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BACKGROUND: Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on the safety and efficacy of statins in pediatric CKD is limited. METHODS: Patients with CKD stage 2-5 and aged 5-18 years with low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL and/or non-high-density lipoprotein cholesterol (non-HDL-C) > 145 mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, which was escalated to 20 mg/day if LDL-C remained > 100 mg/dL and/or non-HDL-C > 120 mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C ≤ 100 mg/dL and non-HDL-C ≤ 120 mg/dL) and adverse events were assessed at 24 weeks. RESULTS: Of 31 patients enrolled, target lipid levels were achieved in 45.2% (95% CI 27.8-63.7%) at 24 weeks; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median lipid level reduction with 10 (n = 9) versus 20 mg/day (n = 22, P = 0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00-1.11) and older age (OR 36.5, 95% CI 2.57-519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT > 3 times upper normal limit (UNL) or CPK > 10 times UNL. No differences were noted in adverse events due to atorvastatin 10 or 20 mg/day. CONCLUSION: Atorvastatin (10-20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non-HDL-C in children with CKD stages 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Anticolesterolemiantes , Dislipidemias , Ácidos Heptanoicos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insuficiencia Renal Crónica , Humanos , Niño , Atorvastatina/efectos adversos , LDL-Colesterol , Ácidos Heptanoicos/efectos adversos , Pirroles/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Colesterol , Dislipidemias/complicaciones , Dislipidemias/diagnóstico , Dislipidemias/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/inducido químicamente , Resultado del TratamientoRESUMEN
Data on the effect of vitamin D supplementation on fibroblast growth factor 23 (FGF23), in chronic kidney disease (CKD) are scarce. In a prospective interventional study, the effect of vitamin D supplementation on cFGF23 (C-terminal FGF23) levels in children with CKD stages 2-4 was examined. Forty-one children with CKD and vitamin D insufficiency were administered 600,000 units of cholecalciferol over 3 d; 88% of patients achieved sufficiency at 8 wk. Significant increase in serum cFGF23 and phosphate levels was observed in CKD stage 2 after supplementation, but not in CKD stages 3 and 4. There was no correlation of the change in cFGF23 level with baseline or change in bone health parameters (calcium, phosphate, parathormone or alkaline phosphatase) or with change in flow-mediated dilatation (FMD) of the brachial artery. It is concluded that cholecalciferol supplementation increases serum calcium and reduces PTH, but does not adversely affect FGF23 levels in CKD.
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Insuficiencia Renal Crónica , Deficiencia de Vitamina D , Fosfatasa Alcalina , Calcio , Niño , Colecalciferol/uso terapéutico , Suplementos Dietéticos , Factores de Crecimiento de Fibroblastos , Humanos , Hormona Paratiroidea , Fosfatos , Estudios Prospectivos , Insuficiencia Renal Crónica/terapia , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , VitaminasRESUMEN
Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis, despite preserved glomerular filtration rate. RTA are classified into chiefly three types (1, 2 and 4) based on pathophysiology and clinical and laboratory characteristics. Most patients have primary RTA that presents in infancy with polyuria, growth retardation, rickets and/or hypotonia. Diagnosis requires careful evaluation, including exclusion of other entities that can cause acidosis. A variety of tests, administered stepwise, are useful for the diagnosis and characterization of RTA. A genetic or acquired basis can be determined in majority of patients through focused evaluation. Management involves correction of acidosis and dyselectrolytemia; patients with proximal RTA with Fanconi syndrome and rickets require additional supplements of phosphate and vitamin D.
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Acidosis Tubular Renal , Acidosis , Síndrome de Fanconi , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/terapia , Tasa de Filtración Glomerular , Humanos , FosfatosRESUMEN
Fibroblast growth factor-23 (FGF23) is central to phosphate homeostasis. The author examined if blood levels of FGF23 allow discrimination of classic hypophosphatemic rickets from other causes of non-nutritional rickets with hypophosphatemia. Forty-two children (median age: 102 mo) with non-nutritional rickets and hypophosphatemia were clinically classified as having distal renal tubular acidosis (RTA, n = 12), Fanconi syndrome (n = 8), classic hypophosphatemic rickets (n = 11), vitamin D dependent rickets (n = 7) and Dent disease (n = 4). Median blood FGF23 (measured by C-terminal ELISA) concentrations were similar in all groups (P = 0.24). These levels did not correlate with phosphate, tubular maximum for phosphate, calcium, 25-hydroxyvitamin D, creatinine, and parathormone levels. Patients with distal RTA showed variable degree of proximal tubular dysfunction that resolved following alkali supplements. Blood FGF23 levels did not satisfactorily differentiate classic hypophosphatemic rickets from other causes of hypophosphatemic rickets.
