Skip to main content
Erschienen in: Pediatric Nephrology 8/2017

08.03.2017 | Original Article

Longitudinal assessment of myocardial function in childhood chronic kidney disease, during dialysis, and following kidney transplantation

verfasst von: Rawan K. Rumman, Ronand Ramroop, Rahul Chanchlani, Mikaeel Ghany, Diane Hebert, Elizabeth A. Harvey, Rulan S. Parekh, Luc Mertens, Michael Grattan

Erschienen in: Pediatric Nephrology | Ausgabe 8/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

Childhood chronic kidney disease (CKD) and dialysis are associated with increased long-term cardiovascular risk. We examined subclinical alterations in myocardial mechanics longitudinally in children with CKD, during dialysis, and following renal transplantation.

Methods

Forty-eight children with CKD (stage III or higher) who received kidney transplants from 2008 to 2014 were included in a retrospective study and compared to 192 age- and sex-matched healthy children. Measurements of cardiac systolic and diastolic function were performed, and global longitudinal strain (GLS) and circumferential strain (GCS) were measured by speckle-tracking echocardiography at CKD, during dialysis, and 1 year following kidney transplantation. Mixed-effects modeling examined changes in GLS and GCS over different disease stages.

Results

Children with CKD had a mean age of 10 ± 5 years and 67% were male. Eighteen children received preemptive transplantation. Children with CKD had increased left ventricular mass, lower GLS, and impaired diastolic function (lower E/A ratio and E′ velocities) than healthy children. Changes in left ventricular diastolic parameters persisted during dialysis and after renal transplantation. Dialysis was associated with reduced GLS compared to CKD (β = 1.6, 95% confidence interval 0.2–3.0); however, this was not significant after adjustment for systolic blood pressure and CKD duration. Post-transplantation GLS levels were similar to those at CKD assessment. GCS was unchanged during dialysis but significantly improved following transplantation.

