Chapter 33: Falls in Elderly Patients With KidneyDisease
St. Louis University School of Medicine and GRECC, VA Medical Center, St. Louis, Missouri
Falls and associated fragility fractures are a major
brain, e.g., pulmonary embolus, myocardial infarc-
cause of morbidity and mortality in older persons
tion, anemia, stroke, seizures, dehydration, meta-
with kidney disease. In a longitudinal study from
bolic abnormalities, and subdural hematoma (Ta-
one dialysis center for a median of 468 d, 47% fell.1
ble 4). Problems with lower limb strength and
The fall incident rate was 1.60 falls per year. Overall
balance disorders are common in older dialysis pa-
studies suggest that the fall rate is much greater in
tients and treatable with physical therapy. Drugs
dialysis patients than in the general population. In
associated with falling are listed in Table 6. Studies
the general population over 75 yr of age, 30% of
in older diabetics suggest that falls are reduced
persons fall each year, with one in five having an
injury. Hip fractures in persons on dialysis occurthree to four times more commonly than in thegeneral population. One-year mortality in dialysis
patients who have a hip fracture is two to threetimes of that in older community-dwelling persons
Postural hypotension is a major cause of falls. It can
who have a fracture. A single fall in a dialysis patient
occur without any dizziness. For this reason, BP
over 65 yr increases the risk of death after adjust-
needs to be regularly measured in the standing po-
ment for comorbidities.2 In the first 2 yr after dial-
sition. Orthostatic hypotension occurs more com-
ysis, renal transplant patients have a higher risk of
monly in the morning, and in an individual with
fracture than patients on dialysis.3 Table 1 lists side
severe orthostasis, it may only be present on one
half of the BP measurements. In a group of 23 el-
A community study of fall prevention in Con-
derly on dialysis, orthostasis was present in 8 pa-
necticut showed that a simple education program
tients before dialysis and 16 of 23 after dialysis.5
(focused on medication reduction and balance and
Besides falls, orthostatic hypotension can lead to
gait training) could reduce falls and the need for
syncope, myocardial infarction, stroke, and death.
fall-related medical services4 (www.fallsprevention.
Causes of orthostatic hypotension include anticho-
org). Falls can be either caused by extrinsic (envi-
linergic medications, anemia, prolonged recum-
ronmental) or intrinsic factors. Environmental fac-
bency, dehydration, inadequate salt intake, protein
tors include wet, slippery floors, poor lighting,
energy malnutrition, adrenal insufficiency, diabetic
uneven surfaces, and stairs. Descending stairs is a
autonomic neuropathy, Parkinson’s disease, and
particular risk factor. There are multiple causes of
multiple system atrophy (Shy-Drager syndrome).
falls caused by intrinsic factors as shown in Tables 2
Postprandial hypotension (a fall in BP of Ͼ20
and 3.4 Specific dialysis-related causes of delirium
mmHg) occurs in up to 25% of older persons and
include uremic encephalopathy, dialysis dementia,
persons with diabetes. Its nadir is reached 1 to 2 h
Wernicke’s encephalopathy, and dialysis dysequi-
after a meal. It is not necessarily associated with
orthostasis. It has also been shown to be present
New onset falls are often caused by delirium. De-
during dialysis in nondiabetic patients.6 Postpran-
lirium can present as purely the inability to pay at-tention. Delirium should be considered as a causeof falling in any patient on dialysis who suddenly
Correspondence: John E. Morley, MB, BCh, Division of GeriatricMedicine, St. Louis University School of Medicine, 1402 S. Grand
starts falling. Delirium has multiple causes such as
Boulevard, M238, St. Louis, MO 63104. E-mail: [email protected]
drugs, infection, active decrease in oxygenation to
Copyright ᮊ 2009 by the American Society of Nephrology
Table 3. Safe and sound mnemonic for renal disease–associated falls
Decreased activity and functional decline
Systolic blood pressure (low predialysis)
dial hypotension is associated with falls, syncope, stroke, myo-
No Vitamin D (Ͻ30 ng/ml)Dialysis disequilibrium or other causes of delirium
cardial infarction, and death. Treatment can consist of multi-ple small meals with limited carbohydrate content. Because it iscaused by the release of a vasodilatory intestinal peptide, calci-
Rarely is a diagnosis made when a person has a single syncopal
tonin gene–related peptide, it can be treated with somatostatin
event. If a person has multiple syncopal events, they should be
analogs. Recent studies have shown that ␣-1-glucosidase in-
given an event recorder that should be used.
hibitors, acarbose and miglitol, can markedly attenuate post-prandial hypotension.
