Renal Failure: A Modern Semiology for an Old Disease

Abstract

Chronic kidney disease (CKD) is a complex systemic disease that induces mineral metabolic dysfunction leading to bone fragility and tissue calcifications. Bone abnormalities in CKD can include increased bone turnover and resorption due to secondary hyperparathyroidism, decreased bone turnover and bone formation, defective bone mineralization, or a mixed pattern of these abnormalities. Other features of musculoskeletal involvement include synovial, tendon, and ligament thickening due to β2-microglobulin amyloidosis, soft tissue masses, or axial and peripheral arthropathies. The accurate assessment of bone involvement in early-stage CKD is crucial for the success of therapeutic interventions. We summarize the key semiologic features of bone abnormalities in CKD and review musculoskeletal complications as depicted by conventional radiography, computed tomography, magnetic resonance, and ultrasound imaging. We also discuss different experimental diagnostic approaches developed for the purpose of identifying changes in bone quality and structure in early-stage CKD.

Keywords

chronic kidney disease-mineral and bone disorder - renal failure - bone - magnetic resonance imaging - bone resorption

• References

• 1 Eknoyan G, Lameire N, Barsoum R , et al. The burden of kidney disease: improving global outcomes. Kidney Int 2004; 66 (4) 1310-1314
• 2 Moe S, Drüeke T, Cunningham J , et al. Kidney Disease: Improving Global Outcomes (KDIGO). Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 69 (11) 1945-1953
• 3 Babayev R, Nickolas TL. Bone disorders in chronic kidney disease: an update in diagnosis and management. Semin Dial 2015; 28 (6) 645-653
• 4 Malluche HH, Mawad HW, Monier-Faugere MC. Renal osteodystrophy in the first decade of the new millennium: analysis of 630 bone biopsies in black and white patients. J Bone Miner Res 2011; 26 (6) 1368-1376
• 5 Kim SM, Long J, Montez-Rath M, Leonard M, Chertow GM. Hip fracture in patients with non-dialysis-requiring chronic kidney disease. J Bone Miner Res 2016; 5: 4
• 6 Kazama JJ, Matsuo K, Iwasaki Y, Fukagawa M. Chronic kidney disease and bone metabolism. J Bone Miner Metab 2015; 33 (3) 245-252
• 7 Jamal SA, Nickolas TL. Bone imaging and fracture risk assessment in kidney disease. Curr Osteoporos Rep 2015; 13 (3) 166-172
• 8 Vervloet MG, Massy ZA, Brandenburg VM , et al; CKD-MBD Working Group of ERA-EDTA. Bone: a new endocrine organ at the heart of chronic kidney disease and mineral and bone disorders. Lancet Diabetes Endocrinol 2014; 2 (5) 427-436
• 9 Bricker NS. On the pathogenesis of the uremic state. An exposition of the “trade-off hypothesis”. N Engl J Med 1972; 286 (20) 1093-1099
• 10 Bauer W, Albright F, Aub JC. A case of osteitis fibrosa cystica (osteomalacia?) with evidence of hyperactivity of the parathyroid bodies. Metabolic Study II. J Clin Invest 1930; 8 (2) 229-248
• 11 Massry SG, Bluestone R, Klinenberg JR, Coburn JW. Abnormalities of the musculoskeletal system in hemodialysis patients. Semin Arthritis Rheum 1975; 4 (4) 321-349
• 12 Murphey MD, Sartoris DJ, Quale JL, Pathria MN, Martin NL. Musculoskeletal manifestations of chronic renal insufficiency. Radiographics 1993; 13 (2) 357-379
• 13 Jensen PS, Kliger AS. Early radiographic manifestations of secondary hyperparathyroidism associated with chronic renal disease. Radiology 1977; 125 (3) 645-652
• 14 Lim CY, Ong KO. Various musculoskeletal manifestations of chronic renal insufficiency. Clin Radiol 2013; 68 (7) e397-e411
• 15 Rousselin B, Helenon O, Zingraff J , et al. Pseudotumor of the craniocervical junction during long-term hemodialysis. Arthritis Rheum 1990; 33 (10) 1567-1573
