Renal Research Novum – Bengt Lindholm Group

Renal Research Novum, a section within the Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, is focused on chronic kidney disease and its complications such as cardiovascular disease and metabolic and nutritional alterations, and the treatment of kidney failure with dialysis, especially peritoneal dialysis.

Renal Research Novum is built on the unique conditions and opportunities for integrated research (academia- industry - healthcare), translational research (epidemiological, clinical and basic research) and collaborative research (collaborations with researchers from many countries) at Novum, Karolinska University Hospital and Karolinska Institutet.

We focus on research on chronic kidney disease and kidney failure, its complications such as cardiovascular disease, metabolic alterations, malnutrition and inflammation, and its treatment with dialysis, especially peritoneal dialysis. 

The group has about 10-15 co-workers including visiting post doc physician scientists, from Europe, Asia, and the Americas, and depend on the close cooperation with nephrologists from the Division of Renal Medicine (of which we are a part) including among others Peter Stenvinkel, Olof Heimbürger, Peter Bárány and Marie Evans. 

We provide visiting clinical researchers with research training and continue training, mentoring and collaboration with clinical researchers after their return to home universities for the mutual benefit of involved institutions

We have many ongoing research collaborations with centers in Europe, Asia and the Americas.

We publish more than 25 original papers and 10 review papers or book chapters each year and participate at international meetings with invited lectures and presentations of abstracts.

We organize - together with Peter Stenvinkel and Marie Evans - weekly hybrid renal research seminars where diverse topics in renal medicine are discussed among participants from Europe, Asia, and the Americas. 

We organize also other regular meeting activities such as the bi-annual Nordic/Northern PD Council (NPDC) meetings and annual Peritoneal Transport Meetings. 

Bengt Lindholm, MD, PhD, nephrologist, Associate Professor and Senior Research Specialist, is head of Renal Research Novum, a section within the Division of Renal Medicine at Karolinska Institutet. 

Bengt Lindholm was previously head of the Nephrology department at Karolinska University Hospital, Stockholm, Sweden 1990-1993, and serves/served as Associate Professor/Adjunct Professor, Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, since 1989 and as Director Scientific Affairs Renal Care Europe, Baxter Healthcare 1993-2022. 

His research focuses on peritoneal dialysis, especially peritoneal dialysis solutions and peritoneal transport of solutes and fluid, and factors influencing clinical outcomes in patients with kidney failure such as malnutrition, inflammation, and cardiovascular disease.

Bengt Lindholm has authored more than 800 publications including 30 book chapters and has been invited as speaker to 400 international and national conferences.

Bengt Lindholms biography at Orcid

Google Scholar Citations, Bengt Lindholm

Bengt Lindholm at ResearchGate               

Renal Research Novum serves as a center for statistical analyses led by Abdul Rashid Tony Qureshi and houses clinical-epidemiological databases linked to studies performed at Division of Renal Medicine and other institutions. 

Renal Research Novum also serves as a center for clinical nutritional studies in patients with chronic kidney disease and kidney failure led by Carla M Avesani

Research

Predictors of clinical outcome in end-stage renal disease (ESRD) patients.

Peter Stenvinkel/Bengt Lindholm

Malnutrition, inflammation and atherosclerosis (MIA) and other determinants of clinical outcome in ESRD patients are investigated in collaboration with Division of Renal Medicine. This project has identified several novel risk factors for cardiovascular disease such as CRP, pro-inflammatory cytokines (IL-6), low fetuin (a potent circulating inhibitor of vascular calcification), markers of oxidative stress (such as plasmalogens and 8-OHdG), markers of endothelial dysfunction (ICAM/VCAM) and markers of wasting (low lean body mass). On the other hand, a high serum cholesterol, high homocysteine, and high BMI, predicts better survival and are examples of so called reverse epidemiology in ESRD. The impact of genetic variations are studied (see below).

Peritoneal dialysis (PD): Interactions between dialysis solutions, peritoneal membrane and systemic alterations in PD patients.

Bengt Lindholm

Peritoneal dialysis is a major research focus of Renal Research Novum.  Bengt Lindholm introduced in Sweden 1978, continuous ambulatory peritoneal dialysis (CAPD), a machine-free home dialysis treatment method for patients with kidney failure and has since then authored more than 300 papers on peritoneal dialysis and supervised or co-supervised 14 PhD theses involving peritoneal dialysis. 

