Jack F M Wetzels

Radboud University Medical Centre (Radboudumc), Nymegen, Gelderland, Netherlands

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Publications (257)1437.26 Total impact

  • Kidney International 06/2015; 87(6):1263-1264. DOI:10.1038/ki.2015.34 · 8.52 Impact Factor
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    ABSTRACT: The Modification of Diet in Renal Disease (MDRD) formula is widely used in clinical practice to assess the correct drug dose. This formula is based on serum creatinine levels which might be influenced by chronic diseases itself or the effects of the chronic diseases. We conducted a systematic review to determine the validity of the MDRD formula in specific patient populations with renal impairment: elderly, hospitalized and obese patients, patients with cardiovascular disease, cancer, chronic respiratory diseases, diabetes mellitus, liver cirrhosis and human immunodeficiency virus. We searched for articles in Pubmed published from January 1999 through January 2014. Selection criteria were (1) patients with a glomerular filtration rate (GFR) < 60 ml/min (/1.73m2), (2) MDRD formula compared with a gold standard and (3) statistical analysis focused on bias, precision and/or accuracy. Data extraction was done by the first author and checked by a second author. A bias of 20% or less, a precision of 30% or less and an accuracy expressed as P30% of 80% or higher were indicators of the validity of the MDRD formula. In total we included 27 studies. The number of patients included ranged from 8 to 1831. The gold standard and measurement method used varied across the studies. For none of the specific patient populations the studies provided sufficient evidence of validity of the MDRD formula regarding the three parameters. For patients with diabetes mellitus and liver cirrhosis, hospitalized patients and elderly with moderate to severe renal impairment we concluded that the MDRD formula is not valid. Limitations of the review are the lack of considering the method of measuring serum creatinine levels and the type of gold standard used. In several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity.
    PLoS ONE 03/2015; 10(3):e0116403. DOI:10.1371/journal.pone.0116403 · 3.53 Impact Factor
  • Jack F.M. Wetzels, Nicole C.A.J. van de Kar
    American Journal of Kidney Diseases 02/2015; 65(2). DOI:10.1053/j.ajkd.2014.04.039 · 5.76 Impact Factor
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    ABSTRACT: Cardiovascular risk is increased in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) has emerged as an important, independent predictor of outcome in CKD patients. High FGF23 may, however, be a reflection of renal tissue resistance to its actions, reflected by low fractional excretion of phosphate (FePi). We evaluated the modifying effect of FePi on the association between FGF23 and outcome in patients with CKD stage 3-4. An analysis was performed in a subset of 166 adult patients of two participating centers of the MASTERPLAN trial of whom urine samples at baseline were available to calculate FePi. Outcome was defined as a composite of death, renal failure (defined as need for renal replacement therapy or doubling of serum creatinine) and cardiovascular events (myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty or coronary artery bypass graft. Patients were categorized by FGF23 and FePi. A product term was added to Cox regression and RERIs were calculated. Patients had a median estimated glomerular filtration rate (eGFR) of 36 ml/min/1.73 m(2) [interquartile range (IQR) 27-44], serum phosphate 1.04 mmol/l (IQR 0.92-1.20), FGF23 140 RU/ml (IQR 81-236) and FePi 0.32 (IQR 0.25-0.44). A total of 96 events occurred during 5 years of follow up. LnFGF23 was a significant, independent predictor for the composite outcome [hazard ratio (HR) 2.13, 95 % confidence interval (CI) 1.53-2.95]. FePi did not modify the relation between FGF23 and outcome in these patients with CKD. Our study shows that FGF23 itself, but not its renal tissue resistance as reflected by FePi, is an important risk factor for clinical events in subjects with CKD stage 3-4.
