Clinical Research
Clinical research in the Division of Nephrology of the Cliniques universitaires Saint-Luc includes 4 mains axes of research:
- Progression, complications and treatment of autosomal dominant polycystic kidney disease, the most frequent form of inherited kidney disease;
- Mechanisms of water transport in peritoneal dialysis;
- Clinical nephrology, including crystal and complement-mediated kidney diseases;
- Long-term outcome of patients after renal transplantation.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and accounts for up to 10% of all patients on renal replacement therapy worldwide. It is characterized by relentless development and growth of cysts causing progressive kidney enlargement associated with hypertension, abdominal fullness and pain, episodes of cyst hemorrhage, gross hematuria, nephrolithiasis, cyst infections, and reduced quality of life. ADPKD is a systemic disorder affecting other organs with potentially serious complications such as massive hepatomegaly and intracranial aneurysm rupture. Mutations in the PKD1 (80-85%) and PKD2 (15-20%) genes account for the overwhelming majority of ADPKD cases.
The diagnosis of ADPKD relies primarily on imaging, although some cases are diagnosed by genetic testing. Typical imaging findings from patients with ADPKD reveal large kidneys with multiple bilateral cysts. Given its availability, safety, and low cost, ultrasonography is the imaging modality of choice for pre-symptomatic diagnosis. As kidney function may remain in the normal range despite severe destruction of the renal parenchyma, total kidney volume (TKV) is currently the best tool for monitoring and prognosticating in early stages of ADPKD. TKV, measured by magnetic resonance imaging or computed tomography, is an accurate estimate of kidney cyst burden and correlates with multiple kidney manifestations in ADPKD, such as pain, hypertension, hematuria, and proteinuria. TKV and cyst volume increase exponentially in all patients with ADPKD, but at variable rates (5%-6% per year on average). A classification of ADPKD has been developed based on age- and height-adjusted TKV.
Identifying patients at risk for progression is also important to select those who might benefit from novel therapeutic approaches specifically interfering with cyst growth and disease progression. Until recently, ADPKD has indeed been considered as an incurable disease, and its management only relied on early detection and treatment of hypertension, lifestyle modifications, treatment of renal and extra-renal complications, management of chronic kidney disease-related complications, and renal replacement therapy. In recent years, novel therapies have been developed and validated based on the improved understanding of ADPKD pathophysiology. Our group participated in the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes) 3:4 trial, an international randomized controlled trial which evaluated the effect of tolvaptan, a vasopressin V2 receptor antagonist, on ADPKD disease progression in 1445 ADPKD patients. Treatment with tolvaptan in patients with ADPKD with GFRs >60 mL/min and TKVs ≥ 750 mL showed significant effect on the rate of growth of TKV (-48%) and the rate of eGFR decline (-26%). Based on the findings of this landmark study, tolvaptan has been approved to delay the progression of ADPKD in patients with a rapid increase in TKV, and is now reimbursed in Belgium (September 2016).
Autosomal dominant polycystic kidney disease and other inherited kidney diseases
Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Dandurand A, Ouyang J, Czerwiec FS, Blais JD Nephrol Dial Transplant. 2017 Mar 31.
Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 Trial Devuyst O, Chapman AB, Gansevoort RT, Higashihara E, Perrone RD, Torres VE, Blais JD, Zhou W, Ouyang J, Czerwiec FS J Am Soc Nephrol. 2017 May;28(5):1592-1602.
Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome Belge H, Dahan K, Cambier JF, Benoit V, Morelle J, Bloch J, Vanhille P, Pirson Y, Demoulin N Nephrol Dial Transplant. 2017 May 1;32(5):830-837.
Paradoxical response to furosemide in uromodulin-associated kidney disease Labriola L, Olinger E, Belge H, Pirson Y, Dahan K, Devuyst O Nephrol Dial Transplant. 2015 Feb;30(2):330-5.
Dialysis
Efficiency and safety of a Double Icodextrin dose in elderly incident CAPD patients on incremental Peritoneal Dialysis therapy: the DIDo study. Goffin E. EudraCT: 2011-005274-30 - ClinicalTrials.gov Identifier: NCT01944852
Infectious complications following conversion to buttonhole cannulation of native arteriovenous fistulas: a quality improvement report. Labriola L, Crott R, Desmet C, André G, Jadoul M Am J Kidney Dis. 2011 Mar;57(3):442-8.
Clinical nephrology, including crystal nephropathies and complement-mediated kidney diseases
Enteric hyperoxaluria in chronic pancreatitis. Demoulin N, Issa Z, Crott R, Morelle J, Danse E, Wallemacq P, Jadoul M, Deprez PH Medicine (Baltimore). 2017 May;96(19):e6758.
Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis. Jayne DR, Bruchfeld AN, Harper L, Schaier M, Venning MC, Hamilton P, Burst V, Grundmann F, Jadoul M, Szombati I, Tesař V, Segelmark M, Potarca A, Schall TJ, Bekker P J Am Soc Nephrol. 2017 Apr 11. pii: ASN.2016111179.
Long-term outcome of patients after renal transplantation
Long-term Outcome of Kidney Recipients Transplanted for Aristolochic Acid Nephropathy. Kanaan N, Hassoun Z, Raggi C, Jadoul M, Mourad M, De Meyer M, Aydin S, Schmeiser HH, Cosyns JP, Goffin E Transplantation. 2016 Feb;100(2):416-21.
Outcome of hepatitis B and C virus-associated hepatocellular carcinoma occurring after renal transplantation Kanaan N, Raggi C, Goffin E, De Meyer M, Mourad M, Jadoul M, Beguin C, Kabamba B, Borbath I, Pirson Y, Hassoun Z J Viral Hepat. 2017 May;24(5):430-435.