth, Dawn; Zerres, Klaus; Waeber, Gerard; Wareham, Nicholas J; Maxwell, Patrick H; McCarthy, Mark I; Jarvelin, Marjo-Riitta; Mooser, Vincent; Abecasis, Goncalo R; Lightstone, Liz; Scott, James; Navis, Gerjan; Elliott, Paul; Kooner., Jaspal S

    2013-01-01

    Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD. PMID:20383145

  20. Solitary Kidney

    MedlinePlus

    ... How They Work Kidney Disease A-Z Solitary Kidney What is a solitary kidney? When a person has only one kidney or ... ureter are removed (bottom right). What are the kidneys and what do they do? The kidneys are ...

  1. A transcriptional network underlies susceptibility to kidney disease progression

    PubMed Central

    Laouari, Denise; Burtin, Martine; Phelep, Aurélie; Bienaime, Frank; Noel, Laure-Hélène; Lee, David C; Legendre, Christophe; Friedlander, Gérard; Pontoglio, Marco; Terzi, Fabiola

    2012-01-01

    The molecular networks that control the progression of chronic kidney diseases (CKD) are poorly defined. We have recently shown that the susceptibility to development of renal lesions after nephron reduction is controlled by a locus on mouse chromosome 6 and requires epidermal growth factor receptor (EGFR) activation. Here, we identified microphthalmia-associated transcription factor A (MITF-A), a bHLH-Zip transcription factor, as a modifier of CKD progression. Sequence analysis revealed a strain-specific mutation in the 5′ UTR that decreases MITF-A protein synthesis in lesion-prone friend virus B NIH (FVB/N) mice. More importantly, we dissected the molecular pathway by which MITF-A modulates CKD progression. MITF-A interacts with histone deacetylases to repress the transcription of TGF-α, a ligand of EGFR, and antagonizes transactivation by its related partner, transcription factor E3 (TFE3). Consistent with the key role of this network in CKD, Tgfa gene inactivation protected FVB/N mice from renal deterioration after nephron reduction. These data are relevant to human CKD, as we found that the TFE3/MITF-A ratio was increased in patients with damaged kidneys. Our study uncovers a novel transcriptional network and unveils novel potential prognostic and therapeutic targets for preventing human CKD progression. PMID:22711280

  2. A transcriptional network underlies susceptibility to kidney disease progression.

    PubMed

    Laouari, Denise; Burtin, Martine; Phelep, Aurélie; Bienaime, Frank; Noel, Laure-Hélène; Lee, David C; Legendre, Christophe; Friedlander, Gérard; Pontoglio, Marco; Terzi, Fabiola

    2012-08-01

    The molecular networks that control the progression of chronic kidney diseases (CKD) are poorly defined. We have recently shown that the susceptibility to development of renal lesions after nephron reduction is controlled by a locus on mouse chromosome 6 and requires epidermal growth factor receptor (EGFR) activation. Here, we identified microphthalmia-associated transcription factor A (MITF-A), a bHLH-Zip transcription factor, as a modifier of CKD progression. Sequence analysis revealed a strain-specific mutation in the 5' UTR that decreases MITF-A protein synthesis in lesion-prone friend virus B NIH (FVB/N) mice. More importantly, we dissected the molecular pathway by which MITF-A modulates CKD progression. MITF-A interacts with histone deacetylases to repress the transcription of TGF-α, a ligand of EGFR, and antagonizes transactivation by its related partner, transcription factor E3 (TFE3). Consistent with the key role of this network in CKD, Tgfa gene inactivation protected FVB/N mice from renal deterioration after nephron reduction. These data are relevant to human CKD, as we found that the TFE3/MITF-A ratio was increased in patients with damaged kidneys. Our study uncovers a novel transcriptional network and unveils novel potential prognostic and therapeutic targets for preventing human CKD progression.

  3. Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients.

    PubMed

    Chen, Szu-chi; Tseng, Chin-Hsiao

    2013-01-01

    This article reviews the relationship between dyslipidemia, chronic kidney disease, and cardiovascular diseases in patients with diabetes. Diabetes mellitus is associated with complications in the cardiovascular and renal system, and is increasing in prevalence worldwide. Modification of the multifactorial risk factors, in particular dyslipidemia, has been suggested to reduce the rates of diabetes-related complications. Dyslipidemia in diabetes is a condition that includes hypertriglyceridemia, low high-density lipoprotein levels, and increased small and dense low-density lipoprotein particles. This condition is associated with higher cardiovascular risk and mortality in diabetic patients. Current treatment guidelines focus on lowering the low-density lipoprotein cholesterol level; multiple trials have confirmed the cardiovascular benefits of treatment with statins. Chronic kidney disease also contributes to dyslipidemia, and dyslipidemia in turn is related to the occurrence and progression of diabetic nephropathy. Different patterns of dyslipidemia are associated with different stages of diabetic nephropathy. Some trials have shown that treatment with statins not only decreased the risk of cardiovascular events, but also delayed the progression of diabetic nephropathy. However, studies using statins as the sole treatment of hyperlipidemia in patients on dialysis have not shown benefits with respect to cardiovascular risk. Diabetic patients with nephropathy have a higher risk of cardiovascular events than those without nephropathy. The degree of albuminuria and the reduction in estimated glomerular filtration rate are also correlated with the risk of cardiovascular events. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to reduce albuminuria in diabetic patients has been shown to decrease the risk of cardiovascular morbidity and mortality.

  4. Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy.

    PubMed

    Sweeney, William E; Avner, Ellis D

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are significant causes of morbidity and mortality in children and young adults. ADPKD, with an incidence of 1:400 to 1:1,000, affects more than 13 million individuals worldwide and is a major cause of end-stage renal disease in adults. However, symptomatic disease is increasingly recognized in children. ARPKD is a dual-organ hepatorenal disease with an incidence of 1:20,000 to 1:40,000 and a heterozygote carrier rate of 1 in 70. Currently, no clinically significant disease-specific therapy exists for ADPKD or ARPKD. The genetic basis of both ADPKD and ARPKD have been identified, and delineation of the basic molecular and cellular pathophysiology has led to the discovery that abnormal ADPKD and ARPKD gene products interact to create "polycystin complexes" located at multiple sites within affected cells. The extracellular matrix and vessels produce a variety of soluble factors that affect the biology of adjacent cells in many dynamic ways. This review will focus on the molecular and cellular bases of the abnormal cystic phenotype and discuss the clinical translation of such basic data into new therapies that promise to alter the natural history of disease for children with genetic PKDs.

  5. 76 FR 31618 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-01

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Polycystic Kidney Disease. Date: June 23, 2011. Time: 1:30 p.m... Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology...

  6. 75 FR 56119 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Fellowships in Digestive Diseases and Nutrition. Date: October 18... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel. Kidney Disease Ancillary Studies....

  7. Kidney Transplantation as Primary Therapy for End-Stage Renal Disease: A National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) Conference

    PubMed Central

    Abecassis, Michael; Bartlett, Stephen T.; Collins, Allan J.; Davis, Connie L.; Delmonico, Francis L.; Friedewald, John J.; Hays, Rebecca; Howard, Andrew; Jones, Edward; Leichtman, Alan B.; Merion, Robert M.; Metzger, Robert A.; Pradel, Francoise; Schweitzer, Eugene J.; Velez, Ruben L.; Gaston, Robert S.

    2008-01-01

    Background and objectives: Kidney transplantation is the most desired and cost-effective modality of renal replacement therapy for patients with irreversible chronic kidney failure (end-stage renal disease, stage 5 chronic kidney disease). Despite emerging evidence that the best outcomes accrue to patients who receive a transplant early in the course of renal replacement therapy, only 2.5% of incident patients with end-stage renal disease undergo transplantation as their initial modality of treatment, a figure largely unchanged for at least a decade. Design, setting, participants, & measurements: The National Kidney Foundation convened a Kidney Disease Outcomes Quality Initiative (KDOQI) conference in Washington, DC, March 19 through 20, 2007, to examine the issue. Fifty-two participants representing transplant centers, dialysis providers, and payers were divided into three work groups to address the impact of early transplantation on the chronic kidney disease paradigm, educational needs of patients and professionals, and finances of renal replacement therapy. Results: Participants explored the benefits of early transplantation on costs and outcomes, identified current barriers (at multiple levels) that impede access to early transplantation, and recommended specific interventions to overcome those barriers. Conclusions: With implementation of early education, referral to a transplant center coincident with creation of vascular access, timely transplant evaluation, and identification of potential living donors, early transplantation can be an option for substantially more patients with chronic kidney disease. PMID:18256371

  8. Clinical management of the uraemic syndrome in chronic kidney disease.

    PubMed

    Vanholder, Raymond; Fouque, Denis; Glorieux, Griet; Heine, Gunnar H; Kanbay, Mehmet; Mallamaci, Francesca; Massy, Ziad A; Ortiz, Alberto; Rossignol, Patrick; Wiecek, Andrzej; Zoccali, Carmine; London, Gérard Michel

    2016-04-01

    The clinical picture of the uraemic syndrome is a complex amalgam of accelerated ageing and organ dysfunction, which progress in parallel to chronic kidney disease. The uraemic syndrome is associated with cardiovascular disease, metabolic bone disease, inflammation, protein energy wasting, intestinal dysbiosis, anaemia, and neurological and endocrine dysfunction. In this Review, we summarise specific, modern management options for the uraemic syndrome in chronic kidney disease. Although large randomised controlled trials are scarce, based on data from randomised controlled trials and observational studies, as well as pathophysiological reasoning, a therapeutic algorithm can be developed for this complex and multifactorial condition, with interventions targeting several modifiable factors simultaneously.

  9. Frailty in elderly people with chronic kidney disease.

    PubMed

    Portilla Franco, Maria Eugenia; Tornero Molina, Fernando; Gil Gregorio, Pedro

    In recent years, the concept of frailty as a "state of pre-disability" has been widely accepted by those involved in the care of the elderly. Its importance lies not only in its high prevalence - more than 25% in people over 85 years of age - but it is also considered an independent risk factor of disability, institutionalisation and mortality amongst the elderly. The study of renal function is relevant in patients with major comorbidities. Studies have shown a significant association between chronic kidney disease and the development of adverse clinical outcomes such as heart disease, heart failure, end-stage renal disease, increased susceptibility to infections and greater functional impairment. Frailty can be reversed, which is why a study of frailty in patients with chronic kidney disease is of particular interest. This article aims to describe the association between ageing, frailty and chronic kidney disease in light of the most recent and relevant scientific publications.

  10. Influence of race, ethnicity and socioeconomic status on kidney disease

    PubMed Central

    Patzer, Rachel E.; McClellan, William M.

    2014-01-01

    Low socioeconomic status (SES) influences disease incidence and contributes to poor health outcomes throughout an individual's life course across a wide range of populations. Low SES is associated with increased incidence of chronic kidney disease, progression to end-stage renal disease, inadequate dialysis treatment, reduced access to kidney transplantation, and poor health outcomes. Similarly, racial and ethnic disparities, which in the USA are strongly associated with lower SES, are independently associated with poor health outcomes. In this Review, we discuss individual-level and group-level SES factors, and the concomitant role of race and ethnicity that are associated with and mediate the development of chronic kidney disease, progression to end-stage renal disease and access to treatment. PMID:22735764

  11. Kidney bioengineering in regenerative medicine: An emerging therapy for kidney disease.

    PubMed

    Lin, Yi-Qian; Wang, Li-Ren; Pan, Liang-Liang; Wang, Hui; Zhu, Gui-Qi; Liu, Wen-Yue; Wang, Jiang-Tao; Braddock, Martin; Zheng, Ming-Hua

    2016-02-01

    The prevalence of end-stage renal disease is emerging as a serious worldwide public health problem because of the shortage of donor organs and the need to take lifelong immunosuppressive medication in patients who receive a transplanted kidney. Recently, tissue bioengineering of decellularization and recellularization scaffolds has emerged as a novel strategy for organ regeneration, and we review the critical technologies supporting these methods. We present a summary of factors associated with experimental protocols that may shed light on the future development of kidney bioengineering and we discuss the cell sources and bioreactor techniques applied to the recellularization process. Finally, we review some artificial renal engineering technologies and their future prospects, such as kidney on a chip and the application of three-dimensional and four-dimensional printing in kidney tissue engineering.

  12. Kidney disease in children: latest advances and remaining challenges.

    PubMed

    Bertram, John F; Goldstein, Stuart L; Pape, Lars; Schaefer, Franz; Shroff, Rukshana C; Warady, Bradley A

    2016-03-01

    To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients.

  13. Clinical relevance of epigenetic dysregulation in chronic kidney disease-associated cardiovascular disease.

    PubMed

    Zawada, Adam M; Rogacev, Kyrill S; Heine, Gunnar H

    2013-07-01

    Across the spectrum of clinical medicine, the field of epigenetics has gained substantial scientific interest in recent years. Epigenetics refers to modifications in gene expression which are not explained by changes in DNA sequence. Classical components of epigenetic regulation comprise DNA methylation, histone modifications and RNA interference. In chronic kidney disease (CKD), several features of uraemia, such as hyperhomocysteinemia and inflammation, may contribute to changes in epigenetic gene regulation. It has been suggested that these changes may affect genes related to cardiovascular disease. Thereby, a uraemia-associated disturbance in epigenetic regulation may contribute to the substantial increase in cardiovascular morbidity in CKD patients. The present review aims to summarize current knowledge of epigenetic dysregulation in cardiovascular disease from a nephrological perspective, with a special focus on DNA methylation. We first describe the impact of altered epigenetic regulation in non-CKD-associated arteriosclerosis, and next characterize uraemic features which may affect epigenetic gene regulation in the context of cardiovascular disease. Finally, we conclude that substantial additional work is needed before epigenetic regulatory mechanisms may become therapeutic targets in CKD-associated cardiovascular disease.

