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Sample records for kidney disease gene

  1. Kidney Disease

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? 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 ...

  2. Kidney Diseases

    MedlinePlus

    ... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

  3. Kidney Diseases

    MedlinePlus

    ... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You are at greater risk for kidney disease if you have diabetes, high blood pressure, or ...

  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. PKDB: Polycystic Kidney Disease Mutation Database--a gene variant database for autosomal dominant polycystic kidney disease.

    PubMed

    Gout, Alexander M; Martin, Neilson C; Brown, Alastair F; Ravine, David

    2007-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) arises from mutations in the PKD1 and PKD2 genes. The Polycystic Kidney Disease Mutation Database (PKDB) is an internet-accessible relational database containing comprehensive information about germline and somatic disease-causing variants within these two genes, as well as polymorphisms and variants of indeterminate pathogenicity. The PKDB database structure incorporates an interface between these gene variant data and any associated patient clinical data. An initiative of the Polycystic Kidney Disease Foundation, PKDB is a publicly accessible database that aims to streamline the evaluation of PKD1 and PKD2 gene variants detected in samples from those with ADPKD, as well as to assist ongoing clinical and molecular research in the field. As the accurate reporting of nucleotide variants is essential for ensuring the quality of data within PKDB, a mutation checker has been mounted on the PKDB server allowing contributors to assess the accuracy of their PKD1 and PKD2 variant reports. Researchers and clinicians may submit their PKD1/PKD2 gene variants and any associated deidentified clinical data via standardized downloadable data entry forms accessible through the PKDB site. PKDB has been launched with the full details of PKD1 and PKD2 gene variant reports published in 73 peer-reviewed articles. Through a series of user-friendly advanced search facilities, users are able to query the database as required. The PKDB server is accessible at http://pkdb.mayo.edu. PMID:17370309

  6. A transducin-like gene maps to the autosomal dominant polycystic kidney disease gene region

    SciTech Connect

    Weinstat-Saslow, D.L.; Reeders, S.T.; Germino, G.G.; Somlo, S. )

    1993-12-01

    A novel human gene (sazD) that maps to the autosomal dominant polycystic kidney disease region shares sequence similarity with members of the [beta]-transducin superfamily. The cDNA sazD-c predicts an [approximately]58-kDa protein (sazD) with seven internal repeats, similar to the WD-40 motif of the transducin family. The size of this protein family has been expanding rapidly; however, neither the structure nor the function of this repeated motif is known. Preliminary data do not suggest that sazD is mutated in patients with polycystic kidney disease. 13 refs., 2 figs.

  7. HIV and Kidney Disease

    MedlinePlus

    ... FOR KIDNEY DISEASE? HIV MEDICATIONS AND THE KIDNEYS DIALYSIS AND KIDNEY TRANSPLANTATION THE BOTTOM LINE WHY SHOULD ... disease (ESRD) or kidney failure. This can require dialysis or a kidney transplant. The rate of kidney ...

  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. 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.

  10. A novel cyclin gene (CCNF) in the region of the polycystic kidney disease gene (PKD1)

    SciTech Connect

    Kraus, B.; Pohlschmidt, M.; Leung, L.S.

    1994-11-01

    The major locus for autosomal dominant polycystic kidney disease (PKD1) is located in a gene-rich region on chromosome 16p13.3. Recently the identification of the gene responsible for PKD1 has been described. While searching for candidate genes in this region, the authors isolated a new member of the cyclin family. They have characterized the transcript by sequencing, determination of the exon intron boundaries, and Northern blot analysis. Cyclin F is related to A- and B-type cyclins by sequence, but its function is unknown.

  11. Chronic Kidney Diseases

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes 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 ...

  12. Polycystic Kidney Disease (PKD)

    MedlinePlus

    MENU Return to Web version Polycystic Kidney Disease Overview What is polycystic kidney disease? Polycystic kidney disease (PKD) is an inherited disease that affects the kidneys. Sacs of fluid (called ...

  13. 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 ...

  14. Chronic kidney disease

    MedlinePlus

    Chronic kidney disease is the slow loss of kidney function over time. The main job of the kidneys is to ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some time. ...

  15. Kidney Disease Basics

    MedlinePlus

    ... Links Take the first step Alternate Language URL Kidney Disease Basics Page Content Your kidneys filter extra water ... blood pressure are the most common causes of kidney disease. ​These conditions can slowly damage the kidneys over ...

  16. Testing for Kidney Disease

    MedlinePlus

    ... Education Program > Learn About Kidney Disease > What Causes Kidney Disease? > Testing for Kidney Disease | Share External Link Disclaimer What ... from our online catalog . Alternate Language URL Español Testing for Kidney Disease Page Content Early kidney disease usually does not ...

  17. 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. PMID:26722532

  18. 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

  19. [Cystic kidney diseases].

    PubMed

    Zerres, K; Ortiz Brüchle, N

    2012-04-01

    Cystic kidney diseases are clinically and genetically heterogeneous. The most important entities are autosomal-dominant and autosomal-recessive polycystic kidney diseases. The proteins encoded by the involved genes are referred to as cystoproteins, which are located predominantly in the primary cilia. Primary cilia play an important role in cyst formation. Inherited polycystic kidney diseases belong to the increasing number of reported ciliopathies, including several syndromic entities. An exact diagnosis is the basis for medical care and genetic counselling; thus, the diagnostic algorithm should include clinical, ultrasonographic and morphological features of the underlying kidney disease, knowledge about further features and family history. Molecular genetic testing may contribute important information towards a definite diagnosis. PMID:22410941

  20. Diabetes and Kidney Disease

    MedlinePlus

    ... Disease, and Other Dental Problems Diabetic Eye Disease Diabetes and Kidney Disease What are my kidneys and ... urine until releasing it through urination. How can diabetes affect my kidneys? Too much glucose , also called ...

  1. Diabetes and Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  2. Pregnancy and Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  3. About Chronic Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  4. Chronic kidney disease

    MedlinePlus

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some ...

  5. 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 ...

  6. Kidney Disease (Nephropathy)

    MedlinePlus

    ... or to have the blood filtered by machine (dialysis). Who Gets Kidney Disease? Not everyone with diabetes ... health care team. Kidney Failure Once kidneys fail, dialysis is necessary. The person must choose whether to ...

  7. Acquired Cystic Kidney Disease

    MedlinePlus

    ... a kidney transplant or blood-filtering treatments called dialysis. The cysts are more likely to develop in people who are on kidney dialysis. The chance of developing acquired cystic kidney disease ...

  8. 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.

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

    PubMed

    Coady, Alison M; Murray, Anthony L; Elliott, Diane G; Rhodes, Linda D

    2006-04-01

    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. PMID:16597972

  10. Both msa Genes in Renibacterium salmoninarum Are Needed for Full Virulence in Bacterial Kidney Disease

    PubMed Central

    Coady, Alison M.; Murray, Anthony L.; Elliott, Diane G.; Rhodes, Linda 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. PMID:16597972

  11. 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

  12. Genetic kidney diseases

    PubMed Central

    Hildebrandt, Friedhelm

    2010-01-01

    Knowledge of the primary cause of a disease is essential for understanding its mechanisms and for adequate classification, prognosis, and treatment. Recently, the etiologies of many kidney diseases have been revealed as single-gene defects. This is exemplified by steroid-resistant nephrotic syndrome, which is caused by podocin mutations in ~25% of childhood and ~15% of adult cases. Knowledge of a disease-causing mutation in a single-gene disorder represents one of the most robust diagnostic examples of “personalized medicine”, because the mutation conveys an almost 100% risk of developing the disease by a certain age. Whereas single-gene diseases are rare disorders, polygenic “risk alleles” are found in common adult-onset diseases. This review will discuss prominent renal single-gene kidney disorders and polygenic risk alleles of common disorders. We delineate how emerging techniques of total exome capture and large-scale sequencing will facilitate molecular genetic diagnosis, prognosis and specific therapy and lead to a better understanding of disease mechanisms, thus enabling development of new targeted drugs. PMID:20382325

  13. A microbial TRP-like polycystic-kidney-disease-related ion channel gene

    PubMed Central

    Palmer, Christopher P.; Aydar, Ebru; Djamgoz, Mustafa B. A.

    2004-01-01

    Ion channel genes have been discovered in many microbial organisms. We have investigated a microbial TRP (transient receptor potential) ion channel gene which has most similarity to polycystic-kidney-disease-related ion channel genes. We have shown that this gene (pkd2) is essential for cellular viability, and is involved in cell growth and cell wall synthesis. Expression of this gene increases following damage to the cell wall. This fission yeast pkd2 gene, orthologues of which are found in all eukaryotic cells, appears to be a key signalling component in the regulation of cell shape and cell wall synthesis in yeast through an interaction with a Rho1-GTPase. A model for the mode of action of this Schizosaccharomyces pombe protein in a Ca2+ signalling pathway is hypothesized. PMID:15537393

  14. At Risk for Kidney Disease?

    MedlinePlus

    ... or organization Alternate Language URL At Risk for Kidney Disease? Page Content You are at risk for kidney ... failure by treating kidney disease early. Diabetes and Kidney Disease Diabetes is the leading cause of kidney failure. ...

  15. 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

  16. Polycystic Kidney Disease

    MedlinePlus

    ... and requires immediate medical attention. [ Top ] How do health care providers diagnose autosomal dominant polycystic kidney disease? Health ... when test results are available. [ Top ] How do health care providers treat autosomal dominant polycystic kidney disease? Although ...

  17. Kidney Disease of Diabetes

    MedlinePlus

    ... Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Español Kidney Disease of Diabetes Page Content On this page: The ... and Human Services, 2008. [ Top ] The Course of Kidney Disease Diabetic kidney disease takes many years to develop. ...

  18. Linkage disequilibrium in the region of the autosomal dominant polycystic kidney disease gene (PKD1)

    SciTech Connect

    Snarey, A. ); Thomas, S.; Harris, P.C. ); Schneider, M.C. ); Pound, S.E.; Wright, A.F. ); Barton, N.; Somlo, S.; Germino, G.G.; Reeders, S.T.

    1994-08-01

    The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6 prox). This region is 750 kb long and has been cloned. The authors have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. They report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Their results favor a location of the PKD1 gene in the proximal part of the candidate region. 25 refs., 1 fig., 4 tabs.

  19. Complement factor H gene associations with end-stage kidney disease in African Americans

    PubMed Central

    Bonomo, Jason A.; Palmer, Nicholette D.; Hicks, Pamela J.; Lea, Janice P.; Okusa, Mark D.; Langefeld, Carl D.; Bowden, Donald W.; Freedman, Barry I.

    2014-01-01

    Background Mutations in the complement factor H gene (CFH) region associate with renal-limited mesangial proliferative forms of glomerulonephritis including IgA nephropathy (IgAN), dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Lack of kidney biopsies could lead to under diagnosis of CFH-associated end-stage kidney disease (ESKD) in African Americans (AAs), with incorrect attribution to other causes. A prior genome-wide association study in AAs with non-diabetic ESKD implicated an intronic CFH single nucleotide polymorphism (SNP). Methods Thirteen CFH SNPs (8 exonic, 2 synonymous, 2 3′UTR, and the previously associated intronic variant rs379489) were tested for association with common forms of non-diabetic and type 2 diabetes-associated (T2D) ESKD in 3770 AAs (1705 with non-diabetic ESKD, 1305 with T2D-ESKD, 760 controls). Most cases lacked kidney biopsies; those with known IgAN, DDD or C3GN were excluded. Results Adjusting for age, gender, ancestry and apolipoprotein L1 gene risk variants, single SNP analyses detected 6 CFH SNPs (5 exonic and the intronic variant) as significantly associated with non-diabetic ESKD (P = 0.002–0.01), three of these SNPs were also associated with T2D-ESKD. Weighted CFH locus-wide Sequence Kernel Association Testing (SKAT) in non-diabetic ESKD (P = 0.00053) and T2D-ESKD (P = 0.047) confirmed significant evidence of association. Conclusions CFH was associated with commonly reported etiologies of ESKD in the AA population. These results suggest that a subset of cases with ESKD clinically ascribed to the effects of hypertension or glomerulosclerosis actually have CFH-related forms of mesangial proliferative glomerulonephritis. Genetic testing may prove useful to identify the causes of renal-limited kidney disease in patients with ESKD who lack renal biopsies. PMID:24586071

  20. Diabetes and kidney disease

    MedlinePlus

    Diabetic nephropathy; Nephropathy - diabetic; Diabetic glomerulosclerosis; Kimmelstiel-Wilson disease ... Diabetic kidney disease is a major cause of sickness and death in people with diabetes. It can ...

  1. 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- ...

  2. 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- ...

  3. Refined localisation of the second gene for autosomal dominant polycystic kidney disease

    SciTech Connect

    Peters, D.J.M.; Saris, J.J.; Spruit, L.

    1994-09-01

    The PKD1-gene responsible for autosomal dominant polycystic kidney disease in 85% of the families maps to chromosome 16q13. Last year the PKD2-gene was localized on chromosome 4q21-23 between the markers D4S231 and D4S231 and D4S423, an interval of about 8cM. In a collaborative effort to narrow down the PKD2-region, families with recombinants have been analyzed with several markers within the interval. First, an integrated map had to be constructed which contains previously published markers of different sources. To construct this map, cosmids and/or YACs isolated with the markers have been mapped by two-color FISH and were screened with the other markers. Affected recombinants localize the disease between D4S1534 and D4S1544.

  4. Gene expression programs of mouse endothelial cells in kidney development and disease.

    PubMed

    Brunskill, Eric W; Potter, S Steven

    2010-01-01

    Endothelial cells are remarkably heterogeneous in both morphology and function, and they play critical roles in the formation of multiple organ systems. In addition endothelial cell dysfunction can contribute to disease processes, including diabetic nephropathy, which is a leading cause of end stage renal disease. In this report we define the comprehensive gene expression programs of multiple types of kidney endothelial cells, and analyze the differences that distinguish them. Endothelial cells were purified from Tie2-GFP mice by cell dissociation and fluorescent activated cell sorting. Microarrays were then used to provide a global, quantitative and sensitive measure of gene expression levels. We examined renal endothelial cells from the embryo and from the adult glomerulus, cortex and medulla compartments, as well as the glomerular endothelial cells of the db/db mutant mouse, which represents a model for human diabetic nephropathy. The results identified the growth factors, receptors and transcription factors expressed by these multiple endothelial cell types. Biological processes and molecular pathways were characterized in exquisite detail. Cell type specific gene expression patterns were defined, finding novel molecular markers and providing a better understanding of compartmental distinctions. Further, analysis of enriched, evolutionarily conserved transcription factor binding sites in the promoters of co-activated genes begins to define the genetic regulatory network of renal endothelial cell formation. Finally, the gene expression differences associated with diabetic nephropathy were defined, providing a global view of both the pathogenic and protective pathways activated. These studies provide a rich resource to facilitate further investigations of endothelial cell functions in kidney development, adult compartments, and disease. PMID:20706631

  5. Gene Expression Programs of Mouse Endothelial Cells in Kidney Development and Disease

    PubMed Central

    Brunskill, Eric W.; Potter, S. Steven

    2010-01-01

    Endothelial cells are remarkably heterogeneous in both morphology and function, and they play critical roles in the formation of multiple organ systems. In addition endothelial cell dysfunction can contribute to disease processes, including diabetic nephropathy, which is a leading cause of end stage renal disease. In this report we define the comprehensive gene expression programs of multiple types of kidney endothelial cells, and analyze the differences that distinguish them. Endothelial cells were purified from Tie2-GFP mice by cell dissociation and fluorescent activated cell sorting. Microarrays were then used to provide a global, quantitative and sensitive measure of gene expression levels. We examined renal endothelial cells from the embryo and from the adult glomerulus, cortex and medulla compartments, as well as the glomerular endothelial cells of the db/db mutant mouse, which represents a model for human diabetic nephropathy. The results identified the growth factors, receptors and transcription factors expressed by these multiple endothelial cell types. Biological processes and molecular pathways were characterized in exquisite detail. Cell type specific gene expression patterns were defined, finding novel molecular markers and providing a better understanding of compartmental distinctions. Further, analysis of enriched, evolutionarily conserved transcription factor binding sites in the promoters of co-activated genes begins to define the genetic regulatory network of renal endothelial cell formation. Finally, the gene expression differences associated with diabetic nephropathy were defined, providing a global view of both the pathogenic and protective pathways activated. These studies provide a rich resource to facilitate further investigations of endothelial cell functions in kidney development, adult compartments, and disease. PMID:20706631

  6. 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.

  7. Diabetes and kidney disease

    MedlinePlus

    ... occurs over time in people with diabetes. This type of kidney disease is called diabetic nephropathy. Causes Each kidney is made of hundreds ... ACE inhibitors Diabetes - what to ask your doctor - type 2 Update Date ... Diabetic Kidney Problems Browse the Encyclopedia A.D.A. ...

  8. Mutation analysis of the polycystic kidney disease 1 (PKD1) gene

    SciTech Connect

    Peral, B.; Ward, C.J.; Thomas, S.

    1994-09-01

    The gene which is mutated in most cases of autosomal dominant polycystic kidney disease (ADPKD), PKD1, has recently been identified on chromosome 16. Three quarters of this gene lies in a region of genomic DNA that is duplicated elsewhere on chromosome 16. Consequently, the search for mutations has proved difficult and our efforts so far have concentrated on screening the single copy 3{prime} region of the gene. We have employed the methods of field inversion gel electrophoresis, conventional Southern blotting, RT-PCR and heteroduplex analysis. From the examination of DNA of approximately 300 PKD1 patients, two deletions have been identified. One is a 5.5 kb genomic deletion, which is transmitted with the disease and results in a 3 kb deletion of the PKD1 transcript. The other is a de novo genomic deletion of 2 kb which removes {approximately}500 bp of the transcript. In addition, analysis of lymphoblast RNA by RT-PCR from 50 patients has revealed one splicing mutation resulting in the removal of a 135 bp exon. Further analysis of the single copy region of this gene is underway and strategies to screen the duplicated area of the gene for mutations are being explored.

  9. 2008 Homer W. Smith Award: insights into the pathogenesis of polycystic kidney disease from gene discovery.

    PubMed

    Harris, Peter C

    2009-06-01

    Polycystic kidney diseases (PKD) are a group of inherited disorders characterized by morbidity-associated development of renal cysts. Three forms of PKD are described here: The common, late onset, autosomal dominant PKD (ADPKD); the mainly infantile, autosomal recessive PKD (ARPKD); and the lethal, syndromic, Meckel syndrome that also includes central nervous system and digital defects. Positional cloning approaches based on genetic linkage have identified the disease genes in these disorders. Completion of the Human Genome Project, cases with atypical mutation, and animal models have greatly aided gene identification, and characterization of the disease genes has allowed establishment of molecular diagnostics. Genetic and allelic heterogeneity, plus genetic modification, underlie the significant phenotypic variability in each disorder. Positional cloning identified novel disease-associated protein families: The polycystins (ADPKD); fibrocystins (ARPKD); and meckelin. A common feature of pathogenesis in each disorder seems to be the primary cilia, implicating detection of fluid flow and the developmental process of planar cell polarity. Identifying the primary defect has contributed to our understanding of defective cellular processes and highlights potential therapeutic targets. A number of agents are now in Phase 3 trials, and many others show promise preclinically, providing hope of effective treatments for ADPKD in the foreseeable future. PMID:19423684

  10. Amyloidosis and Kidney Disease

    MedlinePlus

    ... Foundation Genetic and Rare Diseases Information Center MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... PDF, 345 KB)​​​​​ Alternate Language URL Amyloidosis and Kidney Disease Page Content On this page: What is ...

  11. Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice.

    PubMed

    Lantinga-van Leeuwen, Irma S; Leonhard, Wouter N; van der Wal, Annemieke; Breuning, Martijn H; de Heer, Emile; Peters, Dorien J M

    2007-12-15

    Autosomal dominant polycystic kidney disease, caused by mutations in the PKD1 gene, is characterized by progressive deterioration of kidney function due to the formation of thousands of cysts leading to kidney failure in mid-life or later. How cysts develop and grow is currently unknown, although extensive research revealed a plethora of cellular changes in cyst lining cells. We have constructed a tamoxifen-inducible, kidney epithelium-specific Pkd1-deletion mouse model. Upon administration of tamoxifen to these mice, a genomic fragment containing exons 2-11 of the Pkd1-gene is specifically deleted in the kidneys and cysts are formed. Interestingly, the timing of Pkd1-deletion has strong effects on the phenotype. At 1 month upon gene disruption, adult mice develop only a very mild cystic phenotype showing some small cysts and dilated tubules. Young mice, however, show massive cyst formation. In these mice, at the moment of gene disruption, cell proliferation takes place to elongate the nephron. Our data indicate that Pkd1 gene deficiency does not initiate sufficient autonomous cell proliferation leading to cyst formation and that additional stimuli are required. Furthermore, we show that one germ-line mutation of Pkd1 is already associated with increased proliferation. PMID:17932118

  12. Identification of the autosomal dominant polycystic kidney disease gene, PKD1

    SciTech Connect

    Schneider, M.C.; Zhang, F.; Geng, L.

    1994-09-01

    The PKDl gene was localized to an {approximately}480 kb interval of chromosome 16pl3. More than 20 independent transcripts were found in the interval. In view of the high new mutation rate in autosomal dominant polycystic kidney diseases (ADPKD), we anticipated the PKD1 gene would be large. The largest transcript in the region was represented by five cDNA clones located adjacent to the tuberin gene (TSC2). Two of these clones, KG8 and NKG9, contain {approximately}4.5 kb of contiguous sequence corresponding to the 3{prime} end of the 14 kb mRNA which is transcribed from telomeric to centromeric. They spans 11 exons, and to evaluate the reading frame of the cDNA, we have compared the human and monkey sequence using human primers, and found 90-94% identity at the DNA level, and by observing amino acid conservation, determined the reading frame. To date, our open-reading frame of {approximately}800 amino-acids contained only a potential threonine kinase site, but no other recognizable peptide motifs or repeats, and was not homologous to sequences in Swissprot and GenBank. No Southern blot abnormalities have been detected with the cDNA probes used. However, an exon-by-exon scan of 8 exons for mutations by SSCP and genomic sequencing (predicted missense changes) has identified 3 patients with mutations not found in normals, and identify the KG8 gene as the PKD1 gene.

  13. Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    PubMed Central

    Yoshihara, Daisuke; Kugita, Masanori; Yamaguchi, Tamio; Aukema, Harold M.; Kurahashi, Hiroki; Morita, Miwa; Hiki, Yoshiyuki; Calvet, James P.; Wallace, Darren P.; Toyohara, Takafumi; Abe, Takaaki; Nagao, Shizuko

    2012-01-01

    Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. PMID:22666229

  14. Identification of Gene Mutations in Autosomal Dominant Polycystic Kidney Disease through Targeted Resequencing

    PubMed Central

    Hopp, Katharina; Sikkink, Robert A.; Sundsbak, Jamie L.; Lee, Yean Kit; Kubly, Vickie; Eckloff, Bruce W.; Ward, Christopher J.; Winearls, Christopher G.; Torres, Vicente E.; Harris, Peter C.

    2012-01-01

    Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant polycystic kidney disease (ADPKD). The duplication of PKD1 exons 1–32 as six pseudogenes on chromosome 16, the high level of allelic heterogeneity, and the cost of Sanger sequencing complicate mutation analysis, which can aid diagnostics of ADPKD. We developed and validated a strategy to analyze both the PKD1 and PKD2 genes using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries. We used this approach to characterize a cohort of 230 patients with ADPKD. This process detected definitely and likely pathogenic variants in 115 (63%) of 183 patients with typical ADPKD. In addition, we identified atypical mutations, a gene conversion, and one missed mutation resulting from allele dropout, and we characterized the pattern of deep intronic variation for both genes. In summary, this strategy involving next-generation sequencing is a model for future genetic characterization of large ADPKD populations. PMID:22383692

  15. National Kidney Disease Education Program

    MedlinePlus

    ... from our online catalog . Alternate Language URL National Kidney Disease Education Program (NKDEP) Page Content Improving the ... kidney disease. Minorities Are at Higher Risk for Kidney Disease. If you are African American, Hispanic, or ...

  16. National Kidney Disease Education Program

    MedlinePlus

    ... from our online catalog . Alternate Language URL National Kidney Disease Education Program (NKDEP) Page Content Improving the understanding, ... kidney disease. Minorities Are at Higher Risk for Kidney Disease. If you are African American, Hispanic, or American ...

  17. Diabetes and Chronic Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  18. Sexuality and Chronic Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  19. Staying Fit with Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  20. 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.

  1. The polycystic kidney disease 1 gene lies in a duplicated genomic region

    SciTech Connect

    Ward, C.J.; Hughes, J.; Peral, B. |

    1994-09-01

    The polycystic kidney disease 1 (PKD1) gene is situated in chromosomal band 16p13.3 and encodes a 14 kb transcript. The 5{prime} region of the PKD1 gene is located within a 40-50 kb stretch of genomic DNA which is duplicated several times in the more proximal region, 16p13.1. This proximal area gives rise to at least three transcripts designated homologous gene A (HG-A; 21 kb), HG-B (17 kb) and HG-C (8.5 kb). These three transcripts share substantial homology with each other and the PKD1 transcript. However, the 3{prime} 3.8 kb section of the PKD1 transcript is unique because it is encoded by a region of the gene that lies outside the duplicated area. The presence of the duplicate transcripts in all tissues analyzed has hampered attempts to clone and sequence the bone fide PKD1 gene. Comparison of cDNAs known to arise from the PKD1 transcript to those from the HG transcripts reveals that divergence of 2-3% has occurred between these sequences. To overcome the problem of the duplication, a large 15 kb section of genomic DNA has been sequenced together with several large HG cDNAs. Utilizing a radiation hybrid which contains only the 16p13.3 region and expresses low levels of the PKD1 transcript, we are now attempting to clone the duplicated part of the PKD1 gene by exon linking.

  2. Chronic Kidney Disease and Medicines

    MedlinePlus

    ... our online catalog. Alternate Language URL Español Chronic Kidney Disease and Medicines: What You Need to Know Page ... you need to know Because you have chronic kidney disease, you should take steps to protect your kidneys. ...

  3. Kidney Disease and Diabetes

    MedlinePlus

    ... Blood Pressure Tools & Resources Stroke More Kidney Disease & Diabetes Updated:Jan 26,2016 One of the more ... thereafter.) This content was last reviewed January 2016. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  4. Neonatal polycystic kidney disease.

    PubMed

    Verghese, Priya; Miyashita, Yosuke

    2014-09-01

    This article provides an up-to-date comprehensive review and summary on neonatal polycystic kidney disease (PKD) with emphasis on the differential diagnosis, clinical manifestations, diagnostic techniques, and potential therapeutic approaches for the major causes of neonatal PKD, namely hereditary disease, including autosomal recessive and autosomal dominant PKD and nonhereditary PKD, with particular emphasis on multicystic dysplastic kidney. A brief overview of obstructive cystic dysplasia and simple and complex cysts is also included. PMID:25155726

  5. Diabetic kidney disease.

    PubMed

    Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

    2015-01-01

    The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg. PMID:27188921

  6. 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

  7. Kidney Disease: A Silent Problem

    MedlinePlus

    ... dialysis or a transplant might work for you. Medicare And Kidney Disease Medicare may help pay for some kidney disease education and treatment. Contact Medicare to learn more about what is covered. Look ...

  8. 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 Central

    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. PMID:26046536

  9. Fine genetic map of mouse chromosome 10 around the polycystic kidney disease gene, jcpk, and ankyrin 3

    SciTech Connect

    Bryda, E.C.; Ling, H.; Rathbun, D.E.

    1996-08-01

    A chlorambucil (CHL)-induced mutation of the jcpk (juvenile congenital polycystic kidney disease) gene causes a severe early onset polycystic kidney disease. In an intercross involving Mus musculus castaneus, jcpk was precisely mapped 0.2 cM distal to D10Mit115 and 0.8 cM proximal to D10Mit173. In addition, five genes, Cdc2a, Col6al, Col6a2, Bcr, and Ank3 were mapped in both this jcpk intercross and a (BALB/c X CAST/Ei)F{sub 1} x BALB/c backcross. All five genes were eliminated as possible candidates for jcpk based on the mapping data. The jcpk intercross allowed the orientation of the Ank3 gene relative to the centromere to be determined. D10Mit115, D10Mit173, D10Mit199, and D10Mit200 were separated genetically in this cross. The order and genetic distances of all markers and gene loci mapped in the jcpk intercross were consistent with those derived from the BALB/c backcross, indicating that the CHL-induced lesion has not generated any gross chromosomal abnormalities detectable in these studies. 39 refs., 3 figs.

  10. Polycystic Kidney Disease

    MedlinePlus

    ... a kidney transplant or blood-filtering treatments called dialysis. The two main types of PKD are autosomal ... so people with kidney failure must receive either dialysis or a kidney transplant to replace kidney function. ...

  11. Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract

    PubMed Central

    Hwang, Daw-Yang; Dworschak, Gabriel C.; Kohl, Stefan; Saisawat, Pawaree; Vivante, Asaf; Hilger, Alina C.; Reutter, Heiko M.; Soliman, Neveen A.; Bogdanovic, Radovan; Kehinde, Elijah O.; Tasic, Velibor; Hildebrandt, Friedhelm

    2014-01-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease. CAKUT can be caused by monogenic mutations, however, data are lacking on their frequency. Genetic diagnosis has been hampered by genetic heterogeneity and lack of genotype-phenotype correlation. To determine the percentage of cases with CAKUT that can be explained by mutations in known CAKUT genes, we analyzed the coding exons of the 17 known dominant CAKUT-causing genes in a cohort of 749 individuals from 650 families with CAKUT. The most common phenotypes in this CAKUT cohort were 288 with vesicoureteral reflux, 120 with renal hypodysplasia and 90 with unilateral renal agenesis. We identified 37 different heterozygous mutations (33 novel) in 12 of the 17 known genes in 47 patients from 41 of the 650 families (6.3%). These mutations include (number of families): BMP7 (1), CDC5L (1), CHD1L (5), EYA1 (3), GATA3 (2), HNF1B (6), PAX2 (5), RET (3), ROBO2 (4), SALL1 (9), SIX2 (1), and SIX5 (1). Furthermore, several mutations previously reported to be disease-causing are most likely benign variants. Thus, in a large cohort over 6% of families with isolated CAKUT are caused by a mutation in 12 of 17 dominant CAKUT genes. Our report represents one of the most in-depth diagnostic studies of monogenic causes of isolated CAKUT in children. PMID:24429398

  12. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... 345 KB)​​​​​ Alternate Language URL Anemia in Chronic Kidney Disease Page Content On this page: What is anemia? ... should. [ Top ] How is anemia related to chronic kidney disease? Anemia commonly occurs in people with chronic kidney ...

  13. Chronic Kidney Disease and Medicines

    MedlinePlus

    ... Alternate Language URL Español Chronic Kidney Disease and Medicines: What You Need to Know Page Content What ... pharmacist and provider need to know about your medicine and supplement use Your kidneys do not filter ...

  14. 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- ...

  15. Role of renin-angiotensin-aldosterone system gene polymorphisms and hypertension-induced end-stage renal disease in autosomal dominant polycystic kidney disease.

    PubMed

    Ramanathan, Gnanasambandan; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar

    2014-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidneys and is marked by progressive cyst growth and decline in kidney function, resulting in end-stage renal disease (ESRD). Hypertension is thought to be a significant modifying factor in the progression of renal failure in ADPKD. A number of genetic variations involved in renin-angiotensin-aldosterone system (RAAS) pathway genes have clinical or physiological impacts on pathogenesis of hypertension-induced ESRD in ADPKD. Information on RAAS pathway gene polymorphisms and their association with ESRD and ADPKD, published till March 2013, was collected using MEDLINE search. The present review deals with RAAS gene polymorphisms focused on hypertension-induced ESRD in ADPKD in different populations. The results were inconclusive and limited by heterogeneity in the study designs and the population stratification. In lieu of applying next generation sequencing technologies to study complex diseases, it is also possible to apply the same to unravel the complexity of ESRD in ADPKD. PMID:25001132

  16. 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. PMID:26134528

  17. Novel Mutation in the PKHD1 Gene Diagnosed Prenatally in a Fetus with Autosomal Recessive Polycystic Kidney Disease.

    PubMed

    Thakur, Pankaj; Speer, Paul; Rajkovic, Aleksandar

    2014-01-01

    We report a 29-year-old gravida 2, para 0100, who presented at 19 weeks and 4 days of gestation for ultrasound to assess fetal anatomy. Routine midtrimester fetal anatomy ultrasound revealed enlarged, hyperechoic fetal kidneys and normal amniotic fluid index. Follow-up ultrasound at 23 weeks and 5 days revealed persistently enlarged, hyperechoic fetal kidneys. Progressive oligohydramnios was not evident until 29 weeks of gestation, with anhydramnios noted by 35 weeks of gestation. Amniocentesis was performed for karyotype and to search for mutations in the PKHD1 for the presumptive diagnosis of autosomal recessive polycystic kidney disease (ARPKD). In our patient, a maternally inherited, previously reported pathogenic missense mutation in the PKHD1 gene, c.10444C>T, was identified. A second, previously unreported de novo mutation, c.5909-2delA, was also identified. This mutation affects the canonical splice site and is most likely pathogenic. Our case highlights PKHD1 allelic heterogeneity and the importance of genetic testing in the prenatal setting where many other genetic etiologies can phenocopy ARPKD. PMID:25114813

  18. Screening the 3{prime} region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations

    SciTech Connect

    Peral, B.; San Millan, J.L.; Ong, A.C.M.

    1996-01-01

    Recently, the gene for the most common form of autosomal dominant polycystic kidney disease (ADPKD), PKD1 (polycystic kidney disease 1), has been fully characterized and shown to encode an integral membrane protein, polycystin, involved in cell-cell and/or cell-matrix interactions. Study of the PKD1 gene has been complicated because most of the gene lies in a genomic region reiterated several times elsewhere on the same chromosome, and consequently only seven mutations have been described so far. Here we report a systematic screen covering {approximately}80% of the {approximately}-2.75 kb of translated transcript that is encoded by single-copy DNA. We have identified and characterized six novel mutations that, together with the previously described changes, amount to a detection rate of 10%-15% in the population studied. The newly described mutations are two deletions, an insertion of a T-nucleotide causing a frameshift, two single-base-pair substitutions resulting in premature stop codons, and a G{yields}C transversion that may be a missense mutation. These results have important implications for genetic diagnosis of PKD1 because they indicate that the majority of mutations lie within the duplicated area, which is difficult to study. The regions of polycystin removed in each mutation so far described are assessed for their functional significance; an area disrupted by two new small in-frame changes is highlighted. PKD1 mutations are contrasted with those in the PKD1/TSC2 contiguous-gene syndrome, and the likely mutational mechanism in PKD1 is considered. 36 refs., 6 figs., 2 tabs.

  19. 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, ...

  20. Kidney Disease: Early Detection and Treatment

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter 2008 ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, which ...

  1. Chronic kidney disease.

    PubMed

    Drawz, Paul; Rahman, Mahboob

    2015-06-01

    This issue provides a clinical overview of chronic kidney disease, focusing on prevention, diagnosis, treatment, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic. PMID:26030647

  2. Acquired Cystic Kidney Disease

    MedlinePlus

    ... Catherine Kelleher, M.D., University of Colorado Health Sciences Center, Denver. About the Kidney Failure Series The NIDDK Kidney Failure Series includes booklets and fact sheets that can help you learn more about treatment methods for kidney failure, complications of dialysis, financial help ...

