Chronic Kidney Disease in the Older Adult Patient with Diabetes
Abstract
:1. Introduction
2. Definition, Epidemiology, and Burden of Diabetes in Older Adult Patients with CKD
3. Pathophysiology of CKD in DM and DKD among Older Adults
4. Diagnosis of CKD in Older Patients with DM
5. Treatment Considerations
5.1. Non-Pharmaceutical Interventions and Goals of Therapy
5.1.1. Exercise
5.1.2. Dietary Considerations
5.1.3. Blood Pressure, Lipid, and Glycemia Control in Older Adults with CKD in DM
5.2. Pharmaceutical Interventions to Reduce Cardiorenal Risk in Older Patients with CKD in DM
5.2.1. Inhibitors of the Renin Angiotensin System
- Kidney function and potassium levels should be checked within 7 to 10 days after initiation.
- Up to 30% of eGFR decline may be tolerated.
- Drops in kidney function of more than 30% should prompt investigation for RAS, sepsis, volume depletion, or concomitant medications, e.g., NSAIDs.
- If an alternative explanation for a marked decline in renal function cannot be inferred, the dose of the RASi may be reduced.
- Potassium binders (Patiromer and sodium zirconium cyclosilicate) may be used to reduce the serum potassium if it rises over 5 mEq/L and allow the RASi to be continued.
- Combination therapy with ACEi, direct renin inhibitor, and ARBs should not be used, since multiple clinical trials have shown greater risks of hypotension, hyperkalemia, and acute renal injury with these combinations [101].
- In advanced (stage 4 and 5) CKD, discontinuation [102] of the RASi was associated with a lower risk for hyperkalemia (HR, 0.65; 95% CI, 0.54–0.79) but a higher risk of death (HR, 1.39, 95% CI 1.20–1.60) and a higher risk of progression to ESKD (HR 1.19, 95% CI: 0.86–1.65). The STOP-ACEi [103,104] RCT examined the benefits vs. harm of stopping the RASi in patients with advanced CKD (eGFR was ~18 mL/min/1.73 m2 at baseline). There was no difference in the eGFR (primary outcome) at 3 years between participants older than 65 years (−0.32, 95% CI −2.72–2.09 mL/min/1.73 m2) and those younger than 65 years (−0.32, 95%CI −2.92–2.28 mL/min/1.73 m2). ESKD occurred in 128 patients (62%) among those who discontinued the RASi and in 115 patients (56%) who continued them (HR, 1.28; 95% CI, 0.99 to 1.65). There were similar numbers of cardiovascular events (108 vs. 88) and deaths (20 vs. 22) in the two arms.
5.2.2. Sodium Glucose Co-Transporter 2 Inhibitors
5.2.3. Mineralocorticoid Antagonists
5.2.4. GLP1 and Dual GLP1/GIP1 Receptor Agonists
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030. Diabetes Care 2004, 27, 1047–1053. [Google Scholar] [CrossRef] [PubMed]
- Mottl, A.K.; Alicic, R.; Argyropoulos, C.; Brosius, F.C.; Mauer, M.; Molitch, M.; Nelson, R.G.; Perreault, L.; Nicholas, S.B. KDOQI US Commentary on the KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD. Am. J. Kidney Dis. 2022, 79, 457–479. [Google Scholar] [CrossRef] [PubMed]
- Rossing, P.; Caramori, M.L.; Chan, J.C.N.; Heerspink, H.J.L.; Hurst, C.; Khunti, K.; Liew, A.; Michos, E.D.; Navaneethan, S.D.; Olowu, W.A.; et al. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022, 102, S1–S127. [Google Scholar] [CrossRef] [PubMed]
- Afkarian, M.; Zelnick, L.R.; Hall, Y.N.; Heagerty, P.J.; Tuttle, K.; Weiss, N.S.; de Boer, I.H. Clinical Manifestations of Kidney Disease Among US Adults with Diabetes, 1988–2014. JAMA 2016, 316, 602–610. [Google Scholar] [CrossRef] [PubMed]
- Halimi, J.M. The Emerging Concept of Chronic Kidney Disease without Clinical Proteinuria in Diabetic Patients. Diabetes Metab. 2012, 38, 291–297. [Google Scholar] [CrossRef] [PubMed]
- Ho, K.; McKnight, A.J. The Changing Landscape of Diabetic Kidney Disease: New Reflections on Phenotype, Classification, and Disease Progression to Influence Future Investigative Studies and Therapeutic Trials. Adv. Chronic Kidney Dis. 2014, 21, 256–259. [Google Scholar] [CrossRef] [PubMed]
- Robles, N.R.; Villa, J.; Gallego, R.H. Non-Proteinuric Diabetic Nephropathy. J. Clin. Med. 2015, 4, 1761–1773. [Google Scholar] [CrossRef] [PubMed]
- Williams, M.E. Diabetic Kidney Disease in Elderly Individuals. Med. Clin. N. Am. 2013, 97, 75–89. [Google Scholar] [CrossRef]
- McClure, M.; Jorna, T.; Wilkinson, L.; Taylor, J. Elderly Patients with Chronic Kidney Disease: Do They Really Need Referral to the Nephrology Clinic? Clin. Kidney J. 2017, 10, 698–702. [Google Scholar] [CrossRef]
- Liu, P.; Quinn, R.R.; Lam, N.N.; Al-Wahsh, H.; Sood, M.M.; Tangri, N.; Tonelli, M.; Ravani, P. Progression and Regression of Chronic Kidney Disease by Age Among Adults in a Population-Based Cohort in Alberta, Canada. JAMA Netw. Open 2021, 4, e2112828. [Google Scholar] [CrossRef]
- Afkarian, M.; Sachs, M.C.; Kestenbaum, B.; Hirsch, I.B.; Tuttle, K.R.; Himmelfarb, J.; Boer, I.H. de Kidney Disease and Increased Mortality Risk in Type 2 Diabetes. JASN 2013, 24, 302–308. [Google Scholar] [CrossRef] [PubMed]
- Wu, B.; Bell, K.; Stanford, A.; Kern, D.M.; Tunceli, O.; Vupputuri, S.; Kalsekar, I.; Willey, V. Understanding CKD among Patients with T2DM: Prevalence, Temporal Trends, and Treatment Patterns—NHANES 2007–2012. BMJ Open Diabetes Res. Care 2016, 4, e000154. [Google Scholar] [CrossRef] [PubMed]
- Hallan, S.I.; Matsushita, K.; Sang, Y.; Mahmoodi, B.K.; Black, C.; Ishani, A.; Kleefstra, N.; Naimark, D.; Roderick, P.; Tonelli, M.; et al. Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease. JAMA 2012, 308, 2349–2360. [Google Scholar] [CrossRef] [PubMed]
- Nelson, R.G.; Pavkov, M.E. The Pandemic of Diabetes and Kidney Disease. Kidney News 2020, 12, 7–9. [Google Scholar]
- National Diabetes Statistics Report 2020. Estimates of Diabetes and Its Burden in the United States. 2020, 32. Available online: https://www.cdc.gov/diabetes/data/statistics-report/index.html (accessed on 7 January 2024).