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    ABSTRACT: Since the beginning of living donor kidney transplantation, physicians have expressed concern about the possibility that unilateral nephrectomy can be harmful to a healthy individual. To investigate if the elevated intra-abdominal pressure (IAP) during laparoscopic donor nephrectomy causes early damage to the remaining kidney we evaluated urine biomarkers after laparoscopic donor nephrectomy. We measured albumin and alpha-1-microglobulin (α-1-MGB) in urine samples collected during and after open and laparoscopic donor nephrectomy and laparoscopic cholecystectomy and colectomy. Additionally, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured in urine samples collected during and after laparoscopic donor nephrectomy and colectomy. The same biomarkers were studied in patients randomly assigned to standard or low IAP during laparoscopic donor nephrectomy. We observed a peak in urinary albumin excretion during all procedures. Urine α-1-MGB rose in the post-operative period with a peak on the third postoperative day after donor nephrectomy. Urine α-1-MGB did not increase after laparoscopic cholecystectomy and colectomy. After laparoscopic nephrectomy we observed slight increases in urine KIM 1 during surgery and in urine NGAL at day 2-3 after the procedure. After laparoscopic colectomy both KIM-1, and NGAL were increased in the postoperative period. There were no differences between the high and low pressure procedure. Elevated urinary α-1-MGB suggests kidney damage after donor nephrectomy, occurring irrespective of IAP during the laparoscopic procedure. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Transplant International 01/2015; 28(5). DOI:10.1111/tri.12523 · 3.16 Impact Factor
  • M. A. G. J. ten Dam, J. F. M. Wetzels
    The Netherlands Journal of Medicine 01/2015; 73(1):45-45. · 2.21 Impact Factor
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    ABSTRACT: Background & AimSeveral trials have demonstrated that somatostatin analogues decrease liver volume in mixed populations of patients with autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of lanreotide and possibly enhances risk for adverse events. The aim of this open-label clinical trial (RESOLVE trial) was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously every 4 weeks in ADPKD patients with symptomatic polycystic liver disease.Methods Primary outcome was change in liver volume after 6 months, secondary outcomes were changes in kidney volume, eGFR, symptom relief and health-related quality of life (Euro-Qol5D). We excluded patients with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2. We used the Wilcoxon signed-rank test or paired two-sided t-test to analyze within-group differences.ResultsWe included 43 ADPKD patients with polycystic liver disease (84% female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver volume decreased from 4,859 ml to 4,595 ml (-3.1%;p<0.001), and median kidney volume decreased from 1,023 ml to 1,012 ml (-1.7%;p=0.006). eGFR declined 3.5% after the first injection, remained stable up to study end, to decline again after lanreotide withdrawal. Lanreotide significantly relieved postprandial fullness, shortness of breath and abdominal distension. Three participants had a suspected episode of hepatic or renal cyst infection during the study.Conclusion Lanreotide reduced polycystic liver and kidney volumes and decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely after starting lanreotide, stabilized thereafter and declined again after withdrawal.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 11/2014; 35(5). DOI:10.1111/liv.12726 · 4.41 Impact Factor
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    ABSTRACT: The haemolytic uraemic syndrome (HUS) is part of a spectrum of thrombotic microangiopathies. The most common etiologies of HUS are the ones seen in childhood caused by an infection of Shiga toxin-producing Escherichia coli, HUS caused by an infection with Streptococcus pneumoniae and HUS due to abnormalities in the alternative pathway of the complement system. In the past decade, enormous progress has been made in understanding the pathogenesis in the latter group of patients. The analysis of genes that encode for complement regulatory proteins and the development of assays for measuring the activity of ADAMTS13 and the detection of antibodies against factor H contributed significantly to the diagnostic tools in patients with HUS. These assays have made it possible to clearly differentiate between thrombotic thrombocytopenic purpura and various forms of HUS. With the introduction of eculizumab, a monoclonal anti-C5 inhibitor, in the clinical arena as effective treatment of most complement-mediated forms of HUS, a new era of treatment in HUS has begun. We review the recent advances in HUS, with the focus on treatment. We discuss unsolved questions, which should be addressed in future studies.
    Nephrology Dialysis Transplantation 09/2014; 29(suppl 4):iv131-iv141. DOI:10.1093/ndt/gfu235 · 3.49 Impact Factor
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    ABSTRACT: The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA.RESULTS: In total, 48 patients (37 men) were included. The median age was 55 years (range, 34-75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98-3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab-positive patients, treatment resulted in a rapid decrease of antibodies: median anti-PLA2R-ab, 428 U/ml (range, 41-16,260 U/ml) at baseline and 24 U/ml (range, 0-505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003).CONCLUSIONS: These data suggest that in PLA2R-ab-positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course.