  3. Myeloperoxidase in kidney disease.

    PubMed

    Malle, Ernst; Buch, Thomas; Grone, Hermann-Josef

    2003-12-01

    In glomerular and tubulointerstitial disease, polymorphonuclear- and monocyte-derived reactive oxygen species may contribute to oxidative modification of proteins, lipids, and nucleic acids. In part, the processes instigated by reactive oxygen species parallel events that lead to the development of atherosclerosis. Myeloperoxidase (MPO), a heme protein and catalyst for (lipo)protein oxidation is present in these mononuclear cells. The ability of MPO to generate hypochlorous acid/hypochlorite (HOCl/OCl-) from hydrogen peroxide in the presence of chloride ions is a unique and defining activity for this enzyme. The MPO-hydrogen peroxide-chloride system leads to a variety of chlorinated protein and lipid adducts that in turn may cause dysfunction of cells in different compartments of the kidney. The aim of this article is to cover and interpret some experimental and clinical aspects in glomerular and tubulointerstitial diseases in which the MPO-hydrogen peroxide-chloride system has been considered an important pathophysiologic factor in the progression but also the attenuation of experimental renal disease. The colocalization of MPO and HOCl-modified proteins in glomerular peripheral basement membranes and podocytes in human membranous glomerulonephritis, the presence of HOCl-modified proteins in mononuclear cells of the interstitium and in damaged human tubular epithelia, the inflammation induced and exacerbated by MPO antibody complexes in necrotizing glomerulonephritis, and the presence of HOCl-modified epitopes in urine following hyperlipidemia-induced renal damage in rodents suggest that MPO is an important pathogenic factor in glomerular and tubulointerstitial diseases. Specifically, the interaction of MPO with nitric oxide metabolism adds to the complexity of actions of oxidants and may help to explain bimodal partly detrimental partly beneficial effects of the MPO-hydrogen peroxide-chloride system in redox-modulated renal diseases. PMID:14633118

  4. Kidney Disease Statistics for the United States

    MedlinePlus

    ... also order print versions from our online catalog. Kidney Disease Statistics for the United States Page Content On ... for Vascular Access Acknowledgments The Growing Burden of Kidney Disease Kidney disease statistics for the United States convey ...

  5. Lupus and Kidney Disease (Lupus Nephritis)

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  6. Working with Kidney Disease: Rehabilitation and Employment

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  7. Vitamins and Minerals in Kidney Disease

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  8. Association of the receptor for advanced glycation end-products (RAGE) gene polymorphisms in Malaysian patients with chronic kidney disease

    PubMed Central

    Wong, Foo Nian; Chua, Kek Heng; Kuppusamy, Umah Rani; Wong, Chew Ming; Lim, Soo Kun

    2016-01-01

    Background: Chronic kidney disease (CKD) is a condition associated with progressive loss of kidney function and kidney damage. The two common causes of CKD are diabetes mellitus and hypertension. Other causes of CKD also include polycystic kidney disease, obstructive uropathy and primary glomerulonephritis. The receptor for advanced glycation end-products (RAGE) is a multi-ligand cell surface receptor of the immunoglobulin superfamily and it has been associated with kidney disease in both non-diabetic and diabetic patients. Presently, data on the association between RAGE polymorphisms and CKD in the Malaysian population is limited, while numerous studies have reported associations of RAGE polymorphisms with diabetic complications in other populations. The present study aims to explore the possibility of using RAGE polymorphisms as candidate markers of CKD in Malaysian population by using association analysis. Methods: A total of 102 non-diabetic CKD patients, 204 diabetic CKD patients and 345 healthy controls were enrolled in the study. DNA isolated from blood samples were subjected to genotyping of RAGE G82S, −374T/A, −429T/C, 1704G/T and 2184A/G polymorphisms using real-time polymerase chain reaction (PCR). The 63-bp deletion, a polymorphism in the RAGE gene promoter, was genotyped using conventional PCR method and visualized using agarose gel electrophoresis. The collective frequencies of genotypes with at least one copy of the minor alleles of the four polymorphisms were compared between the non-diabetic CKD patients, diabetic CKD patients and healthy controls. Results: After adjustment of age, gender and ethnic groups in binary logistic regression analysis, the G82S CT + TT genotypes were associated with non-diabetic CKD patients when compared with diabetic CKD patients (p = 0.015, OR = 1.896, 95% CI = 1.132–3.176). After further adjustment of CKD comorbidities, the G82S CT + TT genotypes were still associated with non-diabetic CKD patients when compared

  9. [Chronic Kidney Disease and Bone].

    PubMed

    James, Junichiro

    2016-08-01

    Both bone and kidney are members of the physiological network sharing a purpose of systemic mineral metabolism. In patients with chronic kidney disease whose kidney function is lost, the organ functions of other mineral metabolism network member including bone fail into uncontrollable due to dysregulated feedback system. This is the concept of Chronic Kidney Disease(related)- Mineral and Bone Disorder(CKD-MBD). However, the bone metabolic abnormalities in patients with chronic kidney disease cannot be explained merely by the framework of this mineral metabolism network. Although dialysis patients show several times higher hip fracture risk than general population, the main pathogenesis seems not to be their disordered mineral metabolism. We need to consider "uremic osteoporosis" characterized by deteriorated bone material properties due to uremic condition. PMID:27461505

  10. Polymorphisms of the ELANE Gene Promoter Region in End-Stage Chronic Kidney Disease Patients

    PubMed Central

    Fernandes, Rafael; Freitas, Bruno; Miranda, Vasco; Costa, Elísio; Santos-Silva, Alice; Bronze-da-Rocha, Elsa

    2016-01-01

    End-stage renal disease (ESRD) patients have a high mortality rate that exceeds that of non-ESRD population. The hemodialysis procedure induces neutrophil activation and elastase release, which might have a role in the inflammatory process and in the development of oxidative stress. The ELANE gene encodes the neutrophil elastase. We analyzed the effect of ELANE promoter region polymorphisms and its relation with the circulating levels of elastase, as well as several clinical, biochemical and inflammatory markers in 123 ESRD patients. We found two duplications in heterozygosity in the promoter region and a new polymorphism, the c.-801G>A. ESRD patients heterozygous for the c.-903T>G polymorphism had no changes in the circulating levels of elastase or other evaluated variables, and those homozygous for the c.-741G>A polymorphism showed significant effects on neutrophils count, as well as in neutrophils/lymphocytes ratio, which might be associated with an increased inflammatory process. PMID:27136588

  11. Ultrasound in Acute Kidney Disease.

    PubMed

    Meola, Mario; Nalesso, Federico; Petrucci, Ilaria; Samoni, Sara; Ronco, Claudio

    2016-01-01

    Kidneys' imaging provides useful information in acute kidney injury (AKI) diagnosis and management. Today, several imaging techniques give information on kidneys anatomy, urinary obstruction, differential diagnosis between AKI and chronic kidney disease (CKD), renal blood flow and glomerular filtration rate. Ultrasound is a safe, non-invasive and repeatable imaging technique so it is widely used in the first level work-up of AKI. The utility of contrast-enhanced computed tomography and magnetic resonance imaging in AKI or in AKI during CKD is limited because of renal toxicity associated with contrast agents used. PMID:27169556

  12. Autosomal dominant polycystic kidney disease: Localization of the second gene to chromosome 4q13-q23

    SciTech Connect

    Kimberling, W.J.; Kumar, S.; Kenyon, J.B.; Connolly, C.J. ); Gabow, P.A. ); Somlo, S. )

    1993-12-01

    At least two loci are known to exist for autosomal dominant polycystic kidney disease (ADPKD). One was localized to 16p, but the second less common locus has remained unlinked. Over 100 microsatellite markers, distributed across all chromosomes, have been typed on informative family members from the large Sicilian kindred in which the genetic heterogeneity was first discovered. Both the affected and the unaffected status of every family member used in the study were consulted in the successful localization of a second ADPKD gene to chromosome 4q. It was found to be flanked by the markers D4S231 and D4S414, defining a segment that spans about 9 cM. The new locus has been designated PKD4. This second localization will allow researchers to target another ADPKD gene for isolation in an effort to understand the pathogenesis of this common disorder. Furthermore, when flanking markers for the second ADPKD gene are used in conjunction with flanking markers for PKD1, the accuracy of the diagnosis of the subtype of ADPKD present in any particular family will be enhanced. This will improve the accuracy of linkage-based presymptomatic diagnoses by reducing the error due to genetic heterogeneity. 42 refs., 3 figs., 1 tab.

  13. High Blood Pressure and Kidney Disease

    MedlinePlus

    ... Information Center National Kidney Foundation Smokefree.gov MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Alternate Language URL Español High Blood Pressure and Kidney Disease Page Content On this page: What is ...

  14. End-stage kidney disease

    MedlinePlus

    ... Transplantation: Principles and Practice . 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 3. Inker LA, Astor BC, ... Primer on Kidney Diseases . 6th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 53. Taal M. Risk factors ...

  15. Diet - chronic kidney disease

    MedlinePlus

    ... this special diet to limit the buildup of waste products in the body. Limiting fluids between dialysis ... up when the kidneys no longer function well. Dangerous heart rhythms may result, which can lead to ...

  16. Amyloidosis and Kidney Disease

    MedlinePlus

    ... body has fewer red blood cells than normal. Dialysis-related Amyloidosis People who suffer from kidney failure ... weight loss [ Top ] What are the symptoms of dialysis-related amyloidosis? The symptoms of dialysis-related amyloidosis ...

  17. Kidney Injury in Liver Disease.

    PubMed

    Regner, Kevin R; Singbartl, Kai

    2016-07-01

    Acute kidney injury (AKI) occurs frequently in patients with liver disease and increases morbidity and mortality. Hepatorenal syndrome is a common cause of AKI in patients with decompensated cirrhosis and is due to alterations in systemic and renal hemodynamics. Serum creatinine-based estimation of kidney function is a key component of the Model for End-stage Liver Disease score in liver transplant candidates. Continuous renal replacement therapy is used in critically ill patients with liver failure and AKI. Simultaneous liver-kidney transplantation (SLK) may be required in patients with liver failure and prolonged AKI. Identification of appropriate candidates for SLK remains controversial. PMID:27339675

  18. Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease.

    PubMed

    Harris, Peter C; Bae, Kyongtae T; Rossetti, Sandro; Torres, Vicente E; Grantham, Jared J; Chapman, Arlene B; Guay-Woodford, Lisa M; King, Bernard F; Wetzel, Louis H; Baumgarten, Deborah A; Kenney, Philip J; Consugar, Mark; Klahr, Saulo; Bennett, William M; Meyers, Catherine M; Zhang, Qin Jean; Thompson, Paul A; Zhu, Fang; Miller, J Philip

    2006-11-01

    Data from serial renal magnetic resonance imaging of the Consortium of Radiologic Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD) population showed that cystic expansion occurs at a consistent rate per individual, although it is heterogeneous in the population, and that larger kidneys are associated with more rapid disease progression. The significance of gene type to disease progression is analyzed in this study of the CRISP cohort. Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and 27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst number increased with age, and more cysts were detected in PKD1 kidneys (P < 0.0001). PKD1 is more severe because more cysts develop earlier, not because they grow faster, implicating the disease gene in cyst initiation but not expansion. These insights will inform the development of targeted therapies in autosomal dominant PKD. PMID:17035604

  19. CD74 in Kidney Disease

    PubMed Central

    Valiño-Rivas, Lara; Baeza-Bermejillo, Ciro; Gonzalez-Lafuente, Laura; Sanz, Ana Belen; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

    2015-01-01

    CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics. PMID:26441987

  20. Candidate Gene Association Study of Coronary Artery Calcification in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort Study

    PubMed Central

    Ferguson, Jane F; Matthews, Gregory J; Townsend, Raymond R; Raj, Dominic S; Kanetsky, Peter A.; Budoff, Matthew; Fischer, Michael J; Rosas, Sylvia E; Kanthety, Radhika; Rahman, Mahboob; Master, Stephen R; Qasim, Atif; Li, Mingyao; Mehta, Nehal N.; Shen, Haiqing; Mitchell, Braxton D; O’Connell, Jeffrey R; Shuldiner, Alan R; Ho, Weang Kee; Young, Robin; Rasheed, Asif; Danesh, John; He, Jiang; Kusek, John W; Ojo, Akinlolu O; Flack, John; Go, Alan S; Gadegbeku, Crystal A; Wright, Jackson T; Saleheen, Danish; Feldman, Harold I; Rader, Daniel J; Foulkes, Andrea S; Reilly, Muredach P

    2014-01-01

    Objectives To identify loci for coronary artery calcification (CAC) in patients with chronic kidney disease (CKD). Background CKD is associated with increased CAC and subsequent coronary heart disease (CHD) but the mechanisms remain poorly defined. Genetic studies of CAC in CKD may provide a useful strategy for identifying novel pathways in CHD. Methods We performed a candidate gene study (~2,100 genes; ~50,000 SNPs) of CAC within the Chronic Renal Insufficiency Cohort (CRIC) Study (n=1,509; 57% European, 43% African ancestry). SNPs with preliminary evidence of association with CAC in CRIC were examined for association with CAC in PennCAC (n=2,560) and Amish Family Calcification Study (AFCS; n=784) samples. SNPs with suggestive replication were further analyzed for association with myocardial infarction (MI) in the Pakistan Risk of Myocardial Infarction study (PROMIS) (n=14,885). Results Of 268 SNPs reaching P <5×10−4 for CAC in CRIC, 28 SNPs in 23 loci had nominal support (P <0.05 and in same direction) for CAC in PennCAC or AFCS. Besides chr9p21 and COL4A1, known loci for CHD, these included SNPs having reported GWAS association with hypertension (e.g., ATP2B1). In PROMIS, four of the 23 suggestive CAC loci (chr9p21, COL4A1, ATP2B1 and ABCA4) had significant associations with MI consistent with their direction of effect on CAC. Conclusions We identified several loci associated with CAC in CKD that also relate to MI in a general population sample. CKD imparts a high risk of CHD and may provide a useful setting for discovery of novel CHD genes and pathways. PMID:23727086

  1. Bacterial kidney disease (Renibacterium salmoninarum)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum, is a prevalent disease of salmonid fish that impacts sustainable production for consumption and species conservation efforts. The disease is chronic in nature and mortality most often occurs in juvenile salmonids and prespawning a...

  2. Acquired Cystic Kidney Disease

    MedlinePlus

    ... Fax: 813–636–8122 Email: info@aakp.org Internet: www.aakp.org American Kidney Fund 6110 Executive ... Fax: 301–881–0898 Email: helpline@kidneyfund.org Internet: www.kidneyfund.org Life Options Rehabilitation Resource Center ...

  3. 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- ...

  4. Isolation of a P1 phagemid encompassing the autosomal dominant polycystic kidney disease gene (PKD1)

    SciTech Connect

    Zhang, F.; Schneider, M.C.; Reeders, S.T.

    1994-09-01

    We have isolated a P1 phagemid using primers for the 3 prime end of the tuberin gene (TSC2) on chromosome 16p13, which encompasses a large gene (KG8) which shows PKD1-specific mutations. The approximately 90-100 kilobase phagemid encompasses at least 4 genes (KG8, Nik7, KG3, and KM17). The CA repeats SM6 (upstream of the KG8 gene) and KG8 localized to the gene itself (3 prime untranslated) are found in the phagemid, as well as a number of trinucleotide repeat elements. One, a CCT-hybridizing fragment maps internal to the KG8 cDNA and appears to make the cosmid corresponding to the region (cGGG10) unstable. None of the previously published cosmids from the region completely encompasses the KG8 gene. A detailed R1 map of the region has been prepared and compared to the cosmid maps. Sequence of the regional genes will be presented. The phagemid will provide an alternative genomic source for evaluating the genomic sequence/map. In addition, this phagemid will potentially be useful as a vector for transfection of the entire PKD1 gene and its regulatory sequences.

  5. Kidney Disease and Multiple Myeloma

    PubMed Central

    Rennke, Helmut G.; Laubach, Jacob P.; Richardson, Paul G.

    2013-01-01

    Summary Kidney injury is a common complication of multiple myeloma and other plasma cell dyscrasias, and it is associated with increased mortality. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal Ig and some of which are independent of paraprotein deposition. The pathogenic mechanisms that underlie paraprotein-related kidney disease are increasingly well understood. A novel assay allowing the quantification of free light chains in the serum has aided the diagnosis of new onset disease and allowed for the earlier detection of relapse. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes. Stem cell transplantation remains a mainstay of management for younger patients with myeloma who are suitable candidates for intensive therapy, whereas the role of new drugs, plasma exchange, and kidney transplantation continues to evolve. PMID:23868898

  6. 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

  7. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  8. Kidney stone disease

    PubMed Central

    Coe, Fredric L.; Evan, Andrew; Worcester, Elaine

    2005-01-01

    About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics. PMID:16200192

  9. Regenerative medicine in kidney disease.

    PubMed

    Little, Melissa H; Kairath, Pamela

    2016-08-01

    The treatment of renal failure has changed little in decades. Organ transplantation and dialysis continue to represent the only therapeutic options available. However, decades of fundamental research into the response of the kidney to acute injury and the processes driving progression to chronic kidney disease are beginning to open doors to new options. Similarly, continued investigations into the cellular and molecular basis of normal kidney development, together with major advances in stem cell biology, are now delivering options in regenerative medicine not possible as recently as a decade ago. In this review, we will discuss advances in regenerative medicine as it may be applied to the kidney. This will cover cellular therapies focused on ameliorating injury and improving repair as well as advancements in the generation of new renal tissue from stem/progenitor cells. PMID:27234568

  10. STAT3 Signaling in Polycystic Kidney Disease

    PubMed Central

    Weimbs, Thomas; Talbot, Jeffrey J.

    2015-01-01

    Mutations in the gene coding for the integral membrane protein polycystin-1 (PC1) are the cause of most cases of autosomal-dominant polycystic kidney disease (ADPKD), a very common disease that leads to kidney failure and currently lacks approved treatment. Recent work has revealed that PC1 can regulate the transcription factor STAT3, and that STAT3 is aberrantly activated in the kidneys of ADPKD patients and PKD mouse models. Recent approaches to directly inhibit STAT3 in PKD mouse models have been promising. Numerous signaling pathways are known to activate STAT3 and many have long been implicated in the pathogenesis of PKD - such as EGF/EGFR, HGF/c-Met, Src. However, a role of STAT3 in the pathogenesis of PKD had never been considered until now. Here, we review the current findings that suggest that STAT3 is a promising target for the treatment of PKD. PMID:26523147

  11. A novel mutation of the HNF1B gene associated with hypoplastic glomerulocystic kidney disease and neonatal renal failure: a case report and mutation update.

    PubMed

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

    2015-02-01

    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

  12. New Insights Into Molecular Mechanisms of Diabetic Kidney Disease

    PubMed Central

    Badal, Shawn S.; Danesh, Farhad R.

    2014-01-01

    Diabetic kidney disease remains a major microvascular complication of diabetes and the most common cause of chronic kidney failure requiring dialysis in the United States. Medical advances over the past century have substantially improved the management of diabetes mellitus and thereby have increased patient survival. However, current standards of care reduce but do not eliminate the risk of diabetic kidney disease, and further studies are warranted to define new strategies for reducing the risk of diabetic kidney disease. In this review, we highlight some of the novel and established molecular mechanisms that contribute to the development of the disease and its outcomes. In particular, we discuss recent advances in our understanding of the molecular mechanisms implicated in the pathogenesis and progression of diabetic kidney disease, with special emphasis on the mitochondrial oxidative stress and microRNA targets. Additionally, candidate genes associated with susceptibility to diabetic kidney disease and alterations in various cytokines, chemokines, and growth factors are addressed briefly. PMID:24461730

  13. Congenital Hepatic Fibrosis in the Franches-Montagnes Horse Is Associated with the Polycystic Kidney and Hepatic Disease 1 (PKHD1) Gene

    PubMed Central

    Drögemüller, Michaela; Jagannathan, Vidhya; Welle, Monika M.; Graubner, Claudia; Straub, Reto; Gerber, Vinzenz; Burger, Dominik; Signer-Hasler, Heidi; Poncet, Pierre-André; Klopfenstein, Stéphane; von Niederhäusern, Ruedi; Tetens, Jens; Thaller, Georg; Rieder, Stefan; Drögemüller, Cord; Leeb, Tosso

    2014-01-01

    Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosomal recessive polycystic kidney and hepatic disease (ARPKD) as well as several mouse and rat mutants. Whereas most pathogenic PKHD1 variants lead to polycystic defects in kidney and liver, a small subset of the human ARPKD patients have only liver symptoms, similar to our horses with congenital hepatic fibrosis. The PKHD1 gene is one of the largest genes in the genome with multiple alternative transcripts that have not yet been fully characterized. We sequenced the genomes of an affected foal and 46 control horses to establish a comprehensive list of variants in the critical interval. We identified two missense variants in the PKHD1 gene which were strongly, but not perfectly associated with congenital hepatic fibrosis. We speculate that reduced penetrance and/or potential epistatic interactions with hypothetical modifier genes may explain the imperfect association of the detected PKHD1 variants. Our data thus indicate that horses with congenital hepatic fibrosis represent an interesting large animal model for the liver-restricted subtype of human ARPKD. PMID:25295861

  14. Sirtuin and metabolic kidney disease

    PubMed Central

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-01-01

    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. PMID:26083654

  15. [Diabetic kidney disease - Update 2016].

    PubMed

    Sourij, Harald; Edlinger, Roland; Prischl, Friedrich; Auinger, Martin; Kautzky-Willer, Alexandra; Säemann, Marcus D; Prager, Rudolf; Clodi, Martin; Schernthaner, Guntram; Mayer, Gert; Oberbauer, Rainer; Rosenkranz, Alexander R

    2016-04-01

    Recent epidemiological evaluations have shown that approximately 5% of all Austrians suffer from diabetes including renal involvement, i. e. 400.000 people in Austria are affected. The risk of start and progression of this disease can be ameliorated by lifestyle interventions as well as optimization of blood pressure and glucose levels. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society for Nephrology for the prevention and treatment of diabetic kidney disease. PMID:27052231

  16. Study Links Climate Change to Kidney Disease

    MedlinePlus

    ... medlineplus.gov/news/fullstory_158680.html Study Links Climate Change to Kidney Disease Rising temperatures, less rain seen ... 5, 2016 THURSDAY, May 5, 2016 (HealthDay News) -- Climate change may boost rates of chronic kidney disease worldwide ...

  17. Growth Failure in Children with Kidney Disease

    MedlinePlus

    ... Language URL Growth Failure in Children with Chronic Kidney Disease Page Content On this page: What is growth ... What is growth failure in children with chronic kidney disease (CKD)? Growth failure is a complication of CKD ...

  18. Study Links Climate Change to Kidney Disease

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158680.html Study Links Climate Change to Kidney Disease Rising temperatures, less rain ... 5, 2016 THURSDAY, May 5, 2016 (HealthDay News) -- Climate change may boost rates of chronic kidney disease ...

  19. NAFLD and Chronic Kidney Disease

    PubMed Central

    Marcuccilli, Morgan; Chonchol, Michel

    2016-01-01

    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. PMID:27089331

  20. Representing Kidney Development Using the Gene Ontology

    PubMed Central

    Alam-Faruque, Yasmin; Hill, David P.; Dimmer, Emily C.; Harris, Midori A.; Foulger, Rebecca E.; Tweedie, Susan; Attrill, Helen; Howe, Douglas G.; Thomas, Stephen Randall; Davidson, Duncan; Woolf, Adrian S.; Blake, Judith A.; Mungall, Christopher J.; O’Donovan, Claire; Apweiler, Rolf; Huntley, Rachael P.

    2014-01-01

    Gene Ontology (GO) provides dynamic controlled vocabularies to aid in the description of the functional biological attributes and subcellular locations of gene products from all taxonomic groups (www.geneontology.org). Here we describe collaboration between the renal biomedical research community and the GO Consortium to improve the quality and quantity of GO terms describing renal development. In the associated annotation activity, the new and revised terms were associated with gene products involved in renal development and function. This project resulted in a total of 522 GO terms being added to the ontology and the creation of approximately 9,600 kidney-related GO term associations to 940 UniProt Knowledgebase (UniProtKB) entries, covering 66 taxonomic groups. We demonstrate the impact of these improvements on the interpretation of GO term analyses performed on genes differentially expressed in kidney glomeruli affected by diabetic nephropathy. In summary, we have produced a resource that can be utilized in the interpretation of data from small- and large-scale experiments investigating molecular mechanisms of kidney function and development and thereby help towards alleviating renal disease. PMID:24941002

  1. Angiogenesis and chronic kidney disease

    PubMed Central

    2010-01-01

    The number of patients requiring renal replacement therapy due to end-stage renal disease (ESRD) is increasing worldwide. The prevalence of chronic kidney disease (CKD), and the importance of CKD as a risk factor in development of ESRD and in complicating cardiovascular disease (CVD) have been confirmed. In recent years, the involvement of angiogenesis-related factors in the progression of CKD has been studied, and the potential therapeutic effects on CKD of modulating these factors have been identified. Vascular endothelial growth factor (VEGF)-A, a potent pro-angiogenic factor, is involved in the development of the kidney, in maintenance of the glomerular capillary structure and filtration barrier, and in the renal repair process after injury. VEGF-A is also involved in the development of early diabetic nephropathy, demonstrated by the therapeutic effects of anti-VEGF-A antibody. Angiopoietin (Ang)-1 induces the maturation of newly formed blood vessels, and the therapeutic effects of Ang-1 in diabetic nephropathy have been described. In experimental models of diabetic nephropathy, the therapeutic effects of angiogenesis inhibitors, including angiostatin, endostatin and tumstatin peptides, the isocoumarin NM-3, and vasohibin-1, have been reported. Further analysis of the involvement of angiogenesis-related factors in the development of CKD is required. Determining the disease stage at which therapy is most effective and developing an effective drug delivery system targeting the kidney will be essential for pro-or anti-angiogenic strategies for patients with CKD. PMID:20687922

  2. [Cardiovascular risk in polycystic kidney disease].

    PubMed

    Di Lorenzo, Adelaide; Stallone, Giovanni; Infante, Barbara; Grandaliano, Giuseppe; Schena, Francesco Paolo

    2015-09-01

    Hypertension is common and occurs in the 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 depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in 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 levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications. PMID:26418387

  3. Kidney disease in Paraguay.

    PubMed

    Santa Cruz, Francisco; Cabrera, Walter; Barreto, Susana; Mayor, María Magdalena; Báez, Diana

    2005-08-01

    Paraguay is a landlocked country located in South America with a total population of 5,884,491. Most of the population (95%) is mestizo, a mixture of Spanish and American/Indian races. The total number of indigenous people in the country has increased from 38,703 in 1981 to 85,674 in 2002. The gross domestic product per capita was US $932.00 annually per person in the year 2002. Between 1992 and 1997, there were 380 patients on chronic dialysis in Paraguay and 75 patients received renal transplants, mostly living-related. The prevalence of renal replacement therapy was 87 patients per million, and the incidence of renal disease continues to rise. Seventy percent of cases of ESRD are of unknown etiology and 15% have diabetes-related renal disease. Only citizens covered by the employee's national health insurance have complete coverage for dialysis and transplantation. The remainder of the population has to apply to public hospitals when the need for hemodialysis arises. At such hospitals, they can receive hemodialysis coverage from the National Institute of Nephrology or from other medical foundations to obtain entrance to these programs. They must otherwise use their own resources to pay for treatment. Seventy percent of patients on chronic dialysis turn to public hospitals for treatment. Hospital hemodialysis is the method most widely used. Home dialysis is rarely performed and there are very few programs for ambulatory peritoneal dialysis. Thus, a large number of patients are not able to enter chronic dialysis programs. In a recent survey of 4655 ill children registered, the distribution of main renal disease was acute glomerulonephritis in 42 cases (9 per 1000), nephrotic syndrome in 40 cases (8.5 per 1000), systemic lupus erythematosis in 28 cases (6 per 1000), and hematuria alone in 11 cases (2.3 per 1000). In ambulatory pediatric practice, urinary tract infection is the leading reason for seeking medical advice. Two thirds of such cases are associated with

  4. [Chronic kidney disease and nutrition].

    PubMed

    Yoshida, Takuya; Kumagai, Hiromichi

    2016-03-01

    Abnormalities of mineral metabolism develop with decline of renal function in chronic kidney disease (CKD), and it is called as a CKD-mineral and bone disorder (CKD-MBD). The standard approach for management of CKD-MBD is to keep serum phosphorus, calcium, and parathyroid hormone in the reference range by dietary intervention and medications. It has been recently pointed out that starting the treatment from early CKD is important for suppressing CKD-MBD. PMID:26923973

  5. Arterial disease in chronic kidney disease.

    PubMed

    Moody, William E; Edwards, Nicola C; Chue, Colin D; Ferro, Charles J; Townend, Jonathan N

    2013-03-01

    End stage renal disease is associated with a very high risk of premature cardiovascular death and morbidity. Early stage chronic kidney disease (CKD) is also associated with an increased frequency of cardiovascular events and is a common but poorly recognised and undertreated risk factor. Cardiovascular disease in CKD can be attributed to two distinct but overlapping pathological processes, namely atherosclerosis and arteriosclerosis. While the risk of athero-thrombotic events such as myocardial infarction is elevated, arteriosclerosis is the predominant pathophysiological process involving fibrosis and thickening of the medial arterial layer. This results in increased arterial stiffness causing left ventricular hypertrophy and fibrosis and the exposure of vulnerable vascular beds such as the brain and kidney to high pressure fluctuations causing small vessel disease. These pathophysiological features are manifest by a high risk of lethal arrhythmia, congestive heart failure, myocardial infarction and stroke. Recent work has highlighted the importance of aldosterone and disordered bone mineral metabolism. PMID:23118349

  6. 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. PMID:20424573

  7. Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis).

    PubMed

    Fisher, S E; van Bakel, I; Lloyd, S E; Pearce, S H; Thakker, R V; Craig, I W

    1995-10-10

    Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, and eventual renal failure. We have previously used positional cloning to identify the 3' part of a novel kidney-specific gene (initially termed hClC-K2, but now referred to as CLCN5), which is deleted in patients from one pedigree segregating Dent disease. Mutations that disrupt this gene have been identified in other patients with this disorder. Here we describe the isolation and characterization of the complete open reading frame of the human CLCN5 gene, which is predicted to encode a protein of 746 amino acids, with significant homology to all known members of the ClC family of voltage-gated chloride channels. CLCN5 belongs to a distinct branch of this family, which also includes the recently identified genes CLCN3 and CLCN4. We have shown that the coding region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and have determined the sequence of each exon-intron boundary. The elucidation of the coding sequence and exon-intron organization of CLCN5 will both expedite the evaluation of structure/function relationships of these ion channels and facilitate the screening of other patients with renal tubular dysfunction for mutations at this locus. PMID:8575751

  8. Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis)

    SciTech Connect

    Fisher, S.E.; Van Bakel, I.; Craig, I.W.

    1995-10-10

    Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, and eventual renal failure. We have previously used positional cloning to identify the 3{prime} part of a novel kidney-specific gene (initially termed hClC-K2, but now referred to as CLCN5), which is deleted in patients from one pedigree segregating Dent disease. Mutations that disrupt this gene have been identified in other patients with this disorder. Here we describe the isolation and characterization of the complete open reading frame of the human CLCN5 gene, which is predicted to encode a protein of 746 amino acids, with significant homology to all known members of the ClC family of voltage-gated chloride channels. CLCN5 belongs to a distinct branch of this family, which also includes the recently identified genes CLCN3 and CLCN4. We have shown that the coding region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and have determined the sequence of each exon-intron boundary. The elucidation of the coding sequence and exon-intron organization of CLCN5 will both expedite the evaluation of structure/function relationships of these ion channels and facilitate the screening of other patients with renal tubular dysfunction for mutations at this locus. 31 refs., 5 figs.

  9. [Renal failure and cystic kidney diseases].

    PubMed

    Correas, J-M; Joly, D; Chauveau, D; Richard, S; Hélénon, O

    2011-04-01

    Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50-60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficult to distinguish from autosomal dominant PKD. These cystic kidney diseases should not be confused with non-hereditary incidental multiple renal cysts. In tuberous sclerosis, renal cysts are associated with angiomyolipomas and sometimes pulmonary lymphangioleiomyomatosis. Renal failure is inconstant. Other hereditary cystic kidney diseases, including MCKD and nephronophtisis, are usually associated with renal failure. Non-hereditary cystic kidney diseases include multicystic renal dysplasia (due to complete pelvi-ureteric atresia or hydronephrosis), acquired multicystic kidney disease (chronic renal failure, chronic hemodialysis) and varied cystic kidney diseases (multicystic renal disease, glomerulocystic kidney disease, microcystic kidney disease). PMID:21549887

  10. 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

  11. Nephrology Update: Chronic Kidney Disease.

    PubMed

    Saha, Sharmeela; Rahman, Mahboob

    2016-05-01

    Chronic kidney disease (CKD) affects more than 1 in 10 individuals in the United States. The care of these patients must be managed by family physicians and nephrology subspecialists. The kidneys often are affected by systemic processes such as diabetes and hypertension, and optimal management of these conditions is critical to slow decline in renal function in CKD patients. These patients are at high risk of cardiovascular disease, and statin therapy is recommended for adults with CKD who are at least age 50 years and not receiving dialysis. Patients with CKD and anemia can be treated with iron therapy and often with an erythropoietin-stimulating agent. Electrolyte abnormalities are managed with dietary changes and drugs. Sodium restriction and modification of dietary protein intake also may be needed. Consultation with a renal dietitian may be helpful. Because many drugs are metabolized by the kidneys, physicians should ensure that drug dosages are appropriate for the level of renal function. Early consultation with or referral to a nephrology subspecialist for patients with reduced renal function, resistant hypertension or electrolyte levels, and other conditions have been associated with improved outcomes in CKD patients. PMID:27163761

  12. Pregnancy in chronic kidney disease.

    PubMed

    Vellanki, Kavitha

    2013-05-01

    Despite vast improvements in fetal outcomes, pregnancy in women with CKD is fraught with hazards; worsening of renal function and complications like preeclampsia and premature delivery are common. To date, there is no accurate formula to calculate glomerular filtration rate (GFR). Also, whether the current CKD classification is better than the older classification at predicting outcomes in pregnant women with CKD is unknown. Women with an estimated GFR ≥1.4 mg/dL are at increased risk of progressive worsening of renal function regardless of the cause of the underlying kidney disease. Preeclampsia is difficult to diagnose in pregnant women with underlying CKD, and serum markers such as soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PIGF) may lead the way for definitive diagnosis. New-onset lupus or lupus flare is an indication for kidney biopsy during pregnancy; cyclosporine is safe and is the most effective agent that can be used during pregnancy. Women with adult polycystic kidney disease are at increased risk of hypertension and preeclampsia during pregnancy, as well as hepatic cysts later in life, the latter occurring with multiple pregnancies. Strict blood pressure control is important in pregnant women with diabetic nephropathy. A multidisciplinary team that includes nephrologists and obstetricians who deal with high-risk pregnancies should be involved in the care of pregnant women with CKD for successful pregnancy outcomes. PMID:23928386

  13. Polycystic kidney disease: The cadence of kidney growth in ADPKD.

    PubMed

    Chapman, Arlene

    2009-06-01

    Autosomal-dominant polycystic kidney disease is characterized by the development and expansion of cysts, which ultimately results in kidney failure. The rate of this expansion can now be quantified within a short period of time, which has implications for assessing the risk of renal failure in affected patients. PMID:19474826

  14. 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.