  14. Role of proximal tubules in the pathogenesis of kidney disease.

    PubMed

    Nakhoul, Nazih; Batuman, Vecihi

    2011-01-01

    The proximal tubules make up a significant portion of the kidneys; proximal tubule epithelial cells are the most populous cell type in the kidney, and carry out diverse regulatory and endocrine functions where numerous transporters are located. Under normal circumstances, more than two thirds of filtered salt and water, and all filtered bicarbonate is reabsorbed in the proximal tubule. A number of inherited and acquired acid-base and tubule disorders are linked to impaired transporters in the proximal tubule cells. Equally important is the intrinsic immune characteristics of proximal tubule cells that give them the ability to also function as immune responders to a wide range of immunologic, ischemic or toxic injury. It is therefore not surprising that proximal tubule-related phenomena are closely related to the pathogenesis of a vast array of kidney diseases. Many kidney diseases, acute and chronic, first manifest with proximal tubule disorders. Recent insight into molecular characteristics of transport functions in the proximal tubules, and the recognition that proximal tubule cells possess intrinsic immune responses have contributed to an improved understanding of important areas in nephrology, such as Fanconi's syndrome, renal tubular acidosis, phosphate wasting syndromes, Dent's disease, cystinuria and other amino acid transport disorders, acute kidney injury, and the role of proximal tubules in progressive kidney disease. Megalin/ cubilin-mediated endocytosis by proximal tubule cells of increased quantities of filtered proteins (protein overloading) in glomerular diseases appears to evoke cell stress responses resulting in increased inflammatory cytokines leading to tubulointerstitial inflammation and fibrosis. Finally, the proximal tubule may be the site of both active vitamin D synthesis through the action of 1-α-hydroxylase, and the site where erythropoietin synthesis takes place. Thus, proximal tubule injury also contributes to two distressing

  15. Cat-scratch disease relapse in a kidney transplant recipient.

    PubMed

    Rheault, Michelle N; van Burik, Jo-Anne; Mauer, Michael; Ingulli, Elizabeth; Ferrieri, Patricia; Jessurun, Jose; Chavers, Blanche M

    2007-02-01

    Cat-scratch disease, an infectious illness infrequently reported in kidney transplant patients, is caused by the organism Bartonella henselae and is transmitted through contact with cats or kittens. It is a self-limited disorder in the general pediatric population. Here we present a case of unsuspected cat-scratch disease in a pediatric kidney transplant patient who presented with fever and lymphadenopathy. Eight months after treatment with a short course of azithromycin, the patient developed a recurrence of cat-scratch disease. We emphasize that the evaluation of a young immunocompromised kidney transplant patient presenting with fever and lymphadenopathy should include unusual infections such as cat-scratch disease. We review the diagnosis and treatment of this uncommon infection in the organ transplant population.

  16. Present and Future in the Treatment of Diabetic Kidney Disease

    PubMed Central

    de Arriba, Gabriel

    2015-01-01

    Diabetic kidney disease is the leading cause of end-stage renal disease. Albuminuria is recognized as the most important prognostic factor for chronic kidney disease progression. For this reason, blockade of renin-angiotensin system remains the main recommended strategy, with either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, other antiproteinuric treatments have begun to be studied, such as direct renin inhibitors or aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as pentoxifylline or bardoxolone have yielded conflicting results. Finally, alternative pathogenic pathways are being explored, and emerging therapies including antifibrotic agents, endothelin receptor antagonists, or transcription factors show promising results. The aim of this review is to explain the advances in newer agents to treat diabetic kidney disease, along with the background of the renin-angiotensin system blockade. PMID:25945357

  17. Expression of lumbosacral HOX genes, crucial in kidney organogenesis, is systematically deregulated in clear cell kidney cancers.

    PubMed

    Cantile, Monica; Schiavo, Giulia; Franco, Renato; Cindolo, Luca; Procino, Alfredo; D'Armiento, Maria; Facchini, Gaetano; Terracciano, Luigi; Botti, Gerardo; Cillo, Clemente

    2011-06-01

    Homeobox-containing genes are involved in different stages of kidney organogenesis, from the early events in intermediate mesoderm to terminal differentiation of glomerular and tubular epithelia. The HOX genes show a unique genomic network organization and regulate normal development. The targeted disruption of paralogous group 11 HOX genes (HOX A11, HOX C11 and HOX D11) results in a complete loss of metanephric kidney induction. Despite a large amount of data are related to the early events in the kidney development, not much is known about HOX genes in advanced kidney organogenesis and carcinogenesis. Here, we compare the expression of the whole HOX gene network in late-stage human foetal kidney development with the same patterns detected in 25 pairs of normal clear cell renal carcinomas (RCCs) and 15 isolated RCC biopsy samples. In the majority of RCCs tested, HOX C11 is upregulated, whereas HOX D11, after an early involvement becomes active again at the 23rd week of the foetal kidney development, is always expressed in normal adult kidneys and is deregulated, together with HOX A11 and lumbosacral locus D HOX genes. Thus, through its function of regulating phenotype cell identity, the HOX network plays an important role in kidney carcinogenesis. Lumbosacral HOX genes are involved in the molecular alterations associated with clear cell kidney cancers and represent, through their deregulation, a molecular mark of tubular epithelial dedifferentiation occurring along tumour evolution, with the restoration of genetic programs associated with kidney organogenesis. The deregulation of lumbosacral HOX genes in RCCs supports (i) the consideration of the HOX gene transcriptome as the potential prognostic tool in kidney carcinogenesis and (ii) the possibility to foresee clinical trials with the purpose of targeting these genes to achieve a therapeutic effect in RCC patients.

  18. 76 FR 57747 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-16

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group; Kidney, Urologic and Hematologic Diseases D Subcommittee. Date....gov . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases...

  19. 76 FR 24897 - National Institute of Diabetes And Digestive and Kidney Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes And Digestive and Kidney... Kidney Diseases Initial Review Group, Kidney, Urologic and Hematologic Diseases D Subcommittee. Date..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney...

  20. 78 FR 72683 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, PAR13-228: Biomarkers for Diabetes, Digestive, Kidney and..., Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

  1. 78 FR 14312 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; George M. O'Brien Kidney Research Core Centers (P30). Date: April... Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research,...

  2. 78 FR 22273 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Acute Kidney Injury. Date: June 6, 2013. Time: 2:00 p.m. to 5:00... Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology...

  3. 77 FR 6130 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Cellular Biology of Kidney Function and Disease. Date: March 15... and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney...

  4. 78 FR 41941 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... Institute of Diabetes and Digestive and Kidney Diseases Special, Emphasis Panel; CRIC Ancillary Studies... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; PAR12-265 Ancillary Studies in Kidney Disease and...

  5. Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

    PubMed Central

    2012-01-01

    Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the

  6. Autosomal recessive polycystic kidney disease: the prototype of the hepato-renal fibrocystic diseases.

    PubMed

    Guay-Woodford, Lisa M

    Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Among neonatal survivors, a subset of ARPKD patients has clinically significant congenital hepatic fibrosis, which can lead to portal hypertension, requiring close monitoring by pediatric hepatologists. Surgical consultation may be sought to access pre-emptive nephrectomy to relieve mass effect, placement of dialysis access, surgical shunting procedures, and kidney and/or liver transplantation. Recent data suggest that children with ARPKD may be at risk of neurocognitive dysfunction, and may require neuropsychological referral. In addition to these morbidities, families of patients with ARPKD face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. These issues require the input of genetic counselors, geneticists, and reproductive endocrinologists. As a result, the management of ARPKD requires the involvement of multiple subspecialists, as well as the general pediatrician, in a complex care network. In this review, we discuss the genetics of this disorder and provide an overview of the associated pathobiology; outline the spectrum of clinical manifestations of ARPKD and the management of organ-specific complications

  7. The double challenge of resistant hypertension and chronic kidney disease.

    PubMed

    Rossignol, Patrick; Massy, Ziad A; Azizi, Michel; Bakris, George; Ritz, Eberhard; Covic, Adrian; Goldsmith, David; Heine, Gunnar H; Jager, Kitty J; Kanbay, Mehmet; Mallamaci, Francesca; Ortiz, Alberto; Vanholder, Raymond; Wiecek, Andrzej; Zoccali, Carmine; London, Gérard Michel; Stengel, Bénédicte; Fouque, Denis

    2015-10-17

    Resistant hypertension is defined as blood pressure above goal despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease is the most frequent of several patient factors or comorbidities associated with resistant hypertension. The prevalence of resistant hypertension is increased in patients with chronic kidney disease, while chronic kidney disease is associated with an impaired prognosis in patients with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation, are under investigation especially in patients with advanced chronic kidney disease. We discuss resistant hypertension in chronic kidney disease stages 3-5 (ie, patients with an estimated glomerular filtration rate below 60 mL/min per 1·73 m(2) and not on dialysis), in terms of worldwide epidemiology, outcomes, causes and pathophysiology, evidence-based treatment, and a call for action.

  8. Temporal trends in the incidence of kidney stone disease.

    PubMed

    Edvardsson, Vidar O; Indridason, Olafur S; Haraldsson, Gudjon; Kjartansson, Olafur; Palsson, Runolfur

    2013-01-01

    Recent reports show an increased occurrence of kidney stone disease worldwide. To further evaluate and quantify this observation, we examined recent trends in the incidence of kidney stone disease in the adult population of Iceland over a 24-year period. Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases, radiologic and surgical procedure codes indicative of kidney stones in patients aged 18 years and older. The time trends in stone frequency of 5945 incident patients (63% men) were assessed by Poisson regression analysis. The majority of patients (90.5%) had symptomatic stone disease. The total incidence of kidney stones rose significantly from 108 per 100,000 in the first 5-year interval of the study to 138 per 100,000 in the last interval. The annual incidence of symptomatic stones did not increase significantly in either men or women. There was, however, a significant increase in the annual incidence of asymptomatic stones over time, from 7 to 24 per 100,000 for men and from 7 to 21 per 100,000 for women. The increase in the incidence of asymptomatic stones was only significant for women above 50 years of age and for men older than 40 years. Thus, we found a significant increase in the incidence of kidney stone disease resulting from increased detection of asymptomatic stones. This was largely due to a more frequent use of high-resolution imaging studies in older patients.

  9. Survey Shows Blacks Not Concerned Enough about Kidney Disease

    ERIC Educational Resources Information Center

    Black Issues in Higher Education, 2004

    2004-01-01

    Health officials may have an uphill battle in educating Blacks about a disease that's being called a "silent killer," a recent survey shows. Kidney disease is an illness that's become more prevalent, especially in the nation's Black population, but a survey conducted in Jackson, Atlanta, Baltimore and Cleveland shows only 15 percent of those…

  10. Nutrition interventions to address cardiovascular outcomes in chronic kidney disease.

    PubMed

    Beto, Judith A; Bansal, Vinod K

    2004-10-01

    The high mortality in chronic kidney disease has been linked to cardiovascular risk and these patients are considered at high risk. Dietary intervention can directly address nutritional risk factors in lipid management, calcium-phorphorus balance, and body composition to reduce risk of cardiovascular disease. Nutrient intake can also indirectly address less overt risks of dental health, nutritional supplements, and compliance issues.

  11. Renin and angiotensinogen gene expression in maturing rat kidney

    SciTech Connect

    Gomez, R.A.; Lynch, K.R.; Chevalier, R.L.; Wilfong, N.; Everett, A.; Carey, R.M.; Peach, M.J. )

    1988-04-01

    To determine whether angiotensinogen (A{sub o}) and renin are synthesized by the immature kidney and to assess the changes in intrarenal reinin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and A{sub o} relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and A{sub o} cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I{center dot}h{sup {minus}1}{center dot}mg protein{sup {minus}1} in the incubation media. RRC was higher in newborn than in adult SHR (979 {+-} 164 vs. 206 {+-} 47) and WKY. In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animals. A{sub o} mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and A{sub o} genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.

  12. 75 FR 14605 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases, including consideration of personnel qualifications and performance, and the competence..., Director, Division of Intramural Research, National Institute of Diabetes and Digestive and Kidney...

  13. History of kidney stones and risk of chronic kidney disease: a meta-analysis

    PubMed Central

    Shang, Weifeng; Li, Lixi; Ren, Yali; Ge, Qiangqiang; Ku, Ming

    2017-01-01

    Background Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. Methods PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Results Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23–1.76])], with significant heterogeneity among these studies (I2 = 93.6%, P < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. Conclusion A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures. PMID:28149686

  14. Development and Validation of a Mass Spectrometry-Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease.

    PubMed

    Blumenstiel, Brendan; DeFelice, Matthew; Birsoy, Ozge; Bleyer, Anthony J; Kmoch, Stanislav; Carter, Todd A; Gnirke, Andreas; Kidd, Kendrah; Rehm, Heidi L; Ronco, Lucienne; Lander, Eric S; Gabriel, Stacey; Lennon, Niall J

    2016-07-01

    Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene. Because of variable age of disease onset and often subtle signs and symptoms, clinical diagnosis of mucin-1 kidney disease and differentiation from other forms of hereditary kidney disease have been difficult. The causal insertion resides in a variable number tandem repeat region with high GC content, which has made detection by standard next-generation sequencing impossible to date. The inherently difficult nature of this mutation required an alternative method for routine detection and clinical diagnosis of the disease. We therefore developed and validated a mass spectrometry-based probe extension assay with a series of internal controls to detect the insertion event using 24 previously characterized positive samples from patients with mucin-1 kidney disease and 24 control samples known to be wild type for the variant. Validation results indicate an accurate and reliable test for clinically establishing the molecular diagnosis of mucin-1 kidney disease with 100% sensitivity and specificity across 275 tests called.

  15. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

    PubMed

    Chapman, Arlene B; Devuyst, Olivier; Eckardt, Kai-Uwe; Gansevoort, Ron T; Harris, Tess; Horie, Shigeo; Kasiske, Bertram L; Odland, Dwight; Pei, York; Perrone, Ronald D; Pirson, Yves; Schrier, Robert W; Torra, Roser; Torres, Vicente E; Watnick, Terry; Wheeler, David C

    2015-07-01

    Autosomal-dominant polycystic kidney disease (ADPKD) affects up to 12 million individuals and is the fourth most common cause for renal replacement therapy worldwide. There have been many recent advances in the understanding of its molecular genetics and biology, and in the diagnosis and management of its manifestations. Yet, diagnosis, evaluation, prevention, and treatment vary widely and there are no broadly accepted practice guidelines. Barriers to translation of basic science breakthroughs to clinical care exist, with considerable heterogeneity across countries. The Kidney Disease: Improving Global Outcomes Controversies Conference on ADPKD brought together a panel of multidisciplinary clinical expertise and engaged patients to identify areas of consensus, gaps in knowledge, and research and health-care priorities related to diagnosis; monitoring of kidney disease progression; management of hypertension, renal function decline and complications; end-stage renal disease; extrarenal complications; and practical integrated patient support. These are summarized in this review.

