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Karin G. F. Gerritsen
Department of Nephrology and Hypertension University Medical Center Utrecht Utrecht The Netherlands

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Main text article
Published: 12 July 2021 in Artificial Organs
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A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO-based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3-deoxyglucosone) were measured in EO- and non-EO-treated fluids. Glyoxal and methylglyoxal concentrations increased 26- and 11-fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209- and 353-fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.

ACS Style

Maaike K. van Gelder; Jeroen C. Vollenbroek; Babette H. Lentferink; Diënty H. M. Hazenbrink; Paul J. Besseling; Frank Simonis; Silvia Giovanella; Giulia Ligabue; Maria A. Bajo Rubio; Gianni Cappelli; Jaap A. Joles; Marianne C. Verhaar; Karin G. F. Gerritsen. Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products. Artificial Organs 2021, 1 .

AMA Style

Maaike K. van Gelder, Jeroen C. Vollenbroek, Babette H. Lentferink, Diënty H. M. Hazenbrink, Paul J. Besseling, Frank Simonis, Silvia Giovanella, Giulia Ligabue, Maria A. Bajo Rubio, Gianni Cappelli, Jaap A. Joles, Marianne C. Verhaar, Karin G. F. Gerritsen. Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products. Artificial Organs. 2021; ():1.

Chicago/Turabian Style

Maaike K. van Gelder; Jeroen C. Vollenbroek; Babette H. Lentferink; Diënty H. M. Hazenbrink; Paul J. Besseling; Frank Simonis; Silvia Giovanella; Giulia Ligabue; Maria A. Bajo Rubio; Gianni Cappelli; Jaap A. Joles; Marianne C. Verhaar; Karin G. F. Gerritsen. 2021. "Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products." Artificial Organs , no. : 1.

Journal article
Published: 23 May 2021 in Biology
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The preclinical evaluation of novel therapies for chronic kidney disease requires a simple method for the assessment of kidney function in a uremic large animal model. An intravenous bolus of iohexol was administered to goats (13 measurements in n = 3 goats) and pigs (23 measurements in n = 5 pigs) before and after induction of kidney failure, followed by frequent blood sampling up to 1440 min. Plasma clearance (CL) was estimated by a nonlinear mixed-effects model (CLNLME) and by a one-compartmental pharmacokinetic disposition model using iohexol plasma concentrations during the terminal elimination phase (CL1CMT). A simple method (CLSM) for the calculation of plasma clearance was developed based on the most appropriate relationship between CLNLME and CL1CMT. CLSM and CLNLME showed good agreement (CLNLME/CLSM ratio: 1.00 ± 0.07; bias: 0.03 ± 1.64 mL/min; precision CLSM and CLNLME: 80.9% and 80.7%, respectively; the percentage of CLSM estimates falling within ±30% (P30) or ±10% (P10) of CLNLME: 53% and 12%, respectively). For mGFRNLME vs. mGFRSM, bias was −0.25 ± 2.24 and precision was 49.2% and 53.6%, respectively, P30 and P10 for mGFR based on CLSM were 71% and 24%, respectively. A simple method for measurement of GFR in healthy and uremic goats and pigs was successfully developed, which eliminates the need for continuous infusion of an exogenous marker, urine collection and frequent blood sampling.

ACS Style

Maaike van Gelder; Jasper Stevens; Tobias Pieters; Koen Vaessen; Jaap Joles; Marianne Verhaar; Karin Gerritsen. Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs. Biology 2021, 10, 461 .

AMA Style

Maaike van Gelder, Jasper Stevens, Tobias Pieters, Koen Vaessen, Jaap Joles, Marianne Verhaar, Karin Gerritsen. Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs. Biology. 2021; 10 (6):461.

Chicago/Turabian Style

Maaike van Gelder; Jasper Stevens; Tobias Pieters; Koen Vaessen; Jaap Joles; Marianne Verhaar; Karin Gerritsen. 2021. "Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs." Biology 10, no. 6: 461.

Journal article
Published: 03 April 2021 in Biology
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A large animal model of (end-stage) kidney disease (ESKD) is needed for the preclinical testing of novel renal replacement therapies. This study aimed to create stable uremia via subtotal renal artery embolization in goats and induce a temporary further decline in kidney function by administration of gentamicin. Renal artery embolization was performed in five Dutch white goats by infusing polyvinyl alcohol particles in branches of the renal artery, aiming for the embolization of ~80% of one kidney and complete embolization of the contralateral kidney. Gentamicin was administered to temporarily further increase the plasma concentrations of uremic toxins. After initial acute kidney injury, urea and creatinine plasma concentrations stabilized 1.5 ± 0.7 months post-embolization and remained elevated (12 ± 1.4 vs. 5.6 ± 0.8 mmol/L and 174 ± 45 vs. 65 ± 5.6 µmol/L, resp.) during follow-up (16 ± 6 months). Gentamicin induced temporary acute-on-chronic kidney injury with a variable increase in plasma concentrations of small solutes (urea 29 ± 15 mmol/L, creatinine 841 ± 584 µmol/L, phosphate 2.2 ± 0.3 mmol/L and potassium 5.0 ± 0.6 mmol/L) and protein-bound uremic toxins representative of patients with ESKD. A uremic goat model characterized by stable moderate uremia was established via subtotal renal artery embolization with the induction of temporary severe acute-on-chronic kidney injury by the administration of gentamicin, allowing preclinical in vivo validation of novel renal replacement technologies.

