{"id":85703,"date":"2020-08-28T09:09:00","date_gmt":"2020-08-28T00:09:00","guid":{"rendered":"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/"},"modified":"2024-12-10T18:23:38","modified_gmt":"2024-12-10T09:23:38","slug":"nephronophthisis","status":"publish","type":"post","link":"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en","title":{"rendered":"Nephronophthisis Type 1 (Deletion 2q13) [Medical Review]"},"content":{"rendered":"\n<div class=\"toc\">\n\t<ul>\n\t\t<li><a href=\"#c1\">Pathology of nephronophthisis<\/a>\n\t\t\t<ul>\n\t\t\t\t<li><a href=\"#c1-1\">Mechanism of urine formation<\/a><\/li>\n\t\t\t\t<li><a href=\"#c1-2\">Urine reabsorption disorder in nephronophthisis<\/a><\/li>\n\t\t\t\t<li><a href=\"#c1-3\">Clinical symptoms of nephronophthisis<\/a><\/li>\n\t\t\t\t<li><a href=\"#c1-4\">Clinical types of nephronophthisis<\/a><\/li>\n\t\t\t<\/ul>\n\t\t<\/li>\n\t\t<li><a href=\"#c2\">Responsible gene for nephron aplasia type 1<\/a>\n\t\t\t<ul>\n\t\t\t\t<li><a href=\"#c2-1\">Nephrocystin-1<\/a><\/li>\n\t\t\t\t<li><a href=\"#c2-2\">Other NPHP gene mutations<\/a>\n\t\t\t\t\t<ul>\n\t\t\t\t\t\t<li><a href=\"#c2-2-1\">Recessive genetic disease<\/a><\/li>\n\t\t\t\t\t<\/ul>\n\t\t\t\t<\/li>\n\t\t\t<\/ul>\n\t\t<\/li>\n\t\t<li><a href=\"#c3\">Epidemiology of nephronophthisis<\/a><\/li>\n\t\t<li><a href=\"#c4\">Diagnosis of nephronophthisis type 1<\/a>\n\t\t\t<ul>\n\t\t\t\t<li><a href=\"#4-1\">Clinical findings<\/a><\/li>\n\t\t\t\t<li><a href=\"#c4-2\">Kidney tissue findings<\/a><\/li>\n\t\t\t\t<li><a href=\"#c4-3\">Genetic testing<\/a><\/li>\n\t\t\t<\/ul>\n\t\t<\/li>\n\t\t<li><a href=\"#c5\">Treatment of nephronophthisis type 1<\/a><\/li>\n\t\t<li><a href=\"#c6\">Future challenges<\/a><\/li>\n\t\t<li><a href=\"#c7\">Nephronophthisis and NIPT (New Prenatal Diagnosis) of Hiro Clinic NIPT<\/a><\/li>\n\t<\/ul>\n  <button class=\"toc_more\">Open table of contents<\/button>\n<\/div>\n\n\n\n\n<p style=\"width:100%;max-width:300px;margin:0 auto;\"><a href=\"\/nipt\/\" class=\"content-bnr about\"><img decoding=\"async\" src=\"\/nipt\/wp-content\/themes\/hiro_nipt\/img\/banner\/nipt04pc.png\" alt=\"\u80ce\u5150\u306e\u6027\u5225\u306f10\u9031\u76ee\u3067\u308f\u304b\u308b\"><\/a> <\/p>\n\n\n\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_83 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">\u76ee\u6b21<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Pathogenesis_of_nephronophthisis\" >Pathogenesis of nephronophthisis<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#The_mechanism_of_urine_production\" >The mechanism of urine production<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Impaired_urine_reabsorption_in_nephronophthisis\" >Impaired urine reabsorption in nephronophthisis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Clinical_manifestations_of_nephronophthisis\" >Clinical manifestations of nephronophthisis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Clinical_forms_of_nephronophthisis\" >Clinical forms of nephronophthisis<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#The_gene_responsible_for_nephronophthisis_type_1\" >The gene responsible for nephronophthisis type 1<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Nephrocystin-1\" >Nephrocystin-1<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Other_NPHP_gene_mutations\" >Other NPHP gene mutations<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Epidemiology_of_nephronophthisis\" >Epidemiology of nephronophthisis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Diagnosis_of_Nephronophthisis_Type_1\" >Diagnosis of Nephronophthisis Type 1<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-11\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Clinical_Findings\" >Clinical Findings<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-12\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Kidney_Tissue_Findings\" >Kidney Tissue Findings<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-13\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Genetic_Testing\" >Genetic