  16. [Clinical diagnosis of Autosomal Dominant Polycystic Kidney Disease].

    PubMed

    Magistroni, Riccardo; Izzi, Claudia; Scolari, Francesco

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder related to kidney. ADPKD is usually easy to diagnose in people who have a family history of ADPKDs developing typical symptoms, including flank, abdominal pain or macroscopic hematuria. In this setting, diagnosis in adults at risk for ADPKD is commonly performed by ultrasonography, which reveals two enlarged kidneys with multiple bilateral cysts. ADPKD may be more difficult to diagnose in the absence of family history or in subjects with atypical presentation, including asymmetric or focal renal imaging findings, discordant disease within family, early onset of ADPKD and development of ESRD before 30 yr of age. The presence of a total of three or more renal cysts for at-risk subjects aged 15-39 years and two cysts or more in each kidney for at-risk subjects aged 40-59 years are sufficient for the diagnosis of ADPKD. The absence of any renal cyst is sufficient for disease exclusion only for at-risk subjects aged 40 years or older. If the family history is negative, the diagnosis of ADPKD can be made in a patient with enlarged kidneys, numerous cysts, presence of liver cysts and absence of findings suggesting a different cystic disease. If the imaging diagnosis is not clear or showing atypical manifestations in subjects, molecular genetic testing should be performed.

  17. Hepatitis C and kidney disease: A narrative review.

    PubMed

    Barsoum, Rashad S; William, Emad A; Khalil, Soha S

    2017-03-01

    Hepatitis-C (HCV) infection can induce kidney injury, mostly due to formation of immune-complexes and cryoglobulins, and possibly to a direct cytopathic effect. It may cause acute kidney injury (AKI) as a part of systemic vasculitis, and augments the risk of AKI due to other etiologies. It is responsible for mesangiocapillary or membranous glomerulonephritis, and accelerates the progression of chronic kidney disease due to other causes. HCV infection increases cardiovascular and liver-related mortality in patients on regular dialysis. HCV-infected patients are at increased risk of acute post-transplant complications. Long-term graft survival is compromised by recurrent or de novo glomerulonephritis, or chronic transplant glomerulopathy. Patient survival is challenged by increased incidence of diabetes, sepsis, post-transplant lymphoproliferative disease, and liver failure. Effective and safe directly acting antiviral agents (DAAs) are currently available for treatment at different stages of kidney disease. However, the relative shortage of DAAs in countries where HCV is highly endemic imposes a need for treatment-prioritization, for which a scoring system is proposed in this review. It is concluded that the thoughtful use of DAAs, will result in a significant change in the epidemiology and clinical profiles of kidney disease, as well as improvement of dialysis and transplant outcomes, in endemic areas.

  18. The NLRP3 inflammasome in kidney disease and autoimmunity.

    PubMed

    Hutton, Holly L; Ooi, Joshua D; Holdsworth, Stephen R; Kitching, A Richard

    2016-09-01

    The NLRP3 inflammasome is an intracellular platform that converts the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 to their active forms in response to 'danger' signals, which can be either host or pathogen derived, and mediates a form of inflammatory cell death called pyroptosis. This component of the innate immune system was initially discovered because of its role in rare autoinflammatory syndromes called cryopyrinopathies, but it has since been shown to mediate injurious inflammation in a broad range of diseases. Inflammasome activation occurs in both immune cells, primarily macrophages and dendritic cells, and in some intrinsic kidney cells such as the renal tubular epithelium. The NLRP3 inflammasome has been implicated in the pathogenesis of a number of renal conditions, including acute kidney injury, chronic kidney disease, diabetic nephropathy and crystal-related nephropathy. The inflammasome also plays a role in autoimmune kidney disease, as IL-1β and IL-18 influence adaptive immunity through modulation of T helper cell subsets, skewing development in favour of Th17 and Th1 cells that are important in the development of autoimmunity. Both IL-1 blockade and two recently identified specific NLRP3 inflammasome blockers, MCC950 and β-hydroxybutyrate, have shown promise in the treatment of inflammasome-mediated conditions. These targeted therapies have the potential to be of benefit in the growing number of kidney diseases in which the NLRP3 inflammasome has been implicated.

  19. Recurrent atypical haemolytic uraemic syndrome post kidney transplant due to a CD46 mutation in the setting of SMARCAL1-mediated inherited kidney disease.

    PubMed

    Chan, Samuel; Mallett, Andrew J; Patel, Chirag; Francis, Ross S; Johnson, David W; Mudge, David W; Isbel, Nicole M

    2017-02-01

    Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney. However, some patients with CD46 mutations have a second variant in other complement regulatory genes increasing the severity of disease. The following case report illustrates the course of a young adult patient with end-stage kidney disease initially ascribed to seronegative systemic lupus erythematosus, who presented with biopsy-proven thrombotic microangiopathy following kidney transplantation. It highlights the complexity associated with disorders of complement regulation and the need for a high index of suspicion and genetic testing in patients who present with thrombotic microangiopathy post-transplant.

  20. Endocrine Abnormalities in Patients with Chronic Kidney Disease.

    PubMed

    Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

    2015-01-01

    In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

  1. Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

    PubMed

    Roncal-Jimenez, C; Lanaspa, M A; Jensen, T; Sanchez-Lozada, L G; Johnson, R J

    2015-01-01

    Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health.

  2. [Infectious complications in autosomal dominant polycystic kidney disease].

    PubMed

    Pirson, Yves; Kanaan, Nada

    2015-04-01

    Despite advances in the management of autosomal dominant polycystic kidney disease over the past two decades, infection of liver and kidney cysts remains a serious and potentially threatening complication. Kidney cyst infection is the most frequent complication. It is differentiated from hemorrhage by the clinical presentation (mainly the severity and duration of fever), C-reactive protein (CRP) and white blood cells levels, and the density of the suspected cyst on computed tomography. Liver cyst infection occurs more frequently in patients with large cysts volumes. It can be life threatening and has a tendency to recur. In both infections, the best radiological imaging technique is positron emission tomography after intravenous injection of [18F]-fluorodeoxyglucose combined with computed tomography. Treatment with a fluoroquinolone should be continued for 6 weeks. Cyst aspiration is necessary only when cysts are very large and/or when infection is resistant to antibiotic treatment. In patients who are candidates to kidney transplantation, a history of recurrent kidney cyst infection justifies pre-transplant nephrectomy, while a past history of recurrent liver cyst infection or angiocholitis leads to consider liver transplantation. Among extrarenal and extrahepatic complications of polycystic disease, colic diverticulosis is reported to be associated with increased risk of infection in patients on hemodialysis and after kidney transplantation. However, this observation needs to be confirmed.

  3. Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

    PubMed Central

    Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

    2009-01-01

    Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

  4. 75 FR 4094 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... Kidney Diseases Special Emphasis Panel; Hematology Program Projects. Date: March 9, 2010. Time: 1 p.m. to... Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research,...

  5. Multiple kidney cysts in thin basement membrane disease with proteinuria and kidney function impairment

    PubMed Central

    Sevillano, Angel M.; Gutierrez, Eduardo; Morales, Enrique; Hernandez, Eduardo; Molina, Maria; Gonzalez, Ester; Praga, Manuel

    2014-01-01

    Background Some patients with thin basement membrane disease (TBMD) develop proteinuria, hypertension and different degrees of CKD, besides the persistent microhaematuria characteristic of the disease. Little is known about factors associated with this unfavourable outcome. Methods We reviewed clinical, pathological and radiological features of 32 patients with biopsy-proven TBMD. Patients were divided in two groups: those with persistent normal kidney function and negative or minimal proteinuria (n = 16) and those with persistent proteinuria >0.5 g/day (n = 16). Results Patients with proteinuria had a worse kidney function at baseline than those with negative proteinuria. Global or segmental glomerulosclerosis, together with interstitial fibrosis, was found in 37% of patients with proteinuria. All proteinuric patients were treated with renin–angiotensin system blockers. At the end of follow-up (198 months in proteinuric patients and 210 months in patients with negative proteinuria) the prevalence of hypertension was 68% in proteinuric patients (12% at baseline), compared with 12 and 6%, respectively, in non-proteinuric patients. A slow decline of renal function was observed in proteinuric patients, although no patient developed end-stage kidney disease. Ultrasound studies showed bilateral kidney cysts in nine patients (56%) with proteinuria. Cysts were bilateral and countless in six patients, and bilateral but with a limited number of cysts in the three remaining patients. No cysts were found in patients with negative proteinuria. Conclusions Some patients with TBMD develop hypertension, proteinuria and CKD. Multiple bilateral kidney cysts were found in a majority (56%) of these patients. Further studies are needed to investigate the pathogenesis and the influence on long-term outcome of this TBMD-associated multiple kidney cysts. PMID:25852885

  6. Pre-pregnancy counseling for women with chronic kidney disease.

    PubMed

    Bramham, Kate; Lightstone, Liz

    2012-01-01

    Pre-pregnancy counseling should be available for all women with chronic kidney disease (CKD) so that conception occurs at the right time in the course of their disease and while they are on the right medications, with the aims of minimizing risks for both mother and fetus. Key areas to consider are the factors which are associated with worse prognosis and the influence of underlying kidney conditions and their treatment, in particular lupus nephritis, advanced renal impairment and transplantation. This experience-based review provides a guide to clinicians managing women with CKD, before and during their pregnancy.

  7. Use of sevelamer in chronic kidney disease: beyond phosphorus control.

    PubMed

    Rodríguez-Osorio, Laura; Zambrano, Diana Pazmiño; Gracia-Iguacel, Carolina; Rojas-Rivera, Jorge; Ortiz, Alberto; Egido, Jesus; González Parra, Emilio

    2015-01-01

    Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertise.

  8. Therapeutic Area Data Standards for Autosomal Dominant Polycystic Kidney Disease: A Report From the Polycystic Kidney Disease Outcomes Consortium (PKDOC).

    PubMed

    Perrone, Ronald D; Neville, Jon; Chapman, Arlene B; Gitomer, Berenice Y; Miskulin, Dana C; Torres, Vicente E; Czerwiec, Frank S; Dennis, Eslie; Kisler, Bron; Kopko, Steve; Krasa, Holly B; LeRoy, Elizabeth; Castedo, Juliana; Schrier, Robert W; Broadbent, Steve

    2015-10-01

    Data standards provide a structure for consistent understanding and exchange of data and enable the integration of data across studies for integrated analysis. There is no data standard applicable to kidney disease. We describe the process for development of the first-ever Clinical Data Interchange Standards Consortium (CDISC) data standard for autosomal dominant polycystic kidney disease (ADPKD) by the Polycystic Kidney Disease Outcomes Consortium (PKDOC). Definition of common data elements and creation of ADPKD-specific data standards from case report forms used in long-term ADPKD registries, an observational cohort (Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease [CRISP] 1 and 2), and a randomized clinical trial (Halt Progression of Polycystic Kidney Disease [HALT-PKD]) are described in detail. This data standard underwent extensive review, including a global public comment period, and is now available online as the first PKD-specific data standard (www.cdisc.org/therapeutic). Submission of clinical trial data that use standard data structures and terminology will be required for new electronic submissions to the US Food and Drug Administration for all disease areas by the end of 2016. This data standard will allow for the mapping and pooling of available data into a common data set in addition to providing a foundation for future studies, data sharing, and long-term registries in ADPKD. This data set will also be used to support the regulatory qualification of total kidney volume as a prognostic biomarker for use in clinical trials. The availability of consensus data standards for ADPKD has the potential to facilitate clinical trial initiation and increase sharing and aggregation of data across observational studies and among completed clinical trials, thereby improving our understanding of disease progression and treatment.

  9. Parasitic kidney disease: milestones in the evolution of our knowledge.

    PubMed

    Barsoum, Rashad S

    2013-03-01

    Of the 342 parasites that infect humans, 20 are associated with kidney disease, yet of these, only schistosomes, plasmodia, filariae, and leishmanias are held responsible for significant clinical or epidemiologic impact. Reviewing the evolution of human knowledge for these parasites discloses a lot of similarities regarding their discovery, patterns of kidney injury, and pathogenic mechanisms. From a historical perspective, our relevant information may be classified into 4 phases: (1) disease documentation in ancient and medieval scripts as far back as 2000-3000 bce; (2) discovery of the parasites, their life cycles, and clinical correlates by European clinicians working in African and Asian colonies during the second half of the 19th century; (3) discovery and characterization of the renal manifestations of monoparasitic infections during the second half of the 20th century; and (4) recognition of the confounding effects of coinfection with bacteria, viruses, or other parasites. The spectrum of respective kidney diseases extends all the way from acute kidney injury to glomerulonephritis, amyloidosis, urologic disorders, and malignancy. Discovery of the common immunopathogenetic host response to parasitic infections has provided a knowledge core that explains the similarities, diversities, and interactions with regard to kidney injury.

  10. Dietary sodium in chronic kidney disease: a comprehensive approach.

    PubMed

    Wright, Julie A; Cavanaugh, Kerri L

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.

  11. Dietary Sodium in Chronic Kidney Disease: A Comprehensive Approach

    PubMed Central

    Wright, Julie A.; Cavanaugh, Kerri L.

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake. PMID:20557489

  12. Obesity and kidney disease: Hidden consequences of the epidemic.

    PubMed

    Kovesdy, Csaba P; Furth, Susan; Zoccali, Carmine

    2017-01-01

    Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

  13. IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease.

    PubMed

    Baek, Jea-Hyun; Zeng, Rui; Weinmann-Menke, Julia; Valerius, M Todd; Wada, Yukihiro; Ajay, Amrendra K; Colonna, Marco; Kelley, Vicki R

    2015-08-03

    Macrophages (Mø) are integral in ischemia/reperfusion injury-incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mø survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34-dependent, Mø-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mø-mediated AKI and subsequent CKD were markedly reduced in IL-34-deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase ζ (PTP-ζ) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mø-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mø proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP-ζ in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mø-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD.