Conclusions

There are differences in diastolic parameters in childhood CKD that persist during dialysis and after transplantation. Systolic parameters are preserved, with significant improvement in systolic myocardial deformation following transplantation. The impact of persistent diastolic changes on long-term outcomes requires further investigation.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Wilson AC, Mitsnefes MM (2009) Cardiovascular disease in CKD in children: update on risk factors, risk assessment, and management. Am J Kidney Dis 54:345–360CrossRefPubMedPubMedCentral Wilson AC, Mitsnefes MM (2009) Cardiovascular disease in CKD in children: update on risk factors, risk assessment, and management. Am J Kidney Dis 54:345–360CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Lal AK, de Biasi AR, Alexander S, Rosenthal DN, Sutherland SM (2012) End-stage renal disease and cardiomyopathy in children: cardiac effects of renal transplantation. Transplantation 93:182–187CrossRefPubMed Lal AK, de Biasi AR, Alexander S, Rosenthal DN, Sutherland SM (2012) End-stage renal disease and cardiomyopathy in children: cardiac effects of renal transplantation. Transplantation 93:182–187CrossRefPubMed
4.
Zurück zum Zitat Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2004) Abnormal cardiac function in children after renal transplantation. Am J Kidney Dis 43:721–726CrossRefPubMed Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2004) Abnormal cardiac function in children after renal transplantation. Am J Kidney Dis 43:721–726CrossRefPubMed
5.
Zurück zum Zitat Kim GB, Kwon BS, Kang HG, Ha JW, Ha IS, Noh CI, Choi JY, Kim SJ, Yun YS, Bae EJ (2009) Cardiac dysfunction after renal transplantation; incomplete resolution in pediatric population. Transplantation 87:1737–1743CrossRefPubMed Kim GB, Kwon BS, Kang HG, Ha JW, Ha IS, Noh CI, Choi JY, Kim SJ, Yun YS, Bae EJ (2009) Cardiac dysfunction after renal transplantation; incomplete resolution in pediatric population. Transplantation 87:1737–1743CrossRefPubMed
6.
Zurück zum Zitat Shamszad P, Slesnick TC, Smith EO, Taylor MD, Feig DI (2012) Association between left ventricular mass index and cardiac function in pediatric dialysis patients. Pediatr Nephrol 27:835–841CrossRefPubMed Shamszad P, Slesnick TC, Smith EO, Taylor MD, Feig DI (2012) Association between left ventricular mass index and cardiac function in pediatric dialysis patients. Pediatr Nephrol 27:835–841CrossRefPubMed
7.
Zurück zum Zitat Bozbas H, Altin C, Karacaglar E, Kanyilmaz S, Yildirir A, Muderrisoglu H, Haberal M (2013) The prevalence and types of cardiovascular disease in patients with end-stage renal disease undergoing renal transplantation. Transplant Proc 45:3478–3480CrossRefPubMed Bozbas H, Altin C, Karacaglar E, Kanyilmaz S, Yildirir A, Muderrisoglu H, Haberal M (2013) The prevalence and types of cardiovascular disease in patients with end-stage renal disease undergoing renal transplantation. Transplant Proc 45:3478–3480CrossRefPubMed
8.
Zurück zum Zitat Dounousi E, Mitsis M, Naka KK, Pappas C, Lakkas L, Harisis C, Pappas K, Koutlas V, Tzalavra I, Spanos G, Michalis LK, Siamopoulos KC (2014) Differences in cardiac structure assessed by echocardiography between renal transplant recipients and chronic kidney disease patients. Transplant Proc 46:3194–3198CrossRefPubMed Dounousi E, Mitsis M, Naka KK, Pappas C, Lakkas L, Harisis C, Pappas K, Koutlas V, Tzalavra I, Spanos G, Michalis LK, Siamopoulos KC (2014) Differences in cardiac structure assessed by echocardiography between renal transplant recipients and chronic kidney disease patients. Transplant Proc 46:3194–3198CrossRefPubMed
9.
Zurück zum Zitat Gu H, Sinha MD, Li Y, Simpson J, Chowienczyk PJ (2015) Elevated ejection-phase myocardial wall stress in children with chronic kidney disease. Hypertension. 66(4):823–829 Gu H, Sinha MD, Li Y, Simpson J, Chowienczyk PJ (2015) Elevated ejection-phase myocardial wall stress in children with chronic kidney disease. Hypertension. 66(4):823–829
10.
