COVID-19 in patients with advanced stages of diabetic kidney disease: new onset renal replacement therapy as one of the predictors of adverse outcome

Background: patients with Diabetes Mellitus 2 (DM2) and advanced stages of Diabetic Kidney Disease (DKD) are at high risk for the lethal outcome of COVID-19. The causes of high mortality and the prognostic significance of the new onset of renal replacement therapy (hemodialysis de novo, HD de novo) among these patients are still points of debate. Aim: the identification of risk factors (RF) of lethal outcome in patients with DKD 4-5D stages and evaluation of the prognostic value of HD de novo in patients not receiving HD at the time of hospital admission. Methods: the patients with COVID-19 and advanced stages of DKD were included in a retrospective observational study from 04.01. to 10.30.2020. The endpoints were the outcome of hospitalization (discharge/death) and HD de novo initiation during the inpatient course. Several demographic, DM2, DKD, and COVID-19-associated signs and laboratory parameters were analyzed as independent variables. The subgroup of patients with HD de novo was selected from the general cohort. Results: 120 patients with DKD 4-5D stages were included, with a mean age of 69±10 y, females - 52%. Initially, the observation cohort was divided into subgroups: DKD 4-5 and DKD 5D on maintenance hemodialysis (MHD). The mortality among patients with DKD 4-5 was comparable with the patients on MHD (38,2% vs 38,5%, р=0,975). The independent predictors of lethal outcome in group DKD 4-5 were: age ≥65 y (OR 12,30; 95% CI 1,40-33,5; р=0,009), initial prandial glycemia ≥10 mmol/l (OR 14,5; 95% CI 3,7-55,4; р<0,001), albuminemia at admission ≤35 g/l (OR 5,17; 95% CI 1,52-17,50; р=0,012), Charlson comorbidity index (CCI) ≥10 (OR 6,69; 95% CI 1,95-23,00; р=0,002), News2 >4 at admission (OR 7,58; 95% CI 2,18-26,37; р=0,001), lung damage CT 3-4 at admission (OR 3,39; 95% CI 1,09-10,58; р=0,031). In subgroup DKD 5D the independent predictors of lethal outcome were prandial glycemia at admission ≥10 mmol/l (OR 28,5; 95% CI 7,1-33,5; р<0,001), lung damage at admission CT 3-4 (OR 8,35; 95% CI 2,64-26,40; р<0,001), CCI ≥10 (OR 6,00; 95% CI 1,62-22,16; р=0,006). To determine the risk of lethal outcome predictive models were created using identified risk factors and variables. The predictive value for DKD 4-5 group was 93%, and for DKD 5D was 88%. The assessment of the overall predictive value of these models was carried out using ROC analysis. The mortality among patients with DKD 4-5 without HD de novo was 21,6% vs 72,2% in patients with initiated HD de novo (р<0,001). The independent predictors of HD de novo during the inpatient course were: prandial glycemia at admission ≥10 mmol/l (OR 3,38; 95% CI 1,04-10,98; р=0,050), albuminemia at admission ≤35 г/л (OR 3,41; 95% CI 1,00-11,55; р=0,050), News2 >4 at admission (OR 5,60; 95% CI 1,67-19,47; р=0,006), eGFR ≤20 ml/min/1,73 m2 at admission (OR 4,24; 95% CI 1,29-13,99; р=0,020). HD de novo was identified as an independent predictor of adverse outcomes (OR 9,42; 95% CI 2,58-34,4; р=0,001). The analysis of cumulative survival demonstrated comparable results in DKD 4-5 without HD de novo group and DKD 5D group. The cumulative 55-day survival in the subgroup with HD de novo was only 10%. Conclusion: the need to start HD de novo is one of the most powerful predictors of adverse outcomes of COVID-19 in patients with advanced DKD. The comparable mortality rate in DKD 4-5 and DKD 5D groups is due to extremely high mortality in the subgroup with HD de novo. The strict control and correction of HD de novo risk factors could turn them into modifiable ones and thus improve the survival prognosis of patients with advanced stages of DKD.