- International Diabetes Federation. IDF Diabetes Atlas, 10th ed.; International Diabetes Federation: Brussels, Belgium, 2021. [Google Scholar]
- Tuttle, K.R.; Jones, C.R.; Daratha, K.B.; Koyama, A.K.; Nicholas, S.B.; Alicic, R.Z.; Duru, O.K.; Neumiller, J.J.; Norris, K.C.; Ríos Burrows, N.; et al. Incidence of Chronic Kidney Disease among Adults with Diabetes, 2015–2020. N. Engl. J. Med. 2022, 387, 1430–1431. [Google Scholar] [CrossRef]
- Johansen, K.L.; Chertow, G.M.; Gilbertson, D.T.; Herzog, C.A.; Ishani, A.; Israni, A.K.; Ku, E.; Li, S.; Li, S.; Liu, J.; et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am. J. Kidney Dis. 2022, 79, A8–A12. [Google Scholar] [CrossRef] [PubMed]
- Russo, G.T.; De Cosmo, S.; Viazzi, F.; Mirijello, A.; Ceriello, A.; Guida, P.; Giorda, C.; Cucinotta, D.; Pontremoli, R.; Fioretto, P.; et al. Diabetic Kidney Disease in the Elderly: Prevalence and Clinical Correlates. BMC Geriatr. 2018, 18, 38. [Google Scholar] [CrossRef] [PubMed]
- McCullough, K.P.; Morgenstern, H.; Saran, R.; Herman, W.H.; Robinson, B.M. Projecting ESRD Incidence and Prevalence in the United States through 2030. J. Am. Soc. Nephrol. 2019, 30, 127–135. [Google Scholar] [CrossRef]
- Dias, J.P.; Shardell, M.; Golden, S.H.; Ahima, R.S.; Crews, D.C. Racial/Ethnic Trends in Prevalence of Diabetic Kidney Disease in the United States. Kidney Int. Rep. 2018, 4, 334–337. [Google Scholar] [CrossRef]
- Center for Medicare & Medical Services, Office of Minority Health. Racial and Ethnic Disparities in Diabetes Prevalence, Self-Management, and Health Outcomes among Medicare Beneficiaries; Center for Medicare & Medical Services, Office of Minority Health: Baltimore, MD, USA, 2017; pp. 1–22.
- Rule, A.D.; Amer, H.; Cornell, L.D.; Taler, S.J.; Cosio, F.G.; Kremers, W.K.; Textor, S.C.; Stegall, M.D. The Association between Age and Nephrosclerosis on Renal Biopsy among Healthy Adults. Ann. Intern. Med. 2010, 152, 561–567. [Google Scholar] [CrossRef]
- Najafian, B.; Fogo, A.B.; Lusco, M.A.; Alpers, C.E. AJKD Atlas of Renal Pathology: Diabetic Nephropathy. Am. J. Kidney Dis. 2015, 66, e37–e38. [Google Scholar] [CrossRef] [PubMed]
- Murshed, K.; Noheir, T.; Akhtar, M. Diabetic Kidney Disease. Available online: https://www.pathologyoutlines.com/topic/kidneydiabetes.html?callback=in&code=YZQ4NDDIYZITYJZMZI0ZMGUXLTK1YTKTNJUWYMY5ZJBJMZI1&state=d4271297609e47d1b1890e08bec967dc (accessed on 12 December 2023).
- Tervaert, T.W.C.; Mooyaart, A.L.; Amann, K.; Cohen, A.H.; Cook, H.T.; Drachenberg, C.B.; Ferrario, F.; Fogo, A.B.; Haas, M.; de Heer, E.; et al. Pathologic Classification of Diabetic Nephropathy. J. Am. Soc. Nephrol. 2010, 21, 556–563. [Google Scholar] [CrossRef] [PubMed]
- Alsaad, K.O.; Herzenberg, A.M. Distinguishing Diabetic Nephropathy from Other Causes of Glomerulosclerosis: An Update. J. Clin. Pathol. 2007, 60, 18–26. [Google Scholar] [CrossRef] [PubMed]
- Mauer, S.M.; Steffes, M.W.; Ellis, E.N.; Sutherland, D.E.; Brown, D.M.; Goetz, F.C. Structural-Functional Relationships in Diabetic Nephropathy. J. Clin. Investig. 1984, 74, 1143–1155. [Google Scholar] [CrossRef] [PubMed]
- Denic, A.; Lieske, J.C.; Chakkera, H.A.; Poggio, E.D.; Alexander, M.P.; Singh, P.; Kremers, W.K.; Lerman, L.O.; Rule, A.D. The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. J. Am. Soc. Nephrol. 2017, 28, 313–320. [Google Scholar] [CrossRef] [PubMed]
- Denic, A.; Mathew, J.; Lerman, L.O.; Lieske, J.C.; Larson, J.J.; Alexander, M.P.; Poggio, E.; Glassock, R.J.; Rule, A.D. Single-Nephron Glomerular Filtration Rate in Healthy Adults. N. Engl. J. Med. 2017, 376, 2349–2357. [Google Scholar] [CrossRef] [PubMed]
- Tan, J.C.; Busque, S.; Workeneh, B.; Ho, B.; Derby, G.; Blouch, K.L.; Sommer, F.G.; Edwards, B.; Myers, B.D. Effects of Aging on Glomerular Function and Number in Living Kidney Donors. Kidney Int. 2010, 78, 686–692. [Google Scholar] [CrossRef]
- Tsaih, S.-W.; Pezzolesi, M.G.; Yuan, R.; Warram, J.H.; Krolewski, A.S.; Korstanje, R. Genetic Analysis of Albuminuria in Aging Mice and Concordance with Loci for Human Diabetic Nephropathy Found in a Genome-Wide Association Scan. Kidney Int. 2010, 77, 201–210. [Google Scholar] [CrossRef]
- Verzola, D.; Gandolfo, M.T.; Gaetani, G.; Ferraris, A.; Mangerini, R.; Ferrario, F.; Villaggio, B.; Gianiorio, F.; Tosetti, F.; Weiss, U.; et al. Accelerated Senescence in the Kidneys of Patients with Type 2 Diabetic Nephropathy. Am. J. Physiol. Ren. Physiol. 2008, 295, F1563–F1573. [Google Scholar] [CrossRef]
- Wiley, C.D. Role of Senescent Renal Cells in Pathophysiology of Diabetic Kidney Disease. Curr. Diabetes Rep. 2020, 20, 33. [Google Scholar] [CrossRef]
- Kasper, M.; Funk, R.H. Age-Related Changes in Cells and Tissues Due to Advanced Glycation End Products (AGEs). Arch. Gerontol. Geriatr. 2001, 32, 233–243. [Google Scholar] [CrossRef] [PubMed]
- Mei, C.; Zheng, F. Chronic Inflammation Potentiates Kidney Aging. Semin. Nephrol. 2009, 29, 555–568. [Google Scholar] [CrossRef] [PubMed]
- Vlassara, H.; Torreggiani, M.; Post, J.B.; Zheng, F.; Uribarri, J.; Striker, G.E. Role of Oxidants/Inflammation in Declining Renal Function in Chronic Kidney Disease and Normal Aging. Kidney Int. Suppl. 2009, 76, S3–S11. [Google Scholar] [CrossRef] [PubMed]
- Vlassara, H.; Uribarri, J.; Ferrucci, L.; Cai, W.; Torreggiani, M.; Post, J.B.; Zheng, F.; Striker, G.E. Identifying Advanced Glycation End Products as a Major Source of Oxidants in Aging: Implications for the Management and/or Prevention of Reduced Renal Function in Elderly Persons. Semin. Nephrol. 2009, 29, 594–603. [Google Scholar] [CrossRef] [PubMed]
- Guo, J.; Zheng, H.J.; Zhang, W.; Lou, W.; Xia, C.; Han, X.T.; Huang, W.J.; Zhang, F.; Wang, Y.; Liu, W.J. Accelerated Kidney Aging in Diabetes Mellitus. Oxid. Med. Cell Longev. 2020, 2020, 1234059. [Google Scholar] [CrossRef] [PubMed]