One line of research involves studies on peritoneal dialysis solutions with currently clinically used osmotic agents including glucose, amino acids, and icodextrin (glucose polymers) and the use of glucose -sparing combinations of glucose free dialysis fluids to reduce the systemic and local consequences of high peritoneal glucose exposure. Peritoneal dialysis solutions are investigated in experimental and clinical studies as regards their effects on peritoneal transport kinetics, peritoneal membrane function, infections, and metabolic and nutritional changes. Mathematical modeling is applied to better understand diffusive and convective transport, and to predict possible consequences of altered PD fluid composition and different dialysis regimens. The impact of genetic variations on peritoneal membrane characteristics has been investigated in several studies

Another line of research involves studies on clinical outcomes in patients undergoing peritoneal dialysis in Sweden and other countries to identify risk factors for cardiovascular disease, infections and mortality and to investigate links between malnutrition, inflammation and atherosclerosis (MIA syndrome) and other determinants of clinical outcomes including inflammatory and metabolic parameters.

Other research areas are impact of remote patient monitoring on clinical outcomes of peritoneal dialysis patients, barriers to the access and implementation of peritoneal dialysis therapy and factors influencing clinical outcomes, healthcare resource utilization and time on therapy in PD patients.

Activities

Peritoneal Transport Meetings

Renal Research Novum and Bengt Lindholm organize - together with international collaborating academic partners including the International Center for Biocybernetics at Polish Academy of Sciences, Warsaw, Poland – the annual Peritoneal Transport Meetings either as separate events or in conjunction with international congresses. These meetings focus on peritoneal transport of fluid and solutes provides a platform for presenting and discussing structural and functional changes of peritoneal membrane and the vasculature and causes, consequences, and methods to describe these changes, as well as impact of various factors on peritoneal fluid and solute transport and changes in the vascular system that may affect patients with kidney failure undergoing peritoneal dialysis. 

Nordic/Northern Peritoneal Dialysis Council (NPDC) meetings 

Another regular scientific and educational meeting activity is the  access to participants from Asia, Europe and the Americas) meetings with peritoneal dialysis (PD) experts in the Nordic and Baltic countries plus Poland. These meetings have since 2006 been organized by Bengt Lindholm and Renal Research Novum together with alternating hosts in the different countries. The aim of NPDC meetings is to improve quality of care and promote the use of PD in the Nordic and Baltic countries through sharing knowledge and experiences and initiating collaborative projects among PD experts in the region.

Statistics and clinical-epidemiological studies

Statistics and clinical-epidemiological studies are the foundation of evidence-based healthcare. Our research is primarily based on databases and registries and focuses on chronic kidney disease and its complications, including cardiovascular disease, inflammation, and disorders of nutrition and metabolism, as well as the treatment of patients with kidney failure using especially peritoneal dialysis. 

One main reason why Renal Research Novum attracts doctoral students from CLINTEC and other departments at KI such as the division of Orthopedics and Biotechnology as well as many foreign visiting researchers is that we provide support for statistical analyses, interpretation of results and writing of manuscripts.  This expertise is primarily provided by Abdul Rashid Tony Qureshi, MD, PhD, who is employed as statistician and researcher at Renal Research Novum (and its predecessors), Division of Renal Medicine. 

Renal Research Novum serves as a repository for several clinical experimental and cohort studies in patients with kidney failure. Major cohort studies - initiated and led by Peter Stenvinkel, together with Peter Bárány and Olof Heimbürger - at Renal Medicine include the Malnutrition, Inflammation and Atherosclerosis (MIA) study in incident dialysis patients, Mapping of Inflammatory Markers in Chronic Kidney Disease (MIMICK) Study in prevalent hemodialysis patients (MIMICK 1) and in prevalent peritoneal dialysis patients (MIMICK2), and the KärlTx Study of kidney failure patients undergoing living donor kidney transplantation. These cohort studies have formed the basis for many publications and PhD theses at the Division of Renal Medicine.

Renal Research Novum also has access - direct or indirect through collaborations - to national quality registries that may include closer links to the Swedish Renal Registry in collaboration with Professor Marie Evans. 

Databases brought by visiting researchers or sent by collaborators from different countries represent another important source of clinical data for comparative analyses and specific studies in cohorts of patients with chronic kidney disease including peritoneal dialysis patients. 

Predictors of clinical outcome in kidney failure patients.

Malnutrition, inflammation and atherosclerosis (MIA) and other determinants of clinical outcomes in kidney failure patients are investigated in collaboration with Peter Stenvinkel, together with Peter Bárány and Olof Heimbürger. This project has identified several novel risk factors for cardiovascular disease such as CRP, pro-inflammatory cytokines (IL-6), low fetuin (a potent circulating inhibitor of vascular calcification), markers of oxidative and glycoxidative stress (such as plasmalogens and 8-OHdG, advanced glycation end products (AGEs) and their receptor (RAGE) as well as mitochondrial-derived peptides (MDPs), including humanin (HN), MOTS-c, and humanin-like 1 (HN-L1), markers of endothelial dysfunction (ICAM/VCAM) and markers of wasting or malnutrition (such as low lean body mass and low handgrip strength). On the other hand, many traditional risk factors such as high serum cholesterol, high homocysteine, and high BMI, appear to predict better survival in patients with kidney failure and are examples of so-called reverse epidemiology in ESRD. 