ACS Style

Maaike van Gelder; Joost de Vries; Sabbir Ahmed; Anneke Monninkhof; Gérard de Kort; Evert-Jan Vonken; Diënty Hazenbrink; Koen Vaessen; Tri Nguyen; Marianne Verhaar; Jaap Joles; Karin Gerritsen. A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin. Biology 2021, 10, 292 .

AMA Style

Maaike van Gelder, Joost de Vries, Sabbir Ahmed, Anneke Monninkhof, Gérard de Kort, Evert-Jan Vonken, Diënty Hazenbrink, Koen Vaessen, Tri Nguyen, Marianne Verhaar, Jaap Joles, Karin Gerritsen. A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin. Biology. 2021; 10 (4):292.

Chicago/Turabian Style

Maaike van Gelder; Joost de Vries; Sabbir Ahmed; Anneke Monninkhof; Gérard de Kort; Evert-Jan Vonken; Diënty Hazenbrink; Koen Vaessen; Tri Nguyen; Marianne Verhaar; Jaap Joles; Karin Gerritsen. 2021. "A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin." Biology 10, no. 4: 292.

Journal article
Published: 12 January 2021 in Acta Biomaterialia
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Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients’ health. Prolonged hemodialysis (with adequate anticoagulation) could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients’ overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, the time that patients’ blood is exposed to the dialyzer material is longer during prolonged hemodialysis, and blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers. Current hemodialysis therapy cannot effectively remove protein-bound toxins. Prolonged hemodialysis could improve toxin removal. However, during prolonged hemodialysis, blood clots could obstruct the fiber lumen, resulting in decreased effective membrane surface area available for toxin removal. We have prepared, for the first time, dual layer mixed matrix hollow fiber membranes (MMM) for outside-in filtration (OIF). The OIF mode wherein blood would flow through the inter-fiber space instead of through the fiber lumina could prevent fiber clotting. Moreover, the MMMs combine diffusion and adsorption to improve (protein-bound) toxin removal. We believe that the new design of our MMM fibers is an important contribution concerning the development of artificial kidney systems and the improvement of the health and well-being of patients with renal failure.

ACS Style

O.E.M. ter Beek; M.K. van Gelder; C. Lokhorst; D.H.M. Hazenbrink; B.H. Lentferink; K.G.F. Gerritsen; D. Stamatialis. In vitro study of dual layer mixed matrix hollow fiber membranes for outside-in filtration of human blood plasma. Acta Biomaterialia 2021, 123, 244 -253.

AMA Style

O.E.M. ter Beek, M.K. van Gelder, C. Lokhorst, D.H.M. Hazenbrink, B.H. Lentferink, K.G.F. Gerritsen, D. Stamatialis. In vitro study of dual layer mixed matrix hollow fiber membranes for outside-in filtration of human blood plasma. Acta Biomaterialia. 2021; 123 ():244-253.

Chicago/Turabian Style

O.E.M. ter Beek; M.K. van Gelder; C. Lokhorst; D.H.M. Hazenbrink; B.H. Lentferink; K.G.F. Gerritsen; D. Stamatialis. 2021. "In vitro study of dual layer mixed matrix hollow fiber membranes for outside-in filtration of human blood plasma." Acta Biomaterialia 123, no. : 244-253.

Original research
Published: 05 December 2020 in Physiological Reports
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A system for sorbent‐assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single‐lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma‐to‐dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8‐hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day‐ (n = 3) and nighttime system (n = 15) for 4–8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (p = .039)). Sorbent‐assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD.

ACS Style

Maaike K. Van Gelder; Joost C. De Vries; Frank Simonis; Anneke S. Monninkhof; Diënty H. M. Hazenbrink; Giulia Ligabue; Silvia Giovanella; Jaap A. Joles; Marianne C. Verhaar; Maria A. Bajo Rubio; Rafael Selgas; Gianni Cappelli; Karin G. F. Gerritsen. Evaluation of a system for sorbent‐assisted peritoneal dialysis in a uremic pig model. Physiological Reports 2020, 8, e14593 .

AMA Style

Maaike K. Van Gelder, Joost C. De Vries, Frank Simonis, Anneke S. Monninkhof, Diënty H. M. Hazenbrink, Giulia Ligabue, Silvia Giovanella, Jaap A. Joles, Marianne C. Verhaar, Maria A. Bajo Rubio, Rafael Selgas, Gianni Cappelli, Karin G. F. Gerritsen. Evaluation of a system for sorbent‐assisted peritoneal dialysis in a uremic pig model. Physiological Reports. 2020; 8 (23):e14593.