• 16 Sundaram M, Joyce PF, Shields JB, Riaz MA, Sagar S. Terminal phalangeal tufts: earliest site of renal osteodystrophy findings in hemodialysis patients. AJR Am J Roentgenol 1979; 133 (1) 25-29
• 17 Moe SM, Drüeke T, Lameire N, Eknoyan G. Chronic kidney disease-mineral-bone disorder: a new paradigm. Adv Chronic Kidney Dis 2007; 14 (1) 3-12
• 18 Resnick D, Deftos LJ, Parthemore JG. Renal osteodystrophy: magnification radiography of target sites of absorption. AJR Am J Roentgenol 1981; 136 (4) 711-714
• 19 Jevtic V. Imaging of renal osteodystrophy. Eur J Radiol 2003; 46 (2) 85-95
• 20 Wittenberg A. The rugger jersey spine sign. Radiology 2004; 230 (2) 491-492
• 21 Griffiths HJ, Ennis JT, Bailey G. Skeletal changes following renal transplantation. Radiology 1974; 113 (3) 621-626
• 22 Katz AI, Hampers CL, Merrill JP. Secondary hyperparathyroidism and renal osteodystrophy in chronic renal failure. Analysis of 195 patients, with observations on the effects of chronic dialysis, kidney transplantation and subtotal parathyroidectomy. Medicine (Baltimore) 1969; 48 (5) 333-374
• 23 Meema HE, Oreopoulos DG, Murray TM. Periosteal resorption and periosteal neostosis: comparison of normal subjects and renal failure patients on chronic ambulatory peritoneal dialysis using MOP-3 image analysis system and a grading method. Skeletal Radiol 1986; 15 (1) 14-20
• 24 Parnell AP, Simpson W, Ward MK. Periosteal new bone formation in chronic renal failure. Clin Radiol 1989; 40 (5) 490-493
• 25 Ritchie WG, Winney RJ, Davison AM, Robson JS. Periosteal new bone formation developing during haemodialysis for chronic renal failure. Br J Radiol 1975; 48 (572) 656-661
• 26 Resnick D. Parathyroid disorders and renal osteodystrophy. In: Resnick D, , et al., eds. Diagnosis of Bone and Joint Disorders. 4th ed. Philadelphia, PA: Saunders; 2002: 2043-2111
• 27 Goldman AB, Lane JM, Salvati E. Slipped capital femoral epiphyses complicating renal osteodystrophy: a report of three cases. Radiology 1978; 126 (2) 333-339
• 28 Fusaro M, Noale M, Viola V , et al; VItamin K Italian (VIKI) Dialysis Study Investigators. Vitamin K, vertebral fractures, vascular calcifications, and mortality: Vitamin K Italian (VIKI) dialysis study. J Bone Miner Res 2012; 27 (11) 2271-2278
• 29 Hercz G, Pei Y, Greenwood C , et al. Aplastic osteodystrophy without aluminum: the role of “suppressed” parathyroid function. Kidney Int 1993; 44 (4) 860-866
• 30 Kriegshauser JS, Swee RG, McCarthy JT, Hauser MF. Aluminum toxicity in patients undergoing dialysis: radiographic findings and prediction of bone biopsy results. Radiology 1987; 164 (2) 399-403
• 31 Sundaram M, Dessner D, Ballal S. Solitary, spontaneous cervical and large bone fractures in aluminum osteodystrophy. Skeletal Radiol 1991; 20 (2) 91-94
• 32 Drüeke TB, Massy ZA. Changing bone patterns with progression of chronic kidney disease. Kidney Int 2016; 89 (2) 289-302
• 33 Barreto FC, Barreto DV, Canziani ME , et al. Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients. J Bras Neurol 2014; 36 (3) 289-296
• 34 Coen G, Mazzaferro S, Ballanti P , et al. Renal bone disease in 76 patients with varying degrees of predialysis chronic renal failure: a cross-sectional study. Nephrol Dial Transplant 1996; 11 (5) 813-819
• 35 Fang Y, Ginsberg C, Seifert M , et al. CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol 2014; 25 (8) 1760-1773
• 36 D'Haese PC, Couttenye MM, De Broe ME. Diagnosis and treatment of aluminium bone disease. Nephrol Dial Transplant 1996; 11 (Suppl. 03) 74-79
• 37 Andreoli SP, Bergstein JM, Sherrard DJ. Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 1984; 310 (17) 1079-1084
