Association of Familial Hyperkalemia and Hypertension with Proximal Renal Tubular Acidosis and Epileptic Seizures
Introduction: Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule. FHHt is caused by mutation in eith...
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| Published in | Nephron (2015) Vol. 148; no. 3; pp. 179 - 184 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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Basel, Switzerland
01.03.2024
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| ISSN | 1660-8151 2235-3186 |
| DOI | 10.1159/000531868 |
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| Abstract | Introduction: Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule. FHHt is caused by mutation in either WNK1, WNK4, KLHL3, or Cul3. The mechanism of HCA is not completely understood. Methods: Clinical and genetic data were collected from the largest family with FHHt described in the literature. Urine ammonia was measured in 26 family members. Epilepsy was diagnosed clinically. Results: Of the 85 family members, 44 are affected by the Q565E WNK4 mutation, and 28 are newly described. In genetically engineered mice, urinary ammonium was decreased. In our study, urine ammonium did not change. In 11 unaffected subjects, urine ammonia per creatinine was 8.013 ± 3.620 m m /mm, and in 15 subjects affected by FHHt, it was 8.990 ± 4.300 m m /mm (p = 0.546, not significant). Due to the large family size and prolonged follow-up, rare conditions can be identified. Indeed, two children have genetic generalized epilepsy and one child has migraine. The prevalence of epilepsy is 4.545% (2/44) much higher than in the general population (0.681%). This difference is statistically significant (χ 2 with Yates correction = 5.127, p = 0.023). Conclusions: We provide further evidence that the origin of HCA in FHHt lies in the proximal renal tubule. The association of FHHt with epilepsy leads us to speculate that the raised serum K in susceptible subjects may cause a rise in CSF K, and extracellular cerebral K, leading to epilepsy. |
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| AbstractList | Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule. FHHt is caused by mutation in either WNK1, WNK4, KLHL3, or Cul3. The mechanism of HCA is not completely understood.
Clinical and genetic data were collected from the largest family with FHHt described in the literature. Urine ammonia was measured in 26 family members. Epilepsy was diagnosed clinically.
Of the 85 family members, 44 are affected by the Q565E WNK4 mutation, and 28 are newly described. In genetically engineered mice, urinary ammonium was decreased. In our study, urine ammonium did not change. In 11 unaffected subjects, urine ammonia per creatinine was 8.013 ± 3.620 mm/mm, and in 15 subjects affected by FHHt, it was 8.990 ± 4.300 mm/mm (p = 0.546, not significant). Due to the large family size and prolonged follow-up, rare conditions can be identified. Indeed, two children have genetic generalized epilepsy and one child has migraine. The prevalence of epilepsy is 4.545% (2/44) much higher than in the general population (0.681%). This difference is statistically significant (χ2 with Yates correction = 5.127, p = 0.023).
We provide further evidence that the origin of HCA in FHHt lies in the proximal renal tubule. The association of FHHt with epilepsy leads us to speculate that the raised serum K in susceptible subjects may cause a rise in CSF K, and extracellular cerebral K, leading to epilepsy. Introduction: Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule. FHHt is caused by mutation in either WNK1, WNK4, KLHL3, or Cul3. The mechanism of HCA is not completely understood. Methods: Clinical and genetic data were collected from the largest family with FHHt described in the literature. Urine ammonia was measured in 26 family members. Epilepsy was diagnosed clinically. Results: Of the 85 family members, 44 are affected by the Q565E WNK4 mutation, and 28 are newly described. In genetically engineered mice, urinary ammonium was decreased. In our study, urine ammonium did not change. In 11 unaffected subjects, urine ammonia per creatinine was 8.013 ± 3.620 m m /mm, and in 15 subjects affected by FHHt, it was 8.990 ± 4.300 m m /mm (p = 0.546, not significant). Due to the large family size and prolonged follow-up, rare conditions can be identified. Indeed, two children have genetic generalized epilepsy and one child has migraine. The prevalence of epilepsy is 4.545% (2/44) much higher than in the general population (0.681%). This difference is statistically significant (χ 2 with Yates correction = 5.127, p = 0.023). Conclusions: We provide further evidence that the origin of HCA in FHHt lies in the proximal renal tubule. The association of FHHt with epilepsy leads us to speculate that the raised serum K in susceptible subjects may cause a rise in CSF K, and extracellular cerebral K, leading to epilepsy. |
