Pathophysiologische Mechanismen der Progression von Nierenerkrankungen

Zusammenfassung

Chronische Nierenerkrankungen betreffen mehr als 10 % der Weltbevölkerung und belasten das Gesundheitssystem und den individuellen Patienten erheblich. Um die Pathophysiologie dieser Erkrankungen adäquat zu erfassen, ist ein Verständnis der Mechanismen essenziell. Dieser Beitrag fasst zentrale Mechanismen der Krankheitsprogression zusammen, die bei jeder Nierenerkrankung, unabhängig von ihrer Ätiologie eine zentrale Rolle spielt, und stellt relevante wissenschaftliche Erkenntnisse vor, die für das Verständnis von Bedeutung sind.

Publication History

Article published online:
21 July 2025

• Literatur

• 1 Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011) 2022; 12: 7-11
• 2 Eckardt KU, Coresh J, Devuyst O. et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 2013; 382: 158-169
• 3 Titze S, Schmid M, Kottgen A. et al. Disease burden and risk profile in referred patients with moderate chronic kidney disease: composition of the German Chronic Kidney Disease (GCKD) cohort. Nephrol Dial Transplant 2015; 30: 441-451
• 4 Abro A, Greenhall GHB, Nitsch D. Chronic Kidney Disease: Epidemiology and Causes. In: Harber M. Primer on Nephrology. Cham: Springer International Publishing; 2022: 1123-1133
• 5 Bonsib SM. Renal Vascular Diseases. In: Stephen M, Bonsib MD. Atlas of Medical Renal Pathology. New York: Springer New York; 2013: 147-177
• 6 Levey AS, Coresh J. Chronic kidney disease. Lancet 2012; 379: 165-180
• 7 Jordans I. Bundesverband Niere e. V. Chronische Nierenerkrankungen – Allgemeine Informationen über die Erkrankung. Im Internet: Accessed April 14, 2025 at: https://www.bundesverband-niere.de/informationen/chronische-nierenerkrankungen
• 8 Kaartinen K, Safa A, Kotha S. et al. Complement dysregulation in glomerulonephritis. Semin Immunol 2019; 45: 101331
• 9 Floege J, Amann K. Primary glomerulonephritides. Lancet 2016; 387: 2036-2048
• 10 Shah PP, Brady TM, Meyers KEC. et al. Association of Obesity with Cardiovascular Risk Factors and Kidney Disease Outcomes in Primary Proteinuric Glomerulopathies. Nephron 2021; 145: 245-255
• 11 Sulaiman MK. Diabetic nephropathy: recent advances in pathophysiology and challenges in dietary management. Diabetol Metab Syndr 2019; 11: 7
• 12 Bakris GL. Recognition, pathogenesis, and treatment of different stages of nephropathy in patients with type 2 diabetes mellitus. Mayo Clin Proc 2011; 86: 444-456
• 13 VR ALBVR. Tan SH, Candasamy M. et al. Diabetic nephropathy: An update on pathogenesis and drug development. Diabetes Metab Syndr 2019; 13: 754-762
• 14 Samsu N. Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Res Int 2021; 2021: 1497449
• 15 Lopez-Novoa JM, Martinez-Salgado C, Rodriguez-Pena AB. et al. Common pathophysiological mechanisms of chronic kidney disease: therapeutic perspectives. Pharmacol Ther 2010; 128: 61-81
• 16 Fogo AB. Mechanisms of progression of chronic kidney disease. Pediatr Nephrol 2007; 22: 2011-2022
• 17 Wolf G, Ritz E. Diabetic nephropathy in type 2 diabetes prevention and patient management. J Am Soc Nephrol 2003; 14: 1396-1405
• 18 Wolf G, Ziyadeh FN. The role of angiotensin II in diabetic nephropathy: emphasis on nonhemodynamic mechanisms. Am J Kidney Dis 1997; 29: 153-163