Testing<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-14\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Treatment_of_Nephronophthisis_Type_1\" >Treatment of Nephronophthisis Type 1<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-15\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Future_challenges\" >Future challenges<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-16\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\/#Nephronophthisis_and_Hiro_Clinic_NIPT_New_Prenatal_Test\" >Nephronophthisis and Hiro Clinic NIPT (New Prenatal Test)<\/a><\/li><\/ul><\/nav><\/div>\n<h2 class=\"wp-block-heading\" id=\"c1\"><span class=\"ez-toc-section\" id=\"Pathogenesis_of_nephronophthisis\"><\/span>Pathogenesis of nephronophthisis<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c1-1\"><span class=\"ez-toc-section\" id=\"The_mechanism_of_urine_production\"><\/span>The mechanism of urine production<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Nephronophthisis (NPH) is often described as a representative disease in which cysts form in the renal medulla. So, what exactly is the function of the renal medulla in the kidney?<\/p>\n\n\n\n<p>The kidney consists of the outer cortex, the inner medulla, and the innermost renal pelvis. The cortex contains many glomeruli that filter blood and produce urine, and the medulla contains tubules that reabsorb the primary urine produced in the glomeruli, which is then sent to the renal pelvis. It is said that 170 liters of primary urine is filtered by the glomerulus per day, but the concentration and volume of urine is adjusted by the renal tubules in the medulla reabsorbing water and electrolytes such as sodium into the capillaries, ultimately resulting in an amount of about 1-2 liters of urine being produced per day.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c1-2\"><span class=\"ez-toc-section\" id=\"Impaired_urine_reabsorption_in_nephronophthisis\"><\/span>Impaired urine reabsorption in nephronophthisis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>On the other hand, in kidneys with nephronophthisis, which I will explain in detail later, there is an abnormality in the&nbsp;<em>NPHP<\/em>&nbsp;gene, which plays an important role in the function of epithelial cells in the renal tubules, and reabsorption in the renal tubules is impaired by the formation of small cysts in the renal tubules and their atrophy. As a result, urine is not concentrated and polyuria occurs, and large amounts of sodium are excreted in the urine, causing a decrease in blood sodium and leading to hyponatremia and hyperkalemia.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"600\" height=\"400\" src=\"\/nipt\/wp-content\/uploads\/2022\/10\/nephronophthisis02.jpg\" alt=\"\u30cd\u30d5\u30ed\u30f3\u7646\u306e\u75c5\u614b\" class=\"wp-image-44619\"\/><\/figure><\/div>\n\n\n<h3 class=\"wp-block-heading\" id=\"c1-3\"><span class=\"ez-toc-section\" id=\"Clinical_manifestations_of_nephronophthisis\"><\/span>Clinical manifestations of nephronophthisis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>The main symptoms of nephronophthisis include polyuria as explained above, the associated polydipsia and enuresis (peeing oneself), and growth and development disorders associated with chronic renal failure.<br>Electrolyte abnormalities such as hyponatremia and hyperkalemia are observed due to impaired renal tubular resorption, but in the early stages, renal symptoms such as edema, hematuria, and proteinuria are not observed, and blood pressure is normal. As the atrophy of the renal tubules progresses, renal function declines, eventually leading to renal failure. It is only when the decline in renal function progresses that the amount of urine decreases, and sodium retention and the associated high blood pressure and anemia appear.<\/p>\n\n\n\n<p>Since the responsible gene,&nbsp;<em>NPHP<\/em>&nbsp;, is present in other organs, including the brain and nerves, in addition to the kidneys, symptoms other than those of the kidneys may be observed in 10-20% of cases. Representative symptoms include retinitis pigmentosa (Senior-Loken syndrome), ocular ataxia (Cogan syndrome), cerebellar ataxia (Jourbert syndrome), liver fibrosis, skeletal and facial abnormalities, and mental retardation.