Diyabetik Kronik Böbrek Hastalığı
Özet
Diyabetik kronik böbrek hastalığı (DKBH), tüm dünyada halk sağlığını tehdit eden, son dönem böbrek hastalığı (SDBH) ve kardiyovasküler riskleri artıran karmaşık bir tablodur. Tahmini glomerüler filtrasyon hızının (eGFR) 60 mL/dk/1.73 m²'nin altında olması veya albümin atılımının artmasıyla klinik olarak tanımlanır. Yaş, etnik köken, obezite ve sigara gibi faktörler riski artırırken; patogenezde hiperglisemi kaynaklı inflamasyon ve glomerüler hiperfiltrasyon kritik rol oynar. Tedavide ACE inhibitörleri veya ARB'ler ile kan basıncı yönetimi, yaşam tarzı değişiklikleri ve HbA1c hedefinin bireyselleştirilmesi esastır. Özellikle tip 2 diyabetli hastalarda, böbrek fonksiyonlarının evresine (G1-G5) göre metformin, SGLT-2 inhibitörleri ve DPP-4 inhibitörleri gibi ajanlar kardiyovasküler ve renal koruma sağlamak adına hassasiyetle yönetilmelidir.
Diabetic chronic kidney disease (DCKD) is a complex condition that threatens public health globally, increasing the risks of end-stage renal disease (ESRD) and cardiovascular events. Clinically defined by an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m² or elevated albumin excretion, its risk factors include age, ethnicity, obesity, and smoking, while hyperglycemia-induced inflammation and glomerular hyperfiltration drive its pathogenesis. Management relies on lifestyle changes, individualized HbA1c targets, and blood pressure control using ACE inhibitors or ARBs. Especially in type 2 diabetes, agents like metformin, SGLT-2 inhibitors, and DPP-4 inhibitors must be carefully tailored according to the eGFR stages (G1-G5) to ensure cardioprofessional and renal protection.
Referanslar
Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020; 98(4S): 1-115.
Batuman V, Schmidt RJ, Anjana S Soman AS, et al. Diabetic Nephropathy Medication. Medscape Diabetic kidney Medicine [online]. Available from https://emedicine.medscape.com/article/238946. (Acessed 2 November 2021
Gungor Ö, Ulu MS, Arıkan H ve ark. Dı̇yabetı̇k böbrek hastalarında hı̇perglı̇semı̇nı̇n ı̇laçlarla yönetı̇mı̇: Türk Nefrolojı̇ Derneğı̇ Uzman Görüşü Raporu 2020 (Nisan 2021 tarihinde https://nefroloji.org.tr/uploads/pdf/TND_Diyabetik_Bobrek_Hiperglisemi_Yoonetimi_Raporu_2020.pdf adresinden ulaşılmıştır)
Mottl AK, Tuttle KR. Diabetic kidney disease: Pathogenesis and epidemiology. Kaynak: Up To Date Diabetic kidney Medicine [online]. Şu adreste bulunabilir: www.uptodate.com. Erişim tarihi: 14 Eylül 2021.
Kidney Disease: Improving Global Outcomes CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013; Suppl 3(1): 1-163.
Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System-United States 2018 [online]. Available from http://www.cdc.gov/ckd (Acessed 19 June 2019)
United States Renal Data System. USRDS 2018 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institutes of Health, editor, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2017.
Bryson CL, Ross HJ, Boyko EJ, et al. Racial and ethnic variations in albuminuria in the US Third National Health and Nutrition Examination Survey (NHANES III) population: associations with diabetes and level of CKD. Am J Kidney Dis. 2006; 48: 720.
Narres M, Claessen H, Droste S, et al. The Incidence of End-Stage Renal Disease in the Diabetic (Compared to the Non-Diabetic) Population: A Systematic Review. PLoS One. 2016; 11: e0147329
Hostetter TH. Hyperfiltration and glomerulosclerosis. Semin Nephrol. 2003; 23:194.
Tsai WC, Wu HY, Peng YS, et al. Risk Factors for Development and Progression of Chronic Kidney Disease: A Systematic Review and Exploratory Meta-Analysis. Medicine (Baltimore). 2016; 95: e3013.
Choi AI, Weekley CC, Chen SC, et al. Association of educational attainment with chronic disease and mortality: the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis .2011; 58: 228.
Choung HG, Bomback AS, Stokes MB, et al. The spectrum of kidney biopsy findings in patients with morbid obesity. Kidney Int. 2019; 95: 647.
Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014; 34: 509.
Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med.1993; 329: 977.
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321: 405.
Ku E, McCulloch CE, Mauer M, et al. Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes. Diabetes Care. 2016; 39: 2218.
Rossing K, Christensen PK, Hovind P, et al. Progression of nephropathy in type 2 diabetic patients. Kidney Int 2004; 66: 1596.