• 38 Solal ME, Sebert JL, Boudailliez B , et al. Comparison of intact, midregion, and carboxy terminal assays of parathyroid hormone for the diagnosis of bone disease in hemodialyzed patients. J Clin Endocrinol Metab 1991; 73 (3) 516-524
• 39 Van de Vyver FL, Visser WJ, D'Haese PC, De Broe ME. Iron overload and bone disease in chronic dialysis patients. Nephrol Dial Transplant 1990; 5 (9) 781-787
• 40 Bucur RC, Panjwani DD, Turner L, Rader T, West SL, Jamal SA. Low bone mineral density and fractures in stages 3-5 CKD: an updated systematic review and meta-analysis. Osteoporos Int 2015; 26 (2) 449-458
• 41 Ensrud KE, Lui LY, Taylor BC , et al; Osteoporotic Fractures Research Group. Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med 2007; 167 (2) 133-139
• 42 Alem AM, Sherrard DJ, Gillen DL , et al. Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int 2000; 58 (1) 396-399
• 43 Dukas L, Schacht E, Stähelin HB. In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures. Osteoporos Int 2005; 16 (12) 1683-1690
• 44 Guglielmi G, Haslam J, DʼErrico F, Steiger P, Nasuto M. Comprehensive vertebral deformity and vertebral fracture assessment in clinical practice: intra- and inter-reader agreement of a clinical workflow tool. Spine 2013; 38 (26) 1676-1683
• 45 Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009; 113 (113) S1-S130
• 46 Jamal SA, Hayden JA, Beyene J. Low bone mineral density and fractures in long-term hemodialysis patients: a meta-analysis. Am J Kidney Dis 2007; 49 (5) 674-681
• 47 Yenchek RH, Ix JH, Shlipak MG , et al. Health, Aging, and Body Composition Study. Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol 2012; 7 (7) 1130-1136
• 48 Iimori S, Mori Y, Akita W , et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—a single-center cohort study. Nephrol Dial Transplant 2012; 27 (1) 345-351
• 49 Jamal SA, Swan VJ, Brown JP , et al. Canadian Multicentre Osteoporosis Study Research Group. Kidney function and rate of bone loss at the hip and spine: the Canadian Multicentre Osteoporosis Study. Am J Kidney Dis 2010; 55 (2) 291-299
• 50 Ketteler M, Elder GJ, Evenepoel P , et al. Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int 2015; 87 (3) 502-528
• 51 Malluche HH, Davenport DL, Cantor T, Monier-Faugere MC. Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 2014; 9 (7) 1254-1262
• 52 West SL, Lok CE, Langsetmo L , et al. Bone mineral density predicts fractures in chronic kidney disease. J Bone Miner Res 2015; 30 (5) 913-919
• 53 Drüeke TB. Foreword: extraskeletal calcifications in patients with chronic renal failure. Nephrol Dial Transplant 2002; 17 (2) 330-331
• 54 Setiawati R, Di Chio F, Rahardjo P, Nasuto M, Dimpudus FJ, Guglielmi G. Quantitative assessment of abdominal aortic calcifications using lateral lumbar radiograph, dual-energy X-ray absorptiometry, and quantitative computed tomography of the spine. J Clin Densitom 2016; 19 (2) 242-249
• 55 Gipstein RM, Coburn JW, Adams DA , et al. Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure. Arch Intern Med 1976; 136 (11) 1273-1280
• 56 McGregor D, Burn J, Lynn K, Robson R. Rapid resolution of tumoral calcinosis after renal transplantation. Clin Nephrol 1999; 51 (1) 54-58
• 57 McKee PH, Liomba NG, Hutt MS. Tumoral calcinosis: a pathological study of fifty-six cases. Br J Dermatol 1982; 107 (6) 669-674
• 58 Durant DM, Riley III LH, Burger PC, McCarthy EF. Tumoral calcinosis of the spine: a study of 21 cases. Spine 2001; 26 (15) 1673-1679
• 59 Kokubun S, Ozawa H, Sakurai M, Tanaka Y. Tumoral calcinosis in the upper cervical spine: a case report. Spine 1996; 21 (2) 249-252
• 60 Matsukado K, Amano T, Itou O, Yuhi F, Nagata S. Tumoral calcinosis in the upper cervical spine causing progressive radiculomyelopathy—case report. Neurol Med Chir (Tokyo) 2001; 41 (8) 411-414
