Therapeutic Insights in Chronic Kidney Disease Progression
Tóm tắt
Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. Through its effect on cardiovascular risk and end-stage kidney disease, CKD directly affects the global burden of morbidity and mortality. Classical optimal management of CKD includes blood pressure control, treatment of albuminuria with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, avoidance of potential nephrotoxins and obesity, drug dosing adjustments, and cardiovascular risk reduction. Diabetes might account for more than half of CKD burden, and obesity is the most important prompted factor for this disease. New antihyperglycemic drugs, such as sodium-glucose-cotransporter 2 inhibitors have shown to slow the decline of GFR, bringing additional benefit in weight reduction, cardiovascular, and other kidney outcomes. On the other hand, a new generation of non-steroidal mineralocorticoid receptor antagonist has recently been developed to obtain a selective receptor inhibition reducing side effects like hyperkalemia and thereby making the drugs suitable for administration to CKD patients. Moreover, two new potassium-lowering therapies have shown to improve tolerance, allowing for higher dosage of renin-angiotensin system inhibitors and therefore enhancing their nephroprotective effect. Regardless of its cause, CKD is characterized by reduced renal regeneration capacity, microvascular damage, oxidative stress and inflammation, resulting in fibrosis and progressive, and irreversible nephron loss. Therefore, a holistic approach should be taken targeting the diverse processes and biological contexts that are associated with CKD progression. To date, therapeutic interventions when tubulointerstitial fibrosis is already established have proved to be insufficient, thus research effort should focus on unraveling early disease mechanisms. An array of novel therapeutic approaches targeting epigenetic regulators are now undergoing phase II or phase III trials and might provide a simultaneous regulatory activity that coordinately regulate different aspects of CKD progression.
Từ khóa
Tài liệu tham khảo
Hill, 2016, Global prevalence of chronic kidney disease - a systematic review and meta-analysis, PLoS ONE., 11, e0158765, 10.1371/journal.pone.0158765
2020, Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017, Lancet, 395, 709, 10.1016/S0140-6736(20)30045-3
2016, DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015, Lancet, 388, 1603, 10.1016/S0140-6736(16)31460-X
Vallianou, 2019, Chronic kidney disease and cardiovascular disease: is there any relationship?, Curr Cardiol Rev., 15, 55, 10.2174/1573403X14666180711124825
Schnaper, 2017, The tubulointerstitial pathophysiology of progressive kidney disease, Adv Chronic Kidney Dis., 24, 107, 10.1053/j.ackd.2016.11.011
Lee, 2012, Mechanisms and consequences of TGF-ß overexpression by podocytes in progressive podocyte disease, Cell Tissue Res., 347, 129, 10.1007/s00441-011-1169-7
2018, Glomerular endothelial cell stress and cross-talk with podocytes in early [corrected] diabetic kidney disease, Front Med., 5, 76, 10.3389/fmed.2018.00076
Ruiz-Ortega, 2020, Targeting the progression of chronic kidney disease, Nat Rev Nephrol., 16, 269, 10.1038/s41581-019-0248-y
Burgess, 2009, Supramaximal dose of candesartan in proteinuric renal disease, J Am Soc Nephrol., 20, 893, 10.1681/ASN.2008040416
Fernandez Juarez, 2013, Effect of dual blockade of the renin-angiotensin system on the progression of type 2 diabetic nephropathy: a randomized trial, Am J Kidney Dis., 61, 211, 10.1053/j.ajkd.2012.07.011
Parving, 2008, Aliskiren combined with losartan in type 2 diabetes and nephropathy, N Engl J Med, 358, 2433, 10.1056/NEJMoa0708379
Persson, 2009, Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria, Diabetes Care., 32, 1873, 10.2337/dc09-0168
Heerspink, 2016, Renal outcomes with aliskiren in patients with type 2 diabetes: a prespecified secondary analysis of the ALTITUDE randomised controlled trial, Lancet Diabetes Endocrinol., 4, 309, 10.1016/S2213-8587(15)00469-6
O'Hare, 2014, Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults, JAMA Intern Med., 174, 391, 10.1001/jamainternmed.2013.13328
