Resources

From NIER

NIER welcomes presentations and articles of scientists, science educators, doctors and PhD students on key issues related to renal research to advance renal research, scientific knowledge, and education. Please contact the NIER editorial board for submissions or enquiries.

1 Methods in Renal Research on NIER
2 Articles on NIER
3 Meeting Reports on NIER
4 Presentations on NIER

[edit] Methods in Renal Research on NIER

[edit] The in vivo model of bilateral ischemia reperfusion injury

by Wilco Pulskens and Gwendoline Teske (Winners of the NIER Essay Contest 2008)

Acute renal failure is often a consequence of ischemia/reperfusion (I/R) injury that is associated with a high mortality rate. Therefore, it is of crucial importance to get more insight into the underlying molecular and cellular processes. The in vivo model of I/R injury represents an easy, valuable and reproducible model to investigate the contribution of individual genes/proteins in the complex interplay of underlying pathophysiology and subsequent recovery upon renal I/R injury. This essay can be used as guide to set up an in vivo model to mimic acute renal injury and to aware people of essential steps within this model.

[edit] Impact of chronic renal failure on bone marrow vascular progenitor cells

by Matthieu Monge (Second Prize NIER Essay Contest 2008)

Chronic renal failure (CRF) is associated with an increased risk for cardiovascular (CV) mortality and morbidity. Impaired angiogenesis, arteriogenesis, vasculogenesis, medial and intimal calcifications and left ventricular hypertrophy are features of CV disease in CRF, and may be associated with endothelial progenitor cells (EPCs) dysfunction, a well-established non-traditional CV risk factor. The aim of the study is to evaluate the impact of chronic uremia on circulating and bone marrow-derived EPCs and inflammatory cells in a murine model of CRF.

[edit] Proteomics in nephrology: from proteins to patients

by Ewout Hoorn (Winner of the NIER Essay Contest 2007)

In the post-genomics era, proteomics has evolved as a powerful, new technique that aims to identify, quantify, and analyze a large number of proteins in a functional context. Therefore, proteomics can be used to study cellular pathways and identify disease biomarkers. Technically speaking, the birth of proteomics resulted from the coupling of protein separation techniques to mass spectrometry. Currently, many different proteomics platforms are recognized, including techniques based on two-dimensional electrophoresis, liquid chromatography, and chip-based techniques. Here, proteomics in nephrology is reviewed, including the principles of the main proteomics techniques, potential basic and clinical applications, and practical research protocols.

[edit] The model of Unilateral Ureter Obstruction

by Geurt Stokman (Second prize NIER Essay Contest 2007)

The unilateral ureter obstruction model is a relevant method to study cellular aspects involved in the pathogenesis of tubulo-interstitial fibrosis in experimental animal models. The amount of publications with respect to this model is immense and may be overwhelming for those new or inexperienced to this field of kidney research. This review is written to provide the reader with basic information concerning the model from both a theoretical and practical point of view.

[edit] Detection of functional binding partners for adhesion molecules, chemokines and growth factors in tissue sections

by Patricia J.W.A.M. Celie and Jaap van den Born (Third Prize NIER Essay Contest 2007)

Detection of binding partners for proteins of interest in tissue sections offers a way to detect relevant interactions without being biased towards known candidates (e.g. when selecting antibodies). In addition, functional binding is detected directly, rather than detecting just the presence of a certain candidate ligand. From this perspective, we present a protocol for the detection of binding of L-selectin, monocyte chemoattractant protein-1 and fibroblast growth factor-2 proteins to tissue sections, with a focus on the complex binding interaction with heparan sulfate proteoglycans. This protocol can be used as a starting point to study interactions with other proteins of interest.