  14. Disseminated kidney tuberculosis complicating autosomal dominant polycystic kidney disease: a case report.

    PubMed

    Takeshita, Hideki; Amemiya, Morimasa; Chiba, Koji; Urushibara, Masayasu; Satoh, Jun-Ichi; Noro, Akira

    2012-03-01

    Mycobacterium tuberculosis infection in patients with autosomal dominant polycystic kidney disease (ADPKD) is rare, and its diagnosis and treatment are difficult because numerous cysts are exposed to infection and antibiotics do not easily penetrate infected cysts. Here, we report the case of a 43-year-old Japanese man with disseminated urogenital tuberculosis (TB) and ADPKD without human immunodeficiency virus (HIV) infection. Delayed diagnosis and ineffective anti-TB chemotherapy worsened his condition. Finally, he underwent bilateral nephrectomy but experienced postoperative complications. In conclusion, kidney TB should be recognized as a cause of renal infection in ADPKD, and surgical treatment should be instituted without delay. The importance of early diagnosis and treatment cannot be overemphasized to prevent kidney TB deterioration.

  15. Light chain crystalline kidney disease: diagnostic urine microscopy as the "liquid kidney biopsy".

    PubMed

    Luciano, Randy L; Castano, Ekaterina; Fogazzi, Giovanni B; Perazella, Mark A

    2014-12-01

    Multiple myeloma (MM) is a plasma cell disorder, which often causes parenchymal kidney disease. Light chain (LC) cast nephropathy represents the most common renal lesion. In some instances, LC crystals precipitate within renal tubular lumens and deposit within proximal tubular cell cytoplasms. Importantly, urine microscopy in such patients can provide insight into the underlying LC-related lesion. Here we present two patients with MM complicated by acute kidney injury (AKI) where LC crystalline casts were observed on urinary sediment analysis. Kidney biopsy revealed acute tubular injury with LC crystal casts within both tubular lumens and renal tubular epithelial cell cytoplasms. These findings suggest that the urinary sediment may be a non-invasive way to diagnose LC crystalline-induced AKI in patients with MM.

  16. Neurocognitive Outcomes in Children with Chronic Kidney Disease: Current Findings and Contemporary Endeavors

    ERIC Educational Resources Information Center

    Gerson, Arlene C.; Butler, Robert; Moxey-Mims, Marva; Wentz, Alicia; Shinnar, Shlomo; Lande, Marc B.; Mendley, Susan R.; Warady, Bradley A.; Furth, Susan L.; Hooper, Stephen R.

    2006-01-01

    Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early…

  17. 75 FR 23782 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ....nih.gov . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Bariatric Surgery and Kidney Function. Date: June 8, 2010....

  18. Predictors of autosomal dominant polycystic kidney disease progression.

    PubMed

    Schrier, Robert W; Brosnahan, Godela; Cadnapaphornchai, Melissa A; Chonchol, Michel; Friend, Keith; Gitomer, Berenice; Rossetti, Sandro

    2014-11-01

    Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.

  19. Renal progenitors: Roles in kidney disease and regeneration

    PubMed Central

    Chambers, Brooke E; Wingert, Rebecca A

    2016-01-01

    Kidney disease is a devastating condition that affects millions of people worldwide, and its prevalence is predicted to significantly increase. The kidney is a complex organ encompassing many diverse cell types organized in a elaborate tissue architecture, making regeneration a challenging feat. In recent years, there has been a surge in the field of stem cell research to develop regenerative therapies for various organ systems. Here, we review some recent progressions in characterizing the role of renal progenitors in development, regeneration, and kidney disease in mammals. We also discuss how the zebrafish provides a unique experimental animal model that can provide a greater molecular and genetic understanding of renal progenitors, which may contribute to the development of potential regenerative therapies for human renal afflictions. PMID:27928463

  20. Clinical Trials in Pediatric Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Cadnapaphornchai, Melissa A.

    2017-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is associated with concerning long-term implications for kidney function and cardiovascular health. Early intervention is needed in order to mitigate these long-term complications. Herein, we review important findings from recent clinical trials in ADPKD and their relevance to affected children and young adults and consider future directions for intervention. Recent clinical trials support aggressive control of blood pressure with blockade of the renin-angiotensin-aldosterone system as well as potential benefit of pravastatin therapy in children and young adults with ADPKD. There are several other candidate therapies, some of which have shown benefit in adult ADPKD, which require further investigation in affected children. PMID:28386535

  1. Chronic kidney disease in an adolescent with hyperuricemia: familial juvenile hyperuricemic nephropathy.

    PubMed

    Alaygut, Demet; Torun-Bayram, Meral; Soylu, Alper; Kasap, Belde; Türkmen, Mehmet; Kavukçu, Salih

    2013-01-01

    Chronic kidney disease (CKD) is a life-long condition associated with substantial morbidity and premature death due to complications from a progressive decrease in kidney function. Especially in children, early diagnosis and detection of the etiologic factors are important to improve their health outcomes. Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal-dominant disorder characterized by hyperuricemia with renal uric acid under-excretion and CKD. Genetic studies have revealed mutations in the uromodulin (UMOD) gene. Highlighting the importance of CKD in children, a 14-year-old girl with the rare diagnosis of FJHN is reported herein.

  2. Glomerulocystic kidney disease in an adult with enlarged kidneys: a case report and review of the literature.

    PubMed

    Obata, Y; Furusu, A; Miyazaki, M; Nishino, T; Kawazu, T; Kanamoto, Y; Nishikido, M; Taguchi, T; Kohno, S

    2011-02-01

    We report the case of a 31-year-old male with enlarged kidneys and glomerulocystic kidney disease (GCKD). The patient had no family history of renal disease or other diseases. On initial presentation he complained of poor eyesight, and hypertensive retinopathy and elevated serum creatinine (5.0 mg/dl) were found at that time. Renal biopsy showed cystic dilatation of Bowman's capsule and atrophy of the glomerular tuft. Thus, an adult case of sporadic GCKD was diagnosed. Based on previous reports, kidney size in patients with adult type GCKD varies from small to large. Our patient's kidneys are the largest ever reported (right kidney was 22 cm×10 cm, left kidney was 19 cm×10 cm). A review of the literature dealing with sporadic adult GCKD suggested that it is difficult to diagnose this disease early in its course.

  3. Kidney and eye diseases: common risk factors, etiological mechanisms, and pathways.

    PubMed

    Wong, Chee Wai; Wong, Tien Yin; Cheng, Ching-Yu; Sabanayagam, Charumathi

    2014-06-01

    Chronic kidney disease is an emerging health problem worldwide. The eye shares striking structural, developmental, and genetic pathways with the kidney, suggesting that kidney disease and ocular disease may be closely linked. A growing number of studies have found associations of chronic kidney disease with age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract. In addition, retinal microvascular parameters have been shown to be predictive of chronic kidney disease. Chronic kidney disease shares common vascular risk factors including diabetes, hypertension, smoking, and obesity, and pathogenetic mechanisms including inflammation, oxidative stress, endothelial dysfunction, and microvascular dysfunction, with ocular diseases supporting the 'Common Soil Hypothesis.' In this review, we present major epidemiological evidence for these associations and explore underlying pathogenic mechanisms and common risk factors for kidney and ocular disease. Understanding the link between kidney and ocular disease can lead to the development of new treatment and screening strategies for both diseases.

  4. Indoxyl sulphate and kidney disease: Causes, consequences and interventions.

    PubMed

    Ellis, Robert J; Small, David M; Vesey, David A; Johnson, David W; Francis, Ross; Vitetta, Luis; Gobe, Glenda C; Morais, Christudas

    2016-03-01

    In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2) ) and/or evidence of kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney.

  5. Kidney Transplantation From a Donor With Sickle Cell Disease.

    PubMed

    Rossidis, A; Lim, M A; Palmer, M; Levine, M H; Naji, A; Bloom, R D; Abt, P L

    2017-02-01

    In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37-year-old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.

  6. Chronic kidney disease: identification and management in primary care

    PubMed Central

    Fraser, Simon DS; Blakeman, Tom

    2016-01-01

    Chronic kidney disease (CKD) is an important and common noncommunicable condition globally. In national and international guidelines, CKD is defined and staged according to measures of kidney function that allow for a degree of risk stratification using commonly available markers. It is often asymptomatic in its early stages, and early detection is important to reduce future risk. The risk of cardiovascular outcomes is greater than the risk of progression to end-stage kidney disease for most people with CKD. CKD also predisposes to acute kidney injury – a major cause of morbidity and mortality worldwide. Although only a small proportion of people with CKD progress to end-stage kidney disease, renal replacement therapy (dialysis or transplantation) represents major costs for health care systems and burden for patients. Efforts in primary care to reduce the risks of cardiovascular disease, acute kidney injury, and progression are therefore required. Monitoring renal function is an important task, and primary care clinicians are well placed to oversee this aspect of care along with the management of modifiable risk factors, particularly blood pressure and proteinuria. Good primary care judgment is also essential in making decisions about referral for specialist nephrology opinion. As CKD commonly occurs alongside other conditions, consideration of comorbidities and patient wishes is important, and primary care clinicians have a key role in coordinating care while adopting a holistic, patient-centered approach and providing continuity. This review aims to summarize the vital role that primary care plays in predialysis CKD care and to outline the main considerations in its identification, monitoring, and clinical management in this context. PMID:27822135

  7. The HALT Polycystic Kidney Disease Trials: Design and Implementation

    PubMed Central

    Torres, Vicente E.; Perrone, Ronald D.; Steinman, Theodore I.; Bae, Kyongtae T.; Miller, J. Philip; Miskulin, Dana C.; Oskoui, Frederic Rahbari; Masoumi, Amirali; Hogan, Marie C.; Winklhofer, Franz T.; Braun, William; Thompson, Paul A.; Meyers, Catherine M.; Kelleher, Cass; Schrier, Robert W.

    2010-01-01

    Background and objectives: Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m2 were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively. Results: This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life. Conclusions: HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD. PMID:20089507

  8. A Drosophila model identifies a critical role for zinc in mineralization for kidney stone disease.

    PubMed

    Chi, Thomas; Kim, Man Su; Lang, Sven; Bose, Neelanjan; Kahn, Arnold; Flechner, Lawrence; Blaschko, Sarah D; Zee, Tiffany; Muteliefu, Gulinuer; Bond, Nichole; Kolipinski, Marysia; Fakra, Sirine C; Mandel, Neil; Miller, Joe; Ramanathan, Arvind; Killilea, David W; Brückner, Katja; Kapahi, Pankaj; Stoller, Marshall L

    2015-01-01

    Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall's plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.

  9. 76 FR 60507 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Digestive Diseases Core Centers. Date: December 2, 2011. Time: 8..., Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

  10. 78 FR 13360 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Kidney Diseases Special Emphasis Panel; Chronic Kidney Disease in Children. Date: April 4, 2013. Time: 11... and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  11. 78 FR 58322 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group, Digestive Diseases and Nutrition C Subcommittee. Date: October 23... Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research,...

  12. 75 FR 38817 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Acute Liver Failure Study...; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and...

  13. 76 FR 20692 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group; Diabetes, Endocrinology and Metabolic Diseases B Subcommittee. Date...; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and...

  14. 77 FR 34396 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel;; Digestive Diseases Research Core Centers. Date: July 23, 2012..., Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

  15. Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney

    PubMed Central

    Westland, Rik; Verbitsky, Miguel; Vukojevic, Katarina; Perry, Brittany J.; Fasel, David A.; Zwijnenburg, Petra J.G.; Bökenkamp, Arend; Gille, Johan J.P.; Saraga-Babic, Mirna; Ghiggeri, Gian Marco; D’Agati, Vivette D.; Schreuder, Michiel F.; Gharavi, Ali G.; van Wijk, Joanna A.E.; Sanna-Cherchi, Simone

    2016-01-01

    Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to be difficult. Here we studied the role of rare copy number variations in 80 patients from the KIMONO-study cohort for which pathogenic mutations in three genes commonly implicated in CAKUT were excluded. In total, 13 known or novel genomic imbalances in 11 of 80 patients were absent or extremely rare in 23,362 population controls. To identify the most likely genetic drivers for the CAKUT phenotype underlying these rare copy number variations, we used a systematic in silico approach based on frequency in a large dataset of controls, annotation with publicly available databases for developmental diseases, tolerance and haploinsufficiency scores, and gene expression profile in the developing kidney and urinary tract. Five novel candidate genes for CAKUT were identified that showed specific expression in the human and mouse developing urinary tract. Among these genes, DLG1 and KIF12 are likely novel susceptibility genes for CAKUT in humans. Thus, there is a significant role of genomic imbalance in the determination of kidney developmental phenotypes. Additionally, we defined a systematic strategy to identify genetic drivers underlying rare copy number variations. PMID:26352300

  16. Ubiquitin, Proteasomes and Proteolytic Mechanisms Activated by Kidney Disease

    PubMed Central

    Rajan, Vik; Mitch, William E.