Lipworth L, Mumma MT, Cavanaugh KL, et al. Incidence and predictors of end stage renal disease among low-income blacks and whites. PLoS One. 2012; 7: e48407.
Zuk A, Bonventre JV. Recent advances in acute kidney injury and its consequences and impact on chronic kidney disease. Curr Opin Nephrol Hypertens. 2019; 28: 397.
Yu SM, Bonventre JV. Acute Kidney Injury and Progression of Diabetic Kidney Disease. Adv Chronic Kidney Dis. 2018; 25: 166.
Vallon V, Komers R. Pathophysiology of the diabetic kidney. Compr Physiol. 2011; 1: 1175.
Sheetz MJ, King GL. Molecular understanding of hyperglycemia's adverse effects for diabetic complications. JAMA. 2002; 288: 2579.
Pichler R, Afkarian M, Dieter BP, et al. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Renal Physiol. 2017; 312: F716.
Tonneijck L, Muskiet MH, Smits MM, et al. Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment. J Am Soc Nephrol. 2017; 28: 1023.
Helal I, Fick-Brosnahan GM, Reed-Gitomer B, et al. Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol. 2012; 8: 293.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019; 380: 2295.
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016; 375: 323.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019; 380: 347.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017; 377: 644.
van Bommel EJM, Lytvyn Y, Perkins BA, et al. Renal hemodynamic effects of sodium-glucose cotransporter 2 inhibitors in hyperfiltering people with type 1 diabetes and people with type 2 diabetes and normal kidney function. Kidney Int. 2020; 97: 631.
Hostetter TH. Diabetic nephropathy. Metabolic versus hemodynamic considerations. Diabetes Care. 1992; 15: 1205.
Magee GM, Bilous RW, Cardwell CR, et al. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia. 2009; 52: 691.
Ruggenenti P, Porrini EL, Gaspari F, et al. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. 2012; 35: 2061.
Ibrahim HN, Rosenberg ME, Hostetter TH. Role of the renin-angiotensin-aldosterone system in the progression of renal disease: a critical review. Semin Nephrol. 1997; 17: 431.
Heerspink HJL, Kosiborod M, Inzucchi SE, et al. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int. 2018; 94: 26.
Olivarius Nde F, Andreasen AH, Keiding N, et al. Epidemiology of renal involvement in newly-diagnosed middle-aged and elderly diabetic patients. Cross-sectional data from the population-based study "Diabetes Care in General Practice", Denmark. Diabetologia. 1993; 36: 1007
Mottl AK, Tuttle KR, Bakris GL. Diabetic kidney disease: Manifestations, evaluation, and diagnosis. Up To Date Diabetic kidney Medicine [online]. Available from www.uptodate.com [Acessed 13 November 2020]
Krolewski AS, Niewczas MA, Skupien J, et al. Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care. 2014; 37: 226.
Krolewski AS. Progressive renal decline: the new paradigm of diabetic nephropathy in type 1 diabetes. Diabetes Care. 2015; 38: 954.
Denic A, Glassock RJ, Rule AD. Structural and Functional Changes With the Aging Kidney. Adv Chronic Kidney Dis. 2016; 23: 19.
de Boer IH, Sun W, Cleary PA, et al. Longitudinal changes in estimated and measured GFR in type 1 diabetes. J Am Soc Nephrol. 2014; 25: 810.
Gaspari F, Ruggenenti P, Porrini E, et al. The GFR and GFR decline cannot be accurately estimated in type 2 diabetics. Kidney Int. 2013; 84: 164.
Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018; 6:605.
Adler AI, Stevens RJ, Manley SE, et al. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003; 63: 225.
Packham DK, Alves TP, Dwyer JP, et al. Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database. Am J Kidney Dis. 2012; 59: 75.
Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013; 24: 302.
Afkarian M, Katz R, Bansal N, et al. Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson Heart Study. Clin J Am Soc Nephrol. 2016; 11: 1384.
Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012; 380: 1662.
Orchard TJ, Secrest AM, Miller RG, et al. In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia. 2010; 53: 2312.
de Boer IH, Afkarian M, Rue TC, et al. Renal outcomes in patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol. 2014; 25: 2342.
O'Shaughnessy MM, Hogan SL, Poulton CJ, et al. Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986-2015. Clin J Am Soc Nephrol. 2017; 12: 614.
American Diabetes Association. 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019; 42: S124.
Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives-a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007; 72: 247.
Mogensen CE, Vestbo E, Poulsen PL, et al. Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion. Diabetes Care. 1995; 18: 572.
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150: 604.
Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130: 461.
Jiang S, Wang Y, Zhang Z, et al. Accuracy of hematuria for predicting non-diabetic renal disease in patients with diabetes and kidney disease: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2018; 143: 288.