  15. 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.

  16. Multiple Myeloma and Kidney Disease

    PubMed Central

    Noiri, Eisei

    2013-01-01

    Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis. PMID:24288486

  17. Prevalence of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism in South Indian population with hypertension and chronic kidney disease

    PubMed Central

    Shanmuganathan, R; Kumaresan, R; Giri, P

    2015-01-01

    Context: Chronic Kidney Disease (CKD) is associated with a high risk of developing further severe complications such as, cardiovascular disease and eventually End Stage Renal Disease (ESRD) leading to death. Hypertension plays a key role in the progression of renal failure and is also a chief risk factor for the occurrence of End Stage Renal Disease (ESRD). Aim: This study investigates the possible association of insertion (I) and deletion (D) polymorphism of ACE gene in patients of Chronic Kidney Disease (CKD) with and without hypertension (HT). Settings and Design: Total 120 participants with 30 members in each group (Control, HT, CKD and CKD-HT) were chosen followed by informed consent. Materials and Methods: Blood samples were collected and subjected to biochemical analyses and nested PCR amplification was performed to genotype the DNA, for ACE I/D using specific primers. Statistical Analysis: Statistical analyses were performed using SPSS version 13. Allele and genotypic frequency was calculated by direct gene counting method. Comparison of the different genotypes was done by using Chi square test. Odd's ratios were calculated with a 95% confidence interval limit. Results: The ACE genotype were distributed as II, 27 (90%); DD, 2 (6.67%) and ID, 1 (3.33%) in control, II, 1 (3.33%); DD, 5 (16.67%) and ID, 24 (80%) in HT, II, 4 (13.33%); DD, 24 (80%) and ID, 2 (6.67%) in CKD and II, 0 (0%); DD, 2 (6.67%) and ID, 28 (93.33%) in CKD-HT group. Conclusions: D allele of ACE gene confers a greater role in genetic variations underlying CKD and hypertension. This result suggest that CKD patients should be offered analysis for defects in ACE I/D polymorphisms, especially if they are hypertensive. PMID:26440392

  18. Chronic kidney disease (CKD) in disadvantaged populations

    PubMed Central

    Garcia-Garcia, Guillermo; Jha, Vivekanand

    2015-01-01

    Twelve March 2015 will mark the 10th anniversary of World Kidney Day (WKD), an initiative of the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort ever mounted to raise awareness among decision-makers and the general public about the importance of kidney disease. Each year WKD reminds us that kidney disease is common, harmful and treatable. The focus of WKD 2015 is on chronic kidney disease (CKD) in disadvantaged populations. This article reviews the key links between poverty and CKD and the consequent implications for the prevention of kidney disease and the care of kidney patients in these populations. PMID:25713703

  19. Genetic Considerations in Pediatric Chronic Kidney Disease.

    PubMed

    Harshman, Lyndsay A; Zepeda-Orozco, Diana

    2016-03-01

    Chronic kidney disease (CKD) in children is an irreversible process that, in some cases, may lead to end-stage renal disease. The majority of children with CKD have a congenital disorder of the kidney or urological tract arising from birth. There is strong evidence for both a genetic and epigenetic component to progression of CKD. Utilization of gene-mapping strategies, ranging from genome-wide association studies to single-nucleotide polymorphism analysis, serves to identify potential genetic variants that may lend to disease variation. Genome-wide association studies evaluating population-based data have identified different loci associated with CKD progression. Analysis of single-nucleotide polymorphisms on an individual level suggests that secondary systemic sequelae of CKD are closely related to dysfunction of the cardiovascular-inflammatory axis and may lead to advanced cardiovascular disease through abnormal vascular calcification and activation of the renin-angiotensin system. Similarly, genetic variants affecting cytokine control, fibrosis, and parenchymal development may modulate CKD through development and acceleration of renal interstitial fibrosis. Epigenetic studies evaluate modification of the genome through DNA methylation, histone modification, or RNA interference, which may be directly influenced by external or environmental factors directing genomic expression. Lastly, improved understanding of the genetic and epigenetic contribution to CKD progression may allow providers to identify a population at accelerated risk for disease progression and apply novel therapies targeted at the genetic mechanism of disease. PMID:27617141

  20. Genetic loci influencing kidney function and chronic kidney disease.

    PubMed

    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 J L; Beckmann, Jacqui; Bilo, Henk J G; Bochud, Murielle; Brown, Morris J; Caulfield, Mark J; Connell, John M C; Cook, H Terence; Cotlarciuc, Ioana; Davey Smith, George; 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; Homan van der Heide, Jaap J; 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; Peltonen, Leena; Penninx, Brenda W; Perucha, Esperanza; Pouta, Anneli; Prokopenko, Inga; Roderick, Paul J; Ruokonen, Aimo; Samani, Nilesh J; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Seelen, Marc A J; Shuldiner, Alan R; Sjögren, Marketa; Smit, Johannes H; Snieder, Harold; Soranzo, Nicole; Spector, Timothy D; Stenvinkel, Peter; Sternberg, Michael J E; 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

    2010-05-01

    Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease. PMID:20383145

  1. 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

  2. Bone Disease after Kidney Transplantation.

    PubMed

    Bouquegneau, Antoine; Salam, Syrazah; Delanaye, Pierre; Eastell, Richard; Khwaja, Arif

    2016-07-01

    Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high- or low-turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients. PMID:26912549

  3. Hereditary Causes of Kidney Stones and Chronic Kidney Disease

    PubMed Central

    Edvardsson, Vidar O.; Goldfarb, David S.; Lieske, John C.; Beara-Lasic, Lada; Anglani, Franca; Milliner, Dawn S.; Palsson, Runolfur

    2013-01-01

    Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC and PH with emphasis on childhood manifestations. PMID:23334384

  4. [Skin and chronic kidney disease].

    PubMed

    Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

    2014-01-01

    Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process. PMID:25315722

  5. A Review of Pediatric Chronic Kidney Disease.

    PubMed

    Kaspar, C D W; Bholah, R; Bunchman, T E

    2016-01-01

    Chronic kidney disease is complex in both adults and children, but the disease is far from the same between these populations. Here we review the marked differences in etiology, comorbidities, impact of disease on growth and quality of life, issues unique to adolescents and transitions to adult care, and special considerations of congenital kidney and urinary tract anomalies for transplantation. PMID:26766175

  6. Kidney disease associated with plasma cell dyscrasias

    PubMed Central

    Goes, Nelson B.; Spitzer, Thomas R.; Raje, Noopur S.; Humphreys, Benjamin D.; Anderson, Kenneth C.; Richardson, Paul G.

    2010-01-01

    Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve. PMID:20462963

  7. 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

  8. [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. PMID:21544793

  9. Risk of stroke in kidney disease.

    PubMed

    Ninomiya, Toshiharu

    2013-01-01

    Stroke is a leading cause of mortality and morbidity worldwide. Traditional cardiovascular risk factors - hypertension, diabetes and dyslipidemia - are related to the incidence of stroke. Chronic kidney disease has also been recognized to be a major public health problem as a cardiovascular risk factor. Growing evidence has suggested that chronic kidney disease is associated with an increased risk of cardiovascular disease including stroke in general populations. Those with chronic kidney disease have a greater prevalence of traditional cardiovascular risk factors. Several meta-analyses assessing the association between chronic kidney disease and stroke have found that the magnitude of the risk estimates adjusted for known traditional cardiovascular risk factors were reduced as compared with the age-adjusted risk estimates. While these findings on the surface seem to downplay the effect of chronic kidney disease on stroke, they may actually suggest that an accumulation of traditional cardiovascular risk factors in those with chronic kidney disease increases the risk of stroke, and that applying appropriate treatments to those with chronic kidney disease is important for reducing the risk of stroke. Additionally, other large-scale meta-analyses demonstrated that chronic kidney disease was a significant risk factor for stroke independent of known cardiovascular risk factors. Chronic kidney disease may also be associated with an increase in nontraditional risk factors such as hyperhomocysteinemia, inflammation, asymmetric dimethylarginine, oxidative stress, and anemia, and thrombogenic factors such as left ventricular hypertrophy, endothelial dysfunction, and arterial stiffness. Herein, we review the results of meta-analyses of published cohort studies for a better understanding of the precise nature of the relationship between chronic kidney disease and stroke, important to both the clinical and public health fields. Further studies are warranted to determine whether

  10. MicroRNAs and in kidney function and disease

    PubMed Central

    Akkina, Sanjeev; Becker, Bryan N.

    2011-01-01

    MicroRNAs (miRNA) are short non-coding RNA sequences that regulate gene expression by blocking protein translation or inducing mRNA degradation. miRNA is found in various tissues with variable expression and changes in expression are related to various disease processes. Evidence suggests that changes in miRNA expression are critical for the normal development of kidney tissue. Alternatively, in diseases such as diabetic nephropathy, polycystic kidney disease, and lupus nephritis, specific miRNAs may enhance disease manifestations in a myriad of ways, ranging from activation of fibrotic pathways to anatomical changes that abet proteinuria. The variable expression of miRNA in kidney tissue, whether in the context of normal development or disease processes, makes miRNAs a valuable new tool for understanding, diagnosing, and discovering therapeutic options for pathological processes that affect the kidney. PMID:21420034

  11. Phenotype Standardization for Drug Induced Kidney Disease

    PubMed Central

    Mehta, Ravindra L; Awdishu, Linda; Davenport, Andrew; Murray, Patrick; Macedo, Etienne; Cerda, Jorge; Chakaravarthi, Raj; Holden, Arthur; Goldstein, Stuart L.

    2015-01-01

    Drug induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular and nephrolithiasis, along with primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease and chronic kidney disease. Establishing causality in drug induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is first step to recognizing drug induced kidney disease and developing strategies to prevent and manage this condition. PMID:25853333

  12. 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

  13. 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

  14. Three exonic mutations in polycystic kidney disease-2 gene (PKD2) alter splicing of its pre-mRNA in a minigene system.

    PubMed

    Gonzalez-Paredes, Francisco J; Ramos-Trujillo, Elena; Claverie-Martin, Felix

    2016-03-01

    Exonic mutations are usually classified as missense, synonymous or nonsense mutations, however, they can affect pre-mRNA splicing either by disrupting splice sites, by creating new ones or by changing splicing regulatory sequences. In this study, we examined 21 mutations of the PKD2 gene, encoding polycystin-2, previously reported as missense or synonymous for their possible effects on pre-mRNA splicing using bioinformatics tools. All these mutations except one have been identified in patients with autosomal dominant polycystic kidney disease, a common genetic disorder characterized by the development and progressive enlargement of cysts in the kidneys leading to end-stage renal disease. We selected 12 missense mutations and 1 synonymous variant for the minigene assay, and found that three, c.1532A>T (p.D511V), c.1716G>A (p.K572K) and c.2657A>G (p.D886G) caused alterations in pre-mRNA splicing. Mutation c.1532A>T resulted in skipping of exon 6 and incorporation of a defective exon lacking the 3' end, while c.1716G>A led to skipping of exon 7. Mutation c.2657A>G resulted in incorporation of an incomplete exon 14, which is in agreement with previous results obtained with the patient's lymphoblast RNA. Our findings should be taken into account with regard to the pathogenicity of these PKD2 exonic mutations. These results together with previous reports highlight the importance to evaluate the effects of exonic single nucleotide substitutions in autosomal dominant polycystic kidney disease. PMID:26692149

  15. Hypertension in Cardiovascular and Kidney Disease

    PubMed Central

    Botdorf, Joshua; Chaudhary, Kunal; Whaley-Connell, Adam

    2011-01-01

    The relationship between hypertension and chronic kidney disease (CKD) is bidirectional in nature and, generally, management strategies for cardiovascular risk reduction also attenuate progression of CKD. Prevalent hypertension increases with diminishing kidney function, and the management strategy changes with level of kidney function. In this review, we will examine the evidence for management of hypertension, as a modifiable risk factor for cardiovascular disease in CKD, and the impact of this management on progression of CKD. PMID:22096454

  16. Kidney Failure and Vascular Disease

    MedlinePlus

    ... toxic level, they can be removed artificially through dialysis, or a kidney transplant can be performed. A ... can be treated with an artificial kidney machine (dialysis) which removes toxins from the blood. Patients requiring ...

  17. Midkine in nephrogenesis, hypertension and kidney diseases

    PubMed Central

    Sato, Waichi; Sato, Yuka

    2014-01-01

    Midkine (MK; K; gene abbreviation, Mdk: mus musculus, MDK: homo sapiens) is a multifunctional heparin-binding growth factor that regulates cell growth, survival and migration as well as anti-apoptotic activity in nephrogenesis and development. Proximal tubular epithelial cells are the main sites of MK expression in the kidneys. The pathophysiological roles of MK are diverse, ranging from the development of acute kidney injury (AKI) to the progression of chronic kidney disease, often accompanied by hypertension, renal ischaemia and diabetic nephropathy. The obvious hypertension that develops in Mdk+/+ mouse models of renal ablation compared with Mdk−/− mice eventually leads to progressive renal failure, such as glomerular sclerosis and tubulointerstitial damage associated with elevated plasma angiotensin (Ang) II levels. MK is also induced in the lung endothelium by oxidative stress and subsequently up-regulated by ACE, which hydrolyzes Ang II to induce further oxidative stress, thus accelerating MK generation; this leads to a vicious cycle of positive feedback in the MK-Ang II pathway. Kidney–lung interactions involving positive feedback between the renin-angiotensin system and MK might partly account for the pathogenesis of hypertension and kidney damage. MK is also involved in the pathogenesis of AKI and diabetic nephropathy through the recruitment of inflammatory cells. In contrast, MK plays a protective role against crescentic glomerulonephritis, by down-regulating plasminogen activator inhibitor-1. These diverse actions of MK might open up new avenues for targeted approaches to treating hypertension and various renal diseases. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24106831

  18. Imaging in Chronic Kidney Disease.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Chronic kidney disease (CKD) diagnosis and staging are based on estimated or calculated glomerular filtration rate (GFR), urinalysis and kidney structure at renal imaging techniques. Ultrasound (US) has a key role in evaluating both morphological changes (by means of B-Mode) and patterns of vascularization (by means of color-Doppler and contrast-enhanced US), thus contributing to CKD diagnosis and to the follow-up of its progression. In CKD, conventional US allows measuring longitudinal diameter and cortical thickness and evaluating renal echogenicity and urinary tract status. Maximum renal length is usually considered a morphological marker of CKD, as it decreases contemporarily to GFR, and should be systematically recorded in US reports. More recently, it has been found to be a significant correlation of both renal longitudinal diameter and cortical thickness with renal function. Conventional US should be integrated by color Doppler, which shows parenchymal perfusion and patency of veins and arteries, and by spectral Doppler, which is crucial for the diagnosis of renal artery stenosis and provides important information about intrarenal microcirculation. Different values of renal resistive indexes (RIs) have been associated with different primary diseases, as they reflect vascular compliance. Since RIs significantly correlate with renal function, they have been proposed to be independent risk factors for CKD progression, besides proteinuria, low GFR and arterial hypertension. Despite several new applications, US and color Doppler contribute to a definite diagnosis in <50% of cases of CKD, because of the lack of specific US patterns, especially in cases of advanced CKD. However, US is useful to evaluate CKD progression and to screen patients at risk for CKD. The indications and the recommended frequency of color Doppler US could differ in each case and the follow-up should be tailored. PMID:27170301

  19. Pirfenidone Is Renoprotective in Diabetic Kidney Disease

    PubMed Central

    Zhu, Yanqing; Ravasi, Timothy; McGowan, Tracy A.; Toh, Irene; Dunn, Stephen R.; Okada, Shinichi; Shaw, Michael A.

    2009-01-01

    Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. Here, we evaluated the role of PFD in regulation of the extracellular matrix. In mouse mesangial cells, PFD decreased TGF-β promoter activity, reduced TGF-β protein secretion, and inhibited TGF-β–induced Smad2-phosphorylation, 3TP-lux promoter activity, and generation of reactive oxygen species. To explore the therapeutic potential of PFD, we administered PFD to 17-wk-old db/db mice for 4 wk. PFD treatment significantly reduced mesangial matrix expansion and expression of renal matrix genes but did not affect albuminuria. Using liquid chromatography with subsequent electrospray ionization tandem mass spectrometry, we identified 21 proteins unique to PFD-treated diabetic kidneys. Analysis of gene ontology and protein–protein interactions of these proteins suggested that PFD may regulate RNA processing. Immunoblotting demonstrated that PFD promotes dosage-dependent dephosphorylation of eukaryotic initiation factor, potentially inhibiting translation of mRNA. In conclusion, PFD is renoprotective in diabetic kidney disease and may exert its antifibrotic effects, in part, via inhibiting RNA processing. PMID:19578007

  20. Subclinical Celiac Disease and Crystal-Induced Kidney Disease Following Kidney Transplant

    PubMed Central

    Capolongo, Giovanna; Abul-Ezz, Sameh; Moe, Orson W.; Sakhaee, Khashayar

    2015-01-01

    Decreased kidney function from kidney deposition of calcium oxalate has been previously described in inflammatory bowel disease as well as following jejuno-ileal and Roux-en-Y gastric bypass surgeries. Although celiac disease is the most prevalent bowel abnormality associated with intestinal malabsorption, its relationship to high kidney oxalate burden and decreased kidney function has not been established. We report a case of subclinical celiac disease and hyperoxaluria that presented with loss of kidney function as a result of high oxalate load in the absence of overt diarrhea, documented intestinal fat malabsorption, and nephrolithiasis. Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients. We propose that this entity should be suspected in patients with chronic kidney disease in which the etiology of kidney damage has not been clearly established. PMID:22739230

  1. Polycystic kidney disease in the medaka (Oryzias latipes) pc mutant caused by a mutation in the Gli-Similar3 (glis3) gene.

    PubMed

    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. MicroRNAs and Polycystic Kidney Disease

    PubMed Central

    Noureddine, Lama; Hajarnis, Sachin; Patel, Vishal

    2013-01-01

    Polycystic kidney disease (PKD), the most common genetic cause of chronic renal failure, is characterized by the presence of numerous fluid-filled cysts in renal parenchyma. Despite recent progress, no FDA-approved therapy is available to retard cyst growth. Here, we review current evidence implicating two groups of miRNAs – the miR-17~92 cluster and miR-200s - in the pathogenesis of PKD. We present a new hypothesis for cyst growth involving miRNAs and regulation of PKD gene dosage. We propose that manipulating miRNA function in an attempt to normalize PKD gene dosage represents a novel therapeutic strategy in PKD. PMID:25221607

  3. Is My Child at Risk for Kidney Disease?

    MedlinePlus

    ... URL Español Is My Child at Risk for Kidney Disease? Page Content Some diseases and conditions put children ... blood and keep the bones strong. What is kidney disease? Infections or other health problems can cause kidney ...

  4. 78 FR 36554 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Gene-Environment Interactions in TEDDY. Date: July 25, 2013. Time... and Kidney Diseases Special Emphasis Panel; Artificial Pancreas SBIR Applications. Date: July 31,...

  5. [Troponins and chronic kidney disease].

    PubMed

    Di Lullo, Luca; Barbera, Vincenzo; Santoboni, Alberto; Bellasi, Antonio; Cozzolino, Mario; De Pascalis, Antonio; Rivera, Rodolfo; Balducci, Alessandro; Russo, Domenico; Ronco, Claudio

    2015-01-01

    Coronary thrombosis was recognized since 19th century as clinical entity with bad outcomes; only in 1912 it was reported that acute myocardial infarction had to been distinguished from angina pectoris. First diagnostic test was electrocardiogram, while white blood cells count and erythrocytes sedimentation rate were the only available laboratory tests. Late in the 60s and 70s glutammic oxaloacetic and glutamic pyravate transaminase, lactate dehydrogenase and creatine kinase were added to biomarkers pool to provide a diagnosis of myocardial infarction related to myocardial cells injury. Only in 1987 assays for cardiac troponin were developed to assess structural damage of myocardial cells and in 2010 high sensibility troponins first dosage kits became available. It is well known that the population with chronic kidney disease (CKD) is at greater risk for cardiovascular disease and death than the general population. The use and interpretation of high sensitivity cardiac troponin (hs-cTn) assays have been particularly challenging in these patients with the majority having elevated levels at baseline. Aim of this review is to evaluate hs-cTn in patients with CKD for the diagnosis of AMI and for the prognostic significance of elevated levels in CKD patients without AMI. PMID:26252257

  6. Insights into kidney diseases from genome-wide association studies.

    PubMed

    Wuttke, Matthias; Köttgen, Anna

    2016-09-01

    Over the past decade, genome-wide association studies (GWAS) have considerably improved our understanding of the genetic basis of kidney function and disease. Population-based studies, used to investigate traits that define chronic kidney disease (CKD), have identified >50 genomic regions in which common genetic variants associate with estimated glomerular filtration rate or urinary albumin-to-creatinine ratio. Case-control studies, used to study specific CKD aetiologies, have yielded risk loci for specific kidney diseases such as IgA nephropathy and membranous nephropathy. In this Review, we summarize important findings from GWAS and clinical and experimental follow-up studies. We also compare risk allele frequency, effect sizes, and specificity in GWAS of CKD-defining traits and GWAS of specific CKD aetiologies and the implications for study design. Genomic regions identified in GWAS of CKD-defining traits can contain causal genes for monogenic kidney diseases. Population-based research on kidney function traits can therefore generate insights into more severe forms of kidney diseases. Experimental follow-up studies have begun to identify causal genes and variants, which are potential therapeutic targets, and suggest mechanisms underlying the high allele frequency of causal variants. GWAS are thus a useful approach to advance knowledge in nephrology. PMID:27477491

  7. MicroRNAs in the pathogenesis of cystic kidney disease

    PubMed Central

    Phua, Yu Leng; Ho, Jacqueline

    2015-01-01

    Purpose of review Cystic kidney diseases are common renal disorders characterized by the formation of fluid-filled epithelial cysts in the kidneys. The progressive growth and expansion of the renal cyst replaces existing renal tissue within the renal parenchyma, leading to reduced renal function. While several genes have been identified in association with inherited causes of cystic kidney disease, the molecular mechanisms that regulate these genes in the context of post-transcriptional regulation are still poorly understood. There is Increasing evidence that miRNA dysregulation is associated with the pathogenesis of cystic kidney disease. Recent findings In this review, recent studies that implicate dysregulation of miRNA expression in cystogenesis will be discussed. The relationship of specific specific miRNAs, such as the miR-17~92 cluster and cystic kidney disease, miR-92a and von Hippel-Lindau (VHL) syndrome, and alterations in LIN28-LET7 expression in Wilms tumor will be explored. Summary At present, there are no specific treatments available for patients with cystic kidney disease. Understanding and identifying specific miRNAs involved in the pathogenesis of these disorders may have the potential to lead to the development of novel therapies and biomarkers. PMID:25490692

  8. 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 For ... Javascript on. Wait too long to talk about kidney disease and you could be waiting for a kidney. ...

  9. ASK1: a new therapeutic target for kidney disease.

    PubMed

    Tesch, Greg H; Ma, Frank Y; Nikolic-Paterson, David J

    2016-08-01

    Stress-induced activation of p38 MAPK and JNK signaling is a feature of both acute and chronic kidney disease and is associated with disease progression. Inhibitors of p38 MAPK or JNK activation provide protection against inflammation and fibrosis in animal models of kidney disease; however, clinical trials of p38 MAPK and JNK inhibitors in other diseases (rheumatoid arthritis and pulmonary fibrosis) have been disappointing. Apoptosis signal-regulating kinase 1 (ASK1) acts as an upstream regulator for the activation of p38 MAPK and JNK in kidney disease. Mice lacking the Ask1 gene are healthy with normal homeostatic functions and are protected from acute kidney injury induced by ischemia-reperfusion and from renal interstitial fibrosis induced by ureteric obstruction. Recent studies have shown that a selective ASK1 inhibitor substantially reduced renal p38 MAPK activation and halted the progression of nephropathy in diabetic mice, and this has led to a current clinical trial of an ASK1 inhibitor in patients with stage 3 or 4 diabetic kidney disease. This review explores the rationale for targeting ASK1 in kidney disease and the therapeutic potential of ASK1 inhibitors based on current experimental evidence. PMID:27226108

  10. 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. PMID:26598845

  11. Stop chronic kidney disease progression: Time is approaching.

    PubMed

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

    2016-05-01

    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

  12. 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

  13. Intestinal Microbiota-Kidney Cross Talk in Acute Kidney Injury and Chronic Kidney Disease

    PubMed Central

    Noel, Sanjeev; Martina-Lingua, Maria N.; Bandapalle, Samatha; Pluznick, Jennifer; Hamad, Abdel Rahim A.; Peterson, Daniel A.; Rabb, Hamid

    2016-01-01

    The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool. PMID:25343838

  14. Chronic kidney disease - pediatric risk factors.

    PubMed

    Tasic, Velibor; Janchevska, Aleksandra; Emini, Nora; Sahpazova, Emilija; Gucev, Zoran; Polenakovic, Momir

    2016-01-01

    The knowledge about the progression of chronic kidney disease is an important issue for every pediatric nephrologist and pediatrician in order to implement appropriate measures to prevent wasting of renal function and the final consequence - end stage renal disease with the need for the dialysis and transplantation. Therefore it is important to know, treat or ameliorate the standard risk factors such as hypertension, proteinuria, anemia, hyperparathyroidism etc. In this review devoted to the World Kidney Day 2016 we will pay attention to the low birth parameters, obesity, hyperuricemia and smoking which emerged as particularly important risk factors for children and adolescent with chronic kidney disease. PMID:27442412

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

    PubMed

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

    2011-10-01

    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. PMID:21862990

  16. Chronic Kidney Disease and Medicines: What You Need to Know

    MedlinePlus

    Chronic Kidney Disease and Medicines What You Need to Know Because you have chronic kidney disease, you should take steps to protect your kidneys. ... n n n Notes: For more information National Kidney Disease Education Program 1-866-4 KIDNEY (1-866- ...

  17. [Polycystic kidney disease: from genetics to dialysis].

    PubMed

    Ortiz Arduan, Alberto

    2012-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease. In addition, end-stage renal disease is complicated by acquired polycystic kidney disease. Recent advances in our understanding of the pathogenesis of ADPKD have identified the primary cilium as key to cystogenesis, and have defined the molecular, cellular and tissue pathogenesis of the disease, leading to the design of clinical trials that may ultimately lead to effective therapy of the disease. In 2012 a key trial has shown that blockade of vasopressin receptors with tolvaptan slows the rate of cyst growth and may slow the loss of renal function. PMID:24298871

  18. 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

  19. 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

  20. 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…

  1. 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

  2. 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 ...

  3. Genetics Home Reference: polycystic kidney disease

    MedlinePlus

    ... aneurysm ) in a large blood vessel called the aorta or in blood vessels at the base of ... Additional NIH Resources (1 link) National Institute of Diabetes and Digestive and Kidney Diseases Educational Resources (8 ...

  4. Autosomal Dominant Polycystic Kidney Disease

    MedlinePlus

    ... the U.S. The high cardiovascular death rate in dialysis patients with ADPKD remains a problem. Kidney transplantation ... who develop ESRD receive a transplant before beginning dialysis therapy. Limited organ availability has resulted in longer ...

  5. End-stage kidney disease

    MedlinePlus

    ... changes the results of many tests. People receiving dialysis will need these and other tests done often: ... ESRD may need to be treated with dialysis or kidney transplant . ... or take medicines to help your body work well. DIALYSIS Dialysis ...

  6. Glomerulocystic kidney disease in a kitten.

    PubMed

    Harkin, Kenneth R; Biller, David S; Balentine, Heather L

    2003-12-15

    A 4-month-old 1-kg female Siamese-Manx cross kitten was evaluated because of renomegaly and renal failure. Ultrasonography and cytologic examination of a renal aspirate failed to provide an antemortem diagnosis. Histologic lesions included diffuse cystic dilatation of all tubules and Bowman's spaces in the renal cortex and occasional small glomerular tufts; the lesions were similar to those of glomerulocystic kidney disease of humans. Glomerulocystic kidney disease is a rare cause of early-onset renal failure, but should be considered when renomegaly is detected, cysts are not detected in the kidney by ultrasonography, and cytologic examination of a renal aspirate is nondiagnostic. PMID:14690206

  7. Clinical Scenarios in Chronic Kidney Disease: Cystic Renal Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Cysts are frequently found in chronic kidney disease (CKD) and they have a different prognostic significance depending on the clinical context. Simple solitary parenchymal cysts and peripelvic cysts are very common and they have no clinical significance. At US, simple cyst appears as a round anechoic pouch with regular and thin profiles. On the other hand, hereditary polycystic disease is a frequent cause of CKD in children and adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the best known cystic hereditary diseases. ADPKD and ARPKD show a diffused cystic degeneration with cysts of different diameters derived from tubular epithelium. Medullary cystic disease may be associated with tubular defects, acidosis and lithiasis and can lead to CKD. Acquired cystic kidney disease, finally, is secondary to progressive structural end-stage kidney remodelling and may be associated with renal cell carcinoma. PMID:27169740

  8. 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

  9. Diagnosis and treatment of diabetic kidney disease.

    PubMed

    Gosmanov, Aidar R; Wall, Barry M; Gosmanova, Elvira O

    2014-05-01

    Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease in the United States. In the last several years, there have been several new developments in the field of the DKD. In 2007, the National Kidney Foundation and Kidney Disease Outcomes Quality Initiative released clinical practice guidelines that included new definitions and summarized diagnostic and therapeutic approaches for DKD. The results of several recent randomized controlled trials provided novel insights regarding effects of glycemic and lipid control on vascular and renal outcomes in patients with diabetes. Additionally, the findings of the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure trial played a critical role in the revision of blood pressure target guidelines in patients with diabetes. The goal of this review article is to summarize recent updates and recommendations for the diagnosis and treatment of DKD. PMID:24553399

  10. 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. PMID:25993323

  11. Recent Developments in Epigenetics of Acute and Chronic Kidney Diseases

    PubMed Central

    Reddy, Marpadga A.; Natarajan, Rama

    2015-01-01

    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 DNA me and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  12. Applications of Metabolomics for Kidney Disease Research

    PubMed Central

    Wettersten, Hiromi I.; Weiss, Robert H.

    2013-01-01

    Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research. PMID:23538740

  13. Epidemiologic insights into pediatric kidney stone disease.

    PubMed

    Matlaga, Brian R; Schaeffer, Anthony J; Novak, Thomas E; Trock, Bruce J

    2010-12-01

    The epidemiology of pediatric kidney stone has not yet been as rigorously defined as that of adult kidney stone disease. Herein, we review our recent epidemiologic works characterizing pediatric stone disease using the Kids' Inpatient Database (KID). Specifically we investigated the age and gender distribution of pediatric kidney stone disease, changes in disease prevalence over time, and medical comorbidities associated with this disorder. We identified patients by International Classification of Disease 9th Edition (ICD-9) codes for renal and ureteral calculi as the primary diagnosis. Medical comorbidities were identified using specific comorbidity software. Statistical comparisons between children with and without stone disease were performed. In the first decade of life, stone disease was more prevalent among males than females; however, in the second decade of life females were more commonly affected. Of note, there was a significant increase in treated stone disease across both genders between 1997 and 2003. We also found that the risk of kidney stone diagnosis in children younger than 6 years of age was significantly associated with hypertension and diabetes mellitus. The gender distribution among pediatric stone formers varies significantly by age, although overall females have a greater prevalence than males. There is also a strong association of stone disease and both diabetes and hypertension, although this was only observed in children less than 6 years of age. Taken all together, these findings suggest that urolithiasis in the young child is a complex systemic disease process. PMID:20967433

  14. The ras responsive transcription factor RREB1 is a novel candidate gene for type 2 diabetes associated end-stage kidney disease

    PubMed Central

    Bonomo, Jason A.; Guan, Meijian; Ng, Maggie C.Y.; Palmer, Nicholette D.; Hicks, Pamela J.; Keaton, Jacob M.; Lea, Janice P.; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.

    2014-01-01

    Familial clustering and presumed genetic risk for type 2 diabetic (T2D) and non-diabetic end-stage kidney disease (ESKD) appear strong in African Americans. Examination of exome sequencing data in African American T2D-ESKD cases and non-diabetic non-nephropathy controls identified two low-frequency variants in the RREB1 gene, a repressor of the angiotensinogen (AGT) gene previously associated with kidney function, as being associated with T2D-ESKD: rs9379084 (P = 0.00087, OR = 0.26; D1171N) and rs41302867 (P = 0.00078, OR = 0.21; splice site variant). Rs41302867 replicated association in an independent sample of African Americans with T2D-ESKD [rs41302867 P = 0.033 (OR = 0.50)], and a trend towards rs9379084 association was observed (P = 0.070). In European Americans with T2D-ESKD compared with European American population based controls, both RREB1 variants replicated association [rs9379084 P = 1.67 × 10−4 (OR = 0.54) and rs41302867 P = 0.013 (OR = 0.69)]. Rs9379084 was not associated with non-T2D-ESKD or T2D in African Americans (P = 0.55 and P = 0.37, respectively), but was associated with T2D in European Americans (P = 0.014, OR = 0.65). In African Americans, rs41302867 was associated with non-T2D-ESKD [P = 0.036 (OR = 0.54)] and hypertension attributed ESKD [H-ESKD, P = 0.029 (OR = 0.50)]. A meta-analysis combining African American and European American T2D-ESKD data revealed P = 3.52 × 10−7 and 3.70 × 10−5 for rs9379084 and rs41302867 association, respectfully. A locus-wide analysis evaluating putatively functional SNPs revealed several nominal associations with T2D-ESKD, non-T2D-ESKD and T2D in African and European Americans. RREB1 is a large, complex gene which codes a multidomain zinc finger binding protein and transcription factor. We posit that variants in RREB1 modulate seemingly disparate phenotypes (i.e. T2D, T2D-ESKD and non-T2D-ESKD) through altered activity resulting from splice site and missense variants. PMID:25027322

  15. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO).

    PubMed

    Herzog, Charles A; Asinger, Richard W; Berger, Alan K; Charytan, David M; Díez, Javier; Hart, Robert G; Eckardt, Kai-Uwe; Kasiske, Bertram L; McCullough, Peter A; Passman, Rod S; DeLoach, Stephanie S; Pun, Patrick H; Ritz, Eberhard

    2011-09-01

    Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes. PMID:21750584

  16. Differences in the timing and magnitude of Pkd1 gene deletion determine the severity of polycystic kidney disease in an orthologous mouse model of ADPKD.