Uremic toxicity: The impact of small, middle and large solutes on clinical outcome in kidney failure

The state of uremia is associated with changes in almost all cells, tissues and organs as a consequence of accumulation of small and large solutes following the decline of excretory, metabolic and endocrine functions of the diseased kidneys. Dialysis can only partly compensate for this, suggesting that large solutes such as peptides and proteins which are not dialyzable account for a major part of the residual uremic toxicity in renal patients. In addition, deficiencies or functional alterations of genes, proteosomes and protein/peptides can be of importance. We have studied the impact of uremia on DNA (epigenetics), RNA expression, and protein/peptides due to changes in nucleotides, lipids and amino acids, peptides because of oxidative stress, reactive carbonyls, advanced glycated end-products (AGEs) and other pathways.

Nutrition and metabolism in kidney failure and peritoneal dialysis

Kidney failure is associated with profound metabolic and nutritional alterations including insulin resistance, anorexia, dyslipoproteinemia, amino acid alterations and malnutrition, which are worsened by co-existing co-morbidities, medications and dialysis therapy. We study this in experimental, interventional and prospective studies.

Because patients undergoing peritoneal dialysis are exposed to glucose absorption from the dialysate and protein losses to the dialysate in addition to catabolic conditions related to the disease itself, they are at risk for both protein-energy wasting (PEW), sarcopenia and obesity, requiring tailored recommendations for the intake of energy, protein, phosphorus, potassium, sodium, and fluid. These are important areas for Renal Research Novum. 

Studies on clinical nutrition in patients with chronic kidney disease and kidney failure are performed by Carla Avesani and researchers in her group who study nutritional interventions in patients with different stages of chronic kidney disease and patients with kidney failure patients treated by peritoneal dialysis. 

Food as Medicine is a research line launched by Peter Stenvinkel and Carla Avesani to investigate the role of healthy eating patterns and of foods rich in bioactive compounds to avoid and treat metabolic disorders arising from obesity, hypertension, diabetes and chronic kidney disease.

The impact of genetic factors on clinical outcome in ESRD.

Martin Schalling/Bengt Lindholm

Single nucleotide polymorphisms (SNPs) and other forms of genetic variations are analyzed in collaboration with Louise Nordfors and colleagues at Center for Molecular Medicine. This project has so far analyzed about 50 different candidate genes (with established or suspected influence on clinical outcome in other patient cohorts), and more than 10 genes have so far been shown to be associated with clinical outcome in ESRD patients.

Uremic toxicity: The impact of small, middle and large solutes on clinical outcome in ESRD.

Bengt Lindholm

The state of uremia is associated with changes in almost all cells, tissues and organs as a consequence of accumulation of small and large solutes following the decline of excretory, metabolic and endocrine functions of the diseased kidneys. Dialysis can only partly compensate for this, suggesting that large solutes such as peptides and proteins which are not dialyzable account for a major part of the residual uremic toxicity in renal patients. In addition, deficiencies or functional alterations of genes, proteosomes and protein/peptides can be of importance. We study the impact of uremia on DNA (epigenetics), RNA expression, and protein/peptides due to changes in nucleotides, lipids and amino acids/peptides/proteins as a consequence of oxidative stress, reactive carbonyls, advanced glycated end-products (AGEs) and other pathways.

Nutrition and metabolism in ESRD.

Bengt Lindholm

Kidney failure is associated with profound metabolic and nutritional alterations including insulin resistance, anorexia, dyslipoproteinemia, amino acid alterations and malnutrition, which are worsened by co-existing co-morbidities, medications and dialysis therapy. We study this in experimental, interventional and prospective studies.

Publications

All publications from group members

Funding

Renal Research Novum is supported by a grant from Vantive to the Department of Clinical Science, Intervention and Technology, Karolinska Institutet.

Staff and contact

Group leader

All members of the group

Visiting address

Institutionen för klinisk vetenskap, intervention och teknologi, Karolinska Institutet, Renal Research Novum, Hälsovägen 7, Novum plan 5, Huddinge, 141 57

Postal address

Institutionen för klinisk vetenskap, intervention och teknologi, Karolinska Institutet, Renal Research Novum, M99 Karolinska Huddinge, Stockholm, 14186