Lin HY, Niu SW, Kuo IC, et al. Hematuria and Renal Outcomes in Patients With Diabetic Chronic KidneyDisease. Am J Med Sci. 2018; 356: 268.
O'Neill WM Jr, Wallin JD, Walker PD. Hematuria and red cell casts in typical diabetic nephropathy. Am J Med. 1983; 74: 389.
KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007; 49: S12.
Dong Z, Wang Y, Qiu Q, et al. Clinical predictors differentiating non-diabetic renal diseases from diabetic nephropathy in a large population of type 2 diabetes patients. Diabetes Res Clin Pract. 2016; 121: 112.
Li L, Zhang X, Li Z, et al. Renal pathological implications in type 2 diabetes mellitus patients with renal involvement. J Diabetes Complications. 2017; 31: 114.
Tan J, Zwi LJ, Collins JF, et al. Presentation, pathology and prognosis of renal disease in type 2 diabetes. BMJ Open Diabetes Res Care. 2017; 5: e000412.
Fiorentino M, Bolignano D, Tesar V, et al. Renal biopsy in patients with diabetes: a pooled meta-analysis of 48 studies. Nephrol Dial Transplant. 2017; 32: 97.
Shlipak M. Diabetic nephropathy. Clin Evid (Online). 2009; 14: 2009:
Burney BO, Kalaitzidis RG, Bakris GL. Novel therapies of diabetic nephropathy. Curr Opin Nephrol Hypertens. 2009; 18(2): 107-11.
Vlado Perkovic V, Badve SV, Bakris GL. Treatment of diabetic kidney disease.Up To Date Diabetic kidney Medicine [online]. Available from www.uptodate.com [Acessed 23 September 2021]
Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008; 359: 2417.
DCCT/EDIC Research Group, de Boer IH, Sun W, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011; 365: 2366.
Fullerton B, Jeitler K, Seitz M, et al. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2014; CD009122.
Fioretto P, Steffes MW, Sutherland DE, et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med. 1998; 339: 69.
Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. Kidney Int. 1995; 47: 1703.
Hemmingsen B, Lund SS, Gluud C, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013; CD008143.
Amod A, Buse JB, McGuire DK, et al. Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes: Secondary Analysis (DEVOTE 11). Diabetes Ther. 2020; 11: 53.
Alsahli M, Gerich JE. Hypoglycemia, chronic kidney disease, and diabetes mellitus. Mayo Clin Proc. 2014; 89: 1564.
Flynn C, Bakris GL. Noninsulin glucose-lowering agents for the treatment of patients on dialysis. Nat Rev Nephrol. 2013; 9: 147.
American Diabetes Association. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes-2021. Diabetes Care. 2021; 44(Suppl 1): S111-S4.
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255-323.
de Boer IH, Caramori ML, Chan JCN, et al. Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment. Kidney Int. 2020; 98(4): 839-48.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015; 58(3): 429-42
Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association Of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm. Endocr Pract. 2020; 26(1): 107-39.
Association of British Clinical Diabetologists 2018. Available from https://renal.org/wp content/uploads/2017/07/ ABCD%E2%80%93RA_Managing-glycaemiaguideline_2018Publication.pdf
Sarafidis P, Ferro CJ, Morales E, et al. SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA. Nephrol Dial Transplant. 2019; 34(2): 208-30.
National Institute for Health and Care Excellence. Type 2 diabetes in adults: management. NICE guideline 2015. Available from https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-pdf-1837338615493
Inker LA, Astor BC, Fox CH, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014; 63(5): 713-35.
Türkiye Endokrinoloji Metabolizma Derneği (TEMD) Diyabetes Mellitus ve Komplikasyonlarının Tanı, Tedavi ve İzlem Kılavuzu 2019 (http://temd.org.tr/admin/uploads/tbl_kilavuz/ 201908190958542019tbl_kilavuzb48da47363. Pdf adresinden ulaşılmıştır).
KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2012; 60 (5): 850-886.
Barnett AH, Bain SC, Bouter P, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004; 351: 1952.
ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008; 358: 1547.
Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008; 372: 547.
Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012; 367: 2204.
Clase CM, Carrero JJ, Ellison DH, et al. Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020; 97: 42.
Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000; 160: 685.
Collard D, Brouwer TF, Peters RJG, et al. Creatinine Rise During Blood Pressure Therapy and the Risk of Adverse Clinical Outcomes in Patients With Type 2 Diabetes Mellitus. Hypertension. 2018; 72: 1337.
Malhotra R, Craven T, Ambrosius WT, et al. Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT. Am J Kidney Dis. 2019; 73: 21.
Cheung AK, Chang TI, Cushman WC, et al. Blood pressure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019; 95: 1027.
American Diabetes Association. 3. Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42: S29.
Ohkuma T, Jun M, Rodgers A, et al. Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus. Hypertension. 2019; 73: 84.
