Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities.

CONTEXT: Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD); however, systematic analyses are lacking. OBJECTIVE: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD. DESIGN: Cross-sectional multicenter study. SETTING: Hospital clinics. PATIENTS: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage. MAIN OUTCOME MEASURES: Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity. RESULTS: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate. CONCLUSIONS: Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.

Robotic-assisted laparoscopic transplant-to-native ureteroureterostomy in a pediatric patient.

OBJECTIVE: Management of late-occurring or long (>3 cm) post-transplant ureteral strictures usually requires open surgery, which includes ureteroureterostomy (UU) as an option. Recently, robotic-assisted laparoscopic UU for ectopic ureters in a duplicated system has been described. We report a case of a robotic-assisted laparoscopic transplant-to-native side-to-side UU in a 14-year-old girl with a stricture of nearly two-thirds of her transplant ureter 5 years after a cadaveric renal transplant. RESULTS: Robotic-assisted laparoscopic native-to-transplant UU was performed with resultant durable improvement in the patient's hydronephrosis and kidney function. CONCLUSION: Based on our case and review of the literature, robotic-assisted laparoscopic UU should be part of the armamentarium for long or late-occurring transplant ureteral strictures.

Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy.

BACKGROUND: The full burden of nephropathic cystinosis in adulthood and the effects of long-term oral cysteamine therapy on its nonrenal complications have not been elucidated. OBJECTIVE: To assess the severity of cystinosis in adults receiving and not receiving oral cysteamine therapy. DESIGN: Case series. SETTING: National Institutes of Health Clinical Center. PATIENTS: 100 persons (58 men and 42 women) age 18 to 45 years with nephropathic cystinosis examined between January 1985 and May 2006. MEASUREMENTS: Historical data were collected on renal transplantation, administration of oral cysteamine, and time and cause of death. Patients were evaluated for height and weight; thyroid, pulmonary, and swallowing function; muscle atrophy; hypogonadism (in men); retinopathy; vascular and cerebral calcifications; diabetes mellitus; and homozygosity for the common 57-kb deletion in CTNS. Laboratory studies were also performed. RESULTS: Of 100 adults with nephropathic cystinosis, 92 had received a renal allograft and 33 had died. At least half of the patients had hypothyroidism, hypergonadotropic hypogonadism (in men), pulmonary insufficiency, swallowing abnormalities, or myopathy. One third of the patients had retinopathy or vascular calcifications, and 24% had diabetes. Homozygosity for the 57-kb CTNS deletion was associated with an increased risk for death and morbidity. The 39 patients who received long-term (> or =8 years) oral cysteamine therapy were taller and heavier, had a renal allograft later in life, had lower cholesterol levels, and experienced fewer complications and deaths than patients who received cysteamine for fewer than 8 years. The frequency of diabetes mellitus, myopathy, pulmonary dysfunction, hypothyroidism, and death increased as time off cysteamine treatment increased, and it decreased as time on cysteamine therapy increased. LIMITATIONS: The study was retrospective and not randomized. The criteria used to measure adequacy of treatment were arbitrary. CONCLUSIONS: Untreated nephropathic cystinosis causes extensive morbidity and death in adulthood. Long-term oral cysteamine therapy mitigates these effects.

Effect on growth parameters of bone marrow transplantation with a chemotherapy-only conditioning regimen.

INTRODUCTION: The increasing use of bone marrow transplantation (BMT) has increased survival among a growing number of children and young adults afflicted by malignant and nonmalignant hematologic disorders. Accordingly, quality of life has emerged as an important issue. Because they are a concern in this group, we assessed growth and development, following chemotherapy-only conditioning regimens. MATERIALS AND METHODS: Twelve prepubertal children (8 boys, G(1)P(1) and 4 girls, B(1)P(1)) with a mean age of 6 +/- 2 years (age range: 3.5 to 10 years) before and at 3, 6, 9, and 12 months post-BMT. RESULTS: Growth velocity at 1 year posttransplant was 10.0 +/- 3.5 cm/y. One year post-BMT, the statistical deviation saturation for growth velocity was 4.31 +/- 4.21. Height standard deviation score was -1.4 +/- 1.2 before and -0.5 +/- 1.3 1 year post-BMT (P <.004). The average weight of our subjects was 20 +/- 6 kg before and 26 +/- 9.5 kg 1 year post-BMT. DISCUSSION: BMT with a chemotherapy-only conditioning regimen not only does not disturb growth in children; it is actually associated with a relative growth spurt afterward.

[Multiple pathological fractures within the scope of DeToni-Debre-Fanconi syndrome after fumarate therapy in psoriasis]. / Multiple pathologische Frakturen im Rahmen eines DeToni-Debré-Fanconi-Syndroms nach Fumarattherapie bei Psoriasis.

We report about a rare case of a pathological fracture of the shank following earlier pathological fractures at other locations in a comparatively young female patient with no history of trauma. There were no known diseases other than psoriasis. The shank fracture was treated surgically by osteosynthesis. Osteoporosis, myeloma, or malignancy as causative factors of this fracture could be excluded. Scintigraphy showed an enhancement, especially at the extremities. Other than reactive bone growth, histological examination revealed no further aspects. Laboratory analysis indicated a massive lack of vitamin D3. After transferring the patient to the internal department of our hospital, long-term medication with fumaric acid was determined to be the reason for the osteomalacia of a Fanconi's syndrome. Three months after cessation of these medicaments and treatment with active vitamin D3 metabolites, the patient was free of complaints. The radiographs showed an essential improvement of the demineralization.

Cadaver renal transplantation in children with cystinosis.

Five children with end-stage renal disease resulting from cystinosis received seven cadaver renal allografts. Four recipients have functioning grafts eight to 55 months after receiving the transplant and one recipient lost two grafts at 17 and 26 months after the transplant. There was no florid recurrence of the Fanconi syndrome although proximal renal tubular dysfunction developed in two patients, in one in association with chronic rejection and in one without apparent etiology. Free cystine content of white blood cells, cultured skin fibroblasts and allograft tissue was significantly increased. Cystine crystals were observed in the mesangium of two grafts and in the interstitial tissue of all grafts; however, no cystine crystals were found in the tubules. The location of the cystine crystals, as well as the fact that the highest free level of cystine of allograft tissue was observed in the graft undergoing chronic rejection. led to the hypothesis that recipient cells infiltrating the graft were the source of cystine deposition. The data indicate that successful cadaveric transplantation does not correct the primary metabolic defect in cystinosis, thereby explaining the persistence of the extrarenal clinical manifestations, such as photophobia and hypothyroidism, after renal transplantation in cystinosis.