    Clinical Journal of the American Society of Nephrology 07/2014; 9(8). DOI:10.2215/CJN.10471013 · 5.25 Impact Factor
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    ABSTRACT: Background Activating mutations in the Transient Receptor Potential channel C6 (TRPC6) cause autosomal dominant focal segmental glomerular sclerosis (FSGS). TRPC6 expression is upregulated in renal biopsies of patients with idiopathic membranous glomerulopathy (iMN) and animal models thereof. In iMN, disease progression is characterized by glomerulosclerosis. In addition, a context-dependent TRPC6 overexpression was recently suggested in complement-mediated podocyte injury in e.g. iMN. Hence, we hypothesized that genetic variants in TRPC6 might affect susceptibility to development or progression of iMN. Methods & Results Genomic DNA was isolated from blood samples of 101 iMN patients and 292 controls. By direct sequencing of the entire TRPC6 gene, 13 single nucleotide polymorphisms (SNPs) were identified in the iMN cohort, two of which were causing an amino acid substitution (rs3802829; Pro15Ser and rs36111323, Ala404Val). No statistically significant differences in genotypes or allele frequencies between patients and controls were observed. Clinical outcome in patients was determined (remission n = 26, renal failure n = 46, persistent proteinuria n = 29, follow-up median 80 months {range 51–166}). The 13 identified SNPs showed no association with remission or renal failure. There were no differences in genotypes or allele frequencies between patients in remission and progressors. Conclusions Our data suggest that TRPC6 polymorphisms do not affect susceptibility to iMN, or clinical outcome in iMN.
    PLoS ONE 07/2014; 9(7):e102065. DOI:10.1371/journal.pone.0102065 · 3.53 Impact Factor
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    ABSTRACT: Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer.RESULTS: Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6-9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively.CONCLUSION: Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival.
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    ABSTRACT: Achtergrond In de eerste lijn komt chronische nierschade onder patiënten met diabetes of hypertensie veel voor. Deze cardiovasculaire risicofactor wordt echter vaak onvoldoende aangepakt. Een samenwerkingsmodel waarin huisartsen en praktijkondersteuners via internet een nefroloog kunnen consulteren, zou dat kunnen verbeteren. Methode Wij voerden een cluster-RCT uit in negen huisartsenpraktijken, onder patiënten met diabetes of hypertensie en chronische nierschade (geschatte glomerulaire filtratiesnelheid < 60ml/min/1,73 m2), Vijf praktijken pasten een jaar lang het samenwerkingsmodel toe en vier praktijken leverden reguliere zorg. Onze belangrijkste uitkomstmaten waren de gemiddelde bloeddrukverlaging en het percentage deelnemers dat de streefbloeddruk (≤ 130/80 mmHg) bereikte. Resultaten Wij analyseerden de gegevens van 90 patiënten in de interventiegroep en 74 in de controlegroep. De kans dat een patiënt een systolische bloeddruk van 130 mmHg bereikte, was in de interventiegroep 2,9 keer zo groot als in de controlegroep (95%-BI 1,4 tot 5,8), de kans op een diastolische bloeddruk van 90 mmHg was 2,5 keer zo groot (95%-BI 1,3 tot 4,7). In de interventiegroep nam de systolische bloeddruk af met 8,1 mmHg (95%-BI 4,8 tot 11,3), de diastolische met 1,1 mmHg (95%-BI –1,0 tot 3,2), tegenover –0,2 mmHg (95%-BI –3,8 tot 3,3) respectievelijk –0,5 mmHg (95%-BI –2,9 tot 1,8) in de controlegroep. In de interventiegroep lag bovendien het gebruik van lipidenverlagende middelen, RAS-remmers en vitamine D hoger en waren de concentraties parathormoon lager. Conclusie Een samenwerkingsmodel waarin huisarts, praktijkondersteuner en nefroloog samenwerken in de begeleiding van patiënten met diabetes of hypertensie en chronische nierschade, leidt tot een significant lagere systolische bloeddruk dan reguliere zorg.
    Huisarts en wetenschap 05/2014; 57(5):232-235. DOI:10.1007/s12445-014-0123-9
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    ABSTRACT: Slit diaphragm and podocyte damage is crucial in proteinuria pathogenesis in diabetic nephropathy (DNP). Gain-of-function mutations in TRPC6, a slit diaphragm-associated ion channel, cause glomerulosclerosis; TRPC6 expression is increased in acquired glomerular disease. Hyperglycemia and high intrarenal angiotensin II (AngII) levels could contribute to podocyte injury in DNP. We determined whether glucose regulates TRPC6 expression and TRPC6-mediated Ca(2+) influx into the podocyte and whether these effects are AngII dependent. High glucose levels increased TRPC6 mRNA and protein expression in cultured podocytes; however, TRPC1 and TRPC5 mRNA expression was unaltered. AngII and induced podocyte injury also specifically increased TRPC6 expression. Angiotensin receptor blockade and inhibition of local AngII production through angiotensin-converting enzyme inhibition prevented glucose-mediated increased TRPC6 expression. In addition, high glucose concentration pretreatment enhanced Ca(2+) influx in podocytes, which was prevented by concomitant angiotensin receptor blockade application and TRPC6 knockdown. Studies with a TRPC6 luciferase promoter construct demonstrated a glucose concentration-dependent effect on TRPC6 promoter activity. In vivo, podocyte TRPC6 protein expression was increased in proteinuric streptozotocin-induced diabetic rats. These data suggest that glucose can activate a local renin-angiotensin system in the podocyte, leading to increased TRPC6 expression, which enhances TRPC6-mediated Ca(2+) influx. Regulation of TRPC6 expression could be an important factor in podocyte injury due to chronic hyperglycemia and the antiproteinuric effect of angiotensin receptor blockade or angiotensin-converting enzyme inhibition in DNP.