Chicago/Turabian Style

Maaike K. Van Gelder; Joost C. De Vries; Frank Simonis; Anneke S. Monninkhof; Diënty H. M. Hazenbrink; Giulia Ligabue; Silvia Giovanella; Jaap A. Joles; Marianne C. Verhaar; Maria A. Bajo Rubio; Rafael Selgas; Gianni Cappelli; Karin G. F. Gerritsen. 2020. "Evaluation of a system for sorbent‐assisted peritoneal dialysis in a uremic pig model." Physiological Reports 8, no. 23: e14593.

Journal article
Published: 12 June 2020 in Toxins
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In chronic kidney disease (CKD), the secretion of uremic toxins is compromised leading to their accumulation in blood, which contributes to uremic complications, in particular cardiovascular disease. Organic anion transporters (OATs) are involved in the tubular secretion of protein-bound uremic toxins (PBUTs). However, OATs also handle a wide range of drugs, including those used for treatment of cardiovascular complications and their interaction with PBUTs is unknown. The aim of this study was to investigate the interaction between commonly prescribed drugs in CKD and endogenous PBUTs with respect to OAT1-mediated uptake. We exposed a unique conditionally immortalized proximal tubule cell line (ciPTEC) equipped with OAT1 to a panel of selected drugs, including angiotensin-converting enzyme inhibitors (ACEIs: captopril, enalaprilate, lisinopril), angiotensin receptor blockers (ARBs: losartan and valsartan), furosemide and statins (pravastatin and simvastatin), and evaluated the drug-interactions using an OAT1-mediated fluorescein assay. We show that selected ARBs and furosemide significantly reduced fluorescein uptake, with the highest potency for ARBs. This was exaggerated in presence of some PBUTs. Selected ACEIs and statins had either no or a slight effect at supratherapeutic concentrations on OAT1-mediated fluorescein uptake. In conclusion, we demonstrate that PBUTs may compete with co-administrated drugs commonly used in CKD management for renal OAT1 mediated secretion, thus potentially compromising the residual renal function.

ACS Style

Silvia M. Mihaila; João Faria; Maurice F. J. Stefens; Dimitrios Stamatialis; Marianne C. Verhaar; Karin G. F. Gerritsen; Rosalinde Masereeuw. Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion. Toxins 2020, 12, 391 .

AMA Style

Silvia M. Mihaila, João Faria, Maurice F. J. Stefens, Dimitrios Stamatialis, Marianne C. Verhaar, Karin G. F. Gerritsen, Rosalinde Masereeuw. Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion. Toxins. 2020; 12 (6):391.

Chicago/Turabian Style

Silvia M. Mihaila; João Faria; Maurice F. J. Stefens; Dimitrios Stamatialis; Marianne C. Verhaar; Karin G. F. Gerritsen; Rosalinde Masereeuw. 2020. "Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion." Toxins 12, no. 6: 391.

Journal article
Published: 07 April 2020 in Toxins
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Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (−15.3 to 34.6) in patients treated with HDF and increased by 11.9% (−15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

ACS Style

Maaike K. Van Gelder; Igor R. Middel; Robin W. M. Vernooij; Michiel L. Bots; Marianne C. Verhaar; Rosalinde Masereeuw; Muriel P. Grooteman; Menso J. Nubé; M. A. Van Den Dorpel; Peter J. Blankestijn; Maarten B. Rookmaaker; Karin G.F. Gerritsen. Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome. Toxins 2020, 12, 234 .

AMA Style

Maaike K. Van Gelder, Igor R. Middel, Robin W. M. Vernooij, Michiel L. Bots, Marianne C. Verhaar, Rosalinde Masereeuw, Muriel P. Grooteman, Menso J. Nubé, M. A. Van Den Dorpel, Peter J. Blankestijn, Maarten B. Rookmaaker, Karin G.F. Gerritsen. Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome. Toxins. 2020; 12 (4):234.

Chicago/Turabian Style

Maaike K. Van Gelder; Igor R. Middel; Robin W. M. Vernooij; Michiel L. Bots; Marianne C. Verhaar; Rosalinde Masereeuw; Muriel P. Grooteman; Menso J. Nubé; M. A. Van Den Dorpel; Peter J. Blankestijn; Maarten B. Rookmaaker; Karin G.F. Gerritsen. 2020. "Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome." Toxins 12, no. 4: 234.

Review article
Published: 06 January 2020 in Biomaterials
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The availability of a wearable artificial kidney (WAK) that provides dialysis outside the hospital would be an important advancement for dialysis patients. The concept of a WAK is based on regeneration of a small volume of dialysate in a closed-loop. Removal of urea, the primary waste product of nitrogen metabolism, is the major challenge for the realization of a WAK since it is a molecule with low reactivity that is difficult to adsorb while it is the waste solute with the highest daily molar production. Currently, no efficient urea removal technology is available that allows for miniaturization of the WAK to a size and weight that is acceptable for patients to carry. Several urea removal strategies have been explored, including enzymatic hydrolysis by urease, electro-oxidation and sorbent systems. However, thus far, these methods have toxic side effects, limited removal capacity or slow removal kinetics. This review discusses different urea removal strategies for application in a wearable dialysis device, from both a chemical and a medical perspective.