• 19 Chen S, Wolf G, Ziyadeh FN. The renin-angiotensin system in diabetic nephropathy. Contrib Nephrol 2001; 212-221
• 20 Wolf G, Mueller E, Stahl RA. et al. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta. J Clin Invest 1993; 92: 1366-1372
• 21 Wolf G, Ziyadeh FN, Stahl RA. Angiotensin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells. J Mol Med (Berl) 1999; 77: 556-564
• 22 Wolf G, Zahner G, Schroeder R. et al. Transforming growth factor beta mediates the angiotensin-II-induced stimulation of collagen type IV synthesis in cultured murine proximal tubular cells. Nephrol Dial Transplant 1996; 11: 263-269
• 23 Wolf G, Wenzel U, Burns KD. et al. Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors. Kidney Int 2002; 61: 1986-1995
• 24 Wolf G, Bohlender J, Bondeva T. et al. Angiotensin II upregulates toll-like receptor 4 on mesangial cells. J Am Soc Nephrol 2006; 17: 1585-1593
• 25 Huang R, Fu P, Ma L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal Transduct Target Ther 2023; 8: 129
• 26 Duffield JS. Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest 2014; 124: 2299-2306
• 27 Liu Y. Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol 2011; 7: 684-696
• 28 Vanhove T, Goldschmeding R, Kuypers D. Kidney Fibrosis: Origins and Interventions. Transplantation 2017; 101: 713-726
• 29 Matovinovic MS. 1. Pathophysiology and Classification of Kidney Diseases. EJIFCC 2009; 20: 2-11
• 30 Noronha IL, Fujihara CK, Zatz R. The inflammatory component in progressive renal disease–are interventions possible?. Nephrol Dial Transplant 2002; 17: 363-368
• 31 Yamashita N, Kramann R. Mechanisms of kidney fibrosis and routes towards therapy. Trends Endocrinol Metab 2024; 35: 31-48
• 32 Wu D, Wu J, Liu H. et al. A biomimetic renal fibrosis progression model on-chip evaluates anti-fibrotic effects longitudinally in a dynamic fibrogenic niche. Lab Chip 2023; 23: 4708-4725
• 33 Loeffler I, Wolf G. Transforming growth factor-beta and the progression of renal disease. Nephrol Dial Transplant 2014; 29 (Suppl. 1) i37-i45
• 34 Fu H, Tian Y, Zhou L. et al. Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis. J Am Soc Nephrol 2017; 28: 785-801
• 35 Li L, Fu H, Liu Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat Rev Nephrol 2022; 18: 545-557
• 36 Yuan Q, Tan RJ, Liu Y. Myofibroblast in Kidney Fibrosis: Origin, Activation, and Regulation. In: Liu B-C, Lan H-Y, Lv L-L. et al. Renal Fibrosis: Mechanisms and Therapies. Singapore: Springer Singapore; 2019: 253-283
• 37 Herrera J, Henke CA, Bitterman PB. Extracellular matrix as a driver of progressive fibrosis. J Clin Invest 2018; 128: 45-53
• 38 McWilliam SJ, Wright RD, Welsh GI. et al. The complex interplay between kidney injury and inflammation. Clin Kidney J 2021; 14: 780-788
• 39 Ernandez T, Mayadas TN. The Changing Landscape of Renal Inflammation. Trends Mol Med 2016; 22: 151-163
• 40 Tecklenborg J, Clayton D, Siebert S. et al. The role of the immune system in kidney disease. Clin Exp Immunol 2018; 192: 142-150
• 41 Andrade-Oliveira V, Foresto-Neto O, Watanabe IKM. et al. Inflammation in Renal Diseases: New and Old Players. Front Pharmacol 2019; 10: 1192
• 42 Panzer U, Steinmetz OM, Stahl RA. et al. Kidney diseases and chemokines. Curr Drug Targets 2006; 7: 65-80
• 43 Salvadori M, Tsalouchos A. Microbiota, renal disease and renal transplantation. World J Transplant 2021; 11: 16-36
