Nephrology

The Kidney Diseases Research Group is dedicated to advancing understanding and improving outcomes across a broad spectrum of kidney disorders, with a strong focus on inherited kidney diseases. Key projects explore autosomal dominant polycystic kidney disease from a gender and reproductive perspective, improve genetic diagnostics using advanced genomic tools, and develop predictive models for autosomal dominant Alport syndrome. Innovative approaches, including artificial intelligence and natural language processing, aim to revolutionize diagnostic precision and patient identification through deep phenotyping and electronic health record analysis.

Beyond inherited conditions, the group investigates glomerulopathies—such as IgA nephropathy and thrombotic microangiopathy—as well as renal implications of inflammatory bowel disease. In chronic kidney disease (CKD), research spans bone health, dialysis-related genetic damage, and the gut microbiota’s role. The group also delves into the mechanisms of inflammation-induced fibrosis and transplant-related complications, including graft inflammation, fibrosis pathways, and EPLETS in kidney transplantation.

Uniting clinical, molecular, and computational approaches, this multidisciplinary team is at the forefront of kidney research, aiming to enhance diagnosis, treatment, and long-term management for diverse patient populations.

Consolidated group of the Sant Pau Research Institute that belongs to:

Main Lines of Research

Inherited Kidney Diseases:

• The FEMALE PKD project, which focuses on a comprehensive approach to autosomal dominant polycystic kidney disease from a gender perspective, with a primary emphasis on reproduction and hormonal aspects, assessing the impact on hepatic and renal factors in women. (Furlano, Monica Maria).
• To improve the genetic diagnostic yield of patients with suspected monogenic nephropathy, with previous negative genetic tests (gene panel/exome/MUC1), incorporating new genomic techniques that can contribute to identifying the etiological diagnosis of their kidney disease. (Ars Criach, Elisabet).
• A cohort of individuals with Autosomal Dominant Alport Syndrome (ADAS) is being studied to identify genetic and epigenetic determinants of phenotypic variability, as well as transcriptomic profiling for characterization of associated molecular signatures. Clinical data are being integrated to develop a predictive tool for assessing the risk of progression to advanced chronic kidney disease in ADAS patients. (Pilco Teran, Melissa Lorena; Torra Balcells, Roser; Furlano, Monica Maria; Ars Criach, Elisabet).
• Inherited kidney diseases remain underdiagnosed, despite being the most common cause of early-onset chronic kidney disease (CKD), partly due to the challenges posed by clinical diagnosis given their heterogeneity. The use of artificial intelligence to develop clinical diagnostic tools represents a paradigm shift. Currently, clinical diagnostic tools for rare diseases (none of which are specifically designed for inherited kidney diseases) are based on ontologies, but they have not been widely implemented due to their limited precision in describing these particular conditions. Within the framework of this project, an extensive curation of terms using HPO (Human Phenotype Ontology) annotations has been carried out, achieving a precise description of these diseases in the context of deep phenotyping. The quality of this data will enable the development of clinical diagnostic tools, enriched not only with this curated information but also with real patient data using machine learning techniques. (Torra Balcells, Roser).
• Identification of undiagnosed patients with inherited kidney disease by using natural language processing to extract data from electronic health records. (Torra Balcells, Roser).

Glomerulopathies:

• Study of the role of crescents in IgA nephropathy. Characteristics, prognosis, and treatment optimization. (Marco Rusiñol, Helena).
• Study of kidney diseases in patients with inflammatory bowel disease. Investigating possible associations and prognosis. (Marco Rusiñol, Helena).
• Clinical and histological patterns of renal thrombotic microangiopathy (TMA). TMA is a renal histological lesion caused by endothelial injury, usually associated with microangiopathic hemolysis, but in some cases it may be limited to the kidney, requiring renal biopsy (RB) for diagnosis. Current knowledge of its histopathology is insufficient to understand its etiopathogenesis and thus to guide its treatment. We would like to describe the clinical and histological presentation of renal TMA to observe whether there are differences between patients with and without peripheral hemolysis, as well as between the different etiologies or triggers of TMA. This information would improve the diagnostic and etiological approach of renal TMA and guide its management.

Chronic Kidney Disease:

• Patients with chronic kidney disease (CKD) have a higher risk of fractures compared to the general population. Bone strength is determined not only by quantity (measured by DXA) but also by bone quality. Impact microindentation (IMI) is a technique that globally measures bone strength. This project investigates the behavior of bone strength, as measured by IMI, in different CKD scenarios: prevalent hemodialysis patients, peritoneal dialysis patients, and newly transplanted patients. We study the relationship between IMI and other aspects of the bone phenotype (biomarkers, DXA, TBS, and 3D-DXA), as well as its evolution over time. (Lloret Cora, Maria Jesus).

Cardiovascular risk:

• This line investigates how positional (e.g., standing vs. lying down) and temporal (day-night) variability in blood pressure affects target organ damage in elderly patients with hypertension. The study focuses on identifying patterns of blood pressure fluctuation that may contribute to cardiovascular, renal, or cerebrovascular complications. Preliminary results suggest that greater variability in blood pressure—especially exaggerated nocturnal dips or postural changes—is significantly associated with increased markers of organ damage, including left ventricular hypertrophy, microalbuminuria, and white matter lesions on brain imaging. These findings underscore the importance of monitoring blood pressure dynamics beyond static measurements and support personalized approaches in managing hypertension in older adults. (Fernandez De La Llama, Patricia).

Dialysis:

• Evaluation of genetic damage in CKD and hemodialysis patients and search for solutions (supplementation with antioxidants, switch to another hemodialysis technique, elimination of bisphenol A) and starting a new line about genetic damage and gut microbiota in hemodialysis patients. (Coll Piera, Elisabet).

Inflammation and fibrosis:

• The main aim of this topic is to study inflammation-induced fibrosis. The focus is on the infiltration of M2 macrophages in renal tissue and their relationship with fibrosis and progression to chronic kidney disease. This study has produced several articles on cadaveric vs. living donor transplantation and, more recently, the role of macrophages in the difference in prognosis between ANCAS MPO vs. PR3 vasculitis (in preparation). (Diaz Encarnacion, Maria Montserrat; Bardaji De Quixano, Beatriz).

Transplantation:

• Advances in molecular HLA typing have made it possible to quantify mismatches at the epitope level, revealing that eplet incompatibility—particularly at HLA-DR/DQ loci—may play a critical role in graft outcomes and the development of donor-specific antibodies in kidney transplant recipients. Our research focuses on the impact of HLA class II eplet mismatches (HLA-DR/DQ) on kidney transplant outcomes, particularly their association with tacrolimus levels, graft survival, and acute rejection. (Guirado Perich, Lluis).

Scientific Challenges

Dialysis:

• To evaluate mortality in patients with malnutrition in hemodialysis.
• To evaluate of low acute phase angle as a marker of increased mortality in hemodialysis patients.

Genetic kidney diseases:

• To set up a targeted RNA sequencing approach using a comprehensive renal gene panel to enrich RNA obtained from blood samples with transcripts involved in kidney diseases.
• To procure a multicentric cohort of pregnant women with ADPKD.
• To validate the curation of HPO terms for inherited kidney diseases by European expert centers.
• To test the safety and efficacy of many new molecules for glomerular and genetic diseases.

Contact

Lluís Guirado
lguirado@fundacio-puigvert.es