CKD;

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

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

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)?

What’s the connection between elevated troponins and Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Elevated cardiac troponins or myocardial injury (defined as troponin levels above the 99th percentile upper reference range) are not uncommon in Covid-19, having been reported in ~10-30% of hospitalized patient and usually observed in the absence of acute coronary syndrome (ACS) (1-4).

 
Elevated troponins have been associated with increased risk of in-hospital mortality in Covid-19. The prevalence of elevated troponins among patients who died was 76% compared to 10% among survivors in 1 Chinese study (3). Another study from China found increasing troponin levels over a 22 day period among those who died while troponin levels remained low in those who survived (5).

 
Risk factors for elevated troponins in Covid-19 include older age, cardiovascular comorbidities (eg, hypertension, coronary heart disease, heart failure), diabetes, chronic obstructive pulmonary disease, chronic renal failure, and the presence of a high inflammatory state, as indicated by elevated inflammatory markers such as C-reactive protein (CRP) (3).

 
Several mechanisms have been proposed to explain elevated troponins in Covid-19, including cytokine-induced myocardial injury, microangiopathy due to prothrombotic state, myocardial infarction (type I due to plaque rupture or type II due to oxygen supply/demand imbalance), and myocarditis either due to direct viral invasion or indirectly through immune-mediated mechanisms (1,2).

 
Patients with Covid-19 and modest troponin elevation with rapid fall in the absence of signs or symptoms of ACS, may have type II myocardial infarction due to demand ischemia, particularly in the setting of coronary disease. In contrast, more protracted elevation of troponins associated with high inflammatory markers such as CRP is suggestive of hyperinflammatory myocardial injury (1).

 

It will be interesting to see if trials of anti-inflammatory agents, such as colchicine and anti-interleukin-I, will have an impact on the troponin levels in Covid-19 patients (1).

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References
1. Cremer PC. SARS-CoV-2 and myocardial injury: few answers, many questions. Clev Clin J Med. Posted April 8, 2020. Doi:10.3949/ccjm.87a.ccc001 https://www.ccjm.org/content/early/2020/05/12/ccjm.87a.ccc001
2. Tersalvi G, Vicenzi M, Calabretta D, et al. Elevated troponin in patients with coronavirus disease 2019:possible mechanisms. J Card Failure 2020; https://pubmed.ncbi.nlm.nih.gov/32315733/
3. Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J 2020. https://pubmed.ncbi.nlm.nih.gov/32391877/
4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-59. https://jamanetwork.com/journals/jama/fullarticle/2765184
5. Zhou F, YU T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

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 elevated troponins and Covid-19?

Is my patient with gout at higher risk of cancer?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

Although the association of gout with cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus or obesity is well known, increasingly number of epidemiologic studies support the association of gout with higher risk of malignancy. 1,2

A 2015 meta-analysis of 3 studies involving over 50,000 persons concluded that gout was an independent risk factor for cancer, particularly urological, gastrointestinal and lung cancers. 1

A population-based study of comorbidities in over 2 million persons in Sweden found that in addition to an increased risk of diabetes mellitus, hypertension, chronic heart failure, chronic kidney disease and alcohol abuse, gout was associated with increased risk of malignancy: odds ratio 1.3 (1.2-1.5) in men and 1.1 (1.1-1.2) in women. 2

Although serum uric acid has been considered to have anti-oxidant properties, a prospective study of over 28,000 women followed over a median of 15.2 years did not find high serum acid levels to be protective of cancer.3 In fact, uric acid levels > 5.4 mg/dL at the time of subject enrollment was independently associated with increased risk of total cancer mortality and deaths from a variety of malignant neoplasms, including those of breast, female genital organs, and nervous systems. 3 In a similar prospective study involving men, high uric acid levels (>6.7 mg/dL) were associated with increased risk of mortality from gastrointestinal, respiratory and intrathoracic organ malignancies. 4

Whether the observed association between gout and higher risk of malignancy is causal or due to the company that gout often keeps (eg, lifestyle) is unclear.

Fun fact: Did you know that among mammals, only humans, great apes and certain breeds of dogs (eg, Dalmation) produce elevated levels of uric acid in the urine and blood? 5

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References

  1. Wang W, Xu D, Wang B, et al. Increased risk of cancer in relation to gout: a review of three prospective cohort studies with 50,358 subjects. Mediators of Inflammation 2015, Article ID 680853, 6 pages. https://www.ncbi.nlm.nih.gov/pubmed/26504360
  2. Wandell P. Gout and its comorbidities in the total population of Stockholm. Preventive Medicine 2015; 81:387-91. ISSN 0091-7435. https://www.ncbi.nlm.nih.gov/pubmed/26500085
  3. Strasak AM, Rapp K, Hilbe W, et al. The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28000 older Austrian women. Ann Onc 2007;18:1893-97. https://www.ncbi.nlm.nih.gov/pubmed/17785768
  4. Strasak Am, Hilbe RK, Oberaingner W, et al. Serum uric acid and risk of cancer mortality in a large prospective male cohort. Cancer Causes Control 2007;18:1021-9. https://www.ncbi.nlm.nih.gov/pubmed/17665312
  5. Bannasch D, Safra N, Young A, et al. Mutations in the SLC2A9 gene cause hyperuriosuria and hyperuricemia in the dog. PLOS Genet 2008;4:e1000246. https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000246&type=printable
Is my patient with gout at higher risk of cancer?