    American Journal Of Pathology 04/2014; DOI:10.1016/j.ajpath.2014.02.008 · 4.60 Impact Factor
  • Julia M Hofstra, Jack F M Wetzels
    Journal of the American Society of Nephrology 03/2014; 25(6). DOI:10.1681/ASN.2014010091 · 9.47 Impact Factor
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    ABSTRACT: Membranous nephropathy, focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD) are the most common causes of idiopathic nephrotic syndrome. For many years prednisone, alkylating agents, and calcineurin inhibitors have been the standard of therapy for these patients. More effective or better tolerated treatment modalities are needed. B cell targeted therapy was recently introduced in clinical practice. In this review, we briefly summarize the current standard therapy and discuss the efficacy of B cell targeted therapy in primary glomerular diseases. Observational, short-term studies suggest that rituximab is effective and comparable to standard therapy in maintaining remissions in patients with frequently relapsing or steroid-dependent MCD or FSGS. In contrast, response is limited in patients with steroid-resistant nephrotic syndrome. Rituximab also induces remissions in patients with membranous nephropathy. Controlled clinical trials on kidney endpoints are urgently needed to position B cell targeted therapy in clinical practice.
    Advances in chronic kidney disease 03/2014; 21(2):166-181. DOI:10.1053/j.ackd.2014.01.005 · 1.94 Impact Factor
  • Rutger J H Maas, Jack F M Wetzels, Jeroen K J Deegens
    Kidney International 03/2014; 85(3):711. DOI:10.1038/ki.2013.513 · 8.52 Impact Factor
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    ABSTRACT: Promising renal replacement therapies include the development of a bio-artificial kidney using functional human kidney cell models. In this study, human conditionally immortalized proximal tubular epithelial cell (ciPTEC) lines originating from kidney tissue (ciPTEC-T1 and ciPTEC-T2) were compared to ciPTEC previously isolated from urine (ciPTEC-U). Subclones of all ciPTEC isolates formed tight cell layers on Transwell inserts as determined by transepithelial resistance, inulin diffusion, E-cadherin expression and immunocytochemisty. Extracellular matrix genes collagen I and -IV α1 were highly present in both kidney tissue derived matured cell lines (p<0.001) compared to matured ciPTEC-U, whereas matured ciPTEC-U showed a more pronounced fibronectin I and laminin 5 gene expression (p<0.01 and p<0.05, respectively). Expression of the influx carrier Organic Cation Transporter 2 (OCT-2), and the efflux pumps P-glycoprotein (P-gp), Multidrug Resistance Protein 4 (MRP4) and Breast Cancer Resistance Protein (BCRP) were confirmed in the three cell lines using real-time PCR and Western blotting. The activities of OCT-2 and P-gp were sensitive to specific inhibition in all models (p<0.001). The highest activity of MRP4 and BCRP was demonstrated in ciPTEC-U (p<0.05). Finally, active albumin reabsorption was highest in ciPTEC-T2 (p<0.001), while Na(+)-dependent phosphate reabsorption was most abundant in ciPTEC-U (p<0.01). In conclusion, ciPTEC established from human urine or kidney tissue display comparable functional PTEC specific transporters and physiological characteristics, providing ideal human tools for bioartificial kidney development.