| Author | Karlish, Steven J.D. Farfel, Zvi Shirin, Neta Mayan, Haim Blatt, Ilan Rabinowitz, Grace |
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| Issue | 3 |
| Keywords | Hypertension Hyperkalemia Hyperchloremic acidosis Epilepsy |
| Language | English |
| License | This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher. 2023 The Author(s). Published by S. Karger AG, Basel. |
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| References | MacAulay N. Molecular mechanisms of brain water transport. Nat Rev Neurosci. 2021;22(6):326–44. De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L. Haploinsuficiency of ATP1A2 encoding the Na++ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003;33:192–6. Farfel Z, Iaina A, Levi J, Gafni J. Proximal renal tubular acidosis: association with familial normaldosteronemic hyperpotassemia and hypertension. Arch Intern Med. 1978;138(12):1837–40. Harris AN, Grimm PR, Lee HW, Delpire E, Fang L, Verlander JW. Mechanism of hyperkalemia-induced metabolic acidosis. J Am Soc Nephrol. 2018;29(5):1411–25. Ayata C, Lauritzen M. Spreading depression, spreading depolarizations and the cerebral vasculature. Physiol Rev. 2015;95(3):953–93. Obrenovitch TP, Zilkha E, Urenjak J. High extracellular potassium, and not extracellular glutamate, is required for the propagation of spreading depression. J Neurophysiol. 1995;73(5):2107–14. Urine ammonia assay kit. Sigma-AldrichUSA2016. Farfel A, Mayan H, Melnikov S, Holtzman EJ, Pinhas-Hamiel O, Farfel Z. Effect of age and affection status on blood pressure, serum potassium and stature in familial hyperkalaemia and hypertension. Nephrol Dial Transpl. 2011;26(5):1547–53. Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012;482(7383):98–102. Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I. Human hypertension caused by mutations in WNK kinases. Science. 2001;293(5532):1107–12. Lemoine S, Eladari D, Juillard L, Bonnefond A, Froguel P, Dubourg L. The Case|Hypokalemia and severe renal loss of sodium. Kidney Int. 2020;97(6):1305–6. Batlle DC, Hizon M, Cohen E, Gutterman C, Gupta R. The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Engl J Med. 1988;318(10):594–9. Farfel Z, Mayan H, Karlish JD. Familial hyperkalemia and hypertension and a hypothesis to explain proximal renal tubular acidosis. Proc Natnl Acad Sci USA. 2019;116:16173–4. Louis-Dit-Picard H, Barc J, Trujillano D, Miserey-Lenkei S, Bouatia-Naji N, Pylypenko O. KLHL3 Mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat Genet. 2012;44(4):456–60, S1-3. Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B. WNK4 regulates apical and basolateral Cl− flux in extrarenal epithelia. Proc Natl Acad Sci USA. 2004;101(7):2064–9. Mayan H, Munter G, Shaharabany M, Mouallem M, Pauzner R, Holtzman EJ. Hypercalciuria in familial hyperkalemia and hypertension accompanies hyperkalemia and precedes hypertension: description of a large family with the Q565E WNK4 mutation. J Clin Endocrinol Metab. 2004;89(8):4025–30. Mathew AA, Panonnummal R. Cortical spreading depression. Culprits and mechanisms. Exp Brain Res. 2022;240(3):733–49. Benarroch EE. ++-ATPase. Functions in the nervous system and involvement in neurologic disease. Neurology. 2011;76(3):287–93. Lopez-Cayuqueo KI, Chavez-Canales M, Pillot A, Houillier P, Jayat M, Baraka-Vidot J. A mouse model of Pseudohypoaldosteronism type II reveals a novel mechanism of renal tubular acidosis. Kidney Int. 2018;94(3):514–23. Mayan H, Vered I, Mouallem M, Tzadok-Witkon M, Pauzner R, Farfel Z. Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J Clin Endocrinol Metab. 2002;87(7):3248–54. Uribarri J, Oh M. The urine anion gap: common misconceptions. J Am Soc Nephrol. 2021;32(5):1025–8. Brennan KC, Pietrobon D. A systems neuroscience approach to migraine. Neuron. 2018;97(5):1004–21. Rehman MZ, Melamed M, Harris A, Shankar M, Rosa RM, Batlle D. Urinary ammonium in clinical medicine: direct measurement and the urine anion gap as a surrogate marker during metabolic acidosis. Adv Kidney Dis Health. 2023;30(2):197–206. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 2017;88(3):296–303. Hureaux M, Mazurkiewicz S, Boccio V, Vargas-Poussou R, Jeunemaitre X. The variety of genetic defects explains the phenotypic heterogeneity of familial hyperkalemic hypertension. Kidney Int Rep. 2021;6(10):2639–52. |