[edit] Investigating the role of bone marrow-derived stem cells in renal repair

by Miriam Huls, Frans G.M. Russel and Rosalinde Masereeuw

Acute kidney injury (AKI) is a frequent clinical problem with a high mortality rate generally caused by ischemic insults. Nevertheless, the kidney has a high capacity to regenerate after ischemic injury. Tubular cells can restore renal function by proliferation and dedifferentiation in a mesenchymal cell-type. Additionally, stem cells residing in bone marrow may contribute. We have provoked AKI in mice by inducing ischemic-reperfusion injury, and studied the contribution of bone marrow-derived cells to renal regeneration after transplantation of labeled bone marrow. In this essay the advantages and shortcomings of our procedure are critically discussed with respect to other methods described.

[edit] Isolation and expansion of human mesenchymal stem cells from perirenal adipose tissue of kidney donors

by M.J. Crop, C.C. Baan, J.N.M. IJzermans, I.P.J. Alwayn, W. Weimar and M.J. Hoogduijn

Human mesenchymal stem cells (MSCs) have multilineage differentiation potential and immunomodulatory capacity with promising clinical applications. MSCs are primarily derived from bone marrow, but also reside in other tissues. We examined the use of perirenal adipose tissue, a waste product during the kidney donation procedure, as a source of MSCs. The fat was surgically obtained during kidney transplantation, mechanically disrupted, digested enzymatically and the isolated MSCs were expanded in culture. This method demonstrates that perirenal fat is a new and rich source of MSCs that are relevant for immunomodulatory and tissue repair studies in a kidney transplantation setting.

[edit] A Porcine Model for Hemodialysis Access Failure

by Joris Rotmans

Hemodialysis access complications constitute a major cause of morbidity in hemodialysis patients. The failure of hemodialysis access grafts is predominantly because of progressive intimal hyperplasia at the venous anastomosis, resulting in a decline of graft flow, which ultimately gives rise to graft thrombosis. Thus far, procedures developed for improving patency of these grafts have proven unsuccessful, which can be partly explained by the lack of relevant animal models. For this purpose, we developed a porcine model for arteriovenous graft failure that will allow the assessment of promising new therapeutic strategies to improve the patency of vascular grafts for hemodialysis.

[edit] Assessment of the novel renin angiotenin sytem enzyme, ACE2 in the kidney using fluorescent enzymatic assay, immunocytochemistry, and real time polymerase chain reaction

by JaNae Joyner

Recently, angiotensin converting enzyme 2 (ACE2), a novel enzyme of the renin angiotensin system (RAS), has been found to convert angiotensin II (Ang II) to angiotensin-(1-7) [Ang-(1-7)] with high catalytic efficiency. Since the RAS is a known regulator of body fluid homeostasis with Ang II serving as an antidiuretic and Ang-(1-7) serving as a diuretic, the presence and abundance of ACE2 in the kidney could be important in regulating fluids in the body. Methodologies including the ACE2 fluorescent enzymatic assay, ACE2 immunocytochemistry, and real time polymerase chain reaction for ACE2 were optimized to completely assess kidney ACE2.

[edit] Articles on NIER

[edit] Articles from 2008

[edit] The proximal tubular cell, a key player in renal damage

by Dr. Mirjan M. van Timmeren (2008)

An overview is given on proteinuria-induced renal damage, with special focus on the effects of albumin and albumin-bound fatty acids. In addition an introduction on Kidney Injury Molecule-1 (KIM-1), a tubular protein that is heavily expressed after renal damage, is given.
Originally published as General Introduction to the PhD thesis by Dr. Mirjan M. van Timmeren (2008).

[edit] Articles from 2007

[edit] Bone marrow-derived cells in kidney repair: A double-edged sword?

by Dr. Martine Broekema (2007)

Bone marrow-derived cells (BMDC) possibly play a therapeutic role in organ repair after injury. Here, an overview is provided on some general aspects of renal damage, repair, and the possible therapeutic potential of BMDC therein.
Originally published as General Introduction to the PhD thesis by Dr. Martine Broekema (2007).

