Chronic renal failure presenting as

musculoskeletal pain in a young adult

Alastair A A Browne, Gary J Browne and Ian Barrett

Sydney, Australia

Author Affiliations: Children's Hospital Institute of Sports Medicine & Academic Emergency Medicine, the Children's Hospital at Westmead (Browne AAA and Browne GJ); Northern Clinical School, University of Sydney, Faculty of Medicine (Browne AAA); Department of Orthopedic Surgery, the Children's Hospital at Westmead (Barrett I), Australia

Corresponding Author: Gary J Browne, MD, Associate Professor, the University of Sydney; the Children's Hospital at Westmead Clinical School, Children's Hospital Institute of Sports Medicine and Department of Emergency Medicine; Visiting Fellow in Sports Medicine & Associate Professor, the University of New South Wales; Head of Academic Emergency Medicine, the Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia (Tel: 61-2-98453055; Fax: 61-2-98453082; Email: garyb@chw.edu.au)

We describe a case of renal osteodystrophy presenting as an unresolved musculoskeletal injury. The injury from playing soccer had been treated unsuccessfully with conservative rehabilitation. Although the patient presented in a subtle way, his persistent symptoms high-lighted the need to search for other systemic problems. Once evident that he had a complex agglomeration of skeletal and radiologic abnormalities a diagnosis of chronic renal failure was made. The patient was subjected to immediate evaluation by a specialist in this hospital. Earlier diagnosis of children with renal osteodystrophy will result in more timely management of the associated metabolic and bony complications of this condition.

Key words: sports; musculoskeletal pain; renal osteodystrophy; children

World J Pediatr 2006;1:67-71

Introduction

The presentation of young people with chronic renal failure (CRF) can be subtle and often involves the musculoskeletal system. In children, congenital or genetic disorders are frequently recognised as being the underlying cause.[1,2] Any young person who is constitutionally unwell (unexplained lethargy or exercise intolerance) as well as presenting with multiple musculoskeletal problems should be urgently screened for underlying renal disease.[3]

We report a case of renal osteodystrophy presenting as an unresolved musculoskeletal injury. The injury occurred as the result of playing soccer and was initially managed unsuccessfully with conservative rehabilitation. Although the patient presented in a subtle way his persistent symptoms should have highlighted the need to search for other systemic problems. Once evident that he had a complex agglomeration of skeletal and radiologic abnormalities, a diagnosis of chronic renal failure was entertained. This patient then required immediate evaluation by a specialist in a specialist hospital.

Earlier diagnosis of children with renal osteo-dystrophy will result in more timely management of the associated metabolic and bony complications of this condition.[2,4] Although renal osteodystrophy is relatively rare in children and adolescents, with the increase in primary renal disease throughout the world, physicians must be aware of this possibility. Many of these patients will eventually undergo renal transplantation.

Case report

A 15-year-old elite high school soccer player developed severe pain in his right knee after a miss-kick during a club soccer game. He had immediate pain in the right knee although he had not fallen directly onto the knee or twisted the knee during the injury. There was no swelling or popping sensation noted at the time of injury. Examination by the family physician was unremarkable and revealed a stable knee joint. A diagnosis of simple sprain was made and the physician prescribed RICE (Rest, Ice, Compression and Elevation) together with a simple rehabilitation program which included graded exercises to strengthen the knee. Over the next few weeks he persisted with the program although stopping at regular intervals due to aggravation of the injury. An orthopedic follow-up was organized, however this appointment was not kept by the patient. He had been carrying a niggling injury to his knee for over 6 months which was diagnosed as a persistent ligamentous sprain. Prior to this episode on each occasion his knee had settled with simple first aid and rehabilitation.

Subsequently he reappeared four weeks after the initial injury presenting to his family physician. At this time he had developed right hip pain that was so severe he needed to stop and rest frequently even with the most simple activities such as walking to school. He was noticed to have an intermittent alternating limp that favoured on one occasion his right side and on another occasion his left side. He had a reduced exercise tolerance and was easily fatigued on minimal exertion. The patient was not sleeping well due to restlessness in his legs. He returned to his family physician who noted his painful right knee and difficulty walking. An X-ray examination was performed of his right knee which was reported as normal and a further referral was made for an orthopedic opinion. While waiting for his orthopedic assessment his physician organized some gentle physiotherapy. This made his knee and hip pain significantly worse. He was waking at night with pain. The family were now so concerned that they attended an urgent consultation in the emergency department.