    2008-01-01

    Summary The ubiquitin-proteasome system (UPS) includes 3 enzymes that conjugate ubiquitin to intracellular proteins that are then recognized and degraded in the proteasome. The process participates in the regulation of cell metabolism. In the kidney, the UPS regulates the turnover of transporters and signaling proteins and its activity is down regulated in acidosis-induced proximal tubular cell hypertrophy. In chronic kidney disease (CKD), muscle wasting occurs because complications of CKD including acidosis, insulin resistance, inflammation, and increased angiotensin II levels stimulate the UPS to degrade muscle proteins. This response also includes caspase-3 and calpains which act to cleave muscle proteins to provide substrates for the UPS. For example, caspase-3 degrades actomyosin, leaving a 14kD fragment of actin in muscle. The 14 kD actin fragment is increased in muscle of patient with kidney disease, burn injury and surgery. In addition, acidosis, insulin resistance, inflammation and angiotensin II stimulate glucocorticoid production. Glucocorticoids are also required for the muscle wasting that occurs in CKD. Thus, the UPS is involved in regulating kidney function and participates in highly organized responses that degrade muscle protein in response to loss of kidney function. PMID:18723090

  17. Urotensin II levels in patients with chronic kidney disease and kidney transplants

    PubMed Central

    2012-01-01

    Objective. Urotensin II is a potent vasoactive peptide that has been implicated in the pathophysiology of many diseases. There is no study reporting the role and level of this peptide in recipients of kidney transplant. So we aimed to study the plasma levels of urotensin II in this group of patients. Methods. Plasma urotensin II levels were analyzed in 110 subjects, who were divided into three groups: group 1 (35 kidney transplant recipients), group 2 (36 patients with chronic kidney disease), and group 3 (39 healthy controls). Results. Analysis of logarithmic transformation of urotensin II, i.e. log (urotensin II × 1000) levels, with a one-way analysis of variance yielded a P value of 0.001. Post-hoc analysis showed significantly higher log (urotensin II × 1000) levels in group 1 than groups 2 and 3 (P = 0.001 and 0.017, respectively). One of the important features of the subjects of this group was that they were taking immunosuppressive drugs because of renal transplantation. Conclusions. High urotensin II levels in recipients of kidney transplants could be drug-related (immunosuppressive drugs) and may be of practical importance that may be used to improve the long-term outcome of the patients. PMID:22098077

  18. Tear drops of kidney: a historical overview of Polycystic Kidney Disease.

    PubMed

    Balat, Ayse

    2016-02-01

    Polycystic kidneydisease (PKD) is one of the most common inheritedkidneydiseases causing end stage renal disease. Although it has been in existence with humanity, it was defined in 18th century. The most detailed observations on PKD have been written after the disease of Stephen Bathory, the King of Poland. He had fatigue and chest pain accompanied by unconsciousness within a few days after a hunting trip, and died within 9 days, at the age of 53 years in 1586. Surgeon Jan Zigulitz described the cysts in his kidneys as large like those of a bull, with an uneven and bumpy surface during the mummification. Based on available information, 347 years later, a group of physicians and historians in Krakow concluded that the probable cause of Kings death was PKD and uremia. Unfortunately, PKD did not attracted the interest of physicians until the 18th century. In late 18th century, Matthew Baillie noted that these vesicular cysts in kidney were different from hydatid cysts, and described them as "false hydatids of kidney". In 1888, Flix Lejars used the term of "polycystic kidney" for the first time, and stressed that these cysts were bilateral, and causing clinically identifiable symptoms. At the end of 19th century, the basic clinical signs, and genetic basis of the disease have been better defined. However, the inheritance pattern could only be understood long years later. In this study, the history of PKD, i.e., the tear drops (cysts) of kidney will try to be explained by the light of old and current knowledge.

  19. Using Digital Media to Promote Kidney Disease Education

    PubMed Central

    Goldstein, Karen; Briggs, Michael; Oleynik, Veronica; Cullen, Mac; Jones, Jewel; Newman, Eileen

    2013-01-01

    Healthcare providers and patients increasingly turn to the Internet—websites as well as social media platforms—for health-related information and support. Informed by research on audience behaviors and preferences related to digital health information, the National Kidney Disease Education Program (NKDEP) developed a comprehensive and user-friendly digital ecosystem featuring content and platforms relevant for each audience. NKDEP's analysis of website metrics and social media conversation mapping related to chronic kidney disease revealed gaps and opportunities, informing the development of a digital strategy to position NKDEP as a trustworthy digital source for evidence-based kidney disease information. NKDEP launched a redesigned website (www.nkdep.nih.gov) with enhanced content for multiple audiences as well as a complementary social media presence on Twitter and Facebook, serving to drive traffic to the website as well as actively engage target audiences in conversations about kidney disease. The results included improved website metrics and increasing social media engagement among consumers and healthcare providers. NKDEP will continue to monitor trends, explore new directions, and work to improve communication across digital platforms. PMID:23809289

  20. Toward a more collaborative federal response to chronic kidney disease.

    PubMed

    Narva, Andrew S; Briggs, Michael; Jordan, Regina; Pavkov, Meda E; Burrows, Nilka Rios; Williams, Desmond E

    2010-05-01

    Chronic kidney disease (CKD) is a significant public health problem in the United States. However, data from the United States Renal Data System and other sources suggest that care for people with CKD does not meet recommended standards. The Federal government has developed the infrastructure to promote population-based interventions which have reduced the burden of other chronic illnesses. An effective, coordinated response by Federal health agencies to the public health challenge of CKD could have a significant effect on the morbidity, mortality, and costs associated with CKD. In recent years, initiatives undertaken by three Federal agencies have made important advances in coordinating efforts. The Centers for Disease Control and Prevention has begun to develop public health infrastructure for monitoring the burden of CKD. The Centers for Medicare and Medicaid Services has, through the successful Fistula First Breakthrough Initiative (FFBI) and inclusion of CKD in the scope of work of Quality Improvement Organizations, promoted earlier diagnosis and treatment of CKD. The National Institute of Diabetes and Digestive and Kidney Diseases, through its National Kidney Disease Education Program, has reinvigorated and expanded the Kidney Interagency Coordinating Committee so that it is a robust vehicle to share information about activities, identify and disseminate promising practices and tools, and foster cross-agency collaboration. Collaboration among Federal health agencies has the potential to enhance efforts to reduce the burden of CKD.

  1. Diabetes mellitus and kidney disease in the elderly.

    PubMed

    Iglesias, Pedro; Heras, Manuel; Díez, Juan J

    2014-05-21

    Management of diabetic elderly patients with chronic kidney disease involves specific characteristics that affect both metabolic control and therapeutic measures. Blood glucose control targets should be individualised based on life expectancy, renal function, hypoglycaemia risk and comorbidity. Metformin may be used alone or in combination with other oral anti-diabetic drugs but must be discontinued when the glomerular filtration rate is less than 30 mL/min. Gliclazide and glipizide are sulfonylureas that do not require dose adjustment in chronic kidney disease but they should be avoided in cases of advanced kidney disease because of the risk of hypoglycaemia. Repaglinide is the only meglitinide recommended in these patients. Alpha-glucosidase inhibitors must be avoided in patients with a glomerular filtration rate of less than 25 mL/min or those undergoing dialysis. Pioglitazone does not require dose adjustment but it has potentially adverse effects in this population. Dipeptidyl peptidase-4 inhibitors are effective and well tolerated. Of the latter, linagliptin does not require dose adjustment. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are not recommended in elderly patients with advanced kidney disease. Lastly, insulin therapy, particularly using the new insulin analogues, allows adequate management of hyperglycaemia in these patients, with different therapeutic regimens that must be individualised in order to avoid hypoglycaemia.

  2. Modeling Kidney Disease with iPS Cells.

    PubMed

    Freedman, Benjamin S

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and 'disease in a dish' laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field.

  3. Modeling Kidney Disease with iPS Cells

    PubMed Central

    Freedman, Benjamin S.

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and ‘disease in a dish’ laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field. PMID:26740740

  4. Ghrelin and leptin pathophysiology in chronic kidney disease.

    PubMed

    Gunta, Sujana S; Mak, Robert H

    2013-04-01

    Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD.

  5. Diabetic kidney disease: world wide difference of prevalence and risk factors

    PubMed Central

    Gheith, Osama; Farouk, Nashwa; Nampoory, Narayanan; Halim, Medhat A; Al-Otaibi, Torki

    2016-01-01

    Diabetic kidney disease – which is defined by elevated urine albumin excretion or reduced glomerular filtration rate (GFR) or both – is a serious complication that occurs in 20% to 40% of all diabetics. In this review we try to highlight the prevalence of diabetic nephropathy which is not uncommon complication of diabetes all over the world. The prevalence of diabetes worldwide has extended epidemic magnitudes and is expected to affect more than 350 million people by the year 2035. There is marked racial/ethnic besides international difference in the epidemiology of diabetic kidney disease which could be explained by the differences in economic viability and governmental infrastructures. Approximately one-third of diabetic patients showed microalbuminuria after 15 years of disease duration and less than half develop real nephropathy. Diabetic kidney disease (DKD) is more frequent in African-Americans, Asian-Americans, and Native Americans. Progressive kidney disease is more frequent in Caucasians patients with type 1 than type 2 diabetes mellitus (DM), although its overall prevalence in the diabetic population is higher in patients with type 2 DM while this type of DM is more prevalent. Hyperglycemia is well known risk factor for in addition to other risk factors like male sex, obesity, hypertension, chronic inflammation, resistance to insulin, hypovitaminosis D, and dyslipidemia and some genetic loci and polymorphisms in specific genes. Management of its modifiable risk factors might help in reducing its incidence in the nearby future. PMID:28197499

  6. Role of Bone Biopsy in Stages 3 to 4 Chronic Kidney Disease

    PubMed Central

    Gal-Moscovici, Anca; Sprague, Stuart M.

    2008-01-01

    Secondary hyperparathyroidism develops relatively early in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. The disease state in chronic kidney disease, which includes the histologic features of bone disease, defined as renal osteodystrophy, and the hormonal and biochemical disturbances, have recently been redefined as a disease syndrome and is referred to as “chronic kidney disease–mineral and bone disorder.” As chronic kidney disease progresses, specific histologic disturbances in the bone develop, which may or may not be predictable from the biochemical and hormonal changes that are associated with chronic kidney disease. In addition, patients may have had underlying bone disease before developing kidney failure or may have been treated with agents that will alter the classical pathologic findings of the bones in chronic kidney disease and their relation to parathyroid hormone. Thus, in stage 5 chronic kidney disease, bone biopsy with quantitative histomorphometric analysis is considered the gold standard in the diagnosis of renal osteodystrophy. In contrast to stage 5 chronic kidney disease, there are very few data on the histologic changes in bone in earlier stages of chronic kidney disease. There also is no adequate information on the etiopathogenesis of bone disease in stages 3 and 4 chronic kidney disease. Thus, because biochemical data cannot predict bone pathology in stages 3 and 4 chronic kidney disease, bone biopsy should be used to define these bone changes and to allow appropriate therapeutic approaches. PMID:18988703

  7. Role of Myeloperoxidase in Patients with Chronic Kidney Disease

    PubMed Central

    Kisic, Bojana; Miric, Dijana; Dragojevic, Ilija; Rasic, Julijana; Popovic, Ljiljana

    2016-01-01

    Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure. PMID:27127544

  8. Cadmium, diabetes and chronic kidney disease

    SciTech Connect

    Edwards, Joshua R. Prozialeck, Walter C.

    2009-08-01

    Recent epidemiological studies suggest a positive association between exposure to the environmental pollutant cadmium (Cd) and the incidence and severity of diabetes. In this review, we examine the literature suggesting a relationship between Cd exposure, elevated blood glucose levels, and the development of diabetes. In addition we review human and animal studies indicating that Cd potentiates or exacerbates diabetic nephropathy. We also review the various possible cellular mechanisms by which Cd may alter blood glucose levels. In addition, we present some novel findings from our own laboratories showing that Cd elevates fasting blood glucose levels in an animal model of subchronic Cd exposure before overt signs of renal dysfunction are evident. These studies also show that Cd reduces insulin levels and has direct cytotoxic effects on the pancreas. Together, these findings indicate that Cd may be a factor in the development of some types of diabetes and they raise the possibility that Cd and diabetes-related hyperglycemia may act synergistically to damage the kidney.

  9. Renin-angiotensin system in ureteric bud branching morphogenesis: implications for kidney disease.

    PubMed

    Yosypiv, Ihor V

    2014-04-01

    Failure of normal branching morphogenesis of the ureteric bud (UB), a key ontogenic process that controls organogenesis of the metanephric kidney, leads to congenital anomalies of the kidney and urinary tract (CAKUT), the leading cause of end-stage kidney disease in children. Recent studies have revealed a central role of the renin-angiotensin system (RAS), the cardinal regulator of blood pressure and fluid/electrolyte homeostasis, in the control of normal kidney development. Mice or humans with mutations in the RAS genes exhibit a spectrum of CAKUT which includes renal medullary hypoplasia, hydronephrosis, renal hypodysplasia, duplicated renal collecting system and renal tubular dysgenesis. Emerging evidence indicates that severe hypoplasia of the inner medulla and papilla observed in angiotensinogen (Agt)- or angiotensin (Ang) II AT 1 receptor (AT 1 R)-deficient mice is due to aberrant UB branching morphogenesis resulting from disrupted RAS signaling. Lack of the prorenin receptor (PRR) in the UB in mice causes reduced UB branching, resulting in decreased nephron endowment, marked kidney hypoplasia, urinary concentrating and acidification defects. This review provides a mechanistic rational supporting the hypothesis that aberrant signaling of the intrarenal RAS during distinct stages of metanephric kidney development contributes to the pathogenesis of the broad phenotypic spectrum of CAKUT. As aberrant RAS signaling impairs normal renal development, these findings advocate caution for the use of RAS inhibitors in early infancy and further underscore a need to avoid their use during pregnancy and to identify the types of molecular processes that can be targeted for clinical intervention.

  10. Bone imaging and fracture risk assessment in kidney disease.

    PubMed

    Jamal, Sophie A; Nickolas, Thomas L

    2015-06-01

    Fractures are more common and are associated with greater morbidity and morality in patients with kidney disease than in members of the general population. Thus, it is troubling that in chronic kidney disease (CKD) patients there has been a paradoxical increase in fracture rates over the past 20 years compared to the general population. Increased fracture incidence in CKD patients may be driven in part by the lack of screening for fracture risk. In the general population, dual energy X-ray absorptiometry (DXA) is the clinical standard to stratify fracture risk, and its use has contributed to decreases in fracture incidence. In contrast, in CKD, fracture risk screening with DXA has been uncommon due to its unclear efficacy in predicting fracture and its inability to predict type of renal osteodystrophy. Recently, several prospective studies conducted in patients across the spectrum of kidney disease have demonstrated that bone mineral density measured by DXA predicts future fracture risk and that clinically relevant information regarding fracture risk is provided by application of the World Health Organization cutoffs for osteopenia and osteoporosis to DXA measures. Furthermore, novel high-resolution imaging tools, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have been used to elucidate the effects of kidney disease on cortical and trabecular microarchitecture and bone strength and to identify potential targets for strategies that protect against fractures. This review will discuss the updated epidemiology of fractures in CKD, fracture risk screening by DXA, and the utility of state-of-the art imaging methods to uncover the effects of kidney disease on the skeleton.

  11. [Chronic kidney diseases do not always pass unnoticed].

    PubMed

    Alves, Cyrielle; Pruijma, Menno; Rotman, Samuel; Bonny, Olivier

    2016-02-24

    Kidney diseases are frequent, but most of the time, they develop unnoticed. This paucity of symptoms may lead to delayed diagnosis with important consequences on their outcome. Nevertheless, specific systemic signs such as skin lesions, joint pain or electrolytes disturbances may sometimes alert the clinician and direct the diagnosis to an underlying nephropathy. A high awareness of clinicians is warranted to recognize these red flags and diagnose these diseases early, as illustrated by two clinical cases discussed in this article.