• 61 Chang CC, Sung CC, Hsia CC, Lin SH. Uremic tumoral calcinosis causing atlantoaxial subluxation and spinal cord compression in a patient on continuous ambulatory peritoneal dialysis. Int Urol Nephrol 2013; 45 (5) 1511-1516
• 62 Cofan F, García S, Combalia A, Campistol JM, Oppenheimer F, Ramón R. Uremic tumoral calcinosis in patients receiving longterm hemodialysis therapy. J Rheumatol 1999; 26 (2) 379-385
• 63 Hamada J, Tamai K, Ono W, Saotome K. Uremic tumoral calcinosis in hemodialysis patients: clinicopathological findings and identification of calcific deposits. J Rheumatol 2006; 33 (1) 119-126
• 64 Baek D, Lee SE, Kim WJ , et al. Greater trochanteric pain syndrome due to tumoral calcinosis in a patient with chronic kidney disease. Pain Physician 2014; 17 (6) E775-E782
• 65 Christidou F, Bamichas G, Stangou M, Natse T, Kalpakidis V, Sombolos K. Tumoral calcinosis inducing systemic inflammatory response in a hemodialysis patient. Nephron 2002; 92 (2) 497-498
• 66 García S, Cofán F, Fernández RP, Sala P, Oppenheimer F. Uremic tumoral calcinosis of the foot mimicking infection. Foot Ankle Int 2002; 23 (3) 260-263
• 67 Cribier B, Grosshans E. Cutaneous calcinosis [in French]. Ann Dermatol Venereol 1992; 119 (2) 151-168
• 68 Ben Taarit C, el Younsi F, Turki S, Mestiri M, Zlitni M, Ben Maïz H. La calcinose tumorale des hémodialysés: étude anatomoclinique: à propos de trois cas. Nephrologie 2001; 22 (7) 349-352
• 69 Hodnett P, Moore M, Kinsella S, Kelly D, Plant WD, Maher MM. Radiological features of progressive tumoral calcinosis in chronic renal failure. Australas Radiol 2007; 51 (Spec No): B115-B118
• 70 Remy-Leroux V, Reguiaï Z, Labrousse AL, Zakine EM, Clavel P, Bernard P. Tumorous calcinosis in hemodialysis: anatomo-clinical study apropos of 3 cases [in French]. Ann Dermatol Venereol 2009; 136 (4) 350-354
• 71 Meltzer CC, Fishman EK, Scott Jr WW. Tumoral calcinosis causing bone erosion in a renal dialysis patient. Clin Imaging 1992; 16 (1) 49-51
• 72 Kuzela DC, Huffer WE, Conger JD, Winter SD, Hammond WS. Soft tissue calcification in chronic dialysis patients. Am J Pathol 1977; 86 (2) 403-424
• 73 Fukuda K, Yamamoto H. Dialysis-related amyloidosis. Semin Musculoskelet Radiol 2001; 5 (2) 113-119
• 74 Masakane I, Nakai S, Ogata S , et al. An overview of regular dialysis treatment in Japan (as of 31 December 2013). Ther Apher Dial 2015; 19 (6) 540-574
• 75 Kiss E, Keusch G, Zanetti M , et al. Dialysis-related amyloidosis revisited. AJR Am J Roentgenol 2005; 185 (6) 1460-1467
• 76 Danesh F, Ho LT. Dialysis-related amyloidosis: history and clinical manifestations. Semin Dial 2001; 14 (2) 80-85
• 77 Blanco P, Viallard JF, Bonotto B, Buy E, Pellegrin JL, Leng B. Joint involvement in AL amyloidosis [in French]. Ann Med Interne (Paris) 1999; 150 (4) 287-293
• 78 Lanteri M, Ptasznik R, Constable L, Dawborn JK. Ultrasound changes in the wrist and hand in hemodialysis patients. Clin Nephrol 1997; 48 (6) 375-380
• 79 Takahashi T, Kato A, Ikegaya N , et al. Ultrasound changes of the carpal tunnel in patients receiving long-term hemodialysis: a cross-sectional and longitudinal study. Clin Nephrol 2002; 57 (3) 230-236
• 80 Cardinal E, Buckwalter KA, Braunstein EM, Raymond-Tremblay D, Benson MD. Amyloidosis of the shoulder in patients on chronic hemodialysis: sonographic findings. AJR Am J Roentgenol 1996; 166 (1) 153-156
• 81 Jadoul M, Malghem J, vande Berg B, van Ypersele de Strihou C. Ultrasonography of joint capsules and tendons in dialysis-related amyloidosis. Kidney Int Suppl 1993; 41: S106-S110
• 82 Nessi R, Anelli A, Brancaccio D, Raiteri R, Chiara Bossi M, Uslenghi C. Use of echography for the diagnosis of joint amyloidosis in dialyzed patients [in French]. J Radiol 1991; 72 (1) 17-22
