scholarly journals Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease

2021 ◽  
Author(s):  
Holly Mabillard ◽  
John A Sayer ◽  
Eric Olinger
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Interstitial Fibrosis ◽  
Tubular Damage ◽  
Disease Mutations ◽  
Clinical Presentations ◽  
Common Causes ◽  
Diagnostic Approaches ◽  
Cellular Pathways ◽  
Generation Sequencing

Abstract Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a clinical entity defined by interstitial fibrosis with tubular damage, bland urinalysis and progressive kidney disease. Mutations in UMOD and MUC1 are the most common causes of ADTKD but other rarer (REN, SEC61A1), atypical (DNAJB11) or heterogeneous (HNF1B) subtypes have been described. Raised awareness, as well as the implementation of next-generation sequencing approaches, have led to a sharp increase in reported cases. ADTKD is now believed to be one of the most common monogenic forms of kidney disease and overall it probably accounts for ∼5% of all monogenic causes of chronic kidney disease. Through international efforts and systematic analyses of patient cohorts, critical insights into clinical and genetic spectra of ADTKD, genotype–phenotype correlations as well as innovative diagnostic approaches have been amassed during recent years. In addition, intense research efforts are addressed towards deciphering and rescuing the cellular pathways activated in ADTKD. A better understanding of these diseases and of possible commonalities with more common causes of kidney disease may be relevant to understand and target mechanisms leading to fibrotic kidney disease in general. Here we highlight recent advances in our understanding of the different subtypes of ADTKD with an emphasis on the molecular underpinnings and its clinical presentations.

scholarly journals Roles of Nrf2 in Protecting the Kidney from Oxidative Damage

2020 ◽  
Vol 21 (8) ◽  
pp. 2951 ◽  
Author(s):  
Masahiro Nezu ◽  
Norio Suzuki
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Ischemia Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Organ Damage ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Renal Vasculature ◽  
Nrf2 Activation

Over 10% of the global population suffers from kidney disease. However, only kidney replacement therapies, which burden medical expenses, are currently effective in treating kidney disease. Therefore, elucidating the complicated molecular pathology of kidney disease is an urgent priority for developing innovative therapeutics for kidney disease. Recent studies demonstrated that intertwined renal vasculature often causes ischemia-reperfusion injury (IRI), which generates oxidative stress, and that the accumulation of oxidative stress is a common pathway underlying various types of kidney disease. We reported that activating the antioxidative transcription factor Nrf2 in renal tubules in mice with renal IRI effectively mitigates tubular damage and interstitial fibrosis by inducing the expression of genes related to cytoprotection against oxidative stress. Additionally, since the kidney performs multiple functions beyond blood purification, renoprotection by Nrf2 activation is anticipated to lead to various benefits. Indeed, our experiments indicated the possibility that Nrf2 activation mitigates anemia, which is caused by impaired production of the erythroid growth factor erythropoietin from injured kidneys, and moderates organ damage worsened by anemic hypoxia. Clinical trials investigating Nrf2-activating compounds in kidney disease patients are ongoing, and beneficial effects are being obtained. Thus, Nrf2 activators are expected to emerge as first-in-class innovative medicine for kidney disease treatment.

scholarly journals Autosomal dominant polycystic kidney disease.

1993 ◽  
Vol 3 (8) ◽  
pp. 1442-1450
Author(s):  
J C Lieske ◽  
F G Toback
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Cellular Proliferation ◽  
Autosomal Dominant ◽  
Interstitial Fibrosis ◽  
Family Members ◽  
The United States ◽  
Screening Tests ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of medical morbidity in the United States that affects one-half million persons and accounts for ESRD in about 10% of the chronic dialysis population. In addition to its effects on the kidney, the disease has important manifestations in the cardiovascular system (aneurysms, hypertension) and the gastrointestinal tract (hepatic cysts). Clinically important renal complications can develop as the disease progresses that require specialized attention, such as urinary tract infection, pain, and nephrolithiasis. The underlying cellular defect that causes ADPKD has eluded investigators thus far, but abnormalities in cellular proliferation, the tubular basement membrane, and cell fluid secretion appear important in pathogenesis. Factors that mediate progressive interstitial fibrosis and failure of renal function are undefined, although rigorous control of blood pressure appears to be an important therapeutic measure. Recent advances in molecular biology have localized the abnormal gene to chromosome 16 in 90% of families, making early genetic screening of asymptomatic family members possible in many cases. A positive diagnosis may have important effects on employment status, as well as health insurance, so that family members sometimes refuse to be assessed for the presence of the disease. Because of such complex social factors, counseling of an asymptomatic individual by his or her physician is required when considering the use of screening tests for ADPKD. Inadequate patient education may still represent an impediment to early detection, genetic counseling, and timely treatment of disease complications.

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