[edit] The renin-angiotensin aldosterone system (RAAS) in renal disease

by Dr. A. Titia Lely (2007)

An overview is provided on the renin-angiotensin aldosterone system (RAAS) and several components of this system, such as angiotensin 1-7 (ang 1-7) and angiotensin converting enzyme 2 (ACE2). Furthermore both genetic and environmental factors influencing the RAAS and the response to intervention are explained.
Originally published as General Introduction to the PhD thesis by Dr. A. Titia Lely (2007).

[edit] Relative blood volume measurements during hemodialysis

by Dr. Judith J. Dasselaar and Dr. Casper F.M. Franssen (2007)

A brief pathophysiological overview is provided concerning the most frequently occurring complication during a hemodialysis treatment: dialysis hypotension. In addition, in light of the continuing and ongoing efforts made to prevent dialysis hypotension an introduction into the measurement of relative blood volume is given.
Originally published as General Introduction to the PhD thesis by Dr. Judith J. Dasselaar (2007).

[edit] Heparan sulfate in glomerular inflammation

by Dr. Angelique Rops and Dr. Johan van der Vlag (2007)

Proliferative forms of glomerulonephritis are characterized by the influx of inflammatory cells (leukocytes), proteinuria, hematuria and decline in renal function. Heparan sulfate proteoglycans (HSPGs) play a prominent role in inflammatory processes. HSPGs consist of a core protein to which linear heparan sulfate (HS) side chains are attached. HS chains consist of up to 150 disaccharide units of α(1-4)-uronic acid-β(1-4)-glucosamine, which can be modified at different positions by numerous enzymes, which include N-deacetylases, N- and O-sulfotransferases, C5-epimerase, sulfatases and hydrolases. The possible HS modifications give rise to an enormous dynamic and structural complexity of the HS chain, which corresponds to the variety of biologic functions mediated by HS, including its role in inflammation. During inflammation, HS in the extracellular matrix (ECM) and at the surfaces of leukocytes and endothelial cells binds chemokines, which directs the movement and activation of leukocytes. Endothelial and leukocyte cell surface HS also interacts directly with adhesion molecules like selectins and integrins. In particular HS on activated endothelium is crucial for the interaction with leukocytes.
Originally published as General Introduction to the PhD thesis by Dr. Angelique Rops (2007).

[edit] The fibrinolytic system in renal disease

By Dr. Joris Roelofs (July 2007)

In recent years, it has been demonstrated that the fibrinolytic system is capable of surpassing its classical role as a dissolver of blood clots. The components of this protein system exert a broad variety of functions at the intersection between fibrinolysis, inflammation and immunity. This article addresses the diverse effects of the fibrinolytic system in acute renal allograft rejection, acute pyelonephritis and renal ischemia-reperfusion injury. For further information, you can contact Joris Roelofs: j.j.roelofs@amc.uva.nl

Originally published as General Introduction to the PhD thesis by Dr. Joris Roelofs (July 2007)

[edit] Cardiorenal interaction - Therapeutic perspectives

By Dr. Willemijn Windt (2007)

Chronic kidney disease is a world wide health problem and has a tremendous impact on both quality of life and mortality. Population based research suggests for example that 11% of the US adult population suffers from chronic kidney disease1;2, which results in poor outcome and high health care costs. Renal insufficiency, defined as a reduced glomerular filtration rate (GFR) or presence of albuminuria, is an independent risk factor for cardiovascular disease3;4, in mild to severe chronic heart failure5-8, post myocardial infarction9;10, in the hypertensive population11, and even in the general population12;13. Therefore, in these populations, cardiovascular events are the main cause of death. In patients with end stage renal failure this is 10-20 times more common than in the general population14. For these reasons, patients should be evaluated for chronic kidney disease to assess the increased risk and optimize treatment strategies.
Originally published as General Introduction to the PhD thesis by Dr. Willemijn Windt (2007)

