Skip to main content

From screening to treatment: the new landscape of diabetic kidney disease


Globally, diabetes mellitus is the leading cause of chronic kidney disease (CKD), and it is predicted to increase in the following years. Despite its high prevalence, CKD remains under diagnosed. In this BMC Medicine collection of articles on diabetic kidney disease (DKD), we place in context the importance of screening and early detection of DKD and the most accurate tools to monitor for optimal glycemic control in this his risk population. Further, we address this population's risk for severe complications such as stroke and all-cause mortality. We close this editorial by summarizing recent advances in management of this vulnerable population of patients with DKD, including guideline-directed medical therapy, novel treatments, and predictors of treatment failure.


The prevalence of diabetes worldwide in 2021 was a staggering 537 million people. This number is predicted to increase to 580 and 700 million cases by 2030 and 2045, respectively [1,2,3]. Further, the number of Americans with diabetes (37 million) was estimated at 10.5% of the population in 2018, which is also predicted to increase to 14% by 2030 [4]. According to the Centers for Disease Control and Prevention (CDC), 1 in 7 Americans had chronic kidney disease (CKD) in 2021, with diabetes being the leading cause in more than half of the cases [5]. The growing numbers of patients with CKD in the USA can be traced in large part to the burgeoning epidemic of diabetes. In fact, the USA is estimated to have more than 1 million patients with end-stage kidney disease by 2030, an increase of nearly 40% since 2015 [6]. Worldwide, in 2010, there were nearly 500 million adults with CKD with more than 75% of them residing in low- and middle-income countries (LMICs) [7]. As a result of these trends, society as a whole but specifically healthcare systems and families will face an increasing financial burden.

From screening to treatment advances

Between 2011 and 2014, only about 21% of people with CKD stages 3 and 4 with diabetes were aware of their diagnosis [5]. This issue led the National Kidney Foundation to label CKD as “the under-recognized public health crisis” in the USA [8]. However, one of the challenges of diagnosing CKD is that patients often remain asymptomatic until the disease has reached an advanced stage [9, 10]. In this collection, George C. and colleagues highlight the disproportionately high burden of CKD and diabetes in LMICs [11]. Some factors that play a role include lack of disease awareness, late referrals, and the cost of screening, among others. The authors found that screening for CKD in people with diabetes is generally infrequent in LMICs, which is contributed by the lack of a fully subsidized healthcare program for people with non-dialysis CKD, resulting in high out-of-pocket costs. In order to reduce the burden and progression of diabetes, Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend that all patients with diabetes undergo annual serum creatinine-based estimated glomerular filtration rate (eGFR) and urine tests to evaluate for albuminuria [12]. However, in LMICs, the dipstick test for urinary protein remains the most frequently used due to its cost-effectiveness and accessibility. As the authors point out, the inclusion of serum cystatin C in the eGFR estimation equations has proven to be more accurate than creatinine-based estimations. However, it remains to be explored whether this is true across different populations in the globe. Finally, prediction models to estimate the risk of undiagnosed CKD and the risk of progression of CKD in diabetics are being increasingly used in the USA. Even though they allow identifying those most likely to benefit from more aggressive interventions, they are population specific. Notably, albuminuria or impaired eGFR alone are associated with 10-year mortality of 18% and 24%, respectively, in people with diabetes. However, mortality is more than additive when both abnormalities are present, reaching nearly 50% [13, 14].

Glycemic monitoring and intensive glycemic control still play an important role in preventing diabetic kidney disease (DKD) in the early stages, although overall CKD progression and cardiovascular mortality may not be significantly reduced after the onset of DKD [15]. KDIGO guidelines recommend a target hemoglobin A1c (HbA1c) ranging from < 6.5 to < 8.0% unless the patient is at increased risk of hypoglycemia [12]. However, as Hassanein and Shafi pointed out in this collection, HbA1c is a less reliable marker for diabetes control due to the concomitant presence of anemia in people with DKD, particularly in those with advanced CKD [16]. Nevertheless, to date, it remains the gold standard method to monitor blood glucose control in this high-risk population. The authors present data showing that continuous glucose monitoring correlates with hemoglobin A1c and other indirect markers such as fructosamine, glycated albumin, and 1,5-anhydroglucitol in people with diabetes. But they also carry their own caveats. Proteinuria and hypoalbuminemia, common findings in CKD patients, can affect fructosamine and glycated albumin levels. Regarding 1,5-anhydroglucitol, it is highly dependent on tubular glucose reabsorption, which could be variable in patients with CKD. As one can realize, none of these markers are reliable in a population with DKD. Therefore, we suggest continuous glucose monitoring as an emerging tool to achieve glycemic control, but certainly, more studies are required to validate its efficacy in this population [16].

