Renal Disease: Chronic Kidney Disease

sec_arr Appendix C:
Effect of CKD on LEOs Fitness for Duty
SECTIONS

Appendix C:  Effect of CKD on LEOs Fitness for Duty

LEOs with CKD have nine broad categories of impairment that can affect their ability to perform their job functions:

  1.  Physical fitness
  2.  Cognitive impairment
  3.  TIA/CVA
  4.  Ischemia
  5.  Sudden Death Syndrome
  6.  Thromboembolic events
  7.  Bleeding/ Thrombosis
  8.  End-stage renal disease (ESRD)
  9.  Renal Transplant (RTP)

 

Physical Fitness

CKD is associated with decreased physical functioning. Kittiskulnam et al.6 reported decreased oxygen consumption during exercise as well as decreased gait speed, and handgrip strength in those with CKD. Leikis et. al.8 reported decreased VO2 measured by cycle ergometry in patients with stage 3-4 CKD versus sedentary age and sex-matched controls. Johansen et al.10 studied stage 3-5 CKD patients and reported many lack the capabilities to perform basic ADLs and would qualify for Social Security disability based on their low VO2 maximum values. Other authors have advocated for aerobic conditioning programs in pre-dialysis patients based on their decreased physical function and aerobic performance.7 Oxygen consumption decreased in persons with CKD during maximum exercise.6, 9, 37, 38 Most of the studies of physical function in patients with CKD have been conducted on elderly persons since half of the people with CKD are over seventy years of age.

No pre-dialysis person could independently arise from a chair with a GFR < 12 cc/min.39 Additional studies have found a limitation in ADLs and instrumental ADLs with GFR’s < 60 cc/min,40 and lower exercise capacities (< 5 METS) and decreased exercise capacity in subjects with GFR < 60 cc/min as compared with a cohort of subjects with GFR’s > 90 ml/min.41

Cystatin is another marker of renal dysfunction and has also been correlated with a diminution of physical abilities, specifically walking distances.42, 43

Several geriatric studies have defined frailty as unintentional weight loss, loss of grip strength, self-reported fatigue, exhaustion, low physical activity, and/or low walking speed.43 These studies found that frailty predicts disability, hospitalization, institutionalization, and death.44 CKD in elderly persons was found associated with frailty.45 Frailty in patients who were referred for nephrology consultation was associated with a 2.5 higher risk of death and/or dialysis,46 and an NHANES study in 2009 revealed that frailty was 20% prevalent amongst participants with GFR < 45 cc/min.6

 

Cognitive impairment 

Persons with CKD have a higher prevalence of cognitive dysfunction when compared to the general population even after being adjusted to age, diabetes, cardiovascular risk, and other comorbid conditions.6, 11 Older patients with CKD have an estimated 20-50% prevalence of cognitive dysfunction when compared with 70% who are on dialysis.6, 11 Mild albuminuria (> 30mg albumin/g creatinine) was independently associated with poor performance on verbal memory testing and persistent albuminuria was associated with poor performance on cognitive testing.6 Several cross-sectional studies have suggested cognitive impairment in moderate to advanced CKD and estimated that GFR was inversely proportional to measures of performance in global cognitive performance.12

Cognitive impairment is commonly defined as a reduction in global cognition that affects at least two areas of cognitive function and can be measured using a standard cognitive function test (e.g., Mini-Mental State Exam [MMSE] or Montreal Cognitive Assessment [MoCA]).6, 47 Impairment may be evident in various cognitive domains: executive function (judgment/planning), language, attention, memory, and/or visual speed learning. A consensus definition of mild cognitive impairment (MCI) is lacking; however, it is associated with a deficit in global cognition and performance decrement of 1.5 – 1.99 standard deviations on a standard cognitive test.48, 49 It is most often manifested clinically as deficits in short-term memory but can also be present as impaired executive and/or language functions. Dementia is a blanket term used for moderate to severe and progressive cognitive impairment when an individual scores below population norms in at least two cognitive domains.12, 47, 50 A recent review demonstrated that persons with CKD are at substantial risk for unsafe driving (some of the study participants were already on dialysis).13 The above studies vary with regard to adjustment for prior CVA, depression, vascular risk factors, and neuropsychological tests utilized.