[edit] Articles from 2006

[edit] Calcineurin-based immunosuppression in renal transplantation: Focus on efficacy, the role of steroids, and the cardiovascular risk

By Dr. Johannes M.M. Boots (2006)

For patients suffering from renal failure, renal transplantation offers several advantages compared to dialysis: it improves survival, and renal transplant recipients experience a better quality of life than patients on either hemodialysis or peritoneal dialysis. Moreover, the costs of a renal transplantation are significantly lower than those associated with dialysis. Unless a transplant recipient receives an organ from an identical twin, a graft will always be recognized as ‘foreign’ and, consequently, rejected. To prevent this, graft recipients need to be treated with immunosuppressive agents, at least during the initial post-transplantation period. A delicate balance exists between efficacy (prevention of rejection) and toxicity (infections, malignancies, agent-specific side effects). Several immunosuppressive agents are currently registered for use in renal transplantation. This review will focus on the efficacy and side effects of steroids, cyclosporine A (CsA), and tacrolimus (TAC), as these agents form the mainstay of immunosuppression.
(originally published as general introduction to Dr. Boot's dissertation)

[edit] Renal Heparan Sulfate Proteoglycans

by Dr. Patricia Celie, and Dr. Jacob van den Born (June, 2006)

Although the process of leukocyte extravasation upon inflammation has been studied quite extensively, the potential role of heparan sulfate proteoglycans (HSPGs) therein remains relatively unclear. In this article, a summary of the multistep model of leukocyte extravasation is given, with a special focus on the role of the leukocyte adhesion molecule L-selectin. Next, the general structure, levels of regulation, as well as functions of HSPGs are discussed, with a special focus on their role in binding and presenting chemokines and growth factors. Historically, the kidney has been the main organ of interest to study HSPG function, as HSPGs are proposed to be important in determining the charge-selectivity of the glomerular basement membrane. Therefore, an overview of HSPG expression in the kidney, the paradigm of HSPG function in glomerular filtration, as well as HSPG alterations upon renal disease and inflammation is given.

(originally published as general introduction to Dr. Celie's dissertation)

[edit] The podocyte and parietal epithelial cell in proteinuria and glomerulosclerosis

by Dr. Henry Dijkman, Dr. K.J.M. Assmann, and Dr. E.J. Steenbergen (November, 2006)

Kidneys are paired structures that lie in the retroperitoneum. Each kidney contains approximately 1,000,000 glomeruli, which are small balls of capillaries (diameter 0.1 mm) through which the blood is filtered. The glomerular capillary wall is composed of three components: the fenestrated endothelium which lines the capillaries; the glomerular basement membrane, a thin sheet composed of negatively charged extracellular matrix proteins; the visceral epithelial cells, which are also called podocytes because of their characteristic interdigitating foot processes that cover the glomerular basement membrane. Proteinuria is considered to be predominantly caused by alterations of the slit diaphragm complex. Proteinuria is mostly accompanied by disturbances of the architecture of the foot processes, so called effacement. Proteinuria is a hallmark of glomerular diseases and an independent predictor of renal function deterioration. Histologically, renal insufficiency is characterised by glomerulosclerosis and tubulo-interstitial fibrosis. Focal segmental glomerulosclerosis (FSGS) has become one of the most common glomerular diseases. In its classical form FSGS is characterized by mesangial sclerosis, obliteration of glomerular capillaries, formation of adhesions between the glomerular tuft and Bowman’s capsule, podocyte hypertrophy, hyalinosis of the vessel wall and intracapillary foam cells. FSGS may be secondary to glomerular hyperfiltration and thus the result of longstanding and ongoing glomerular injury ending with chronic renal disease.