    PubMed

    Rogers, Kelly A; Moreno, Sarah E; Smith, Laurie A; Husson, Hervé; Bukanov, Nikolay O; Ledbetter, Steven R; Budman, Yeva; Lu, Yuefeng; Wang, Bing; Ibraghimov-Beskrovnaya, Oxana; Natoli, Thomas A

    2016-06-01

    Development of a disease-modifying therapy to treat autosomal dominant polycystic kidney disease (ADPKD) requires well-characterized preclinical models that accurately reflect the pathology and biochemical changes associated with the disease. Using a Pkd1 conditional knockout mouse, we demonstrate that subtly altering the timing and extent of Pkd1 deletion can have a significant impact on the origin and severity of kidney cyst formation. Pkd1 deletion on postnatal day 1 or 2 results in cysts arising from both the cortical and medullary regions, whereas deletion on postnatal days 3-8 results in primarily medullary cyst formation. Altering the extent of Pkd1 deletion by modulating the tamoxifen dose produces dose-dependent changes in the severity, but not origin, of cystogenesis. Limited Pkd1 deletion produces progressive kidney cystogenesis, accompanied by interstitial fibrosis and loss of kidney function. Cyst growth occurs in two phases: an early, rapid growth phase, followed by a later, slow growth period. Analysis of biochemical pathway changes in cystic kidneys reveals dysregulation of the cell cycle, increased proliferation and apoptosis, activation of Mek-Erk, Akt-mTOR, and Wnt-β-catenin signaling pathways, and altered glycosphingolipid metabolism that resemble the biochemical changes occurring in human ADPKD kidneys. These pathways are normally active in neonatal mouse kidneys until repressed around 3 weeks of age; however, they remain active following Pkd1 deletion. Together, this work describes the key parameters to accurately model the pathological and biochemical changes associated with ADPKD in a conditional mouse model. PMID:27356569

  17. Microcirculation in Acute and Chronic Kidney Diseases.

    PubMed

    Zafrani, Lara; Ince, Can

    2015-12-01

    The renal microvasculature is emerging as a key player in acute and chronic kidney diseases. Renal microvascular disease involves alterations in endothelial barrier permeability, exaggerated inflammation, impairment of endothelium-dependent vasorelaxation involving the nitric oxide system, increased oxidative stress, and loss of angiogenic factors. Moreover, evidence suggests that there is a microvascular component to the pathogenesis of renal scarring. New technology is being developed to explore renal microcirculation in vivo in experimental models and humans. This technology will provide a better understanding of the pathogenesis of kidney diseases and will help guide specific therapeutic strategies aimed at restoring the renal microcirculation. This article reviews the cellular and molecular mechanisms of renal microvascular dysfunction in acute and chronic kidney diseases and the potential diagnostic and therapeutic implications of these findings. Recent developments in the monitoring of renal microcirculation are described with respect to their advantages and limitations, and future directions are outlined. PMID:26231789

  18. Castleman's disease of the kidney: Sonographic findings.

    PubMed

    Ooi, Chin Chin; Cheah, Foong Koon; Wong, Siew Kune

    2015-09-01

    We report a case of rare Castleman's disease of the kidney that mimicked a renal neoplasm with emphasis on the imaging and histologic findings. A 47-year-old man presented with dyspeptic symptoms. Ultrasound revealed a vascular, heterogeneous mass in the left kidney. Multiphasic CT scan confirmed an enhancing lesion with enlarged left para-aortic lymph nodes suspicious for nodal metastases. The provisional diagnosis was renal cell carcinoma. Percutaneous biopsy yielded a diagnosis of Castleman's disease of the hyaline-vascular type. Despite advancement in imaging modalities, differentiation of hyaline-vascular variant of Castleman's disease from hypervascular renal neoplasm remains difficult and the final diagnosis requires histopathological confirmation. PMID:24947075

  19. The Western Diet and Chronic Kidney Disease.

    PubMed

    Hariharan, Divya; Vellanki, Kavitha; Kramer, Holly

    2015-03-01

    Characteristics of the Western diet that fueled the obesity epidemic may also impact kidney disease incidence and progression. Enlarging portion sizes over the past half century has been accompanied by increased intake of protein, sodium, and processed foods while consumption of fruits and vegetables has declined. Overall dietary patterns play a strong role for chronic disease risk including chronic kidney disease. While dietary patterns high in fresh fruits and vegetables and low in red meats, such as the Mediterranean diet, decrease the risk of chronic diseases, the Western diet, characterized by high intake of red meat, animal fat, sweets, and desserts and low intake of fresh fruits and vegetables and low-fat dairy products, increases risk of chronic diseases. In this article, we review the potential mechanisms whereby several key characteristics of the typical Western diet may impact kidney disease incidence and progression. We also discuss a public health policy initiative to improve dietary choices. Reducing protein intake to the recommended daily allowance of 0.8 g/kg/day and increasing intake of fruit and vegetables and fiber may mitigate kidney disease progression and reduce risk of cardiovascular disease and mortality. PMID:25754321

  20. Practical genetics for autosomal dominant polycystic kidney disease.

    PubMed

    Pei, York

    2011-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common mendelian disorder of the kidney and accounts for ~5% of end-stage renal disease in North America. It is characterized by focal development of renal cysts which increase in number and size with age. Mutations of PKD1 and PKD2 account for most cases. Although the clinical manifestations of both gene types overlap completely, PKD1 is associated with more severe disease than PKD2, with larger kidneys and earlier onset of end-stage renal disease. Furthermore, marked within-family renal disease variability is well documented in ADPKD and suggests a strong modifier effect from as yet unknown genetic and environmental factors. In turn, the significant inter- and intra-familial renal disease variability poses a challenge for diagnosis and genetic counseling. In general, renal ultrasonography is commonly used for the diagnosis, and age-dependent criteria have been defined for subjects at risk of PKD1. However, the utility of the PKD1 ultrasound criteria in the clinical setting is unclear since their performance characteristics have not been defined for the milder PKD2 and the gene type for most test subjects is unknown. Recently, highly predictive ultrasound diagnostic criteria have been derived for at-risk subjects of unknown gene type. Additionally, both DNA linkage and gene-based direct sequencing are available for the diagnosis of ADPKD, especially in subjects with equivocal imaging results, a negative or indeterminate family history, or in younger at-risk individuals being evaluated as potential living related kidney donor. This review will highlight the utility and limitations of clinical predictors of gene types, imaging- and molecular-based diagnostic tests, and present an integrated approach for evaluating individuals suspected to have ADPKD. PMID:21071968

  1. Molecular pathways of chronic kidney disease progression.

    PubMed

    Bienaimé, Frank; Canaud, Guillaume; El Karoui, Khalil; Gallazzini, Morgan; Terzi, Fabiola

    2016-04-01

    Chronic kidney disease is characterized by the progressive loss of functional nephrons. This loss means that the remaining nephrons are put under stress and are forced to adapt in order to maintain kidney function. Over the time, the strains imposed by these adaptations result in a vicious circle in which the loss of damaged nephrons results in the damage of the so far healthy nephrons. Hence, the rate of chronic kidney disease progression depends on the ability of the remaining nephrons to cope with stress. This article reviews the molecular pathways involved in the compensation and deterioration process after nephron reduction. In particular, we examine the role of mammalian target of rapamycin complex (mTORC)/serine-threonine protein kinase AKT, epidermal growth factor receptor (EGFR) and unfolded protein response pathways, as well as the pleiotropic function of Lipocalin 2. We also discuss the dual role played by some of these pathways in acute and chronic kidney disease. Finally, the relevance of these experimental finding to human chronic kidney disease is discussed. PMID:26972095

  2. Chronic kidney disease in disadvantaged populations

    PubMed Central

    Garcia-Garcia, G.; Jha, V.

    2015-01-01

    The increased burden of chronic kidney disease (CKD) in disadvantaged populations is due to both global factors and population-specific issues. Low socioeconomic status and poor access to care contribute to health care disparities and exacerbate the negative effects of genetic or biological predisposition. Provision of appropriate renal care to these populations requires a two-pronged approach: expanding the reach of dialysis through development of low-cost alternatives that can be practiced in remote locations, and implementation and evaluation of cost-effective prevention strategies. Kidney transplantation should be promoted by expansion of deceased donor transplant programs and use of inexpensive, generic immunosuppressive drugs. The message of World Kidney Day 2015 is that a concerted attack against the diseases that lead to end-stage renal disease, by increasing community outreach, better education, improved economic opportunity, and access to preventive medicine for those at highest risk, could end the unacceptable relationship between CKD and disadvantage in these communities. PMID:25760025

  3. HIV-associated immune complex kidney disease.

    PubMed

    Nobakht, Ehsan; Cohen, Scott D; Rosenberg, Avi Z; Kimmel, Paul L

    2016-05-01

    The introduction in the late 20(th) century of combination antiretroviral therapy (cART) to treat patients infected with HIV has changed the natural history of the disease from an acute illness that rapidly culminates in death, to a chronic condition that can be managed with medications. Over the past decade the epidemiology of kidney disease in US patients infected with HIV has changed, perhaps because of the increased availability and use of cART. Patients with HIV infection exhibit unique immunologic characteristics, including immunodeficiency and dysregulation of immunoglobulin synthetic responses and T-cell function, which can result in glomerular immune complex deposition and subsequent kidney injury. This Review examines the differential diagnoses of HIV-associated immune complex kidney diseases (HIVICD), and discusses the clinical manifestations and mechanisms underlying their development. We address the issues associated with treatment, clinical outcomes, and research needs to enhance our ability to diagnose and optimally treat patients with HIVICD. PMID:26782145

  4. Chronic kidney disease in disadvantaged populations.

    PubMed

    Garcia-Garcia, G; Jha, V

    2015-05-01

    The increased burden of chronic kidney disease (CKD) in disadvantaged populations is due to both global factors and population-specific issues. Low socioeconomic status and poor access to care contribute to health care disparities and exacerbate the negative effects of genetic or biological predisposition. Provision of appropriate renal care to these populations requires a two-pronged approach: expanding the reach of dialysis through development of low-cost alternatives that can be practiced in remote locations, and implementation and evaluation of cost-effective prevention strategies. Kidney transplantation should be promoted by expansion of deceased donor transplant programs and use of inexpensive, generic immunosuppressive drugs. The message of World Kidney Day 2015 is that a concerted attack against the diseases that lead to end-stage renal disease, by increasing community outreach, better education, improved economic opportunity, and access to preventive medicine for those at highest risk, could end the unacceptable relationship between CKD and disadvantage in these communities. PMID:25760025

  5. "Exercise as medicine" in chronic kidney disease.

    PubMed

    Wilkinson, T J; Shur, N F; Smith, A C

    2016-08-01

    Exercise and physical activity are increasingly becoming key tools in the treatment and prevention of several medical conditions including arthritis and diabetes; this notion has been termed "exercise as medicine". Exercise has favorable effects on reducing cardiovascular risk, inflammation, cachexia, and hypertension, in addition to increasing physical functioning, strength, and cardio-respiratory capacity. Chronic kidney disease, a condition that affects around 10% of the population, is often overlooked as a target for exercise-based therapy. Despite the vast range of severity in kidney disease (e.g., pre-dialysis, dialysis, transplant), exercise has a potential role in all patients suffering from the condition. In this review, we summarise the important role exercise may have in the clinical management of kidney disease and how this form of 'medicine' should be best administered and 'prescribed'. PMID:27334146

  6. Genetics Home Reference: medullary cystic kidney disease type 1

    MedlinePlus

    ... disease type 1 medullary cystic kidney disease type 1 Enable Javascript to view the expand/collapse boxes. ... Close All Description Medullary cystic kidney disease type 1 (MCKD1) is an inherited condition that affects the ...

  7. Genetics of kidney disease and related cardiometabolic phenotypes in Zuni Indians: the Zuni Kidney Project

    PubMed Central

    Laston, Sandra L.; Voruganti, V. Saroja; Haack, Karin; Shah, Vallabh O.; Bobelu, Arlene; Bobelu, Jeanette; Ghahate, Donica; Harford, Antonia M.; Paine, Susan S.; Tentori, Francesca; Cole, Shelley A.; MacCluer, Jean W.; Comuzzie, Anthony G.; Zager, Philip G.

    2015-01-01

    The objective of this study is to identify genetic factors associated with chronic kidney disease (CKD) and related cardiometabolic phenotypes among participants of the Genetics of Kidney Disease in Zuni Indians study. The study was conducted as a community-based participatory research project in the Zuni Indians, a small endogamous tribe in rural New Mexico. We recruited 998 members from 28 extended multigenerational families, ascertained through probands with CKD who had at least one sibling with CKD. We used the Illumina Infinium Human1M-Duo version 3.0 BeadChips to type 1.1 million single nucleotide polymorphisms (SNPs). Prevalence estimates for CKD, hyperuricemia, diabetes, and hypertension were 24%, 30%, 17% and 34%, respectively. We found a significant (p < 1.58 × 10-7) association for a SNP in a novel gene for serum creatinine (PTPLAD2). We replicated significant associations for genes with serum uric acid (SLC2A9), triglyceride levels (APOA1, BUD13, ZNF259), and total cholesterol (PVRL2). We found novel suggestive associations (p < 1.58 × 10-6) for SNPs in genes with systolic (OLFML2B), and diastolic blood pressure (NFIA). We identified a series of genes associated with CKD and related cardiometabolic phenotypes among Zuni Indians, a population with a high prevalence of kidney disease. Illuminating genetic variations that modulate the risk for these disorders may ultimately provide a basis for novel preventive strategies and therapeutic interventions. PMID:25688259

  8. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms

    PubMed Central

    Wattanakit, Keattiyoat; Cushman, Mary

    2010-01-01

    Purpose of review An estimated 13% of Americans have kidney disease. We sought to describe the association of kidney disease with risk of venous thromboembolism and discuss possible mechanisms explaining this association. Recent findings All severities of kidney disease appear to increase the risk of venous thromboembolism. In the general population the risk associated with mild to moderate kidney disease is 1.3–2-fold increased, and present even for microalbuminuria, although stage 1 chronic kidney disease itself has not been studied. End-stage renal disease is also associated with a 2.3-fold increased risk, compared to the general population. Although data are limited, risk increases after kidney transplant and with nephrotic syndrome as well. Summary Rates of kidney disease are increasing rapidly in the population and kidney disease is a risk factor for venous thromboembolism. An improved understanding of mechanisms linking kidney disease with venous thromboembolism will allow further study of best prevention efforts. PMID:19561505

  9. 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. PMID:27044633

  10. Nephrectomy in Autosomal Dominant Polycystic Kidney Disease: A Patient with Exceptionally Large, Still Functioning Kidneys

    PubMed Central

    Spithoven, Edwin M.; Casteleijn, Niek F.; Berger, Paul; Goldschmeding, Roel

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by progressive cyst formation in both kidneys, often leading to end-stage kidney disease. Indications for surgical removal of an ADPKD kidney include intractable pain, hematuria, infection, or exceptional enlargement and small abdominal cavity hampering implantation of a donor kidney. We report the case of an extraordinarily large ADPKD kidney weighing 8.7 kg (19.3 lb) with a maximal length of 48 cm (19 inch), and with cysts filled with both clear and bloody fluid. PMID:25028584

  11. 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

  12. MicroRNAs and Their Applications in Kidney Diseases

    PubMed Central

    Badal, Shawn S.; Danesh, Farhad R.

    2014-01-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that employ classic Watson-Crick base-pairing to identify their target genes, ultimately resulting in destabilizing their target mRNAs and/or inhibiting 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 will 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 will carefully examine the emerging role of miRNAs in the pathogenesis of various kidney diseases. PMID:24928414

  13. 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

  14. 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 ...

  15. Hypoxia and Dysregulated Angiogenesis in Kidney Disease

    PubMed Central

    Tanaka, Shinji; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2015-01-01

    Background Accumulating evidence has demonstrated that renal hypoxia has a crucial role in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and AKI-to-CKD transition, ultimately culminating in end-stage kidney disease. Renal hypoxia in progressive CKD is intricately linked to persisting capillary loss, which is mainly due to dysregulated angiogenesis. Summary In CKD, hypoxia-inducible factor (HIF) accumulates in the ischemic tubulointerstitium but fails to sufficiently stimulate angiogenic responses, partly because of blunted activation of HIF, which is best exemplified in diabetic kidney disease. In addition, vascular endothelial growth factor (VEGF) expression is downregulated, possibly because injured tubules are not able to express sufficient VEGF and inflammatory circumstances inhibit VEGF expression. The upregulation of antiangiogenic factors and the incompetence of endothelial progenitor cells (EPCs) may also play some roles in the inadequacy of capillary restoration. Administration of VEGF or angiopoietin-1 maintains peritubular capillaries in several kidney diseases; however, administration of a single angiogenic factor may lead to the formation of abnormal vessels and induce inflammation, resulting in worsening of hypoxia and tubulointerstitial fibrosis. HIF stabilization, which aims to achieve the formation of mature and stable vessels by inducing coordinated angiogenesis, is a promising strategy. Given that the effect of systemic HIF activation is highly context-dependent, further studies are needed to elucidate the precise roles of HIF in various kidney diseases. The adoptive transfer of EPCs or mesenchymal stem cells (MSCs) is a fascinating alternative strategy to restore the peritubular capillaries. Key Message Suppressed HIF activation and VEGF expression may be responsible for the dysregulated angiogenesis in progressive CKD. Administration of a single angiogenic factor can cause abnormal vessel formation and

  16. Therapeutic targets for treating fibrotic kidney diseases

    PubMed Central

    Lee, So-Young; Kim, Sung Il; Choi, Mary E.

    2014-01-01

    Renal fibrosis is the hallmark of virtually all progressive kidney diseases and strongly correlates with the deterioration of kidney function. The renin-angiotensin-aldosterone system blockade is central to the current treatment of patients with chronic kidney disease (CKD) for the renoprotective effects aimed to prevent or slow progression to end-stage renal disease (ESRD). However, the incidence of CKD is still increasing, and there is a critical need for new therapeutics. Here, we review novel strategies targeting various components implicated in the fibrogenic pathway to inhibit or retard the loss of kidney function. We focus, in particular, on anti-fibrotic approaches that target transforming growth factor (TGF)-β1, a key mediator of kidney fibrosis, and exciting new data on the role of autophagy. Bone morphogenetic protein (BMP)-7 and connective tissue growth factor (CTGF) are highlighted as modulators of pro-fibrotic TGF-β activity. BMP-7 has a protective role against TGF-β1 in kidney fibrosis, whereas CTGF enhances TGF-β-mediated fibrosis. We also discuss recent advances in the development of additional strategies for anti-fibrotic therapy. These include strategies targeting chemokine pathways via CC chemokine receptor 1 and 2 to modulate the inflammatory response, inhibition of phosphodiesterase to restore nitric oxide (NO)-cyclic 3′,5′ guanosine monophosphate (cGMP) function, inhibition of NADPH oxidase 1 (Nox1) and 4 (Nox4) to suppress reactive oxygen species production, as well as inhibition of endothelin-1 or tumor necrosis factor-α to ameliorate progressive renal fibrosis. Furthermore, a brief overview of some of the biomarkers of kidney fibrosis currently being explored that may improve the ability to monitor anti-fibrotic therapies. It is hoped that evidence based on the preclinical and clinical data discussed in this review leads to novel anti-fibrotic therapies effective in patients with CKD to prevent or delay progression to ESRD. PMID

  17. Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.

    PubMed

    Langefeld, Carl D; Divers, Jasmin; Pajewski, Nicholas M; Hawfield, Amret T; Reboussin, David M; Bild, Diane E; Kaysen, George A; Kimmel, Paul L; Raj, Dominic S; Ricardo, Ana C; Wright, Jackson T; Sedor, John R; Rocco, Michael V; Freedman, Barry I

    2015-01-01

    Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g. PMID:25029429

  18. Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial

    PubMed Central

    Langefeld, Carl D.; Divers, Jasmin; Pajewski, Nicholas M.; Hawfield, Amret T.; Reboussin, David M.; Bild, Diane E.; Kaysen, George A.; Kimmel, Paul L.; Raj, Dominic; Ricardo, Ana C.; Wright, Jackson T.; Sedor, John R.; Rocco, Michael V.; Freedman, Barry I.

    2014-01-01

    Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans. Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2,571 African Americans from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary or carotid artery revascularization) and CKD (eGFR under 60 ml/min/1.73m2 and/or UACR over 30 mg/g). African American SPRINT participants were 45.3% female with mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mmHg, eGFR 76.3 (77.1) ml/min/1.73m2, UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08–1.73) and log UACR estimated slope [β] 0.33) and negatively associated with eGFR (β −3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82–1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not prevalent CVD in African American with a UACR under 1000 mg/g. PMID:25029429

  19. Sex-specific associations of variants in regulatory regions of NADPH oxidase-2 (CYBB) and glutathione peroxidase 4 (GPX4) genes with kidney disease in type 1 diabetes.

    PubMed

    Monteiro, M B; Patente, T A; Mohammedi, K; Queiroz, M S; Azevedo, M J; Canani, L H; Parisi, M C; Marre, M; Velho, G; Corrêa-Giannella, M L

    2013-10-01

    Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2, encoded by the CYBB gene) and the antioxidant enzyme glutathione peroxidase 4 (GPX4) play opposing roles in the balance of cellular redox status. In the present study, we investigated associations of single nucleotide polymorphisms (SNPs) in the regulatory regions of CYBB and GPX4 with kidney disease in patients with type 1 diabetes. Two functional SNPs, rs6610650 (CYBB promoter region, chromosome X) and rs713041 (GPX4 3'untranslated region, chromosome 19), were genotyped in 451 patients with type 1 diabetes from a Brazilian cohort (diabetic nephropathy: 44.6%) and in 945 French/Belgian patients with type 1 diabetes from Genesis and GENEDIAB cohorts (diabetic nephropathy: 62.3%). The minor A-allele of CYBB rs6610650 was associated with lower estimated glomerular filtration rate (eGFR) in Brazilian women, and with the prevalence of established/advanced nephropathy in French/Belgian women (odds ratio 1.75, 95% CI 1.11-2.78, p = 0.016). The minor T-allele of GPX4 rs713041 was inversely associated with the prevalence of established/advanced nephropathy in Brazilian men (odds ratio 0.30, 95% CI 0.13-0.68, p = 0.004), and associated with higher eGFR in French/Belgian men. In conclusion, these heterogeneous results suggest that neither CYBB nor GPX4 are major genetic determinants of diabetic nephropathy, but nevertheless, they could modulate in a gender-specific manner the risk for renal disease in patients with type 1 diabetes. PMID:23919599

  20. [Chronic kidney disease, an often underestimated complication of diabetes].

    PubMed

    Sauvanet, Jean-Pierre

    2015-03-01

    Diabetic kidney chronic kidney disease, an often underestimated complication of diabetes. Diabetic kidney disease is a serious complication which can evolve into severe chronic kidney disease (CKD), or even end-stage renal disease (ESRD). It impacts on the patient's quality of life and that of their family and significantly increases the cost of care. The development and progression of chronic kidney disease is prevented by strictly controlling blood sugar levels and cardiovascular risk factors as well as monitoring the markers of kidney disease. In the case of CKD, treatment may need to be adapted. PMID:26036123

  1. Tissue-Engineered Kidney Disease Models

    PubMed Central

    DesRochers, Teresa M.; Palma, Erica; Kaplan, David L.

    2014-01-01

    Renal disease represents a major health problem that often results in end-stage renal failure necessitating dialysis and eventually transplantation. Historically these diseases have been studied with patient observation and screening, animal models, and two-dimensional cell culture. In this review, we focus on recent advances in tissue engineered kidney disease models that have the capacity to compensate for the limitations of traditional modalities. The cells and materials utilized to develop these models are discussed and tissue engineered models of polycystic kidney disease, drug-induced nephrotoxicity, and the glomerulus are examined in detail. The application of these models has the potential to direct future disease treatments and preclinical drug development. PMID:24361391

  2. 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

  3. Tuberculosis-associated chronic kidney disease.

    PubMed

    de Oliveira, Jobson Lopes; da Silva Junior, Geraldo Bezerra; Daher, Elizabeth De Francesco

    2011-06-01

    Extrapulmonary tuberculosis (TB) account for approximately 15-20% of TB cases in immunocompetent patients. The genitourinary system is the third most commonly affected site. We report the case of a 20-year-old man admitted with fever, chills, dry cough, right flank pain, and oliguria who developed renal function loss. The pyelogram evidenced silence of the right kidney, and the abdominal and pelvic magnetic resonance showed significant dilation of the right pyelocaliceal system and proximal ureter. Biopsies of renal cortex and retroperitoneal lymph nodes showed caseous granuloma consistent with TB. Treatment was started with rifampicin, isoniazid, pyrazinamide, and ethambutol, and the patient presented a favorable outcome but with non-dialytic chronic kidney disease. This case illustrates a case of chronic kidney disease secondary to TB in a young, otherwise healthy man. PMID:21633015

  4. Genetics Home Reference: uromodulin-associated kidney disease

    MedlinePlus

    ... and How They Work Educational Resources (4 links) Disease InfoSearch: Medullary cystic kidney disease 2 Merck Manual Home Edition: ... Registry (3 links) Familial juvenile gout Glomerulocystic kidney disease with hyperuricemia and ... cystic kidney disease 2 Scientific articles on PubMed ( ...

  5. RAGE and glyoxalase in kidney disease.

    PubMed

    Inagi, Reiko

    2016-08-01

    Glycation is an important reaction in the regulation of physiological state. When poorly controlled, however, glycation can also result in the accumulation of glycated proteins (advanced glycation endproducts; AGEs) in the body. This AGE accumulation is termed glycative stress, and is an established pathological factor: to date, glycative stress has been closely associated with not only kidney diseases, but also kidney aging. Accumulating evidence demonstrates that the progression of renal tubular damage and tubular aging are often correlated with activation of the receptor for the AGE (RAGE)-AGE pathway or decreased activity of glyoxalase 1, which is an anti-glycation enzyme to lower glycative stress. Further, glycative stress exacerbates the derangement of protein homeostasis: the posttranslationally modified proteins by glycation often lose or gain their functions. Such deranged protein homeostasis leads to endoplasmic reticulum (ER) stress, a state of ER dysfunction in which the quality control of proteins is defective, as well as to induction of its stress signal, the unfolded protein response (UPR), in the kidney. The lowering of glycative stress via modulation of RAGE-AGE axis or glyoxalase 1 activity is beneficial for tubular homeostasis and the subsequent prevention and treatment of kidney disease, suggesting the possibility of novel therapeutic approaches which target glycative stress. In this review, we focused on the impact of glycative stress in the kidney, especially the role of RAGE and glyoxalase 1. Further we also discuss the crosstalk between glycative stress and ER stress in their effect on protein homeostasis. PMID:27270765

  6. High Blood Pressure and Kidney Disease

    MedlinePlus

    ... in the urine. A urine albumin-to-creatinine ratio above 30 mg/g may be a sign of kidney disease. Blood Test A blood test involves having blood drawn at a health care provider’s office or a commercial facility and sending the sample to a lab for analysis. A health care provider may order a blood ...

  7. 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. PMID:26880442

  8. 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

  9. Screening for cardiovascular disease before kidney transplantation.

    PubMed

    Palepu, Sneha; Prasad, G V Ramesh

    2015-12-24

    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

  10. 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. PMID:24220764

  11. A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys

    PubMed Central

    Huang, Liwei; Xiao, An; Wecker, Andrea; McBride, Daniel A.; Choi, Soo Young; Zhou, Weibin; Lipschutz, Joshua H.

    2015-01-01

    Polycystic kidney disease (PKD) is one of the most common causes of end-stage kidney disease, a devastating disease for which there is no cure. The molecular mechanisms leading to cyst formation in PKD remain somewhat unclear, but many genes are thought to be involved. Wnt5a is a non-canonical glycoprotein that regulates a wide range of developmental processes. Wnt5a works through the planar cell polarity (PCP) pathway that regulates oriented cell division during renal tubular cell elongation. Defects of the PCP pathway have been found to cause kidney cyst formation. Our paper describes a method for developing a zebrafish cystic kidney disease model by knockdown of the wnt5a gene with wnt5a antisense morpholino (MO) oligonucleotides. Tg(wt1b:GFP) transgenic zebrafish were used to visualize kidney structure and kidney cysts following wnt5a knockdown. Two distinct antisense MOs (AUG - and splice-site) were used and both resulted in curly tail down phenotype and cyst formation after wnt5a knockdown. Injection of mouse Wnt5a mRNA, resistant to the MOs due to a difference in primary base pair structure, rescued the abnormal phenotype, demonstrating that the phenotype was not due to “off-target” effects of the morpholino. This work supports the validity of using a zebrafish model to study wnt5a function in the kidney. PMID:25489842

  12. Common Heartburn Drugs Linked to Kidney Disease in Study

    MedlinePlus

    ... fullstory_158313.html Common Heartburn Drugs Linked to Kidney Disease in Study But finding can't show whether ... heartburn may be at increased risk of developing kidney disease, a new study suggests. The research is the ...

  13. 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 ...

  14. Phosphorus: Tips for People with Chronic Kidney Disease (CKD)

    MedlinePlus

    Phosphorus Tips for People with Chronic Kidney Disease (CKD) National Kidney Disease Education Program What Is Phosphorus? Phosphorus is a mineral that helps keep your bones healthy. It also helps ...

  15. Chronic Kidney Disease: What Does It Mean for Me?

    MedlinePlus

    ... online catalog. Alternate Language URL Españ​ol Chronic Kidney Disease: What Does it Mean for Me? Page Content ... My Lifestyle CKD: Tracking My Test Results Chronic Kidney Disease: The Basics You've been told that you ...

  16. Slowing progression of chronic kidney disease.

    PubMed

    Drawz, Paul E; Rosenberg, Mark E

    2013-12-01

    Early identification of chronic kidney disease (CKD) provides an opportunity to implement therapies to improve kidney function and slow progression. The goal of this article is to review established and developing clinical therapies directed at slowing progression. The importance of controlling blood pressure will be discussed along with the target blood pressure that should be achieved in CKD patients. Therapy directed at inhibiting the renin-angiotensin-aldosterone system remains the mainstay of treatment with single-agent inhibition of this system being as good as dual blockade with fewer adverse effects. Other therapies that may be used include correction of metabolic acidosis, dietary protein restriction, and new models for delivering care to patients with CKD. Emerging therapies targeting endothelin, uric acid, kidney fibrosis, and oxidant stress hold promise for the future. PMID:25019022

  17. 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. PMID:26453039

  18. The regulation and function of microRNAs in kidney diseases

    PubMed Central

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

    2013-01-01

    MicroRNAs (miRNA) are endogenous short non-coding 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. PMID:23794512

  19. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... Disease Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Anemia in CKD Page Content On this page: What ... Nutrition Points to Remember Clinical Trials What is anemia? Anemia is a condition in which the body ...

  20. Role of autophagy in chronic kidney diseases

    PubMed Central

    Mao, Song; Zhang, Jianhua

    2015-01-01

    Chronic kidney diseases (CKD), a common pathway of various glomerular diseases, which carries great morbidity and mortality to people. CKD is characterized by progressive kidney fibrosis and remodeling. CKD is also associated with the depletion of glomerular and tubular cells. Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. It plays an important role in both normal and disease states, including immunity, inflammation, and adaptation to stress. Evidence has indicated that impaired autophagic activity is involved in the development of CKD. Here, we review the progress in our understanding of the role of autophagy in the development and progression of CKD. Targeting the autophagic signaling pathways may be a therapeutic strategy for CKD. PMID:26885176

  1. 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...

  2. 42 CFR 410.48 - Kidney disease education services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 patient education services means face-to-face educational services provided to patients with Stage IV chronic...

  3. 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...

  4. 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...

  5. 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...

  6. Keep Your Kidneys Healthy: Catch Kidney Disease Early

    MedlinePlus

    ... point, you may need a kidney transplant or dialysis. It’s a good idea to talk with your ... healthy kidneys and finding a well-matched donor. Dialysis is a treatment that filters wastes and water ...

  7. A Prediction Model for Chronic Kidney Disease Includes Periodontal Disease

    PubMed Central

    Fisher, Monica A.; Taylor, George W.

    2009-01-01

    Background An estimated 75% of the seven million Americans with moderate-to-severe chronic kidney disease are undiagnosed. Improved prediction models to identify high-risk subgroups for chronic kidney disease enhance the ability of health care providers to prevent or delay serious sequelae, including kidney failure, cardiovascular disease, and premature death. Methods We identified 11,955 adults ≥18 years of age in the Third National Health and Nutrition Examination Survey. Chronic kidney disease was defined as an estimated glomerular filtration rate of 15 to 59 ml/minute/1.73 m2. High-risk subgroups for chronic kidney disease were identified by estimating the individual probability using β coefficients from the model of traditional and non-traditional risk factors. To evaluate this model, we performed standard diagnostic analyses of sensitivity, specificity, positive predictive value, and negative predictive value using 5%, 10%, 15%, and 20% probability cutoff points. Results The estimated probability of chronic kidney disease ranged from virtually no probability (0%) for an individual with none of the 12 risk factors to very high probability (98%) for an older, non-Hispanic white edentulous former smoker, with diabetes ≥10 years, hypertension, macroalbuminuria, high cholesterol, low high-density lipoprotein, high C-reactive protein, lower income, and who was hospitalized in the past year. Evaluation of this model using an estimated 5% probability cutoff point resulted in 86% sensitivity, 85% specificity, 18% positive predictive value, and 99% negative predictive value. Conclusion This United States population–based study suggested the importance of considering multiple risk factors, including periodontal status, because this improves the identification of individuals at high risk for chronic kidney disease and may ultimately reduce its burden. PMID:19228085

  8. Arterial Stiffness and Chronic Kidney Disease

    PubMed Central

    Garnier, Anne-Sophie; Briet, Marie

    2016-01-01

    Chronic kidney disease (CKD) is a major public health concern due to the high prevalence of associated cardiovascular (CV) disease. CV mortality is 10-30 times higher in end-stage renal disease patients than in the age-adjusted general population. The last 20 years have been marked by a huge effort in the characterization of the vascular remodeling process associated with CKD and its consequences on the renal, CV and general prognosis. By comparison with patients with normal renal function, with or without hypertension, an increase in large artery stiffness has been described in end-stage renal disease as well as in CKD stages 2-5. Most clinical studies are consistent with the observation that damage to large arteries may contribute to the high incidence of CV disease. By contrast, the impact of large artery stiffening and remodeling on CKD progression is still a matter of debate. Concomitant exposure to other CV risk factors, including diabetes, seems to play a major role in the association between aortic stiffness and estimated GFR. The conflicting results obtained from longitudinal studies designed to evaluate the impact of baseline aortic stiffness on GFR progression are detailed in the present review. Only pulse pressure, central and peripheral, is almost constantly associated with incident CKD and GFR decline. Kidney transplantation improves patients’ CV prognosis, but its impact on arterial stiffness is still controversial. Donor age, living kidney donation and mean blood pressure appear to be the main determinants of improvement in aortic stiffness after kidney transplantation. PMID:27195244

  9. Cystic gene dosage influences kidney lesions after nephron reduction.

    PubMed

    Le Corre, Stéphanie; Viau, Amandine; Burtin, Martine; El-Karoui, Khalil; Cnops, Yvette; Terryn, Sara; Debaix, Huguette; Bérissi, Sophie; Gubler, Marie-Claire; Devuyst, Olivier; Terzi, Fabiola

    2015-01-01

    Cystic kidney disease is characterized by the progressive development of multiple fluid-filled cysts. Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to renal failure. The most frequent form of this disease is the inherited polycystic kidney disease (PKD). Experimental models of PKD showed that an increase of cellular proliferation and apoptosis as well as defects in apico-basal and planar cell polarity or cilia play a critical role in cyst development. However, little is known about the mechanisms and the mediators involved in acquired cystic kidney diseases (ACKD). In this study, we used the nephron reduction as a model to study the mechanisms underlying cyst development in ACKD. We found that tubular dilations after nephron reduction recapitulated most of the morphological features of ACKD. The development of tubular dilations was associated with a dramatic increase of cell proliferation. In contrast, the apico-basal polarity and cilia did not seem to be affected. Interestingly, polycystin 1 and fibrocystin were markedly increased and polycystin 2 was decreased in cells lining the dilated tubules, whereas the expression of several other cystic genes did not change. More importantly, Pkd1 haploinsufficiency accelerated the development of tubular dilations after nephron reduction, a phenotype that was associated to a further increase of cell proliferation. These data were relevant to humans ACKD, as cystic genes expression and the rate of cell proliferation were also increased. In conclusion, our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes involved in PKD is also important in ACKD. PMID:25531116

  10. L-FABP: A novel biomarker of kidney disease.

    PubMed

    Xu, Yao; Xie, Yuanyuan; Shao, Xinghua; Ni, Zhaohui; Mou, Shan

    2015-05-20

    Human liver-type fatty acid-binding protein (hL-FABP), which is found in both the normal and the diseased human kidney, has been observed to bind free fatty acids. Recently, the predictive and prognostic value of L-FABP in kidney diseases has attracted considerable attention. Numerous studies have demonstrated that L-FABP is a promising biomarker of several kidney diseases, and it has also been shown to attenuate renal injury. We performed a literature review regarding the ability of L-FABP to identify patients at risk of developing kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD) and to protect the kidneys in the course of kidney disease. PMID:25797895

  11. Autosomal dominant polycystic kidney disease: time for a change?

    PubMed

    Chapman, Arlene B

    2007-05-01

    Diagnosis and treatment of autosomal dominant polycystic kidney disease (ADPKD) is rapidly changing. Cellular pathways that involve the polycystins are being mapped and involve the primary cilium, intracellular calcium and cAMP regulation, and the mammalian target of rapamycin (mTOR) pathway. With the use of new imaging approaches, earlier diagnosis of hepatic cystic disease is possible, and measurement of kidney and cystic growth as well as kidney blood flow is possible over relatively short periods. PKD gene type, gender, proteinuria, and the presence of hypertension relate to the rate of kidney growth in ADPKD. On the basis of risk factors for progression to ESRD and the pathogenic roles that intracellular cAMP and mTOR play in cystogenesis, novel therapies are now being tested, including maximal inhibition of the renin-angiotensin system, inhibition of renal intracellular cAMP using vasopressin V2 receptor antagonists, and somatostatin analogues, as well as inhibitors of mTOR. This review addresses the current understanding of the pathogenesis and the natural history of ADPKD; accuracy and reliability of diagnostic approaches in utero, childhood, and adulthood; the value of reliable magnetic resonance imaging to measure disease progression early in the course of ADPKD; and novel therapeutic approaches that are being evaluated in ADPKD. PMID:17429048

  12. Vitamin D in Chronic Kidney Disease

    PubMed Central

    Chau, Yahn-Yir

    2016-01-01

    Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease (CKD) population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children (CKiD) and the Cardiovascular Comorbidity in Children with CKD (4 C) should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes. PMID:22544696

  13. 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. PMID:26676663

  14. Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.