Patients with CKD have a higher prevalence of cognitive dysfunction than the general population even after adjustment for age, diabetes, cardiovascular risk, and other co-morbidities.51, 52 The majority of the studies point to a strong association between GFR and cognitive dysfunction.53 Cognitive dysfunction is more prevalent among patients with lower GFR and the burden and severity are higher in ESRD patients versus earlier stages of CKD.34, 54-59 This decline in cognitive function seems to begin in stage 3 of CKD.55

Brodski et al 60 published a meta-analysis of fifteen studies and 9,304 subjects segregated across stages of renal disease. Early CKD (stage 2) was associated with decreased processing speed attention, response speed, and short-term memory. Moderate stage CKD (stages 3, 4) was associated with deficits in executive functioning, verbal fluency, logical memory, orientation, and concentration. End-stage CKD (ESRD) was associated with decrements in all previous cognitive domains and additional impairments in cognitive control, delayed and immediate memory, visuospatial impairment, and overall cognitive impairment. Additional studies have replicated these findings, including decrements in concentration, processing speed, executive functioning, and memory;61 decrements in global cognition, naming, attention, executive function, and delayed memory tests versus subjects with CKD of moderate stage and ESRD;51, 52 decrements in verbal fluency in GFR< 60 cc/min.52 Decreased renal function at baseline was associated with a more rapid decline in cognitive function,12, 54, 58, 62-65, global cognitive functioning, visual memory, and abstract reasoning domains,54 and new cognitive dysfunction.62

Likewise, progressive albuminuria was also associated with a decrease in cognitive function, specifically: the Digit Symbol Substitution Test;36, 66 executive function, procession speed, verbal memory in diabetics; verbal fluency67 and general cognition, verbal memory, verbal fluency, and working memory in the elderly.35 Cognitive studies in the CKD population vary according to the specific neuropsychological test batteries utilized. The most common tests utilized are the Mini-Mental State Exam (MMSE), Modified Mini-Mental State Exam (3 MS), Trailmaking Test B (Trails B), and the Montreal Cognitive Assessment (MoCA).68 The 3 MS measures global cognitive function and is more sensitive to mild cognitive dysfunction versus the MMSE.69 The Trails B test measures executive function, visuospatial ability, and concentration.70 A small study of 51 patients on hemodialysis revealed normal cognitive function on the MMSE (> 28), however, more comprehensive testing revealed MCI.71 A study by Slinin et al72 of 5529 healthy older men found an independent relationship between moderate CKD and executive function at baseline but not at the end of the follow-up period. Another study of 7839 subjects older than 65 years old found that baseline GFR < 60 ml/min was not associated with increased risk for cognitive decline.73 Methodological issues (< 12% of participants with CKD < 60 cc/min) preclude generalization of the findings to subjects with more advanced CKD. A brain MRI should be performed in CKD patients who have cognitive impairment because of the frequency of both clinically apparent and clinically silent cerebrovascular lesions.12

 

TIA/CIA

The risk of CVA in persons on dialysis is reported as 8 to 10 times higher compared to the general population, with rates varying from 10-33/1000 person. Stroke in CKD (including dialysis patients) is reported to be 5 to 30 times higher compared to the general population.15 A recent meta-analysis reported a 43% independent risk of stroke with GFR < 60 ml/min (stage 3).14

Several studies have shown that measurements of CKD (either GFR and/or albuminuria) are associated with poor functional outcomes and mortality after stroke. Defects in the glomerular barrier and/or filtration dysfunction are probably related to small vessel diseases, hypercoagulability, and inflammation, which may affect clinical outcomes in CKD patients following stroke. Evidence for the most effective treatments for stroke is lacking in CKD patients.74 Seventeen percent of patients with ischemic stroke are diagnosed with embolic stroke of undetermined source (ESUS). Stroke recurrence in ESUS is 4.5% per year and is the highest among all subtypes of ischemic stroke. CKD is independently associated with a risk of ischemic stroke recurrence in the general population. Bao et al75 examined retrospectively the percentage of patients diagnosed with ischemic CVA who had CKD. Of 571 patients with diagnosed ischemic CVA, 49.3% had normal renal function (> 90 cc/min); and 289 had decreased renal function (16 – 89 cc/min); 244 patients had GFR of 60-90 ml/min and 45 patients had GFR < 60 ml/min.

