Article
Endocrinology & Metabolism
Qian Li, Dan Tian, Jing Cen, Lian Duan, Weibo Xia
Summary: In the first and largest case series of NDI caused by AQP2 mutation in Chinese population, 9 AQP2 mutations were identified, including 3 novel mutations. Phenotype was found to correlate with genotypes, revealed by higher level of serum sodium in patients with compound het AQP2 mutations than non-compound het mutations.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Marguerite Hureaux, Rosa Vargas-Poussou
Summary: Nephrogenic diabetes insipidus is a condition where the kidneys cannot respond to the antidiuretic hormone, resulting in diluted urine. It is mainly caused by mutations in the AVPR2 and AQP2 genes. About 90% of cases are caused by mutations in the AVPR2 gene, which is inherited in an X-linked recessive manner. The remaining 10% are caused by mutations in the AQP2 gene, which can be inherited in either a recessive or a dominant manner. Symptoms include excessive urination, chronic dehydration, and high blood sodium levels. Diagnosis is based on abnormal urine osmolality response to water restriction or exogenous vasopressin administration. Treatment involves adequate water intake, thiazide diuretics, non-steroidal anti-inflammatory drugs, and a low-salt and protein diet. This review provides an update on the molecular basis of inherited nephrogenic diabetes insipidus.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Qian Li, Bichao Lu, Jia Yang, Chao Li, Yanchun Li, Hui Chen, Naishi Li, Lian Duan, Feng Gu, Jianmin Zhang, Weibo Xia
Summary: This study elucidated the molecular pathogenic mechanism of NDI caused by the AQP2-G215S mutation. Experimental results showed that AQP2-G215S misfolds and remains in the ER, unable to be translocated to the apical membrane to function as a water channel.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Laszlo Sandor Erdelyi, Laszlo Hunyady, Andras Balla
Summary: The diluting and concentrating function of the kidney is regulated by the V2 receptor and antidiuretic hormone, affecting the body's water homeostasis. Mutations of the V2 receptor can lead to X-linked nephrogenic diabetes insipidus or nephrogenic syndrome of inappropriate antidiuresis disease. This review explores potential therapeutic interventions based on recent findings.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
Laura Szalai, Andras Sziraki, Laszlo Sandor Erdelyi, Kinga Bernadett Kovacs, Miklos Toth, Andras David Toth, Gabor Turu, Dominique Bonnet, Bernard Mouillac, Laszlo Hunyady, Andras Balla
Summary: In this study, a point mutation in the AVPR2 gene of a patient with nephrogenic diabetes insipidus (NDI) was identified, and the impaired function of the mutant receptor was characterized. The mutant receptor was primarily located in the endoplasmic reticulum (ER) and had reduced ability to generate cAMP in response to AVP stimulation. Pretreatment with pharmacochaperones partially restored the receptor's function. Both cell permeant agonists and antagonists can function as pharmacochaperones, providing a potential starting point for developing therapies for patients carrying this mutation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Hiroshi Arima, Timothy Cheetham, Mirjam Christ-Crain, Deborah Cooper, Juliana Drummond, Mark Gurnell, Miles Levy, Ann McCormack, John Newell-Price, Joseph G. Verbalis, John Wass, John Wass
Summary: Recent data suggests that patients with diabetes insipidus (DI) are being harmed. The authors propose renaming central and nephrogenic DI as arginine vasopressin deficiency and resistance, respectively.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Medicine, General & Internal
Gheun-Ho Kim
Summary: Drug-induced hyponatremia caused by renal water retention is mainly classified into SIADH and NSIAD. Psychotropic agents, anticancer chemotherapeutic agents, and thiazide diuretics are the major causes. NSIAD, which involves the upregulation of AQP2, is the major mechanism for drug-induced hyponatremia.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Physiology
Sua Kim, Chor Ho Jo, Gheun-Ho Kim
Summary: Hyponatremia is a common condition in clinical practice caused by renal water retention. Many medications can induce hyponatremia by affecting the release of arginine vasopressin or potentiating its action in the kidney. A major mechanism of drug-induced hyponatremia is the upregulation of AQP2 from V2R-cAMP-PKA signaling in the absence of AVP stimulation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Health Care Sciences & Services
Senthil Selvaraj, Dircea Rodrigues, Navaneethakrishnan Krishnamoorthy, Khalid A. Fakhro, Luis R. Saraiva, Manuel C. Lemos
Summary: In this study, we report a rare case of a female patient with X-linked recessive NDI caused by a novel heterozygous missense mutation in the AVPR2 gene. Through genetic analysis and functional studies, we found that the mutation destabilizes the helical structure of AVPR2, disrupts its membrane localization, and affects downstream signaling pathways upon activation with vasopressin. These defects result in deficient membrane translocation of aquaporin 2, explaining the inability to concentrate urine in this patient.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pediatrics
Li Huang, Lina Ma, Linjing Li, Jiajia Luo, Tianhong Sun
Summary: Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused by mutations in AVPR2 gene. Clinical manifestations include polyuria, polydipsia, thirst, and irritability.