    PubMed Central

    Reeders, S T; Breuning, M H; Corney, G; Jeremiah, S J; Meera Khan, P; Davies, K E; Hopkinson, D A; Pearson, P L; Weatherall, D J

    1986-01-01

    The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis. Images FIG 1 PMID:3008903

  15. Haemostasis in chronic kidney disease.

    PubMed

    Lutz, Jens; Menke, Julia; Sollinger, Daniel; Schinzel, Helmut; Thürmel, Klaus

    2014-01-01

    The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency. PMID:24132242

  16. Endothelin Blockade in Diabetic Kidney Disease

    PubMed Central

    Anguiano, Lidia; Riera, Marta; Pascual, Julio; Soler, María José

    2015-01-01

    Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB) within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described. PMID:26239552

  17. Interdisciplinary care clinics in chronic kidney disease.

    PubMed

    Johns, Tanya S; Yee, Jerry; Smith-Jules, Terrian; Campbell, Ruth C; Bauer, Carolyn

    2015-01-01

    The burden of chronic kidney disease (CKD) is substantial, and is associated with high hospitalization rates, premature deaths, and considerable health care costs. These factors provide strong rationale for quality improvement initiatives in CKD care. The interdisciplinary care clinic (IDC) has emerged as one solution to improving CKD care. The IDC team may include other physicians, advanced practice providers, nurses, dietitians, pharmacists, and social workers--all working together to provide effective care to patients with chronic kidney disease. Studies suggest that IDCs may improve patient education and preparedness prior to kidney failure, both of which have been associated with improved health outcomes. Interdisciplinary care may also delay the progression to end-stage renal disease and reduce mortality. While most studies suggest that IDC services are likely cost-effective, financing IDCs is challenging and many insurance providers do not pay for all of the services. There are also no robust long-term studies demonstrating the cost-effectiveness of IDCs. This review discusses IDC models and its potential impact on CKD care as well as some of the challenges that may be associated with implementing these clinics. PMID:26458811

  18. Obesity, hypertension, and chronic kidney disease

    PubMed Central

    Hall, Michael E; do Carmo, Jussara M; da Silva, Alexandre A; Juncos, Luis A; Wang, Zhen; Hall, John E

    2014-01-01

    Obesity is a major risk factor for essential hypertension, diabetes, and other comorbid conditions that contribute to development of chronic kidney disease. Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis, and causing volume expansion via activation of the sympathetic nervous system and renin–angiotensin–aldosterone system and by physical compression of the kidneys, especially when there is increased visceral adiposity. Other factors such as inflammation, oxidative stress, and lipotoxicity may also contribute to obesity-mediated hypertension and renal dysfunction. Initially, obesity causes renal vasodilation and glomerular hyperfiltration, which act as compensatory mechanisms to maintain sodium balance despite increased tubular reabsorption. However, these compensations, along with increased arterial pressure and metabolic abnormalities, may ultimately lead to glomerular injury and initiate a slowly developing vicious cycle that exacerbates hypertension and worsens renal injury. Body weight reduction, via caloric restriction and increased physical activity, is an important first step for management of obesity, hypertension, and chronic kidney disease. However, this strategy may not be effective in producing long-term weight loss or in preventing cardiorenal and metabolic consequences in many obese patients. The majority of obese patients require medical therapy for obesity-associated hypertension, metabolic disorders, and renal disease, and morbidly obese patients may require surgical interventions to produce sustained weight loss. PMID:24600241

  19. Hereditary kidney cancer: unique opportunity for disease-based therapy.

    PubMed

    Linehan, W Marston; Pinto, Peter A; Bratslavsky, Gennady; Pfaffenroth, Elizabeth; Merino, Maria; Vocke, Cathy D; Toro, Jorge R; Bottaro, Donald; Neckers, Len; Schmidt, Laura S; Srinivasan, Ramaprasad

    2009-05-15

    Kidney cancer is not a single disease; it is comprised of several different types of cancer, each with a different histology, with a different clinical course, caused by a different gene, and responding differently to therapy. The VHL gene is the gene for the hereditary cancer syndrome, von Hippel-Lindau, as well as for the common form of sporadic, noninherited, clear cell kidney cancer. Understanding the VHL-hypoxia inducible factor (HIF) pathway has provided the foundation for the development of several agents targeting this pathway, such as sunitinib, sorafenib, and temsirolimus. Hereditary papillary renal carcinoma (HPRC) is a hereditary renal cancer syndrome in which affected individuals are at risk for the development of bilateral, multifocal, type 1 papillary renal cell carcinoma. The genetic defect underlying HPRC is MET, the cell surface receptor for hepatocyte growth factor. Mutations of MET also have been identified in a subset of tumors from patients with sporadic type 1 papillary renal cell carcinoma (RCC). Clinical trials targeting the MET pathway are currently underway in patients with HPRC and in patients with sporadic (nonhereditary) papillary kidney cancer. The BHD gene (also known as folliculin or FLCN) is the gene for Birt-Hogg-Dube syndrome, an autosomal-dominant genodermatosis associated with a hereditary form of chromophobe and oncocytic, hybrid RCC. Preclinical studies are underway targeting the BHD gene pathway in preparation for clinical trials in Birt-Hogg-Dube and sporadic chromophobe RCC. Patients with hereditary leiomyomatosis RCC (HLRCC) are at risk for developing cutaneous and uterine leiomyomas and a very aggressive type of RCC. HLRCC is characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH). Studies of the tricarboxylic acid cycle and the VHL-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer as well as other hereditary and sporadic

  20. Chronic kidney disease: Statins in chronic kidney disease: time to move on?

    PubMed

    Haynes, Richard; Wanner, Christoph

    2015-05-01

    Statins reduce the risk of atherosclerotic vascular disease in healthy individuals and those with chronic kidney disease (CKD); however, clinical trials have suggested a minimal effect of statins on CKD progression. The PLANET trials compared the renal effects of rosuvastatin and atorvastatin, but the findings leave many questions unanswered. PMID:25802077

  1. World Kidney Day 2016: 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 (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 a 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:26884120

  2. Editorial: World Kidney Day 2016: 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 a 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 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 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:27085729

  3. Genome-wide association studies in pediatric chronic kidney disease.

    PubMed

    Gupta, Jayanta; Kanetsky, Peter A; Wuttke, Matthias; Köttgen, Anna; Schaefer, Franz; Wong, Craig S

    2016-08-01

    The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression. PMID:26490952

  4. Cilia and Polycystic Kidney Disease, Kith and Kin

    PubMed Central

    Huang, Liwei; Lipschutz, Joshua H.

    2015-01-01

    In the past decade, cilia have been found to play important roles in renal cystogenesis. Many genes, such as PKD1 and PKD2 which, when mutated, cause autosomal dominant polycystic kidney disease (ADPKD), have been found to localize to primary cilia. The cilium functions as a sensor to transmit extracellular signals into the cell. Abnormal cilia structure and function are associated with the development of polyscystic kidney disease (PKD). Cilia assembly includes centriole migration to the apical surface of the cell, ciliary vesicle docking and fusion with the cell membrane at the intended site of cilium outgrowth, and microtubule growth from the basal body. This review summarizes the most recent advances in cilia and PKD research, with special emphasis on the mechanisms of cytoplasmic and intraciliary protein transport during ciliogenesis. PMID:24898006

  5. Skin manifestations of chronic kidney disease.

    PubMed

    Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

    2015-10-01

    Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. PMID:26093993

  6. 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. PMID:26880450

  7. Autosomal dominant polycystic kidney disease: recent advances in clinical management

    PubMed Central

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C. M.

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  8. Integrin α3 Mutations with Kidney, Lung, and Skin Disease

    PubMed Central

    Has, Cristina; Spartà, Giuseppina; Kiritsi, Dimitra; Weibel, Lisa; Moeller, Alexander; Vega-Warner, Virginia; Waters, Aoife; He, Yinghong; Anikster, Yair; Esser, Philipp; Straub, Beate K.; Hausser, Ingrid; Bockenhauer, Detlef; Dekel, Benjamin; Hildebrandt, Friedhelm; Bruckner-Tuderman, Leena; Laube, Guido F.

    2012-01-01

    SUMMARY Integrin α3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin α3 gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. PMID:22512483

  9. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    PubMed

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  10. APOL1 nephropathy: from gene to mechanisms of kidney injury.

    PubMed

    Kruzel-Davila, Etty; Wasser, Walter G; Aviram, Sharon; Skorecki, Karl

    2016-03-01

    The contribution of African ancestry to the risk of focal segmental glomerulosclerosis and chronic kidney disease has been partially explained by the recently described chromosome 22q variants in the gene apolipoprotein L1 (APOL1). The APOL1 variants appear at a high allele frequency in populations of West African ancestry as a result of apparent adaptive selection of the heterozygous state. Heterozygosity protects from infection with Trypanosoma brucei rhodesiense. This review will describe the role of the approaches in population genetics for the description of APOL1-associated nephropathies and draw inferences as to the biologic mechanisms from genetic epidemiology findings to date. Modifier loci can influence APOL1 risk for the development of kidney disease. 'Second hits', both viral and non-viral, may explain the discrepancy between the remarkably high odds ratios and the low lifetime risks of kidney disease in two allele carriers of APOL1 risk variants. Therapeutic strategies for APOL1-associated nephropathies will require the prevention and treatment of these 'second hits' and the development of drugs to protect the APOL1 downstream renal injury pathways. PMID:25561578

  11. Molecular assessment of disease states in kidney transplant biopsy samples.

    PubMed

    Halloran, Philip F; Famulski, Konrad S; Reeve, Jeff

    2016-09-01

    Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis. TCMR and ABMR share IFNγ-mediated effects and TCMR has emerged as a cognate T cell-antigen presenting cell process in the interstitium, whereas ABMR is a natural-killer-cell-mediated process that occurs in the microcirculation. The specific features of these different processes have led to the creation of classifiers to test for TCMR and ABMR, and revealed that ABMR is the principal cause of kidney transplant deterioration. The molecular changes associated with renal injury are often more extensive than suggested by histology and indicate that the progression to graft failure is caused by continuing nephron injury, rather than fibrogenesis. In summary, advances in the molecular assessment of disease states in biopsy samples has improved understanding of specific processes involved in kidney graft outcomes. PMID:27345248

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

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease and Diabetes: What You Need to Know ... page please turn Javascript on. March is National Kidney Month , a good time to check if you ...

  13. When Your Child Has a Chronic Kidney Disease

    MedlinePlus

    ... two treatment options are available — dialysis and transplant. Dialysis Nearly all kids with end-stage kidney disease ... a living related donor can't be found, dialysis may be required until a donor kidney becomes ...

  14. Assessment of cognitive dysfunction in kidney disease.

    PubMed

    Nasser, Mohamed El Tayeb; Shawki, Sahar; El Shahawy, Yasser; Sany, Dawlat

    2012-11-01

    Cognitive dysfunction includes reduced mental alertness, intellectual impairment, decreased attention and concentration, memory deficits and diminished perceptual-motor coordination. Chronic kidney disease (CKD) patients may suffer from cognitive impairment, which may decrease an individual's quality of life, increase resource utilization and result in suboptimal medical care. This study was carried out on 120 patients with different stages of CKD from our nephrology outpatient clinic divided into three groups: Group I: 50 CKD patients, stage 3 and stage 4; Group II: 50 end-stage renal disease patients on regular hemodialysis with K t/v >1.1; and Group III: 20 acute kidney injury patients, followed-up till their renal functions stabilized besides Group IV: 20 healthy subjects served as controls. All patients underwent laboratory investigations and psychometric tests, which include trial making test part B, digit span test, digit symbol test and mini-mental state examination. There was a significant difference of mean values of cognitive function tests in Groups I, II and III on comparing them with Group IV. Stage 3 CKD scored better than stage 4 CKD, which was worse than hemodialysis patients, and lastly acute kidney injury patients had mild cognitive impairment, which was restored after recovery. We found an association between hemoglobin and cognitive function tests score in the studied groups. The degree of cognitive impairment was associated with the severity of CKD, and dialysis improved cognitive performance. PMID:23168850

  15. Interactions between thyroid disorders and kidney disease

    PubMed Central

    Basu, Gopal; Mohapatra, Anjali

    2012-01-01

    There are several interactions between thyroid and kidney functions in each other organ's disease states. Thyroid hormones affect renal development and physiology. Thyroid hormones have pre-renal and intrinsic renal effects by which they increase the renal blood flow and the glomerular filtration rate (GFR). Hypothyroidism is associated with reduced GFR and hyperthyroidism results in increased GFR as well as increased renin – angiotensin – aldosterone activation. Chronic kidney disease (CKD) is characterized by a low T3 syndrome which is now considered a part of an atypical nonthyroidal illness. CKD patients also have increased incidence of primary hypothyroidism and subclinical hypothyroidism. The physiological benefits of a hypothyroid state in CKD, and the risk of CKD progression with hyperthyroidism emphasize on a conservative approach in the treatment of thyroid hormone abnormalities in CKD. Thyroid dysfunction is also associated with glomerulonephritis often by a common autoimmune etiology. Several drugs could affect both thyroid and kidney functions. There are few described interactions between thyroid and renal malignancies. A detailed knowledge of all these interactions is important for both the nephrologists and endocrinologists for optimal management of the patient. PMID:22470856

  16. Hypertension and chronic kidney disease in Turkey.

    PubMed

    Sengul, Sule; Erdem, Yunus; Batuman, Vecihi; Erturk, Sehsuvar

    2013-12-01

    Worldwide, both hypertension and chronic kidney disease are major public health problems, due to their epidemic proportions and their association with high cardiovascular mortality. In 2003, the first Prevalence, awareness, treatment, and control of hypertension in Turkey (the PatenT) study was conducted in a nationally representative population (n=4910) by the Turkish Society of Hypertension and Renal Diseases, and showed that overall age- and sex-adjusted prevalence of hypertension in Turkey was 31.8%. The PatenT study also reported that overall awareness (40.7%), treatment (31.1%), and control rates (8.1%) of hypertension were strikingly low. Only 20.7% of the patients who were aware of their hypertension and receiving treatment had their blood pressure controlled to <140/90 mm Hg. In the Chronic Renal Disease in Turkey (CREDIT) study (n=10,748), the overall prevalence of chronic kidney (including all stages) disease was 15.7% and increased with advancing age. In the same population, the prevalence of hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome were reported as 32.7%, 12.7%, 76.3%, 20.1%, and 31.3%, respectively. The prevalence and awareness of hypertension in CREDIT population was 32.7% and 48.6%, respectively. According to the data obtained from national surveys, the prevalence of hypertension and chronic kidney disease in Turkey is alarmingly high. To improve prevention, early diagnosis, and treatment of these major public health problems, appropriate health strategies should be implemented by the government, together with medical societies, non-governmental organizations, industry, health-care providers, and academia. PMID:25019009

  17. 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

  18. Mechanisms of progression of chronic kidney disease

    PubMed Central

    2007-01-01

    Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin–angiotensin–aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number. PMID:17647026

  19. Crohnic Kidney Disease: Recurrent Acute Kidney Failure in a Patient With Crohn's Disease

    PubMed Central

    Demir, Mehmet Emin; Ercan, Zafer; Karakas, Emel Yigit; Ulas, Turgay; Buyukhatipoglu, Hakan

    2014-01-01

    Context: Short bowel syndrome is a rare and devastating complication in chronic inflammatory bowel disease following functional or anatomic loss of extensive segments of the intestine. Case Report: A 60-year-old male patient with Crohn's disease had undergone multiple resections of the intestine and developed short bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and magnesium intake, he suffered from recurrent acute kidney injury due to profound volume depletion and those electrolyte deficiencies. Administration of intravenous fluid and electrolyte repleacement treatment at regular intervals prevented further kidney injuries. Conclusion: We present a case of recurrent acute kidney failure in a patient with Crohn's disease, and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome. PMID:25599054

  20. 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...

  1. 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...

  2. 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...

  3. Clinical Scenarios in Chronic Kidney Disease: Chronic Tubulointerstitial Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Chronic tubulointerstitial diseases are a common final pathway toward chronic renal failure regardless the primary damage (glomerular, vascular or directly the tubulointerstitium). Chronic tubulointerstitial nephritis (CTN) is characterized by interstitial scarring, fibrosis and tubule atrophy, resulting in progressive chronic kidney disease. Most frequent causes of CTN are drugs, heavy metals, obstructive uropathy, nephrolithiasis, reflux disease, immunologic diseases, neoplasia, ischemia, metabolic diseases, genetics and miscellaneous. At ultrasound (US), kidneys' morphological aspect is similar in all forms of chronic interstitial nephropathy and only chronic pyelonephritis with or without reflux shows distinguishing characteristics. In interstitial nephropathy, kidneys' profiles are finely irregular and corticomedullary differentiation is altered because of a diffused hyperechogenicity. The only indirect sign of chronic interstitial damage can be derived from the value of intrarenal resistive indexes that hardly overcome 0.75. US is mandatory in clinical chronic pyelonephritis work-up because it provides information on kidney's diameter and on growth nomogram in children. Renal profiles can be more or less altered depending on the number of cortical scars and the presence of pseudonodular areas of segmental compensatory hypertrophy. In the early stages, US diagnosis of renal tuberculosis is difficult because parenchymal lesions are non-specific. US sensitivity in the diagnosis of hydronephrosis is very high, close to 100% and, finally, US is the first choice imaging technique in the diagnosis of urinary lithiasis. PMID:27169608

  4. 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

  5. Tracking kidney volume in mice with polycystic kidney disease by magnetic resonance imaging.

    PubMed

    Wallace, D P; Hou, Y-P; Huang, Z L; Nivens, E; Savinkova, L; Yamaguchi, T; Bilgen, M

    2008-03-01

    Polycystic kidney disease is characterized by the progressive enlargement of kidneys due to expanding fluid-filled cysts with the rate of renal volume increase held to be a marker of disease progression. Magnetic resonance imaging (MRI) is used to monitor changes in renal volume in patients with polycystic kidney disease; however, it has not been effectively used in mice to monitor changes in kidney volume during drug treatment studies. We used a powerful 9.4-T horizontal bore magnetic resonance scanner to track changes in kidney volume in pcy/pcy mice, an ortholog of nephronophthisis type 3. Mice were sequentially scanned from 4 to 30 weeks of age and kidney volumes determined from high-resolution images. Kidney volume and maximal cross-sectional surface area correlated positively with kidney weight and the histologic determination of surface area. The increase in kidney volume was exponential up to 20 weeks of age, after which there was a plateau consistent with the replacement of normal parenchyma by fibrotic tissue. Our study demonstrates that MRI accurately determines the rate of kidney volume increase in mice with polycystic kidney disease and hence may be useful in assessing the effectiveness of therapeutic agents to slow disease progression. PMID:18185504

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

    PubMed Central

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

    2014-01-01

    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. PMID:24856029

  7. Talking with Your Health Care Professionals about Kidney Disease

    MedlinePlus

    ... Topics Information about diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and ... metabólicas, y enfermedades hematológicas Health Statistics Diabetes, digestive, kidney diseases, obesity, weight and more Healthy Moments Radio Broadcast ...

  8. National Institute of Diabetes and Digestive and Kidney Diseases

    MedlinePlus

    ... Topics Information about diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and ... metabólicas, y enfermedades hematológicas Health Statistics Diabetes, digestive, kidney diseases, obesity, weight and more Healthy Moments Radio Broadcast ...

  9. Overview of Kidney Diseases in Children

    MedlinePlus

    ... a kidney transplant or blood-filtering treatments called dialysis. Children with CKD or kidney failure face many ... kidneys do. The two types of treatment are dialysis and transplantation. More information is provided in the ...

  10. 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 (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:26997373

  11. 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

  12. 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

  13. 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. PMID:27536691

  14. MOLECULAR ADVANCES IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

    PubMed Central

    Gallagher, Anna Rachel; Germino, Gregory G.; Somlo, Stefan

    2010-01-01

    Autosomal dominant polycystic disease (ADPKD) is the most common form of inherited kidney disease that results renal failure. The understanding the pathogenesis of ADPKD has advanced significantly since the discovery of the two causative genes, PKD1 or PKD2. Dominantly inherited gene mutations followed by somatic second hit mutations inactivating the normal copy of the respective gene result in renal tubular cyst formation that deforms the kidney and eventually impairs its function. The respective gene products, polycystin-1 and polycystin-2, work together in a common cellular pathway. Polycystin-1, a large receptor molecule, forms a receptor-channel complex with polycystin-2, which is a cation channel belonging to the TRP family. Both polycystin proteins have been localized to the primary cilium, a non-motile microtubule based structure that extends from the apical membrane of tubular cells into the lumen. Here we discuss recent insights in the pathogenesis of ADPKD including the genetics of ADPKD, the properties of the respective polycystin proteins, the role of cilia, and some cell signaling pathways that have been implicated in the pathways related to PKD1 and PKD2. PMID:20219615

  15. 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

  16. 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

  17. 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. PMID:25677715

  18. 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. PMID:25738250

  19. 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

  20. Single-Gene Causes of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) in Humans

    PubMed Central

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

    2015-01-01

    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. PMID:24398540

  1. Life Cycle Analysis of Kidney Gene Expression in Male F344 Rats

    PubMed Central

    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. PMID:24116033

  2. 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

  3. 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.

  4. 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

  5. The expanding phenotypic spectra of kidney diseases: insights from genetic studies.

    PubMed

    Stokman, Marijn F; Renkema, Kirsten Y; Giles, Rachel H; Schaefer, Franz; Knoers, Nine V A M; van Eerde, Albertien M

    2016-08-01

    Next-generation sequencing (NGS) has led to the identification of previously unrecognized phenotypes associated with classic kidney disease genes. In addition to improving diagnostics for genetically heterogeneous diseases and enabling a faster rate of gene discovery, NGS has enabled an expansion and redefinition of nephrogenetic disease categories. Findings from these studies raise the question of whether disease diagnoses should be made on clinical grounds, on genetic evidence or a combination thereof. Here, we discuss the major kidney disease-associated genes and gene categories for which NGS has expanded the phenotypic spectrum. For example, COL4A3-5 genes, which are classically associated with Alport syndrome, are now understood to also be involved in the aetiology of focal segmental glomerulosclerosis. DGKE, which is associated with nephrotic syndrome, is also mutated in patients with atypical haemolytic uraemic syndrome. We examine how a shared genetic background between diverse clinical phenotypes can provide insight into the function of genes and novel links with essential pathophysiological mechanisms. In addition, we consider genetic and epigenetic factors that contribute to the observed phenotypic heterogeneity of kidney diseases and discuss the challenges in the interpretation of genetic data. Finally, we discuss the implications of the expanding phenotypic spectra associated with kidney disease genes for clinical practice, genetic counselling and personalized care, and present our recommendations for the use of NGS-based tests in routine nephrology practice. PMID:27374918

  6. Vaccination against bacterial kidney disease: Chapter 22

    USGS Publications Warehouse

    Elliott, Diane G.; Wiens, Gregory D.; Hammell, K. Larry; Rhodes, Linda D.

    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.

  7. Sleep disorders and chronic kidney disease.

    PubMed

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

    2016-05-01

    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

  8. Mass spectrometry in Chronic Kidney Disease research

    PubMed Central

    Merchant, Michael L.

    2010-01-01

    Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass spectrometer and its application to analyze biological samples. Our need to understand both the identity of proteins and their abundance has led to improvements in mass spectrometers and their ability to analyze complex tryptic peptide mixtures with high sensitivity and high mass accuracy in a high throughput fashion (such as the LTQ-Orbitrap). It should not be surprising that this occurred coincident with dramatic improvements in our understanding chronic kidney disease (CKD), the mechanisms through which CKD progresses and the development of candidate CKD biomarkers. This review attempts to present a basic framework for the operational components of mass spectrometers, basic insight into how they are used in renal research and a discussion of CKD research that was driven by mass spectrometry. PMID:21044768

  9. 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

  10. Report of six kidney disease-associated Castleman's disease cases.

    PubMed

    Sui, Yanxia; Zhao, Dongli

    2015-12-01

    Castleman's disease (CD) is an uncommon, benign, non-neoplastic, lymphoproliferative disease of uncertain etiology. Here, we report 6 cases of kidney disease-associated CD in China. All patients exhibited multicentric CD (MCD) with involvement of the mediastinum, neck, bilateral axillary, and bilateral inguinal regions. Clinical manifestations included fever, fatigue, edema, and swollen lymph nodes. Laboratory examinations of all 6 patients found proteinuria or renal insufficiency. Two of the patients were diagnosed with hyaline vascular type MCD, and 4 patients were diagnosed with plasma cell type CD. The case 1 and case 4 patients had mesangial proliferative glomerulonephritis, case 3 had type I membranoproliferative glomerulonephritis, case 2 and case 5 had interstitial nephritis, and case 6 had AA type amyloidosis nephropathy. Three patients were treated with prednisone plus cyclophosphamide, 1 patient received COP therapy (cyclophosphamide, vincristine and prednisone), and 2 patients received COP therapy supplemented by small doses of radiation therapy delivered to local lymph nodes. In all cases, the clinical manifestations of MCD, including fever, fatigue, edema, swollen lymph nodes, and proteinuria, were alleviated or abolished by treatment. One patient responded to treatment with complete MCD remission, and another 4 patients survived. However, 1 patient died due to renal failure. In conclusion, common diagnosis and treatment techniques are suitable for kidney disease-associated CD. However, treatment efficacy might be difficult to predict, and some cases may have poor prognosis with this treatment strategy. Therefore, additional studies investigating kidney disease-associated CD and treatment outcomes in larger patient populations are needed. PMID:26445003

  11. Chronic kidney disease in pregnancy: Maternal and fetal outcomes and progression of kidney disease

    PubMed Central

    Wolski, Penny; Callaway, Leonie K; Barrett, Helen L; Fagermo, Narelle; Lust, Karin; Shakhovskoy, Rebekah E

    2015-01-01

    Background There is a paucity of Australian data regarding renal disease in pregnancy. We undertook a retrospective cohort study at a tertiary institution to examine the impact of renal disease on pregnancy outcomes and the effect of pregnancy on disease progression. Methods A total of 55 pregnancies of patients with renal disease admitted from 2003 to 2010 to the Royal Brisbane and Women’s Hospital were analysed. Pre-conception variables, fetal/delivery and maternal outcomes were analysed in this group and in a control group of women with normal kidney function pre-pregnancy. Results Of the 55 pregnancies, 71% experienced pre-term delivery, 38% had intra-uterine growth restriction and 62% required caesarean section. Of all, 60% of neonates required neonatal intensive care unit (NICU) admission and six perinatal deaths occurred. Of all, 67% of women suffered preeclampsia, 47% anaemia and 3 patients required dialysis in pregnancy. Postpartum deterioration of renal function occurred in patients with pre-conception chronic kidney disease stage 3–5. Conclusions Chronic kidney disease of all stages is a risk factor for adverse pregnancy outcomes. In a tertiary institution however, there is a high rate of successful pregnancy (84%).

  12. Relationship between ultrasonographically determined kidney volume and progression of chronic kidney disease.

    PubMed

    Vegar Zubović, Sandra; Kristić, Spomenka; Sefić Pašić, Irmina

    2016-08-01

    Aim To investigate a correlation between calculated creatinine clearance as a measure of kidney's functional abilities and ultrasonographically determined kidney volume, which represents actual size of the kidney, in fact residual renal mass in chronic kidney disease, in order to determine possibilities of ultrasound as a diagnostic method in diagnosing and follow up of chronic renal disease. Methods Prospective study included 150 patients with registered demographic and anthropometric data, and also with relevant laboratory tests of renal function. Longitudinal diameter, thickness and width of the kidney and renal volume calculated according to the Dinkel's formula were measured by ultrasound. A correlation between the measured volume of the kidneys and calculated creatinine clearance was done by the Spearman method, with statistical significance of p<0.05. Results Statistically significant correlation between the estimated creatinine clearance values and the average of the calculated values of kidney volume was found (p<0.01). Average value of the kidneys' volume showed a linear decrease with the progression of chronic kidney disease: the kidney volume in the control healthy group was 171.7 ± 32.6 mL (95.22- 229.59 mL), and in the subjects classified in stage IV it was 74.7 ± 24.6 mL (43.22-165.65 mL). Conclusion Calculated volume of kidney well correlated with creatinine clearance as a measure of functional ability of the kidneys and with the stage of chronic renal disease. It can be used in clinical practice for monitoring of chronic kidney disease in conjunction with other clinical and laboratory parameters. PMID:27452323

  13. 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

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

    PubMed

    Wahl, Patricia; Ducasa, Gloria Michelle; Fornoni, Alessia

    2016-03-15

    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

  15. Genetic heterogeneity of polycystic kidney disease in Bulgaria

    SciTech Connect

    Bogdanova, N. |; Dragova, D.; Kalaydiieva, L.

    1994-09-01

    Autosomal dominant polycystic kidney disease (PKD) is a common genetic disorder whose frequency in Bulgaria has been estimated at 1 in 950. One gene (PKD1) causing this disease has been mapped to the short arm of chromosome 16 in 1985. Linkage analysis showed that in a considerable proportion of PKD families (approximately 14% in Europe) the disease is not linked to this locus, suggesting the existance of mutations in additional genes. In 1993 a PKD2-gene has been mapped to the long arm of chromosome 4. Here we report data of the first extensive investigation of PKD in Bulgaria. Initially 35 families with 341 individuals (178 affected, 89 unaffected family members, 74 spouses) were included in the study. Clinical diagnosis, mainly based on ultrasonographic examination of the kidneys, has been performed for all individuals. Linkage analysis was performed on 22 large pedigrees with microsatellites 16SC2.5 (D16S291) and SM7 (D16S283), which are closely linked to the PKD1 locus, as well as microsatellites D4S392, D4S400, D4S231 (proximal to the PDK2 locus) and D4S423, D4S414, D4S411 (distal to PKD2 locus). The study showed that the disease is caused in 14 families by mutations within the PKD1 gene and was clearly linked to the PDK2 locus in 5 families. In 3 families no clear conclusions about the linkage could be reached and analysis of additional markers from this region is in progress. The investigation has revealed the highest proportion of PKD2 families reported so far in Europe (23%). In addition, comparison of the severity of the clinical course of PKD1 and PKD2 families failed to confirm statistically significant differences which have been reported.

