The Genetic Kidney Diseases Laboratory has been established as a research line dedicated to advancing knowledge and improving care for patients affected by rare genetic kidney diseases. By adopting a clinically translational approach, the laboratory aims to bridge the gap between molecular discoveries and clinical practice.
Our focus lies in understanding how genomic variants, inflammation and metabolic disturbances contribute to disease mechanisms, progression, and variability in patient outcomes. The laboratory’s research strategy is built upon two complementary pillars. First, we conduct in-depth monitoring of inflammatory biomarkers, genotyping, and sequencing of well-defined patient cohorts (high laboratory intensity). These efforts allow us to uncover molecular drivers of disease, identify novel biomarkers, and establish potential therapeutic targets. Second, we actively enroll patients into large international registries as well clinical trials (low laboratory intensity). By integrating these two approaches, the Genetic Kidney Diseases Laboratory embodies a bench-to-bedside and bedside-to-bench model of research.
Projects
- Development of a cellular model for Familial Renal Glucosuria: evaluation of mutants and implications for the treatment of Type 2 Diabetes Mellitus.
Hypothesis: a cellular model of the human phenotype of Familial Renal Glucosuria (FRG) can improve outcomes in t2D patients under pharmacological SGLT2 inhibition.
Methods: clinical and molecular characterization of FRG patients and heterologous expression of mutants in HEK293T cell system.
Completion - 31/12/2026
Funding - pharmaceutical.
- Biomarkers in Nephrology: Autosomal Dominant Polycystic Kidney Disease as Inflammatory process - Innovative Therapeutic Strategy IMF-ADPKD.
Hypothesis: inflammation plays a role in cyst growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD).
Methods: monitor urinary and blood inflammation cyto-chemokines profile in a cohort of 60 ADPKD patients and assess the impact of tolvaptan treatment; observational longitudinal study.
Completion - 31/12/2026
Funding - ULS São José.
- Apol1-Mediated Chronic Kidney Disease: Risk Identification in the Population Undergoing Renal Replacement Therapy in Portugal (DRAPOR).
Hypothesis: admixture with genetic variants of African ancestry associated with susceptibility to chronic kidney disease (CKD) is a major contributor to the abnormally high CKD incidence observed in the Portuguese population.
Methods: genotype the APOL1 G1 and G2 risk haplotype in a cohort of 300 end-stage kidney disease Portuguese patients; cross-sectional molecular epidemiology study.
Completion - 31/12/2026
Funding – pharmaceutical
- A Study to Assess Adverse Events and Effectiveness of IntraVenous Infusions of ABBV-CLS-628 in Adult Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (ANCHOR)
Hypothesis: Autosomal Dominant Polycystic Kidney Disease (ADPKD), a cystic renal dysplasia, is the most prevalent genetic cause of chronic kidney disease. The objective of this study is to evaluate the safety and efficacy of ABBV-CLS-628 (an anti-PAPP-A monoclonal antibody targeting the reduction of insulin-like growth factor signaling) for the treatment of ADPKD in adults.
Methods: clinical study phase 2
Completion – 01/08/2029
Funding – pharmaceutical
- Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab Administered Intravenously in Adult Participants at High Risk of Delayed Graft Function After Kidney Transplantation (AWAKE)
Hypothesis: The primary objective of this study is to demonstrate the efficacy of ravulizumab (an anti-C5-9 monoclonal antibody) in reducing late renal graft dysfunction in adult patients who have undergone cadaveric donor transplantation.
Methods: clinical study phase 3
Completion – 06/11/2028
Funding – pharmaceutical
- Alport Syndrome Sema3A Efficacy & Safety Study.
Hypothesis: The study drug, BAY 3401016 (an anti-Semaforin 3A monoclonal antibody), blocks the action of Sema3A and may prevent the development of proteinuria and delay renal failure in Alport Syndrome.
Methods: clinical study phase 2
Conclusão – 27/07/2028
Funding – pharmaceutical
Publications
- McAnallen SM, Elhassan EAE, Stoneman S, et al. Genotype-Phenotype Correlations and Clinical Outcomes of Genetic TRPC6 Podocytopathies. Nephrol Dial Transplant. 2025 May 19:gfaf086. doi: 10.1093/ndt/gfaf086.
- Gimpel C, Fieuws S, Hofstetter J, et al. RaDaR ADPKD Rare Disease Group; ERKReg Collaborators; ADPedKD Collaborators. Insights from ADPedKD, ERKReg and RaDaR registries provide a multi-national perspective on the presentation of childhood autosomal dominant polycystic kidney disease in high- and middle-income countries. Kidney Int. 2025 Jul;108(1):105-118. doi: 10.1016/j.kint.2025.02.026.
- Lapão T, Barata R, Jorge C, Flores C, Calado J. Autosomal Dominant Polycystic Kidney Disease Inflammation Biomarkers in the Tolvaptan Era. Int J Mol Sci. 2025 Jan 28;26(3):1121. doi: 10.3390/ijms26031121.
- Kavanagh D, Ardissino G, Brocklebank V, et al. Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. Kidney Int. 2024 Dec;106(6):1038-1050. doi: 10.1016/j.kint.2024.09.012.
- Iglesias-Romero AB, Kaminska K, Quinodoz M, Folcher M, Lin S, Arno G, Calado J, Webster AR, Moulin A, Sousa AB, Coutinho-Santos L, Santos C, Rivolta C. Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa. Am J Hum Genet. 2024 Oct 3;111(10):2299-2306. doi: 10.1016/j.ajhg.2024.08.005.
- Barata R, Fila M, Dalla-Vale F, Bogarin R, Nunes P, Ramalho J, Rueff J, Calado J. Performance of the ACMG-AMP criteria in a large familial renal glucosuria cohort with identified SLC5A2 sequence variants. Clin Genet. 2023 Nov;104(5):582-586. doi: 10.1111/cge.14395.
- Oliveira I, Jacinto R, Pestana S, Nolasco F, Calado J, Lopes SS, Roxo-Rosa M. Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease. Int J Mol Sci. 2021 Aug 20;22(16):9013.
- Kidd K, Vylet'al P, Schaeffer C, Olinger E, Živná M, Hodaňová K, Robins V, Johnson E, Taylor A, Martin L, Izzi C, Jorge SC, Calado J, Torres RJ, Lhotta K, Steubl D, Gale DP, Gast C, Gombos E, Ainsworth HC, Chen YM, Almeida JR, de Souza CF, Silveira C, Raposeiro R, Weller N, Conlon PJ, Murray SL, Benson KA, Cavalleri GL, Votruba M, Vrbacká A, Amoroso A, Gianchino D, Caridi G, Ghiggeri GM, Divers J, Scolari F, Devuyst O, Rampoldi L, Kmoch S, Bleyer AJ. Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations. Kidney Int Rep. 2020 Jul 3;5(9):1472-1485. doi: 10.1016/j.ekir.2020.06.029.
- Calado J, Santos AR, Aires I, Lebre F, Nolasco F, Rueff J, Ramalho J. The Na+ -coupled glucose transporter SGLT2 interacts with its accessory unit MAP17 in vitro and their expressions overlap in the renal proximal tubule. FEBS Lett. 2018 Oct;592(19):3317-3326. doi: 10.1002/1873-3468.13233.
Colaborations
- Anthony J. Bleyer, Wake Forest University School of Medicine
Rare Kidney Disease Foundation
- Franz Schaefer, Heidelberg University Hospital
European Reference Network for Rare Kidney Diseases Registry