  12. Metformin in Patients With Type 2 Diabetes and Kidney Disease

    PubMed Central

    Inzucchi, Silvio E.; Lipska, Kasia J.; Mayo, Helen; Bailey, Clifford J.; McGuire, Darren K.

    2015-01-01

    IMPORTANCE Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus

  13. Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

    PubMed

    Glassock, Richard J; Rule, Andrew D

    2016-01-01

    The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD.

  14. Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two South Indian families with primary hyperoxaluria type 1 causing later onset end-stage kidney disease

    PubMed Central

    Dutta, A. K.; Paulose, B. K.; Danda, S.; Alexander, S.; Tamilarasi, V.; Omprakash, S.

    2016-01-01

    Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase deficiency. Here, we describe two unrelated patients who were diagnosed to have primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation was detected in both the patients and the parents were found to be heterozygous carriers. Our patients developed end-stage renal disease at 23 years and 35 years of age. However, in the largest series published from OxalEurope cohort, the median age of end-stage renal disease for null mutations carriers was 9.9 years, which is much earlier than our cases. Our patients had slower progressions as compared to three unrelated patients from North India and Pakistan, who had homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further, patients need to be studied to find out if c.445_452delGTGCTGCT mutation represents a founder mutation in Southern India. PMID:27512303

  15. 77 FR 62520 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Ancillary Studies to Major Ongoing Clinical Research Studies..., Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research;...

  16. 75 FR 56552 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... need special assistance, such as sign language interpretation or other reasonable accommodations... Kidney Diseases Initial Review Group; Digestive Diseases and Nutrition C Subcommittee. Date: November...

  17. KIDNEY DISEASE GENETICS AND THE IMPORTANCE OF DIVERSITY IN PRECISION MEDICINE.

    PubMed

    Cooke Bailey, Jessica N; Wilson, Sarah; Brown-Gentry, Kristin; Goodloe, Robert; Crawford, Dana C

    2016-01-01

    Kidney disease is a well-known health disparity in the United States where African Americans are affected at higher rates compared with other groups such as European Americans and Mexican Americans. Common genetic variants in the myosin, heavy chain 9, non-muscle (MYH9) gene were initially identified as associated with non-diabetic end-stage renal disease in African Americans, and it is now understood that these variants are in strong linkage disequilibrium with likely causal variants in neighboring APOL1. Subsequent genome-wide and candidate gene studies have suggested that MYH9 common variants among others are also associated with chronic kidney disease and quantitative measures of kidney function in various populations. In a precision medicine setting, it is important to consider genetic effects or genetic associations that differ across racial/ethnic groups in delivering data relevant to disease risk or individual-level patient assessment. Kidney disease and quantitative trait-associated genetic variants have yet to be systematically characterized in multiple racial/ethnic groups. Therefore, to further characterize the prevalence of these genetic variants and their association with kidney related traits, we have genotyped 10 kidney disease or quantitative trait-associated single nucleotide polymorphisms (SNPs) (rs2900976, rs10505955, rs10502868, rs1243400, rs9305354, rs12917707, rs17319721, rs2467853, rs2032487, and rs4821480) in 14,998 participants from the population-based cross-sectional National Health and Nutrition Examination Surveys (NHANES) III and 1999-2002 as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study. In this general adult population ascertained regardless of health status (6,293 non-Hispanic whites, 3,013 non-Hispanic blacks, and 3,542 Mexican Americans), we observed higher rates of chronic kidney disease among non-Hispanic blacks compared with the other groups as expected. We performed single SNP tests of

  18. Cell therapy in kidney disease: cautious optimism... but optimism nonetheless.

    PubMed

    Zenovich, Andrey G; Taylor, Doris A

    2007-06-01

    The recently discovered therapeutic potential of stem or progenitor cells has initiated development of novel treatments in a number of diseases-treatments that could not only improve patients' quality of life, but also halt or even prevent disease progression. Hypertension; fluctuations in glycemia, electrolytes, nutrient levels, and circulating volume; and frequent infections and the associated inflammation all greatly impair the endothelium in patients undergoing peritoneal dialysis. As our understanding of the regulatory function of the endothelium advances, focus is increasingly being placed on endothelial repair in acute and chronic renal failure and after renal transplantation. The potential of progenitor cells to repair damaged endothelium and to reduce inflammation in patients with renal failure remains unexamined; however, a successful cell therapy could reduce morbidity and mortality in kidney disease. Important contributions have been made in identifying progenitor cell populations in the kidney, and further investigations into the relationships of these cells with the pathophysiology of the disease are underway. As the kidney disease field prepares for the first human trials of progenitor cell therapies, we deemed it important to review representative original research, and to share our perspectives and lessons learned from clinical trials of progenitor cell-based therapies that have commenced in patients with cardiovascular disease.

  19. Barriers to successful care for chronic kidney disease

    PubMed Central

    Lenz, Oliver; Mekala, Durga P; Patel, Daniel V; Fornoni, Alessia; Metz, David; Roth, David

    2005-01-01

    Background The National Kidney Foundation has formulated clinical practice guidelines for patients with chronic kidney disease (K/DOQI). However, little is know about how many patients actually achieve these goals in a dedicated clinic for chronic kidney disease. Methods We performed a cross-sectional analysis of 198 patients with an estimated glomerular filtration rate of less than 30 ml/min/1.73 m2 and determined whether K/DOQI goals were met for calcium, phosphate, calcium-phosphate product, parathyroid hormone, albumin, bicarbonate, hemoglobin, lipids, and blood pressure. Results We found that only a small number of patients achieved K/DOQI targets. Recent referral to the nephrologist, failure to attend scheduled clinic appointments, African American ethnicity, diabetes, and advanced renal failure were significant predictors of low achievement of K/DOQI goals. Conclusion We conclude that raising awareness of chronic kidney disease and K/DOQI goals among primary care providers, early referral to a nephrologist, the exploration of socioeconomic barriers and cultural differences, and both patient and physician education are critical to improve CKD care in patients with Stage 4 and 5 CKD. PMID:16250919

  20. Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease

    ClinicalTrials.gov

    2014-04-16

    Proteinuric Kidney Disease; Diabetic Nephropathy; Hypertensive Nephrosclerosis; IgA Nephropathy; Focal Segmental Glomerulosclerosis; Glomerulopathy (Obesity-associated); Glomerulonephritis, Membranous

  1. Modeling Red Blood Cell and Iron Dynamics in Patients with Chronic Kidney Disease

    DTIC Science & Technology

    2012-02-10

    Abstract Chronic kidney disease causes a slow loss of kidney function over time and can even- tually lead to End Stage Renal Disease, where a patient must...AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Chronic kidney disease causes a slow...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 1 Introduction It is estimated that 31 million Americans have chronic kidney disease ( CKD

  2. The Roles of Primary cilia in Polycystic Kidney Disease

    PubMed Central

    Kathem, Sarmed H.; Mohieldin, Ashraf M.; Nauli, Surya M.

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles of primary cilia in ADPKD. The primary cilia have been shown to have not only a mechanosensory function but also a chemosensory function. Both structural and functional defects in primary cilia result in cystic kidney disease and vascular hypertension. Thus, the mechanosenory and chemosensory functions will be analyzed in regards to ADPKD. PMID:25599087

  3. Kidney Disease and the Westernization and Industrialization of Food.

    PubMed

    Kramer, Holly

    2017-01-23

    The industrialization of food in the United States has led to lower prices, and families now spend a smaller percentage of their total income on food compared with past generations. The decline in prices for food commodities has led to sharp increases in food consumption, with average caloric intake in the United States now more than 500 calories higher per day compared to the 1970s. This increase in total food consumption has fueled the ongoing obesity epidemic, which in turn has likely played a role in the epidemic of end-stage renal disease during the last 2 decades. A close examination of dietary behaviors in the United States reveals high consumption of salt and animal protein, which negatively affects kidney disease progression. An interprofessional approach is necessary to address obesity, and studies are needed to identify best practices for integrating medical nutrition therapy into the long-term care of patients with chronic kidney disease.

  4. Foam Cells and the Pathogenesis of Kidney Disease

    PubMed Central

    Eom, Minseob; Hudkins, Kelly L.; Alpers, Charles E.

    2015-01-01

    Purpose of review Foam cells in human glomeruli can be encountered in various renal diseases including focal segmental glomerulosclerosis and diabetic nephropathy. Although foam cells are a key participant in atherosclerosis, surprisingly little is known about their pathogenicity in the kidney. We review our understanding (or lack thereof) of foam cells in the kidney as well as insights gained in studies of foam cells and macrophages involved in atherosclerosis, to suggest areas of investigation that will allow better characterization of the role of these cells in renal disease. Recent findings There is a general dearth of animal models of disease with renal foam cell accumulation, limiting progress in our understanding of the pathobiology of these cells. Recent genetic modifications of hyperlipidemic mice have resulted in some new disease models with renal foam cell accumulation. Recent studies have challenged older paradigms by findings that indicate many tissue macrophages are derived from cells permanently residing in the tissue from birth rather than circulating monocytes. Summary Renal foam cells remain an enigma. Extrapolating from studies of atherosclerosis suggests that therapeutics targeting mitochondrial ROS production or modulating cholesterol and lipoprotein uptake or egress from these cells may prove beneficial for kidney diseases in which foam cells are present. PMID:25887903

  5. Kidney disease physician workforce: where is the emerging pipeline?

    PubMed

    Pogue, Velvie A; Norris, Keith C; Dillard, Martin G

    2002-08-01

    A predicted increase in the number of patients with end-stage renal disease in coming years, coupled with significant numbers of qualified nephrologists reaching retirement age, will place great demands on the renal physician workforce. Action is required on several fronts to combat the predicted shortfall in full-time nephrologists. Of particular importance is the need to recruit and train greater numbers of physicians from ethnic minority groups. Changes in the demographics of kidney disease make it increasingly a disease of ethnic minorities and the poor. These demographic changes, together with the existing racial disparities in the diagnosis and treatment of kidney disease, highlight the specific need for nephrologists who are cognizant of the issues and barriers that prevent optimal care of high-risk minority populations. The current lack of academic role models and the drive by medical schools and residency programs to encourage minority group physicians to become primary care providers, rather than specialists, are issues that must be urgently addressed. Equally, changes in the training of renal fellows are required to merge the critical need for cutting edge research activity in renal science and with the insights and sensitivity to equip clinicians with the necessary skills for the team-based approach to patient care that increasingly characterizes the management and care of the patient with chronic kidney disease.

  6. Perspectives on Systems Biology Applications in Diabetic Kidney Disease

    PubMed Central

    Komorowsky, Claudiu V.; Brosius, Frank C.; Pennathur, Subramaniam; Kretzler, Matthias

    2012-01-01

    Diabetic kidney disease (DKD) is a microvascular complication of type 1 and 2 diabetes with a devastating impact on individuals with the disease, their families and society as a whole. DKD is the single most frequent cause of incident chronic kidney disease (CKD) cases and accounts for over 40% of the population with end stage renal disease (ESRD). Contributing factors for the high prevalence are the increase in obesity and subsequent diabetes combined with an improved long–term survival with diabetes. Environment and genetic variations contribute to DKD susceptibility and progressive loss of kidney function. How the molecular mechanisms of genetic and environmental exposures interact during DKD initiation and progression are the focus of ongoing research efforts. The development of standardized, unbiased high throughput profiling technologies of human DKD samples opens new avenues in capturing the multiple layers of DKD pathobiology. These techniques routinely interrogate analytes on a genome–wide scale generating comprehensive DKD associated fingerprints. Linking the molecular fingerprints to deep clinical phenotypes may ultimately elucidate the intricate molecular interplay in a disease stage and subtype specific manner. This insight will form the basis for accurate prognosis and facilitate targeted therapeutic interventions. In this review, we present ongoing efforts from large scale data integration translating “–omics” research efforts into improved and individualized health care in DKD. PMID:22733404

  7. Chronic kidney disease of unknown etiology in agricultural communities.

    PubMed

    Almaguer, Miguel; Herrera, Raúl; Orantes, Carlos M

    2014-04-01

    In recent years, Central America, Egypt, India and Sri Lanka have reported a high prevalence of chronic kidney disease of unknown etiology in agricultural communities, predominantly among male farmworkers. This essay examines the disease's case definitions, epidemiology (disease burden, demographics, associated risk factors) and causal hypotheses, by reviewing published findings from El Salvador, Nicaragua, Costa Rica, Sri Lanka, Egypt and India. The range of confirmed chronic kidney disease prevalence was 17.9%-21.1%. Prevalence of reduced glomerular filtration (<60 mL/min/1.73 m2 body surface area) based on a single serum creatinine measurement was 0%-67% men and 0%-57% women. Prevalence was generally higher in male farmworkers aged 20-50 years, and varied by community economic activity and altitude. Cause was unknown in 57.4%-66.7% of patients. The dominant histopathological diagnosis was chronic tubulointerstitial nephritis. Associations were reported with agricultural work, agrochemical exposure, dehydration, hypertension, homemade alcohol use and family history of chronic kidney disease. There is no strong evidence for a single cause, and multiple environmental, occupational and social factors are probably involved. Further etiological research is needed, plus interventions to reduce preventable risk factors.

  8. Bilineal Disease and Trans-Heterozygotes in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Pei, York; Paterson, Andrew D.; Wang, Kai Rong; He, Ning; Hefferton, Donna; Watnick, Terry; Germino, Greg G.; Parfrey, Patrick; Somlo, Stefan; St. George-Hyslop, Peter

    2001-01-01

    In searching for a putative third gene for autosomal dominant polycystic kidney disease (ADPKD), we studied the genetic inheritance of a large family (NFL10) previously excluded from linkage to both the PKD1 locus and the PKD2 locus. We screened 48 members of the NFL10 pedigree, by ultrasonography, and genotyped them, with informative markers, at both the PKD1 locus and the PKD2 locus. Twenty-eight of 48 individuals assessed were affected with ADPKD. Inspection of the haplotypes of these individuals suggested the possibility of bilineal disease from independently segregating PKD1 and PKD2 mutations. Using single-stranded conformational analysis, we screened for and found a PKD2 mutation (i.e., 2152delA; L736X) in 12 affected pedigree members. Additionally, when the disease status of these individuals was coded as “unknown” in linkage analysis, we also found, with markers at the PKD1 locus, significant LOD scores (i.e., >3.0). These findings strongly support the presence of a PKD1 mutation in 15 other affected pedigree members, who lack the PKD2 mutation. Two additional affected individuals had trans-heterozygous mutations involving both genes, and they had renal disease that was more severe than that in affected individuals who had either mutation alone. This is the first documentation of bilineal disease in ADPKD. In humans, trans-heterozygous mutations involving both PKD1 and PKD2 are not necessarily embryonically lethal. However, the disease associated with the presence of both mutations appears to be more severe than the disease associated with either mutation alone. The presence of bilineal disease as a confounder needs to be considered seriously in the search for the elusive PKD3 locus. PMID:11156533

  9. 78 FR 15728 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

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    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, DILIN Applications. Date: April 19, 2013. Time: 2:00 p.m. to 4:00... Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology...