• 83 Sommer R, Valen GJ, Ori Y , et al. Sonographic features of dialysis-related amyloidosis of the shoulder. J Ultrasound Med 2000; 19 (11) 765-770
• 84 Decourt A, Gondouin B, Delaroziere JC , et al. Trends in survival and renal recovery in patients with multiple myeloma or light-chain amyloidosis on chronic dialysis. Clin J Am Soc Nephrol 2016; 11 (3) 431-441
• 85 Ross LV, Ross GJ, Mesgarzadeh M, Edmonds PR, Bonakdarpour A. Hemodialysis-related amyloidomas of bone. Radiology 1991; 178 (1) 263-265
• 86 Theodorou DJ, Theodorou SJ, Resnick D. Imaging in dialysis spondyloarthropathy. Semin Dial 2002; 15 (4) 290-296
• 87 Escobedo EM, Hunter JC, Zink-Brody GC, Andress DL. Magnetic resonance imaging of dialysis-related amyloidosis of the shoulder and hip. Skeletal Radiol 1996; 25 (1) 41-48
• 88 Kuntz D, Naveau B, Bardin T, Drueke T, Treves R, Dryll A. Destructive spondylarthropathy in hemodialyzed patients. A new syndrome. Arthritis Rheum 1984; 27 (4) 369-375
• 89 Cotten A, Flipo RM, Boutry N , et al. Natural course of erosive arthropathy of the hand in patients undergoing hemodialysis. Skeletal Radiol 1997; 26 (1) 20-26
• 90 M'Bappé P, Grateau G. Manifestations ostéoarticulaires de l'amylose. EMC – Appareil locomoteur 2015; 10 (2) 1-9
• 91 Javier RM, Moulin B. Complications ostéoarticulaires des hémodialysés (hors ostéodystrophie rénale). EMC – Appareil locomoteur 2009; 4 (4) 1-11
• 92 Shiota E, Tsuchiya K, Yamaoka K, Kawano O. Spontaneous major tendon ruptures in patients receiving long-term hemodialysis. Clin Orthop Relat Res 2002; (394) 236-242
• 93 Moorthi RN, Moe SM. Recent advances in the noninvasive diagnosis of renal osteodystrophy. Kidney Int 2013; 84 (5) 886-894
• 94 Schellinger D, Lin CS, Lim J, Hatipoglu HG, Pezzullo JC, Singer AJ. Bone marrow fat and bone mineral density on proton MR spectroscopy and dual-energy X-ray absorptiometry: their ratio as a new indicator of bone weakening. AJR Am J Roentgenol 2004; 183 (6) 1761-1765
• 95 Pansini V, Monnet A, Salleron J, Hardouin P, Cortet B, Cotten A. 3.  Tesla (1) H MR spectroscopy of hip bone marrow in a healthy population, assessment of normal fat content values and influence of age and sex. J Magn Reson Imaging 2014; 39 (2) 369-376
• 96 Hu HH, Kan HE. Quantitative proton MR techniques for measuring fat. NMR Biomed 2013; 26 (12) 1609-1629
• 97 Bley TA, Wieben O, François CJ, Brittain JH, Reeder SB. Fat and water magnetic resonance imaging. J Magn Reson Imaging 2010; 31 (1) 4-18
• 98 Moorthi RN, Fadel W, Eckert GJ, Ponsler-Sipes K, Moe SM, Lin C. Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy. Osteoporos Int 2015; 26 (6) 1801-1807
• 99 Leonard MB. A structural approach to skeletal fragility in chronic kidney disease. Semin Nephrol 2009; 29 (2) 133-143
• 100 Nickolas TL, Stein E, Cohen A , et al. Bone mass and microarchitecture in CKD patients with fracture. J Am Soc Nephrol 2010; 21 (8) 1371-1380
• 101 Trombetti A, Stoermann C, Chevalley T , et al. Alterations of bone microstructure and strength in end-stage renal failure. Osteoporos Int 2013; 24 (5) 1721-1732
• 102 Link TM, , Saborowski, Kisters K. , et al. Changes in calcaneal trabecular bone structure assessed with high-resolution MR imaging in patients with kidney transplantation. Osteoporos Int 2002; 13 (2) 119-129
• 103 Wehrli FW, Leonard MB, Saha PK, Gomberg BR. Quantitative high-resolution magnetic resonance imaging reveals structural implications of renal osteodystrophy on trabecular and cortical bone. J Magn Reson Imaging 2004; 20 (1) 83-89
• 104 Jamal S, Cheung AM, West S, Lok C. Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease. Osteoporos Int 2012; 23 (12) 2805-2813