What’s the connection between dialysis and cognitive impairment in patients with chronic kidney disease (CKD)?

Cognitive impairment (CI) is extremely common among dialysis patients affecting  up to ~70% or more  of patients (1-3).   Pre-existing conditions, dialysis process itself and uremic, metabolic and vascular disturbances associated with end stage renal failure may all contribute to the CI in patients on dialysis (1-5).

Among pre-existing conditions, vascular disease is considered the major contributing factor to the risk of CI in dialysis patients (3). The prevalence of stroke is very high among hemodialysis (HD) ( ~15%) and CKD patients (~10%) compared to non-CKD patients (~2%).  History of stroke also doubles the risk of dementia in both the non-CKD and HD patients. Subclinical cerebrovascular disease due to silent strokes and white matter disease —common in CKD and dialysis patients—are also associated with increased risk of cognitive and physical decline and incident dementia.  White matter disease is thought to be related to microvascular disease and chronic hypoperfusion (1).

Dialysis itself may be associated with acute confusional state due to cerebral edema caused by  acute fluid, urea, and electrolyte shifts during dialysis (particularly among newly initiated HD patients).  Some have suggested that the optimal cognitive function in HD patients is around 24 h after HD (1).

Chronic rapid fluctuations in blood pressure, removal of large fluid volumes and hemoconcentrations can further increase the risk of cerebral hypoperfusion, potentially accelerating vascular cognitive impairment in HD patients (1).

 Bonus Pearl: Did you know that while cerebral ischemia (measured by PET-CT or other non-invasive means) is common during HD, it may occur in the absence of intra-dialysis hypotension (6,7)?

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References

  1. Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis 2008;15:123-32. https://www.ackdjournal.org/article/S1548-5595(08)00011-6/pdf
  2. Murray AM, Tupper DE, Knopman DS, et al. Cognitive impairment in hemodialysis patients is common. Neurology 2006;67:216-223. https://experts.umn.edu/en/publications/cognitive-impairment-in-hemodialysis-patients-is-common
  3. Van Zwieten A, Wong G, Ruospo M, et al. Prevalence and patterns of cognitive impairment in adult hemodialysis patients: the COGNITIVE-HD study. Nephrol Dial Transplant 208;33:1197-1206. https://pubmed.ncbi.nlm.nih.gov/29186522/
  4. Seliger SL, Weiner DE. Cognitive impairment in dialysis patients: focus on the blood vessels? Am J Kidney Dis 2013;61:187-90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433757/
  5. Findlay MD, Dawaon J, Dickie DA, et al. Investigating the relationship between cerebral blood flow and cognitive function in hemodialysis patients. J Am Soc Nephrol 30:147-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317612/
  6. Polinder-Bos HA, Garcia DV, Kuipers J, et al. Hemodiaysis induces an acute decline in cerebral blood flow in elderly patients. J Am Soc Nephrol 208;29:1317-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875962/
  7. MacEwen C, Sutherland S, Daly J, et al. Relationship between hypotension and cerebral ischemia during hemodialysis. J Am Soc Nephrol 2017;38:2511-20. https://www.researchgate.net/publication/314298128_Relationship_between_Hypotension_and_Cerebral_Ischemia_during_Hemodialysis

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the connection between dialysis and cognitive impairment in patients with chronic kidney disease (CKD)?

Why is my patient with systemic amyloidosis at higher risk of bleeding?

The major mechanism of bleeding tendency in primary systemic amyloidosis (AL) appears to revolve around amyloid deposit infiltration of the vasculature and musculature, leading to amyloid angiopathy, fragility, impaired vasoconstriction, tears and hemorrhage. 1,2 Other potential mechanisms include:

  • Presence of plasma inhibitors of fibrinogen conversion to fibrin
  • Deficiencies of factor X, IX and V due to their affinity for amyloid substance
  • Presence of circulating heparin-like anticoagulants
  • Uremic platelet dysfunction in the presence of renal involvement

In a study involving 36 patients with AL, ~30% had bleeding symptoms with alterations of 1 or more clotting tests found in ~85%: prolonged prothrombin time (PT) ratio (22%), activated partial thromboplastin time (aPTT) (65%) and thrombin time (85%).

Clinical manifestations of amyloidosis related to its bleeding diathesis include petechiae, ecchymoses, purpura (“raccoon eyes when periorbital), uncontrollable epistaxis, gingival bleeding, and gastrointestinal bleed or submucosal hematomas. 1-6

Due to its convenience and relative safety, a biopsy of abdominal fat or minor salivary glands is often initially performed for definitive diagnosis of amyloidosis, followed by biopsy of specific organs (eg, kidney, liver), if needed. 3,6

Due to the potential risk of bleeding complications, transjugular liver biopsy is preferred over percutaneous approach. This is because the liver capsule is not perforated with transjugular liver biopsy and if bleeding occurs, the blood returns directly into the venous system rather than into the peritoneum. 7-8 

Bonus Pearl: Did you know that AL amyloidosis is the most common type of systemic amyloidosis in western countries? This is because the incidence of the other major type of amyloidosis (AA), often related to chronic infections or inflammatory diseases, has been dropping in these countries.3

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References

  1. Gamba G, Montani N, Anesi E, et al. Clotting alterations in primary systemic amyloidosis. Haematologica 2000;85:289-92. https://moh-it.pure.elsevier.com/en/publications/clotting-alterations-in-primary-systemic-amyloidosis
  2. Marconcini LAL, Stewart FM, Sonntag L, et al. AL amyloidosis complicated by persistent oral bleeding. Case Reports in Hematology 2015, Article ID 981346. https://www.hindawi.com/journals/crihem/2015/981346/
  3. Desport E, Bridoux F, Sirac C, et al. AL Amyloidosis. Orphanet Journal of Rare Diseases 2012, 7:54. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-54
  4. Yoshii S, Mabe K, Nosho K, et al. Submucosal hematoma is a highly suggestive finding for amyloid light-chain amyloidosis: Two case reports. W J Gastroenterol 2012;4:434-37. https://www.ncbi.nlm.nih.gov/pubmed/23125904
  5. Kon T, Nakagawa N, Yoshikawa F, et al. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptoms. Clin J Gastroenterol 2016;9:243. http://europepmc.org/article/med/27318996
  6. Petre S, Shah IA, Gilani N. Review article:gastrointestinal amyloidosis-clinical features, diagnosis and therapy. Alim Pharmacol Ther 2008;27:1006-16. https://www.ncbi.nlm.nih.gov/pubmed/18363891
  7. Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. Gut 1999;45(Suppl IV):IV1-IV11. https://www.ncbi.nlm.nih.gov/pubmed/10485854
  8. Dohan A, Guerrache Y, Boudiaf M, et al. Transjugular liver biopsy: Indications, technique and results. Diagnostic and Interventional Imaging 2014;95:11-15. https://www.ncbi.nlm.nih.gov/pubmed/24007769
Why is my patient with systemic amyloidosis at higher risk of bleeding?