Genotype and Phenotype Analysis in Pediatric Patients with Cystinuria

Cystinuria is an inherited disorder characterized by defective renal reabsorption of cystine and dibasic amino acids leading to nephrolithiasis. This study was conducted to analyze the genotypes and phenotypes of pediatric patients with cystinuria. Eight children from Seoul National University Hospital and Asan Medical Center presenting with cystinuria from January 2003 to June 2016 were retrospectively analyzed. Mutational studies were performed by direct sequencing. Two of the 8 were male and 6 were female. The median ages at onset and diagnosis were 1.5 (range, 0.3–13.6) and 2.6 (range, 0.7–16.7) years, respectively. The median followed up was 7.7 (range, 3.4–14.0) years. Mutational analyses were performed in 7 patients and revealed biallelic SLC3A1 mutations (AA genotype) in 4 patients, a single heterozygous SLC3A1 mutation (A- genotype) in 1 patient, biallelic SLC7A9 mutations (BB genotype) in 1 patient, and a single heterozygous SLC7A9 mutation (B- genotype) in 1 patient. Two of the mutations were novel. No genotype-phenotype correlations were observed, except for earlier onset age in patients with non-AA genotypes than in patients with the AA genotype. All patients suffered from recurrent attacks of symptomatic nephrolithiasis, which lead to urologic interventions. At the last follow-up, 3 patients had a mild-to-moderate degree of renal dysfunction. This is the first study of genotypic and phenotypic analyses of patients with cystinuria in Korea.

Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients / Inibicao da reabsorcao renal de glicose como uma nova forma de tratamento para pacientes com diabetes

The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation”) were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients. .

A importância do rim na homeostase de glicose é reconhecida desde há muitos anos. Observações recentes, indicando um papel maior do metabolismo renal da glicose em várias condições fisiológicas e patológicas, reavivaram o interesse no manuseio renal de glicose como um alvo em potencial para o tratamento do diabetes. A enorme capacidade das células tubulares proximais para reabsorver a carga total de glicose filtrada, utilizando o sistema de co-transporte de sódio e glicose (SGLT), tornou-se o foco de atenção. Estudos originais realizados em animais experimentais com o uso do inibidor não-específico da SGLT florizina, demonstraram que a hiperglicemia após pancreatectomia diminuiu como resultado de glicosúria forçada. Posteriormente, foram desenvolvidas diversas substâncias com propriedades mais seletivas de inibição da SGLT-2 ("segunda geração"). Vários agentes foram usados em ensaios pré-clínicos e clínicos, e alguns já foram aprovados para uso comercial no tratamento da diabetes tipo 2. Em geral, os dados clinicos mostram que um período de 6 meses de tratamento com inibidores da SGLT-2 é seguido por uma taxa de excreção de glicose urinária média de ~ 80 g/dia, acompanhado por uma queda na glicemia de jejum e pós-prandial e com redução média na HbA1C de - 1.0%. Também foram relatados perda concomitante no peso corpóreo e uma leve mas consistente queda da pressão arterial. Em contraste, eventos adversos transitórios como poliúria, sede com desidratação e hipotensão ocasional foram descritos na fase inicial de tratamento. Além disso, um aumento significativo na ocorrência de infecções urogenitais, particularmente em mulheres, foi documentado com o uso de inibidores da SGLT-2. Os efeitos ...