Prevalence and incidence of chronic kidney disease stage 3-5, rates and risk factors of acute myocardial infarction and referral rates to nephrologists - Data from the Kidney Disease Cohort (KidDiCo)

Background: Although renal impairment is a common, communicable disease that affects approximately 10% of the global population, reliable data on the prevalence and incidence of renal disease are sparse and highly heterogeneous. The Kidney Disease: Improving Global Outcomes guidelines have staged chronic kidney disease (CKD) according to glomerular filtration rates into stages 1–5. Stages 3–5 represent the loss of at least 50% of the glomerular filtration rate. CKD is a well-known independent risk factor for cardiovascular disease. Prevention of cardiovascular disease in CKD patients is, therefore, pivotal. However, studies investigating risk factors for incident of acute myocardial infarction in patients with CKD are sparse. To our knowledge, data on incidence rates of acute myocardial infarction after CKD debut are not available. Preventive measures should be in the hands of experts, but very few CKD patients are followed in a nephrology outpatient setting. The factors associated with nephrology outpatient care have not been investigated in detail. Data based on creatinine measurements paired with register data make research on kidney disease and cardiovascular disease feasible. Danish registers are known to be valid and comprehensive and are an invaluable source of data on these research topics. The Region of Southern Denmark is representative of most socioeconomic and healthcare aspects of Denmark.

The hypotheses were that CKD are a huge burden in the general population. That the risk of myocardial infarction is higher in these patients and very few patients with chronic kidney disease are followed by a nephrologist. In order to test these hypotheses, we created a representative cohort and answered the following questions:

1) What is the prevalence and incidence of CKD in Southern Denmark?
2) What is the incidence rate and what are the risk factors associated with incident acute myocardial infarction after CKD debut?
3) What is the rate of referral to nephrologists and what are the associated characteristics of those who are been followed?

Methods: The kidney disease cohort of the Region of Southern Denmark formed the base of the study. All individuals of at least 18 years of age who lived in the geographically defined region from 2006 to 2013, and who had at least one serum creatinine measurement, were included. The included individuals were linked with the Danish Civil Registration System, the National Patient Register, the Danish National Prescription Registry, the Population Register, the Education and Knowledge Register, the Employment Classification Module, and the Danish Register of Death. In addition to serum creatinine, urinary albumin/creatinine ratios and serum troponin observations were obtained from the laboratory databases. The glomerular filtration rate was calculated with the Chronic Kidney Disease Epidemiology Collaboration formula. Studies 1 and 2 were descriptive studies., Cox regression was used to calculate risk factors for acute myocardial infarction. We used logistic regression to calculate factors associated with visits to a nephrology outpatient clinic. All articles were written and studies performed in accordance with the STROBE guidelines. Stata 16 was used for the statistical analysis.

Results: Our cohort consists of individuals aged 18 years or older who had a minimum of one creatinine measurement in the Region of Southern Denmark between 2006 and 2013. The cohort consists of 684,287 individuals with a total of 8,650,805 creatinine measurements. Additionally, we analyzed 322,025 urinary albumin/creatinine ratios and completed 322,510 troponin observations. The coverage was at 78%. In the cohort 53% were women compared to 49% in the background population. The median age was slightly higher with 6.4 years in our cohort when compared to the background population. The coverage according to age increased steadily with age from 71% in the 18-29 year olds to 94% in the over 80 year olds. Albuminuria testing was sparse.

We identified patients with CKD stages 3–5. The prevalence per year of CKD was between 4.83% and 4.98%. The incidence rate was four out of 1,000 people per year. The proportion of individuals with CKD stages 3–5 in the entire population increased consistently by age. In the age group of 70–79 year olds, 33% had CKD stages 3–5 and, in the 80+ age group, the amount of CKD patients was just over 50%. The percentage of women in the CKD stages 3–5 group was higher. Socioeconomic data showed shorter educational levels and more individuals not active on the job market in the CKD group.

We concluded that the incident rate for AMI after CKD stage 3–5 debut was 2.5 /1,000 people/year. Risk factors included CKD stage 4 (hazard ratio (HR) = 1.402; 95% confidence interval (CI) = 1.08–1.81; P-value = 0.010) and stage 5 (HR = 1.491; 95% CI = 1.01–2.19; P-value = 0.042), hypertension (HR = 1.219; 95% CI = 1.03–1.45; P-value = 0.024) and age with increasing risk along age groups. Females (HR = 0.567; 95% CI = 0.50–0.64; P-value<0.001) and patients with medium educational level (HR = 0.75; 95% CI = 0.60–0.94; P-value = 0.013) had lower risk of incident AMI after CKD debut. When including CKD 3–5 with previous AMI, a previous AMI was the most prominent risk factor for an additional AMI after CKD debut (HR = 2.615; 95% CI = 2.241–3.05; P-value<0.001).

We estimated how many patients were followed by a nephrologist. Three percent of patients with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 were followed by a nephrologist. In our study, only 16% with an eGFR <30 ml/min/1.73m2 were referred to a nephrology outpatient clinic. Patients with terminal renal insufficiency at incidence, males, younger patients, patients with hypertension and/or diabetes, patients living in a municipality with a nephrology outpatient clinic and those with longer educational levels had a higher probability of being followed by a nephrologist.

Clinical perspective: The kidney disease cohort of Southern Denmark has been demonstrated to be a valid research tool for present studies on chronic and acute kidney disease, which indicates its value for future studies. Our study did not find an increase in prevalence of CKD stages 3–5. However, the increase of the older population and the fact, that more than 50% of the 80 years and older age group have CKD in our cohort points toward an increase of patients with CKD in the future. The incident rate of AMI after CKD stages 3–5 debut is high in comparison to the general population. In patients with incident AMI after CKD stages 3–5 debut prophylactic efforts should focus especially, however not exclusively, on preservation of renal function. The low number of patients with CKD followed by a nephrologist should prompt rethinking of nephrology guideline distribution and implementation. A strategy to integrate care for patients with CKD together with general practitioners should be established.

Conclusion: Our findings are based on a representative cohort with a thorough coverage. CKD is a common disease in Southern Denmark, especially among older adults.

There is a need to improve screening for CKD in order to prevent CKD stages 3–5, to slow progression of CKD and to avoid presentation of CKD patients with acute need of dialysis. This is especially true for 18-29 year olds. Albuminuria screening was sparse in our cohort and should be expandeded. Further studies are, therefore, necessary to improve screening strategies for CKD in order to prevent CKD stages 3–5 and cardiovascular disease. In older individuals the aim should be to increase awareness of having the diagnosis of CKD among patients and doctors alike. Our study suggests an incidence rate of AMI after CKD stages 3–5 debut of 2.5/1,000 person/year. Risk factors for AMI incident CKD stages 3–5 patients include CKD stages 4–5 as risk factor. Other risk factors include sex, age, educational level and hypertension.

Only few CKD patient are followed by a nephrologist. Guidelines for CKD patients should be distributed to general practitioners and nephrologists alike. The main aim should be an improvement of the integration of services in treatment of CKD patients between nephrologists and general practitioners.