Zurück zum Zitat Malatesta-Muncher R, Wansapura J, Taylor M, Lindquist D, Hor K, Mitsnefes M (2012) Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant. Pediatr Nephrol 27:1157–1164CrossRefPubMedPubMedCentral Malatesta-Muncher R, Wansapura J, Taylor M, Lindquist D, Hor K, Mitsnefes M (2012) Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant. Pediatr Nephrol 27:1157–1164CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Krishnasamy R, Hawley CM, Stanton T, Pascoe EM, Campbell KL, Rossi M, Petchey W, Tan KS, Beetham KS, Coombes JS, Leano R, Haluska BA, Isbel NM (2015) Left ventricular global longitudinal strain is associated with cardiovascular risk factors and arterial stiffness in chronic kidney disease. BMC Nephrol 16:106CrossRefPubMedPubMedCentral Krishnasamy R, Hawley CM, Stanton T, Pascoe EM, Campbell KL, Rossi M, Petchey W, Tan KS, Beetham KS, Coombes JS, Leano R, Haluska BA, Isbel NM (2015) Left ventricular global longitudinal strain is associated with cardiovascular risk factors and arterial stiffness in chronic kidney disease. BMC Nephrol 16:106CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Krishnasamy R, Isbel NM, Hawley CM, Pascoe EM, Leano R, Haluska BA, Stanton T (2014) The association between left ventricular global longitudinal strain, renal impairment and all-cause mortality. Nephrol Dial Transplant 29:1218–1225CrossRefPubMed Krishnasamy R, Isbel NM, Hawley CM, Pascoe EM, Leano R, Haluska BA, Stanton T (2014) The association between left ventricular global longitudinal strain, renal impairment and all-cause mortality. Nephrol Dial Transplant 29:1218–1225CrossRefPubMed
13.
Zurück zum Zitat Kramann R, Erpenbeck J, Schneider RK, Rohl AB, Hein M, Brandenburg VM, van Diepen M, Dekker F, Marx N, Floege J, Becker M, Schlieper G (2014) Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD. J Am Soc Nephrol 25:2351–2365CrossRefPubMedPubMedCentral Kramann R, Erpenbeck J, Schneider RK, Rohl AB, Hein M, Brandenburg VM, van Diepen M, Dekker F, Marx N, Floege J, Becker M, Schlieper G (2014) Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD. J Am Soc Nephrol 25:2351–2365CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Kovacs A, Tapolyai M, Celeng C, Gara E, Faludi M, Berta K, Apor A, Nagy A, Tisler A, Merkely B (2014) Impact of hemodialysis, left ventricular mass and FGF-23 on myocardial mechanics in end-stage renal disease: a three-dimensional speckle tracking study. Int J Cardiovasc Imaging 30:1331–1337CrossRefPubMed Kovacs A, Tapolyai M, Celeng C, Gara E, Faludi M, Berta K, Apor A, Nagy A, Tisler A, Merkely B (2014) Impact of hemodialysis, left ventricular mass and FGF-23 on myocardial mechanics in end-stage renal disease: a three-dimensional speckle tracking study. Int J Cardiovasc Imaging 30:1331–1337CrossRefPubMed
15.
Zurück zum Zitat Fukushima K, Javadi MS, Higuchi T, Bravo PE, Chien D, Lautamaki R, Merrill J, Nekolla SG, Bengel FM (2012) Impaired global myocardial flow dynamics despite normal left ventricular function and regional perfusion in chronic kidney disease: a quantitative analysis of clinical 82Rb PET/CT studies. J Nucl Med 53:887–893CrossRefPubMed Fukushima K, Javadi MS, Higuchi T, Bravo PE, Chien D, Lautamaki R, Merrill J, Nekolla SG, Bengel FM (2012) Impaired global myocardial flow dynamics despite normal left ventricular function and regional perfusion in chronic kidney disease: a quantitative analysis of clinical 82Rb PET/CT studies. J Nucl Med 53:887–893CrossRefPubMed
16.
Zurück zum Zitat Edwards NC, Hirth A, Ferro CJ, Townend JN, Steeds RP (2008) Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: the precursor of uremic cardiomyopathy? J Am Soc Echocardiogr 21:1293–1298CrossRefPubMed Edwards NC, Hirth A, Ferro CJ, Townend JN, Steeds RP (2008) Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: the precursor of uremic cardiomyopathy? J Am Soc Echocardiogr 21:1293–1298CrossRefPubMed
17.
Zurück zum Zitat Panoulas VF, Sulemane S, Konstantinou K, Bratsas A, Elliott SJ, Dawson D, Frankel AH, Nihoyannopoulos P (2015) Early detection of subclinical left ventricular myocardial dysfunction in patients with chronic kidney disease. Eur Heart J Cardiovasc Imaging 16:539–548CrossRefPubMed Panoulas VF, Sulemane S, Konstantinou K, Bratsas A, Elliott SJ, Dawson D, Frankel AH, Nihoyannopoulos P (2015) Early detection of subclinical left ventricular myocardial dysfunction in patients with chronic kidney disease. Eur Heart J Cardiovasc Imaging 16:539–548CrossRefPubMed
18.