- Selye, H.; Hall, C.E.; Rowley, E.M. Malignant Hypertension Produced by Treatment with Desoxycorticosterone Acetate and Sodium Chloride. Can. Med. Assoc. J. 1943, 49, 88–92. [Google Scholar] [PubMed]
- Ferreira, N.S.; Tostes, R.C.; Paradis, P.; Schiffrin, E.L. Aldosterone, Inflammation, Immune System, and Hypertension. Am. J. Hypertens. 2021, 34, 15–27. [Google Scholar] [CrossRef]
- Fuller, P.J.; Yang, J.; Young, M.J. 30 Years of the Mineralocorticoid Receptor: Coregulators as Mediators of Mineralocorticoid Receptor Signalling Diversity. J. Endocrinol. 2017, 234, T23–T34. [Google Scholar] [CrossRef]
- Kawanami, D.; Takashi, Y.; Muta, Y.; Oda, N.; Nagata, D.; Takahashi, H.; Tanabe, M. Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease. Front. Pharmacol. 2021, 12, 754239. [Google Scholar] [CrossRef]
- Sawicki, P.T.; Kaiser, S.; Heinemann, L.; Frenzel, H.; Berger, M. Prevalence of Renal Artery Stenosis in Diabetes Mellitus—An Autopsy Study. J. Intern. Med. 1991, 229, 489–492. [Google Scholar] [CrossRef]
- Moriya, T.; Omura, K.; Matsubara, M.; Yoshida, Y.; Hayama, K.; Ouchi, M. Arteriolar Hyalinosis Predicts Increase in Albuminuria and GFR Decline in Normo- and Microalbuminuric Japanese Patients with Type 2 Diabetes. Diabetes Care 2017, 40, 1373–1378. [Google Scholar] [CrossRef] [PubMed]
- Ekinci, E.I.; Jerums, G.; Skene, A.; Crammer, P.; Power, D.; Cheong, K.Y.; Panagiotopoulos, S.; McNeil, K.; Baker, S.T.; Fioretto, P.; et al. Renal Structure in Normoalbuminuric and Albuminuric Patients with Type 2 Diabetes and Impaired Renal Function. Diabetes Care 2013, 36, 3620–3626. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, M.; Furuichi, K.; Yokoyama, H.; Toyama, T.; Iwata, Y.; Sakai, N.; Kaneko, S.; Wada, T. Kidney Lesions in Diabetic Patients with Normoalbuminuric Renal Insufficiency. Clin. Exp. Nephrol. 2014, 18, 305–312. [Google Scholar] [CrossRef] [PubMed]
- Dai, Q.; Chen, N.; Zeng, L.; Lin, X.-J.; Jiang, F.-X.; Zhuang, X.-J.; Lu, Z.-Y. Clinical Features of and Risk Factors for Normoalbuminuric Diabetic Kidney Disease in Hospitalized Patients with Type 2 Diabetes Mellitus: A Retrospective Cross-Sectional Study. BMC Endocr. Disord. 2021, 21, 104. [Google Scholar] [CrossRef] [PubMed]
- Retnakaran, R.; Cull, C.A.; Thorne, K.I.; Adler, A.I.; Holman, R.R.; UKPDS Study Group. Risk Factors for Renal Dysfunction in Type 2 Diabetes: U.K. Prospective Diabetes Study 74. Diabetes 2006, 55, 1832–1839. [Google Scholar] [CrossRef] [PubMed]
- Shi, S.; Ni, L.; Gao, L.; Wu, X. Comparison of Nonalbuminuric and Albuminuric Diabetic Kidney Disease Among Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Front. Endocrinol. 2022, 13, 871272. [Google Scholar] [CrossRef] [PubMed]
- Liu, P.; Quinn, R.R.; Lam, N.N.; Elliott, M.J.; Xu, Y.; James, M.T.; Manns, B.; Ravani, P. Accounting for Age in the Definition of Chronic Kidney Disease. JAMA Intern. Med. 2021, 181, 1359–1366. [Google Scholar] [CrossRef] [PubMed]
- Delanaye, P.; Jager, K.J.; Bökenkamp, A.; Christensson, A.; Dubourg, L.; Eriksen, B.O.; Gaillard, F.; Gambaro, G.; van der Giet, M.; Glassock, R.J.; et al. CKD: A Call for an Age-Adapted Definition. J. Am. Soc. Nephrol. 2019, 30, 1785–1805. [Google Scholar] [CrossRef]
- Delanaye, P.; Glassock, R.J.; Pottel, H.; Rule, A.D. An Age-Calibrated Definition of Chronic Kidney Disease: Rationale and Benefits. Clin. Biochem. Rev. 2016, 37, 17–26. [Google Scholar]
- de Zeeuw, D.; Parving, H.-H.; Henning, R.H. Microalbuminuria as an Early Marker for Cardiovascular Disease. J. Am. Soc. Nephrol. 2006, 17, 2100–2105. [Google Scholar] [CrossRef]
- Stehouwer, C.D.A.; Henry, R.M.A.; Dekker, J.M.; Nijpels, G.; Heine, R.J.; Bouter, L.M. Microalbuminuria Is Associated with Impaired Brachial Artery, Flow-Mediated Vasodilation in Elderly Individuals without and with Diabetes: Further Evidence for a Link between Microalbuminuria and Endothelial Dysfunction—The Hoorn Study. Kidney Int. Suppl. 2004, 66, S42–S44. [Google Scholar] [CrossRef]
- Hwang, S.; Lee, K.; Park, J.; Kim, D.H.; Jeon, J.; Jang, H.R.; Hur, K.Y.; Kim, J.H.; Huh, W.; Kim, Y.-G.; et al. Prognostic Significance of Albuminuria in Elderly of Various Ages with Diabetes. Sci. Rep. 2023, 13, 7079. [Google Scholar] [CrossRef]
- Anders, H.-J.; Huber, T.B.; Isermann, B.; Schiffer, M. CKD in Diabetes: Diabetic Kidney Disease versus Nondiabetic Kidney Disease. Nat. Rev. Nephrol. 2018, 14, 361–377. [Google Scholar] [CrossRef] [PubMed]
- Iqbal, Z.; Meguira, S.; Friedman, E.A. Geriatric Diabetic Nephropathy: An Analysis of Renal Referral in Patients Age 60 or Older. Am. J. Kidney Dis. 1990, 16, 312–316. [Google Scholar] [CrossRef] [PubMed]
- Marshall, S.M.; Alberti, K.G. Comparison of the Prevalence and Associated Features of Abnormal Albumin Excretion in Insulin-Dependent and Non-Insulin-Dependent Diabetes. Q. J. Med. 1989, 70, 61–71. [Google Scholar] [PubMed]
- Parving, H.H.; Gall, M.A.; Skøtt, P.; Jørgensen, H.E.; Løkkegaard, H.; Jørgensen, F.; Nielsen, B.; Larsen, S. Prevalence and Causes of Albuminuria in Non-Insulin-Dependent Diabetic Patients. Kidney Int. 1992, 41, 758–762. [Google Scholar] [CrossRef] [PubMed]
- Torffvit, O.; Agardh, E.; Agardh, C.D. Albuminuria and Associated Medical Risk Factors: A Cross-Sectional Study in 476 Type I (Insulin-Dependent) Diabetic Patients. Part 1. J. Diabet. Complicat. 1991, 5, 23–28. [Google Scholar] [CrossRef] [PubMed]
- Joseph, A.J.; Friedman, E.A. Diabetic Nephropathy in the Elderly. Clin. Geriatr. Med. 2009, 25, 373–389. [Google Scholar] [CrossRef] [PubMed]
- Nair, R.; Bell, J.M.; Walker, P.D. Renal Biopsy in Patients Aged 80 Years and Older. Am. J. Kidney Dis. 2004, 44, 618–626. [Google Scholar] [CrossRef]
- Fedi, M.; Bobot, M.; Torrents, J.; Gobert, P.; Magnant, É.; Knefati, Y.; Verhelst, D.; Lebrun, G.; Masson, V.; Giaime, P.; et al. Kidney Biopsy in Very Elderly Patients: Indications, Therapeutic Impact and Complications. BMC Nephrol. 2021, 22, 362. [Google Scholar] [CrossRef]