Despite the alarming statistics about the projected rates of increase in diabetes and the room for improvement in screening for DKD, among US adults with diabetes, all-cause mortality has declined by 20% [5]. This has been attributed to intensified, targeted therapies and lower cardiovascular disease (CVD). However, people with diabetes still have higher mortality than the rest of the population, suggesting the role of other risk factors. Previous literature has shown that estimated glucose disposal rates (eGDRs), a surrogate of insulin resistance, predict all-cause mortality in type 2 diabetes, independent of DKD. Therefore, in this collection, Penno and colleagues observed that the more insulin resistance, the higher the CVD risk. This relationship was independent of traditional CVD risk factors. Furthermore, eGDRs significantly affected mortality in people with non-DKD and normoalbuminuric DKD but not in those with albuminuric DKD. The authors suggest that mortality could be mediated by albuminuria in people with albuminuric DKD and not by insulin resistance [17].

Overall, patients with CKD are over 5 times more likely to die from cardiovascular causes than to progress to ESKD [9]. Cardiovascular morbidity also plays an essential role in people with diabetes. A major public health concern is the impact of coronary artery disease and stroke on disability and healthcare costs. In this collection, Kaze and colleagues looked at factors that increase the risk of stroke in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The authors reported that the higher the albuminuria (above 30 mg/g) and the lower the eGFR (below 60 mL/min/1.73 m2), the higher was the risk of stroke. Further, compared to no CKD, worsening CKD stages defined by the KDIGO criteria were associated with an increased risk of stroke [18].

As outlined by Hanouneh and colleagues in this collection, treatment can be targeted to the stage of DKD. Therefore, in the early stages, intensive glycemic control is critical, with metformin and sodium-glucose cotransporter 2 inhibitors (SGLT2is) being excellent candidates when the eGFR is above 30 ml/min per 1.73 m2 [19]. Glucagon-like peptide-1 receptor agonists are an additional tool to manage hyperglycemia in this high-risk population. Further, optimal blood pressure control should be achieved with a blood pressure goal below 130/80 mmHg, ideally with a renin–angiotensin–aldosterone system (RAAS) blockade agent [12, 20]. In addition, KDIGO guidelines suggest that individuals with DKD follow a diet low in sodium (< 2 g/day), maintain a protein intake of 0.8 g/kg/day for those not on dialysis, and exercise for at least 150 min per week as tolerated [12]. Fortunately, new treatment strategies have emerged to help curve the epidemic of DKD. SGLT2is were found to have significant cardiovascular benefits and to be renoprotective, independent of the blood-glucose-lowering effect [21,22,23]. Additionally, finerenone, a highly selective nonsteroidal mineralocorticoid receptor antagonist (MRA), produces potent anti-inflammatory and antifibrotic effects beyond RAAS blockade agents and significantly reduces proteinuria and DKD progression [24]. These therapeutic advances are summarized in Table 1.

Table 1 Recent chronic kidney disease randomized clinical trials of SGLT2is and selective nonsteroidal mineralocorticoid receptor antagonist

Importantly, a recent study highlighted in this series on DKD identified predictors of cardio-kidney complications and treatment failure in this high-risk population treated with SGLT2 inhibitors. Using a retrospective study design and analyzing data from a large administrative health claims database of a national insurer, Kovesdy and colleagues identified the following risk factors, such high baseline CVD risk profile, atrial fibrillation, peripheral arterial disease, and heart failure [25].


The diagnosis and treatment of DKD have recently seen significant progress in slowing down CKD progression, reducing cardiovascular events, and reducing mortality, but we still have a lot to learn; progress is still needed to further reduce the progression of DKD and hopefully one day, halt the disease process altogether. In the meantime, we need to intensify our DKD screening efforts, making sure that every patient with diabetes is appropriately tested for albuminuria and reduced GFR, particularly in LMICs. Optimal management of diabetes remains a cornerstone of the primary prevention of DKD, with intensive glycemic control starting early in the course of diabetes and implementing adequate blood pressure control and lifestyle modifications. There is also room for improvement in uptake of proven treatment with RAAS blockade agents, in addition to novel therapies such as SGLT2is and the highly selective nonsteroidal MRA finerenone [26]. All these interventions can only be successful if we have full patient engagement in the process.

Availability of data and materials

Not applicable.


