Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

O impacto da função do enxerto renal e da ocorrência de infecção intra-abdominal na sobrevida em 1 ano do paciente após o transplante simultâneo de pâncreas-rim (TSPR) / The impact of kidney function and intra-abdominal infection on patient 1-yr survival after simultaneous pancreas-kidney transplantation (SPKT)

O transplante de pâncreas-rim (TSPR) é um dos tratamentos mais efetivos para o paciente com diabetes melito e insuficiência renal crônica. Métodos: Foram realizadas análises retrospectivas da sobrevida de 150 pacientes submetidos ao TSPR pela regressão de COX e determinação das curvas de Kaplan-Meier, além das análises uni - e multivariadas para identificação dos fatores de risco tradicionais e aqueles relacionados ao transplante. Resultados: As taxas de sobrevidas em um ano dos pacientes, dos enxertos renais e pancreáticos foram de 82,0%, 80,0% e 76,7%, respectivamente. Função retardada do enxerto renal (FRR) (P = 0,001, RR 5,41), rejeição aguda renal (P = 0,016, RR 3,36) e infecção intra-abdominal (IIA) (P < 0,0001, RR 4,15) foram os principais fatores de risco que influenciaram a sobrevida do paciente em um ano. A sobrevida do paciente em um ano esteve relacionada à ocorrência de FRR (P = 0,013, RC 3,39), à rejeição aguda renal (P = 0,001, RC 4,74) e à IIA (P = 0,003, RC 6,29). A sobrevida do enxerto pancreático em um ano esteve relacionada à IIA (P < 0,0001, RC 12,83), à trombose vascular (P = 0,002, RC 40,55), à rejeição aguda renal (P = 0,027, RC 3,06), ao sódio do doador > 155 mEq/L (P = 0,02, RC 3,27) e ao uso de dopamina > 7,6 µcg/kg/min (P = 0,046, RC 2,85). Discussão: A ocorrência de função retardada do enxerto renal e infecção intraabdominal teve impacto na sobrevida em um ano tanto do paciente quanto dos enxertos renal e pancreático

Simultaneous pancreas-kidney transplantation (SPKT) is one of the treatments for insulin-dependent patients with chronic renal failure. Methods: One-year patient and kidney allograft survival rates of 150 patients submitted to SPKT analyzed by COX regression and Kaplan-Meier. Uni- and multivariate analysis identified the risk factors involved with either allograft or patient survival. Results: One-year patient and kidney allograft survival rates were 82% and 80%, respectively. Delayed graft function from kidney (DGF) (P = 0.001, HR 5.41), acute kidney rejection (P = 0.016, HR 3.36) and intra-abdominal infection (IAI) (P < 0.0001, HR 4.15) were related to the 1-yr patient survival. One-year kidney allograft survival was also related to DGF (P = 0.013, OR 3.39), acute rejection (P = 0.001, OR 4.74) and IAI (P = 0.003, OR 6.29). Main risk factors for DGF: time on dialysis > 27 months (P = 0.046, OR 2.59), kidney cold ischemia time > 14 hours (P = 0.027, OR 2.94), donor age > 25 years (P = 0.03, OR 2.82) and donor serum sodium > 155 mEq/l (P < 0.0001, OR 1.09). Conclusions: Delayed kidney allograft function and IAI had an important impact on either patient or kidney allograft survival rates. Improving deceased donor care may reduce DGF occurrence.