- Kohli, H.S.; Jairam, A.; Bhat, A.; Sud, K.; Jha, V.; Gupta, K.L.; Sakhuja, V. Safety of Kidney Biopsy in Elderly: A Prospective Study. Int. Urol. Nephrol. 2006, 38, 815–820. [Google Scholar] [CrossRef] [PubMed]
- Uezono, S.; Hara, S.; Sato, Y.; Komatsu, H.; Ikeda, N.; Shimao, Y.; Hayashi, T.; Asada, Y.; Fujimoto, S.; Eto, T. Renal Biopsy in Elderly Patients: A Clinicopathological Analysis. Ren. Fail. 2006, 28, 549–555. [Google Scholar] [CrossRef] [PubMed]
- Blicklé, J.F.; Doucet, J.; Krummel, T.; Hannedouche, T. Diabetic Nephropathy in the Elderly. Diabetes Metab. 2007, 33 (Suppl. S1), S40–S55. [Google Scholar] [CrossRef] [PubMed]
- Espinel, E.; Agraz, I.; Ibernon, M.; Ramos, N.; Fort, J.; Serón, D. Renal Biopsy in Type 2 Diabetic Patients. J. Clin. Med. 2015, 4, 998–1009. [Google Scholar] [CrossRef] [PubMed]
- Fiorentino, M.; Bolignano, D.; Tesar, V.; Pisano, A.; Biesen, W.V.; Tripepi, G.; D’Arrigo, G.; Gesualdo, L.; ERA-EDTA Immunonephrology Working Group. Renal Biopsy in Patients with Diabetes: A Pooled Meta-Analysis of 48 Studies. Nephrol. Dial. Transpl. 2017, 32, 97–110. [Google Scholar] [CrossRef]
- Glassock, R.J.; Hirschman, G.H.; Striker, G.E. Workshop on the Use of Renal Biopsy in Research on Diabetic Nephropathy: A Summary Report. Am. J. Kidney Dis. 1991, 18, 589–592. [Google Scholar] [CrossRef] [PubMed]
- Faller, B.; Beuscart, J.-B.; Frimat, L. Competing-Risk Analysis of Death and Dialysis Initiation among Elderly (≥80 Years) Newly Referred to Nephrologists: A French Prospective Study. BMC Nephrol. 2013, 14, 103. [Google Scholar] [CrossRef] [PubMed]
- Tuttle, K.R.; Wong, L.; St Peter, W.; Roberts, G.; Rangaswami, J.; Mottl, A.; Kliger, A.S.; Harris, R.C.; Gee, P.O.; Fowler, K.; et al. Moving from Evidence to Implementation of Breakthrough Therapies for Diabetic Kidney Disease. Clin. J. Am. Soc. Nephrol. 2022, 17, 1092–1103. [Google Scholar] [CrossRef]
- Umpierre, D.; Ribeiro, P.A.B.; Kramer, C.K.; Leitão, C.B.; Zucatti, A.T.N.; Azevedo, M.J.; Gross, J.L.; Ribeiro, J.P.; Schaan, B.D. Physical Activity Advice Only or Structured Exercise Training and Association with HbA1c Levels in Type 2 Diabetes: A Systematic Review and Meta-Analysis. JAMA 2011, 305, 1790–1799. [Google Scholar] [CrossRef]
- Hoffmann, T.C.; Maher, C.G.; Briffa, T.; Sherrington, C.; Bennell, K.; Alison, J.; Singh, M.F.; Glasziou, P.P. Prescribing Exercise Interventions for Patients with Chronic Conditions. CMAJ 2016, 188, 510–518. [Google Scholar] [CrossRef]
- Izquierdo, M.; Rodriguez-Mañas, L.; Sinclair, A.J. Editorial: What Is New in Exercise Regimes for Frail Older People–How Does the Erasmus Vivifrail Project Take Us Forward? J. Nutr. Health Aging 2016, 20, 736–737. [Google Scholar] [CrossRef]
- Horikawa, C.; Aida, R.; Tanaka, S.; Kamada, C.; Tanaka, S.; Yoshimura, Y.; Kodera, R.; Fujihara, K.; Kawasaki, R.; Moriya, T.; et al. Sodium Intake and Incidence of Diabetes Complications in Elderly Patients with Type 2 Diabetes-Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT). Nutrients 2021, 13, 689. [Google Scholar] [CrossRef] [PubMed]
- Klahr, S.; Levey, A.S.; Beck, G.J.; Caggiula, A.W.; Hunsicker, L.; Kusek, J.W.; Striker, G. The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease. Modification of Diet in Renal Disease Study Group. N. Engl. J. Med. 1994, 330, 877–884. [Google Scholar] [CrossRef] [PubMed]
- Pijls, L.T.J.; de Vries, H.; van Eijk, J.T.M.; Donker, A.J.M. Protein Restriction, Glomerular Filtration Rate and Albuminuria in Patients with Type 2 Diabetes Mellitus: A Randomized Trial. Eur. J. Clin. Nutr. 2002, 56, 1200–1207. [Google Scholar] [CrossRef] [PubMed]
- Volkert, D.; Beck, A.M.; Cederholm, T.; Cruz-Jentoft, A.; Goisser, S.; Hooper, L.; Kiesswetter, E.; Maggio, M.; Raynaud-Simon, A.; Sieber, C.C.; et al. ESPEN Guideline on Clinical Nutrition and Hydration in Geriatrics. Clin. Nutr. 2019, 38, 10–47. [Google Scholar] [CrossRef] [PubMed]
- Piccoli, G.B.; Cederholm, T.; Avesani, C.M.; Bakker, S.J.L.; Bellizzi, V.; Cuerda, C.; Cupisti, A.; Sabatino, A.; Schneider, S.; Torreggiani, M.; et al. Nutritional Status and the Risk of Malnutrition in Older Adults with Chronic Kidney Disease–Implications for Low Protein Intake and Nutritional Care: A Critical Review Endorsed by ERN-ERA and ESPEN. Clin. Nutr. 2023, 42, 443–457. [Google Scholar] [CrossRef] [PubMed]
- American Diabetes Association Professional Practice Committee; Draznin, B.; Aroda, V.R.; Bakris, G.; Benson, G.; Brown, F.M.; Freeman, R.; Green, J.; Huang, E.; Isaacs, D.; et al. 13. Older Adults: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022, 45 (Suppl. S1), S195–S207. [Google Scholar] [CrossRef] [PubMed]
- Kahn, S.E. Glucose Control in Type 2 Diabetes: Still Worthwhile and Worth Pursuing. JAMA 2009, 301, 1590–1592. [Google Scholar] [CrossRef] [PubMed]
- Shorr, R.I.; Franse, L.V.; Resnick, H.E.; Di Bari, M.; Johnson, K.C.; Pahor, M. Glycemic Control of Older Adults with Type 2 Diabetes: Findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J. Am. Geriatr. Soc. 2000, 48, 264–267. [Google Scholar] [CrossRef]
- Whitmer, R.A.; Karter, A.J.; Yaffe, K.; Quesenberry, C.P.; Selby, J.V. Hypoglycemic Episodes and Risk of Dementia in Older Patients with Type 2 Diabetes Mellitus. JAMA 2009, 301, 1565–1572. [Google Scholar] [CrossRef]
- UK Prospective Diabetes Study (UKPDS) Group. Effect of Intensive Blood-Glucose Control with Metformin on Complications in Overweight Patients with Type 2 Diabetes (UKPDS 34). Lancet 1998, 352, 854–865. [Google Scholar] [CrossRef]
- UK Prospective Diabetes Study (UKPDS) Group. Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes (UKPDS 33). Lancet 1998, 352, 837–853. [Google Scholar] [CrossRef]
- Cheung, A.K.; Chang, T.I.; Cushman, W.C.; Furth, S.L.; Hou, F.F.; Ix, J.H.; Knoll, G.A.; Muntner, P.; Pecoits-Filho, R.; Sarnak, M.J.; et al. Executive Summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021, 99, 559–569. [Google Scholar] [CrossRef] [PubMed]