  16. Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study

    PubMed Central

    Drechsler, Christiane; Kollerits, Barbara; Meinitzer, Andreas; März, Winfried; Ritz, Eberhard; König, Paul; Neyer, Ulrich; Pilz, Stefan; Wanner, Christoph; Kronenberg, Florian

    2013-01-01

    Background Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD). Methods We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54–5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. Results Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min), 2.64±1.06 µmol/L (GFR 60–90 ml/min), 2.52±1.24 µmol/L (GFR 30–60 ml/min) and 2.05±0.78 µmol/L (GFR<30 ml/min), respectively (p = 0.002). The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L) of homoarginine (HR 1.62, 95% CI 1.16–2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95% CI 1.11–2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98–1.98, p = 0.06). Conclusions Homoarginine concentrations are directly correlated with kidney function and are significantly

  17. Clinical Scenarios in Chronic Kidney Disease: Kidneys' Structural Changes in End-Stage Renal Disease.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Acquired cystic kidney disease (ACKD) and renal cell carcinoma (RCC) are the most important manifestations of end-stage kidneys' structural changes. ACKD is caused by kidney damage or scarring and it is characterized by the presence of small, multiple cortical and medullary cysts filled with a fluid similar to preurine. ACKD prevalence varies according to predialysis and dialysis age and its pathogenesis is unknown, although it is stated that progressive destruction of renal tissue induces hypertrophy/compensatory hyperplasia of residual nephrons and may trigger the degenerative process. ACKD is almost asymptomatic, but it can lead to several complications (bleeding, rupture, infections, RCC). Ultrasound (US) is the first level imaging technique in ACKD, because of its sensitivity and reliability. The most serious complication of ACKD is RCC, which is stimulated by the same growth factors and proto-oncogenes that lead to the genesis of cysts. Two different histological types of RCC have been identified: (1) RCC associated with ACKD and (2) papillary renal clear cell carcinoma. Tumors in end-stage kidneys are mainly small, multifocal and bilateral, with a papillary structure and a low degree of malignancy. At US, RCC appears as a small inhomogeneous nodule (<3 cm), clearly outlined from the renal profile and hypoechoic if compared with sclerotic parenchyma. In some cases, tumor appears as a homogeneous and hyperechoic multifocal mass. The most specific US sign of a small tumor in end-stage kidney is the important arterial vascularization, in contrast with renal parenchymal vascular sclerosis. PMID:27169876

  18. COX-2 gene dosage-dependent defects in kidney development.

    PubMed

    Slattery, Patrick; Frölich, Stefanie; Schreiber, Yannik; Nüsing, Rolf M

    2016-05-15

    Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4-8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2(+/+), COX-2(+/-), and COX-2(-/-) mice as well as in C57Bl6 mice treated postnatally with low (5 mg·kg(-1)·day(-1)) and high (10 mg·kg(-1)·day(-1)) doses of the selective COX-2 inhibitor SC-236. COX-2(+/-) mice exhibit impaired kidney development leading to reduced glomerular size but, in contrast to COX-2(-/-) mice, only marginal cortical thinning. Moreover, in COX-2(+/-) and COX-2(-/-) kidneys, juxtamedullary glomeruli, which develop in the very early stages of nephrogenesis, also showed a size reduction. In COX-2(+/-) kidneys at the age of 8 days, we observed significantly less expression of COX-2 mRNA and protein and less PGE2 and PGI2 synthetic activity compared with COX-2(+/+) kidneys. The renal defects in COX-2(-/-) and COX-2(+/-) kidneys could be mimicked by high and low doses of SC-236, respectively. In aged COX-2(+/-) kidneys, glomerulosclerosis was observed; however, in contrast to COX-2(-/-) kidneys, periglomerular fibrosis was absent. COX-2(+/-) mice showed signs of kidney insufficiency, demonstrated by enhanced serum creatinine levels, quite similar to COX-2(-/-) mice, but, in contrast, serum urea remained at the control level. In summary, function of both COX-2 gene alleles is absolutely necessary to ensure physiological development of the mouse kidney. Loss of one copy of the COX-2 gene or partial COX-2 inhibition is associated with distinct renal damage and reduced kidney function. PMID:26984955

  19. Kidney diseases in children - early diagnosis and prevention.

    PubMed

    Polenakovic, Momir; Gucev, Zoran; Tasic, Velibor

    2016-01-01

    Pediatric kidney diseases were in the focus of the World Kidney Day 2016. Macedonian pediatric nephrologists gave their contribution with public appearance in kindergartens, primary and secondary schools, with interactive lectures and discussion with the youngest about the kidney function, healthy life style and simple measures to prevent kidney and urinary tract diseases. Besides promotive appearance in the media, series of lectures were presented in front of the health professionals. The aim was to attract the attention of the professionals for early diagnosis and prevention of kidney disease. The action starts in utero, followed by early postnatal imaging and assessment, conservative treatment and in selected cases surgical treatment. The emphasis is on the multidisciplinary and comprehensive approach to children and adolescents with kidney diseases. PMID:27442411

  20. Phenotype standardization for drug-induced kidney disease.

    PubMed

    Mehta, Ravindra L; Awdishu, Linda; Davenport, Andrew; Murray, Patrick T; Macedo, Etienne; Cerda, Jorge; Chakaravarthi, Raj; Holden, Arthur L; Goldstein, Stuart L

    2015-08-01

    Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition. PMID:25853333

  1. [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. PMID:27284847

  2. APOL1 Kidney Risk Alleles: Population Genetics and Disease Associations

    PubMed Central

    Limou, Sophie; Nelson, George W.; Kopp, Jeffrey B.; Winkler, Cheryl A.

    2014-01-01

    APOL1 kidney disease is a unique case in the field of the genetics of common disease: 2 variants (termed G1 and G2) with high population frequency have been repeatedly associated with nondiabetic CKDs, with very strong effect size (odds ratios 3–29) in populations of sub-Saharan African descent. This review provides an update on the spectrum of APOL1 kidney disease and on the worldwide distribution of these kidney risk variants. We also summarize the proper way to run a recessive analysis on joint and independent effects of APOL1 G1 and G2 kidney risk variants. PMID:25168832

  3. 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

  4. 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. PMID:25140014

  5. Risk Factors for Chronic Kidney Disease

    MedlinePlus

    ... for answers to your questions about kidney function, dialysis, keeping a job, Medicare, exercise, and more. With ... touch of the sugar". About 44% of new dialysis patients have diabetes. What you can do: Kidney ...

  6. Hyperuricemia-induced inflammasome and kidney diseases.

    PubMed

    Isaka, Yoshitaka; Takabatake, Yoshitsugu; Takahashi, Atsushi; Saitoh, Tatsuya; Yoshimori, Tamotsu

    2016-06-01

    Classically, urate nephropathy has been postulated to cause kidney disease by depositing intraluminal crystal in the collecting duct. Recently, molecular mechanisms of inflammasome have been investigated. Urate-induced inflammasome pathway is comprised of urate crystal uptake into intracellular lysosomes and subsequent lysosomal rupture with mitochondrial reactive oxygen species (ROS) production, which activates the NLRP3 inflammasome. Against the lysosomal rupture and mitochondrial ROS production, autophagy acts to protect proximal tubular cells by isolating them from expanding the inflammation. In addition, increased cellular urate, directly or indirectly via xanthine oxidase-induced oxidative stress, may be associated with inflammasome. In addition to the traditional therapy against hyperuricemia, management of urate-induced inflammasome or augmentation of autophagy may offer the new effective therapies. PMID:25829326

  7. Insomnia in Patients With Chronic Kidney Disease.

    PubMed

    Lindner, Anett V; Novak, Marta; Bohra, Miqdad; Mucsi, Istvan

    2015-07-01

    Insomnia and poor self-perceived sleep are very common in patients with chronic kidney disease (CKD). Poor sleep is associated with fatigue, sleepiness, impaired daytime functioning, impaired health-related quality of life, and increased morbidity and mortality. Many illness- and treatment-related factors (metabolic changes, inflammation, altered sleep regulatory mechanisms, symptoms and complications of CKD, comorbid conditions, medications, and renal replacement therapies) may disturb sleep and contribute to the high prevalence of insomnia in this patient population. Accordingly, the approach to both diagnosing and treating this condition is quite complex. Although sleep-related problems are very important for patients with CKD, they largely are under-recognized and undertreated. Very few intervention trials provide an evidence base to support treatment decisions in this particular patient population. With this review we hope to increase awareness of insomnia among professionals involved in the management of patients with CKD and to provide guidance in recognizing and treating this important condition. PMID:26355254

  8. Nutrition for Early Chronic Kidney Disease in Adults

    MedlinePlus

    ... Information Center Medical Education Institute, Inc. (MEI) MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... KB)​​​​​ Alternate Language URL Nutrition for Early Chronic Kidney Disease in Adults Page Content On this page: ...

  9. Skin problems in chronic kidney disease.

    PubMed

    Kuypers, Dirk R J

    2009-03-01

    Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a kappa-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking. PMID:19190625

  10. Addressing Health Disparities in Chronic Kidney Disease

    PubMed Central

    Chan, Ta-Chien; Fan, I.-Chun; Liu, Michael Shi-Yung; Su, Ming-Daw; Chiang, Po-Huang

    2014-01-01

    According to the official health statistics, Taiwan has the highest prevalence of end stage renal disease (ESRD) in the world. Each year, around 60,000 ESRD patients in Taiwan consume 6% of the national insurance budget for dialysis treatment. The prevalence of chronic kidney disease (CKD) has been climbing during 2008–2012. However, the spatial disparities and clustering of CKD at the public health level have rarely been discussed. The aims of this study are to explore the possible population level risk factors and identify any clusters of CKD, using the national health insurance database. The results show that the ESRD prevalence in females is higher than that in males. ESRD medical expenditure constitutes 87% of total CKD medical expenditure. Pre-CKD and pre-ESRD disease management might slow the progression from CKD to ESRD. After applying ordinary least-squares regression, the percentages of high education status and the elderly in the townships are positively correlated with CKD prevalence. Geographically weighted regression and Local Moran’s I are used for identifying the clusters in southern Taiwan. The findings can be important evidence for earlier and targeted community interventions and reducing the health disparities of CKD. PMID:25514144

  11. 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. PMID:27485279

  12. 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. PMID:26031596

  13. 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. PMID:18971924

  14. JAK inhibition in the treatment of diabetic kidney disease.

    PubMed

    Brosius, Frank C; Tuttle, Katherine R; Kretzler, Matthias

    2016-08-01

    Diabetic kidney disease (DKD) is the most common cause of kidney failure in many countries today, but treatments have not improved in the last 20 years. Recently, systems biology methods have allowed the elucidation of signalling pathways and networks involved in the progression of DKD that were not well appreciated previously. A prominent pathway found to be integrally associated with DKD progression is the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Increased expression of JAK-STAT genes was found in multiple cells in the kidney, including glomerular podocytes, in both early and progressive DKD. Subsequent experiments in a mouse diabetic model showed that enhanced expression of JAK2 selectively in glomerular podocytes increased functional and pathological features of DKD. Finally, a yet unpublished Phase 2 multicentre, randomised, double-blind, placebo-controlled study of the efficacy of a selective JAK1 and JAK2 inhibitor has been conducted in type 2 diabetic participants with DKD. In this trial there was a reduction of albuminuria in participants who received the active inhibitor compared with those who received a placebo These results support the further study of JAK inhibitors as a new therapy for DKD. This review summarises a presentation given at the 'Anti-inflammatory interventions in diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by an overview by the Session Chair, Hiddo Heerspink (DOI: 10.1007/s00125-016-4030-4 ). PMID:27333885

  15. Reproductive issues for adults with autosomal dominant polycystic kidney disease.

    PubMed

    Vora, Neeta; Perrone, Ronald; Bianchi, Diana W

    2008-02-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder. However, the consequences of ADPKD on male and female reproductive health are not widely known. Several abnormalities are found in men with ADPKD, including necrospermia, immotile sperm, seminal vesicle cysts, and ejaculatory duct cysts. Female fertility is not affected. Affected women with ADPKD and normal renal function have a high rate of successful uncomplicated pregnancies. Pregnant women with ADPKD with compromised kidney function should be monitored carefully for the development of hypertension and preeclampsia. Their fetuses should be examined sonographically for signs of uteroplacental insufficiency, such as intrauterine growth restriction and oligohydramnios. The diagnosis of ADPKD should always be considered when prenatal sonographic findings of hyperechogenic enlarged kidneys are found. In this setting, a family history and renal sonogram of both parents is indicated. Sequencing of the PKD1 and PKD2 genes is available and can be used for both prenatal and preimplantation genetic diagnosis. We review in detail these topics to familiarize physicians taking care of patients with ADPKD with the reproductive issues that confront affected individuals. PMID:18215709

  16. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

    PubMed

    Levey, Andrew S; Eckardt, Kai-Uwe; Tsukamoto, Yusuke; Levin, Adeera; Coresh, Josef; Rossert, Jerome; De Zeeuw, Dick; Hostetter, Thomas H; Lameire, Norbert; Eknoyan, Garabed

    2005-06-01

    Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death. A simple definition and classification of kidney disease is necessary for international development and implementation of clinical practice guidelines. Kidney Disease: Improving Global Outcomes (KDIGO) conducted a survey and sponsored a controversies conference to (1) provide a clear understanding to both the nephrology and nonnephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI), (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD. The K/DOQI definition and classification were accepted, with clarifications. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause. Kidney damage in many kidney diseases can be ascertained by the presence of albuminuria, defined as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens. GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. Kidney disease severity is classified into five stages according to the level of GFR. Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed. PMID:15882252

  17. Helicobacter cinaedi kidney cyst infection and bacteremia in a patient with autosomal dominant polycystic kidney disease.

    PubMed

    Mandai, Shintaro; Kasagi, Yuri; Kusaka, Keita; Shikuma, Satomi; Akita, Wataru; Kuwahara, Michio

    2014-11-01

    A 48-year-old man with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital with a 5-day history of lower right back pain, high-grade fever, and arthralgia. He was diagnosed with right kidney cyst infection and bacteremia due to Helicobacter cinaedi (H. cinaedi) based on these symptoms, highly elevated CRP (32.25 mg/dL), abdominal magnetic resonance imaging findings, and the identification of H. cinaedi from blood cultures using PCR and sequence analysis of the 16S ribosomal DNA gene. Intravenous cefotaxime 0.5 g twice daily followed by meropenem 0.5 g twice daily and ciprofloxacin 200 mg twice daily were partially effective; oral doxycycline added at 200 mg/day finally eradicated the infection. Total duration of antimicrobial therapy was 9 weeks. H. cinaedi infections typically present as bacteremia with or without cellulitis in immunocompromised patients such as those with AIDS or malignant disease. To our knowledge, this is the first report describing an ADPKD patient with H. cinaedi cyst infection. Although H. cinaedi infections are increasingly recognized, even in immunocompetent subjects, numerous cases may still be overlooked given that this bacterium is slow-growing, and is difficult to culture, be Gram-stained, and identify on phenotypic tests. Consideration of this bacterium as a possible pathogen and sufficient duration of incubation with molecular testing are necessary in treating ADPKD patients with cyst infection. PMID:25131293

  18. 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. PMID:26817244

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

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz; On Behalf Of The World Kidney Day Steering Committee

    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.  Since 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. "For in every adult there dwells the child that was, and in every child there lies the adult that will be."-John Connolly, The Book of Lost Things. PMID:27417242

  20. 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...

  1. 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;...

  2. 78 FR 9401 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ... Digestive and Kidney Diseases Special Emphasis Panel; R24 Collaborative Interdisciplinary Team Science-3... Digestive and Kidney Diseases Special Emphasis Panel; R24 Collaborative Interdisciplinary Team Science-8... Digestive and Kidney Diseases Special Emphasis Panel; R24 Collaborative Interdisciplinary Team...

  3. A mitotic transcriptional switch in polycystic kidney disease

    PubMed Central

    Verdeguer, Francisco; Corre, Stephanie Le; Fischer, Evelyne; Callens, Celine; Garbay, Serge; Doyen, Antonia; Igarashi, Peter; Terzi, Fabiola; Pontoglio, Marco

    2011-01-01

    Hepatocyte nuclear factor-1β(HNF-1β) is a transcription factor required for the expression of several renal cystic genes and whose prenatal deletion leads to polycystic kidney disease (PKD)1. We show here that inactivation of Hnf1b from postnatal day 10 onward does not elicit cystic dilations in tubules after their proliferative morphogenetic elongation is over. Cystogenic resistance is intrinsically linked to the quiescent state of cells. In fact, when Hnf1b deficient quiescent cells are forced to proliferate by an ischemiareperfusion injury, they give rise to cysts, owing to loss of oriented cell division. Remarkably, in quiescent cells, the transcription of crucial cystogenic target genes is maintained even in the absence of HNF-1β. However, their expression is lost as soon as cells proliferate and the chromatin of target genes acquires heterochromatin marks. These results unveil a previously undescribed aspect of gene regulation. It is well established that transcription is shut off during the mitotic condensation of chromatin2,3. We propose that transcription factors such as HNF-1β might be involved in reprogramming gene expression after transcriptional silencing is induced by mitotic chromatin condensation. Notably, HNF-1β remains associated with the mitotically condensed chromosomal barrels. This association suggests that HNF-1β is a bookmarking factor that is necessary for reopening the chromatin of target genes after mitotic silencing. PMID:19966811

  4. Identification of the polycystic kidney disease 1 (PKD1)

    SciTech Connect

    Harris, P.C.

    1994-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders, affecting 1/1000 individuals, and a major cause of renal failure. The PKD1 locus, which is in chromosome region 16p13.3, accounts for {approximately}85% of ADPKD. We have identified a chromosome translocation associated with ADPKD which disrupts a gene in the PKD1 candidate region. Three additional mutations of this gene have been identified in PKD1 patients, including a de novo mutation, showing that this is the PKD1 gene. This gene encodes an {approximately}14 transcript and is located adjacent to the tuberous sclerosis 2 gene in a genomic region that is duplicated elsewhere on chromosome 16: the duplicate area encodes three transcripts which are partially homologous to the PKD1 transcript. Duplication of this region has made characterization of the gene particularly difficult, but {approximately}6 kb of the transcript has been cloned and sequenced. No significant homologies with known proteins have been detected. Studies are underway to clone and characterize a full length transcript and to determine the normal role of the PKD1 protein.

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

    ClinicalTrials.gov

    2016-01-28

    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

  6. Chronic kidney disease and erectile dysfunction.

    PubMed

    Suzuki, Etsu; Nishimatsu, Hiroaki; Oba, Shigeyoshi; Takahashi, Masao; Homma, Yukio

    2014-11-01

    Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack. PMID:25374815

  7. Chronic kidney disease alters intestinal microbial flora.

    PubMed

    Vaziri, Nosratola D; Wong, Jakk; Pahl, Madeleine; Piceno, Yvette M; Yuan, Jun; DeSantis, Todd Z; Ni, Zhenmin; Nguyen, Tien-Hung; Andersen, Gary L

    2013-02-01

    The population of microbes (microbiome) in the intestine is a symbiotic ecosystem conferring trophic and protective functions. Since the biochemical environment shapes the structure and function of the microbiome, we tested whether uremia and/or dietary and pharmacologic interventions in chronic kidney disease alters the microbiome. To identify different microbial populations, microbial DNA was isolated from the stools of 24 patients with end-stage renal disease (ESRD) and 12 healthy persons, and analyzed by phylogenetic microarray. There were marked differences in the abundance of 190 bacterial operational taxonomic units (OTUs) between the ESRD and control groups. OTUs from Brachybacterium, Catenibacterium, Enterobacteriaceae, Halomonadaceae, Moraxellaceae, Nesterenkonia, Polyangiaceae, Pseudomonadaceae, and Thiothrix families were markedly increased in patients with ESRD. To isolate the effect of uremia from inter-individual variations, comorbid conditions, and dietary and medicinal interventions, rats were studied 8 weeks post 5/6 nephrectomy or sham operation. This showed a significant difference in the abundance of 175 bacterial OTUs between the uremic and control animals, most notably as decreases in the Lactobacillaceae and Prevotellaceae families. Thus, uremia profoundly alters the composition of the gut microbiome. The biological impact of this phenomenon is unknown and awaits further investigation. PMID:22992469

  8. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy. PMID:27521115

  9. The Chronic Kidney Disease - Colonic Axis.

    PubMed

    Pahl, Madeleine V; Vaziri, Nosratola D

    2015-01-01

    Chronic kidney disease (CKD) has long been known to cause significant gastrointestinal and colonic pathology. Recent advances in understanding of the role of colonic bacterial microbiome and its function and composition in health and disease have revealed previously unappreciated effects of CKD-associated colonic pathology on the development of uremic complications. CKD can result in profound changes in the microbiome composition and biosynthetic pattern, and the structure and function of the colon. Increases in bacteria that produce urease, uricase, p-cresol- and indole-forming enzymes and the depletion of bacteria that possess short chain fatty acid forming enzymes have been described in human and animal models. Disruption of the colonic epithelial tight junction in different animal models of CKD has been reported and is largely due to the conversion of luminal urea to ammonia by urease possessing bacteria. Together, these changes contribute to the pathogenesis of systemic inflammation and uremic toxicity by allowing the translocation of endotoxin and microbial fragments into the circulation. Additionally, colonic bacteria are the main source of several well-known pro-inflammatory uremic toxins such as indoxyl sulfate, P-cresol sulfate. This review is intended to provide an overview of the effects of CKD on the colonic microbiome and the intestinal epithelial barrier structure and function and their role in the pathogenesis the systemic inflammation and uremic toxicity. PMID:25855516

  10. Chronic kidney disease and erectile dysfunction

    PubMed Central

    Suzuki, Etsu; Nishimatsu, Hiroaki; Oba, Shigeyoshi; Takahashi, Masao; Homma, Yukio

    2014-01-01

    Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack. PMID:25374815

  11. Pediatric kidney disease: tracking onset and improving clinical outcomes.

    PubMed

    Bates, Carlton M; Charlton, Jennifer R; Ferris, Maria E; Hildebrandt, Friedhelm; Hoshizaki, Deborah K; Warady, Bradley A; Moxey-Mims, Marva M

    2014-06-01

    Recent studies confirm that much of adult kidney disease may have its origins in childhood, often as a result of abnormal or suboptimal fetal kidney development. Understanding of the etiology and pathogenesis of CKD in children is rapidly evolving because of robust longitudinal clinical data, identification of monogenic mutations related to common causes of CKD, and improved knowledge of factors that influence the onset and progression of CKD. The Kidney Research National Dialogue, supported by the National Institute of Diabetes and Digestive and Kidney Diseases, asked the research and clinical communities to formulate and prioritize research objectives that would improve understanding of kidney function and diseases. This commentary outlines high-priority research objectives to assess factors associated with the predisposition to develop renal disease in children, and address the unique challenges in treating this population. PMID:24651076

  12. Autosomal Recessive Polycystic Kidney Disease: Antenatal Diagnosis and Histopathological Correlation

    PubMed Central

    Rajanna, Dayananda Kumar; Reddy, Anjani; Srinivas, Naren Satya; Aneja, Ankur

    2013-01-01

    Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common inheritable disease manifesting in infancy and childhood with a frequency of 1:6,000 to 1:55,000 births. The patient in her second trimester presented with a history of amenorrhea. Ultrasound examination revealed bilateral, enlarged, hyperechogenic kidneys, placentomegaly, and severe oligohydramnios. The pregnancy was terminated. An autopsy was performed on the fetus. Both the kidneys were found to be enlarged and the cut surface showed numerous cysts. The liver sections showed changes due to fibrosis. The final diagnosis of autosomal recessive polycystic kidney disease was made based on these findings. In this article, we correlate the ante-natal ultrasound and histopathological findings in autosomal recessive polycystic kidney disease. PMID:23814685

  13. Chronic kidney disease in an adult with propionic acidemia.

    PubMed

    Vernon, H J; Bagnasco, S; Hamosh, A; Sperati, C J

    2014-01-01

    We report an adult male with classic propionic acidemia (PA) who developed chronic kidney disease in the third decade of his life. This diagnosis was recognized by an increasing serum creatinine and confirmed by reduced glomerular filtration on a (99m)Tc-diethylenetriamine pentaacetate (DTPA) scan. Histopathology of the kidney showed moderate glomerulo- and tubulointerstitial fibrosis with very segmental mesangial IgA deposits. This is the second reported case of kidney disease in an individual with propionic acidemia possibly indicating that chronic kidney disease may be a late-stage complication of propionic acidemia. Additionally, this is the first description of the histopathology of kidney disease in an individual with propionic acidemia. As more cases emerge, the clinical course and spectrum of renal pathology in this disorder will be better defined. PMID:23756992

  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. PMID:26194155

  15. Heterotrimeric G protein signaling in polycystic kidney disease.

    PubMed

    Hama, Taketsugu; Park, Frank

    2016-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a signalopathy of renal tubular epithelial cells caused by naturally occurring mutations in two distinct genes, polycystic kidney disease 1 (PKD1) and 2 (PKD2). Genetic variants in PKD1, which encodes the polycystin-1 (PC-1) protein, remain the predominant factor associated with the pathogenesis of nearly two-thirds of all patients diagnosed with PKD. Although the relationship between defective PC-1 with renal cystic disease initiation and progression remains to be fully elucidated, there are numerous clinical studies that have focused upon the control of effector systems involving heterotrimeric G protein regulation. A major regulator in the activation state of heterotrimeric G proteins are G protein-coupled receptors (GPCRs), which are defined by their seven transmembrane-spanning regions. PC-1 has been considered to function as an unconventional GPCR, but the mechanisms by which PC-1 controls signal processing, magnitude, or trafficking through heterotrimeric G proteins remains to be fully known. The diversity of heterotrimeric G protein signaling in PKD is further complicated by the presence of non-GPCR proteins in the membrane or cytoplasm that also modulate the functional state of heterotrimeric G proteins within the cell. Moreover, PC-1 abnormalities promote changes in hormonal systems that ultimately interact with distinct GPCRs in the kidney to potentially amplify or antagonize signaling output from PC-1. This review will focus upon the canonical and noncanonical signaling pathways that have been described in PKD with specific emphasis on which heterotrimeric G proteins are involved in the pathological reorganization of the tubular epithelial cell architecture to exacerbate renal cystogenic pathways. PMID:27199453

  16. Hepatitis C virus-related kidney disease: an overview.

    PubMed

    Kamar, N; Izopet, J; Alric, L; Guilbeaud-Frugier, C; Rostaing, L

    2008-03-01

    Hepatitis C virus (HCV)-infection leads to chronic liver disease, but also to extra-hepatic manifestations, including kidney disease. We provide an overview of HCV-related kidney diseases in non-transplanted and in kidney transplant patients, and their therapies. Membranoproliferative glomerulonephritis, associated with Type 2 cryoglobulinemia, is the predominant Type of HCV-related glomerulonephritis. Membranous glomerulonephritis and focal segmental glomerular sclerosis are less commonly described. HCV infection seems to be linked to Type 2 diabetes mellitus, and might alter the progression of diabetic-related nephropathy. Patients infected by HCV should be annually screened for markers of kidney disease and, similarly, patients with membranoproliferative or membranous glomerulonephritis should be screened for HCV infection. After transplantation, cryoglobulinemia is frequent and is associated with HCV markers. HCV-related kidney disease requires specific treatment. In non-kidney-transplant patients, treatment relies on either only anti-HCV therapy in cases of moderate renal disease, or combined anti-viral and immunosuppressive therapies in cases of severe renal disease, i.e., nephrotic syndrome and/or progressive renal failure, and in diseases that are refractory to anti-HCV therapy. In kidney transplant patients, ribavirin monotherapy could be used cautiously, whereas rituximab might be a treatment of choice in the presence of cryoglobulinemia. In liver-transplant patients, in addition to anti-HCV therapy, rituximab might be also used. PMID:18397713

  17. 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. PMID:25960302

  18. High Blood Pressure and Chronic Kidney Disease in Children: A Guide for Parents

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  19. New Study Shows 59 Percent of Americans Will Develop Kidney Disease in Their Lifetime

    MedlinePlus

    ... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...

  20. Organization of the pronephric kidney revealed by large-scale gene expression mapping

    PubMed Central

    Raciti, Daniela; Reggiani, Luca; Geffers, Lars; Jiang, Qiuhong; Bacchion, Francesca; Subrizi, Astrid E; Clements, Dave; Tindal, Christopher; Davidson, Duncan R; Kaissling, Brigitte; Brändli, André W

    2008-01-01

    Background The pronephros, the simplest form of a vertebrate excretory organ, has recently become an important model of vertebrate kidney organogenesis. Here, we elucidated the nephron organization of the Xenopus pronephros and determined the similarities in segmentation with the metanephros, the adult kidney of mammals. Results We performed large-scale gene expression mapping of terminal differentiation markers to identify gene expression patterns that define distinct domains of the pronephric kidney. We analyzed the expression of over 240 genes, which included members of the solute carrier, claudin, and aquaporin gene families, as well as selected ion channels. The obtained expression patterns were deposited in the searchable European Renal Genome Project Xenopus Gene Expression Database. We found that 112 genes exhibited highly regionalized expression patterns that were adequate to define the segmental organization of the pronephric nephron. Eight functionally distinct domains were discovered that shared significant analogies in gene expression with the mammalian metanephric nephron. We therefore propose a new nomenclature, which is in line with the mammalian one. The Xenopus pronephric nephron is composed of four basic domains: proximal tubule, intermediate tubule, distal tubule, and connecting tubule. Each tubule may be further subdivided into distinct segments. Finally, we also provide compelling evidence that the expression of key genes underlying inherited renal diseases in humans has been evolutionarily conserved down to the level of the pronephric kidney. Conclusion The present study validates the Xenopus pronephros as a genuine model that may be used to elucidate the molecular basis of nephron segmentation and human renal disease. PMID:18492243

  1. Fatty Acid Oxidation is Impaired in An Orthologous Mouse Model of Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Menezes, Luis F.; Lin, Cheng-Chao; Zhou, Fang; Germino, Gregory G.

    2016-01-01

    Background The major gene mutated in autosomal dominant polycystic kidney disease was first identified over 20 years ago, yet its function remains poorly understood. We have used a systems-based approach to examine the effects of acquired loss of Pkd1 in adult mouse kidney as it transitions from normal to cystic state. Methods We performed transcriptional profiling of a large set of male and female kidneys, along with metabolomics and lipidomics analyses of a subset of male kidneys. We also assessed the effects of a modest diet change on cyst progression in young cystic mice. Fatty acid oxidation and glycolytic rates were measured in five control and mutant pairs of epithelial cells. Results We find that females have a significantly less severe kidney phenotype and correlate this protection with differences in lipid metabolism. We show that sex is a major determinant of the transcriptional profile of mouse kidneys and that some of this difference is due to genes involved in lipid metabolism. Pkd1 mutant mice have transcriptional profiles consistent with changes in lipid metabolism and distinct metabolite and complex lipid profiles in kidneys. We also show that cells lacking Pkd1 have an intrinsic fatty acid oxidation defect and that manipulation of lipid content of mouse chow modifies cystic disease. Interpretation Our results suggest PKD could be a disease of altered cellular metabolism. PMID:27077126

  2. Chronic kidney disease and the skeleton

    PubMed Central

    Miller, Paul D

    2014-01-01

    Fractures across the stages of chronic kidney disease (CKD) could be due to osteoporosis, some form of renal osteodystrophy defined by specific quantitative histomorphometry or chronic kidney disease–mineral and bone disorder (CKD–MBD). CKD–MBD is a systemic disease that links disorders of mineral and bone metabolism due to CKD to either one or all of the following: abnormalities of calcium, phosphorus, parathyroid hormone or vitamin D metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Osteoporosis, as defined by the National Institutes of Health, may coexist with renal osteodystrophy or CKD–MBD. Differentiation among these disorders is required to manage correctly the correct disorder to reduce the risk of fractures. While the World Health Organization (WHO) bone mineral density (BMD) criteria for osteoporosis can be used in patients with stages 1–3 CKD, the disorders of bone turnover become so aberrant by stages 4 and 5 CKD that neither the WHO criteria nor the occurrence of a fragility fracture can be used for the diagnosis of osteoporosis. The diagnosis of osteoporosis in stages 4 and 5 CKD is one of the exclusion—excluding either renal osteodystrophy or CKD–MBD as the cause of low BMD or fragility fractures. Differentiations among the disorders of renal osteodystrophy, CKD–MBD or osteoporosis are dependent on the measurement of specific biochemical markers, including serum parathyroid hormone (PTH) and/or quantitative bone histomorphometry. Management of fractures in stages 1–3 CKD does not differ in persons with or without CKD with osteoporosis assuming that there is no evidence for CKD–MBD, clinically suspected by elevated PTH, hyperphosphatemia or fibroblast growth factor 23 due to CKD. Treatment of fractures in persons with osteoporosis and stages 4 and 5 CKD is not evidence-based, with the exception of post-hoc analysis suggesting efficacy and

  3. 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

  4. 78 FR 52937 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes... Kidney Diseases Special Emphasis Panel; Time-Sensitive Obesity Research. Date: September 16, 2013....

  5. The role of high mobility group box 1 (HMGB1) in the pathogenesis of kidney diseases

    PubMed Central

    Chen, Qingjie; Guan, Xiaofeng; Zuo, Xiaocong; Wang, Jianglin; Yin, Wenjun

    2016-01-01

    High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. PMID:27175328

  6. The role of high mobility group box 1 (HMGB1) in the pathogenesis of kidney diseases.

    PubMed

    Chen, Qingjie; Guan, Xiaofeng; Zuo, Xiaocong; Wang, Jianglin; Yin, Wenjun

    2016-05-01

    High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. PMID:27175328

  7. Protein biomarkers associated with acute renal failure and chronic kidney disease.

    PubMed

    Perco, P; Pleban, C; Kainz, A; Lukas, A; Mayer, G; Mayer, B; Oberbauer, R

    2006-11-01

    Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired. This review summarizes protein markers discussed in the context of ARF as well as CKD, and provides an overview on currently available discovery results following 'omics' techniques. The identified set of candidate marker proteins is discussed in their cellular and functional context. The systematic review of proteomics and genomics studies revealed 56 genes to be associated with acute or chronic kidney disease. Context analysis, i.e. correlation of biological processes and molecular functions of reported kidney markers, revealed that 15 genes on the candidate list were assigned to the most significant ontology groups: immunity and defence. Other significantly enriched groups were cell communication (14 genes), signal transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein markers, nine proteins were also identified by gene expression studies. Next generation candidate marker proteins with improved diagnostic and prognostic values for kidney diseases will be derived from whole genome scans and protemics approaches. Prospective validation still remains elusive for all proposed candidates. PMID:17032342

  8. APOL1 kidney disease risk variants – an evolving landscape

    PubMed Central

    Dummer, Patrick D.; Limou, Sophie; Rosenberg, Avi Z.; Heymann, Jurgen; Nelson, George; Winkler, Cheryl A.; Kopp, Jeffrey B.

    2015-01-01

    APOL1 genetic variants account for much of the excess risk of chronic and end stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. Experimental evidence suggests a direct role of APOL1 in pore formation, cellular injury, and programmed cell death in renal injury. The APOL1 BH3 motif, often associated with cell death, is unlikely to play a role in APOL1-induced cytotoxicity as it is not conserved within the APOL family and is dispensable for cell death in vitro. We discuss two models for APOL1 trypanolytic activity: one involving lysosome permeabilization and another colloid-osmotic swelling of the cell body, as well as their relevance to human pathophysiology. Experimental evidence from human cell culture models suggests that both mechanisms may be operative. A systems biology approach whereby APOL1-associated perturbations in gene and protein expression in affected individuals are correlated with molecular pathways may be productive to elucidate APOL1 function in vivo. PMID:26215860

  9. Nutrition in Children with Chronic Kidney Disease

    MedlinePlus

    ... or 212–889–2210 Fax: 212–689–9261 Internet: www.kidney.org A Healthy Food Guide for ... Riverside Plaza, Suite 2000 Chicago, IL 60606–6995 Internet: www.eatright.org Your Kidney Test Results Solving ...

  10. 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

  11. [Chronic kidney disease: therapy and care].