    Experimental Cell Research 02/2014; 323(1). DOI:10.1016/j.yexcr.2014.02.011 · 3.37 Impact Factor
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    ABSTRACT: The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found an inverse correlation between the estimated glomerular filtration rate (eGFR) and suPAR. As patients with FSGS present at different eGFRs, we studied the relationship between eGFR and suPAR in a cohort of 476 non-FSGS patients and 54 patients with biopsy-proven idiopathic FSGS. In the non-FSGS patients, eGFR was the strongest significant determinant of suPAR. The proposed cutoff for suPAR in FSGS patients was exceeded in 17%, 39%, and 88% in patients with eGFRs of more than 60, 45-60, and 30-45 ml/min per 1.73 m(2), respectively. In patients with eGFR of <30 ml/min per 1.73 m(2), suPAR exceeded the cutoff in 95% of patients. Levels of suPAR in patients with idiopathic FSGS overlapped with non-FSGS controls and for any given eGFR did not discriminate FSGS cases from non-FSGS controls. In the overall cohort, there was a negative association between idiopathic FSGS and suPAR, and idiopathic FSGS was not an independent predictor of FSGS concentration over 3000 pg/ml. Thus, this study does not support an absolute, eGFR-independent, suPAR concentration cutoff as a biomarker for underlying FSGS pathology and questions the validity of relative, eGFR-dependent suPAR cutoff values.Kidney International advance online publication, 8 January 2014; doi:10.1038/ki.2013.505.
    Kidney International 01/2014; 85(3). DOI:10.1038/ki.2013.505 · 8.52 Impact Factor
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    ABSTRACT: Lithium is the most common cause of nephrogenic diabetes insipidus (Li-NDI). Hydrochlorothiazide (HCTZ) combined with amiloride is the mainstay treatment in Li-NDI. The paradox antidiuretic action of HCTZ in Li-NDI is generally attributed to increased sodium and water uptake in proximal tubules as a compensation for increased volume loss due to HCTZ inhibition of the NaCl-co-transporter (NCC), but alternative actions for HCTZ have been suggested. Here, we investigated whether HCTZ exerted an NCC-independent effect in Li-NDI. In polarized mouse cortical collecting duct (mpkCCD) cells, HCTZ treatment attenuated the Li-induced downregulation of the Aquaporin-2 (AQP2) water channel abundance. In these cells, amiloride reduces cellular Li influx through the epithelial sodium channel ENaC. HCTZ also reduced Li influx, but to a lower extent. HCTZ increased AQP2 abundance on top of that of amiloride and did not affect the ENaC-mediated transcellular voltage. MpkCCD cells did not express NCC mRNA or protein. These data indicated that in mpkCCD cells, HCTZ attenuated lithium-induced downregulation of AQP2 independent from NCC and ENaC. Treatment of Li-NDI NCC knockout mice with HCTZ revealed a significantly reduced urine volume, unchanged urine osmolality and increased cortical AQP2 abundance as compared to Li-treated NCC knockout mice. HCTZ treatment further resulted in reduced blood Li levels, creatinine clearance, and alkalinized urinary pH. Our in vitro and in vivo data indicate that part of the antidiuretic effect of HCTZ in Li-NDI is NCC-independent and may involve a tubuloglomerular feedback response mediated reduction in glomerular filtration rate due to proximal tubular carbonic anhydrase inhibition.
    AJP Renal Physiology 12/2013; 306(5). DOI:10.1152/ajprenal.00617.2013 · 4.42 Impact Factor

Publication Stats

4k Citations
1,437.26 Total Impact Points

Institutions

  • 1988–2015
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1989–2014
    • Radboud University Nijmegen
      • • Department of Nephrology
      • • Department of Physiology
      Nymegen, Gelderland, Netherlands
  • 2013
    • University of Zurich
      • Institute of Physiology
      Zürich, Zurich, Switzerland
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
    • Bridgeport Hospital
      Bridgeport, Connecticut, United States
  • 2012
    • Oxford University Hospitals NHS Trust
      • Department of Radiology
      Oxford, ENG, United Kingdom
  • 2010–2012
    • University Medical Center Utrecht
      • Department of Nephrology
      Utrecht, Provincie Utrecht, Netherlands
  • 2011
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2009–2011
    • University Hospital RWTH Aachen
      • Division of Internal Medicine
      Aachen, North Rhine-Westphalia, Germany
  • 2003
    • Gelderse Vallei Hospital
      • Department of Internal Medicine
      Ede, Gelderland, Netherlands
  • 1998
    • University Hospital Essen
      Essen, North Rhine-Westphalia, Germany
  • 1993–1995
    • University of Colorado Hospital
      • Department of Medicine
      Denver, Colorado, United States
  • 1986
    • St. Joseph's Hospital
      Savannah, Georgia, United States