- Group, T.S.R. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N. Engl. J. Med. 2015, 373, 2103–2116. [Google Scholar] [CrossRef] [PubMed]
- Gencer, B.; Marston, N.A.; Im, K.; Cannon, C.P.; Sever, P.; Keech, A.; Braunwald, E.; Giugliano, R.P.; Sabatine, M.S. Efficacy and Safety of Lowering LDL Cholesterol in Older Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Lancet 2020, 396, 1637–1643. [Google Scholar] [CrossRef] [PubMed]
- Yourman, L.C.; Cenzer, I.S.; Boscardin, W.J.; Nguyen, B.T.; Smith, A.K.; Schonberg, M.A.; Schoenborn, N.L.; Widera, E.W.; Orkaby, A.; Rodriguez, A.; et al. Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 Years: A Meta-Analysis. JAMA Intern. Med. 2021, 181, 179–185. [Google Scholar] [CrossRef] [PubMed]
- Cheung, A.K.; Chang, T.I.; Cushman, W.C.; Furth, S.L.; Hou, F.F.; Ix, J.H.; Knoll, G.A.; Muntner, P.; Pecoits-Filho, R.; Sarnak, M.J. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021, 99, S1–S87. [Google Scholar] [CrossRef]
- Baigent, C.; Landray, M.J.; Reith, C.; Emberson, J.; Wheeler, D.C.; Tomson, C.; Wanner, C.; Krane, V.; Cass, A.; Craig, J.; et al. The Effects of Lowering LDL Cholesterol with Simvastatin plus Ezetimibe in Patients with Chronic Kidney Disease (Study of Heart and Renal Protection): A Randomised Placebo-Controlled Trial. Lancet 2011, 377, 2181–2192. [Google Scholar] [CrossRef]
- Lewis, E.J.; Hunsicker, L.G.; Clarke, W.R.; Berl, T.; Pohl, M.A.; Lewis, J.B.; Ritz, E.; Atkins, R.C.; Rohde, R.; Raz, I.; et al. Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes. N. Engl. J. Med. 2001, 345, 851–860. [Google Scholar] [CrossRef]
- Brenner, B.M.; Cooper, M.E.; de Zeeuw, D.; Keane, W.F.; Mitch, W.E.; Parving, H.H.; Remuzzi, G.; Snapinn, S.M.; Zhang, Z.; Shahinfar, S.; et al. Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. N. Engl. J. Med. 2001, 345, 861–869. [Google Scholar] [CrossRef]
- Lambers Heerspink, H.J.; Gansevoort, R.T.; Brenner, B.M.; Cooper, M.E.; Parving, H.H.; Shahinfar, S.; de Zeeuw, D. Comparison of Different Measures of Urinary Protein Excretion for Prediction of Renal Events. J. Am. Soc. Nephrol. 2010, 21, 1355–1360. [Google Scholar] [CrossRef] [PubMed]
- de Zeeuw, D.; Remuzzi, G.; Parving, H.-H.; Keane, W.F.; Zhang, Z.; Shahinfar, S.; Snapinn, S.; Cooper, M.E.; Mitch, W.E.; Brenner, B.M. Proteinuria, a Target for Renoprotection in Patients with Type 2 Diabetic Nephropathy: Lessons from RENAAL. Kidney Int. 2004, 65, 2309–2320. [Google Scholar] [CrossRef] [PubMed]
- Fried, L.F.; Petruski-Ivleva, N.; Folkerts, K.; Schmedt, N.; Velentgas, P.; Kovesdy, C.P. ACE Inhibitor or ARB Treatment among Patients with Diabetes and Chronic Kidney Disease. Am. J. Manag. Care 2021, 27, S360–S368. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Thumula, V.; Pace, P.F.; Banahan, B.F.; Wilkin, N.E.; Lobb, W.B. High-Risk Diabetic Patients in Medicare Part D Programs: Are They Getting the Recommended ACEI/ARB Therapy? J. Gen. Intern. Med. 2010, 25, 298–304. [Google Scholar] [CrossRef] [PubMed]
- Rosen, A.B.; Karter, A.J.; Liu, J.Y.; Selby, J.V.; Schneider, E.C. Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in High-Risk Clinical and Ethnic Groups with Diabetes. J. Gen. Intern. Med. 2004, 19, 669–675. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, D.; Winocour, P.; Chowdhury, T.A.; De, P.; Wahba, M.; Montero, R.; Fogarty, D.; Frankel, A.H.; Karalliedde, J.; Mark, P.B.; et al. Management of Hypertension and Renin-Angiotensin-Aldosterone System Blockade in Adults with Diabetic Kidney Disease: Association of British Clinical Diabetologists and the Renal Association UK Guideline Update 2021. BMC Nephrol. 2022, 23, 9. [Google Scholar] [CrossRef] [PubMed]
- Fried, L.F.; Emanuele, N.; Zhang, J.H.; Brophy, M.; Conner, T.A.; Duckworth, W.; Leehey, D.J.; McCullough, P.A.; O’Connor, T.; Palevsky, P.M.; et al. Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. N. Engl. J. Med. 2013, 369, 1892–1903. [Google Scholar] [CrossRef] [PubMed]
- Qiao, Y.; Shin, J.-I.; Chen, T.K.; Inker, L.A.; Coresh, J.; Alexander, G.C.; Jackson, J.W.; Chang, A.R.; Grams, M.E. Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons with Low Estimated Glomerular Filtration Rate. JAMA Intern. Med. 2020, 180, 718–726. [Google Scholar] [CrossRef]
- Bhandari, S.; Ives, N.; Brettell, E.A.; Valente, M.; Cockwell, P.; Topham, P.S.; Cleland, J.G.; Khwaja, A.; El Nahas, M. Multicentre Randomized Controlled Trial of Angiotensin-Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Withdrawal in Advanced Renal Disease: The STOP-ACEi Trial. Nephrol. Dial. Transpl. 2016, 31, 255–261. [Google Scholar] [CrossRef]
- Bhandari, S.; Mehta, S.; Khwaja, A.; Cleland, J.G.F.; Ives, N.; Brettell, E.; Chadburn, M.; Cockwell, P.; STOP ACEi Trial Investigators. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N. Engl. J. Med. 2022, 387, 2021–2032. [Google Scholar] [CrossRef]
- Xie, X.; Liu, Y.; Perkovic, V.; Li, X.; Ninomiya, T.; Hou, W.; Zhao, N.; Liu, L.; Lv, J.; Zhang, H.; et al. Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-Analysis of Randomized Clinical Trials. Am. J. Kidney Dis. 2016, 67, 728–741. [Google Scholar] [CrossRef] [PubMed]
- Tsapas, A.; Karagiannis, T.; Avgerinos, I.; Matthews, D.R.; Bekiari, E. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes. Ann. Intern. Med. 2021, 173, 278–286. [Google Scholar] [CrossRef] [PubMed]
- Cherney, D.Z.I.; Charbonnel, B.; Cosentino, F.; Dagogo-Jack, S.; McGuire, D.K.; Pratley, R.; Shih, W.J.; Frederich, R.; Maldonado, M.; Pong, A.; et al. Effects of Ertugliflozin on Kidney Composite Outcomes, Renal Function and Albuminuria in Patients with Type 2 Diabetes Mellitus: An Analysis from the Randomised VERTIS CV Trial. Diabetologia 2021, 64, 1256–1267. [Google Scholar] [CrossRef] [PubMed]