COVID-19, факторы риска, сахарный диабет, хроническая болезнь почек, инициальный гемодиализ, гипергликемия, гипоальбуминемия, COVID-19, risk factors, Diabetes Mellitus, Diabetic Kidney Disease, Chronic Kidney Disease, Hemodialysis de novo, Hyperglycemia, Hypoalbuminemia

1. John Hopkins University in medicine coronavirus resource Center. Available at: https://coronavirus.jhu.edu. Accessed on March 1, 2022

2. Singh A.K., Gillies C.L., Singh R. et al. Prevalence of co-morbidities and their association with mortality in patients with COVID-19: A systematic review and meta-analysis. Diabetes Obes Metab. 2020. 22(10):1915-1924. doi: 10.1111/dom.14124

3. Williamson E.J., Walker A.J., Bhaskaran K. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020. 584(7821):430-436. doi: 10.1038/s41586-020-2521-4

4. Зелтынь-Абрамов Е.М., Лысенко М.А., Фролова Н.Ф. и соавт. Факторы риска неблагоприятного прогноза COVID-19 и опыт применения тоцилизумаба у пациентов на программном гемодиализе в исходе диабетической болезни почек. Сахарный диабет. 2021. 24(1):7-31. doi.org/10.14341/DM12688

5. Шестакова М.В., Мокрышева Н.Г., Дедов И.И. Сахарный диабет в условиях вирусной пандемии COVID-19: особенности течения и лечения. Сахарный диабет. 2020. 23(2):132-139. doi.org/10.14341/DM12418

6. Orioli L., Hermans M.P., Thissen J.P. et al. COVID-19 in diabetic patients: Related risks and specifics of management. Ann Endocrinol (Paris). 2020. 81(2-3):101-109. doi: 10.1016/j.ando.2020.05.001

7. Scheen A.J., Marre M., Thivolet C. Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports. Diabetes Metab. 2020. 6(4):265-271. doi: 10.1016/j.diabet.2020.05.008

8. Apicella M., Campopiano M.C., Mantuano M. et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes [published correction appears in Lancet Diabetes Endocrinol. 2020 Oct;8(10):e5] [published correction appears in Lancet Diabetes Endocrinol. 2020 Nov;8(11):e6]. Lancet Diabetes Endocrinol. 2020. 8(9):782-792. doi: 10.1016/S2213-8587(20)30238-2

9. Smati S., Tramunt B., Wargny M. et al. COVID-19 and Diabetes Outcomes: Rationale for and Updates from the CORONADO Study. Curr Diab Rep. 2022. 22(2):53-63. doi: 10.1007/s11892-022-01452-5

10. ERA-EDTA Council; ERACODA Working Group. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA. Nephrol Dial Transplant. 2021. 36(1):87-94. doi: 10.1093/ndt/gfaa314

11. Appelman B., Oppelaar J.J., Broeders L. et al. Mortality and readmission rates among hospitalized COVID-19 patients with varying stages of chronic kidney disease: a multicenter retrospective cohort. Sci Rep. 2022. 12(1):2258. Published 2022 Feb 10. doi: 10.1038/s41598-022-06276-7

12. Шестакова М.В., Викулова О.К., Исаков М.А., Дедов И.И. Сахарный диабет и COVID-19: анализ клинических исходов по данным регистра сахарного диабета российской федерации. Проблемы Эндокринологии. 2020. 66(1):35-46. https://doi.org/10.14341/probl12458

13. Jdiaa S.S., Mansour R., El Alayli A. et al. COVID-19 and chronic kidney disease: an updated overview of reviews. J Nephrol. 2022. 35(1):69-85. doi: 10.1007/s40620-021-01206-8

14. Зелтынь-Абрамов Е.М., Белавина Н.И., Фролова Н.Ф. и соавт. Факторы риска неблагоприятного прогноза у пациентов на программном гемодиализе с Covid-19. Акцент на сердечно-сосудистую коморбидность. Опыт одного центра. Нефрология и диализ. 2020. 22(Спецвыпуск):9-20. doi: 10.28996/2618-9801-2020-Special_Issue-9-20

15. Зубкин М.Л., Ким И.Г., Фролова Н.Ф. и соавт. Новая коронавирусная инфекция и гемодиализ: течение и предикторы неблагоприятного исхода. Нефрология и диализ. 2021. 23(4).489-498. doi: 10.28996/2618-9801-2021-4-489-498

16. Tang H., Tu C., Xiong F. et al. Risk factors for the mortality of hemodialysis patients with COVID-19: A multicenter study from the overall hemodialysis population in Wuhan. Semin Dial. 2022. 35(1):71-80. doi: 10.1111/sdi.12995