    PubMed

    Noel, Natacha; Gaha, Khaled; Rieu, Philippe

    2012-01-01

    Chronic kidney disease (CKD) is a major public health problem. It is therefore important to slow its progression and to treat its complications. Regardless of the causal nephropathy, arterial hypertension and proteinuria are the major progression factors of CKD. Thus, optimal control of blood pressure, reduction of proteinuria by using rennin angiotension system inhibitors can slow the progression of CKD. This effect can be enhanced by reducing sodium intake. The recent recommendations suggest that blood pressure should not be higher than 130/80 mmHg and proteinuria should not exceed 0,5 g/day. The consequences of advanced stages of the CKD have to be diagnosed and treated early: anemia, abnormal bone metabolism, hyperkalemia, fluid overload, metabolic acidosis... A particular emphasis has to be given to cardiovascular complications and risk factors. Monitoring data are well defined by the actual recommandations. Nephrologist can provide a set of recommended intervention to the primary care physician. The most accepted criterion of initiation of dialysis, in absence of clinic uremic manifestation is a glomerular filtration rate lower than 7 ml/min/1,73m2. Psychological and medical preparation of the patient to dialysis is essential. The possibility of renal transplantation should be evaluated during the following of patient with CKD PMID:22335066

  12. 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

  13. 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

  14. Hypoxia: The Force that Drives Chronic Kidney Disease.

    PubMed

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

    2016-03-01

    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

  15. Sexual dysfunction in men and women with chronic kidney disease and end-stage kidney disease.

    PubMed

    Palmer, Biff F

    2003-01-01

    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 psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward 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. PMID:12616463

  16. The pathogenesis of autosomal dominant polycystic kidney disease: an update.

    PubMed

    Somlo, S; Markowitz, G S

    2000-07-01

    The identification of PKD1 and PKD2, the two major genes responsible for autosomal dominant polycystic kidney disease, are the seminal discoveries upon which much of the current investigation into the pathogenesis of this common heritable disease is based. A major mechanistic insight was achieved with the discovery that autosomal dominant polycystic kidney disease occurs by a two-hit mechanism requiring somatic inactivation of the normal allele in individual polarized epithelial cells. Most recent advances are focused on the function of the respective protein products, polycystin-1 and polycystin-2. Indirect evidence supports an interaction between polycystin-1 and -2, albeit it is unlikely that they work in concert in all tissues and at all times. They associate in yeast two hybrid and cotransfection assays and there is a striking similarity in the renal and pancreatic cystic phenotypes of Pkd2-/- and Pkd1del34/del34 mice. Also, the respective homologues of both proteins are expressed in the same sensory neuronal cells in the nematode and the human disease phenotypes remain completely overlapping with the major difference being in relative severity. Mounting evidence supports the hypothesis that polycystin-1 is a cell surface receptor. A close homologue in the sea urchin sperm mediates the acrosome reaction in response to contact with egg-jelly, the nematode homologue functions in mechano- or chemosensation, and the solution structure of the repeated extracellular polycystic kidney disease domains reveals a beta-sandwich fold commonly found in surface receptor molecules. Indirect evidence also supports the initial hypothesis that polycystin-2 is a calcium channel subunit. Several closely related homologues retain the calcium channel signature motif but differ in their predicted interaction domains, and one of these homologues has been shown to be a calcium regulated cation channel. Several important distinctions in polcystin-1 and -2 function have also been

  17. Role of calcium in polycystic kidney disease: From signaling to pathology.

    PubMed

    Mangolini, Alessandra; de Stephanis, Lucia; Aguiari, Gianluca

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 (PC1), a large multi-functional membrane receptor protein able to regulate ion channel complexes, whereas polycystin-2 (PC2), encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum (ER). In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this field could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression. PMID:26788466

  18. 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. PMID:27318934

  19. Rufus of Ephesus and his "Diseases of the Kidneys".

    PubMed

    Eknoyan, Garabed

    2002-07-01

    The first book on diseases of the kidneys, titled "Diseases of the Kidneys and Bladder", was written by Ruphus of Ephesus at the close of the 1st century AD. Little is known of Rufus, who seems to have attained fame and was considered an equal of Hippocrates and Galen. He was highly respected and extensively quoted by authors of Byzantine, Arabic and Middle Ages medicine. In his description of diseases of the kidneys he makes a concerted effort to correlate structure and function, and to provide a rational explanation of the altered function of the kidneys in disease. The section of his monograph "On Hardening of the Kidneys" is brief, but constitutes the first description of morbid and clinical features of the end-stage kidneys. Like many of his contemporaries, Rufus wrote several monographs on selected topics and organs. That he chose diseases of the kidneys as the subject of one of his monographs makes him especially pertinent to the history of nephrology. PMID:12119467

  20. Mammalian target of rapamycin inhibition in polycystic kidney disease: From bench to bedside.

    PubMed

    Kim, Hyun-Jung; Edelstein, Charles L

    2012-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the USA resulting in chronic kidney disease and the need for dialysis and transplantation. Approximately 85% of cases of ADPKD are caused by a mutation in the Pkd1 gene that encodes polycystin-1, a large membrane receptor. The Pkd1 gene mutation results in abnormal proliferation in tubular epithelial cells, which plays a crucial role in cyst development and/or growth in PKD. Activation of the proliferative mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated in polycystic kidneys from rodents and humans. mTOR inhibition with sirolimus or everolimus decreases cysts in most animal models of PKD including Pkd1 and Pkd2 gene deficient orthologous models of human disease. On the basis of animal studies, human studies were undertaken. Two large randomized clinical trials published in the New England Journal of Medicine of everolimus or sirolimus in ADPKD patients were very unimpressive and associated with a high side-effect profile. Possible reasons for the unimpressive nature of the human studies include their short duration, the high drop-out rate, suboptimal dosing, lack of randomization of "fast" and "slow progressors" and the lack of correlation between kidney size and kidney function in ADPKD. The future of mTOR inhibition in ADPKD is discussed. PMID:26894018

  1. 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

  2. Therapeutic role of sirolimus in non-transplant kidney disease.

    PubMed

    Rangan, Gopala K; Nguyen, Tina; Mainra, Rahul; Succar, Lena; Schwensen, Kristina G; Burgess, Jane S; Ho, Kok On

    2009-08-01

    Sirolimus is a member of a novel class of immunosuppressant drug that potently suppresses T cell proliferation and expansion by inhibition of the Target of Rapamycin Complex 1 (TORC1) protein kinase. Sirolimus also has anti-proliferative effects on intrinsic cells of the kidney, and increasing evidence suggests that it may have a therapeutic role in non-transplant renal diseases. In the normal kidney, sirolimus is considered to be non-nephrotoxic. In the diseased kidney, sirolimus may be beneficial or detrimental, depending on the type of renal injury. In polycystic kidney disease, TORC1 activation mediates renal tubular epithelial cell (TEC) proliferation and cyst growth in animals, and Phase III clinical trials are underway to determine the effect of sirolimus in attenuating disease progression in humans. In contrast, in acute kidney injury, sirolimus transiently impairs proximal TEC regeneration and delays renal recovery. In animal models of lupus nephritis and diabetic kidney disease, sirolimus prevents disease progression. However, the efficacy of sirolimus in human glomerulonephritis as well as in diabetic chronic kidney disease remains unclear, as it paradoxically exacerbates renal dysfunction when the baseline glomerular filtration rate is low (< 40 ml/min/1.73 m(2)) and there is heavy proteinuria (> 300 mg/day). This may, in part, be due to inhibition of compensatory glomerular capillary repair through the suppression of endothelial cell proliferation and angiogenic growth factor production by podocytes. Therefore, at present, polycystic kidney disease is the most promising therapeutic application for sirolimus in non-transplant renal diseases, and further studies are needed to clarify its role in other situations. PMID:19374918

  3. [Ultrasound and color Doppler applications in chronic kidney disease].

    PubMed

    Meola, Mario; Petrucci, Ilaria

    2012-01-01

    Chronic kidney disease (CKD) encompasses all clinical features and complications during the progression of various kidney conditions towards end-stage renal disease. These conditions include immune and inflammatory diseases such as primary and HCV-related glomerulonephritis; infectious diseases such as pyelonephritis with or without reflux and tuberculosis; vascular diseases such as chronic ischemic nephropathy; hereditary and congenital diseases such as polycystic disease and congenital cystic dysplasia; metabolic diseases including diabetes and hyperuricemia; and systemic diseases (collagen disease, vasculitis, myeloma). During the progression of CKD, ultrasound imaging can differentiate the nature of the renal damage in only 50-70% of cases. Infact, the end-stage kidney appears shrunken, reduced in volume (Ø <9 cm), unstructured, amorphous, with acquired cystic degeneration (small and multiple cysts involving the cortex and medulla) or nephrocalcinosis, but there are rare exceptions, such as polycystic kidney disease, diabetic nephropathy, and secondary inflammatory nephropathies. The main difficulties in the differential diagnosis are encountered in multifactorial CKD, which is commonly presented to the nephrologist at stage 4-5, when the kidney is shrunken, unstructured and amorphous. As in acute renal injury and despite the lack of sensitivity, ultrasonography is essential for assessing the progression of the renal damage and related complications, and for evaluating all conditions that increase the risk of CKD, such as lithiasis, recurrent urinary tract infections, vesicoureteral reflux, polycystic kidney disease and obstructive nephropathy. The timing and frequency of ultrasound scans in CKD patients should be evaluated case by case. In this review we will consider the morphofunctional features of the kidney in all nephropathies that may lead to progressive CKD. PMID:23229668

  4. 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...

  5. 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...

  6. 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....

  7. 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...

  8. 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...

  9. 77 FR 47082 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-07

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel; Clinical Trial Cooperative Agreement Grant Review Meeting. ] Date... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National...

  10. 76 FR 38193 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel, Endogenous Insulin Secretion Preservation. Date: July 27, 2011... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National...

  11. 77 FR 10540 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Kidney Diseases Special Emphasis Panel: Genetic and Lifestyle Factors and Risk of Gastrointestinal... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National...

  12. 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..., Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS) Dated: October...

  13. 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...

  14. Kidney disease postorbital lesions in spring chinook salmon (Oncorhynchus tshawytscha)

    USGS Publications Warehouse

    Hendricks, Jerry D.; Leek, Steve L.

    1975-01-01

    Gross exophthalmos in one or both eyes of yearling spring chinook salmon (Oncorhynchus tshawytscha) was caused by postorbital, granulomatous inflammatory tissue that developed in response to invasion of the site by Corynebacterium sp., the causative agent of bacterial kidney disease.

  15. Medicare Spends Billions on Chronic Kidney Disease, Study Finds

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158020.html Medicare Spends Billions on Chronic Kidney Disease, Study Finds ... affects nearly 14 percent of Americans and costs Medicare billions of dollars a year, a new study ...

  16. Overview of Kidney Diseases in Children

    MedlinePlus

    ... an intravenous (IV) tube. Some children may need dialysis for a short time to take over the work the kidneys usually do. Most children recover completely with no long-term consequences. More information is provided in the NIDDK ...

  17. 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

  18. 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. PMID:26613807

  19. Application of regenerative medicine for kidney diseases.

    PubMed

    Yokoo, Takashi; Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application. PMID:19279698

  20. Application of Regenerative Medicine for Kidney Diseases

    PubMed Central

    Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF). The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application. PMID:19279698

  1. Hints to the diagnosis of uromodulin kidney disease

    PubMed Central

    Onoe, Tamehito; Yamada, Kazunori; Mizushima, Ichiro; Ito, Kiyoaki; Kawakami, Takahiro; Daimon, Shoichiro; Muramoto, Hiroaki; Konoshita, Tadashi; Yamagishi, Masakazu; Kawano, Mitsuhiro

    2016-01-01

    Background Uromodulin kidney disease (UKD) is an inherited kidney disease caused by a uromodulin (UMOD) gene mutation. The UMOD gene encodes the Tamm–Horsfall protein (THP), which is the most abundant protein in healthy human urine. Because of its rarity, the incidence of UKD has not been fully elucidated. The purpose of the present study is to clarify the frequency of UKD among patients who underwent renal biopsy. Methods Immunostaining for THP was performed for patients <50 years of age with renal insufficiency and hyperuricemia without overt urinalysis abnormality from renal biopsy databases. Serum and urinary THP concentrations were evaluated in available individuals. Results Fifteen patients were selected for immunostaining from a total of 3787 patients. In three independent patients, abnormal THP accumulation in renal tubular cells was observed. A novel missense A247P UMOD mutation was detected in two of the three patients, including one having a typical family history of familial juvenile hyperuricemic nephropathy. Serum and urinary THP concentrations of all available patients with UMOD A247P mutation were significantly lower than those of controls. Conclusions In the present study, UKD was detected in <1 in 1000 subjects who underwent renal biopsies. However, in subjects meeting all of the above criteria, abnormal THP accumulation was detected in 20% (3/15), suggesting that renal biopsy with immunostaining for THP is a good tool for diagnosing UKD. Also, low serum THP concentration detected in the present subjects might be a good diagnostic marker or important in understanding the pathogenesis of UKD. PMID:26798464

  2. OCCUPATIONAL SILICA EXPOSURE AND CHRONIC KIDNEY DISEASE

    PubMed Central

    Vupputuri, Suma; Parks, Christine G.; Nylander-French, Leena A.; Owen-Smith, Ashli; Hogan, Susan L.; Sandler, Dale P.

    2012-01-01

    Introduction Occupational exposure to silica may be associated with chronic kidney disease (CKD). Most studies have been conducted in occupational cohorts with high levels of exposure but small numbers of cases. We analyzed data from a population-based case-control study of occupational silica exposure and CKD. Methods Cases were hospital patients with newly diagnosed CKD and community controls were selected using random digit dialing and frequency matched by age, gender, race and proximity to the hospital. Silica exposure estimates were assigned by industrial hygiene review of lifetime job history data and weighted for certainty and intensity. Conditional logistic regression was used to estimate the odds ratios (ORs) for CKD conditioned on demographic, lifestyle and clinical variables. Results The mean age of participants was 62 years (range, 30-83 years), 56% were male and 54% were white. Any silica exposure (compared to none) was associated with a 40% increased risk of CKD (OR=1.40, 95% confidence interval [CI]: 1.04, 1.89) in a multivariable adjusted model. The mean cumulative duration of silica exposure was significantly higher in exposed cases than in exposed controls (33.4 vs. 24.8 years, respectively). Overall, compared to non-exposed participants, the ORs (95% CI) for those below and above the median duration of silica exposure were 1.20 (95% CI: 0.77, 1.86) and 1.76 (95% CI: 1.14, 2.71), respectively. Conclusions We found a positive relationship between occupational silica exposure and CKD. A dose-response trend of increasing CKD risk with increasing duration of silica exposure was observed and was particularly strong among non-whites. PMID:22032652

  3. [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. PMID:24315083

  4. The epidermal growth factor receptor pathway in chronic kidney diseases.

    PubMed

    Harskamp, Laura R; Gansevoort, Ron T; van Goor, Harry; Meijer, Esther

    2016-08-01

    The epidermal growth factor receptor (EGFR) pathway has a critical role in renal development, tissue repair and electrolyte handling. Numerous studies have reported an association between dysregulation of this pathway and the initiation and progression of various chronic kidney diseases such as diabetic nephropathy, chronic allograft nephropathy and polycystic kidney disease through the promotion of renal cell proliferation, fibrosis and inflammation. In the oncological setting, compounds that target the EGFR pathway are already in clinical use or have been evaluated in clinical trials; in the renal setting, therapeutic interventions targeting this pathway by decreasing ligand availability with disintegrin and metalloproteinase inhibitors or with ligand-neutralizing antibodies, or by inhibiting receptor activation with tyrosine kinase inhibitors or monoclonal antibodies are only just starting to be explored in animal models of chronic kidney disease and in patients with autosomal dominant polycystic kidney disease. In this Review we focus on the role of the EGFR signalling pathway in the kidney under physiological conditions and during the pathophysiology of chronic kidney diseases and explore the clinical potential of interventions in this pathway to treat chronic renal diseases. PMID:27374915

  5. 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

  6. 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. PMID:24380085

  7. Scattered Deletion of PKD1 in Kidneys Causes a Cystic Snowball Effect and Recapitulates Polycystic Kidney Disease.

    PubMed

    Leonhard, Wouter N; Zandbergen, Malu; Veraar, Kimberley; van den Berg, Susan; van der Weerd, Louise; Breuning, Martijn; de Heer, Emile; Peters, Dorien J M

    2015-06-01

    In total, 1 in 1000 individuals carries a germline mutation in the PKD1 or PKD2 gene, which leads to autosomal dominant polycystic kidney disease (ADPKD). Cysts can form early in life and progressively increase in number and size during adulthood. Extensive research has led to the presumption that somatic inactivation of the remaining allele initiates the formation of cysts, and the progression is further accelerated by renal injury. However, this hypothesis is primarily on the basis of animal studies, in which the gene is inactivated simultaneously in large percentages of kidney cells. To mimic human ADPKD in mice more precisely, we reduced the percentage of Pkd1-deficient kidney cells to 8%. Notably, no pathologic changes occurred for 6 months after Pkd1 deletion, and additional renal injury increased the likelihood of cyst formation but never triggered rapid PKD. In mildly affected mice, cysts were not randomly distributed throughout the kidney but formed in clusters, which could be explained by increased PKD-related signaling in not only cystic epithelial cells but also, healthy-appearing tubules near cysts. In the majority of mice, these changes preceded a rapid and massive onset of severe PKD that was remarkably similar to human ADPKD. Our data suggest that initial cysts are the principal trigger for a snowball effect driving the formation of new cysts, leading to the progression of severe PKD. In addition, this approach is a suitable model for mimicking human ADPKD and can be used for preclinical testing. PMID:25361818

  8. Comprehensive Care for People With Diabetic Kidney Disease

    PubMed Central

    Jain, Koyal

    2015-01-01

    IN BRIEF Diabetic kidney disease carries a heavy burden, both economically and in terms of quality of life, largely because of its very high risk for vascular disease. Coordinated, multidisciplinary care with attention to appropriate, timely screening and preventive management is crucial to reducing the morbidity and mortality of this devastating disease. PMID:26300612

  9. Population genetics of chronic kidney disease: the evolving story of APOL1.

    PubMed

    Wasser, Walter G; Tzur, Shay; Wolday, Dawit; Adu, Dwomoa; Baumstein, Donald; Rosset, Saharon; Skorecki, Karl

    2012-01-01

    Advances in human genome sequencing and generation of public databases of genomic diversity enable nephrologists to re-examine the genetics of common, complex kidney diseases. Non-diabetic kidney diseases prevalent in African ancestry populations and the allelic variation described in chromosome 22q12.3 is one such illustrative example. Newly available genomic database information enabled research groups to discover common functional DNA sequence risk variants in the APOL1 gene. These variants (termed G1 and G2) evolved to confer protection from a species of trypanosomal infection and thus achieved high prominence in many geographic regions of Africa and have been carried over to African diaspora communities worldwide. Since these discoveries two years ago, new insights have been gained: localization of APOL1 in normal and disease kidney tissues; influence of the APOL1 variants on the histopathology of HIV kidney disease; possible association with kidney transplant durability; onset of kidney failure at a younger age; association with blood lipid concentrations; more precise geographic localization of individuals with these variants to western and southern African ancestry; and the absence of the variants and kidney disease predisposition in Ethiopians. The definition of APOL1 nephropathy also confirms the long-held assumption by many clinicians that kidney disease attributed to hypertension in African populations represents an underlying glomerulopathy. Still awaited is the delineation of the biologic mechanisms of cellular injury related to these variants, to provide biologic proof of the APOL1 association and to provide potential targets for preventive and therapeutic intervention. PMID:22878977

  10. Macrophage Migration Inhibitory Factor in Clinical Kidney Disease

    PubMed Central

    Bruchfeld, Annette; Wendt, Mårten; Miller, Edmund J.

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in acute and chronic inflammatory conditions, including sepsis, autoimmune disease, atherogenesis, plaque instability, and pulmonary arterial hypertension. MIF in plasma and urine is significantly elevated in patients with acute kidney injury (AKI) and elevated MIF in serum is associated with markers of oxidative stress, endothelial dysfunction, arterial stiffness, and markers of myocardial damage in chronic kidney disease (CKD). Furthermore, MIF seems to be involved in vascular processes and cardiovascular disease associated with CKD, glomerulonephritis, autosomal dominant polycystic kidney disease, and possibly also in progression to renal failure. Moreover, in active anti-neutrophil cytoplasmatic antibody-associated vasculitis, plasma MIF levels have been shown to be significantly elevated as compared with samples from patients in remission. A significant difference in the genotype frequency of high production MIF -173 G/C genotype has been found in end-stage renal disease, compared to controls. Inhibition of MIF in a diabetic nephropathy model ameliorated blood glucose and albuminuria and in a model of adult polycystic kidney disease cyst growth was delayed. Preclinical studies support a potential therapeutic role for MIF in AKI and in a number of CKDs, whereas these data in human disease are still observational. Future interventional studies are needed to delineate the role of MIF as a treatment target in clinical kidney disease. PMID:26858715

  11. 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....

  12. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease

    PubMed Central

    Riwanto, Meliana; Kapoor, Sarika; Rodriguez, Daniel; Edenhofer, Ilka; Segerer, Stephan; Wüthrich, Rudolf P.

    2016-01-01

    Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD). Here we tested whether metabolic reprogramming towards aerobic glycolysis (“Warburg effect”) plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+), a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha) and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1) in cystic kidneys of Cy/+ rats compared with wild-type (+/+) rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG) on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day) for 5 weeks resulted in significantly lower kidney weights (-27%) and 2-kidney/total-body-weight ratios (-20%) and decreased renal cyst index (-48%) compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min), BUN (0.69±0.26 vs 0.40±0.10 ml/min) and uric acid (0.38±0.20 vs 0.21±0.10 ml/min), and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD. PMID:26752072

  13. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

    PubMed

    Riwanto, Meliana; Kapoor, Sarika; Rodriguez, Daniel; Edenhofer, Ilka; Segerer, Stephan; Wüthrich, Rudolf P

    2016-01-01

    Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD). Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect") plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+), a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha) and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1) in cystic kidneys of Cy/+ rats compared with wild-type (+/+) rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG) on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day) for 5 weeks resulted in significantly lower kidney weights (-27%) and 2-kidney/total-body-weight ratios (-20%) and decreased renal cyst index (-48%) compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min), BUN (0.69±0.26 vs 0.40±0.10 ml/min) and uric acid (0.38±0.20 vs 0.21±0.10 ml/min), and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD. PMID:26752072

  14. Targeting Cell Death Pathways for Therapeutic Intervention in Kidney Diseases.

    PubMed

    Garg, Jay P; Vucic, Domagoj

    2016-05-01

    Precise regulation of cell death and survival is essential for proper maintenance of organismal homeostasis, development, and the immune system. Deregulated cell death can lead to developmental defects, neuropathies, infections, and cancer. Kidney diseases, especially acute pathologies linked to ischemia-reperfusion injury, are among illnesses that profoundly are affected by improper regulation or execution of cell death pathways. Attempts to develop medicines for kidney diseases have been impacted by the complexity of these pathologies given the heterogeneous patient population and diverse etiologies. By analyzing cell death pathways activated in kidney diseases, we attempt to differentiate their importance for these pathologies with a goal of identifying those that have more profound impact and the best therapeutic potential. Although classic apoptosis still might be important, regulated necrosis pathways including necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-associated cell death play a significantly role in kidney diseases, especially in acute kidney pathologies. Although targeting receptor-interacting protein 1 kinase appears to be the best therapeutic strategy, combination with inhibitors of other cell death pathways is likely to bring superior benefit and possible cure to patients suffering from kidney diseases. PMID:27339381

  15. Altered trafficking and stability of polycystins underlie polycystic kidney disease

    PubMed Central

    Cai, Yiqiang; Fedeles, Sorin V.; Dong, Ke; Anyatonwu, Georgia; Onoe, Tamehito; Mitobe, Michihiro; Gao, Jian-Dong; Okuhara, Dayne; Tian, Xin; Gallagher, Anna-Rachel; Tang, Zhangui; Xie, Xiaoli; Lalioti, Maria D.; Lee, Ann-Hwee; Ehrlich, Barbara E.; Somlo, Stefan

    2014-01-01

    The most severe form of autosomal dominant polycystic kidney disease occurs in patients with mutations in the gene (PKD1) encoding polycystin-1 (PC1). PC1 is a complex polytopic membrane protein expressed in cilia that undergoes autoproteolytic cleavage at a G protein–coupled receptor proteolytic site (GPS). A quarter of PKD1 mutations are missense variants, though it is not clear how these mutations promote disease. Here, we established a cell-based system to evaluate these mutations and determined that GPS cleavage is required for PC1 trafficking to cilia. A common feature among a subset of pathogenic missense mutations is a resulting failure of PC1 to traffic to cilia regardless of GPS cleavage. The application of our system also identified a missense mutation in the gene encoding polycystin-2 (PC2) that prevented this protein from properly trafficking to cilia. Using a Pkd1-BAC recombineering approach, we developed murine models to study the effects of these mutations and confirmed that only the cleaved form of PC1 exits the ER and can rescue the embryonically lethal Pkd1-null mutation. Additionally, steady-state expression levels of the intramembranous COOH-terminal fragment of cleaved PC1 required an intact interaction with PC2. The results of this study demonstrate that PC1 trafficking and expression require GPS cleavage and PC2 interaction, respectively, and provide a framework for functional assays to categorize the effects of missense mutations in polycystins. PMID:25365220

  16. 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. PMID:26948372

  17. Next-generation sequencing for research and diagnostics in kidney disease.

    PubMed

    Renkema, Kirsten Y; Stokman, Marijn F; Giles, Rachel H; Knoers, Nine V A M

    2014-08-01

    The advent of next-generation sequencing technologies has enabled genetic nephrology research to move beyond single gene analysis to the simultaneous investigation of hundreds of genes and entire pathways. These new sequencing approaches have been used to identify and characterize causal factors that underlie inherited heterogeneous kidney diseases such as nephronophthisis and congenital anomalies of the kidney and urinary tract. In this Review, we describe the development of next-generation sequencing in basic and clinical research and discuss the implementation of this novel technology in routine patient management. Widespread use of targeted and nontargeted approaches for gene identification in clinical practice will require consistent phenotyping, appropriate disease modelling and collaborative efforts to combine and integrate data analyses. Next-generation sequencing is an exceptionally promising technique that has the potential to improve the management of patients with inherited kidney diseases. However, identifying the molecular mechanisms that lead to renal developmental disorders and ciliopathies is difficult. A major challenge in the near future will be how best to integrate data obtained using next-generation sequencing with personalized medicine, including use of high-throughput disease modelling as a tool to support the clinical diagnosis of kidney diseases. PMID:24914583

  18. Case Report: Whole-exome analysis of a child with polycystic kidney disease and ventriculomegaly.

    PubMed

    Nabhan, M M; Abdelaziz, H; Xu, Y; El Sayed, R; Santibanez-Koref, M; Soliman, N A; Sayer, J A

    2015-01-01

    Autosomal recessive polycystic kidney disease (ARPKD) is an inherited ciliopathy leading to progressive kidney and liver disease. Biallelic mutations in the PKHD1 gene underlie this condition. We describe a child with bilaterally enlarged cystic kidneys, portal hypertension, and cerebral ventriculomegaly. Molecular genetic investigations using whole-exome sequencing and confirmation using Sanger sequencing revealed a homozygous pathogenic mutation in PKHD1 underlying the clinical phenotype of ARPKD. Whole-exome data analysis was used to search for additional rare variants in additional ciliopathy genes that may have contributed to the unusual brain phenotype. Aside from a rare hypomorphic allele in MKS1, no other pathogenic variants were detected. We conclude that the homozygous pathogenic mutation in PKHD1 underlies the ciliopathy phenotype in this patient. PMID:25966130

  19. Beta-2 Microglobulin Kidney Disease Test

    MedlinePlus

    ... accumulate in joint spaces ( synovitis ) in long-term dialysis patients; this is called dialysis-related amyloidosis (DRA). A B2M test may be ... early kidney dysfunction. People who have been on dialysis for five years or more may develop dialysis- ...

  20. Mitochondrial dysfunction in inherited renal disease and acute kidney injury.

    PubMed

    Emma, Francesco; Montini, Giovanni; Parikh, Samir M; Salviati, Leonardo

    2016-05-01

    Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue. PMID:26804019

  1. 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. PMID:26596504

  2. Feline glomeruli: morphologic comparisons in normal, autolytic, and diseased kidneys.

    PubMed

    Crowell, W A; Leininger, J R

    1976-09-01

    Twelve cats were used to study autolytic changes in glomerular morphology and compare these with lesions of naturally occurring feline renal disease. The 12 cats had normal clinical, urinary, and blood features. One kidney (0-hour control) was excised immediately after a given cat was euthanatized, and portions of it were prepared for light and electron microscopy. The opposite kidney (autolytic) remained in situ for selected postmortem intervals, up to 24 hours, at which time it was similarly processed. Renal tissues from 4 additional cats (3 with proteinuria and 1 with diabetes mellitus) were processed and examined for comparison. Zero-hour control kidneys had the following mean quantitations: renal weight was 9.9 g; glomerular diameter, 83 mum; number of cells per glomerulus in 1-mum section was 63; and diameter of cell nuclei was 6.3 mum for mesangial, 6.7 mum for visceral epithelial, and 6.4 mum for endothelial. In comparison with 0-hour control kidneys, autolytic kidneys had increased weight and glomerular diameter, but the diameter of cell nuclei decreased. Basement membrane thickness and glomerular cell numbers did not differ between 0-hour control and autolytic kidneys. Kidneys from 4 diseased cats had increased glomerular diameter and glomerular basement membrane changes characterized by hyalin thickening and dense deposits. These changes are compatible with a lesion diagnosis of membranous glomerulonephritis. PMID:962208

  3. Race and kidney disease: role of social and environmental factors.

    PubMed Central

    Nzerue, Chike M.; Demissochew, Haliu; Tucker, J. Kevin

    2002-01-01

    Numerous studies have documented the presence of racial disparities among Americans in health outcomes with respect to cardiovascular disease, infant mortality, cancer, and kidney disease. With regard to kidney diseases, these disparities are more dramatic. African, Hispanic, and Native Americans have the highest risks of end-stage renal disease (ESRD). The incidence of ESRD is four times higher in African Americans than in whites. Diseases causing chronic kidney failure, such as diabetes mellitus, hypertension, systemic lupus erythematosus, and human immunodeficiency virus-associated nephropathy, are particularly prevalent among African-American patients. In addition to the higher prevalence, the morbidity associated with kidney complications of these diseases appears worse in African-American patients. African Americans also have worse outcomes and a relatively reduced access to kidney transplantation--the best therapy for ESRD. It is highly likely that social and environmental factors play a very significant role in the persistence of these disparities. A detailed understanding of these socioeconomic and environmental factors will be critical in formulating rational public health strategies to redress these disparities. This paper reviews the social, economic and environmental factors that impact on the incidence of ESRD in minority groups. PMID:12152910

  4. Aortic stiffness and kidney disease in an elderly population

    PubMed Central

    Michener, Katherine H.; Mitchell, Gary F.; Noubary, Farzad; Huang, Naya; Harris, Tamara; Andresdottir, Margret B.; Palsson, Runolfur; Gudnason, Vilmundur; Levey, Andrew S.

    2015-01-01

    Background/Aims The causes of chronic kidney disease (CKD) in older people are not well understood. Aortic stiffness increases with age and results in transmission of increased pulsatility into the kidney microvasculature, potentially contributing to CKD in older populations. Methods We utilized data from the Age, Gene/Environment, Susceptibility-Reykjavik Study, a community-based prospective cohort study of cardiovascular disease (CVD) in Iceland. Associations of carotid pulse pressure (CPP) and carotid femoral pulse wave velocity (CFPWV) with estimated glomerular filtration rate based on creatinine and cystatin C (eGFR) and urine albumin-creatinine ratio (ACR) were assessed using linear regression, adjusting for demographics and CVD risk factors. Results 940 participants [mean (SD) age 75.8 (4.7) years, mean (SD) CFPWV 12.9 (4.2) m/s, mean (SD) CPP 69 (21) mm Hg, mean (SD) eGFR 68 (16) ml/min/1.73m2, and median (IQR) ACR 3 (2–6) mg/g) were studied. At CPP greater than 85 mmHg, higher CPP was associated with lower eGFR in unadjusted analyses but not after adjustment. CPP was significantly associated with higher ACR in fully adjusted models [β (95% CI)=0.14 (0.03, 0.24) ln mg/g per SD]. Higher CFPWV was associated with lower eGFR and higher ACR in unadjusted analyses but not after adjustment. Conclusion Greater aortic stiffness may be associated with modestly higher levels of albuminuria in the elderly. The association with lower eGFR may be confounded by age and CVD risk factors. PMID:26067356

  5. Gut microbiota and inflammation in chronic kidney disease patients

    PubMed Central

    Mafra, Denise; Fouque, Denis

    2015-01-01

    Inflammation is a multifactorial phenotype that in chronic kidney disease is associated with adverse patient outcomes. Recently, alterations in gut microbiota composition and intestinal barrier have been associated with inflammation and oxidative stress in CKD patients. Vanholder and Glorieux recently critically reviewed [Clin Kidney J (2015) 8 (2): 168-179] the current understanding of the role of gut microbiota in the production of uraemic toxins and the therapeutic implications. Where do we stand now? The basic mechanisms of the gut-kidney crosstalk must still be clarified. In addition, the efficacy and safety of therapeutic strategies to modulate the gut microbiota in order to decrease uraemic toxin production and inflammation in chronic kidney disease should be evaluated. Finally, an impact of such strategies on hard outcomes should be demonstrated before incorporation into routine clinical practice. PMID:26034597

  6. Sonar and its Use in Kidney Disease in Children

    PubMed Central

    Lyons, E. A.; Murphy, A. V.; Arneil, G. C.

    1972-01-01

    The basic principles of diagnostic ultrasound or sonar are given, together with the special technique required for scanning newborn infants and small children for kidney abnormalities. Illustrative examples of the potential of this procedure, both in diagnosis and in monitoring changes include a normal neonatal and preadolescent kidney, unilateral renal agenesis, duplex kidney, renal cyst, polycystic disease, nephroblastoma, and examples of mild and severe hydronephrosis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7FIG. 8FIG. 9FIG. 10FIG. 11FIG. 12 PMID:4343783

  7. MicroRNAs as potential therapeutic targets in kidney disease

    PubMed Central

    Gomez, Ivan G; Grafals, Monica; Portilla, Didier; Duffield, Jeremy S

    2014-01-01

    One cornerstone of Chronic Kidney Disease (CKD) is fibrosis, as kidneys are susceptible due to their high vascularity and predisposition to ischemia. Presently, only therapies targeting the angiotensin receptor are used in clinical practice to retard the progression of CKD. Thus, there is a pressing need for new therapies designed to treat the damaged kidney. Several independent laboratories have identified a number of microRNAs that are dysregulated in human and animal models of CKD. We will explore the evidence suggesting that by blocking the activity of such dysregulated microRNAs, new therapeutics could be developed to treat the progression of CKD. PMID:23660218

  8. Diabetic kidney disease in Australia: current burden and future projections.

    PubMed

    White, Sarah; Chadban, Steve

    2014-08-01

    Diabetes mellitus is now the most common cause of new cases of end-stage kidney disease treated with kidney replacement therapy in Australia. In addition to the approximately 5000 Australians receiving maintenance dialysis or living with a kidney transplant as a consequence of diabetes, many die from untreated end-stage kidney disease due to diabetes (DM-ESKD) each year. For every Australian receiving renal replacement therapy due to diabetes, at least 50 others have earlier stages of diabetic kidney disease (DKD). Based on projected increases in type 2 diabetes prevalence, the size of this underlying population with DKD will potentially exceed half a million by 2025. In addition to the risk of developing DM-ESKD, this population is at increased risk of premature cardiovascular morbidity and all-cause mortality. Higher rates of hospitalization, use of specialist services and prescription drugs mean that those with DKD also incur significantly greater health care costs compared with those with diabetes or chronic kidney disease alone. However, in contrast to the increasing prevalence of diabetes and early stages of DKD, recent trends in the incidence of DM-ESKD suggest that better management in the earlier stages of DKD has been successful in slowing rates of disease progression. Simultaneous improvements in use of renin-angiotensin inhibitors and improved glycaemic and blood pressure control are likely to be largely responsible for this trend. Primary prevention, maximizing early detection of DKD and optimal management of diabetes and kidney disease hold great potential to attenuate the future health burden attributable to DKD in Australia. PMID:24888506

  9. 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

  10. Smaller caliber renal arteries are a novel feature of uromodulin-associated kidney disease.

    PubMed

    Prejbisz, Aleksander; Sellin, Lorenz; Szwench-Pietrasz, Elżbieta; Woznowski, Magdalena; Michałowska, Ilona; Blondin, Dirk; Sajnaga, Dariusz; Epplen, Jorg T; Litwin, Mieczysław; Dekomien, Gabriele; Januszewicz, Magdalena; Helmchen, Udo; Matuszkiewicz-Rowińska, Joanna; Adamczak, Marcin; Więcek, Andrzej; Januszewicz, Andrzej; Rump, Lars C

    2015-07-01

    Hyperuricemia is very common in industrialized countries and known to promote vascular smooth muscle cell proliferation. Juvenile hyperuricemia is a hallmark of uromodulin-associated kidney disease characterized by progressive interstitial renal fibrosis leading to end-stage renal disease within decades. Here we describe a member of a Polish-German family with a history of familial background of chronic kidney disease, hyperuricemia, and gout. This patient had hypertension because of bilateral small renal arteries, hyperuricemia, and chronic kidney disease. Clinical and molecular studies were subsequently performed in 39 family members, which included a physical examination, Duplex ultrasound of the kidneys, laboratory tests for renal function, and urine analysis. In eight family members contrast-enhanced renal artery imaging by computed tomography-angiography or magnetic resonance imaging was conducted and showed that bilateral non-arteriosclerotic small caliber renal arteries were associated with hyperuricemia and chronic kidney disease. Of the 26 family members who underwent genotyping, 11 possessed the P236R mutation (c.707C>G) of the uromodulin gene. All family members with a small caliber renal artery carried the uromodulin P236R mutation. Statistical analysis showed a strong correlation between reduced renal artery lumen and decreased estimated glomerular filtration rate. Thus, bilateral small caliber renal arteries are a new clinical phenotype associated with an uromodulin mutation. PMID:25671765

  11. High-resolution genetic localization of a modifying locus affecting disease severity in the juvenile cystic kidneys (jck) mouse model of polycystic kidney disease.