ACS Style

Maaike K. van Gelder; Jacobus A.W. Jong; Laura Folkertsma; Yong Guo; Christian Blüchel; Marianne C. Verhaar; Mathieu Odijk; Cornelus F. Van Nostrum; Wim E. Hennink; Karin G.F. Gerritsen. Urea removal strategies for dialysate regeneration in a wearable artificial kidney. Biomaterials 2020, 234, 119735 .

AMA Style

Maaike K. van Gelder, Jacobus A.W. Jong, Laura Folkertsma, Yong Guo, Christian Blüchel, Marianne C. Verhaar, Mathieu Odijk, Cornelus F. Van Nostrum, Wim E. Hennink, Karin G.F. Gerritsen. Urea removal strategies for dialysate regeneration in a wearable artificial kidney. Biomaterials. 2020; 234 ():119735.

Chicago/Turabian Style

Maaike K. van Gelder; Jacobus A.W. Jong; Laura Folkertsma; Yong Guo; Christian Blüchel; Marianne C. Verhaar; Mathieu Odijk; Cornelus F. Van Nostrum; Wim E. Hennink; Karin G.F. Gerritsen. 2020. "Urea removal strategies for dialysate regeneration in a wearable artificial kidney." Biomaterials 234, no. : 119735.

Multicenter study
Published: 13 May 2019 in Toxins
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Connective tissue growth factor (CTGF) plays a key role in the pathogenesis of tissue fibrosis. The aminoterminal fragment of CTGF is a middle molecule that accumulates in chronic kidney disease. The aims of this study are to explore determinants of plasma CTGF in hemodialysis (HD) patients, investigate whether CTGF relates to all-cause mortality in HD patients, and investigate whether online-hemodiafiltration (HDF) lowers CTGF. Data from 404 patients participating in the CONvective TRAnsport STudy (CONTRAST) were analyzed. Patients were randomized to low-flux HD or HDF. Pre-dialysis CTGF was measured by sandwich ELISA at baseline, after six and 12 months. CTGF was inversely related in multivariable analysis to glomerular filtration rate (GFR) (p < 0.001) and positively to cardiovascular disease (CVD) (p = 0.006), dialysis vintage (p < 0.001), interleukin-6 (p < 0.001), beta-2-microglobulin (p = 0.045), polycystic kidney disease (p < 0.001), tubulointerstitial nephritis (p = 0.002), and renal vascular disease (p = 0.041). Patients in the highest quartile had a higher mortality risk compared to those in the lowest quartile (HR 1.7, 95% CI: 1.02–2.88, p = 0.043). HDF lowered CTGF with 4.8% between baseline and six months, whereas during HD, CTGF increased with 4.9% (p < 0.001). In conclusion, in HD patients, CTGF is related to GFR, CVD and underlying renal disease and increased the risk of all-cause mortality. HDF reduces CTGF.

ACS Style

Claire H. Den Hoedt; Maaike K. Van Gelder; Muriel P. Grooteman; Menso J. Nubé; Peter J. Blankestijn; Roel Goldschmeding; Robbert Jan Kok; Michiel L. Bots; Marinus A. Van Den Dorpel; Karin G. F. Gerritsen. Connective Tissue Growth Factor Is Related to All-cause Mortality in Hemodialysis Patients and Is Lowered by On-line Hemodiafiltration: Results from the Convective Transport Study. Toxins 2019, 11, 268 .

AMA Style

Claire H. Den Hoedt, Maaike K. Van Gelder, Muriel P. Grooteman, Menso J. Nubé, Peter J. Blankestijn, Roel Goldschmeding, Robbert Jan Kok, Michiel L. Bots, Marinus A. Van Den Dorpel, Karin G. F. Gerritsen. Connective Tissue Growth Factor Is Related to All-cause Mortality in Hemodialysis Patients and Is Lowered by On-line Hemodiafiltration: Results from the Convective Transport Study. Toxins. 2019; 11 (5):268.

Chicago/Turabian Style

Claire H. Den Hoedt; Maaike K. Van Gelder; Muriel P. Grooteman; Menso J. Nubé; Peter J. Blankestijn; Roel Goldschmeding; Robbert Jan Kok; Michiel L. Bots; Marinus A. Van Den Dorpel; Karin G. F. Gerritsen. 2019. "Connective Tissue Growth Factor Is Related to All-cause Mortality in Hemodialysis Patients and Is Lowered by On-line Hemodiafiltration: Results from the Convective Transport Study." Toxins 11, no. 5: 268.