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c1-4\"><span class=\"ez-toc-section\" id=\"Clinical_forms_of_nephronophthisis\"><\/span>Clinical forms of nephronophthisis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Nephronophthisis is clinically classified into three disease types depending on the time it takes to develop end-stage renal failure. Type 1 develops during childhood to school age, progressing to end-stage renal failure at an average age of 13 to 14 years old, and is also called juvenile nephronophthisis. Type 2 is also called infantile nephronophthisis, and develops renal failure by the age of 3 to 5 years old. Type 3 develops end-stage renal failure at an average age of around 19 years old, and is called adolescent nephronophthisis. As we will discuss later, these three disease types are known to be caused by different gene mutations.<\/p>\n\n\n\n    <a href=\"\/nipt\/albright-2q37\/\" class=\"blog-card\">\n      <div class=\"blog-card-content\">\n          <div class=\"blog-card-title\">\u30aa\u30eb\u30d6\u30e9\u30a4\u30c8\u75c7\u5019\u7fa4\u69d8\u4e2d\u624b\u9aa8\u30fb\u4e2d\u8db3\u9aa8\u77ed\u7e2e(2q37.3\u6b20\u5931\u75c7\u5019\u7fa4) \u306b\u3064\u3044\u3066\u3010\u533b\u5e2b\u76e3\u4fee\u3011 <\/div>\n          <div class=\"blog-card-excerpt\">\u30aa\u30eb\u30d6\u30e9\u30a4\u30c8\u75c7\u5019\u7fa4\u69d8\u4e2d\u624b\u9aa8\u30fb\u4e2d\u811a\u77ed\u7e2e\u306f\u67d3\u8272\u4f53\u306e\u4e00\u90e8\u304c\u6b20\u640d\u3059\u308b\u4e8b\u3067\u3001\u4f53\u306e\u69d8\u3005\u306a\u7b87\u6240\u306b\u7570\u5e38\u304c\u73fe\u308c\u308b\u907a\u4f1d\u5b50\u75be\u60a3\u3067\u3059\u3002\u672c\u8a18\u4e8b\u3067\u306f\u3001\u5f53\u8a72\u75be\u60a3\u306e\u75c7\u4f8b\u5831\u544a...<\/div>\n      <\/div>\n    <\/a>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"c2\"><span class=\"ez-toc-section\" id=\"The_gene_responsible_for_nephronophthisis_type_1\"><\/span>The gene responsible for nephronophthisis type 1<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c2-1\"><span class=\"ez-toc-section\" id=\"Nephrocystin-1\"><\/span>Nephrocystin-1<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>The gene responsible for the onset of nephronophthisis is called&nbsp;<em>NPHP<\/em>&nbsp;, and to date, as many as 20 genes have been reported to be involved. The proteins encoded by these genes play an important role in the normal functioning of renal tubular epithelial cells, and in nephronophthisis, genetic mutations cause renal tubule dysfunction, which leads to poor urine reabsorption and symptoms centered on the kidneys.<\/p>\n\n\n\n<p>Among these, nephronophthisis type 1 is caused by a mutation in the&nbsp;<em>NPHP1<\/em>&nbsp;gene, which encodes a protein called nephrocystin-1 present in the primary cilia of renal tubular epithelial cells, and it has been reported that there are extensive gene deletions and point mutations.&nbsp;<em>NPHP1<\/em>&nbsp;is present on chromosome 2q13 and is approximately 11,000 base pairs in length, and nephrocystin-1, which is translated and synthesized from the&nbsp;<em>NPHP1<\/em>&nbsp;gene, consists of 677 amino acids.<\/p>\n\n\n\n<p>Nephrocystin-1 is thought to be an important protein in adhesion and signal transmission between cells and between cells and the extracellular matrix. Abnormalities in this molecule cause major disruptions to cell adhesion, cilia function, and intracellular and extracellular signal transmission, which is thought to lead to structural and functional disorders of the renal tubular epithelium, such as cyst formation in the renal tubules and impaired urine reabsorption.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c2-2\"><span class=\"ez-toc-section\" id=\"Other_NPHP_gene_mutations\"><\/span>Other NPHP gene mutations<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><em>The responsible gene for nephronophthisis type 2 is NPHP2<\/em>&nbsp;, located on chromosome 9q31&nbsp;, and is known to code for a protein called inversin. The responsible gene for nephronophthisis type 3 is&nbsp;<em>NPHP3<\/em>&nbsp;, located on chromosome 3q22 , and codes for a protein called nephrocystin-3. Both proteins are thought to play important roles in renal tubular epithelial cells, just like nephrocystin-1 in nephronophthisis type 1, and gene mutations significantly reduce kidney function.