Many persons who fall or have disequilibrium develop a “fearof falling.” Studies in older persons suggest that fear of falling
Persons who fall with loss of consciousness either have seizures
puts persons at a marked increased risk of falls and other ad-
or syncope. More than one half of older persons with seizures
have partial complex seizures (unusual behavior not necessar-ily associated with toxic clonic seizures) explaining why it cantake nearly 2 yr to diagnose seizures in older persons. Older
persons with syncope need to undergo carotid sinus massagebecause those who develop bradycardia need a pacemaker.
A 25(OH) vitamin D (calcidiol) level Ͻ75 nmol/L (30 ng/ml)has been identified as a cause of falls that responds to treatment
with a reduction in falls.7 25(OH) Vitamin D deficiency is verycommon in renal failure patients.8 There is some evidence sug-
gesting calcidiol is more effective than calcetriol.9
Poor lightingNo grab bar in toiletStairs cluttered
There is a paucity of studies examining factors associated with
falls in dialysis patients. Cook et al.10 found that age, comor-
bidity, lower predialysis systolic BP, and a history of falls rep-
Table 4. DELIRIUMS mnemonic for multiple causes of
Dementia (poor ability to “dual-task”)
Low PO2 states (pulmonary embolus, myocardial infarction, anemia,
Metabolic (vitamin B12 deficiency, hypothyroidism, thiamine
associated with markedly increased morbidity and mortality in
patients on dialysis. The causes of fragility fractures are falls or
other trauma and bone disease. In the general population that
Treat anemia (if present, with erythopoetin)
usually means osteoporosis (Table 7). In renal failure, the pic-
ture is complicated because of renal osteodystrophy. Osteodys-
trophies include osteomalacia caused by vitamin D deficiency,
osteitis fibrosa cystica caused by excess parathyroid hormone
secretion, and adynamic bone disease caused by aluminum
toxicity and/or parathyroid hormone oversuppression. Low
bone mineral density may be seen in either osteoporosis or in
Midodrine (alpha 1 adrenergic antagonist)
osteodystrophy. Bone mineral loss in older men correlates with
elevated cystatin C and lower estimated GFR.13 Bone mineral
resented the major associated factors. Desmet et al.1 reported
density may be abnormally elevated in the presence of aortic
that age, diabetes, increased number of drugs, antidepressant
calcification. In dialysis patients, the major risk factors for fra-
drug use, and failing a walking test predicted falling in hemo-
gility fracture are older age, female sex, diabetes mellitus, heart
dialysis patients. Angalakudi et al.11 found the following co-
disease, longer periods on dialysis, race other than African
morbidities to be associated with an in-hospital fall in persons
American, lower body mass index, and low parathyroid lev-
with chronic kidney disease (Ͻ60 ml/min GFR): dementia,
els.14 In the Dialysis Outcomes and Practice Patterns Study,
pneumonia, gastrointestinal disease, diabetes, antidepressants,
risk factors were older age, female gender, prior kidney trans-
plant, low serum albumin, selective serotonin reuptake inhib-itors, narcotics, benzodiazepines, adrenal steroids, and veryhigh parathyroid hormone levels.15 Levels of PTH between 600
and 900 pg/ml seemed to have the lowest risk.