Journal article
Published: 01 November 2018 in American Journal of Physiology-Renal Physiology
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The key to success in developing a wearable dialysis device is a technique to safely and efficiently regenerate and reuse a small volume of dialysate in a closed-loop system. In a hemodialysis model in goats, we explored whether urea removal by electro-oxidation (EO) could be effectively and safely applied in vivo. A miniature dialysis device was built, containing 1 or 2 “EO units,” each with 10 graphite electrodes, with a cumulative electrode surface of 585 cm2per unit. The units also contained poly(styrene-divinylbenzene) sulfonate beads, FeOOH beads, and activated carbon for respective potassium, phosphate, and chlorine removal. Urea, potassium, and phosphate were infused to create “uremic” conditions. Urea removal was dependent on total electrode surface area [removal of 8 mmol/h (SD 1) and 16 mmol/h (SD 2) and clearance of 12 ml/min (SD 1) and 20 ml/min (SD 3) with 1 and 2 EO units, respectively] and plasma urea concentration but not on flow rate. Extrapolating urea removal with 2 EO units to 24 h would suffice to remove daily urea production, but for intermittent dialysis, additional units would be required. EO had practically no effects on potassium and phosphate removal or electrolyte balance. However, slight ammonium releasewas observed, and some chlorine release at higher dialysate flow rates. Minor effects on acid-base balance were observed, possibly partly due to infusion of chloride. Mild hemolysis occurred, which seemed related to urea infusion. In conclusion, clinically relevant urea removal was achieved in vivo by electro-oxidation. Efficacy and safety testing in a large-animal model with uremia is now indicated.

ACS Style

Maarten Wester; Maaike K. Van Gelder; Jaap A. Joles; Frank Simonis; Diënty Hazenbrink; Theo W. M. Van Berkel; Koen R. D. Vaessen; Walther H. Boer; Marianne C. Verhaar; Karin G. F. Gerritsen. Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats. American Journal of Physiology-Renal Physiology 2018, 315, F1385 -F1397.

AMA Style

Maarten Wester, Maaike K. Van Gelder, Jaap A. Joles, Frank Simonis, Diënty Hazenbrink, Theo W. M. Van Berkel, Koen R. D. Vaessen, Walther H. Boer, Marianne C. Verhaar, Karin G. F. Gerritsen. Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats. American Journal of Physiology-Renal Physiology. 2018; 315 (5):F1385-F1397.

Chicago/Turabian Style

Maarten Wester; Maaike K. Van Gelder; Jaap A. Joles; Frank Simonis; Diënty Hazenbrink; Theo W. M. Van Berkel; Koen R. D. Vaessen; Walther H. Boer; Marianne C. Verhaar; Karin G. F. Gerritsen. 2018. "Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats." American Journal of Physiology-Renal Physiology 315, no. 5: F1385-F1397.

Review
Published: 19 September 2018 in Advanced Healthcare Materials
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For patients with severe kidney or liver failure the best solution is currently organ transplantation. However, not all patients are eligible for transplantation and due to limited organ availability, most patients are currently treated with therapies using artificial kidney and artificial liver devices. These therapies, despite their relative success in preserving the patients' life, have important limitations since they can only replace part of the natural kidney or liver functions. As blood detoxification (and other functions) in these highly perfused organs is achieved by specialized cells, it seems relevant to review the approaches leading to bioengineered organs fulfilling most of the native organ functions. There, the culture of cells of specific phenotypes on adapted scaffolds that can be perfused takes place. In this review paper, first the functions of kidney and liver organs are briefly described. Then artificial kidney/liver devices, bioartificial kidney devices, and bioartificial liver devices are focused on, as well as biohybrid constructs obtained by decellularization and recellularization of animal organs. For all organs, a thorough overview of the literature is given and the perspectives for their application in the clinic are discussed.

ACS Style

Cecile Legallais; DooLi Kim; Sylvia M. Mihaila; Milos Mihajlovic; Marina Figliuzzi; Barbara Bonandrini; Simona Salerno; Fjodor A. Yousef Yengej; Maarten B. Rookmaaker; Natalia Sanchez Romero; Pilar Sainz-Arnal; Ulysse Pereira; Mattia Pasqua; Karin G. F. Gerritsen; Marianne Verhaar; Andrea Remuzzi; Pedro M. Baptista; Loredana De Bartolo; Rosalinde Masereeuw; Dimitrios Stamatialis. Bioengineering Organs for Blood Detoxification. Advanced Healthcare Materials 2018, 7, e1800430 .

AMA Style

Cecile Legallais, DooLi Kim, Sylvia M. Mihaila, Milos Mihajlovic, Marina Figliuzzi, Barbara Bonandrini, Simona Salerno, Fjodor A. Yousef Yengej, Maarten B. Rookmaaker, Natalia Sanchez Romero, Pilar Sainz-Arnal, Ulysse Pereira, Mattia Pasqua, Karin G. F. Gerritsen, Marianne Verhaar, Andrea Remuzzi, Pedro M. Baptista, Loredana De Bartolo, Rosalinde Masereeuw, Dimitrios Stamatialis. Bioengineering Organs for Blood Detoxification. Advanced Healthcare Materials. 2018; 7 (21):e1800430.