Hou, 2006, Efficacy and safety of benazepril for advanced chronic renal insufficiency, N Engl J Med., 354, 131, 10.1056/NEJMoa053107
Lewis, 1993, The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy, N Engl J Med., 329, 1456, 10.1056/NEJM199311113292004
Lewis, 2001, Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to Type 2 diabetes, N Engl J Med., 345, 851, 10.1056/NEJMoa011303
Brenner, 2001, Effects of losartan on renal and cardiovascular outcomes in patients with Type 2 diabetes and nephropathy, N Engl J Med., 345, 861, 10.1056/NEJMoa011161
Estacio, 2000, Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes, Diabetes Care., 23, B54
Yusuf, 2008, Telmisartan, ramipril, or both in patients at high risk for vascular events, N Engl J Med, 358, 1547, 10.1056/NEJMoa0801317
Fried, 2013, Combined angiotensin inhibition for the treatment of diabetic nephropathy, N Engl J Med., 369, 1892, 10.1056/NEJMoa1303154
Parving, 2012, Cardiorenal end points in a trial of aliskiren for Type 2 diabetes, N Engl J Med., 367, 2204, 10.1056/NEJMoa1208799
Wright Jr, 2002, Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney diseaseresults from the AASK trial, JAMA., 288, 2421, 10.1001/jama.288.19.2421
1997, Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy, Lancet, 349, 1857, 10.1016/S0140-6736(96)11445-8
Parving, 2001, The Effect of irbesartan on the development of diabetic nephropathy in patients with Type 2 diabetes, N Engl J Med., 345, 870, 10.1056/NEJMoa011489
Barnett, 2004, Angiotensin-receptor blockade versus converting–enzyme inhibition in Type 2 diabetes and nephropathy, N Engl J Med., 351, 1952, 10.1056/NEJMoa042274
Rahman, 2012, Long-Term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR, CJASN., 7, 989, 10.2215/CJN.07800811
Rossing, 2005, Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study, Diabetes Care., 28, 2106, 10.2337/diacare.28.9.2106
Bakris, 2020, Effect of finerenone on chronic kidney disease outcomes in Type 2 diabetes, N Engl J Med., 383, 2219, 10.1056/NEJMoa2025845
Mann, 2010, Avosentan for overt diabetic nephropathy, J Am Soc Nephrol., 21, 527, 10.1681/ASN.2009060593
Heerspink, 2019, Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial, Lancet., 393, 1937, 10.1016/S0140-6736(19)30772-X
de, 2009, Bicarbonate supplementation slows progression of CKD and improves nutritional status, J Am Soc Nephrol., 20, 2075, 10.1681/ASN.2008111205
Di Iorio, 2019, Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study, J Nephrol., 32, 989, 10.1007/s40620-019-00656-5
Hollenberg, 2004, Aldosterone in the development and progression of renal injury, Kidney Int., 66, 1, 10.1111/j.1523-1755.2004.00701.x
Kolkhof, 2014, Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury, J Cardiovasc Pharmacol., 64, 69, 10.1097/FJC.0000000000000091
Agarwal, 2019, Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial, Lancet., 394, 1540, 10.1016/S0140-6736(19)32135-X
Kosiborod, 2014, Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial, JAMA., 312, 2223, 10.1001/jama.2014.15688
Mosenzon, 2019, Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial, Lancet Diabetes Endocrinol., 7, 606, 10.1016/S2213-8587(19)30180-9
Wanner, 2016, Empagliflozin and progression of kidney disease in Type 2 diabetes, N Engl J Med., 375, 323, 10.1056/NEJMoa1515920
Neal, 2017, Canagliflozin and cardiovascular and renal events in Type 2 diabetes, N Engl J Med., 377, 644, 10.1056/NEJMoa1611925
Heerspink, 2020, Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study, Lancet Diabetes Endocrinol., 8, 27, 10.1016/S2213-8587(19)30384-5
Perkovic, 2019, Canagliflozin and renal outcomes in Type 2 diabetes and nephropathy, N Engl J Med., 380, 2295, 10.1056/NEJMoa1811744
Heerspink, 2020, Dapagliflozin in patients with chronic kidney disease, N Engl J Med., 383, 1436, 10.1056/NEJMoa2024816
Boesen, 2015, Endothelin receptors, renal effects and blood pressure, Curr Opin Pharmacol., 21, 25, 10.1016/j.coph.2014.12.007
Speed, 2013, Endothelin, kidney disease, and hypertension, Hypertension., 61, 1142, 10.1161/HYPERTENSIONAHA.113.00595
Raina, 2020, The role of endothelin and endothelin antagonists in chronic kidney disease, Kidney Dis., 6, 22, 10.1159/000504623
Trachtman, 2018, DUET: a Phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS, J Am Soc Nephrol., 29, 2745, 10.1681/ASN.2018010091
