Relationship between age at initiation of cysteamine treatment, adherence with therapy, and glomerular kidney function in infantile nephropathic cystinosis.

Infantile nephropathic cystinosis, due to impaired transport of cystine out of lysosomes, occurs with an incidence of 1 in 100-200,000 live births. It is characterized by renal Fanconi syndrome in the first year of life and glomerular dysfunction progression to end-stage kidney disease by approximately 10 years of age. Treatment with oral cysteamine therapy helps preserve glomerular function, but affected individuals eventually require kidney replacement therapy. This is because glomerular damage had already occurred by the time a child is diagnosed with cystinosis, typically in the second year of life. We performed a retrospective multicenter study to investigate the impact of initiating cysteamine treatment within the first 2 months of life in some infants and comparing two different levels of adherence in patients diagnosed at the typical age. We collected 3983 data points from 55 patients born between 1997 and 2020; 52 patients with 1592 data points could be further evaluated. These data were first analyzed by dividing the patient cohort into three groups: (i) standard treatment start with good adherence, (ii) standard treatment start with less good adherence, and (iii) early treatment start. At every age, mean estimated glomerular filtration rate (eGFR) was higher in early-treated patients than in later-treated patients. Second, a generalized additive mixed model (GAMM) was applied showing that patients with initiation of treatment before 2 months of age are expected to have a 34 ml/min/1.73 m2 higher eGFR than patients with later treatment start while controlling for adherence and patients' age. These data strongly suggest that oral cysteamine treatment initiated within 2 months of birth preserves kidney function in infantile nephropathic cystinosis and provide evidence of the utility of newborn screening for this disease.

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVE: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. STUDY DESIGN: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. RESULTS: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. CONCLUSIONS: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.

Chronic recurrent multifocal osteomyelitis: what is it and how should it be treated?

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is the most severe form of chronic nonbacterial osteomyelitis. In children and adolescents, chronic nonbacterial osteomyelitis predominantly affects the metaphyses of the long bones, but lesions can occur at any site in the skeleton. Other organs (the skin, eyes, gastrointestinal tract and lungs) can also be affected. Clinical diagnosis is often difficult because the symptoms and course of disease vary significantly. We present a 10-year-old girl diagnosed with CRMO involving several vertebrae, the femur and the metatarsus. INVESTIGATIONS: Physical examination, abdominal ultra sonography, conventional X-ray, MRI, technetium bone scan, esophagogastroduodenoscopy, colonoscopy, tests for HLA-B27 and thiopurine methyltransferase, polymerase chain reaction and thoracic vertebral bone biopsies. DIAGNOSIS: CRMO and Crohn's disease. MANAGEMENT: The patient's condition improved whilst being treated with NSAIDs for 3 months; however, the patient had an allergic skin reaction to this therapy. Treatment was switched to sulfasalazine, accompanied by 3 weeks of therapy using oral prednisone, but sulfasalazine was discontinued 2 months later because the patient exhibited a minor elevation in the levels of liver enzymes. The patient was free of musculoskeletal symptoms for 6 months, at which time she started to complain again about pain in her back and bowel. Multimodal therapy, consisting of mesasalazine, corticosteroids (budesonide) and azathioprine, induced clinical remission of Crohn's disease.