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Factores de Crecimiento de Fibroblastos/sangre , Raquitismo Hipofosfatémico/sangre , Acidosis Tubular Renal/sangre , Acidosis Tubular Renal/diagnóstico , Niño , Enfermedad de Dent/sangre , Enfermedad de Dent/diagnóstico , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Síndrome de Fanconi/sangre , Síndrome de Fanconi/diagnóstico , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Raquitismo/sangre , Raquitismo/diagnóstico , Raquitismo Hipofosfatémico/diagnósticoRESUMEN
Refractory rickets is a genetic disorder that cannot be treated by vitamin D supplementation and adequate dietary calcium and phosphorus. Hereditary hypophosphatemic rickets is one of the major forms of refractory rickets in Indian children and caused due to mutations in the PHEX , FGF23 , DMP1 , ENPP1 , and SLC34A3 genes. This is the first study in India on a large number of patients reporting on mutational screening of the PHEX gene. Direct sequencing in 37 patients with refractory rickets revealed eight mutations in 13 patients of which 1 was nonsense, 2 were deletions, 1 was a deletion-insertion, and 4 were missense mutations. Of these mutations, four (c.566_567 delAG, c.651_654delACAT, c.1337delinsAATAA, and c.2048T > A) were novel mutations. This article discusses the mutations in Indian patients, collates information on the genetic causes of refractory rickets, and emphasizes the significance of genetic testing for precise diagnosis, timely treatment, and management of the condition, especially in developing countries.
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We report a case of Gitelman syndrome presenting with fatigue, paresthesias, weakness of limbs and neck muscles since 2.5 years of age. Investigations showed hypokalemia and hypomagnesemia with urinary magnesium wasting. Genetic analysis revealed the presence of a novel homozygous mutation in the SLC12A3 gene (c.2879_2883+9ins14bp, p.Val 960 Glu fsx12). Management with potassium and magnesium supplements and spironolactone resulted in a significant improvement in symptoms. Over a follow-up of 11 years, the patient showed satisfactory growth and physical development.
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Síndrome de Gitelman/genética , Hipopotasemia/genética , Receptores de Droga/genética , Simportadores/genética , Niño , Diuréticos/uso terapéutico , Femenino , Estudios de Seguimiento , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamiento farmacológico , Humanos , Magnesio/uso terapéutico , Mutación , Potasio/uso terapéutico , Miembro 3 de la Familia de Transportadores de Soluto 12 , Espironolactona/uso terapéuticoRESUMEN
Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2-4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2--5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2-4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.
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Colecalciferol/uso terapéutico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Enfermedades Renales/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/uso terapéutico , Adolescente , Biomarcadores/sangre , Calcifediol/sangre , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/epidemiología , Hiperparatiroidismo Secundario/etiología , India/epidemiología , Enfermedades Renales/sangre , Enfermedades Renales/epidemiología , Masculino , Hormona Paratiroidea/sangre , Prevalencia , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Relapses in steroid-sensitive nephrotic syndrome (SSNS) often follow infections of the respiratory or gastrointestinal tract. Based on data that zinc supplements reduce the risk of infections, we examined the efficacy of such supplements in reducing relapse rates in these patients. Eighty-one patients with SSNS (1-16 years old) were stratified into frequent (n = 52) and infrequent (n = 29) relapsers and randomized to receive 12-months of therapy with the recommended dietary allowance of zinc (10 mg/day) (n = 40) or placebo (n = 41). Patients with frequent relapses also received long-term, alternate-day prednisolone. Subjects receiving zinc showed a 20% lower frequency of relapses, with 44.7% of the patients having sustained remission compared to 27.5% in the placebo group (P > 0.05). Patients with frequent relapses receiving zinc showed a 28% reduction in relapse rates and a significantly higher likelihood of sustained remission (P = 0.02). Findings from this double blind, randomized study suggest that zinc supplementation results in trends towards remission and reduced relapses, especially in patients with frequent relapses. Prospective, adequately powered studies are required for confirmation of these findings.