  1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9. Diabetes Res Clin Pract. 2019;157:107843.

    Article  Google Scholar 

  2. Lin X, Xu Y, Pan X, Xu J, Ding Y, Sun X, et al. Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Sci Rep. 2020;10(1):14790.

    Article  CAS  Google Scholar 

  3. Ogurtsova K, Guariguata L, Barengo NC, Ruiz PL, Sacre JW, Karuranga S, et al. IDF diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res Clin Pract. 2022;183:109118.

    Article  Google Scholar 

  4. Lin J, Thompson TJ, Cheng YJ, Zhuo X, Zhang P, Gregg E, et al. Projection of the future diabetes burden in the United States through 2060. Popul Health Metr. 2018;16(1):9.

    Article  Google Scholar 

  5. Centers for Disease Control and Prevention. Chronic kidney disease in the United States. 2021. Page last Accessed: 7/4/2022

  6. McCullough KP, Morgenstern H, Saran R, Herman WH, Robinson BM. Projecting ESRD incidence and prevalence in the United States through 2030. J Am Soc Nephrol. 2019;30(1):127–35.

    Article  Google Scholar 

  7. Mills KT, Xu Y, Zhang W, Bundy JD, Chen CS, Kelly TN, et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int. 2015;88(5):950–7.

    Article  Google Scholar 

  8. National Kidney Foundation. Kidney Basics 2022 [Available from: Page last Accessed: 7/3/2022 .

  9. Wen CP, Chang CH, Tsai MK, Lee JH, Lu PJ, Tsai SP, et al. Diabetes with early kidney involvement may shorten life expectancy by 16 years. Kidney Int. 2017;92(2):388–96.

    Article  Google Scholar 

  10. Bellasi A, Di Lullo L, Di Iorio B. Chronic kidney disease: the silent epidemy. J Clin Med. 2019;8(11):17954.

    Article  Google Scholar 

  11. George C, Echouffo-Tcheugui JB, Jaar BG, Okpechi IG, Kengne AP. The need for screening, early diagnosis, and prediction of chronic kidney disease in people with diabetes in low-and-middle income countries-a review of the current literature. BMC Med. 2022;20(1):247 (In Press ed).

    Article  Google Scholar 

  12. Group KDIGOKDW. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(4S):S1–115.

    Google Scholar 

  13. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR, et al. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63(1):225–32.

    Article  Google Scholar 

  14. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302–8.

    Article  CAS  Google Scholar 

  15. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.

    Article  CAS  Google Scholar 

  16. Hassanein M, Shafi T. Assessment of glycemia in chronic kidney disease. BMC Med. 2022;20(1):117.

    Article  Google Scholar 

  17. Penno G, Solini A, Orsi E, Bonora E, Fondelli C, Trevisan R, et al. Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes: a prospective cohort study. BMC Med. 2021;19(1):66.

    Article  CAS  Google Scholar 

  18. Kaze AD, Jaar BG, Fonarow GC, Echouffo-Tcheugui JB. Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes. BMC Med. 2022;20:127.

    Article  CAS  Google Scholar 

  19. Hanouneh M, EchouffoTcheugui JB, Jaar BG. Recent advances in diabetic kidney disease. BMC Med. 2021;19(1):180.

    Article  Google Scholar 

  20. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.

    Article  CAS  Google Scholar 

  21. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46.

    Article  CAS  Google Scholar 

  22. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.

    Article  CAS  Google Scholar 

  23. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306.

    Article  CAS  Google Scholar 

  24. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–29.

    Article  CAS  Google Scholar 

  25. Kovesdy C, Schmedt N, Folkerts K, Bowrin K, Raad H, Batech M, et al. Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors. BMC Med. 2022;20(1):2.

    Article  CAS  Google Scholar 

  26. Tummalapalli SL, Powe NR, Keyhani S. Trends in quality of care for patients with CKD in the United States. Clin J Am Soc Nephrol. 2019;14(8):1142–50.

    Article  Google Scholar 

Download references


Not applicable.


Not applicable.

Author information

Authors and Affiliations



Drafting of manuscript or critical revision of manuscript (all authors; CEC, MH, BGJ). All authors (CEC, MH, BGJ) read and approved the final manuscript.

Corresponding author

Correspondence to Bernard G. Jaar.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

BGJ is a member of the Editorial Board of BMC Medicine. The other authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cervantes, C.E., Hanouneh, M. & Jaar, B.G. From screening to treatment: the new landscape of diabetic kidney disease. BMC Med 20, 329 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: