This document summarizes rheumatological aspects of musculoskeletal disorders in hemodialysis patients. It discusses disorders related to dialysis such as dialysis-related amyloidosis, as well as non-crystalline disorders like tendonitis and uremic myopathy. Crystalline disorders covered include gout, pseudogout, and disorders associated with calcium crystals. Specific clinical manifestations are described for many of these conditions. Treatment focuses on optimizing dialysis and medication management. Musculoskeletal ultrasound is highlighted as a useful diagnostic tool. The conclusion discusses a study assessing quality of life and musculoskeletal discomfort in Egyptian hemodialysis patients using validated questionnaires.

1. RheumatologicalAspects in Hemodialysis Patients
Samar Tharwat Radwan
 Lecturer of Internal Medicine
 (Rheumatology & Immunology )
 Musculoskeletal Ultrasound –EULAR
 Mansoura University

2. Introduction
 Two million people suffer from ESRD worldwide
 The number continues to increase at a rate of 5-7% per year.
 Transplantation and dialysis are the main treatment options
 Hemodialysis is the most common type of dialysis (90%)
 Life expectancy improved with the improvement of this modality.
 Musculoskeletal disorders become a major problem in long term hemodialysis patients.
https://pharm.ucsf.edu/kidney/need/statistics

3. 2018

4. What are the
Musculoskeletal
Disorders among
these Patients?

5. Musculoskeletal
Disorders
among HD
patients
• Dialysis related amyloidosis
Related to
Dialysis
• Non-crystalline–associated
disorders
• Crystalline-associated
disorders
Related to
chronic
renal
failure

6. Dialysis Related
Amyloidosis
Tissue deposition of beta2-
microglobulin (beta2-m) amyloid
Kaneko, S., & Yamagata, K. (2018, November). Hemodialysis‐related amyloidosis: Is it still relevant?. In Seminars in dialysis

7. DialysisRelated
Amyloidosis
Pathogenesis
•bioincompatible membranes
•dialysate contaminated with
endotoxin
Production
Clearance

8. Dialysis
Related
Amyloidosis
Risk Factors
increasing age and dialysis duration
low-flux dialysis membranes
lack of residual renal function
Gejyo, F., & Narita, I. (2003). Current clinical and pathogenetic understanding of β2‐m amyloidosis in long‐term haemodialysis patients. Nephrology

9. DialysisRelated
Amyloidosis
Clinical Manifestations
Scarpioni, R., Ricardi, M., Albertazzi, V., De Amicis, S., Rastelli, F., & Zerbini, L. (2016). Dialysis-related amyloidosis: challenges and solutions. International journal of nephrology and renovascular disease,
Shoulder pain
Shoulder pad sign Glenohumeral
joint amyloidosis
Humeral head
erosion
Totally destroyed
humeral head
Rotator cuff tear

10. Synovial
proliferation
at the
shoulder
joint
Samar Tharwat

11. DialysisRelated
Amyloidosis
Clinical Manifestations
CarpalTunnelSyndrome
• Numbness and dysesthesias in the distribution of the median nerve
• More commonly on the side of the longest-functioning vascular access
• Worsen during dialysis session
• Weakness and atrophy of the muscles of the thenar eminence.
Park, H., Lee, D. S., Yun, T. K., & Ahn, D. S. (2015). Carpal Tunnel Syndrome in Patients Undergoing Long-Term Hemodialysis Therapy: Clinical Characteristics and Results of Surgical Treatment. Journal of the Korean Society for Surgery of the Hand

12. DialysisRelated
Amyloidosis
Clinical Manifestations
Flexor tendons • Amyloid deposition along flexor tendons.
• Irreducible flexion contractures of the fingers
“Guitar string" sign Amyloid hand
CLEVELAND, B. (1999). Beta2^ microglobulin amyloidosis in renal failure: Understanding this recently recognized condition. Cleveland Clinic journal of medicine.

13. DialysisRelated
Amyloidosis
Clinical Manifestations
Neck Pain
Endplate
irregularities
Multiple erosions
at the vertebra
Vertebral
destruction
Lee, G. K., Kang, I. W., Min, S. J., Cho, S. W., Kim, S. W., Jang, W. Y., ... & Suh, K. J. (2006). A case of dialysis-related amyloidosis of the hip and cervical spine: imaging findings. Journal of the Korean Radiological Society
Destructive spondyloarthropathy
DD: infectious diskitis.

14. DialysisRelated
Amyloidosis
Clinical Manifestations
Epidural deposition
Epidural deposition of beta2-m amyloid may compress the
spinal cord, causing quadriparesis or quadriplegia
Vignes, J. R., Eimer, S., Dupuy, R., Donois, E., & Liguoro, D. (2007). β 2-Microglobulin amyloidosis caused spinal cord compression in a long-term haemodialysis patient. Spinal Cord, 45(4), 322.

15. DialysisRelated
Amyloidosis
Clinical Manifestations
Bone cysts
Carpal bones Patella Femoral neck
Nishi, S., Yamamoto, S., Hoshino, J., Takaichi, K., & Naiki, H. (2019). The features of bone articular lesions in dialysis-related amyloidosis (DRA) and criteria for the clinical diagnosis of DRA. Renal Replacement Therapy
• Rapid rate of enlargement
• Pathologic fractures, particularly of the femoral neck

16. DialysisRelated
Amyloidosis
Clinical Manifestations
Subcutaneous nodules
Gargallo, V., Angulo, L., Hernández, E., Peralto, J. L., & Zarco, C. (2015). Massive Subcutaneous Masses on the Back Related to β2-Microglobulin Amyloidosis. JAMA dermatology,

17. DialysisRelatedAmyloidosis:Diagnosis
Ultrasonography may be of use
Increased rotator cuff
thickness
Thickened synovial
sheath of the long
head of the biceps
Thickened median
nerve
Thickened median
nerve
Samar Tharwat

18. DialysisRelatedAmyloidosis:Diagnosis
Biopsy remains the "gold standard"
Acellular glassy pink
amorphous material
Congo red stain
showing apple-green
birefringence
Positive immunohistochemistry
stain confirming β2-
microglobulin amyloidosis
Mendoza, P. D., Fenves, A. Z., Punar, M., & Stone, M. J. (2010, April). Subcutaneous β2-Microglobulin Amyloid Shoulder Nodules in a Long-Term Hemodialysis Patient. In Baylor University Medical Center Proceedings

19. Dialysis-related
Amyloidosis (DRA):
Treatment
Hemodialysis
• biocompatible membranes
• high-flux membranes
• ??super-flux membranes
• increase the dialysis duration
• Increase frequency
• nocturnal or short daily hemodialysis
Peritoneal
dialysis
• insufficient data
Other therapies
• beta2-m column
• doxycycline 100 mg daily
Surgery &
analgesics
• Shoulder
Carpal tunnel surgery
Curettage and bone grafting of amyloid cysts
Joint replacement

20. Dialysis-relatedAmyloidosis (DRA):Treatment
RenalTransplantation is the definite treatment
Scarpioni, R., Ricardi, M., Albertazzi, V., De Amicis, S., Rastelli, F., & Zerbini, L. (2016). Dialysis-related amyloidosis: challenges and solutions. International journal of nephrology and renovascular disease

21. Musculoskeletal
Disorders
among HD
patients
• Dialysis related amyloidosis
Related to
Dialysis
• Non-crystalline–associated
disorders
• Crystalline-associated
disorders
Related to
chronic
renal
failure

22. Non-crystalline–associated disorders
Tendon disorder Olecranon bursitis Uremic myopathy
Nephrogenic
systemic fibrosis
Infection
Hemodialysis
related Aluminium
toxicity
Renal
osteodystrophy
Osteomalacia

23. Tendonitis
TTT:
• analgesic
• immobilization
• physical therapy
Soyupek, F., Demir, M., Süslü, F. E., Baykal, B., Sezer, M. T., & Yesildag, A. (2013). The upper extremity musculoskeletal complications in dialysis patients: comparison between hemodialysisand peritoneal dialysis. Journal of back and musculoskeletal rehabilitation
Due to:
•2ry hyperparathyroidism
•use of fluoroquinolones
•calcium deposition

24. Tenosynovitis:
synovial
hypertrophyor
anechoicfluid
withinthetendon
sheath(13%ofHD
patients)
SamarTharwat

25. Spontaneous
tendon rupture
Aetiology
 Hyperparathyroidism
 Chronic acidosis
 Uremic toxin
 Malnutrition
 B2-amyloidosis
Diagnosis
 Ultrasonography
 MRI
Moerenhout, Kevin, et al. "Simultaneous Ipsilateral Quadriceps and Triceps Tendon Rupture in a Patient with End-Stage Renal Failure." Case reports in orthopedics 2018 (2018).

26. Olecranon bursitis
Dialysis elbow/ Uremic bursitis
 3.3 episodes per 100 person-year
 long-term hemodialysis
 at the same side of AVF
 repeated friction during HD practice

27. Uremic myopathy
• Weakness ,aching of muscles, especially the shoulder or pelvic
girdles (e.g., climbing or descending stairs, cleaning windows, and
reaching for objects on a high shelf)
• 50% of HD patients.
• Multifactorial:Vitamin D deficiency, hyperparathyroidism
• Must be differentiated from uremic neuropathy by NCS
• TTT: adequate dialysis,Vit D , ttt of hyperparathyroidism
Sarraf, P., Kay, J., & Reginato, A. M. (2008). Non-crystalline and crystalline rheumatic disorders in chronic kidney disease. Current rheumatology reports.

28. Nephrogenic systemic fibrosis
Dialysis associated systemic fibrosis.
 gadolinium-containing agents (recent or remote)
 thickening of the skin
 May affect deeper structures: muscle ,fascia , lung
&heart
TTT:
 prophylactic
 extracorporeal photopheresis
 ultraviolet a phototherapy
 plasmapheresis
 kidney transplantation

29. Nephrogenic systemic fibrosis
Endrikat, J., Dohanish, S., Schleyer, N., Schwenke, S., Agarwal, S., & Balzer, T. (2018). 10 Years of Nephrogenic Systemic Fibrosis: A Comprehensive Analysis of Nephrogenic Systemic Fibrosis Reports Received by a Pharmaceutical Company from 2006 to 2016. Investigative radiology

30. Infection
Septic arthritis
Septic tenosynovitis
Osteomyelitis

31. Septic arthritis
 Staphylococcus aureus
Diagnosis is challenging
 synovial fluidWBCs: not reliable
 crystal-induced can coexist
 ESR& CRP may be elevated without infection
 Difinite diagnosis: synovial fluid culture & polarized light microscopy
McGillicuddy, D. C., Shah, K. H., Friedberg, R. P., Nathanson, L. A., & Edlow, J. A. (2007). How sensitive is the synovial fluid white blood cell count in diagnosing septic arthritis?. The American journal of emergency medicine
SamarTharwat

32. Septic tenosynovitis

33. Osteomyelitis
 A high index of suspicion is appropriate
Dudareva, M., Ferguson, J., Riley, N., Stubbs, D., Atkins, B., & McNally, M. (2017). Osteomyelitis of the pelvic bones: a multidisciplinary approach to treatment. Journal of bone and joint infection

34. Hemodialysis related Aluminum toxicity
Due to:
• exposure to aluminum in dialysis fluid
• aluminum-containing phosphate binders
C/P:
• bone and muscle pain, fracture, proximal muscle
weakness, osteomalacia
Diagnosis
• serum aluminum concentrations
• deferoxamine stimulation test
• bone biopsy
Cannata‐Andía, Jorge B., and Jose L. Fernández‐Martín. "The clinical impact of aluminium overload in renal failure." Nephrology Dialysis Transplantation 17.suppl_2 (2002): 9-12.
Treatment
• Removal of all sources of aluminum
• Intensive (six days per week) dialysis with high-
flux dialysis
• Deferoxamine

35. Hemodialysis
related
Aluminum
toxicity
Now uncommon(KDOQI)
guidelines for aluminum
testing
 annually in all HD patients
 / 3ms in patients on aluminum-
containing medications

36. RenalOsteodystrophy

37. Renal
Osteodystrophy
Subperiosteal lace-like
irregular resorption
Granular salt-and-pepper
appearance
Bilateral sacroiliac joint
widening due to
subchondral resorption
well-demarcated lucent
lesion
(brown tumour)
“rugger-jersey
spine”
Lim, C. Y., & Ong, K. O. (2013). Various musculoskeletal manifestations of chronic renal insufficiency. Clinical radiology, 68(7), e397-e411.

38. Osteomalacia
Bonemineralizationabnormality
Duetodeficiencyinconversionof
vitaminDintoitsactiveform
Looser’s zone or pseudofracture

39. Musculoskeletal
Disorders
among HD
patients
• Dialysis related amyloidosis
Related to
Dialysis
• Non-crystalline–associated
disorders
• Crystalline-associated
disorders
Related to
chronic
renal
failure

40. Crystalline-associated disorders
Gout Pseudogout
Arthropathy
associated with
carbonate apatite
crystals
Calcium oxalate

41. Gout
 Hyperuricemia.
 Small joints as the first metatarsophalangeal
 Hyperparathyroidism enhances urate
absorption Hyperuricemia
 However, hyperuricemia is attenuated by urate
removal, especially with high-flux hemodialysis.
GoutyTophi at first MTP joint

42. Pseudogout
 Calcium Pyrophosphate Dihydrate
crystals
 large or medium-sized joints
knees,wrists, hips, and shoulders,
metacarpophalangeal joints..
 Accelerated spinal osteoarthritis
 43% among HD patients
Due to:
 hypercalcemia
 hyperphosphatemia
 vitamin D deficiency
 hyperparathyroidism
 iron overload

43. Pseudogout:MusculoskeletalUltrasound

44. Arthropathy associated with
hydroxy apatite crystals
• HA extraskeletal calcification
late-stage CKD
• may deposit in the small joints of
the hands, wrists, elbows , hips,
and ankles
• shoulders are the joints most
commonly affected.
Schoppet, M., Shroff, R. C., Hofbauer, L. C., & Shanahan, C. M. (2008). Exploring the biology of vascular calcification in chronic kidney disease: what's circulating?. Kidney international

45. CalcificTendinosis of Rotator cuff
Samar Tharwat

46. Calcification at
the achilles
tendon
Samar Tharwat

47. Calcium oxalate
• Due to:
Inefficient removal of oxalate by hemodialysis
Vitamin C
• Deposits of oxalate crystals have been in synovium,
tendon sheaths, articular cartilage, and bone
• Polyarticular pain
• Polarizing light microscopy
• Positive alizarin red S staining of CaOX

48. Treatment ofCrystal-InducedArthropathies
 Infection must be excluded
 Synovial fluid crystals by polarizing light microscopy
The mainstay of therapy
• NSAIDs
• Colchicine :not dialyzable, granulocytopenia, reversible neuropathy,
myopathy...low-dose regimen (0.15–0.3 mg) or an alternate day dosing
regimen (0.3–0.6 mg)
• Corticosteroids
• Adrenocorticotropic hormone (ACTH)
• Hydroxychloroquine

50. Patients &Methods
Thestudywascarriedouton200patientswithchronicrenalfailureonchronicHDat
differentnephrologyunitsinEgypt.TheycompletedtheArabicversionofthe
KidneyDiseaseandQualityofLife-ShortForm(KDQOL-SFTM1.3)Questionnaire
andansweredthequestionsofMSKdiscomfortformbasedontheNordic
MusculoskeletalQuestionnaire.
Results
Ofthe200HDpatients,180patients(90%)hadmusculoskeletalmanifestations.
Themostcommonlyaffectedpartwaskneejointpain(51.5%).
patientswithMSKsymptomshadsignificantlylowerscoresthandidpatients
withoutonthephysicalrole(p꞊0.035),paindomain(p꞊0.003),generalhealth
(p꞊0.017),qualityofsocialinteraction(p꞊0.046)andsleepdomain(p꞊0.022).

52. Hemodialysis patients have a
heavy Muskuloskeletal symptom
burden