- Dekkers, C.C.J.; Wheeler, D.C.; Sjöström, C.D.; Stefansson, B.V.; Cain, V.; Heerspink, H.J.L. Effects of the Sodium-Glucose Co-Transporter 2 Inhibitor Dapagliflozin in Patients with Type 2 Diabetes and Stages 3b-4 Chronic Kidney Disease. Nephrol. Dial. Transpl. 2018, 33, 2005–2011. [Google Scholar] [CrossRef] [PubMed]
- Wanner, C.; Inzucchi, S.E.; Lachin, J.M.; Fitchett, D.; von Eynatten, M.; Mattheus, M.; Johansen, O.E.; Woerle, H.J.; Broedl, U.C.; Zinman, B.; et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N. Engl. J. Med. 2016, 375, 323–334. [Google Scholar] [CrossRef] [PubMed]
- Zinman, B.; Wanner, C.; Lachin, J.M.; Fitchett, D.; Bluhmki, E.; Hantel, S.; Mattheus, M.; Devins, T.; Johansen, O.E.; Woerle, H.J.; et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 2015, 373, 2117–2128. [Google Scholar] [CrossRef]
- Cannon, C.P.; Pratley, R.; Dagogo-Jack, S.; Mancuso, J.; Huyck, S.; Masiukiewicz, U.; Charbonnel, B.; Frederich, R.; Gallo, S.; Cosentino, F.; et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N. Engl. J. Med. 2020, 383, 1425–1435. [Google Scholar] [CrossRef]
- Neal, B.; Perkovic, V.; Matthews, D.R. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N. Engl. J. Med. 2017, 377, 644–657. [Google Scholar] [CrossRef]
- Wiviott, S.D.; Raz, I.; Bonaca, M.P.; Mosenzon, O.; Kato, E.T.; Cahn, A.; Silverman, M.G.; Zelniker, T.A.; Kuder, J.F.; Murphy, S.A.; et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2019, 380, 347–357. [Google Scholar] [CrossRef]
- McMurray, J.J.V.; Solomon, S.D.; Inzucchi, S.E.; Køber, L.; Kosiborod, M.N.; Martinez, F.A.; Ponikowski, P.; Sabatine, M.S.; Anand, I.S.; Bělohlávek, J.; et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N. Engl. J. Med. 2019, 381, 1995–2008. [Google Scholar] [CrossRef]
- Packer, M.; Anker, S.D.; Butler, J.; Filippatos, G.; Pocock, S.J.; Carson, P.; Januzzi, J.; Verma, S.; Tsutsui, H.; Brueckmann, M.; et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N. Engl. J. Med. 2020, 383, 1413–1424. [Google Scholar] [CrossRef] [PubMed]
- Solomon, S.D.; McMurray, J.J.V.; Claggett, B.; de Boer, R.A.; DeMets, D.; Hernandez, A.F.; Inzucchi, S.E.; Kosiborod, M.N.; Lam, C.S.P.; Martinez, F.; et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N. Engl. J. Med. 2022, 387, 1089–1098. [Google Scholar] [CrossRef] [PubMed]
- Anker, S.D.; Butler, J.; Filippatos, G.; Ferreira, J.P.; Bocchi, E.; Böhm, M.; Brunner-La Rocca, H.-P.; Choi, D.-J.; Chopra, V.; Chuquiure-Valenzuela, E.; et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N. Engl. J. Med. 2021, 385, 1451–1461. [Google Scholar] [CrossRef] [PubMed]
- Perkovic, V.; Jardine, M.J.; Neal, B.; Bompoint, S.; Heerspink, H.J.L.; Charytan, D.M.; Edwards, R.; Agarwal, R.; Bakris, G.; Bull, S.; et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N. Engl. J. Med. 2019, 380, 2295–2306. [Google Scholar] [CrossRef] [PubMed]
- Heerspink, H.J.L.; Stefánsson, B.V.; Correa-Rotter, R.; Chertow, G.M.; Greene, T.; Hou, F.-F.; Mann, J.F.E.; McMurray, J.J.V.; Lindberg, M.; Rossing, P.; et al. Dapagliflozin in Patients with Chronic Kidney Disease. N. Engl. J. Med. 2020, 383, 1436–1446. [Google Scholar] [CrossRef] [PubMed]
- EMPA-KIDNEY Collaborative Group; Herrington, W.G.; Staplin, N.; Wanner, C.; Green, J.B.; Hauske, S.J.; Emberson, J.R.; Preiss, D.; Judge, P.; Mayne, K.J.; et al. Empagliflozin in Patients with Chronic Kidney Disease. N. Engl. J. Med. 2022, 388, 117–127. [Google Scholar] [CrossRef] [PubMed]
- van Bommel, E.J.M.; Muskiet, M.H.A.; van Baar, M.J.B.; Tonneijck, L.; Smits, M.M.; Emanuel, A.L.; Bozovic, A.; Danser, A.H.J.; Geurts, F.; Hoorn, E.J.; et al. The Renal Hemodynamic Effects of the SGLT2 Inhibitor Dapagliflozin Are Caused by Post-Glomerular Vasodilatation Rather than Pre-Glomerular Vasoconstriction in Metformin-Treated Patients with Type 2 Diabetes in the Randomized, Double-Blind RED Trial. Kidney Int. 2020, 97, 202–212. [Google Scholar] [CrossRef] [PubMed]
- Heerspink, H.J.L.; Cherney, D.Z.I. Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation. Clin. J. Am. Soc. Nephrol. 2021, 16, 1278–1280. [Google Scholar] [CrossRef]
- Kraus, B.J.; Weir, M.R.; Bakris, G.L.; Mattheus, M.; Cherney, D.Z.I.; Sattar, N.; Heerspink, H.J.L.; Ritter, I.; von Eynatten, M.; Zinman, B.; et al. Characterization and Implications of the Initial Estimated Glomerular Filtration Rate “dip” upon Sodium-Glucose Cotransporter-2 Inhibition with Empagliflozin in the EMPA-REG OUTCOME Trial. Kidney Int. 2021, 99, 750–762. [Google Scholar] [CrossRef]
- Johansen, M.E.; Argyropoulos, C. The Cardiovascular Outcomes, Heart Failure and Kidney Disease Trials Tell That the Time to Use Sodium Glucose Cotransporter 2 Inhibitors Is Now. Clin. Cardiol. 2020, 43, 1376–1387. [Google Scholar] [CrossRef]
- Bhattarai, M.; Salih, M.; Regmi, M.; Al-Akchar, M.; Deshpande, R.; Niaz, Z.; Kulkarni, A.; Siddique, M.; Hegde, S. Association of Sodium-Glucose Cotransporter 2 Inhibitors with Cardiovascular Outcomes in Patients with Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-Analysis. JAMA Netw. Open 2022, 5, e2142078. [Google Scholar] [CrossRef] [PubMed]
- Strain, W.D.; Griffiths, J. A Systematic Review and Meta-Analysis of the Impact of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on Cardiovascular Outcomes in Biologically Healthy Older Adults. Br. J. Diabetes 2021, 21, 30–35. [Google Scholar] [CrossRef]
- Nuffield Department of Population Health Renal Studies Group; SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of Diabetes on the Effects of Sodium Glucose Co-Transporter-2 Inhibitors on Kidney Outcomes: Collaborative Meta-Analysis of Large Placebo-Controlled Trials. Lancet 2022, 400, 1788–1801. [Google Scholar] [CrossRef] [PubMed]
- Jabbour, S.A.; Ibrahim, N.E.; Argyropoulos, C.P. Physicians’ Considerations and Practice Recommendations Regarding the Use of Sodium-Glucose Cotransporter-2 Inhibitors. J. Clin. Med. 2022, 11, 6051. [Google Scholar] [CrossRef] [PubMed]