The use of bisphosphonates in this population is unclear. In
The Cochrane Collaboration examined 62 trials on interven-
persons who do not have adynamic bone disease or hyperpara-
tions to reduce fall risk.12 Multidisciplinary, multifactorial
thyroidism and normal 25(OH) vitamin D levels, bisphospho-
programs reduced falls in community-dwelling older persons
nates at lower doses can be considered. In most cases, a bone
(RR ϭ 0.73; range ϭ 0.63 to 0.85) and residential care facilities
biopsy with tetracycline labeling would be considered neces-
(RR ϭ 0.60; range ϭ 0.50 to 0.73). Programs that had high
sary before using bisphosphonates to not aggravate adynamic
efficacy at reducing falls were muscle strengthening and bal-
bone disease, although it is feasible that bone markers could be
ance retraining; home hazard assessment and modifications;
used in persons where no exposure to aluminum exists.16 Low
withdrawal of psychotropic medications; Tai Chi exercise in-
levels of osteocalcin and bone alkaline phosphatase suggest
tervention; and cardiac pacing for falls with cardio-inhibitory
carotid sinus hypersensitivity (Tables 5 and 6).
Hypogonadism is common in older males and in renal fail-
All persons who fall should be enrolled in a home fall pre-
ure patients. In males with a low free testosterone (either cal-
vention program. This is reimbursed by Medicare Part A if
culated or measured by dialysis) (see www.issam.ch) or bio-
homebound and Medicare Part B if not.
available testosterone (albumin bound and free), the use oftestosterone, which should both increase osteoblastic activity
and muscle strength, can be considered. Total testosteroneshould not be used in view of elevated levels of sex hormone
Fragility fractures (fractures associated with minor trauma) are
Table 6. Medications associated with falls
Other relatives with osteoporosis/fractures
(used for restless legs syndrome in dialysis)
Raloxifene increases bone markers of osteoblastic activity in
patients on hemodialysis and thus could be used to treat osteo-
After renal transplantation, there is a rapid decrease in bone
mineral density over the first year. This decrease in bone isassociated with increased risk of fractures. The causes of this
increased loss of bone include renal osteodystrophy, glucocor-
1. Desmet C, Beguin C, Swine C, Jadoul M: Falls in hemodialysis pa-
ticoids, immunotherapy, vitamin D deficiency, hypophos-
tients: prospective study of incidence, risk factors, and complications.
phatemia, hypogonadism, and osteoporosis. Bisphosphonates
Am J Kidney Dis 45: 148 –153, 2005
(oral and intravenous), vitamin D, and calcitonin have all been
2. Li M, Tomlinson G, Naglie G, Cook WL, Jassal SV: Geriatric comor-
bidities, such as falls, confer an independent mortality risk to elderly
shown to slow the rate of bone loss.17 There are inadequate
dialysis patients. Nephrol Dial Transplant 23: 1396 –1400, 2008
data to conclude what are their effects on fracture prevention.
3. Ball AM, Gillen DL, Sherrard D, Weiss NS, Emerson SS, Seliger SL,
After a hip fracture, a number of factors have been shown to
Kestenbaum BR, Stehman-Breen C: Risk of hip fracture among dialysis
improve outcome in older persons: surgery within 48 h de-
and renal transplant recipients. JAMA 288: 3014 –3018, 2002*
creases length of hospitalization and possibly mortality; sur-
4. Morley JE: Falls and fractures. J Am Med Dir Assoc 8: 276 –278, 2007*5. Roberts RG, Kenny RA, Brierley EJ: Are elderly hemodialysis patients
gery delay for cardiology clearance may increase mortality; bet-
at risk of falls and postural hypotension? Int Urol Nephrol 35: 415– 421,
ter outcomes are obtained with spinal or epidural anesthesia;
early mobilization enhances rehabilitation outcomes; delirium
6. Sherman RA, Torres F, Cody RP: Postprandial blood pressure changes
reduces functional outcomes and it is reduced by a geriatric
during hemodialysis. Am J Kidney Dis 12: 37–39, 1988*
consult; vitamin D (calcidiol or calcitriol) will improve out-
7. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB,
Bazemore MG, Zee RY, Wong JB: Effect of Vitamin D on falls: a
comes; and the use of bisphosphonates depends on the type of
meta-analysis. JAMA 291: 1999 –2006, 2004
8. Blair D, Byham-Gray L, Lewis E, McCaffrey S: Prevalence of vitamin D
[25(OH)D] deficiency and effects of supplementation with ergocalcif-erol (vitamin D2) in stage 5 chronic kidney disease patients. J Ren Nutr18: 375–382, 2008
9. O’Donnell S, Moher D, Thomas K, Hanley DA, Cranney A: Systematic
review of the benefits and harms of calcitriol and alfacalcidol forfractures and falls. J Bone Miner Metab 26: 531–542, 2008
Falls are extremely common in patients with end-stage renal
10. Cook WL, Tomlinson G, Donaldson M, Markowitz SN, Naglie G,
failure on dialysis. Fall prevention programs that include a
Sobolev B, Jassal SV: Falls and fall-related injuries in older dialysis
medication review, prevention of orthostasis, cardiac pacing
patients. Clin J Am Soc Nephrol 1: 1197–1204, 2006*
11. Angalakuditi MV, Gomes J, Coley KC: Impact of drug use and comor-
where appropriate, home hazard assessment and modifica-
bidities on in-hospital falls in patients with chronic kidney disease. Ann
tions, and muscle strengthening and retraining are effective. In
Pharmacother 41: 1638 –1643, 2007
addition, making sure the 25(OH) vitamin D level is Ͼ30
12. McClure R, Turner C, Peel N, Spinks A, Eakin E, Hughes K: Population-
ng/ml has been found to be effective.
