Association between increased serum osteoprotegerin levels and improvement in bone mineral density after parathyroidectomy in hemodialysis patients.

Secondary hyperparathyroidism (SHPT) is a common complication in chronic renal disease. Osteoprotegerin (OPG), an extracellular cytokine receptor secreted by osteoblasts, can promote bone formation by inhibiting the function of osteoclasts. Hemodialysis (HD) patients have elevated serum OPG levels. OPG secretion can be suppressed with high parathyroid hormone (PTH) levels. HD patients with refractory SHPT can benefit from parathyroidectomy (PTX) treatment, but the changes of serum OPG, bone turnover markers and bone mineral density (BMD) following PTX in HD patients remain unclear. In this study, patients on maintenance HD who received PTX for refractory SHPT (n = 28) were prospectively followed for 1 year. Serum intact PTH (iPTH), alkaline phosphatase (Alk-P), and OPG were measured serially; BMD was measured pre-PTX and at 1 year after PTX. After PTX, serum iPTH levels reduced profoundly. Serum Alk-P levels increased rapidly, peaking at 2 weeks post-PTX, while serum OPG levels gradually increased at 2 weeks after PTX and peaked at 2 months. BMD improved in both femoral neck (FN; cancellous and cortical bone) and lumbar spine (LS; cancellous bone). Higher baseline iPTH levels were associated with greater FN and LS BMD improvements at one year after PTX. The increment of serum OPG was correlated with the increase in LS BMD, implying that inhibition of osteoclastic bone resorption may improve BMD within the first year after PTX. These findings suggest that PTX removes the suppressive effects of high PTH on OPG secretion, resulting in the increased serum OPG levels that may contribute to BMD improvement.

Serum bone resorption markers after parathyroidectomy for renal hyperparathyroidism: correlation analyses for the cross-linked N-telopeptide of collagen I and tartrate-resistant acid phosphatase.

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n = 23) or who did not develop refractory SHPT (control subjects; n = 25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

Calcitriol treatment attenuates inflammation and oxidative stress in hemodialysis patients with secondary hyperparathyroidism.

Hemodialysis patients with secondary hyperparathyroidism (SHP) suffer from excessive oxidative stress and inflammation. Vitamin D analogues are currently the first line therapy for SHP, but the influence of vitamin D treatment on inflammation and oxidative stress remains unknown. This study investigated the influence of vitamin D therapy on oxidative stress and inflammatory markers in hemodialysis patients with SHP. Twenty-five patients (mean age 58 ± 12 years, 13 males and 12 females) were enrolled in the study to receive calcitriol treatment for 16 weeks. We evaluated changes in the serum biochemical parameters, inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6) levels], serum oxidative stress condition [total antioxidant status (TAS)], and CD4(+) T-lymphocyte intracellular cytokines [interferon γ (IFN-γ) and interleukin-4 (IL-4)] before and at the end of the 16-week calcitriol treatment. Correlations between each of these factors were also studied. All patients with SHP had low serum 1,25-dihydroxyvitamin D(3) levels and elevated serum levels of intact parathyroid hormone (iPTH), CRP and IL-6. Twenty patients (10 males and 10 females) responded to the calcitriol therapy, with significant decrements in serum iPTH. Our results showed that calcitriol can effectively suppress iPTH secretion, reduce inflammatory markers (CRP and IL-6) and oxidative stress. It can also effectively reduce inflammatory cytokine (CD4(+) IFN-γ) and increase anti-inflammatory cytokine (CD4(+) IL-4). Interestingly, significant correlations between CD4(+) IFN-γ levels and serum iPTH levels, as well as between TAS and iPTH levels were noted. Overall, our study has demonstrated calcitriol treatment significantly attenuates inflammation and oxidative stress in hemodialysis patients with SHP.

Fanconi syndrome and CKD in a patient with paroxysmal nocturnal hemoglobinuria and hemosiderosis.

Fanconi syndrome and chronic kidney disease associated with paroxysmal nocturnal hemoglobinuria is rarely reported. We describe a 51-year-old woman with glomerular filtration rate decrease and hypokalemia, glucosuria, and proteinuria during a 4-year period. Paroxysmal nocturnal hemoglobinuria was diagnosed 17 years earlier, and she has received multiple blood transfusions because of hemolytic episodes during the last 5 years. Deteriorating kidney function and persistent Fanconi syndrome were accompanied by a progressive increase in serum ferritin levels. Laboratory studies showed proximal renal tubular acidosis, hypophosphotemic hyperphosphaturia, normoglycemic glucosuria, and aminoaciduria. Serologic testing, tumor markers, Bence-Jones protein, and heavy-metal screening results were negative. Abdominal magnetic resonance imaging showed characteristic features of iron deposition in the bilateral renal cortices. Kidney biopsy showed chronic interstitial nephritis with prominent hemosiderin deposition in the proximal tubules. With potassium citrate, calcitriol, and deferoxamine therapy, Fanconi syndrome persisted, but kidney function was stable. Renal hemosiderosis secondary to both chronic repetitive hemolytic episodes and transfusion-related iron overload in patients with paroxysmal nocturnal hemoglobinuria can lead to Fanconi syndrome and chronic kidney disease.

Refractory diffuse bony pain 20 years after jejunoileal bypass.

Osteomalacia can be a late but unrecognized complication following jejunoileal bypass. We describe a 53-year-old man who underwent jejunoileal bypass for morbid obesity twenty years earlier who suffered from progressive diffuse bony pain refractory to nonsteroidal anti-inflammatory drugs. He was initially diagnosed with a malignancy with bone metastasis. However, pertinent laboratory data were notable for hypocalcemia (7.5 mg/dL, albumin 4.1 mg/dL) with low urinary calcium excretion (14 mg/day), hypophosphatemia (2.0 mg/dL) with low urinary phosphate excretion (53 mg/day), hypomagnesemia (1.5 mg/dL) with low urine magnesium excretion (23 mg/day), low 1, 25 (OH)2 vitamin D3, and elevated serum alkaline phosphatase and intact parathyroid hormone (iPTH). These laboratory findings pointed to a defect in calcium, phosphate, and magnesium handling in the gastrointestinal tract. Bone biopsy of the iliac crest clearly demonstrated typical changes of osteomalacia with excessive osteoid accumulation and reduced mineralization. His clinical symptoms were refractory to oral 1, 25 (OH)2 vitamin D3 and calcium supplementation but significantly improved with the addition of intermittent intravenous active 1, 25 (OH)2 vitamin D3, calcium, phosphate, and magnesium supplementation. Osteomalacia is an easily misdiagnosed late complication of jejunoileal bypass. Early recognition can avoid circuitous diagnosis and inappropriate management.