Komers, 2020, Study design of the Phase 3 sparsentan versus irbesartan (DUPLEX) Study in patients with focal segmental glomerulosclerosis, Kidney Int Rep., 5, 494, 10.1016/j.ekir.2019.12.017
Łoniewski, 2014, Bicarbonate therapy for prevention of chronic kidney disease progression, Kidney Int., 85, 529, 10.1038/ki.2013.401
Pergola, 2011, Bardoxolone methyl and kidney function in CKD with type 2 diabetes, N Engl J Med., 365, 327, 10.1056/NEJMoa1105351
de Zeeuw, 2013, Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease, N Engl J Med., 369, 2492, 10.1056/NEJMoa1306033
Sharma, 2011, Pirfenidone for diabetic nephropathy, J Am Soc Nephrol., 22, 1144, 10.1681/ASN.2010101049
Cho, 2007, Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis, Clin J Am Soc Nephrol., 2, 906, 10.2215/CJN.01050207
Liu, 2017, Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic kidney disease: a meta-analysis, J Int Med Res., 45, 383, 10.1177/0300060516663094
Lambers Heerspink, 2010, Debate: PRO position. should microalbuminuria ever be considered as a renal endpoint in any clinical trial?, Am J Nephrol., 31, 458, 10.1159/000292501
Coresh, 2014, Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality, JAMA., 311, 2518, 10.1001/jama.2014.6634
Rahman, 2014, Association between chronic kidney disease progression and cardiovascular disease: results from the CRIC Study, Am J Nephrol., 40, 399, 10.1159/000368915
Glassock, 2010, Debate: CON position. should microalbuminuria ever be considered as a renal endpoint in any clinical trial?, Am J Nephrol., 31, 462, 10.1159/000313553
Inker, 2014, GFR decline as an alternative end point to kidney failure in clinical trials: a meta-analysis of treatment effects from 37 randomized trials, Am J Kidney Dis., 64, 848, 10.1053/j.ajkd.2014.08.017
Greene, 2014, Utility and validity of estimated GFR-based surrogate time-to-event end points in CKD: a simulation study, Am J Kidney Dis., 64, 867, 10.1053/j.ajkd.2014.08.019
Zewinger, 2018, Dickkopf-3 (DKK3) in urine identifies patients with short-term risk of eGFR loss, J Am Soc Nephrol., 29, 2722, 10.1681/ASN.2018040405
Schunk, 2019, Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study, Lancet., 394, 488, 10.1016/S0140-6736(19)30769-X
Provenzano, 2020, The role of prognostic and predictive biomarkers for assessing cardiovascular risk in chronic kidney disease patients, Biomed Res Int., 2020, 2314128, 10.1155/2020/2314128
Sabbisetti, 2014, Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes, J Am Soc Nephrol., 25, 2177, 10.1681/ASN.2013070758
Smith, 2013, Urinary neutrophil gelatinase-associated lipocalin may aid prediction of renal decline in patients with non-proteinuric Stages 3 and 4 chronic kidney disease (CKD), Nephrol Dial Transplant., 28, 1569, 10.1093/ndt/gfs586
Boes, 2006, Apolipoprotein A-IV predicts progression of chronic kidney disease: the mild to moderate kidney disease study, J Am Soc Nephrol., 17, 528, 10.1681/ASN.2005070733
Fernández-Juárez, 2017, High levels of circulating TNFR1 increase the risk of all-cause mortality and progression of renal disease in type 2 diabetic nephropathy, Nephrology., 22, 354, 10.1111/nep.12781
Hayek, 2015, Soluble urokinase receptor and chronic kidney disease, N Engl J Med., 373, 1916, 10.1056/NEJMoa1506362
Benigni, 2003, Add-on anti-TGF-beta antibody to ACE inhibitor arrests progressive diabetic nephropathy in the rat, J Am Soc Nephrol., 14, 1816, 10.1097/01.asn.0000074238.61967.b7
Fukasawa, 2004, Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling, Kidney Int., 65, 63, 10.1111/j.1523-1755.2004.00393.x
Murphy, 2012, Renoprotective effects of anti-TGF-β antibody and antihypertensive therapies in Dahl S rats, Am J Physiol Regul Integr Comp Physiol., 303, R57, 10.1152/ajpregu.00263.2011
Li, 2006, Bone marrow cell infusion ameliorates progressive glomerulosclerosis in an experimental rat model, Kidney Int., 69, 323, 10.1038/sj.ki.5000083
Kunter, 2007, Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes, J Am Soc Nephrol., 18, 1754, 10.1681/ASN.2007010044
Papazova, 2015, Cell-based therapies for experimental chronic kidney disease: a systematic review and meta-analysis, Dis Model Mech., 8, 281, 10.1242/dmm.017699
Tan, 2012, Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial, JAMA., 307, 1169, 10.1001/jama.2012.316