(originally published as general introduction to Dr. Dijkman's dissertation)

[edit] The role of intrarenal factors during renal resistance to RAAS-blockade and strategies towards circumvention

by Dr. Andrea B. Kramer (2006)

Chronic renal disease (CRD) is a worldwide public health problem affecting an increasing number of patients. A substantial part of the patients with CRD progress to end-stage renal disease (ESRD) and need renal replacement therapy, such as dialysis or renal transplantation [2]. CRD is also associated with high morbidity and mortality, mainly due to cardio-vascular disease. CRD can result from a wide variety of causes, which eventually lead to progressive renal function loss by a final common pathway towards ESRD. Currently, renoprotection is provided by Renin-Angiotensin-Aldosterone System (RAAS, see below) blockade in many patients by reduction of proteinuria and blood pressure. However, interindividual differences in efficacy of renoprotection remain large, and consequently, progressive loss of renal function still leads to end stage renal damage. Therefore, it is important to elucidate the mechanisms underlying these individual differences in therapy response. Identification of factors involved in therapy resistance may allow to design more effective treatment strategies to protect against end stage renal damage. Before identifying factors involved in therapy resistance, it is important to know which factors are important in the decline of renal function in the natural course of the disease.
(originally published as general introduction to Dr. Kramer's dissertation)

[edit] Management strategies in hemodialysis vascular access

By Dr. Joke van der Linden (2006)

Since the introduction of the arteriovenous fistula (AVF) and the use of interposition graft (AVG) little improvement has been made in the vascular access field. Still, vascular access related complications are one of the most important reasons for hospitalisation, morbidity and mortality. The native arteriovenous fistula is the vascular access of choice because of its low risk of thrombosis and infection. However construction is not always possible, necessitating the use of prosthetic grafts. This review describes the ongoing problems encountered in the vascular access field and describes important pre- and postoperative strategies to improve the care for vascular accesses in hemodialysis.
(originally published as general introduction to Dr. Van der Linden's dissertation)

[edit] Diabetic Nephropathy and the pathogenic role of growth factors

By Dr. Peggy Roestenberg (2006)

This article briefly describes the characteristics of diabetes, diabetic nephropathy and the role of growth factors in this process.
(originally published as general introduction to Dr. Roestenberg's dissertation)

[edit] CD44 in renal disease: friend or foe

by Dr. Kasper Rouschop, and Dr. Sandrine Florquin (2006)

This article provides a general introduction of the kidney, and renal diseases, and focuses on the involvement of the adhesion molecule CD44 and its splice-variants in the development and progression of renal diseases.

(originally published as general introduction to Dr. Rouschops dissertation)

[edit] Effects of hemodialysis on granulocyte adhesion: do they keep on rolling?

by Dr. Marco E. van Teijlingen (2006)

Patients on intermittent hemodialysis (HD) suffer from a high susceptibility to bacterial infections. In the immune defense against invading pathogens, granulocytes play a pivotal role, being the first type of leukocyte recruited. Dr. van Teijlingen has focused on evaluating the effect of HD-treatment per se on granulocyte adhesion, in particular, on the first step herein, i.e. the rolling of these cells along venular endothelium. This article provides some background information on HD, HD-related bio-incompatibilty as well as granulocyte recruitment. Furthermore, it briefly introduces the contents of the Dr. Van Teilingen's thesis.

(originally published as general introduction to Dr. Van Teijlingen's dissertation)

[edit] Articles from 2005

[edit] Technical considerations and analytical issues of expression profiling in tissues and microarray technology

by Dr. Helena Chon (2005)

(originally published as general introduction to Dr. Chon's dissertation)

[edit] Nucleosomes in the development of systemic lupus erythematosus (SLE)

by Dr. J. Dieker (2005)

This review describes the history and current knowledge of the autoimmune disease systemic lupus erythematosus (SLE). The last decade cumulating evidence points to the nucleosome as the major autoantigen that drives the autoimmune response in SLE. The proposed role of nucleosomes in the development in SLE is described, as well as the underlying disturbed clearance of apoptotic cells.