Holzmann identified 16,678 stroke patients during a 12-year-period: 72% were ischemic, 15 % hemorrhagic, and 12% were non-specified. GFR rates of 60-90 cc/min, 30-60 cc/min, and 15-30 cc/min were defined as mild, moderate, and severely depressed GFR’s respectively. Hazard ratios for ischemic stroke were 1.09, 1.24, and 2.27. Likewise, hazard ratios for hemorrhagic strokes were 1.04, 1.26, and 2.31.76 Cerebral microbleeds increase proportionally to decreasing GFR77-79 and specifically, the prevalence of microbleeds was found to be a novel and independent risk factor for both renal and cardiovascular endpoints including death, new MI, revascularization, stroke, and/or amputation/revascularization due to peripheral arterial disease (PAD) or renal outcomes (doubling of creatinine, and/or ESRD) requiring dialysis or transplantation.80 Moreover, the presence of CKD in stroke patients was found to be associated with increased hospital mortality, decreased chance of discharge,81 repeat hospitalization, and thirty-day and one-year mortality.  

 

Ischemia

In 1836, Dr. Bright was the first physician to report the association between CKD and cardiovascular abnormalities.19 The risk of cardiovascular mortality is twice as high with stage 3 CKD and three times as high with stage 4 CKD compared to individuals with normal kidney function. Moreover, at the high end of microalbuminuria (30-299 mg/g) the risk of cardiovascular mortality doubles. Mortality rates were significantly high in patients with CKD17 and increased with the severity of albuminuria.20 The risk of stroke, coronary artery disease, peripheral artery disease, and atrial fibrillation is doubled in patients with GFR < 60 ml/min/1.73m2. Life expectancies are shortened by seventeen and twenty-five years in patients with CKD stages 3b and 4, respectively. The proportion of deaths from cardiovascular disease was reported as 27.5% in persons with CKD stages 1 and 2, 48.8% in persons with CKD stage 4 and 58% in persons with CKD stage 5.(19) The findings of increased mortality in ESRD patients attributable to sudden cardiac death have been confirmed in other studies.16, 18, 21

Yamamoto, et al. indicated that the risk of acute cardiovascular hospitalizations and complications begins below a GFR of 60-80 cc/min.82 Go et al reviewed 1,120,205 patients who were risk stratified by stage of GFR and found elevated hazard ratios for coronary artery disease, CHF, CVA, and peripheral arterial disease and death as GFR’s decreased.83 Deo et al found that hazard ratios of cardiac death were increased in a cohort followed over six years with elevated cystatin and/or GFR < 60 cc/min.(17) Keith et al performed a meta-analysis of 27,998 patients and found that death is more common than dialysis across stages 2, 3, and 4 of CKD.(84) The HR (1.42) for all-cause mortality is also increased with those with mild CKD (creatinine <1.4 – 3 mg/dl.).(85) Similar findings were found in studies of patients with anemia and CKD.86

Low-level albuminuria is also associated with death in those with pre-existing cardiovascular and/or CVA.87 A meta-analysis found that cardiovascular mortality is increased by a factor of 2 in stage 3 and by a factor of 3 in stage 4 CKD with microalbuminuria.88 Albuminuria is also associated with death in CKD patients.(82, 86, 88) Cardiovascular diseases have increased 2 to 4 times in those with CKD and/or albuminuria.19 Post-myocardial infarction (MI) data were analyzed89 and found that 30-40% of post-MI patients and 50-70% of CHF patients have GFR’s < 60 cc/min and, if albuminuria is considered, the overall prevalence of CKD approaches 60% in post-MI patients and 80% in patients with CHF. Other cardiac morbidities including CHF,90, 91 peripheral arterial disease,92 atrial fibrillation,93 CAD and CHF,94 and LVH 94-96 are associated with decreasing GFR. Anemia and CKD are also associated with recurrent cardiac events and cardiac mortality.86

