Clinical Utility of Genetic Testing with Geographical Locations in ADPKD: Describing New Variants.

Background: Our study aims to comment on all ADPKD variants identified in our health area and explain how they are distributed geographically, to identify new variants, and relate the more frequent variants with their renal phenotype in terms of kidney survival. Materials and Methods: We identified patients suffering from ADPKD in a specialized consultation unit; genealogical trees were constructed from the proband. According to the ultrasound-defined modified Ravine-Pei criteria, relatives classified as at risk were offered participation in the genetic study. Socio-demographic, clinical, and genetic factors related to the impact of the variant on the survival of the kidney and the patient, such as age at RRT beginning and age of death, were recorded. Results: In 37 families, 33 new variants of the PKD1 gene were identified, which probably produce a truncated protein. These variants included 2 large deletions, 19 frameshifts, and 12 stop-codons, all of which had not been previously described in the databases. In 10 families, six new probably pathogenic variants in the PKD2 gene were identified. These included three substitutions; two deletions, one of which was intronic and not associated with any family; and one duplication. A total of 11 missense variants in the PKD1 gene were grouped in 14 families and classified as probably pathogenic. We found that 33 VUS were grouped into 18 families and were not described in the databases, while another 15 were without grouping, and there was only 1 in the PKD2 gene. Some of these variants were present in patients with a different pathogenic variant (described or not), and the variant was probably benign. Renal survival curves were compared to nonsense versus missense variants on the PKD1 gene to check if there were any differences. A group of 328 patients with a nonsense variant was compared with a group of 264 with a missense variant; mean renal survival for truncated variants was lower (53.1 ± 0.46 years versus non-truncated variant 59.1 ± 1.36 years; Log Rank, Breslow, and Tarone Ware, p < 0.05). Conclusions: To learn more about ADPKD, it is necessary to understand genetics. By describing new genetic variants, we are approaching creation of an accurate genetic map of the disease in our country, which could have prognostic and therapeutic implications in the future.

Predicting Future Renal Function Decline in Patients with Autosomal Dominant Polycystic Kidney Disease Using Mayo Clinic Classification.

INTRODUCTION: Mayo clinic classification (MCC) has been proposed in patients with autosomal dominant polycystic kidney disease (ADPKD) to identify who may experience a rapid decline of renal function. Our aim was to validate this predictive model in a population from southern Spain. METHODS: ADPKD patients with measurements of height-adjusted total kidney volume (HtTKV) and baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were selected. Last eGFR was estimated with Mayo Clinic (MC) equation and bias and accuracy were studied. We also analyzed predictive capacity of MCC classes using survival analysis and Cox regression models. RESULTS: We included 134 patients with a mean follow-up of 82 months. While baseline eGFR was not different between classes, last eGFR decreased significantly with them. eGFR variation rate was different according to the MCC class with a more rapid decline in 1C, 1D, and 1E classes. Final eGFR predicted was not significantly different from the real one, with an absolute bias of 0.6 ± 17.0 mL/min/1.73 m2. P10 accuracy was low ranging from 37.5 to 59.5% in classes 1C, 1D, and 1E. Using MC equation, the rate of eGFR decline was underestimated in 1C, 1D, and 1E classes. Cox regression analysis showed that MCC class is a predictor of renal survival after adjusting with baseline eGFR, age, sex, and HtTKV, with 1D and 1E classes having the worst prognosis. CONCLUSION: MCC classification is able to identify patients who will undergo a more rapid decline of renal function in a Spanish population. Prediction of future eGFR with MC equation is acceptable as a group, although it shows a loss of accuracy considering individual values. The rate of eGFR decline calculated using MC equation can underestimate the real rate presented by patients of 1C, 1D, and 1E classes.