based interventions for the pr3evention of fall-related injuries in older
Treatment of bone disease is complicated because of the
people. Cochrane Data Sys Rev 1: CD004441, 2005
13. Ishani A, Paudel M, Taylor BC, Barrett-Connor E, Jamal S, Canales M,
coexistence of osteoporosis and renal osteodystrophy. In per-
Steffes M, Fink HA, Orwoll E, Cummings SR, Ensrud KE; Osteoporotic
sons without adynamic bone disease, low-dose bisphospho-
Fractures in Men (MrOS) Study Group: Renal function and rate of hip
nates are possibly indicated. There may be a role for testoster-
bone loss in older men: the Osteoporotic Fractures in Men Study.
one in males and raloxifene in females. Osteoporos Int 19: 1549 –1556, 2008*
14. Kaneko TM, Foley RN, Gilbertson DT, Collins AJ: Clinical epidemiol-
ogy of long-bone fractures in patients receiving hemodialysis. ClinOrthopeadics Rel Res 457: 188 –193, 2007
15. Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL,
Mason N, Prutz KG, Young EW, Pisoni RL: Incidence and risk factorsfor hip or other bone fractures among hemodialysis patients in the
• Fall prevention programs should be instituted for all older dialysis
Dialysis Outcomes and Practice Patterns Study. Kidney Int 70: 1358 –
• All older kidney failure patients should have 25(OH) vitamin D levels
16. Miller PD: Is there a role for bisphosphonates in chronic kidney dis-
ease? Semin Dial 20: 186 –190, 2007*
• Bisphosphonates, testosterone in males, and raloxifene in females can
17. Palmer SC, McGregor DO, Strippoli GF: Intervention for preventing
be used to treat bone disease as long as the type of disease is under-
bone disease in kidney transplant recipients. Cochrane Database Syst
REVIEW QUESTIONS: FALLS IN ELDERLY PATIENTS
1. To prevent falls, 25(OH) vitamin D levels should be greater
3. To determine if there is adynamic bone measure
2. Which of the following drugs can be used to treat postprandial
Affinity modulation of small-molecule ligands by borrowing endogenous protein surfaces ROGER BRIESEWITZ*, GREGORY T. RAY†, THOMAS J. WANDLESS†‡, AND GERALD R. CRABTREE*‡*Howard Hughes Medical Institute and †Department of Chemistry, Stanford University, Stanford, CA 94305 Contributed by Gerald R. Crabtree, December 16, 1998 ABSTRACT A general strategy is described for improving
An Automated Method for Levodopa-Induced Dyskinesia Detection and Severity Classification M.G. Tsipouras1, A.T. Tzallas1, G. Rigas1, P. Bougia1, D.I. Fotiadis1 and S. Konitsiotis21Unit of Medical Technology and Intelligent Information Systems,Department of Material Science and Engineering, University of Ioannina, 45110 Ioannina, Greece2 Department of Neurology, Medical School, University