The Association Between Serum Urea Nitrogen to Creatinine Ratio and the Survival in Patients With DKD
Conditions: Diabetic Kidney Disease
Sponsor: Guangdong Provincial People's Hospital

Project Name: The association between serum urea nitrogen to creatinine ratio and  
the survival in patients with DKD.  
No.: v1.2 version Date: June 1, 2020  
Study unit: Guangdong Provincial People's Hospital  
Sponsor: Guangdong Provincial People's Hospital  
 
Background  
In 2013, the prevalence of adult diabetes in China was as high as 10.9%, with the  
number of patients exceeding 100 million. Diabetic kidney disease (DKD), as one of  
the main microvascular complications of diabetes, occurs in 20% ~ 40% of diabetes.  
Furthermore, Diabetes-related chronic kidney disease, the leading cause of chronic  
kidney disease, has become a serious public health problem and brought huge  
economic burden. How to realize the early prevention and treatment of DKD and  
improve its clinical outcomes raises our concerns.  
Previous studies have shown that a low-protein diet (LPD) can retard renal 
function decline in patients with CKD mainly through the improvement of glomerular 
hyperfiltration/hyperfusion and tubule-interstitial damage, inflammation and fibrosis. 
The lower the baseline dietary protein intake (DPI), the slower the progression toward 
ESRD. Each 0.1 g/kg per day higher DPI at baseline was associated with a loss of 
kidney function that was faster by approximately 0.064 ml/min per year. In 2020, 
standards of medical care in diabetes of American diabetes Association (ADA) 
recommended for people with nondialysisdependent CKD to maintain DPI 
approximately 0.8 g/kg body weight per day. Previous studies provided some methods 
for dietary assessment such as 24-hour dietary recalls, food diaries and food 
frequency questionnaires, which exist limitations including:(1)reliance on patient’s 
memory, compliance and communication ability; (2)reliance on interviewer’s skills, 
comprehensiveness and prompts;(3)lack of ability to represent a longer period. 
Maroni formula, which tests 24-hour urine urea nitrogen, is a relatively objective and 
common method to evaluate protein intake, but can’t be generalized due to its 
complexity and uncertainty. Joel D et.al found that serum urea nitrogen to creatinine 
ratio (sUCR) correlated closely with protein intake and knowledge of its relation to 
protein intake could be used to determine the degree of protein restriction. In our 
previous study, the mathematical model between sUCR and DPI was preliminarily 
established after modeling and verification, and has obtained the patent.  
Protein restriction is a basic but important life intervention to improve the  
prognosis of DKD patients. How to calculate DPI in a simple and effective way to  
overcome the complexities and errors of existing methods attracts our attentions. In  
this study, we hypothesize sUCR can be applied to evaluate of protein intake during  
the follow-up periods and predict the survival in patients with DKD.  
 
Object  
To evaluate the prognostic value of sUCR in the progression of DKD. 
 
 

Methods  
This study is a multicenter, retrospective cohort study. We select patients  
diagnosed with DKD since January 2012. The present study is performed according to  
the principles of the Declaration of Helsinki and has been approved by the Ethics  
Committee of Guangdong Provincial People's Hospital.  
Study population  
We screen DKD patients aged 18-70 years with CKD stages 1-4. DKD was  
defined as those diagnosed by pathological biopsy, or those with eGFR <60 ml/min  
per 1.73 m2 , or presence of clinically detectable albuminuria over 3 months which is  
caused by diabetes. Patients who undergo infection, severe liver disease, malignant  
tumor, acute heart failure, gastrointestinal hemorrhage, pregnancy are excluded.  
Data collection  
At baseline and every medical visit, therapeutic relevant information will be  
collected. Data mainly include demographic characteristics(age, gender, place of  
residence, marriage status, education degree), lifestyle(smoking, drinking, exercise),  
clinical characteristics(body mass index, blood pressure, duration , history of CVD,  
complications, nutrition situation), laboratory indexes(serum creatinine, blood urea  
nitrogen, glycosylated hemoglobin, urinary albumin to creatinine ratio, 24-hour  
urinary albumin, 24-hour urine urea nitrogen, etc.). History of cardiovascular disease  
including coronary artery disease, congestive heart failure, stroke, and peripheral  
vascular disease were ascertained by self-report or doctor's diagnosis.  
Outcomes  
Patients are followed for survival until they reach the end of the study, whichever  
happen first, or are censored because they lose contact or the follow-up interval is less  
than one month. The outcomes are all-cause death, a composite of end-stage kidney  
disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute  
per 1.73 m2 , or increasing by 50% of the serum creatinine level from baseline.  
Evaluated GFR was calculated using Chronic Kidney Disease Epidemiology  
Collaboration (CKD-EPI) formula.  
Statistics  
Data are presented as mean ± SD for continuous variables and as a  
number(percentage) for categorical variables. According to mean sUCR and ΔsUCR  
(fluctuation of sUCR over time, meaning monthly rate of change), patients are divided  
into four groups. The relationship between baseline characteristics among the four  
groups was compared by using one-way analysis of variance test, Kruskal-Wallis test  
or Chi-squared test where appropriate. Survival rates are estimated using Kaplan 
Meier analysis, and the significance of differences are analyzed using the log-rank  
test. Cox proportional hazard regression analysis is used to assess the association  
between the clinical outcomes and mean sUCR and ΔsUCR. In multivariate analysis,  
we enter variables using a P value of <0.10 as the selection criterion or considered  
clinically significant. Hazard ratios (HRs) are presented with 95% CIs. All statistical  
analysis was performed with the use of SPSS (version 19.0, SPSS, Chicago, USA)  
and Prism 7.0 (GraphPad Software, San Diego, CA, USA). A two-tailed P value 
<0.05 was considered to be statistically significant.