- Chung, E.Y.; Ruospo, M.; Natale, P.; Bolignano, D.; Navaneethan, S.D.; Palmer, S.C.; Strippoli, G.F. Aldosterone Antagonists in Addition to Renin Angiotensin System Antagonists for Preventing the Progression of Chronic Kidney Disease. Cochrane Database Syst. Rev. 2020, 2020, CD007004. [Google Scholar] [CrossRef]
- Barrera-Chimal, J.; Kolkhof, P.; Lima-Posada, I.; Joachim, A.; Rossignol, P.; Jaisser, F. Differentiation between Emerging Non-Steroidal and Established Steroidal Mineralocorticoid Receptor Antagonists: Head-to-Head Comparisons of Pharmacological and Clinical Characteristics. Expert. Opin. Investig. Drugs 2021, 30, 1141–1157. [Google Scholar] [CrossRef] [PubMed]
- Ito, S.; Kashihara, N.; Shikata, K.; Nangaku, M.; Wada, T.; Okuda, Y.; Sawanobori, T. Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN): Phase 3 Randomized Controlled Clinical Trial. CJASN 2020, 15, 1715–1727. [Google Scholar] [CrossRef] [PubMed]
- Wada, T.; Inagaki, M.; Yoshinari, T.; Terata, R.; Totsuka, N.; Gotou, M.; Hashimoto, G. Apararenone in Patients with Diabetic Nephropathy: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 2 Dose-Response Study and Open-Label Extension Study. Clin. Exp. Nephrol. 2021, 25, 120–130. [Google Scholar] [CrossRef]
- Bakris, G.L.; Agarwal, R.; Anker, S.D.; Pitt, B.; Ruilope, L.M.; Rossing, P.; Kolkhof, P.; Nowack, C.; Schloemer, P.; Joseph, A.; et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2020, 383, 2219–2229. [Google Scholar] [CrossRef]
- Pitt, B.; Filippatos, G.; Agarwal, R.; Anker, S.D.; Bakris, G.L.; Rossing, P.; Joseph, A.; Kolkhof, P.; Nowack, C.; Schloemer, P.; et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N. Engl. J. Med. 2021, 385, 2252–2263. [Google Scholar] [CrossRef]
- Agarwal, R.; Filippatos, G.; Pitt, B.; Anker, S.D.; Rossing, P.; Joseph, A.; Kolkhof, P.; Nowack, C.; Gebel, M.; Ruilope, L.M.; et al. Cardiovascular and Kidney Outcomes with Finerenone in Patients with Type 2 Diabetes and Chronic Kidney Disease: The FIDELITY Pooled Analysis. Eur. Heart J. 2022, 43, 474–484. [Google Scholar] [CrossRef] [PubMed]
- Ruilope, L.M.; Pitt, B.; Anker, S.D.; Rossing, P.; Kovesdy, C.P.; Pecoits-Filho, R.; Pergola, P.; Joseph, A.; Lage, A.; Mentenich, N.; et al. Kidney Outcomes with Finerenone: An Analysis from the FIGARO-DKD Study. Nephrol. Dial. Transpl. 2023, 38, 372–383. [Google Scholar] [CrossRef] [PubMed]
- Jastreboff, A.M.; Aronne, L.J.; Ahmad, N.N.; Wharton, S.; Connery, L.; Alves, B.; Kiyosue, A.; Zhang, S.; Liu, B.; Bunck, M.C.; et al. Tirzepatide Once Weekly for the Treatment of Obesity. N. Engl. J. Med. 2022, 387, 205–216. [Google Scholar] [CrossRef] [PubMed]
- Del Prato, S.; Kahn, S.E.; Pavo, I.; Weerakkody, G.J.; Yang, Z.; Doupis, J.; Aizenberg, D.; Wynne, A.G.; Riesmeyer, J.S.; Heine, R.J.; et al. Tirzepatide versus Insulin Glargine in Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4): A Randomised, Open-Label, Parallel-Group, Multicentre, Phase 3 Trial. Lancet 2021, 398, 1811–1824. [Google Scholar] [CrossRef] [PubMed]
- Frías, J.P.; Davies, M.J.; Rosenstock, J.; Pérez Manghi, F.C.; Fernández Landó, L.; Bergman, B.K.; Liu, B.; Cui, X.; Brown, K.; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N. Engl. J. Med. 2021, 385, 503–515. [Google Scholar] [CrossRef] [PubMed]
- Min, T.; Bain, S.C. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021, 12, 143–157. [Google Scholar] [CrossRef] [PubMed]
- Rosenstock, J.; Wysham, C.; Frías, J.P.; Kaneko, S.; Lee, C.J.; Fernández Landó, L.; Mao, H.; Cui, X.; Karanikas, C.A.; Thieu, V.T. Efficacy and Safety of a Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide in Patients with Type 2 Diabetes (SURPASS-1): A Double-Blind, Randomised, Phase 3 Trial. Lancet 2021, 398, 143–155. [Google Scholar] [CrossRef] [PubMed]
- Urva, S.; Coskun, T.; Loh, M.T.; Du, Y.; Thomas, M.K.; Gurbuz, S.; Haupt, A.; Benson, C.T.; Hernandez-Illas, M.; D’Alessio, D.A.; et al. LY3437943, a Novel Triple GIP, GLP-1, and Glucagon Receptor Agonist in People with Type 2 Diabetes: A Phase 1b, Multicentre, Double-Blind, Placebo-Controlled, Randomised, Multiple-Ascending Dose Trial. Lancet 2022, 400, 1869–1881. [Google Scholar] [CrossRef]
- American Diabetes Association. Standards of Medical Care in Diabetes-2022 Abridged for Primary Care Providers. Clin. Diabetes 2022, 40, 10–38. [Google Scholar] [CrossRef]
- Gerstein, H.C.; Colhoun, H.M.; Dagenais, G.R.; Diaz, R.; Lakshmanan, M.; Pais, P.; Probstfield, J.; Botros, F.T.; Riddle, M.C.; Rydén, L.; et al. Dulaglutide and Renal Outcomes in Type 2 Diabetes: An Exploratory Analysis of the REWIND Randomised, Placebo-Controlled Trial. Lancet 2019, 394, 131–138. [Google Scholar] [CrossRef]
- Heerspink, H.J.L.; Sattar, N.; Pavo, I.; Haupt, A.; Duffin, K.L.; Yang, Z.; Wiese, R.J.; Tuttle, K.R.; Cherney, D.Z.I. Effects of Tirzepatide versus Insulin Glargine on Kidney Outcomes in Type 2 Diabetes in the SURPASS-4 Trial: Post-Hoc Analysis of an Open-Label, Randomised, Phase 3 Trial. Lancet Diabetes Endocrinol. 2022, 10, 774–785. [Google Scholar] [CrossRef] [PubMed]
- Mann, J.F.E.; Ørsted, D.D.; Brown-Frandsen, K.; Marso, S.P.; Poulter, N.R.; Rasmussen, S.; Tornøe, K.; Zinman, B.; Buse, J.B.; LEADER Steering Committee and Investigators. Liraglutide and Renal Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2017, 377, 839–848. [Google Scholar] [CrossRef] [PubMed]
- Marso, S.P.; Bain, S.C.; Consoli, A.; Eliaschewitz, F.G.; Jódar, E.; Leiter, L.A.; Lingvay, I.; Rosenstock, J.; Seufert, J.; Warren, M.L.; et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N. Engl. J. Med. 2016, 375, 1834–1844. [Google Scholar] [CrossRef] [PubMed]
- Sattar, N.; Lee, M.M.Y.; Kristensen, S.L.; Branch, K.R.H.; Del Prato, S.; Khurmi, N.S.; Lam, C.S.P.; Lopes, R.D.; McMurray, J.J.V.; Pratley, R.E.; et al. Cardiovascular, Mortality, and Kidney Outcomes with GLP-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Trials. Lancet Diabetes Endocrinol. 2021, 9, 653–662. [Google Scholar] [CrossRef] [PubMed]