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"c2-2-1\">Recessive disorders<\/h4>\n\n\n\n<p>Nephronophthisis, including type 1, is known to be primarily a recessive genetic disease. In other words, parents (either affected or carriers) with a recessive gene with a mutation in the same part can have a child with two mutations. If both parents are carriers, there are cases where the child will develop the disease even if the parents are healthy.<br>In addition to recessive genetic diseases, sporadic cases due to mutations have also been reported, although this is rare.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"c3\"><span class=\"ez-toc-section\" id=\"Epidemiology_of_nephronophthisis\"><\/span>Epidemiology of nephronophthisis<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>No detailed epidemiological surveys have been conducted in Japan regarding the incidence of nephronophthisis, but overseas, it has been reported that the incidence rate is about 1 in every tens to hundreds of thousands of people. The number of patients in Japan is said to be about 500 to 600. Nephronophthisis is also said to account for 5 to 10% of the causes of end-stage renal failure in children.<br>Of the three clinical disease types, nephronophthisis type 1, which is juvenile nephronophthisis, is the most frequent, and it has been reported that&nbsp;<em>NPHP1<\/em>&nbsp;mutations are found in 20 to 40% of all nephronophthisis cases.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"c4\"><span class=\"ez-toc-section\" id=\"Diagnosis_of_Nephronophthisis_Type_1\"><\/span>Diagnosis of Nephronophthisis Type 1<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>To diagnose nephronophthisis type 1, the disease is suspected based on symptoms and clinical findings, and a comprehensive diagnosis is made by combining histological and genetic tests. Recently, the research group &#8220;Establishment of diagnostic criteria and treatment guidelines for rare intractable diseases of the kidney and urinary system&#8221; has created diagnostic criteria for nephronophthisis.<\/p>\n\n\n\n    <a href=\"\/nipt\/saethre-chotzen-syndrome\/\" class=\"blog-card\">\n      <div class=\"blog-card-content\">\n          <div class=\"blog-card-title\">\u30bb\u30fc\u30c8\u30ec\u30fb\u30d2\u30e7\u30c3\u30c4\u30a7\u30f3\u75c7\u5019\u7fa4\u3063\u3066\u306a\u306b\uff1fNIPT\u3067\u691c\u67fb\u3067\u304d\u308b\u306e\uff1f\u3010\u533b\u5e2b\u76e3\u4fee\u3011 <\/div>\n          <div class=\"blog-card-excerpt\">\u3053\u306e\u30da\u30fc\u30b8\u306f\u30bb\u30fc\u30c8\u30ec\u30fb\u30d2\u30e7\u30c3\u30c4\u30a7\u30f3\u75c7\u5019\u7fa4\uff08Saethre-Chotzen\u75c7\u5019\u7fa4\uff09\u306e\u77e5\u8b58\u3068\u5bfe\u7b56\u304c\u66f8\u3044\u3066\u3042\u308a\u307e\u3059\u3002\u30bb\u30fc\u30c8\u30ec\u30fb\u30d2\u30e7\u30c3\u30c4\u30a7\u30f3\u75c7\u5019\u7fa4\u306f...<\/div>\n      <\/div>\n    <\/a>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c4-1\"><span class=\"ez-toc-section\" id=\"Clinical_Findings\"><\/span>Clinical Findings<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>As mentioned before, this disease is suspected based on clinical symptoms and test results such as polydipsia, polyuria, decreased urine concentration ability, and decreased renal function in children. The frequency of low specific gravity urine (dilute urine) due to impaired renal tubular reabsorption is high, and when such findings are observed, nephronophthisis must be considered when proceeding with the diagnosis.