| References_xml | – reference: Brennan KC, Pietrobon D. A systems neuroscience approach to migraine. Neuron. 2018;97(5):1004–21. – reference: Mayan H, Vered I, Mouallem M, Tzadok-Witkon M, Pauzner R, Farfel Z. Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J Clin Endocrinol Metab. 2002;87(7):3248–54. – reference: Rehman MZ, Melamed M, Harris A, Shankar M, Rosa RM, Batlle D. Urinary ammonium in clinical medicine: direct measurement and the urine anion gap as a surrogate marker during metabolic acidosis. Adv Kidney Dis Health. 2023;30(2):197–206. – reference: Hureaux M, Mazurkiewicz S, Boccio V, Vargas-Poussou R, Jeunemaitre X. The variety of genetic defects explains the phenotypic heterogeneity of familial hyperkalemic hypertension. Kidney Int Rep. 2021;6(10):2639–52. – reference: Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012;482(7383):98–102. – reference: Mathew AA, Panonnummal R. Cortical spreading depression. Culprits and mechanisms. Exp Brain Res. 2022;240(3):733–49. – reference: Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 2017;88(3):296–303. – reference: Urine ammonia assay kit. Sigma-AldrichUSA2016. – reference: MacAulay N. Molecular mechanisms of brain water transport. Nat Rev Neurosci. 2021;22(6):326–44. – reference: Lemoine S, Eladari D, Juillard L, Bonnefond A, Froguel P, Dubourg L. The Case|Hypokalemia and severe renal loss of sodium. Kidney Int. 2020;97(6):1305–6. – reference: Lopez-Cayuqueo KI, Chavez-Canales M, Pillot A, Houillier P, Jayat M, Baraka-Vidot J. A mouse model of Pseudohypoaldosteronism type II reveals a novel mechanism of renal tubular acidosis. Kidney Int. 2018;94(3):514–23. – reference: Uribarri J, Oh M. The urine anion gap: common misconceptions. J Am Soc Nephrol. 2021;32(5):1025–8. – reference: Louis-Dit-Picard H, Barc J, Trujillano D, Miserey-Lenkei S, Bouatia-Naji N, Pylypenko O. KLHL3 Mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat Genet. 2012;44(4):456–60, S1-3. – reference: Ayata C, Lauritzen M. Spreading depression, spreading depolarizations and the cerebral vasculature. Physiol Rev. 2015;95(3):953–93. – reference: Farfel A, Mayan H, Melnikov S, Holtzman EJ, Pinhas-Hamiel O, Farfel Z. Effect of age and affection status on blood pressure, serum potassium and stature in familial hyperkalaemia and hypertension. Nephrol Dial Transpl. 2011;26(5):1547–53. – reference: Mayan H, Munter G, Shaharabany M, Mouallem M, Pauzner R, Holtzman EJ. Hypercalciuria in familial hyperkalemia and hypertension accompanies hyperkalemia and precedes hypertension: description of a large family with the Q565E WNK4 mutation. J Clin Endocrinol Metab. 2004;89(8):4025–30. – reference: De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L. Haploinsuficiency of ATP1A2 encoding the Na++ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003;33:192–6. – reference: Farfel Z, Mayan H, Karlish JD. Familial hyperkalemia and hypertension and a hypothesis to explain proximal renal tubular acidosis. Proc Natnl Acad Sci USA. 2019;116:16173–4. – reference: Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B. WNK4 regulates apical and basolateral Cl− flux in extrarenal epithelia. Proc Natl Acad Sci USA. 2004;101(7):2064–9. – reference: Farfel Z, Iaina A, Levi J, Gafni J. Proximal renal tubular acidosis: association with familial normaldosteronemic hyperpotassemia and hypertension. Arch Intern Med. 1978;138(12):1837–40. – reference: Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I. Human hypertension caused by mutations in WNK kinases. Science. 2001;293(5532):1107–12. – reference: Batlle DC, Hizon M, Cohen E, Gutterman C, Gupta R. The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Engl J Med. 1988;318(10):594–9. – reference: Obrenovitch TP, Zilkha E, Urenjak J. High extracellular potassium, and not extracellular glutamate, is required for the propagation of spreading depression. J Neurophysiol. 1995;73(5):2107–14. – reference: Benarroch EE. ++-ATPase. Functions in the nervous system and involvement in neurologic disease. Neurology. 2011;76(3):287–93. – reference: Harris AN, Grimm PR, Lee HW, Delpire E, Fang L, Verlander JW. Mechanism of hyperkalemia-induced metabolic acidosis. J Am Soc Nephrol. 2018;29(5):1411–25. |
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| Snippet | Introduction: Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA).... Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary... |
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| SubjectTerms | Acidosis, Renal Tubular - complications Acidosis, Renal Tubular - genetics Ammonia Ammonium Compounds Animals Child Clinical Practice: Research Article Epilepsy - complications Epilepsy - genetics Humans Hyperkalemia - complications Hyperkalemia - genetics Hypertension - complications Hypertension - genetics Mice Protein Serine-Threonine Kinases - genetics Pseudohypoaldosteronism - genetics Seizures |
| Title | Association of Familial Hyperkalemia and Hypertension with Proximal Renal Tubular Acidosis and Epileptic Seizures |
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