FRONTIERS IN PEDIATRICS
(2021)
Article
Biochemistry & Molecular Biology
Hooman Hadidi, Reza Kamali, Alireza Binesh
Summary: This study focused on investigating the gating effects of the selectivity filter in AQP2 and the impact of mutations on its structure. By analyzing free energy and permeability, the wide/narrow states of the SF region were identified and energy barriers caused by mutants were observed. The findings suggest that SF plays a dual role as a selectivity filter and gating site in AQP2, influencing water permeability.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Serena Milano, Fatima Maqoud, Monica Rutigliano, Ilenia Saponara, Monica Carmosino, Andrea Gerbino, Giuseppe Lucarelli, Michele Battaglia, Maria Svelto, Giuseppe Procino
Summary: This study discovered the functional expression of beta 3-AR in the renal tubule and its co-localization with the vasopressin receptor AVPR2. Activation of beta 3-AR triggers antidiuresis by increasing the expression of AQP2 and NKCC2 in renal cells. Treatment with the beta 3-AR agonist mirabegron increased the urinary excretion of AQP2 and NKCC2 in patients with overactive bladder syndrome. This suggests that mirabegron treatment may be able to bypass AVPR2 inactivation, induce antidiuresis, and correct polyuria in XNDI patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Angela Mak, Chih-Chien Sung, Trairak Pisitkun, Sookkasem Khositseth, Mark A. Knepper
Summary: Animal models of acquired nephrogenic diabetes insipidus (NDI) have shown that loss of aquaporin-2 (AQP2) from collecting duct principal cells is a common feature, leading to polyuria. Previous studies using transcriptomics and proteomics have provided contrasting views on the mechanisms of AQP2 loss. In this study, bioinformatic data integration techniques were used to analyze all available transcriptomic and proteomic data sets, revealing autophagy/apoptosis, oxidative stress, and inflammatory signaling as key mechanisms leading to AQP2 loss. Possible triggers for these signaling processes, including death receptors and stress-sensitive protein kinases, are discussed.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Medicine, General & Internal
Lu-Lu Yang, Yan Xu, Jian-Li Qiu, Qian-Yi Zhao, Man-Man Li, Hui Shi
Summary: This is a case report on congenital nephrogenic diabetes insipidus (CNDI), describing a male infant with a novel AVPR2 gene mutation locus and a new clinical manifestation.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Medicine, General & Internal
Esmail Sangey, Kishan Chudasama, Ahmad Mwinyi
Summary: Nephrogenic diabetes insipidus (NDI) is often overlooked in patients with polydipsia and polyuria, who are more commonly diagnosed with diabetes mellitus. Hypokalemia and hypercalcemia are known to induce NDI, but the role of hypomagnesemia is not well understood. Persistent hypokalemia despite therapy should raise suspicion for hypomagnesemia.
CLINICAL CASE REPORTS
(2021)