• 44 Cao C, Zhu H, Yao Y. et al. Gut Dysbiosis and Kidney Diseases. Front Med (Lausanne) 2022; 9: 829349
• 45 Chi M, Ma K, Wang J. et al. The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease. J Immunol Res 2021; 2021: 5516035
• 46 Snelson M, Biruete A, McFarlane C. et al. A Renal Clinician’s Guide to the Gut Microbiota. J Ren Nutr 2020; 30: 384-395
• 47 Mihai S, Codrici E, Popescu ID. et al. Inflammation-Related Mechanisms in Chronic Kidney Disease Prediction, Progression, and Outcome. J Immunol Res 2018; 2018: 2180373
• 48 Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int 2013; 83: 1010-1016
• 49 Krishnan S, Suarez-Martinez AD, Bagher P. et al. Microvascular dysfunction and kidney disease: Challenges and opportunities?. Microcirculation 2021; 28: e12661
• 50 Schlondorff DO. Overview of factors contributing to the pathophysiology of progressive renal disease. Kidney Int 2008; 74: 860-866
• 51 Adamczak M, Zeier M, Dikow R. et al. Kidney and hypertension. Kidney Int Suppl 2002; 62-67
• 52 Udani S, Lazich I, Bakris GL. Epidemiology of hypertensive kidney disease. Nat Rev Nephrol 2011; 7: 11-21
• 53 Mullins LJ, Conway BR, Menzies RI. et al. Renal disease pathophysiology and treatment: contributions from the rat. Dis Model Mech 2016; 9: 1419-1433
• 54 London GM. Arterial Stiffness in Chronic Kidney Disease and End-Stage Renal Disease. Blood Purif 2018; 45: 154-158
• 55 Dusing P, Zietzer A, Goody PR. et al. Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches. J Mol Med (Berl) 2021; 99: 335-348
• 56 Toussaint ND, Kerr PG. Vascular calcification and arterial stiffness in chronic kidney disease: implications and management. Nephrology (Carlton) 2007; 12: 500-509
• 57 Inserra F, Forcada P, Castellaro A. et al. Chronic Kidney Disease and Arterial Stiffness: A Two-Way Path. Front Med (Lausanne) 2021; 8: 765924
• 58 Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension 2004; 44: 595-601
• 59 Brenner BM, Garcia DL, Anderson S. Glomeruli and blood pressure. Less of one, more the other?. Am J Hypertens 1988; 1: 335-347
• 60 Gross ML, Amann K. Progression of renal disease: new insights into risk factors and pathomechanisms. Curr Opin Nephrol Hypertens 2004; 13: 307-312
• 61 Singh GR, Hoy WE. Kidney volume, blood pressure, and albuminuria: findings in an Australian aboriginal community. Am J Kidney Dis 2004; 43: 254-259
• 62 Fassi A, Sangalli F, Maffi R. et al. Progressive glomerular injury in the MWF rat is predicted by inborn nephron deficit. J Am Soc Nephrol 1998; 9: 1399-1406
• 63 Keller G, Zimmer G, Mall G. et al. Nephron number in patients with primary hypertension. N Engl J Med 2003; 348: 101-108
• 64 Reyes L, Manalich R. Long-term consequences of low birth weight. Kidney Int Suppl 2005; S107–111
• 65 Keane WF. Proteinuria: its clinical importance and role in progressive renal disease. Am J Kidney Dis 2000; 35: S97-105
• 66 Chang A, Ko K, Clark MR. The emerging role of the inflammasome in kidney diseases. Curr Opin Nephrol Hypertens 2014; 23: 204-210
• 67 Remuzzi G, Ruggenenti P, Benigni A. Understanding the nature of renal disease progression. Kidney Int 1997; 51: 2-15
• 68 Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage?. J Am Soc Nephrol 2006; 17: 2974-2984
• 69 Wolf G, Ziyadeh FN. Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Nephron Physiol 2007; 106: 26-31