    PubMed

    Beier, David R

    2016-06-01

    We have previously demonstrated that a locus on proximal Chr 4 modifies disease severity in the juvenile cystic kidney (jck) mouse, a model of polycystic kidney disease (PKD) that carries a mutation of the Nek8 serine-threonine kinase. In this study, we used QTL analysis of independently constructed B6.D2 congenic lines to confirm this and showed that this locus has a highly significant effect. We constructed sub-congenic lines to more specifically localize the modifier and have determined it resides in a 3.2 Mb interval containing 28 genes. These include Invs and Anks6, which are both excellent candidates for the modifier as mutations in these genes result in PKD and both genes are known to genetically and physically interact with Nek8. However, examination of strain-specific DNA sequence and kidney expression did not reveal clear differences that might implicate either gene as a modifier of PKD severity. The fact that our high-resolution analysis did not yield an unambiguous result highlights the challenge of establishing the causality of strain-specific variants as genetic modifiers, and suggests that alternative strategies be considered. PMID:27114383

  12. 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,...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. How to Read a Food Label: Tips for People with Chronic Kidney Disease (CKD)

    MedlinePlus

    ... to Read a Tips for People with Chronic Kidney Disease (CKD) National Kidney Disease Education Program If you have CKD, you may ... 4 KIDNEY (1-866-454-3639). The National Kidney Disease Education Program (NKDEP) encourages people to get tested ...

  18. Variable Clinical Presentation of an MUC1 Mutation Causing Medullary Cystic Kidney Disease Type 1

    PubMed Central

    Kmoch, Stanislav; Antignac, Corinne; Robins, Vicki; Kidd, Kendrah; Kelsoe, John R.; Hladik, Gerald; Klemmer, Philip; Knohl, Stephen J.; Scheinman, Steven J.; Vo, Nam; Santi, Ann; Harris, Alese; Canaday, Omar; Weller, Nelson; Hulick, Peter J.; Vogel, Kristen; Rahbari-Oskoui, Frederick F.; Tuazon, Jennifer; Deltas, Constantinos; Somers, Douglas; Megarbane, Andre; Kimmel, Paul L.; Sperati, C. John; Orr-Urtreger, Avi; Ben-Shachar, Shay; Waugh, David A.; McGinn, Stella; Hodaňová, Kateřina; Vylet'al, Petr; Živná, Martina; Hart, Thomas C.; Hart, P. Suzanne

    2014-01-01

    Background and objectives The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. Design, setting, participants, & measurements Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). Results Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. Conclusion MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene–gene

  19. New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications.

    PubMed

    Telega, Grzegorz; Cronin, David; Avner, Ellis D

    2013-06-01

    Improved neonatal medical care and renal replacement technology have improved the long-term survival of patients with ARPKD. Ten-yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life. In addition to renal pathology, patients with ARPKD develop ductal plate malformations with cystic dilation of intra- and extrahepatic bile ducts resulting in CHF and Caroli syndrome. Many patients with CHF will develop portal hypertension with resulting esophageal varices, splenomegaly, hypersplenism, protein losing enteropathy, and gastrointestinal bleeding. Management of portal hypertension may require EBL of esophageal varices or porto-systemic shunting. Complications of hepatic involvement can include ascending cholangitis, cholestasis with malabsorption of fat-soluble vitamins, and rarely benign or malignant liver tumors. Patients with ARPKD who eventually reach ESRD, and ultimately require kidney transplantation, present a unique set of complications related to their underlying hepato-biliary disease. In this review, we focus on new approaches to these challenging patients, including the indications for liver transplantation in ARPKD patients with severe chronic kidney disease awaiting kidney transplant. While survival in patients with ARPKD and isolated kidney transplant is comparable to that of age-matched pediatric patients who have received kidney transplants due to other primary renal diseases, 64-80% of the mortality occurring in ARPKD kidney transplant patients is attributed to cholangitis/sepsis, which is related to their hepato-biliary disease. Recent data demonstrate that surgical mortality among pediatric liver transplant recipients is decreased to <10% at one yr. The immunosuppressive regimen

  20. The case for disease management in chronic kidney disease.

    PubMed

    Chen, Randolph A; Scott, Susan; Mattern, William D; Mohini, Ravinder; Nissenson, Allen R

    2006-04-01

    Chronic kidney disease (CKD) is a growing epidemic in the United States and worldwide, with nearly two thirds of CKD patients also having diabetes, hypertension, or both. Morbidity and mortality among patients with CKD are high, as are the costs associated with care, which is highly fragmented. Disease management (DM) programs are designed to coordinate the delivery of care to patients, improve clinical outcomes, and reduce costs along the continuum of care. The goals of DM programs in CKD patients are to fill the gaps in current care by focusing on four key areas: (1) slowing the progression of CKD, (2) identifying and managing the complications of CKD, (3) identifying and managing associated comorbid conditions, and (4) smoothing the transition to renal replacement therapy (RRT). To be successful, this approach requires multidisciplinary collaboration among physicians (eg, primary care physicians, endocrinologists, cardiologists, nephrologists, surgeons) and participating caregivers including nurses, dieticians, social workers, and pharmacists. Patient identification, limited reimbursement, late patient referral, and lack of primary care physician and nephrologist knowledge about the importance and details of CKD management are all barriers that must be overcome for such programs to be successfully implemented. Considering the magnitude of the opportunity, DM applied to CKD is a promising approach to the care of this vulnerable population. PMID:16620194

  1. 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…

  2. 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. PMID:27157321

  3. Hox11 paralogous genes are essential for metanephric kidney induction.

    PubMed

    Wellik, Deneen M; Hawkes, Patrick J; Capecchi, Mario R

    2002-06-01

    The mammalian Hox complex is divided into four linkage groups containing 13 sets of paralogous genes. These paralogous genes have retained functional redundancy during evolution. For this reason, loss of only one or two Hox genes within a paralogous group often results in incompletely penetrant phenotypes which are difficult to interpret by molecular analysis. For example, mice individually mutant for Hoxa11 or Hoxd11 show no discernible kidney abnormalities. Hoxa11/Hoxd11 double mutants, however, demonstrate hypoplasia of the kidneys. As described in this study, removal of the last Hox11 paralogous member, Hoxc11, results in the complete loss of metanephric kidney induction. In these triple mutants, the metanephric blastema condenses, and expression of early patterning genes, Pax2 and Wt1, is unperturbed. Eya1 expression is also intact. Six2 expression, however, is absent, as is expression of the inducing growth factor, Gdnf. In the absence of Gdnf, ureteric bud formation is not initiated. Molecular analysis of this phenotype demonstrates that Hox11 control of early metanephric induction is accomplished by the interaction of Hox11 genes with the pax-eya-six regulatory cascade, a pathway that may be used by Hox genes more generally for the induction of multiple structures along the anteroposterior axis. PMID:12050119

  4. 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...

  5. Long-term risk of chronic kidney disease in unilateral multicystic dysplastic kidney.

    PubMed

    Mansoor, Omer; Chandar, Jayanthi; Rodriguez, Maria M; Abitbol, Carolyn L; Seeherunvong, Wacharee; Freundlich, Michael; Zilleruelo, Gaston

    2011-04-01

    The clinical spectrum of renal dysplasia includes the non-functioning multicystic dysplastic kidney (MCDK). We report our experience of the outcome of unilateral MCDK and its contralateral kidney in 101 children with the diagnosis of MCDK from 1985 to 2009. Data collected included urine protein/creatinine ratio, estimated GFR (eGFR), blood pressure, surgical intervention, renal length and abnormalities of the contralateral kidney, and the involution rate. There was a predominance of left-sided MCDK. Diagnosis was made prenatally in 86.7%. Contralateral abnormalities included vesicoureteral reflux (16.8%), UPJ obstruction (4.1%), and megaureter (2.4%). Complete involution of MCDK occurred within 5 years in 60%. Compensatory hypertrophy of the contralateral kidney to >97% occurred in 74.1%. Nephrectomy was performed in 19.8%. There was an increased risk of chronic kidney disease (CKD) stage ≥ 2, and hypertension in those with contralateral abnormalities (p<0.0001; p<0.001 respectively). In those without contralateral abnormalities, hyperfiltration with mean eGFR of 149 ± 13 ml/min/1.73 m(2) was seen in 32% and proteinuria in 9.8%. There was a significantly inverse relationship between proteinuria and eGFR (p<0.0001). In conclusion, children with contralateral abnormalities are at risk for developing decreased kidney function, whereas a substantial number of patients with no obvious contralateral abnormalities have markers of renal injury. Therefore, systematic follow-up of all patients is recommended. PMID:21240528

  6. Feline polycystic kidney disease is linked to the PKD1 region.

    PubMed

    Young, Amy E; Biller, David S; Herrgesell, Eric J; Roberts, Heather R; Lyons, Leslie A

    2005-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder (1/1000) in humans characterized by fluid-filled cysts in the kidneys. Defects in the PKD genes, PKD1 and PKD2, cause 85% and 15% of human ADPKD cases, respectively. Mutations in the PKHD1 gene cause autosomal recessive PKD (ARPKD). Mutations in several genes, including Nek8, cause PKD in mice. Although PKD affects 38% of Persian cats worldwide, making it the most prominent inherited feline disease, a causative gene has not been identified. Feline PKD is an autosomal dominant disease with clinical presentations similar to human ADPKD. Forty-three microsatellites were chosen from the feline genetic maps based on known homology with human chromosomal regions containing the PKD1, PKD2, PKHD1, and Nek8 genes. Linkage analysis using seven Persian cat pedigrees segregating for PKD has shown significant linkage and no recombinants (Z=5.83, theta=0) between the PKD disease phenotype and marker FCA476, which is within 10 cR of the feline PKD1 gene on Chromosome E3. This suggests that the PKD1 gene or another gene within this region may cause feline PKD. Further investigation into the cause of PKD will be valuable for feline health and provide insights into human ADPKD. PMID:15674734

  7. High Water Intake and Progression of Chronic Kidney Diseases.

    PubMed

    Choi, Hoon Young; Park, Hyeong Cheon; Ha, Sung Kyu

    2015-12-01

    Impact of water intake on the courses of chronic kidney and urinary tract diseases, such as urolithiasis, urinary tract infections, chronic kidney diseases (CKD), autosomal dominant polycystic kidney diseases and bladder cancer, has recently been studied. It still remains controversial whether increased water intake slows the progression of CKD or not. However, high water intake suppresses plasma levels of arginine vasopressin (AVP), which is expected to be beneficial for the preservation of the kidney function. Previous studies suggest that water intake suppresses plasma levels of AVP, and high levels of AVP have been suggested to play deleterious roles in animal models of kidney disease. Moreover, recent epidemic of CKD of unknown origin, which was supposed to be related to the insufficient water intake and chronic volume depletion, has been reported in Central America, further suggesting that the suppression of AVP by sustained water intake might be beneficial in this CKD population. Indeed, the data from recent studies were consistent with the view that high water intake is associated with slower progression of CKD. However, contradictory findings also exist. The intriguing effects of increased urine volume in preserving the glomerular filtration rate in human patients with CKD require more large and well-designed randomized prospective clinical trials. PMID:26848303

  8. 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. PMID:27011059

  9. [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. PMID:27067212

  10. Acute kidney injury in critically ill patients with lung disease: kidney-lung crosstalk

    PubMed Central

    de Abreu, Krasnalhia Lívia Soares; da Silva Junior, Geraldo Bezerra; Muniz, Thalita Diógenes; Barreto, Adller Gonçalves Costa; Lima, Rafael Siqueira Athayde; Holanda, Marcelo Alcântara; Pereira, Eanes Delgado Barros; Libório, Alexandre Braga; Daher, Elizabeth de Francesco

    2013-01-01

    Objective To examine the factors associated with acute kidney injury and outcome in patients with lung disease. Methods A prospective study was conducted with 100 consecutive patients admitted to a respiratory intensive care unit in Fortaleza (CE), Brazil. The risk factors for acute kidney injury and mortality were investigated in a group of patients with lung diseases. Results The mean age of the study population was 57 years, and 50% were male. The incidence of acute kidney injury was higher in patients with PaO2/FiO2<200 mmHg (54% versus 23.7%; p=0.02). Death was observed in 40 cases and the rate of mortality of the acute kidney injury group was higher (62.8% versus 27.6%; p=0.01). The independent factor that was found to be associated with acute kidney injury was PaO2/FiO2<200 mmHg (p=0.01), and the independent risk factors for death were PEEP at admission (OR: 3.6; 95%CI: 1.3-9.6; p=0.009) and need for hemodialysis (OR: 7.9; 95%CI: 2.2-28.3; p=0.001). Conclusion There was a higher mortality rate in the acute kidney injury group. Increased mortality was associated with mechanical ventilation, high PEEP, urea and need for dialysis. Further studies must be performed to better establish the relationship between kidney and lung injury and its impact on patient outcome. PMID:23917978

  11. 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. PMID:27442377

  12. Focal segmental glomerulosclerosis and chronic kidney disease in pediatric patients.

    PubMed

    Kiffel, Jeremy; Rahimzada, Yael; Trachtman, Howard

    2011-09-01

    Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of acquired glomerular disease leading to end-stage kidney disease. Its incidence is rising around the world. There is no proven therapy for those patients who do not respond to corticosteroids and it can recur in 20% to 25% of patients who receive a kidney transplant. The disease can be primary, or it can be secondary to various conditions including vesicoureteral reflux, obesity, medications, and infections. Recent advances have demonstrated the important role of genetic mutations in podocyte proteins as a cause of FSGS. There is an urgent need for randomized clinical trials to develop safe and effective therapy for FSGS that occurs in the native or transplanted kidney. PMID:21896374

  13. 78 FR 9931 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases... Kidney Diseases Special; Emphasis Panel; Time-Sensitive Obesity Applications Date: March 14, 2013....

  14. 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,...

  15. 76 FR 60057 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-28

    ... Kidney Diseases Special Emphasis Panel, Cognitive Function in Chronic Disease Ancillary Studies. Date..., Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS) Dated: September 21... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  16. 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

  17. Autosomal Dominant Polycystic Kidney Disease (ADPKD) in an Italian family carrying a novel nonsense mutation and two missense changes in exons 44 and 45 of the PKD1 gene

    SciTech Connect

    Rossetti, S.; Bresin, E.; Corra, S.

    1996-10-16

    Sixty-seven Italian patients with autosomal dominant polycystic kidney disease (ADPKD) were screened for mutations in the 3{prime} unique region of the PKD1 gene, using heteroduplex DNA analysis. Novel aberrant bands were detected in 3 patients from the same family. DNA sequencing showed a C to T transition in exon 44 (C12269T), resulting in a premature stop codon (R4020X), predicted to impair the synthesis of the putative intracytoplasmic C-terminus tail of the PKD1 protein, polycystin. The mutation also generates a novel DdeI restriction site, and the abnormal restriction pattern was observed both on genomic DNA and on cDNA from the affected relatives, indicating that this is indeed the pathogenetic molecular lesion. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on lymphocyte mRNA showed that the mutant transcript is normally present and stable. No aberrantly spliced mRNAs were detected. Interestingly, the mutant PKD1 chromosome in this family also bears two missense mutations downstream (A12341G and C12384T), not found in the other ADPKD families studied. 19 refs., 4 figs.

  18. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD. PMID:27553994

  19. 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. PMID:26300515

  20. Imaging Approaches to Patients with Polycystic Kidney Disease

    PubMed Central

    Chapman, Arlene B.; Wei, Wenjing

    2011-01-01

    Imaging is an important approach to diagnosis, monitoring and predicting outcomes for patients with Autosomal Dominant polycystic Kidney Disease (ADPKD). This paper reviews three common clinical imaging techniques, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and their role in management of ADPKD. Ultrasonographic criteria for diagnosis in children and adults are reviewed. Total kidney volume (TKV), as measured by MRI, is suggested as important potential marker to determine disease progression and overall prognosis. Renal blood flow (RBF) and a novel approach to interpreting non-cystic renal parenchymal by CT images are other innovative imaging approaches described. PMID:21784272

  1. MALDI imaging MS reveals candidate lipid markers of polycystic kidney disease.

    PubMed

    Ruh, Hermelindis; Salonikios, Theresia; Fuchser, Jens; Schwartz, Matthias; Sticht, Carsten; Hochheim, Christina; Wirnitzer, Bernhard; Gretz, Norbert; Hopf, Carsten

    2013-10-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a severe, monogenetically inherited kidney and liver disease. PCK rats carrying the orthologous mutant gene serve as a model of human disease, and alterations in lipid profiles in PCK rats suggest that defined subsets of lipids may be useful as molecular disease markers. Whereas MALDI protein imaging mass spectrometry (IMS) has become a promising tool for disease classification, widely applicable workflows that link MALDI lipid imaging and identification as well as structural characterization of candidate disease-classifying marker lipids are lacking. Here, we combine selective MALDI imaging of sulfated kidney lipids and Fisher discriminant analysis (FDA) of imaging data sets for identification of candidate markers of progressive disease in PCK rats. Our study highlights strong increases in lower mass lipids as main classifiers of cystic disease. Structure determination by high-resolution mass spectrometry identifies these altered lipids as taurine-conjugated bile acids. These sulfated lipids are selectively elevated in the PCK rat model but not in models of related hepatorenal fibrocystic diseases, suggesting that they be molecular markers of the disease and that a combination of MALDI imaging with high-resolution MS methods and Fisher discriminant data analysis may be applicable for lipid marker discovery. PMID:23852700

  2. 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

  3. Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

    PubMed Central

    Swan, E J; Salem, R M; Sandholm, N; Tarnow, L; Rossing, P; Lajer, M; Groop, P H; Maxwell, A P; McKnight, A J

    2015-01-01

    Aim To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. Methods The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates. Results A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of effect. Three independent signals (seven SNPs) were common to the replication data for both phenotypes with Type 1 diabetes and persistent proteinuria or end-stage renal disease. Conclusions Our results suggest that SNPs in nuclear genes that influence mitochondrial function are significantly associated with diabetic kidney disease in a white European population. What’s new? Mitochondrial dysfunction has been identified in diabetic kidney disease, but relatively large-scale genetic and epigenetic studies focused on mitochondria have not yet been described. We report a novel case–control analysis, with independent replication, of genetic variation focused on the mitochondrial genome and 1039 nuclear genes that are important for mitochondrial function. Single nucleotide

  4. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys.

    PubMed

    Decramer, Stéphane; Parant, Olivier; Beaufils, Sandrine; Clauin, Séverine; Guillou, Cécile; Kessler, Sylvie; Aziza, Jacqueline; Bandin, Flavio; Schanstra, Joost P; Bellanné-Chantelot, Christine

    2007-03-01

    Prenatal discovery of fetal bilateral hyperechogenic kidneys is very stressful for pregnant women and their family, and accurate diagnosis of the cause of the moderate forms of this pathology is very difficult. Hepatocyte nuclear factor-1beta that is encoded by the TCF2 gene is involved in the embryonic development of the kidneys. Sixty-two pregnancies with fetal bilateral hyperechogenic kidneys including 25 fetuses with inaccurate diagnosis were studied. TCF2 gene anomalies were detected in 18 (29%) of these 62 patients, and 15 of these 18 patients presented a complete heterozygous deletion of the TCF2 gene. Family screening revealed de novo TCF2 anomalies in more than half of the patients. TCF2 anomalies were associated with normal amniotic fluid volume and normal-sized kidneys between -2 and +2 SD in all patients except for two sisters. Antenatal cysts were detected in 11 of 18 patients, unilaterally in eight of 11. After birth, cysts appeared during the first year (17 of 18), and in patients with antenatal cysts, the number increased and developed bilaterally with decreased renal growth. In these 18 patients, the GFR decreased with longer follow-up and was lower in patients with solitary functioning dysplastic kidney. Heterozygous deletion of the TCF2 gene is an important cause of fetal hyperechogenic kidneys in this study and showed to be linked with early disease expression. The renal phenotype and the postnatal evolution were extremely variable and need a prospective long-term follow-up. Extrarenal manifestations are frequent in TCF2-linked pathologies. Therefore, prenatal counseling and follow-up should be multidisciplinary. PMID:17267738

  5. Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats

    PubMed Central

    Ta, Michelle H T; Schwensen, Kristina G; Liuwantara, David; Huso, David L; Watnick, Terry; Rangan, Gopala K

    2016-01-01

    AIM: To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). METHODS: The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofluorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFα and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue. RESULTS: Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with α smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBα protein levels, and TNFα and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identified in the CECs of LPK and human polycystic kidneys. CONCLUSION: Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases. PMID:27458563

  6. 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…

  7. 75 FR 34147 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... Kidney Diseases Special Emphasis Panel; Biomarkers in Acute Kidney Injury Ancillary Studies. Date: July... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes of Health,...

  8. Relationship between chronic kidney disease and metabolic syndrome: current perspectives

    PubMed Central

    Nashar, Khaled; Egan, Brent M

    2014-01-01

    Both metabolic syndrome (MetS) and chronic kidney disease (CKD) are increasing in incidence and lead to significant cardiovascular morbidity and mortality. The relationship between these two entities is complex. Individual components of the MetS are known risk factors for incident kidney disease, but it is not clear how the clustering of these components is linked to the development and progression of kidney disease. Cross-sectional studies show an association of the MetS and prevalent CKD; however, one cannot draw conclusions as to which came first – the MetS or the kidney disease. Observational studies suggest a relationship between MetS and incident CKD, but they also demonstrate the development of MetS in patients with established CKD. These observations suggest a bidirectional relationship. A better understanding of the relationship between components of the MetS and whether and how these components contribute to progression of CKD and incident cardiovascular disease could inform more effective prevention strategies. PMID:25258547

  9. 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. PMID:25295579

  10. Molecular diagnosis of autosomal dominant polycystic kidney disease.

    PubMed

    Torra Balcells, R; Ars Criach, E

    2011-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Its estimated prevalence is 1 per 800 individuals. ADPKD patients constitute 8% of the population on dialysis or kidney transplantation. The disease can be diagnosed using radiological or genetic procedures. Direct genetic diagnosis of the disease can now be performed in Spain; however, it is not an easy or cheap test. This is why every case should be considered individually to determine whether genetic testing is appropriate, and to determine which genetic test is most adequate. Genetic testing in ADPKD is of special interest for living donors and neonatal and sporadic cases. Genetic testing offers the chance of performing prenatal or pre-implantation testing of embryos in families with severe cases of the disease. Also, this will enable the disease to be treated, when specific treatment becomes available, in cases that would not be candidates for treatment without genetic confirmation. PMID:21270911

  11. 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. PMID:24336029

  12. 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. PMID:25970330

  13. A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

    PubMed Central

    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. PMID:25970330

  14. 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

  15. 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. PMID:26239363

  16. Kidney Failure

    MedlinePlus

    ... if You Have Kidney Disease Kidney Failure Expand Dialysis Kidney Transplant Preparing for Kidney Failure Treatment Choosing Not to Treat with Dialysis or Transplant Paying for Kidney Failure Treatment Contact ...

  17. 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,...

  18. 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...

  19. 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

    ... 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 and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  20. 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

    ... Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Kidney Diseases Special Emphasis Panel; PAR12-265 Ancillary Studies in Kidney Disease and Complications... Institute of Diabetes and Digestive and Kidney Diseases Special, Emphasis Panel; CRIC Ancillary...

  1. 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...

  2. Review of tolvaptan for autosomal dominant polycystic kidney disease.

    PubMed

    Baur, Brian P; Meaney, Calvin J

    2014-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by bilateral renal cysts, kidney pain, hypertension, and progressive loss of renal function. It is a leading cause of end-stage renal disease and the most common inherited kidney disease in the United States. Despite its prevalence, disease-modifying treatment options do not currently exist. Tolvaptan is an orally active, selective arginine vasopressin V2 receptor antagonist already in use for hyponatremia. Tolvaptan exhibits dose-proportional pharmacokinetics with a half-life of ~12 hours. Metabolism occurs through the cytochrome P450 3A4 isoenzyme, and tolvaptan is a substrate for P-glycoprotein, resulting in numerous drug interactions. Recent research has highlighted the beneficial effect of tolvaptan on delaying the progression of ADPKD, which is the focus of this review. Pharmacologic, preclinical, and phase II and III clinical trial studies have demonstrated that tolvaptan is an effective treatment option that targets underlying pathogenic mechanisms of ADPKD. Tolvaptan delays the increase in total kidney volume (surrogate marker for disease progression), slows the decline in renal function, and reduces kidney pain. However, tolvaptan has significant adverse effects including aquaretic effects (polyuria, nocturia, polydipsia) and elevation of aminotransferase enzyme concentrations with the potential for acute liver failure. Appropriate patient selection is critical to optimize long-term benefits while minimizing adverse effects and hepatotoxic risk factors. Overall, tolvaptan is the first pharmacotherapeutic intervention to demonstrate significant benefit in the treatment of ADPKD, but practitioners and regulatory agencies must carefully weigh the risks versus benefits. Additional research should focus on incidence and risk factors of liver injury, cost-effectiveness, clinical management of drug-drug interactions, and long-term disease outcomes. PMID:24706579

  3. Genetic analysis of loci that contribute to recessive polycystic kidney disease in the mouse

    SciTech Connect

    Beier, D.R.; Dushkin, H.; Tobin, D.

    1994-09-01

    Identification of genes that play a role in the development of autosomal recessive polycystic kidney disease (ARPKD) is a key to the better understanding of this disorder. We have discovered a new mutation in the mouse we call juvenile cystic kidney (jck) which predisposes to the development of ARPKD and is not allelic with any previously described mutations. In an effort to map and positionally clone the jck gene, an intraspecific intercross between B6/DBA jck/+F1 mice was established and over 100 affected progeny were identified. Genotype analysis using microsatellite markers was employed and the jck mutation has been mapped to a 1 cM interval on mouse chromosome 11. Positional cloning of this mutant locus by employing a YAC contig is in progress. Narrowing the region of interest has been facilitated by the utilization of SSCP analysis to develop informative markers from YAC sequence. In addition, it was noted that severity of disease in the intercross progeny (as measured by the degree of kidney enlargement) was more variable than that observed in the parental B6 strain. This suggested that a modifier locus introduced form the DBA background affects the expression of the jck phenotype. We have determined that two additional regions - one from DBA on distal chromosome 10 and a second from B6 on chromosome 1 - are strongly associated with inheritance of a more severe polycystic kidney disease phenotype. The finding of a highly significant association of a B6-related locus with kidney enlargement was completely unexpected, since the PKD phenotype in the original B6 background is not severe. This finding is unambiguous, with a maximal quantitative trait locus (QTL) analysis LOD score of 15 for association with disease severity. We propose that it is the inheritance of both a homozygous B6 locus on chromosome 1 and a DBA gene that results in the severe phenotype, presumably as a consequence of an interaction between their protein products.

  4. Knowledge, attitudes and beliefs of first-degree relatives of patients with chronic kidney disease toward kidney donation in Nigeria.

    PubMed

    Bello, Babawale T; Raji, Yemi R

    2016-01-01

    In most parts of Sub-Saharan Africa, kidney transplant programs are dependent on the willingness of relatives of patients with kidney failure to donate kidneys. This study assessed the attitudes of relatives of patients with chronic kidney disease (CKD) toward kidney donation. This was a cross-sectional survey of relatives of patients with CKD attending the nephrology service of our hospital. The respondents' socio-demographic characteristics and knowledge and beliefs about kidney transplantation, as well as their willingness to donate a kidney, were assessed using a self-administered questionnaire. There were 161 respondents who returned completed questionnaires; the mean age of the respondents was 34.8±12.6 years and 52.2% of them were female. About 85.1% of the respondents were aware that kidney transplantation was a treatment option for end-stage renal failure, while 70% of them believed that kidney transplantation resulted in an improvement in the quality of life of these patients. However, 25.5% of the respondents believed that kidney donors were at risk of developing kidney failure in the future. Overall, 77.6% of the respondents were willing to donate a kidney, especially if the affected individual was their offspring. The majority of the respondents were willing to donate a kidney to a relative with CKD. PMID:26787577

  5. 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

  6. Kidney and Urinary Tract Involvement in Kawasaki Disease

    PubMed Central

    Watanabe, Toru

    2013-01-01

    Kawasaki disease (KD) is a systemic vasculitis and can develop multiple organ injuries including kidney and urinary tract involvement. These disorders include pyuria, prerenal acute kidney injury (AKI), renal AKI caused by tubulointerstitial nephritis (TIN), hemolytic uremic syndrome (HUS), and immune-complex mediated nephropathy, renal AKI associated with either Kawasaki disease shock syndrome or unknown causes, acute nephritic syndrome (ANS), nephrotic syndrome (NS), renal tubular abnormalities, renal abnormalities in imaging studies, and renal artery lesions (aneurysms and stenosis). Pyuria is common in KD and originates from the urethra and/or the kidney. TIN with AKI and renal tubular abnormalities probably result from renal parenchymal inflammation caused by T-cell activation. HUS and renal artery lesions are caused by vascular endothelial injuries resulting from vasculitis. Some patients with ANS have immunological abnormalities associated with immune-complex formation. Nephromegaly and renal parenchymal inflammatory foci are detected frequently in patients with KD by renal ultrasonography and renal scintigraphy, respectively. Although the precise pathogenesis of KD is not completely understood, renal vasculitis, immune-complex mediated kidney injuries, or T-cell immune-regulatory abnormalities have been proposed as possible mechanisms for the development of kidney and urinary tract injuries. PMID:24288547

  7. 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

  8. Sarcopenia and Physical Inactivity in Patients With Chronic Kidney Disease.

    PubMed

    Hirai, Keiji; Ookawara, Susumu; Morishita, Yoshiyuki

    2016-05-01

    Sarcopenia and physical inactivity synergistically progress in patients with chronic kidney disease (CKD) and are strong predictors of mortality in this population. Exercise training and essential amino acids and vitamin D supplements may contribute to improving sarcopenia and physical inactivity in CKD patients. PMID:27570755

  9. 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. PMID:24798557

  10. 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

  11. Managing diabetes in hospitalized patients with chronic kidney disease.

    PubMed

    Iyer, Shridhar N; Tanenberg, Robert J

    2016-04-01

    Because few randomized trials have been done, little is known about appropriate glycemic control in hospitalized patients with chronic kidney disease (CKD) and diabetes mellitus. These patients are at high risk of hypoglycemia. It is prudent to monitor glucose closely, set less-stringent blood sugar goals, avoid oral antidiabetic agents, and possibly reduce insulin dosage. PMID:27055204

  12. Novel therapeutic approaches to autosomal dominant polycystic kidney disease.

    PubMed

    LaRiviere, Wells B; Irazabal, Maria V; Torres, Vicente E

    2015-04-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the progressive growth of renal cysts that, over time, destroy the architecture of the renal parenchyma and typically lead to kidney failure by the sixth decade of life. ADPKD is common and represents a leading cause of renal failure worldwide. Currently, there are no Food and Drug Administration-approved treatments for the disease, and the existing standard of care is primarily supportive in nature. However, significant advances in the understanding of the molecular biology of the disease have inspired investigation into potential new therapies. Several drugs designed to slow or arrest the progression of ADPKD have shown promise in preclinical models and clinical trials, including vasopressin receptor antagonists and somatostatin analogs. This article examines the literature underlying the rationale for molecular therapies for ADPKD and reviews the existing clinical evidence for their indication for human patients with the disease. PMID:25438190

  13. 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

  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. 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.

  16. Albumin contributes to kidney disease progression in Alport syndrome.

    PubMed

    Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

    2016-07-01

    Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. PMID:27147675

  17. [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. PMID:27039602

  18. 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

  19. A new Internet resource for chronic kidney disease patients.

    PubMed

    Ormandy, P; Vlaminck, H; Harrington, M; Forest, M; Visser, R

    2006-01-01

    This paper focuses on the development of a portal in the World Wide Web (WWW), which captures and locates quality information for patients with chronic kidney disease (CKD). It examines the problems patients face when accessing and understanding information gleaned from Web sites and describes an idea from a Research Board Member to facilitate patient access to quality information. The idea germinated into the development of a patient specific Web site, providing one stop access and links to appropriate CKD information, assessed by patients and health professionals. Collaboration between the EDTNA/ERCA Research Board and CEAPIR the European Federation of Kidney Patients has enhanced the project. PMID:16700172

  20. A New PKD-1 Mutation Discovered in a Black African Woman With Autosomal Polycystic Kidney Disease.

    PubMed

    Seck, Sidy Mohamed; Guèye, Serigne; Diouf, Boucar

    2013-01-01

    Autosomal polycystic kidney disease (ADPKD) is a genetic disorder with two causal PKD-1 and PKD-2. Genetic studies have demonstrated an important allelic variability between patients but few data are known about genetic variants in African populations. We report a new mutation found in a 41-year old women with mild chronic kidney disease secondary to ADPKD. Molecular genetic testing found a deletion of 2 nucleotides A and C at positions 7290 and 7291 followed by insertion of a 5-base pair (CTGCA) located in exon 18 of the PKD1 gene. This newly identified frame shifting was compared to the PKD gene database but no similar mutation was yet reported. Other screened family members did not present any mutation. PMID:23841043