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Prediabetes and Risk for CKD 

Mar 14, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Sandra Zaki, PharmD Candidate, Florida A&M University

People with prediabetes and diabetes are at a higher risk of developing chronic kidney disease (CKD) as well as chronic cardiovascular diseases. 

Prediabetes is a common condition that affects about a third of the entire adult population of the United States. People with prediabetes have an increased risk of getting diabetes, and studies have shown that about 10% of them develop diabetes every year. Prediabetes has come to be known as the middle stage between normal blood sugar levels and diabetes, with many people camping at this stage for years on end without ever progressing to the next stage. Such patients may develop chronic kidney disease (CKD), which features kidney alterations and dysfunction. Acute forms of CKD manifest as an end-stage renal disease (ESRD). The United States of America carries a 14% CKD prevalence. Patients with CKD and diabetes comorbidity have been found to have a higher chance of developing ESRD. This study was focused on establishing a relationship between prediabetes and the progression of CKD to ESRD. 


The study recruited participants aged 21 and 74 years to participate. The sample group had to be predisposed to one or more of several risk factors for CKD. An eGFR of between 20-70 ml/min/1.73m2 was required. HIV/AIDS, liver cirrhosis, polycystic kidney disease, multiple myeloma, and kidney cancer were removed from the sample group. Participants with immunosuppression and those who had undergone chemotherapy recently were also excluded from the study. Pregnant and on dialysis participants were also excluded. Two hundred thirty-eight patients whose glycated hemoglobin was missing at baseline were automatically removed. 

The expected result of the study was to identify the development of ESRD, to determine the development of congenital heart failure or stroke and any other disease that causes death. The follow-up went on until March of 2013. Kruskal-Wallis and ANOVA tests were used to compare the baseline characteristics of the study group participants, respectively, for non-normal and standard variables. Adjusted and unadjusted cox regression model was used to analyze the association between prediabetes or diabetes with the progression of CKD, cardiovascular outcomes, and other mortal diseases. P values of <0.05 were considered statistically significant.  

Three thousand seven hundred one participants made it to the final sample batch and were included in the study. For all of them, the average glycated hemoglobin was 5.3% for healthy people (945), 5.9% for people with prediabetes (847), and was 7.6% for people with actual diabetes (1909). Sample members with prediabetes and diabetes were mainly black, with congestive heart issues and hypertension. The people with diabetes would have higher chances of having reduced eGFR with high blood pressure with occasional proteinuria. People with prediabetes were found to be 85% more likely to develop cardiovascular complications (P<0.001). 

Participants with CKD and prediabetes comorbidity did not show signs of eGFR reduction or development of ESRD. They, however, had a higher risk of developing proteinuria, cardiovascular diseases, and all-cause mortality. Adjusting for glycated hemoglobin did not change the form of association but only strengthened it. When adjusted for fasting glucose, there was a change in the association between the patterns of association. Participants with a higher baseline for eGFR appeared to have their patterns of association restricted. An excessive amount of glucose in the blood has been known to cause reactive oxygen species to be produced at a higher rate. This promotes the build-up of complex glycated products and also activates the cell signaling molecules found inside the cell. Such effects cause patients who have diabetes to undergo hyperfiltration during the process of ultrafiltration at the glomerulus. It also thickens the base of the glomerulus, altering the ultrafiltration process. It brings about glomerular sclerosis, which can progress to CKD and contribute to albuminuria. 

Further study is still warranted. The current study might not have been very robust in checking the minute distinctions between normoglycemia and prediabetes. Also, new research is needed to determine how the risk for patients with CKD can be minimized or removed in its entirety. 

Practice Pearls: 

  • Prediabetes is a stage measured with an A1c between 5.7 % and 6.4%, between normoglycemia and diabetes. 
  • Prediabetes and diabetes are risk factors for the development of ESRD and cardiovascular diseases. 
  • Prediabetes with CKD comorbidity does not necessarily lead to ESRD and low eGFR. 


Neves J.S., Simon Correa, S., Baptista, R. B., Vieira M. B., Waikar S. S., McCausland, F. R. (2020). Association of prediabetes with CKD progression and adverse an analysis of the CRIC cardiovascular outcomes: study. https://academic.oup.com/jcem/advance-articleabstract/doi/10.1210/clinem/dgaa017/5707316 


Sandra ZakiPharmD Candidate, Florida A&M University