Panorámica de la poliquistosis renal autosómica dominante en una región del sur de España / Overview of autosomal dominant polycystic kidney disease in the south of Spain

Introducción: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente aunque los datos disponibles generalmente son tras el inicio del tratamiento renal sustitutivo. Objetivo: Conocer la situación global de la poliquistosis renal autosómica dominante en el ámbito sanitario de Granada. Material y métodos: Desde enero 2007 hasta diciembre 2016 hemos recogido información clínica, familiar y demográfica de todos los pacientes con poliquistosis renal autosómica dominante, estuvieran o no en tratamiento renal sustitutivo, atendidos en el área de Granada. Se han utilizado los programas informáticos SPSS 15.0 y GenoPro. Resultados: Mil ciento siete pacientes diagnosticados, el 50,6% son varones. Se han estudiado 4-6 generaciones/familia. El 99,1% de raza caucásica. Hay áreas geográficas con mayor concentración. No hay antecedentes familiares en el 2,43%. La edad media de diagnóstico es de 34±17,8 años y en el 57,7% de los casos, el diagnóstico se produce después de tener descendencia. El principal motivo de diagnóstico son los antecedentes familiares (46,4%). La edad media de entrada en técnica es de 54,2±11,05 años. El 96,3% de los fallecidos tenían algún grado de insuficiencia renal en el momento del exitus. La edad media del exitus es de 60,9±14,10 años, siendo desconocida la principal causa de muerte (33,5%) seguida de la cardiovascular (27,8%). Conclusiones: Casos y familias se concentran en algunas áreas geográficas, un número importante de individuos están sin diagnosticar, fallecen antes por causa cardiovascular y se diagnostican tarde respecto al momento reproductivo. Dado que no hay tratamiento curativo, la estrategia de prevención primaria mediante el diagnóstico genético preimplantacional adquiere protagonismo (AU)

Introduction: Although autosomal dominant polycystic kidney disease is the most common hereditary kidney disease, available data tend to be limited to after initiation of renal replacement therapy. Objective: To ascertain an overview of autosomal dominant polycystic kidney disease within the health area of Granada in southern Spain. Material and methods: From January 2007 to December 2016, we collected clinical, family and demographic information about all patients with autosomal dominant polycystic kidney disease, irrespective of whether or not they were treated with RRT, in the Granada health area. The computer software SPSS 15.0 and GenoPro were used. Results: 50.6% of the 1,107 diagnosed patients were men. 99.1% were Caucasian and 4-6 generations/family were studied. The geographical distribution was heterogeneous. There was no family history in 2.43%. The mean age of diagnosis was 34.0±17.80 years and the diagnosis was made after having offspring in 57.7% of cases. The main reason for diagnosis was family history (46.4%). The mean age of initiation of renal replacement therapy was 54.2±11.05 years. 96.3% of the deceased had some degree of renal failure at the time of death. The mean age of death was 60.9±14.10 years, the main cause of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%). Conclusions: Cases and families were concentrated in certain geographical areas and a significant number of individuals were undiagnosed prior to cardiovascular death or diagnosed late after reproduction. Given that there is currently no curative treatment, the primary prevention strategy of preimplantation genetic diagnosis should play a leading role (AU)

Overview of autosomal dominant polycystic kidney disease in the south of Spain. / Panorámica de la poliquistosis renal autosómica dominante en una región del sur de España.

INTRODUCTION: Although autosomal dominant polycystic kidney disease is the most common hereditary kidney disease, available data tend to be limited to after initiation of renal replacement therapy. OBJECTIVE: To ascertain an overview of autosomal dominant polycystic kidney disease within the health area of Granada in southern Spain. MATERIAL AND METHODS: From January 2007 to December 2016, we collected clinical, family and demographic information about all patients with autosomal dominant polycystic kidney disease, irrespective of whether or not they were treated with RRT, in the Granada health area. The computer software SPSS 15.0 and GenoPro were used. RESULTS: 50.6% of the 1,107 diagnosed patients were men. 99.1% were Caucasian and 4-6 generations/family were studied. The geographical distribution was heterogeneous. There was no family history in 2.43%. The mean age of diagnosis was 34.0±17.80 years and the diagnosis was made after having offspring in 57.7% of cases. The main reason for diagnosis was family history (46.4%). The mean age of initiation of renal replacement therapy was 54.2±11.05 years. 96.3% of the deceased had some degree of renal failure at the time of death. The mean age of death was 60.9±14.10 years, the main cause of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%). CONCLUSIONS: Cases and families were concentrated in certain geographical areas and a significant number of individuals were undiagnosed prior to cardiovascular death or diagnosed late after reproduction. Given that there is currently no curative treatment, the primary prevention strategy of preimplantation genetic diagnosis should play a leading role.

Varices esofágicas secundarias a trombosis de vena cava superior por catéter yugular para hemodiálisis / Oesophageal varices secondary to thrombosis of the superior vena cava due to jugular haemodialysis catheter

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