Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal-dominant interstitial kidney disease is characterized by slow progression of chronic kidney disease in patients with bland urinary sediment and no or low-grade proteinuria. There are at least three subtypes. Patients with mutations in the UMOD gene encoding uromodulin suffer from precocious gout in addition to chronic kidney failure. Diagnosis can be achieved through genetic analysis of the UMOD gene. Patients with mutations in the REN gene encoding renin suffer from anemia in childhood, hyperuricemia, mild hyperkalemia, and progressive kidney disease. Genetic analysis of the REN gene can be performed to diagnose affected individuals. There is a third form of inherited interstitial kidney disease for which the cause has not been found. These individuals suffer from chronic kidney disease with no other identified clinical signs. Linkage to chromosome 1 has been identified in a number of these families. Proper diagnosis is valuable not only to the affected individual but also to the entire family and can facilitate treatment, transplantation, and research efforts.
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PMID:Hereditary interstitial kidney disease. 2080 9

Uromodulin (Tamm-Horsfall glycoprotein) is the most common protein excreted in the urine of healthy individuals, yet its function remains unclear. Mutations in the UMOD gene encoding uromodulin result in a marked decrease in the synthesis of uromodulin, as well as the accumulation of abnormal uromodulin in tubular cells, leading to tubular cell death. UMOD gene mutations are responsible for the autosomal dominant inheritance of chronic interstitial disease, leading to the need for renal replacement in the third through seventh decades of life. Individuals with UMOD mutations also suffer from hyperuricemia in childhood, and often suffer from gout in their teenage years. A similar clinical syndrome causing the autosomal dominant inheritance of chronic kidney disease, hyperuricemia, and anemia has recently been attributed to mutations in the REN gene encoding renin. Recently, polymorphisms in the UMOD gene have been found responsible for increased urinary uromodulin production and an increased risk of chronic kidney disease. This review summarizes information on uromodulin biology and clinical manifestations of mutations in the UMOD gene, as well as similar inherited interstitial diseases. It provides new information regarding UMOD gene polymorphisms and their association with chronic kidney disease.
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PMID:Uromodulin-associated kidney disease. 2107 70

There are 3 major forms of autosomal dominant tubulointerstitial kidney disease (ADTKD): ADTKD due to UMOD mutations, MUC1 mutations, and mutations in the REN gene encoding renin. Lack of knowledge about these conditions contributes to frequent nondiagnosis, but with even limited knowledge, nephrologists can easily obtain a diagnosis and improve patient care. There are 3 cardinal features of these disorders: (1) the conditions are inherited in an autosomal dominant manner and should be considered whenever both a parent and child suffer from kidney disease; the presence of even more affected family members provides further support. (2) These conditions are associated with a bland urinary sediment, ruling out glomerular disorders. (3) There is a variable rate of decline in kidney function. The mean age of ESRD is approximately 45, but the range is from 17 to >75. ADTKD-UMOD is often but not always associated with gout in the teenage years. ADKTKD-REN is associated with signs of hyporeninemia: mild hypotension, mild hyperkalemia, anemia in childhood, and hyperuricemia and gout in the teenage years. The only clinical manifestation of ADTKD-MUC1 is slowly progressive CKD. Diagnosis should be made by genetic testing, and kidney biopsy should be avoided.
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PMID:Autosomal Dominant Tubulointerstitial Kidney Disease. 2828 84

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.
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PMID:An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes. 3275 Apr 57