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  1. 76 FR 30733 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Initial Review Group, Digestive Diseases and Nutrition C Subcommittee. Date: June 27-28... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National...

  2. 78 FR 5467 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

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    2013-01-25

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; LURN Telephone Review Panel. Date: February 26, 2013. Time: 12:00...; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and...

  3. 77 FR 33751 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

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    2012-06-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special; Emphasis Panel, Islet Transplant. Date: July 24, 2012. Time: 2:00 p.m. to 4:00 p... Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology...

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    ... Kidney Diseases Special Emphasis Panel, Epidemiology of Diabetes. Date: April 19, 2012. Time: 9 a.m. to... . Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, DP3 Reviews. Date: June 28-29,...

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    ... Committee: National Diabetes and Digestive and Kidney Diseases Advisory Council. Date: September 12, 2012... of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Blvd., Room 715, MSC 5452, Bethesda, MD... of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Blvd., Room 715, MSC 5452, Bethesda,...

  8. 76 FR 369 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

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  12. Renal resistive index and mortality in chronic kidney disease.

    PubMed

    Toledo, Clarisse; Thomas, George; Schold, Jesse D; Arrigain, Susana; Gornik, Heather L; Nally, Joseph V; Navaneethan, Sankar D

    2015-08-01

    Renal resistive index (RRI) measured by Doppler ultrasonography is associated with cardiovascular events and mortality in hypertensive, diabetic, and elderly patients. We studied the factors associated with high RRI (≥0.70) and its associations with mortality in chronic kidney disease patients without renal artery stenosis. We included 1962 patients with an estimated glomerular filtration rate of 15 to 59 mL/min per 1.73 m(2) who also had RRI measured (January 1, 2005, to October 2011) from an existing chronic kidney disease registry. Participants with renal artery stenosis (60%-99% or renal artery occlusion) were excluded. Multivariable logistic regression model was used to study factors associated with high RRI (≥0.70), and its association with mortality was studied using Kaplan-Meier plots and Cox proportional hazards model. Hypertension was prevalent in >90% of the patients. In the multivariable logistic regression, older age, female sex, diabetes mellitus, coronary artery disease, peripheral vascular disease, higher systolic blood pressure, and the use of β blockers were associated with higher odds of having RRI≥0.70. During a median follow-up of 2.2 years, 428 patients died. After adjusting for covariates, RRI≥0.70 was associated with increased mortality (adjusted hazard ratio, 1.29; 95% confidence interval, 1.02-1.65; P<0.05). This association was more pronounced among younger patients and those with stage 3 chronic kidney disease. Noncardiovascular/non-malignancy-related deaths were higher in those with RRI≥0.70. RRI≥0.70 is associated with higher mortality in hypertensive chronic kidney disease patients without clinically significant renal artery stenosis after accounting for other significant risk factors. Its evaluation may allow early identification of those who are at risk thereby potentially preventing or delaying adverse outcomes.

  13. IgG4-related kidney disease--A review.

    PubMed

    Pradhan, Dinesh; Pattnaik, Niharika; Silowash, Russell; Mohanty, Sambit Kumar

    2015-10-01

    IgG4-related disease (IgG4-RD) is a recently recognized systemic autoimmune disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive plasma cells in multiple organs. The condition was first described as a disease of the pancreas, and has since been recognized in various organ systems including the kidneys. IgG4 related kidney disease (IgG4-RKD) signifies any form of renal involvement by IgG4-RD. The most common renal involvement by IgG4-RD is tubulointerstitial nephritis. Glomerular disease, in particular membranous glomerulonephritis, may also be seen. Other co-existent glomerular diseases such as IgA nephropathy, membranoproliferative glomerulonephritis, and mesangioproliferative immune complex glomerulonephritis may be identified. IgG4-related plasma cell arteritis has also been noted in the kidney. As with IgG4-RD in general, IgG4 related kidney disease (IgG4-RKD) usually occurs in middle-aged to elderly men. Common findings in IgG4-RKD are plasma cell-rich interstitial inflammatory infiltrate either in a focal or diffuse pattern with increased IgG4+ plasma cells, expansile swirling interstitial fibrosis, high levels of serum IgG and IgG4, hypocomplementemia, high serum IgE levels and/or peripheral blood eosinophilia. By immunofluorescence, most of the cases show IgG4 dominant tubular basement membrane immune complex deposits. Similar to IgG4-RD, IgG4-RKD often shows a rapid response to steroid therapy. In this review, we discuss the current knowledge on IgG4-RKD and its clinical relevance.

  14. Kidney Failure: What to Expect

    MedlinePlus

    ... Kidneys & How They Work Kidney Disease A-Z Kidney Failure What is kidney failure and how is it treated? Kidney failure ... Methods for Kidney Failure: Peritoneal Dialysis . Peritoneal dialysis Kidney Transplant A kidney transplant places a healthy kidney ...

  15. Metabolic syndrome and chronic kidney disease.

    PubMed

    Bhowmik, D; Tiwari, S C

    2008-01-01

    Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.

  16. Development of a Targeted Urine Proteome Assay for Kidney Diseases

    PubMed Central

    Cantley, Lloyd G.; Colangelo, Christopher M.; Stone, Kathryn L.; Chung, Lisa; Belcher, Justin; Abbott, Thomas; Cantley, Jennifer L.; Williams, Kenneth R.; Parikh, Chirag R.

    2016-01-01

    Human urine is the least invasive and most readily available bio fluid whose proteome has been shown to change in response to disease or drug treatment. Urine is thus very amenable to quantitative proteomics and is a logical sample choice for identifying protein biomarkers for kidney diseases. In this study potential biomarkers were identified initially by using a multi-proteomics workflow to compare urine proteomes of kidney transplant patients who exhibited immediate versus delayed graft function. To comprehensively interrogate the urine proteome two “bottom up”, mass spectrometric-based discovery approaches, iTRAQ and Label Free Quantitation (LFQ), were complemented by Differential Fluorescence Gel Electrophoresis (DIGE) analyses of intact urine proteins from kidney transplant recipients who received a deceased donor kidney. Differentially expressed proteins in the two patient groups were identified, and corresponding stable isotope–labeled internal peptide standard (SIS) peptides were synthesized for scheduled multiple reaction monitoring (MRM). The Targeted Urine Proteome Assay (TUPA) was then developed by identifying those peptides for which there were at least 2 transitions for which interference in a urine matrix across 156 MRM runs was less than 30%. This resulted in a final assay that monitors 224 peptides corresponding to 167 quantifiable proteins. PMID:26220717

  17. Agalsidase alfa and kidney dysfunction in Fabry disease.

    PubMed

    West, Michael; Nicholls, Kathy; Mehta, Atul; Clarke, Joe T R; Steiner, Robert; Beck, Michael; Barshop, Bruce A; Rhead, William; Mensah, Robert; Ries, Markus; Schiffmann, Raphael

    2009-05-01

    In male patients with Fabry disease, an X-linked disorder of glycosphingolipid metabolism caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, kidney dysfunction becomes apparent by the third decade of life and invariably progresses to ESRD without treatment. Here, we summarize the effects of agalsidase alfa on kidney function from three prospective, randomized, placebo-controlled trials and their open-label extension studies involving 108 adult male patients. The mean baseline GFR among 54 nonhyperfiltrating patients (measured GFR <135 ml/min per 1.73 m(2)) treated with placebo was 85.4 +/- 29.6 ml/min per 1.73 m(2); during 6 mo of placebo, the mean annualized rate of change in GFR was -7.0 +/- 32.9 ml/min per 1.73 m(2). Among 85 nonhyperfiltrating patients treated with agalsidase alfa, the annualized rate of change was -2.9 +/- 8.7 ml/min per 1.73 m(2). Treatment with agalsidase alfa did not affect proteinuria. Multivariate analysis revealed that GFR and proteinuria category (< 1 or > or = 1 g/d) at baseline significantly predicted the rate of decline of GFR during treatment. This summary represents the largest group of male patients who had Fabry disease and for whom the effects of enzyme replacement therapy on kidney function have been studied. These data suggest that agalsidase alfa may stabilize kidney function in these patients.

  18. [Clinicopathological study of chronic kidney diseases (CKD)].

    PubMed

    Yoshida, Haruyoshi

    2012-02-01

    up-to-date information and techniques in clinical nephrology. From this hospital, I published a paper in Kidney International entitled, "Mesangiolytic glomerulopathy in severe congestive heart failure", based on the autopsy cases collected at the Pathology Department. This paper became a milestone in starting to study the role of chronic hypoxia in CKD. In 1999, I was elected as a professor of the Department of Clinical Laboratories, Faculty of Medicine, University of Fukui. In Fukui, I could extend my hypoxia study to cellular levels and diabetic mouse experiments in collaboration with Dr. Kimura, Dr. Li, Dr. Takahashi and many other doctors and technicians. When overviewing my research history, I realize that I was fortunate to be involved at the starting point of every laboratory with energetic mood and that I was supported and helped by many people.

  19. Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease.

    PubMed

    Nagura, Michito; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto; Uchida, Shunya

    2016-12-01

    Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid. Male Wistar rats were randomly assigned to three groups consisting of Nx group, oxonic acid-treated (Ox) group and sham-operated control group, and sacrificed at 8 weeks. Creatinine and UA were measured and the mRNA expressions of UA transporters in the kidney and intestine were evaluated by a real time PCR. UA transporters in the kidney sections were also examined by immunohistochemistry. Serum creatinine elevated in the Nx group whereas serum UA increased in the Ox group. Both the mRNA expression and the immunohistochemistry of the UA transporters were decreased in the Nx group, suggesting a marginal role in UA elevation in decreased kidney function. In contrast, the mRNA expression of Abcg2 in the ileum significantly increased in the Ox group. These results suggest that the upregulation of Abcg2 mRNA in the ileum triggered by an elevation of serum UA may play a compensatory role in increasing intestinal UA excretion.

  20. [Genetic kidney diseases: new perspectives on diagnosis].

    PubMed

    Bouatou, Yassine; Paoloni-Giacobino, Ariane; Parvex, Paloma; De Seigneux, Sophie

    2016-02-24

    Suspected renal inherited disorders are regularly evaluated in nephrology consultations both in adults and children. A positive family history and/or a typical phenotype should lead to genetic investigations. A confirmatory diagnosis integrated in a multidisciplinary genetic counseling approach gives patient guidance for further pregnancy. It also allows physician to better stratify disease risk and indicates treatment in some cases. The time to diagnosis and costs have been dramatically reduced thanks to next generation sequencing in several cases of complex inherited nephrologic syndromes.

  1. Diabetic kidney disease: a report from an ADA Consensus Conference.

    PubMed

    Tuttle, Katherine R; Bakris, George L; Bilous, Rudolf W; Chiang, Jane L; de Boer, Ian H; Goldstein-Fuchs, Jordi; Hirsch, Irl B; Kalantar-Zadeh, Kamyar; Narva, Andrew S; Navaneethan, Sankar D; Neumiller, Joshua J; Patel, Uptal D; Ratner, Robert E; Whaley-Connell, Adam T; Molitch, Mark E

    2014-10-01

    The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included (1) identification and monitoring, (2) cardiovascular disease and management of dyslipidemia, (3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, (4) glycemia measurement, hypoglycemia, and drug therapies, (5) nutrition and general care in advanced-stage chronic kidney disease, (6) children and adolescents, and (7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD.

  2. Proteomics approaches in the quest of kidney disease biomarkers.

    PubMed

    Frantzi, M; Bitsika, V; Charonis, A; Vlahou, A

    2011-01-01

    Proteomics refers to a group of analytical techniques for high throughput protein analysis, providing evidence for protein expression levels, subcellular localization, post-translational modifications and molecular interactions. As such, proteomics has contributed largely to our knowledge regarding molecular mechanisms underlying health and disease and pinpointed potential disease biomarkers. The scope of this review is to briefly introduce the principles of major proteomics techniques employed in biological research, including novel quantitative and molecular imaging mass spectrometry-based platforms. A few examples from the application of these techniques in biomarker discovery for kidney diseases are also provided.

  3. Vascular Stiffness in Children With Chronic Kidney Disease.

    PubMed

    Savant, Jonathan D; Betoko, Aisha; Meyers, Kevin E C; Mitsnefes, Mark; Flynn, Joseph T; Townsend, Raymond R; Greenbaum, Larry A; Dart, Allison; Warady, Bradley; Furth, Susan L

    2017-05-01

    Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m(2) Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.

  4. Interaction of Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease, with host proteins in the kidney of Salmo trutta.

    PubMed

    Kumar, Gokhlesh; Gotesman, Michael; El-Matbouli, Mansour

    2015-05-01

    Tetracapsuloides bryosalmonae (Myxozoa) is the causative agent of proliferative kidney disease in various species of salmonids which are found in Europe and North America. Less information about the interactions of T. bryosalmonae proteins with salmonid proteins during parasite development is known. In this study, anti-T. bryosalmonae monoclonal antibody-linked to N-hydroxysuccinimide-activated spin columns were used to purify parasite and host proteins from the kidneys of infected and non-infected brown trout (Salmo trutta) Linnaeus, 1758. The samples were next analyzed by electrospray ionization coupled to mass spectrometry to identify proteins that may be involved in the infection and proliferation of T. bryosalmonae within the brown trout host. A total of 6 parasite proteins and 40 different host proteins were identified in this analysis. The identified host proteins function in various processes, which include host defense, enzymatic, and structural components. In conjunction with modern molecular based tools, such siRNA, gene replacement, or gene disruption, this data can ultimately be used to develop novel control methods for T. bryosalmonae, based on the proteins or pathways identified in this study.