<br>Detection of urinary protein is a commonly used test method for screening for kidney disorders, but proteinuria in nephronophthisis is mainly low molecular weight proteinuria such as \u03b22-microgloblin, and is difficult to detect with test strip methods that mainly detect albumin, a large molecule, so it may be overlooked in mass screening including school checkups, so caution is required. In addition to low molecular weight proteins, urinary glucose may also be observed. According to the diagnostic criteria, low specific gravity urine and low molecular weight proteinuria are necessary findings for a definitive diagnosis.<br>Other characteristic findings in ultrasound examinations include increased kidney brightness, disappearance of the border between the cortex and medulla, and small cysts in the renal parenchyma.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c4-2\"><span class=\"ez-toc-section\" id=\"Kidney_Tissue_Findings\"><\/span>Kidney Tissue Findings<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Kidney tissue is mainly collected by renal biopsy, which is performed using a needle outside the body. Therefore, it is a more invasive test than urine tests or ultrasound tests. The<br>histological characteristic of nephronophthisis is the presence of numerous cysts at the boundary between the cortex and medulla. As the disease progresses, atrophy of the renal tubules and thickening and atrophy of the tubular basement membrane are also observed, and in the terminal stage, fibrosis around the glomerulus and sclerotic glomeruli appear. The diagnostic criteria require cystic dilation of the renal tubules and irregular changes in the tubular basement membrane for a definitive diagnosis.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"c4-3\"><span class=\"ez-toc-section\" id=\"Genetic_Testing\"><\/span>Genetic Testing<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>As mentioned above, the diagnosis of nephronophthisis can be narrowed down to a certain extent based on clinical symptoms and histological findings, and the identification rate of gene mutations in nephronophthisis is not very high at about 30%, so it is not an essential test for diagnosis. However, if mutations can be identified by genetic testing, there are advantages such as being able to diagnose the disease without invasive renal biopsy and being able to identify complications characteristic of mutated genes early.<br>Considering the age at which end-stage renal failure is reached, gene mutations in&nbsp;<em>NPHP1<\/em>&nbsp;(the gene responsible for juvenile nephronophthisis) or&nbsp;<em>NPHP2<\/em>&nbsp;(the gene responsible for infantile nephronophthisis) are searched for. If mutations in these genes are not found, other&nbsp;<em>NPHP<\/em>&nbsp;gene mutations will be searched for , referring to the presence or absence of non-renal symptoms such as retinal pigmentary lesions (common in&nbsp;<em>NPHP5<\/em>&nbsp;and&nbsp;<em>NPHP6<\/em>&nbsp;mutations) .<em><\/em><\/p>\n\n\n\n<p>In recent years, whole-exome analysis, a method for comprehensively analyzing the exon sequences of the entire genome that are translated into proteins, has become available, and the number of reports of responsible gene mutations has increased, with reports indicating that more than 60% of genetic abnormalities can be detected.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"600\" height=\"400\" src=\"\/nipt\/wp-content\/uploads\/2022\/10\/nephronophthisis01.jpg\" alt=\"\u907a\u4f1d\u5b50\u691c\u67fb\" class=\"wp-image-44623\"\/><\/figure><\/div>\n\n\n<h2 class=\"wp-block-heading\" id=\"c5\"><span class=\"ez-toc-section\" id=\"Treatment_of_Nephronophthisis_Type_1\"><\/span>Treatment of Nephronophthisis Type 1<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Unfortunately, there is currently no established cure for nephronophthisis, including type 1. Symptomatic treatments such as dietary therapy, ion adsorption resin, and administration of bicarbonate are used to treat hyponatremia, hyperkalemia, and metabolic acidosis caused by impaired renal tubular resorption. If the disease progresses to end-stage renal failure, treatments such as artificial dialysis are used, and ultimately kidney transplantation may be selected. Growth hormone therapy is also indicated for cases of short stature caused by renal failure. In addition to treatment of<br>the disease, it is also important to consider the psychological burden on the family and the impact on relatives in hereditary diseases such as this disease, so it is also important to provide psychological and social support to the patient and their family through genetic counseling and counseling.