Chicago/Turabian Style

Cecile Legallais; DooLi Kim; Sylvia M. Mihaila; Milos Mihajlovic; Marina Figliuzzi; Barbara Bonandrini; Simona Salerno; Fjodor A. Yousef Yengej; Maarten B. Rookmaaker; Natalia Sanchez Romero; Pilar Sainz-Arnal; Ulysse Pereira; Mattia Pasqua; Karin G. F. Gerritsen; Marianne Verhaar; Andrea Remuzzi; Pedro M. Baptista; Loredana De Bartolo; Rosalinde Masereeuw; Dimitrios Stamatialis. 2018. "Bioengineering Organs for Blood Detoxification." Advanced Healthcare Materials 7, no. 21: e1800430.

Review
Published: 16 April 2018 in Expert Review of Medical Devices
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Introduction: Since the advent of peritoneal dialysis (PD) in the 1970s, the principles of dialysis have changed little. In the coming decades, several major breakthroughs are expected. Areas covered: Novel wearable and portable dialysis devices for both hemodialysis (HD) and PD are expected first. The HD devices could facilitate more frequent and longer dialysis outside of the hospital, while improving patient’s mobility and autonomy. The PD devices could enhance blood purification and increase technique survival of PD. Further away from clinical application is the bioartificial kidney, containing renal cells. Initially, the bioartificial kidney could be applied for extracorporeal treatment, to partly replace renal tubular endocrine, metabolic, immunoregulatory and secretory functions. Subsequently, intracorporeal treatment may become possible. Expert commentary: Key factors for successful implementation of miniature dialysis devices are patient attitudes and cost-effectiveness. A well-functioning and safe extracorporeal blood circuit is required for HD. For PD, a double lumen PD catheter would optimize performance. Future research should focus on further miniaturization of the urea removal strategy. For the bio-artificial kidney (BAK), cost effectiveness should be determined and a general set of functional requirements should be defined for future studies. For intracorporeal application, water reabsorption will become a major challenge.

ACS Style

Maaike K. Van Gelder; Silvia M. Mihaila; Jitske Jansen; Maarten Wester; Marianne Verhaar; Jaap A. Joles; Dimitrios Stamatialis; Rosalinde Masereeuw; Karin G. F. Gerritsen. From portable dialysis to a bioengineered kidney. Expert Review of Medical Devices 2018, 15, 323 -336.

AMA Style

Maaike K. Van Gelder, Silvia M. Mihaila, Jitske Jansen, Maarten Wester, Marianne Verhaar, Jaap A. Joles, Dimitrios Stamatialis, Rosalinde Masereeuw, Karin G. F. Gerritsen. From portable dialysis to a bioengineered kidney. Expert Review of Medical Devices. 2018; 15 (5):323-336.

Chicago/Turabian Style

Maaike K. Van Gelder; Silvia M. Mihaila; Jitske Jansen; Maarten Wester; Marianne Verhaar; Jaap A. Joles; Dimitrios Stamatialis; Rosalinde Masereeuw; Karin G. F. Gerritsen. 2018. "From portable dialysis to a bioengineered kidney." Expert Review of Medical Devices 15, no. 5: 323-336.

Article
Published: 29 January 2018 in ChemistrySelect
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Ninhydrin, i. e. the stable hydrate of the reactive species indanetrione, is a well-known compound used for the quantification of ammonia and amino acids. However, substituent effects on the reactivity of ninhydrin with nucleophiles are not described. In this work, the kinetics of the reaction of C4- and C5- substituted ninhydrins with urea was studied and monitored by 13C-NMR. Surprisingly, the obtained results show that electron donating groups (EDGs) as well as electron withdrawing groups (EWGs) decrease the rate of the reaction. EDGs decrease the electrophilicity of indanetrione, resulting in slower overall kinetics than unsubstituted ninhydrin. The calculated Gibbs free energy differences for the dehydration of unsubstituted and substituted ninhydrins and the subsequent reaction with urea showed that the dehydration of the compounds is more sensitive to electronic effects than the subsequent reaction with urea. Therefore, although EWGs increase the electrophilicity of indanetrione, this is more than counterbalanced by an adverse shift of the hydration equilibrium towards the unreactive hydrate (i. e. ninhydrin), resulting in slower kinetics as well.

ACS Style

Jacobus A. W. Jong; Marc-Etienne Moret; Marianne Verhaar; Wim E. Hennink; Karin G. F. Gerritsen; Cornelus F. Van Nostrum. Effect of Substituents on the Reactivity of Ninhydrin with Urea. ChemistrySelect 2018, 3, 1224 -1229.

AMA Style

Jacobus A. W. Jong, Marc-Etienne Moret, Marianne Verhaar, Wim E. Hennink, Karin G. F. Gerritsen, Cornelus F. Van Nostrum. Effect of Substituents on the Reactivity of Ninhydrin with Urea. ChemistrySelect. 2018; 3 (4):1224-1229.