  5. Chronic kidney disease in children and adolescents in Brunei Darussalam

    PubMed Central

    Tan, Shi Ying; Naing, Lin; Han, Aye; Khalil, Muhammad Abdul Mabood; Chong, Vui Heng; Tan, Jackson

    2016-01-01

    AIM: To determine epidemiology of Bruneian paediatric chronic kidney disease (CKD) patients and factors that affect growth and progression of disease. METHODS: A cross-sectional study conducted on all children below 18 years old who were diagnosed with CKD over a ten year period (2004 to 2013). The reference population was all children (< 18 years old) suffering from CKD and attending the tertiary paediatric nephrology clinic in Brunei Darussalam. Demographic (current age, age of diagnosis, gender, ethnicity), anthropometric (weight and height), diagnosis, laboratory data (serum creatinine and haemoglobin, urinalysis) and blood pressure were extracted from the patients’ clinical case notes and recorded using a data collection form. RESULTS: The study revealed a high national prevalence [736 per million child population (pmcp)] and incidence (91 pcmp) of CKD. If CKD was defined at Stage 1, 2, 3, 4 or 5, the associated prevalence figures were 736, 132, 83, 50 and 33 pmcp. Glomerulonephritis accounted for 69% of all prevalent cases, followed by congenital abnormalities of kidney and urinary tract (20%) and tubulointerstitial diseases (8%). Minimal change disease being the most common histological diagnosis. The median age of diagnosis was 4.5 years, with congenital disease patients experiencing an earlier onset of diagnosis. A large proportion of patients were below the 5% percentile for height and weight. Non-glomerular diseases, adolescent and female patients were significantly associated with poor growth, but not glomerular filtration rate, age of diagnosis or steroid usage. CONCLUSION: Brunei has a high prevalence of chronic kidney disease in the paediatric population with glomerulonephritis being the most common disease. PMID:26981447

  6. Bisphenol a in chronic kidney disease.

    PubMed

    González-Parra, Emilio; Herrero, Jose Antonio; Elewa, Usama; Bosch, Ricardo J; Arduán, Alberto Ortiz; Egido, Jesus

    2013-01-01

    Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers. BPA is considered an environmental toxicant based on animal and cell culture studies. Japanese authorities recently banned BPA use in baby bottles based on observational association studies in newborns. BPA is excreted in urine and uremic patients present higher serum levels, but there is insufficient evidence to set cut-off levels or to link BPA to any harmful effect in CKD. However, the renal elimination and potential exposure during dialysis warrant the monitoring of BPA exposure and the design of observational studies in which the potential health risks of BPA for end-stage renal disease patients are evaluated.

  7. Bisphenol A in Chronic Kidney Disease

    PubMed Central

    González-Parra, Emilio; Herrero, Jose Antonio; Elewa, Usama; Arduán, Alberto Ortiz; Egido, Jesus

    2013-01-01

    Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers. BPA is considered an environmental toxicant based on animal and cell culture studies. Japanese authorities recently banned BPA use in baby bottles based on observational association studies in newborns. BPA is excreted in urine and uremic patients present higher serum levels, but there is insufficient evidence to set cut-off levels or to link BPA to any harmful effect in CKD. However, the renal elimination and potential exposure during dialysis warrant the monitoring of BPA exposure and the design of observational studies in which the potential health risks of BPA for end-stage renal disease patients are evaluated. PMID:23997953

  8. Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Protects Against Acute Kidney Injury-Mediated Chronic Kidney Disease: Role of Oxidative Stress.

    PubMed

    Lattenist, Lionel; Lechner, Sebastian M; Messaoudi, Smail; Le Mercier, Alan; El Moghrabi, Soumaya; Prince, Sonia; Bobadilla, Norma A; Kolkhof, Peter; Jaisser, Frédéric; Barrera-Chimal, Jonatan

    2017-05-01

    Acute kidney injury induced by ischemia/reperfusion (IR) is a frequent complication in hospitalized patients. Mineralocorticoid receptor antagonism has shown to be helpful against renal IR consequences; however, the potential benefit of novel nonsteroidal mineralocorticoid receptor antagonists such as finerenone has to be further explored. In this study, we evaluated the efficacy of finerenone to prevent the acute and chronic consequences of ischemic acute kidney injury. For the acute study (24 hours), 18 rats were divided into sham, bilateral renal ischemia of 25 minutes, and rats that received 3 doses of finerenone at 48, 24, and 1 hour before the ischemia. For the chronic study (4 months), 23 rats were divided into sham, rats that underwent 45 minutes of bilateral ischemia, and rats treated with finerenone at days 2 and 1 and 1 hour before IR. We found that after 24 hours of reperfusion, the untreated IR rats presented kidney dysfunction and tubular injury. Kidney injury molecule-1 and neutrophil gelatinase associated to lipolacin mRNA levels were increased. In contrast, the rats treated with finerenone displayed normal kidney function and significantly lesser tubular injury and kidney injury molecule-1 and neutrophil gelatinase associated to lipolacin levels. After 4 months, the IR rats developed chronic kidney disease, evidenced by kidney dysfunction, increased proteinuria and renal vascular resistance, tubular dilation, extensive tubule-interstitial fibrosis, and an increase in kidney transforming growth factor-β and collagen-I mRNA. The transition from acute kidney injury to chronic kidney disease was fully prevented by finerenone. Altogether, our data show that in the rat, finerenone is able to prevent acute kidney injury induced by IR and the chronic and progressive deterioration of kidney function and structure.

  9. Fatigue in chronic kidney disease: Definition, assessment and treatment.

    PubMed

    Zalai, Dora; Bohra, Miqdad

    2016-01-01

    Chronic fatigue--an overwhelming subjective feeling of mental or physical exhaustion--impacts patients' everyday functioning and quality of life, delays recovery after hemodialysis, and increases mortality. There are a number of factors that may perpetuate clinically significant fatigue among individuals with chronic kidney disease, including sleep disorders, depression, sedentary lifestyle, anemia, and chronic inflammation. Some of these factors (i.e., anemia and inflammation) are in the forefront of clinical attention, whereas the other contributing factors often remain unrecognized. This article provides a pragmatic overview of the definition, assessment, maintaining factors, and management of fatigue in chronic kidney disease. Given that chronic fatigue is a major determinant of patients' quality of life, nurses can bring about a fundamental improvement in patients' well-being if they recognize the most common fatigue-perpetuating factors and facilitate fatigue management interventions.

  10. Vasopressin receptor antagonists, heart failure, and polycystic kidney disease.

    PubMed

    Torres, Vicente E

    2015-01-01

    The synthesis of nonpeptide orally bioavailable vasopressin antagonists devoid of agonistic activity (vaptans) has made possible the selective blockade of vasopressin receptor subtypes for therapeutic purposes. Vaptans acting on the vasopressin V2 receptors (aquaretics) have attracted attention as a possible therapy for heart failure and polycystic kidney disease. Despite a solid rationale and encouraging preclinical testing, aquaretics have not improved clinical outcomes in randomized clinical trials for heart failure. Additional clinical trials with select population targets, more flexible dosing schedules, and possibly a different drug type or combination (balanced V1a/V2 receptor antagonism) may be warranted. Aquaretics are promising for the treatment of autosomal dominant polycystic kidney disease and have been approved in Japan for this indication. More studies are needed to better define their long-term safety and efficacy and optimize their utilization.

  11. Sexual and gonadal dysfunction in chronic kidney disease: Pathophysiology.

    PubMed

    Rathi, Manish; Ramachandran, Raja

    2012-03-01

    Sexual and gonadal dysfunction/infertility are quite common in patients with chronic kidney disease. Forty percent of male and 55% of female dialysis patients do not achieve orgasm. The pathophysiology of gonadal dysfunction is multifactorial. It is usually a combination of psychological, physiological, and other comorbid factors. Erectile dysfunction in males is mainly due to arterial factors, venous leakage, psychological factors, neurogenic factors, endocrine factors, and drugs. Sexual dysfunction in females is mainly due to hormonal factors and manifests mainly as menstrual irregularities, amenorrhea, lack of vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in chronic kidney disease is multipronged and an exact understanding of underlying pathology is essential in proper management of these patients.

  12. [Autosomal dominant polycystic kidney disease: is the treatment for tomorrow?].

    PubMed

    Cornec-Le Gall, Emilie; Le Meur, Yannick

    2014-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent Mendelian inherited disorder. It covers 6.1% of incident ESRD patients in France in 2011. Long left untreated, this disease will soon benefit from targeted therapies currently under evaluation. Several molecules have already reached the stage of clinical trials: the evaluation of mTOR inhibitors yielded deceiving results and, more recently, 2 different molecules demonstrated a slight impact on the progression of total kidney volume (TKV): tolvaptan, vasopressin receptor-V2 inhibitor and somatostatin analogues; both of these molecules acting throughout the decrease of intracellular AMPc. The purpose of this review is to briefly describe the signaling pathways involved, then to present both the published and ongoing clinical trials and the promising molecules evaluated in murine models.

  13. Identification of a novel AGXT gene mutation in primary hyperoxaluria after kidney transplantation failure.

    PubMed

    M'dimegh, Saoussen; Omezzine, Asma; Hamida-Rebai, Mériam Ben; Aquaviva-Bourdain, Cécile; M'barek, Ibtihel; Sahtout, Wissal; Zellama, Dorsaf; Souche, Geneviéve; Achour, Abdellatif; Abroug, Saoussen; Bouslama, Ali

    2016-11-01

    Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. The aim of this study was to determine the molecular etiology of kidney transplant loss in a young Tunisian individual. We present a young man with end-stage renal disease who received a kidney allograft and experienced early graft failure. There were no improvement in kidney function; he required hemodialysis and graft biopsy revealed calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Genetic study in the AGXT gene by PCR direct sequencing identified three missense changes in heterozygote state: the p. Gly190Arg mutation next to two other novels not previously described. The classification of the deleterious effect of the missense changes was developed using the summered results of four different mutation assessment algorithms, SIFT, PolyPhen, Mutation Taster, and Align-GVGD. This system classified the changes as polymorphism in one and as mutation in other. The patient was compound heterozygous mutations. Structural analysis showed that the novel mutation, p.Pro28Ser mutation, affects near the dimerization interface of AGT and positioned on binding site instead of the inhibitor, amino-oxyacetic acid (AOA). With the novel AGXT mutation, the mutational spectrum of this gene continues to broaden in our population. The diagnosis of PH1 was not recognized until after renal transplant with fatal consequences, which led us to confirm the importance of screening before planning for kidney transplantation in population with a relatively high frequency of AGXT mutation carriers.

  14. Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments.

    PubMed

    Watanabe, Sumiyo; Ogasawara, Toru; Tamura, Yoshifuru; Saito, Taku; Ikeda, Toshiyuki; Suzuki, Nobuchika; Shimosawa, Tatsuo; Shibata, Shigeru; Chung, Ung-Il; Nangaku, Masaomi; Uchida, Shunya

    2017-01-01

    Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct. The promoters of the three genes were linked to a GFP-coding fragment, the final constructs were then incorporated into an adenovirus vector, and this was then used to generate gene-manipulated viruses. After flushing circulating blood, viruses were directly injected into the renal arteries of rats and were allowed to site-specifically expression in tubule cells, and rats were then euthanized to obtain kidney tissues for immunohistochemistry. Double staining with adenovirus-derived EGFP and endogenous proteins were examined to verify orthotopic expression, i.e. "adenovirus driven NPT2a-EGFP and endogenous NHE3 protein", "adenovirus driven NKCC2-EGFP and endogenous NKCC2 protein" and "adenovirus driven AQP2-EGFP and endogenous AQP2 protein". Owing to a lack of finding good working anti-NPT2a antibody, an antibody against a different protein (sodium-hydrogen exchanger 3 or NHE3) that is also specifically expressed in the proximal tubule was used. Kidney structures were well-preserved, and other organ tissues did not show EGFP staining. Our gene transfer method is easier than using genetically engineered animals, and it confers the advantage of allowing the manipulation of gene transfer after birth. This is the first method to successfully target gene expression to specific cells in the kidney tubules. This study may serve as the first step for safe and effective gene

  15. Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments

    PubMed Central

    Watanabe, Sumiyo; Ogasawara, Toru; Tamura, Yoshifuru; Saito, Taku; Ikeda, Toshiyuki; Suzuki, Nobuchika; Shimosawa, Tatsuo; Shibata, Shigeru; Chung, Ung-il; Nangaku, Masaomi; Uchida, Shunya

    2017-01-01

    effective gene therapy in the kidney tubule diseases. PMID:28253301

  16. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2015-01-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed. PMID:26300611

  17. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease.

    PubMed

    Goldstein-Fuchs, Jordi; Kalantar-Zadeh, Kamyar

    2015-08-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed.

  18. Systems Biology of Polycystic Kidney Disease: a Critical Review

    PubMed Central

    Menezes, Luis Fernando; Germino, Gregory G

    2015-01-01

    The proliferation and diminishing costs of ‘omics’ approaches have finally opened the doors for small and medium laboratories to enter the ‘systems biology era’. This is a welcome evolution that requires a new framework to design, interpret and validate studies. Here we highlight some of the challenges, contributions, and prospects of the“cyst-ems biology” of polycystic kidney disease. PMID:25641951

  19. New oral anticoagulants in patients with chronic kidney disease.

    PubMed

    Belmar Vega, Lara; de Francisco, A L M; Bada da Silva, Jairo; Galván Espinoza, Luis; Fernández Fresnedo, Gema

    2016-12-08

    Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.

  20. Gut Microbiome and Kidney Disease in Pediatrics: Does Connection Exist?

    PubMed

    Vasylyeva, Tetyana L; Singh, Ruchi

    2016-01-01

    Child development is a unique and continuous process that is impacted by genetics and environmental factors. Gut microbiome changes with development and depends on the stage of gut maturation, nutrition, and overall health. In spite of emerging data and active study in adults, the gut-renal axis in pediatrics has not been well considered and investigated. This review will focus on the current knowledge of gut microbiota impacts on kidney disease with extrapolation to the pediatric population.