- Caruso, I.; Di Gioia, L.; Di Molfetta, S.; Cignarelli, A.; Palmer, S.C.; Natale, P.; Strippoli, G.F.M.; Perrini, S.; Natalicchio, A.; Laviola, L.; et al. Glucometabolic Outcomes of GLP-1 Receptor Agonist-Based Therapies in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis. EClinicalMedicine 2023, 64, 102181. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Luo, J.; Jiang, M.; Wang, K. The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Front. Pharmacol. 2022, 13, 838277. [Google Scholar] [CrossRef] [PubMed]
- Neuen, B.L.; Heerspink, H.J.L.; Vart, P.; Claggett, B.L.; Fletcher, R.A.; Arnott, C.; de Oliveira Costa, J.; Falster, M.O.; Pearson, S.-A.; Mahaffey, K.W.; et al. Estimated Lifetime Cardiovascular, Kidney and Mortality Benefits of Combination Treatment with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Non-Steroidal MRA Compared with Conventional Care in Patients with Type 2 Diabetes and Albuminuria. Circulation 2023. [Google Scholar] [CrossRef]
Glomerulus | Arterioles | Mesangium 2 | Tubulo-Interstitium |
---|---|---|---|
Diffuse intra-capillary glomerulosclerosis | Subintimal hyaline deposits | Mesangial matrix expansion | Tubular atrophy/interstitial space expansion |
Nodular (Kimmelstein Wilson) | Capillary walls, Bowman capsules (capsular drops) 1 | Mesangiolysis | Tubular basement membrane thickening |
Glomerulosclerosis | Mesangial cell proliferation | Interstitial fibrosis |
Features on Presentation | Features Developing on Presentation or Follow-Up |
---|---|
Absence of retinopathy | Rapid decline in eGFR (>5 mL/min/1.73 m2/year) |
Albuminuria <5 years or >25 years after the diagnosis of type 1 diabetes | ↓ eGFR by more than 30% after initiation of an inhibitor of the renin angiotensin system |
Active urine sediment or serologies | Acute kidney injury (unexplained/sustained) |
Hematuria/nephritic syndrome | Sudden/acute worsening of albuminuria (unexplained/sustained) |
Healthy | Complex | Very Complex | |
---|---|---|---|
Patient characteristics Health status | Few coexisting chronic illnesses and intact cognitive and functional status | At least three coexisting chronic illnesses or 2+ instrumental ADL impairments or mild-to-moderate cognitive impairment | Long-term care facility resident or end-stage chronic illnesses or moderate-to-severe cognitive impairment or 2+ ADL impairments |
Rationale | Longer remaining life expectancy | Intermediate remaining life expectancy, high treatment burden, hypoglycemia vulnerability, fall risk | Limited remaining life expectancy makes benefit uncertain |
HbA1c | <7.0–7.5% (53–58 mmol/mol) | <8.0% (64 mmol/mol) | Do not rely on HbA1C; glucose control decisions should be based on avoiding hypoglycemia and symptomatic hyperglycemia. |
Fasting/pre-prandial glucose | 80–130 mg/dL (4.4–7.2 mmol/L) | 90–150 mg/dL (5.0–8.3 mmol/L) | 100–180 mg/dL (5.6–10.0 mmol/L) |
Bedtime glucose | 80–180 mg/dL (4.4–10.0 mmol/L) | 100–180 mg/dL (5.6–10.0 mmol/L) | 110–200 mg/dL (6.1–11.1 mmol/L) |
Blood pressure | <140/90 mmHg | <140/90 mmHg | <150/90 mmHg |
Lipid target | Statin unless contraindicated or not tolerated | Statin unless contraindicated or not tolerated | Consider likelihood of benefit with statin |
Adverse Events | At Risk | Preventive Measures |
---|---|---|
Genitourinary infections | Women, uncircumcised men | Adequate perineal hygiene Optimal diabetes care Antifungals Avoid SGLT-2is in patients with history of severe, recurrent infections |
Diabetic ketoacidosis | Insulin deficiency, ketogenic diet, alcohol abuse, acute illness, surgery | Maintain insulin; ≤20% reduction in insulin dosage if necessary Discontinue SGLT-2i temporarily in acute illness or surgery Avoid SGLT-2is in patients with history of DKA Discontinue SGLT-2i if patient is not eating or has vomiting and/or diarrhea |
Acute kidney injury | eGFR dip ≥30%, volume depletion | Reassess SGLT-2i regimen Frequently assess renal function, especially in patients with baseline eGFR <60 mL/min/1.73 m2 Discontinue SGLT-2i temporarily in acute illness |
Volume depletion | eGFR <60 mL/min/1.73 m2, old age, concomitant diuretic, prior volume depletion, hypotension, SBP <110 mm Hg | Reduce diuretic or hypotension-inducing agent use Inform patients to maintain adequate oral hydration Discontinue SGLT-2i temporarily in AKI |
Hypoglycemia | Concomitant insulin or SU, old age | Reduce insulin ≤20% or SU ≤50% if HbA1c <7.0%–8.0% Discontinue SU if HbA1c <8.0% in older patients Gradually reduce SU if HbA1c <8.0% in younger patients |
Amputation | History of amputation, peripheral vascular disease, neuropathy, foot ulcers | Monitor at-risk patients for new pain, skin ulcerations, or infections Inform patients about proper foot care |
Hyperkalemia | No concern |
Clinical Trial | Outcome | Effect in Younger Patients | Effect in Older Patients |
---|---|---|---|
FIGARO-DKD | MACE/HHF 2 | 0.90 0.74–1.10 | 0.85 0.72–1.00 |
FIGARO-DKD 1 | CR 3 | 0.72 0.52–0.99 | 0.92 0.61-1.38 |
FIDELIO-DKD | CR | 0.85 0.72–1.01 | 0.79 0.67–0.94 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ravender, R.; Roumelioti, M.-E.; Schmidt, D.W.; Unruh, M.L.; Argyropoulos, C. Chronic Kidney Disease in the Older Adult Patient with Diabetes. J. Clin. Med. 2024, 13, 348. https://doi.org/10.3390/jcm13020348
Ravender R, Roumelioti M-E, Schmidt DW, Unruh ML, Argyropoulos C. Chronic Kidney Disease in the Older Adult Patient with Diabetes. Journal of Clinical Medicine. 2024; 13(2):348. https://doi.org/10.3390/jcm13020348
Chicago/Turabian StyleRavender, Raja, Maria-Eleni Roumelioti, Darren W. Schmidt, Mark L. Unruh, and Christos Argyropoulos. 2024. "Chronic Kidney Disease in the Older Adult Patient with Diabetes" Journal of Clinical Medicine 13, no. 2: 348. https://doi.org/10.3390/jcm13020348