Chicago/Turabian Style

Jacobus A. W. Jong; Marc-Etienne Moret; Marianne Verhaar; Wim E. Hennink; Karin G. F. Gerritsen; Cornelus F. Van Nostrum. 2018. "Effect of Substituents on the Reactivity of Ninhydrin with Urea." ChemistrySelect 3, no. 4: 1224-1229.

Proceedings
Published: 01 January 2018 in Proceedings
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We present a reference-electrode free sensor able to measure both pH and conductivitybased on impedance spectroscopy. The electrode is made of a layer of indium-tin-oxide (ITO). Theimpedance of this electrode at low frequencies depends on its double layer capacity, which varieswith pH due to modification of oxide groups at the ITO surface. At high frequencies, the impedanceis determined by the resistance in the system, which corresponds to the inverse conductivity of thesolution. Because no reference electrode is needed for this technique, miniaturization of the pHsensor is simple. We demonstrate a proof-of-principle experiment of the sensor for human plasmapH measurements.

ACS Style

Laura Folkertsma; Lennart Gehrenkemper; Jan Eijkel; Karin Gerritsen; Mathieu Odijk. Reference-Electrode Free pH Sensing Using Impedance Spectroscopy. Proceedings 2018, 2, 742 .

AMA Style

Laura Folkertsma, Lennart Gehrenkemper, Jan Eijkel, Karin Gerritsen, Mathieu Odijk. Reference-Electrode Free pH Sensing Using Impedance Spectroscopy. Proceedings. 2018; 2 (13):742.

Chicago/Turabian Style

Laura Folkertsma; Lennart Gehrenkemper; Jan Eijkel; Karin Gerritsen; Mathieu Odijk. 2018. "Reference-Electrode Free pH Sensing Using Impedance Spectroscopy." Proceedings 2, no. 13: 742.

Journal article
Published: 01 January 2013 in Nederlands tijdschrift voor geneeskunde
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Maarten Wester; Karin G F Gerritsen; Walther H Boer; Jaap A Joles; Jeroen P Kooman. [The wearable artificial kidney: a promise for the future?]. Nederlands tijdschrift voor geneeskunde 2013, 157, 1 .

AMA Style

Maarten Wester, Karin G F Gerritsen, Walther H Boer, Jaap A Joles, Jeroen P Kooman. [The wearable artificial kidney: a promise for the future?]. Nederlands tijdschrift voor geneeskunde. 2013; 157 (52):1.

Chicago/Turabian Style

Maarten Wester; Karin G F Gerritsen; Walther H Boer; Jaap A Joles; Jeroen P Kooman. 2013. "[The wearable artificial kidney: a promise for the future?]." Nederlands tijdschrift voor geneeskunde 157, no. 52: 1.

Journal article
Published: 01 May 2012 in American Journal of Kidney Diseases
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Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration. 4 observational studies in patients and 2 pharmacokinetic studies in rodents. 4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session. First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality. Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay. In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (β = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF. Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted. Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session.

ACS Style

Karin G. Gerritsen; Alferso C. Abrahams; Hilde P. Peters; Tri Q Nguyen; Maarten Koeners; Claire H. Den Hoedt; Amelie Dendooven; Marinus A. Van Den Dorpel; Peter J. Blankestijn; Jack F. Wetzels; Jaap A. Joles; Roel Goldschmeding; Robbert J. Kok. Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations. American Journal of Kidney Diseases 2012, 59, 619 -627.

AMA Style

Karin G. Gerritsen, Alferso C. Abrahams, Hilde P. Peters, Tri Q Nguyen, Maarten Koeners, Claire H. Den Hoedt, Amelie Dendooven, Marinus A. Van Den Dorpel, Peter J. Blankestijn, Jack F. Wetzels, Jaap A. Joles, Roel Goldschmeding, Robbert J. Kok. Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations. American Journal of Kidney Diseases. 2012; 59 (5):619-627.

Chicago/Turabian Style

Karin G. Gerritsen; Alferso C. Abrahams; Hilde P. Peters; Tri Q Nguyen; Maarten Koeners; Claire H. Den Hoedt; Amelie Dendooven; Marinus A. Van Den Dorpel; Peter J. Blankestijn; Jack F. Wetzels; Jaap A. Joles; Roel Goldschmeding; Robbert J. Kok. 2012. "Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations." American Journal of Kidney Diseases 59, no. 5: 619-627.