In the emergency department this boy did not appear to be constitutionally unwell. His body build was small for age with a height of 156 cm (5th percentile for age) and underweight at 37.5 kg (<3rd percentile for age), giving him a body mass index of 15.4 (<5th percentile for age). He was comfortable at rest but walked into the emergency department with a limp and severe pain with minimal movement. He was asked where it was most painful. He responded everywhere but particularly in his hips and back. He was afebrile at 36.4°C. His pulse (144 beats/min) and respiration (44 breaths/min) were significantly elevated for age. His blood pressure elevated at 130/75 mmHg (>95% for age). Examination at this time revealed a patient with an antalgic gait and extreme truncal lurch to his right side. His Trendelenburg sign (which was performed with great difficulty as he was unable to effectively support himself unaided) was grossly positive for both sides. He had bilateral genus valgus and pes planus. There was a curvature of the lower lumbar spine with a significant pelvic tilt to the right. Single-leg testing disclosed significant weakness of the hip-girdle musculature of both hips. There was a significant limitation of range of motion in both hips and knee with the slightest movement eliciting pain. He had a full range of motion in his spine although significant pain on hyperextension testing. The remainder of the examination was unremarkable.

He was admitted to this hospital and underwent urgent investigation. Initial musculoskeletal X-ray examinations were performed of his knees, lumbar spine and hips (Figs. 1-3). These revealed generalized osteopenia. There was a widening and irregular appearance of the growth plates of the distal femur and proximal tibia (Figs. 1,2). The lumbar spine demonstrated significant spondylolisthesis of the fifth lumbar vertebrae (Fig. 1). He had bilateral slipped capital femoral epiphyses (SCFE) with greater displacement on the right than the left (Fig. 3). Laboratory studies were carried out including biochemistry, liver and renal function, and coagulation profile (Table 1). The results were consistent with those on acute or chronic renal failure. Renal ultrasonography showed hypoplastic kidneys, the right kidney being more dysplastic in appearance in comparison to the more normal looking left kidney. Both kidneys had a cystic appearance, and moderate hydronephrosis was found in the more normal looking left kidney. There was loss of corticomedullary differentiation consistent with renal dysplasia. A renal DMSA-MAG3 scan demonstrated poor tracer uptake in both kidneys, suggesting poor renal function and being consistent with severe renal dysplasia.

He remained on bed rest and commenced a special diet consisting of low phosphate and modified protein and sodium in addition to vitamin D supplementation. Nine days after admission he was considered stable enough to undergo bilateral femoral pinning/femoral strapping to correct his SCFE involving both hips. He underwent renal biopsy at the same time, showing consistent results with those of severe bilateral renal dysplasia and end-stage renal disease. The rest of his family were investigated to determine if there is a genetic link (none has been found to date). Although his musculoskeletal disease became relatively stable his renal disease progressed to the extent that antihypertensive therapy was commenced. He does not yet require dialysis and is undergoing assessment for future renal transplantation.

Discussion

CRF is being reported with increasing frequency throughout the world.[1] This mostly affects those over 60 years of age. A recent report on the epidemiology of CRF in children and adolescents showed a mean annual incidence of 12.1 new patients per million of the age-related population with a very high proportion (57.6%) of hypodysplastic renal diseases with or without urinary tract malformation.[5] These authors found that by the age of 20 years, the cumulative probability of end-stage renal disease in the population as a whole was 68%. The probability of kidney survival sharply declined during puberty and early post-puberty. With heightened awareness of this disease and better population screening it is becoming evident that CRF is a problem in young people as well.

Despite bone disease caused by renal osteodystrophy being rare in children and adolescents, musculoskeletal problems are common among children with renal failure. Although there have been many advances in medical management such as dialysis, allograft renal transplantation, and an improved understanding of the role of vitamin D and phosphate-binding agents, many patients with end stage renal disease (ESRD) continue to develop renal osteodystrophy.[1,6] The physician who treats musculoskeletal problems in children must therefore be aware of the increase in renal disease and its associated bone problems.

The causes of chronic renal failure in children and adolescents differ significantly from those found in adults.[7] In children and adolescents, congenital and developmental anomalies are frequently found as the underlying cause (Table 2).[4,5,6] The spectrum of bone disease in children with CRF depends on the underlying primary disease process.[5,8,9] The risk of developing overt hyperparathyroid bone disease is high in children with slowly progressing forms of renal pathology such as renal dysplasia as presented in our patient.[8-11]

Thin appearance and low body weight in our patient are consistent with those of patients with anorexia associated with renal failure. He initially complained of reduced exercise tolerance for his sport of choice. This progressed over time to fatigue with minimal exertion. Fatigue and exercise intolerance are well described as early and important features of CRF which can be attributed to uremia.[3] Chronic uremia has also been accompanied by insomnia and even the restless leg syndrome as depicted in this case.[2] Our patient's sleep disturbance was therefore due to all of these factors which were attributable to his underlying CRF and were possibly early indicators of his underlying renal problem.[12] These constitutional features were most likely due to the uncontrolled uremia from underlying chronic renal failure.[2] Any child or adolescent presenting with a complex agglomeration of constitutional features, skeletal and radiological deformity as reported here has a systemic disorder until otherwise proven.[2,3] These children require immediate evaluation by a specialist in a specialist hospital.