Albuminuria in CKD has been independently correlated with cardiovascular disease19, 23, 82, 88 and coronary disease, stroke, and CHF.97 The odds ratio for cardiovascular disease risk increases according to the level of albuminuria and is 1.5 in stage 2; 2 to 4 in stage 3; 4 to 10 in stage 4; 10 to 50 in stage 5; and 20 to 100 with ESRD.23, 24 The European Guidelines for Cardiac Risk Prevention in 201624 incorporated CKD into their risk model for primary prevention. Persons with GFR < 30 cc/min and/or diabetics with proteinuria are at very high risk with a 10-year mortality risk of > 10%. Those who have a GFR of 30-59cc/min are at “high risk” with a 10-year predicted cardiac mortality risk of 5-10%. EKG abnormalities were found to be 78% in a cohort of stage 4 and 5 CKD patients screened. Abnormalities included LVH, Q waves, ST abnormalities, prolonged QRS, tachycardia, and/or atrial enlargement.98 Treadmill stress testing did not prove useful due to the preponderance of baseline EKG abnormalities. Lexiscans stress tests may be less sensitive due to the balanced ischemia in diabetes mellitus.94

 

Sudden Death Syndrome

Fifty-five percent of deaths in dialysis patients are described as cardiac arrest as opposed to 6% in the general population.94 Cardiac diseases are responsible for 50% of deaths in the CKD population.99 Sudden cardiac death (SCD) is the largest cause of natural death in the US and was responsible for 356,461 deaths in 2020.98 In the CKD population, 22% of total deaths are caused by SCD; the incidence of SCD increases with age; 2% per year in 20-40 years old; 3.7 % per year in 45-64 years old; and 7% per year age > 65 years old.   

Caravaca et al. reported all-cause mortality, SCD, and non-sudden cardiac deaths as follows in non-dialysis patients with advanced (stage 4 and 5) CKD: 113/1000 person-years, 18/1000 person-years and 44/1000 person-years.16 SCD accounted for 16% of total deaths and 29% of cardiovascular mortality. The rates for SCD in the general population in Europe are as follows: 4/1000 person-years in the general population; 8/1000 person-years with age over 60 and 17-28/1000 person-years for those on dialysis. Turakhia et al. reported an annual sudden death rate under 0.1% in the general population; 1.5-2.7% in the non-dialysis CKD population; 4% annually in CHF and 5-7% in the hemodialysis population.100

 

Thromboembolic events

Thromboembolic events could be more likely in individuals with individuals with co-existing CKD and atrial fibrillation.83, 101-103 

 

Bleeding/Thrombosis

It is not clear which patients with CKD are more prone to bleeding and which patients are more prone to thrombosis; what is known is that both exist. It is also clear that patients with CKD are more prone to bleeding complications compared to patients without CKD. Preliminary data indicates that the severity of renal failure is directly related to bleeding and preserved renal function is more associated with thrombosis. Definitive recommendations regarding testing are not available.22

 

End-stage renal disease (ESRD)

According to Palmer, hemodialysis and peritoneal dialysis are absolute contraindications for police, firefighters, and divers.104 Also excluded are persons working in hot environments, heavy manual laborers, smelting, construction/scaffolding work, and employment in the armed forces.

 

Renal Transplant (RTP)

Renal transplants increase the quality of life and life expectancy in CKD patients. RTP patients must take daily immunosuppressive therapy (e.g., prednisone, cyclosporine, azathioprine, tacrolimus, sirolimus, and/or mycophenolate) with inherent side effects.105 Some of these side effects include tremors, headaches, GI symptoms, hirsutism, gingival hyperplasia, nephrotoxicity, hypertension, bone marrow suppression, pancreatitis, elevated liver enzymes, bone loss, diabetes, and cataracts. RTP recipients are also at risk for infection and are advised to avoid individuals with common infectious diseases. RTP recipients are also at increased risk for skin malignancies and should be screened at least annually.

Lower levels of physical functioning,106-108 fatigue, decreased physical labor109 and musculoskeletal symptoms (myalgias, joint pain, bone loss, and leg bone pain syndrome) persist post-RTP.110 In summary, it is unlikely that RTP recipients can return to work as full-duty LEOs. However, if they are young, received a live renal transplant, and have had ESRD for a short time, it is possible to return to full duty. The prospective LEO must be willing to accept the risks noted above as well as the risk of organ failure due to trauma.