Journal article
Published: 01 June 2010 in American Journal of Physiology-Renal Physiology
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Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal expression. We investigated how tubular dysfunction affects urinary CTGF levels. To study this, we administered recombinant CTGF intravenously to rodents. We used both full-length CTGF and the NH2-terminal fragment, since the NH2-fragment is the predominant form detected in urine. Renal CTGF extraction, determined by simultaneous arterial and renal vein sampling, was 18 ± 3% for full-length CTGF and 21 ± 1% for the NH2-fragment. Fractional excretion was very low for both CTGFs (0.02 ± 0.006% and 0.10 ± 0.02%, respectively), indicating that >99% of the extracted CTGF was metabolized by the kidney. Immunohistochemistry revealed extensive proximal tubular uptake of CTGF in apical endocytic vesicles and colocalization with megalin. Urinary CTGF was elevated in megalin- and cubilin-deficient mice but not in cubilin-deficient mice. Inhibition of tubular reabsorption by Gelofusine reduced renal uptake of CTGF and increased urinary CTGF. In healthy volunteers, Gelofusine also induced an increase of urinary CTGF excretion, comparable to the increase of β2-microglobulin excretion ( r = 0.99). Furthermore, urinary CTGF correlated with β2-microglobulin ( r = 0.85) in renal disease patients ( n = 108), and only β2-microglobulin emerged as an independent determinant of urinary CTGF. Thus filtered CTGF is normally reabsorbed almost completely in proximal tubules via megalin, and elevated urinary CTGF may largely reflect proximal tubular dysfunction.

ACS Style

Karin G. Gerritsen; Hilde P. Peters; Tri Q. Nguyen; Maarten P. Koeners; Jack F. Wetzels; Jaap A. Joles; Erik I. Christensen; Pierre J. Verroust; Dongxia Li; Noelynn Oliver; Leon Xu; Robbert J. Kok; Roel Goldschmeding. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion. American Journal of Physiology-Renal Physiology 2010, 298, F1457 -F1464.

AMA Style

Karin G. Gerritsen, Hilde P. Peters, Tri Q. Nguyen, Maarten P. Koeners, Jack F. Wetzels, Jaap A. Joles, Erik I. Christensen, Pierre J. Verroust, Dongxia Li, Noelynn Oliver, Leon Xu, Robbert J. Kok, Roel Goldschmeding. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion. American Journal of Physiology-Renal Physiology. 2010; 298 (6):F1457-F1464.

Chicago/Turabian Style

Karin G. Gerritsen; Hilde P. Peters; Tri Q. Nguyen; Maarten P. Koeners; Jack F. Wetzels; Jaap A. Joles; Erik I. Christensen; Pierre J. Verroust; Dongxia Li; Noelynn Oliver; Leon Xu; Robbert J. Kok; Roel Goldschmeding. 2010. "Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion." American Journal of Physiology-Renal Physiology 298, no. 6: F1457-F1464.

Case report
Published: 01 January 2009 in Clinical Medicine Insights: Oncology
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Mucinous cystadenocarcinoma of the appendix is a rare malignancy. This is a report of a 74-year-old man who presented with recurrent pneumonia which turned out to be a postobstructive pneumonia complicating a large mucinous cystadenocarcinoma of the appendix with massive retroperitoneal and intrathoracic extension. Mucinous cystadenocarcinoma of the appendix is a low-grade malignancy characterized by expansive growth due to progressive accumulation of mucinous fluid produced by the cancer cells. The tendency of this tumor to expand massively is well demonstrated by this case. The unusual retroperitoneal location of appendix in this patient probably allowed the tumor to expand massively in the retroperitoneal space and the thoracic cavity. In addition to computed tomography, [18F]fluorodeoxyglucose positron emission tomography (18F-FDG PET) was used as an ancillary method for staging in this patient. The value of 18F-FDG PET in the diagnosis of mucinous cystadenocarcinoma of the appendix has not been determined yet, but it might be promising. The most common presentation of this tumor is abdominal pain or a palpable ileocoecal mass. To the knowledge of the authors, this is the first report of an appendiceal mucinous cystadenocarcinoma with expansion into the thoracic cavity presenting with recurrent pneumonia.

ACS Style

Karin G. Gerritsen; Peter H. Slee; Thomas L. Bollen; Wim. Van Hecke; Cornelis A. Seldenrijk; Ruth G. Keijsers; Vincent A. Duurkens. Recurrent Pneumonia Due to an Appendiceal Mucinous Cystadenocarcinoma: A Rare Presentation of a Rare Malignancy. Clinical Medicine Insights: Oncology 2009, 3, 9 -12.

AMA Style

Karin G. Gerritsen, Peter H. Slee, Thomas L. Bollen, Wim. Van Hecke, Cornelis A. Seldenrijk, Ruth G. Keijsers, Vincent A. Duurkens. Recurrent Pneumonia Due to an Appendiceal Mucinous Cystadenocarcinoma: A Rare Presentation of a Rare Malignancy. Clinical Medicine Insights: Oncology. 2009; 3 ():9-12.

Chicago/Turabian Style

Karin G. Gerritsen; Peter H. Slee; Thomas L. Bollen; Wim. Van Hecke; Cornelis A. Seldenrijk; Ruth G. Keijsers; Vincent A. Duurkens. 2009. "Recurrent Pneumonia Due to an Appendiceal Mucinous Cystadenocarcinoma: A Rare Presentation of a Rare Malignancy." Clinical Medicine Insights: Oncology 3, no. : 9-12.