In individuals with underlying renal disease and normal kidney function, musculoskeletal impairment will predominantly be a loss of mineralized bone, whereas in individuals with impaired kidney function the musculoskeletal impairment will commonly be due to bone deformity, referred to as renal osteodystrophy.[2,13] Renal osteodystrophy is therefore the term used to describe the skeletal complications of end-stage renal disease.[3]

In the early stages of renal failure, hyperpara-thyroidism develops as a compensatory mechanism to control serum levels of calcium, phosphorus and calcitriol.[2,13-15] As kidney disease progresses, this ability to maintain mineral homeostasis is lost, leading to the development of renal osteodystrophy. The severity of skeletal deformity or renal osteodystrophy however does not always correlate with the degree of control of renal failure.[2,3,13,14] In renal osteodystrophy a wide range of skeletal abnormalities has been reported including osteonecrosis, stress fractures, epiphysiolysis genu valgus and varum, ankle valgus and varum, bowing of long bones, scoliosis, pes equinovarus and coxa vara.[3] The syndrome of renal osteodystrophy is manifested clinically by a myriad of musculoskeletal abnormalities including short stature, avascular necrosis, weak musculature, stress fractures, epiphysiolysis, and angular deformities. Epiphysiolysis is more commonly encountered in children with untreated uremia. A variety of sites may be affected (including capital femoral, distal radial and ulnar, distal femoral, metatarsal, metacarpal, capital humeral, distal tibial and fibular), the commonest being the capital femoral epiphysis.[2,3,14,16] It is common that bilateral multifocal involvement is roughly correlated with ages of accelerated growth rates. It is likely that the skeletal problems highlighted in this case, although aggravated by sport was essentially the result of an accelerated growth spurt in the 12 months before his presentation.[2,3] Earlier recognition of this fact may have resulted in an earlier diagnosis for this boy, although would not have changed his outcome significantly.

The management of children with secondary hyperparathyroidism and chronic renal failure should be started early, and should include correction of hypocalcemia and metabolic acidosis, maintenance of age-appropriate serum phosphorus levels, and institution of vitamin D therapy when serum parathyroid hormone (PTH) measurements are elevated to maintain the blood levels within normal limits to prevent the progression of low bone turnover disease.[2,8,10,14,17] The levels of serum calcium, phosphorus, alkaline phosphatase, and PTH should be monitored frequently, especially in infants and very young children.[2,10,11]

SCFE is a well known adolescent hip disorder and may be associated with endocrine and metabolic disorders in children. Two types of slippage have been distinguished in renal osteodystrophy, epiphyseal and metaphyseal.[3,16] Metaphyseal slips occur through fibrous tissue that develops between the epiphysis and metaphysis, and are thought more common in renal osteodystrophy. Once medical therapy has achieved metabolic control and corrected hyperparathyroidism as seen by improved bone quality radiologically, osteotomy can be performed.[16] Patients who required repeated osteotomy generally have poor metabolic control during the initial surgery, as determined by increased alkaline phosphatase.[3] In some patients in whom metabolic control is difficult, surgical treatment may have to be delayed. These patients are considered as candidates with non-weight bearing until renal transplantation.[16]

Genu valgum is often the result of various combinations of slippage of the distal femoral epiphysis and proximal tibial lateral growth plate changes.[3,18] Established deformities such as genu valgum, anterior bowing of the tibia, and equinovarus are not improved medically.[18] If deformity is mild, treatment options include observation until adequate medical control is achieved or medial epiphyseal stapling. If deformity is severe, osteotomy is necessary.[3,18]

Spondylolithesis caused by renal osteodystrophy has to our knowledge not been extensively reported in the literature. Spondylolysis is a common condition causing low back pain in athletes. Because spondylolysis is a stress fracture of the pars interarticularis that generally has a good outcome, it is possible that this boy developed bilateral lesions early in this evolution of his renal osteodystrophy. Although the cause is not clear, this defect was due to and aggravated by his ongoing involvement in sport while being symptomatic (in particular playing mid-field soccer). But there is no evidence supporting this assumption. When pars defect is bilateral, it has almost exclusively been reported to occur at L5. Spondylolisthesis is usually encountered in children after they are able to walk and is more commonly found in sports that require excessive hyperextension.

In summary, we have described a case of renal osteodystrophy in an adolescent who was an elite soccer player. With the increase in reported CRF throughout the world, physicians caring for children and adolescents with musculoskeletal problems are increasingly aware of the association between CRF and bone disease. In this way earlier diagnosis and more effective management may be possible for this group of children.

Ethical approval: Ethical approval was not needed.

Competing interest: No competing interests to declare.

Contributors: BAAA wrote the main body of the article under the supervision of BGJ. BI provided advice on medical aspects. BGJ is the guarantor.

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Received November 15, 2005; Accepted after revision December 16, 2005