# Exercise as it relates to Disease/Physical activity and renal function decline in patients with kidney disease

The following article is a critique of the primary research of C. Robinson-Cohen et al. Physical Activity and Change in Estimated GFR among persons with CKD and is designed to assist health care professionals in providing patient centred care considering recent research developments. This critical analysis was completed as an assessment for University of Canberra unit 8340 Health, Disease and Exercise, due September 2021.

## Research Context
##### What is Chronic Kidney Disease?

CKD is defined as an estimated GFR of less than 60ml/min/1.73m$^2$ present for longer than 3 months or evidence of kidney damage with 1 or more of the following: albuminuria; haematuria without urological cause; structural abnormalities; and or pathological abnormalities. Those at risk of developing CKD in Australia will frequently present with 1 or more of the following risk factors: patients of Aboriginal and Torres Strait Islander origin over 30 years; family history of CKD; smokers; obese; and those diagnosed with co-morbidities including diabetes; hypertension; and CVD. Estimations of GFR are used to categorise CKD progression. It represents the volume of blood filtered by the kidneys each minute. For reference, a healthy individual will have a eGFR of more than 90ml/min/1.73m$^2$.

##### Patient Prognosis if HCP don't interfere with disease progression?

CKD is not curable, however HCP can assist in delaying further eGFR decline. By delaying disease progression we give the patient better health outcomes, improved quality of life and decrease number of DALY. This is achieved by improved management of co-morbidities including hypertension, diabetes mellitus and hyperlipidaemia by pharmacological, surgical and non pharmacological management of disease. Increasing physical activity is a non-pharmacological strategy used to improve CVD management, indirectly slowing renal function decline. CKD mortality is associated with consequences of CVD progression and ESRD.

##### ESSA Position Statement

ESSA previously released a position statement acknowledging the relationship between physical activity and CKD. It was identified that patients with CKD and low VO2 maximum have increased risk of DALY and mortality. ESSA supports prescribing physical activity of 3 or more 30 minute sessions at an intensity of 60% of patient's VO2 max. This supports the 2017 KGIGO clinical guideline recommendations of 5x30 minute sessions per week. Recommendations were made from improved fitness, improve CVD management and additional CVD risk factors, and improved quality of life for the patient. This in turn decreases rate of eGFR decline.

##### How does this study add to current research?

Current research referenced within ESSA position statement and KGIGO guidelines acknowledge that improved management of patient co-morbidities that increase risk of renal decline are managed by prescription of moderate level physical activity. This research aims to support this data, quantifying the rate of eGFR decline in patients with various levels of physical activity.

## About the Study
##### Who Conducted the Study?

The primary author of the study, Dr Cassianne Robinson-Cohen, has been involved in numerous research articles primarily specialising mineral disturbances and burden of cardiovascular disease in patients with CKD. Additional authors have a significant number of research articles to their name within fields of CKD; physical activity and cardiovascular disease in recent years, leading to the production of reputable research article. Many of the researchers were based upon various departments of University of Washington, Seattle.
The study was published in the Journal of the American Society of Nephrology. 2014, Vol. 25(2), p.399-406. There was no disclosed nor obvious reason to assume bias within the research article.

##### What type of research was this?

The study conducted was an observational cohort study. It is important to note that physical activity levels were self-reported data, therefore subject to false reporting by the participant. This is acknowledged by the researchers within clinical limitations, predicting bias towards null hypothesis. Due to the nature of the research topic, the typical gold standard, double blind randomised control trial, was not applicable.

##### Where was the study conducted?

The study was composed of 256 participants which were recruited from Outpatient Nephrology Clinics at Harborview Medical Centre and Veterans’ Affairs Medical Centre. Participants were concurrently enrolled in the Seattle Kidney Study. Despite research being conducted in America, findings remain synchronous with Australian recommendations.

##### What did the study involve?

Participants were required to complete 4-week physical activity history recollection describing frequency and duration of inclusive activities completed at leisure. Included activities included the following:
* moderate difficulty walking
* running outdoors or treadmill
* cycling
* aerobics
* golf
* tennis
* swimming
* resistance training
* use of aerobic machines
The Study aimed to identify correlation between rate of eGFR decline and amount of self-reported physical activity. Primary and secondary analysis of serum, plasma and urine samples was completed. Primary analysis measured serum cystatin-C which was later used to calculate estimated GFR. Secondary analysis featured utilisation of CKD-EPI formula for calculating eGFR with serum creatinine levels. Two analysis methods of eGFR were utilised due to influence of physical activity on creatinine levels. Height, weight, waist circumference, smoking status, alcohol use, prevalence of CV co-morbidities were also monitored.
Limitations to acknowledge is that physical activity was reported once throughout the study. There was no notes as to whether participants time spent exercising changed between commencement and regular follow up appointments. It was assumed that physical activity time per week remained static.