<\/p>\n\n\n\n    <a href=\"\/nipt\/nipt-risk\/\" class=\"blog-card\">\n      <div class=\"blog-card-content\">\n          <div class=\"blog-card-title\">\u51fa\u751f\u524d\u8a3a\u65ad\u306b\u30ea\u30b9\u30af\u306f\u3042\u308b\u306e\uff1f\u3010\u533b\u5e2b\u76e3\u4fee\u3011 <\/div>\n          <div class=\"blog-card-excerpt\">\u8fd1\u5e74\u3001\u53d7\u691c\u3057\u3066\u3044\u308b\u4eba\u304c\u5897\u3048\u3066\u3044\u308bNIPT(\u65b0\u578b\u51fa\u751f\u524d\u8a3a\u65ad)\u3002\u3053\u306e\u8a18\u4e8b\u3067\u306f\u3001NIPT\u306e\u7279\u5fb4\u3084\u30ea\u30b9\u30af\u306b\u3064\u3044\u3066\u89e3\u8aac\u3057\u307e\u3059\u3002...<\/div>\n      <\/div>\n    <\/a>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"c6\"><span class=\"ez-toc-section\" id=\"Future_challenges\"><\/span>Future challenges<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>As mentioned before, nephronophthisis rarely shows abnormal findings in urine in the early stages of onset, and is often overlooked in mass screening tests such as school urinalysis. Therefore, by the time proteinuria is detected, patients often already have end-stage renal failure, and the development of a screening method for early detection is awaited.<br>Recently, a Japanese research group reported that human iPS cells were established from a nephronophthisis type 1 patient with a deletion mutation in the&nbsp;<em>NPHP1<\/em>&nbsp;gene. It is expected that pathological iPS cells will be useful in further elucidating the pathogenesis of nephronophthisis type 1 and developing a fundamental treatment method.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"c7\"><span class=\"ez-toc-section\" id=\"Nephronophthisis_and_Hiro_Clinic_NIPT_New_Prenatal_Test\"><\/span>Nephronophthisis and Hiro Clinic NIPT (New Prenatal Test)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Nephronophthisis\u00a0cannot be detected by testing for chromosomal aneuploidies such as\u00a0<a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/about-down-syndrome\/?lang=en\">Down syndrome (trisomy 21) .\u00a0<\/a><a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt\/\">Hiro Clinic NIPT<\/a>\u00a0also performs full-region chromosomal testing to check for\u00a0<a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt\/partialdeletions\/?lang=en\">partial deletions and duplications of all autosomal regions<\/a>, including nephronophthisis.<\/p>\n\n\n\n<p>Knowing the condition before birth allows families to prepare for their baby.\u00a0We recommend that you also consider full-region chromosome testing, which can test for\u00a0<a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nipt\/partialdeletions\/?lang=en\">all autosomal partial deletions and duplications.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Pathology of nephron&#8230;\n <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/nephronophthisis\/?lang=en\">\u7d9a\u304d\u3092\u8aad\u3080<\/a>","protected":false},"author":1,"featured_media":24818,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[97],"tags":[],"class_list":["post-85703","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85703","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/comments?post=85703"}],"version-history":[{"count":2,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85703\/revisions"}],"predecessor-version":[{"id":85712,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85703\/revisions\/85712"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media\/24818"}],"wp:attachment":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media?parent=85703"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/categories?post=85703"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/tags?post=85703"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}