17. Jager K.J., Kramer A., Chesnaye N.C. et al. Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe. Kidney Int. 2020. 98(6):1540-1548. doi: 10.1016/j.kint.2020.09.006

18. Singh J., Malik P., Patel N. et al. Kidney disease and COVID-19 disease severity-systematic review and meta-analysis. Clin Exp Med. 2022. 22(1):125-135. doi: 10.1007/s10238-021-00715-x

19. Alicic R.Z., Rooney M.T., Tuttle K.R. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017. 12(12):2032-2045. doi: 10.2215/CJN.11491116

20. Saeedi P., Petersohn I., Salpea P. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019. 157:107843. doi: 10.1016/j.diabres.2019.107843

21. Jager K.J., Kovesdy C., Langham R. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019. 34(11):1803-1805. doi: 10.1093/ndt/gfz174

22. Дедов И.И., Шестакова М.В., Викулова О.К. и соавт. Эпидемиологические характеристики сахарного диабета в Российской Федерации: клинико-статистический анализ по данным регистра сахарного диабета на 01.01.2021. Сахарный диабет. 2021. 24(3):204-221. https://doi.org/10.14341/DM12759

23. Андрусев А.М., Томилина Н.А., Перегудова Н.Г., Шинкарев М.Б. Заместительная почечная терапия хронической болезни почек 5 стадии в Российской Федерации 2015-2019 гг. Отчет по данным Общероссийского Регистра заместительной почечной терапии Российского диализного общества. Нефрология и диализ. 2021. 23(3):255-329. doi: 10.28996/2618-9801-2021-3-255-329

24. Jensen M.D., Ryan D.H., Apovian C.M. et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society [published correction appears in Circulation. 2014 Jun 24;129(25 Suppl 2):S139-40]. Circulation. 2014. 129(25 Suppl 2):S102-S138. doi: 10.1161/01.cir.0000437739.71477.ee

25. Hemmelgarn B.R., Manns B.J., Quan H., Ghali W.A. Adapting the Charlson Comorbidity Index for use in patients with ESRD. Am J Kidney Dis. 2003. 42(1):125-132. doi: 10.1016/s0272-6386(03)00415-3.

26. Stevens P.E., Levin A. Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013. 158(11):825-830. doi: 10.7326/0003-4819-158-11 201306040-00007

27. Временные методические рекомендации: профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19), 14-я версия от 27.12.21 (static-0.minzdrav.gov.ru). - Минздрав России, 2021.

28. Royal College of Physicians. National Early Warning Score (NEWS) 2: standardising the assessment of acute-illness severity in the NHS. Updated report of a working party 2017 (2021). https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2

29. Huang I., Lim M.A., Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020. 14(4):395-403. doi: 10.1016/j.dsx.2020.04.018.

30. Lim S., Bae J.H., Kwon H.S., Nauck M.A. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol. 2021. 17(1):11-30. doi: 10.1038/s41574-020-00435-4

31. Kumar A., Arora A., Sharma P. et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr. 2020. 14(4):535-545. doi: 10.1016/j.dsx.2020.04.044

32. Маркова Т.Н., Пономарева А.А., Самсонова И.В. соавт. Факторы риска летального исхода у больных сахарным диабетом 2 типа и новой коронавирусной инфекцией. Эндокринология: новости, мнения, обучение. 2022. 11(1):8-16. doi: https://doi.org/10.33029/2304-9529-2022-11-1-8-16

33. Barmanray R.D., Cheuk N., Fourlanos S. In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): a systematic review and meta-analysis of observational studies prior to COVID-19. BMJ Open Diabetes Res Care. 2022. 10(4):e002880. doi: 10.1136/bmjdrc-2022-002880

34. Mehta P.B., Gosmanov A.R. Inpatient glycemic control and community-acquired pneumonia outcomes in the pre-COVID-19 era: reviewing the evidence to pave the road for future studies. BMJ Open Diabetes Res Care. 2022. 10(4):e003011. doi: 10.1136/bmjdrc-2022-003011

35. McAlister F.A., Majumdar S.R., Blitz S. et al. The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care. 2005. 28(4):810-815. doi: 10.2337/diacare.28.4.810

36. Hirata Y., Tomioka H., Sekiya R. et al. Association of hyperglycemia on admission and during hospitalization with mortality in diabetic patients admitted for pneumonia. Intern Med. 2013. 52(21):2431-2438. doi: 10.2169/internalmedicine.52.9594