Zurück zum Zitat Florescu M, Benea DC, Rimbas RC, Cerin G, Diena M, Lanzzillo G, Enescu OA, Cinteza M, Vinereanu D (2012) Myocardial systolic velocities and deformation assessed by speckle tracking for early detection of left ventricular dysfunction in asymptomatic patients with severe primary mitral regurgitation. Echocardiography 29:326–333CrossRefPubMed Florescu M, Benea DC, Rimbas RC, Cerin G, Diena M, Lanzzillo G, Enescu OA, Cinteza M, Vinereanu D (2012) Myocardial systolic velocities and deformation assessed by speckle tracking for early detection of left ventricular dysfunction in asymptomatic patients with severe primary mitral regurgitation. Echocardiography 29:326–333CrossRefPubMed
19.
Zurück zum Zitat Friedberg MK, Mertens L (2012) Deformation imaging in selected congenital heart disease: is it evolving to clinical use? J Am Soc Echocardiogr 25:919–931CrossRefPubMed Friedberg MK, Mertens L (2012) Deformation imaging in selected congenital heart disease: is it evolving to clinical use? J Am Soc Echocardiogr 25:919–931CrossRefPubMed
20.
Zurück zum Zitat Mignot A, Donal E, Zaroui A, Reant P, Salem A, Hamon C, Monzy S, Roudaut R, Habib G, Lafitte S (2010) Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study. J Am Soc Echocardiogr 23:1019–1024CrossRefPubMed Mignot A, Donal E, Zaroui A, Reant P, Salem A, Hamon C, Monzy S, Roudaut R, Habib G, Lafitte S (2010) Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study. J Am Soc Echocardiogr 23:1019–1024CrossRefPubMed
21.
Zurück zum Zitat Chinali M, Matteucci MC, Franceschini A, Doyon A, Pongiglione G, Rinelli G, Schaefer F (2015) Advanced parameters of cardiac mechanics in children with CKD: the 4C study. Clin J Am Soc Nephrol 10:1357–1363 Chinali M, Matteucci MC, Franceschini A, Doyon A, Pongiglione G, Rinelli G, Schaefer F (2015) Advanced parameters of cardiac mechanics in children with CKD: the 4C study. Clin J Am Soc Nephrol 10:1357–1363
22.
Zurück zum Zitat Chinali M, de Simone G, Matteucci MC, Picca S, Mastrostefano A, Anarat A, Caliskan S, Jeck N, Neuhaus TJ, Peco-Antic A, Peruzzi L, Testa S, Mehls O, Wuhl E, Schaefer F (2007) Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol 18:593–598CrossRefPubMed Chinali M, de Simone G, Matteucci MC, Picca S, Mastrostefano A, Anarat A, Caliskan S, Jeck N, Neuhaus TJ, Peco-Antic A, Peruzzi L, Testa S, Mehls O, Wuhl E, Schaefer F (2007) Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol 18:593–598CrossRefPubMed
23.
Zurück zum Zitat Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Grattan MJ, Mertens L (2014) Echocardiographic assessment of ventricular function in pediatric patients: a comprehensive guide. Future Cardiol 10:511–523CrossRefPubMed Grattan MJ, Mertens L (2014) Echocardiographic assessment of ventricular function in pediatric patients: a comprehensive guide. Future Cardiol 10:511–523CrossRefPubMed
25.
Zurück zum Zitat Koopman LP, McCrindle BW, Slorach C, Chahal N, Hui W, Sarkola T, Manlhiot C, Jaeggi ET, Bradley TJ, Mertens L (2012) Interaction between myocardial and vascular changes in obese children: a pilot study. J Am Soc Echocardiogr 25:401–410CrossRefPubMed Koopman LP, McCrindle BW, Slorach C, Chahal N, Hui W, Sarkola T, Manlhiot C, Jaeggi ET, Bradley TJ, Mertens L (2012) Interaction between myocardial and vascular changes in obese children: a pilot study. J Am Soc Echocardiogr 25:401–410CrossRefPubMed
26.
Zurück zum Zitat Foster BJ, Mackie AS, Mitsnefes M, Ali H, Mamber S, Colan SD (2008) A novel method of expressing left ventricular mass relative to body size in children. Circulation 117:2769–2775CrossRefPubMed Foster BJ, Mackie AS, Mitsnefes M, Ali H, Mamber S, Colan SD (2008) A novel method of expressing left ventricular mass relative to body size in children. Circulation 117:2769–2775CrossRefPubMed
27.
Zurück zum Zitat Falkner B, Daniels SR (2004) Summary of the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Hypertension 44:387–388CrossRefPubMed Falkner B, Daniels SR (2004) Summary of the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Hypertension 44:387–388CrossRefPubMed
28.
Zurück zum Zitat Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL (2002) 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11:1–190 Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL (2002) 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11:1–190
29.