##### What did we learn?

The study identified a correlation between physical activity level and rate of GFR decline. Participants who completed more than 150 minutes of physical activity per week saw a decrease of -6.2% decline per annum compared to 9.6% of the inactive 'control' group. These rates of decline were similar amongst various ranges of baseline kidney function. These findings remained true after the follow up period of 3 years, with higher rates of end stage renal disease being associated to no reported physical activity. However this failed to remain true when adjusted for additional variables. For more information please see table 4 of research article .

##### Research Conclusion

From this study, we can accept the alternate hypothesis in which more time spent completing physical activity per week is associated with a decrease rate of GFR decline. However it is not associated with decrease in end-stage kidney disease, rather delaying disease progression.

## Application to practice
##### Improved Patient Outcomes

By implementing regular physical activity at moderate intensity of 150 minutes or more per week we can expect delayed rate of renal function decline, giving the patient improved quality of life, improved management of co-morbidities and decrease DALY.

## Further reading
##### For HCP

Chronic Kidney Disease (CKD) Management in Primary Care
ESSA Position Statement on exercise and CKD
Australian Institute of Health and Welfare

##### For Patients

Kidney Health Australia
Life Options Resources

## Appendices

Table 1: List of Abbreviations and Meanings :
| Abbreviation | Meaning |
| HCP | Health Care Professional. This includes allied health practitioners. |
| CKD | Chronic Kidney DIsease |
| GFR | Glomerular Filtration Rate |
| eGFR | Estimated Glomerular Filtration Rate |
| CVD | Cardiovascular Disease |
| ESSA | Exercise and Sports Science Australia |
| CAD | Coronary Artery Disease |
| MI | Myocardial Infarction |
| VO2 Max | Maximum volume of oxygen utilised during exercise |
| DALY | Disability Associated Life Years |
| ESRD | End Stage Renal Disease |

## References

* ↑ Robinson-Cohen C, Littman A, Duncan G, Weiss N, Sachs M, Ruzinski J et al. Physical Activity and Change in Estimated GFR among Persons with CKD. Journal of the American Society of Nephrology [Internet]. 2014 [cited 3 September 2021];25(2):399-406. Available from: https://jasn.asnjournals.org/content/25/2/399
* ↑ Chronic Kidney Disease (CKD) Management in Primary Care [Internet]. 4th ed. Melbourne: Kidney Health Australia; 2020 [cited 3 September 2021]. Available from: http://www.kidney.org.au/
* ↑ Chisholm-Burns M, Schwinghammer T, Malone P, Kolesar J, Wells B, Dipiro J. Pharmacotherapy principles & practice. 4th ed. New York: McGraw-Hill Education; 2016.
* ↑ Thomas B, Matsushita K, Abate K, Al-Aly Z, Ärnlöv J, Asayama K et al. Global Cardiovascular and Renal Outcomes of Reduced GFR. Journal of the American Society of Nephrology. 2017;28(7):2167-2179.
* ↑ Nakanishi T, Nanami M, Kuragano T. The pathogenesis of CKD complications; Attack of dysregulated iron and phosphate metabolism. Free Radical Biology and Medicine. 2020;157:55-62.
* ↑ Smart N, Williams A, Levinger I, Selig S, Howden E, Coombes J et al. Exercise & Sports Science Australia (ESSA) position statement on exercise and chronic kidney disease. Journal of Science and Medicine in Sport. 2013;16(5):406-411.
* ↑ KGIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. International Society of Nephrology [Internet]. 2017 [cited 3 September 2021];7(1). Available from: https://kdigo.org/wp-content/uploads/2017/02/2017-KDIGO-CKD-MBD-GL-Update.pdf
* ↑ Cassianne Robinson-Cohen, PhD | Department of Medicine [Internet]. Vanderbilt University Medical Center. 2020 [cited 5 September 2021]. Available from: https://medicine.vumc.org/person/cassianne-robinson-cohen-phd
* ↑ Concato J, Shah N, Horwitz R. Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs. New England Journal of Medicine. 2000;342(25):1887-1892.