• 70 Komada T, Muruve DA. The role of inflammasomes in kidney disease. Nat Rev Nephrol 2019; 15: 501-520
• 71 Aranda-Rivera AK, Srivastava A, Cruz-Gregorio A. et al. Involvement of Inflammasome Components in Kidney Disease. Antioxidants (Basel) 2022; 11
• 72 Zhuang Y, Ding G, Zhao M. et al. NLRP3 inflammasome mediates albumin-induced renal tubular injury through impaired mitochondrial function. J Biol Chem 2014; 289: 25101-25111
• 73 Fang L, Xie D, Wu X. et al. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells. PLoS One 2013; 8: e72344
• 74 Zhou R, Yazdi AS, Menu P. et al. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469: 221-225
• 75 Hsu CN, Tain YL. Developmental Origins of Kidney Disease: Why Oxidative Stress Matters?. Antioxidants (Basel) 2020; 10
• 76 Small DM, Coombes JS, Bennett N. et al. Oxidative stress, anti-oxidant therapies and chronic kidney disease. Nephrology (Carlton) 2012; 17: 311-321
• 77 Krata N, Zagozdzon R, Foroncewicz B. et al. Oxidative Stress in Kidney Diseases: The Cause or the Consequence?. Arch Immunol Ther Exp (Warsz) 2018; 66: 211-220
• 78 Tejchman K, Kotfis K, Sienko J. Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation. Int J Mol Sci 2021; 22: 8010
• 79 Piko N, Bevc S, Hojs R. et al. The Role of Oxidative Stress in Kidney Injury. Antioxidants (Basel) 2023; 12: 1772
• 80 Duann P, Lin PH. Mitochondria Damage and Kidney Disease. Adv Exp Med Biol 2017; 982: 529-551
• 81 Sachse A, Wolf G. Angiotensin II-induced reactive oxygen species and the kidney. J Am Soc Nephrol 2007; 18: 2439-2446
• 82 Ozbek E. Induction of oxidative stress in kidney. Int J Nephrol 2012; 2012: 465897
• 83 Ho HJ, Shirakawa H. Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease. Cells 2022; 12: 88
• 84 Pedraza-Chaverri J, Sanchez-Lozada LG, Osorio-Alonso H. et al. New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease. Oxid Med Cell Longev 2016; 2016: 6043601
• 85 Honda T, Hirakawa Y, Nangaku M. The role of oxidative stress and hypoxia in renal disease. Kidney Res Clin Pract 2019; 38: 414-426
• 86 Wang Y, Chen X, Song Y. et al. Association between obesity and kidney disease: a systematic review and meta-analysis. Kidney Int 2008; 73: 19-33
• 87 Vupputuri S, Sandler DP. Lifestyle risk factors and chronic kidney disease. Ann Epidemiol 2003; 13: 712-720
• 88 Wolf G, Chen S, Han DC. et al. Leptin and renal disease. Am J Kidney Dis 2002; 39: 1-11
• 89 Wolf G. After all those fat years: renal consequences of obesity. Nephrol Dial Transplant 2003; 18: 2471-2474
• 90 Wickman C, Kramer H. Obesity and kidney disease: potential mechanisms. Semin Nephrol 2013; 33: 14-22
• 91 Ruster C, Wolf G. Adipokines promote chronic kidney disease. Nephrol Dial Transplant 2013; 28 (Suppl. 4) iv8-14
• 92 Wolf G, Hamann A, Han DC. et al. et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis [seecomments]. Kidney Int 1999; 56: 860-872
• 93 Han DC, Isono M, Chen S. et al. Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-beta type II receptor expression. Kidney Int 2001; 59: 1315-1323
• 94 Hallan SI, Orth SR. Smoking is a risk factor in the progression to kidney failure. Kidney Int 2011; 80: 516-523
• 95 Orth SR. Smoking--a renal risk factor. Nephron 2000; 86: 12-26
• 96 Shankar A, Klein R, Klein BE. The association among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol 2006; 164: 263-271