(originally published as general introduction to Dr. Dieker's dissertation)

[edit] Assessment of Left Ventricular Function in Hemodialysis Patients

by Dr. Eric H.Y. Ie, Dr. Rob Krams, and Dr. Robert Zietse (2005)

Volume withdrawal by ultrafiltration during hemodialysis (HD) may lead to intravascular hypovolemia and intradialytic hypotension. Left ventricular (LV) function is an important part of the hemodynamic defense. Chronic pressure and volume overload account for a high prevalence of LV hypertrophy in dialysis patients, which may lead to LV dysfunction. However, elevated cardiac filling pressures may reflect volume overload before HD rather than heart failure, and loading conditions are altered by volume withdrawal. These cyclic changes in volume status hamper LV function assessment in dialysis patients. Current LV systolic and diastolic function measurements are reviewed. Their load dependence is discussed. Future perspectives for loadindependent LV function assessment and measurement of pressurevolume relations in clinical dialysis practice are suggested.

(originally published as general introduction to Dr. Ie's dissertation)

[edit] Immuno Modulation in Renal Transplant Recipients

by Dr. Ajda Tahereh Rowshani, and Prof. Dr. Ineke J. M. ten Berge (2005)

Over the past decades, transplantation has become the preferred approach to the treatment of failure of heart, liver, kidneys, and lungs. Recently, progressive improvement in allograft survival, in particular of kidney allografts, has been achieved. Intriguingly, this improvement is seen mainly in recipients who have never experienced an acute rejection episode, emphasizing the recipient's alloimmune response as a major determinant of overall transplant outcome. In this article, first, current policy regarding immunosuppressive drug treatment after renal transplantation is summarized. Second, the need for read out parameters for measurement of drug-efficacy in the light of considerably improved transplant results is discussed. After a brief discussion of mechanisms of allo-immune reactivity, possible pathogenetic mechanisms underlying subclinical rejection are proposed, followed by the current view on its significance for the transplant patient. Finally, one of the major infectious problems in patients after solid organ transplantation, i.e. cytomegalovirus infection is shortly introduced.

(originally published as general introduction to Dr. Rowshani's dissertation)

[edit] Articles from 2004

[edit] The perinatal balance of nitric oxide and reactive oxygen species modulates blood pressure in adult life

by Dr. Simona Racasan (2004)

Emerging evidence supports that fetal adaptation to adverse environmental factors in the perinatal period results in permanent structural and functional changes that become manifest as cardiovascular disease in adult life. This article provides a brief overview of the current data and views on this phenomenon of “perinatal programming” and the possible mechanisms involved, with a particular focus on the role of perinatal levels of nitric oxide and radical oxygen species in the development of hypertension. Furthermore, a commonly used model to study developmental aspects of genetic hypertension, the spontaneuous hypertensive rat (SHR) is discussed.

(originally published as general introduction to Dr. Racasan's dissertation)

[edit] Meeting Reports on NIER

[edit] Meeting reports from 2007

[edit] PLAN Research Day May 25, 2007

by drs. Ingrid Stroo (2007)

[edit] Meeting reports from 2006

[edit] Symposium Cardiorenal failure, October 3, 2006

by Marten Dooper, Roche Nederland B.V.. This report is focused on research of Dr. Gaillard, Dr. Mosterd, Dr. Hillege, Prof. dr. Amann, Prof. dr. Hampl and Dr. Braam.

[edit] PLAN Research Day December 15, 2006

by drs. Mirjan M. van Timmeren (2006)

[edit] Meeting reports from 2005

[edit] Hypertension Summer school 2005

by drs. Peter E. Westerweel and drs. Leendert Oterdoom (2005)

The 2005 European Society of Hypertension Summer School on Hypertension was organized by the Hungarian Society of Hypertension in Visegrad (Hungary). The summer school covered many aspects of hypertension, including parts of the epidemiology, pathophysiology, clinical presentation and clinical course, associated clinical conditions, and treatment. This report summarizes the key points.