The Case | Bilateral severe mechanical joint pain in the lower limbs in a hemodialysis patient
Authors: Christine Hurtgen, Johann Morelle, Bruno Vande Berg, Michel Jadoul
Journal: Kidney International (2015)

A 63-year-old anuric man on chronic hemodialysis started complaining of debilitating, typically mechanical, joint pain in the lower limbs, especially the knees and feet. Past medical history included chronic glomerulonephritis with end-stage renal disease 1.5 year ago and alcohol abuse. At this time, the patient admitted drinking almost 1 bottle of whisky a day. He did not take any phosphate binders or antacids. Dry weight was 67.1 kg and body mass index 22 kg/m2. There were no signs of arthritis and palpation of joints was not painful. Predialysis laboratory tests (with normal range) showed C-reactive protein <0.5 mg/dl, total calcium 2.20 mmol/l (2–2.6), phosphate 0.28 mmol/l (0.8–1.45), bicarbonate 26 mmol/l (22–29), intact parathyroid hormone (PTH) 64 pg/ml (18–81), 25(OH) vitamin D 21 pg/ml (30–80), and 1.25 (OH)2 vitamin D 14.7 pg/ml (18–45). Creatine phosphokinase level was normal, whereas liver enzymes were elevated (alkaline phosphatase 2 × the upper limit, γGT 5 × the upper limit, GOT 1.3 × the upper limit, GPT normal). Aluminum serum level was normal (0.3 μg/dl). Radiographic assessment of the lower limbs demonstrated patchy osteopenia of the left lateral femoral condyle, and of the tarsal and forefeet bones. Radiographs of the pelvic girdle were normal. A nuclear bone scan showed multiple sites of epiphyseal hyperfixation. Magnetic resonance imaging (MRI) (Figure 1) of the lower limbs demonstrated multiple fractures. In some areas, fracture lines were surrounded by marrow changes compatible with edema, suggesting recent fractures, whereas other fractures did not exhibit marrow changes, suggesting thus more chronic fractures. The fractures involved the sacrum, the left lateral femoral condyle, both medial tibial plateaus, and the left calcaneum. What is your diagnosis? The presence of multiple fractures of variable age strongly suggested the presence of bone fragility. The lack of adjacent bone sclerosis in chronic fractures was suggestive of osteomalacia. In end-stage renal disease patients, this disorder of decreased bone mineralization is mostly due to an abnormal vitamin D metabolism, aluminum intoxication, or severe hypophosphatemia. Severe hypophosphatemia is rare in hemodialysis patients, except in patients on chronic nocturnal hemodialysis.1.Pierratos A. Daily nocturnal home hemodialysis.Kidney Int. 2004; 65: 1975-1986Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar Since our patient was on conventional—4 h 3 times a week—hemodialysis, had no residual renal function, and as there was no evidence for internal redistribution, his severe hypophosphatemia likely resulted from reduced gastrointestinal absorption.2.Amanzadeh J. Reilly Jr., R.F. Hypophosphatemia: an evidence-based approach to its clinical consequences and management.Nat Clin Pract Nephrol. 2006; 2: 136-148Crossref PubMed Scopus (254) Google Scholar Complementary questioning and investigations ruled out diarrhea and steatorrhea, chronic pancreatitis, and celiac disease. Additional lab tests showed low serum levels of β-carotene (19 μg/dl), pre-albumin (13 mg/dl), and predialysis urea (26 mg/dl), while serum creatinine was 6.68 mg/dl, overall suggesting malnutrition. Altogether, this strongly supports that osteomalacia and severe hypophosphatemia in the present case were secondary to decreased dietary intake of phosphate in combination with vitamin D deficiency. Fibroblast growth factor (FGF)-23 level, measured recently (enzyme-linked immunosorbent assay from Kainos) on a sample obtained at the time of MRI, was<10 ng/l. This very low level for a dialyzed patient is in line with the strong inhibition of FGF-23 production by severe hypophosphatemia. Cholecalciferol was initiated and dietary counseling reinforced. As hypophosphatemia persisted, a phosphate-enriched dialysate was prepared by adding 79 g of NaH2PO4·2H2O to the liquid bicarbonate-based dialysate.3.Ing T.S. Chebrolu S.B. Cheng Y.L. et al.Phosphorus-enriched hemodialysates: formulations and clinical use.Hemodial Int. 2003; 7: 148-155Crossref PubMed Google Scholar Phosphate level rapidly normalized (Figure 2) and the pain disappeared within 2 months. Intact PTH level increased to 274 pg/ml within a month after normalization of phosphatemia. Once the patient succeeded in reducing alcohol intake, his appetite increased and phosphatemia reached the upper limit of normal. We then reduced by 50% the amount of phosphate added to the dialysate. Control MRI of lower limbs performed 5 months after normalization of phosphatemia demonstrated partial healing of the sacral fractures and complete healing of the knee and ankle fractures (Figure 3). A few months later we stopped adding phosphate to the dialysate and phosphatemia remained normal. The patient has recently been successfully transplanted.Figure 3Follow-up spin-echo T1-weighted coronal image of the left knee demonstrating healing of the lesions.View Large Image Figure ViewerDownload (PPT) The authors wish to thank Prof. Pieter Evenepoel (Leuven, Belgium) for the measurement of FGF-23 level.