37. Akirov A., Shimon I. The prognostic significance of admission blood glucose levels in elderly patients with pneumonia (GAP Study). J Diabetes Complications. 2016. 30(5):845-851. doi: 10.1016/j.jdiacomp.2016.03.021

38. Yang J.K., Feng Y., Yuan MY. et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006. 23(6):623-628. doi: 10.1111/j.1464-5491.2006.01861.x

39. Vargas-Rodriguez J.R., Valdés Aguayo J.J., Garza-Veloz I. et al. Sustained Hyperglycemia and Its Relationship with the Outcome of Hospitalized Patients with Severe COVID-19: Potential Role of ACE2 Upregulation. J Pers Med. 2022. 12(5):805. Published 2022 May 17. doi: 10.3390/jpm12050805

40. Cai Y., Shi S., Yang F. et al. Fasting blood glucose level is a predictor of mortality in patients with COVID-19 independent of diabetes history. Diabetes Res Clin Pract. 2020. 169:108437. doi: 10.1016/j.diabres.2020.108437

41. Martínez-Murillo C., Ramos Peñafiel C., Basurto L. et al. COVID-19 in a country with a very high prevalence of diabetes: The impact of admission hyperglycaemia on mortality. Endocrinol Diabetes Metab. 2021. 4(3):e00279. Published 2021 Jun 14. doi: 10.1002/edm2.279

42. Al-Kuraishy H.M., Al-Gareeb A.I., Alblihed M. COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus. Front Cardiovasc Med. 2021. 8:644095. Published 2021 May 20. doi: 10.3389/fcvm.2021.644095

43. Liu S.P., Zhang Q., Wang W. et al. Hyperglycemia is a strong predictor of poor prognosis in COVID-19. Diabetes Res Clin Pract. 2020. 167:108338. doi: 10.1016/j.diabres.2020.108338

44. Wang S., Ma P., Zhang S. et al. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study. Diabetologia. 2020. 63(10):2102-2111. doi: 10.1007/s00125-020-05209-1.

45. Soetedjo N.N.M., Iryaningrum M.R., Damara F.A. et al. Prognostic properties of hypoalbuminemia in COVID-19 patients: A systematic review and diagnostic meta-analysis. Clin Nutr ESPEN. 2021. 45:120-126. doi:10.1016/j.clnesp.2021.07.003

46. Paliogiannis P., Mangoni A.A., Cangemi M. et al. Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis. Clin Exp Med. 2021. 21(3):343-354. doi: 10.1007/s10238-021-00686-z

47. Haller C. Hypoalbuminemia in renal failure: pathogenesis and therapeutic considerations. Kidney Blood Press Res. 2005. 28(5-6):307-310. doi: 10.1159/000090185

48. de Castro L.L., de Carvalho e Martins Mdo C., Garcez A.M. et al. Hypoalbuminemia and oxidative stress in patients on renal hemodialysis program. Nutr Hosp. 2014. 30(4):952-959. Published 2014 Oct 1. doi: 10.3305/nh.2014.30.4.7667

49. Pranata R., Supriyadi R., Huang I. et al. The Association Between Chronic Kidney Disease and New Onset Renal Replacement Therapy on the Outcome of COVID-19 Patients: A Meta-analysis. Clin Med Insights Circ Respir Pulm Med. 2020. 14:1179548420959165. doi: 10.1177/1179548420959165

50. Passoni R., Lordani T.V.A., Peres L.A.B., Carvalho A.R.D.S. Occurrence of acute kidney injury in adult patients hospitalized with COVID-19: A systematic review and meta-analysis. Nefrologia. 2022. 42(4):404-414. doi: 10.1016/j.nefro.2021.09.002.

51. Esposito P., Russo E., Picciotto D. et al. Changes of Acute Kidney Injury Epidemiology during the COVID-19 Pandemic: A Retrospective Cohort Study. J Clin Med. 2022. 11(12):3349. doi: 10.3390/jcm11123349

52. Hirsch J.S., Ng J.H., Ross D.W. et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020. 98(1):209-218. doi: 10.1016/j.kint.2020.05.006

53. Cau A., Cheng M.P., Lee T. et al. Acute Kidney Injury and Renal Replacement Therapy in COVID-19 Versus Other Respiratory Viruses: A Systematic Review and Meta-Analysis. Can J Kidney Health Dis. 2021. 8:20543581211052185. doi: 10.1177/20543581211052185.