Zurück zum Zitat Simpson JM, Rawlins D, Mathur S, Chubb H, Sinha MD (2013) Systolic and diastolic ventricular function assessed by tissue Doppler imaging in children with chronic kidney disease. Echocardiography 30:331–337CrossRefPubMed Simpson JM, Rawlins D, Mathur S, Chubb H, Sinha MD (2013) Systolic and diastolic ventricular function assessed by tissue Doppler imaging in children with chronic kidney disease. Echocardiography 30:331–337CrossRefPubMed
30.
Zurück zum Zitat Matteucci MC, Chinali M, Rinelli G, Wuhl E, Zurowska A, Charbit M, Pongiglione G, Schaefer F (2013) Change in cardiac geometry and function in CKD children during strict BP control: a randomized study. Clin J Am Soc Nephrol 8:203–210CrossRefPubMed Matteucci MC, Chinali M, Rinelli G, Wuhl E, Zurowska A, Charbit M, Pongiglione G, Schaefer F (2013) Change in cardiac geometry and function in CKD children during strict BP control: a randomized study. Clin J Am Soc Nephrol 8:203–210CrossRefPubMed
31.
Zurück zum Zitat Chen R, Wu X, Shen LJ, Wang B, Ma MM, Yang Y, Zhao BW (2014) Left ventricular myocardial function in hemodialysis and nondialysis uremia patients: a three-dimensional speckle-tracking echocardiography study. PLoS ONE 9:e100265CrossRefPubMedPubMedCentral Chen R, Wu X, Shen LJ, Wang B, Ma MM, Yang Y, Zhao BW (2014) Left ventricular myocardial function in hemodialysis and nondialysis uremia patients: a three-dimensional speckle-tracking echocardiography study. PLoS ONE 9:e100265CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Asp AM, Wallquist C, Rickenlund A, Hylander B, Jacobson SH, Caidahl K, Eriksson MJ (2015) Cardiac remodelling and functional alterations in mild-to-moderate renal dysfunction: comparison with healthy subjects. Clin Physiol Funct Imaging 35:223–230CrossRefPubMed Asp AM, Wallquist C, Rickenlund A, Hylander B, Jacobson SH, Caidahl K, Eriksson MJ (2015) Cardiac remodelling and functional alterations in mild-to-moderate renal dysfunction: comparison with healthy subjects. Clin Physiol Funct Imaging 35:223–230CrossRefPubMed
33.
Zurück zum Zitat Mencarelli F, Fabi M, Corazzi V, Doyon A, Masetti R, Bonetti S, Castiglioni L, Pession A, Montini G (2014) Left ventricular mass and cardiac function in a population of children with chronic kidney disease. Pediatr Nephrol 29:893–900CrossRefPubMed Mencarelli F, Fabi M, Corazzi V, Doyon A, Masetti R, Bonetti S, Castiglioni L, Pession A, Montini G (2014) Left ventricular mass and cardiac function in a population of children with chronic kidney disease. Pediatr Nephrol 29:893–900CrossRefPubMed
34.
Zurück zum Zitat Hayashi SY, Rohani M, Lindholm B, Brodin LA, Lind B, Barany P, Alvestrand A, Seeberger A (2006) Left ventricular function in patients with chronic kidney disease evaluated by colour tissue Doppler velocity imaging. Nephrol Dial Transplant 21:125–132CrossRefPubMed Hayashi SY, Rohani M, Lindholm B, Brodin LA, Lind B, Barany P, Alvestrand A, Seeberger A (2006) Left ventricular function in patients with chronic kidney disease evaluated by colour tissue Doppler velocity imaging. Nephrol Dial Transplant 21:125–132CrossRefPubMed
35.
Zurück zum Zitat Lindblad YT, Axelsson J, Balzano R, Vavilis G, Chromek M, Celsi G, Barany P (2013) Left ventricular diastolic dysfunction by tissue Doppler echocardiography in pediatric chronic kidney disease. Pediatr Nephrol 28:2003–2013 Lindblad YT, Axelsson J, Balzano R, Vavilis G, Chromek M, Celsi G, Barany P (2013) Left ventricular diastolic dysfunction by tissue Doppler echocardiography in pediatric chronic kidney disease. Pediatr Nephrol 28:2003–2013
Metadaten
Titel
Longitudinal assessment of myocardial function in childhood chronic kidney disease, during dialysis, and following kidney transplantation
verfasst von
Rawan K. Rumman
Ronand Ramroop
Rahul Chanchlani
Mikaeel Ghany
Diane Hebert
Elizabeth A. Harvey
Rulan S. Parekh
Luc Mertens
Michael Grattan
Publikationsdatum
08.03.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 8/2017
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-017-3622-7

Weitere Artikel der Ausgabe 8/2017

Pediatric Nephrology 8/2017 Zur Ausgabe

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

23.04.2024 Typ-1-Diabetes Nachrichten

Wenn Kinder an Werktagen zum Arzt gehen, werden neu auftretender Typ-1-Diabetes und diabetische Ketoazidosen häufiger erkannt als bei Arztbesuchen an Wochenenden oder Feiertagen.

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

22.04.2024 Fehlsichtigkeit Nachrichten

Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.