CARDIOVASCULAR AND NEPHROLOGICAL RISK IN PATIENTS WITH CHRONIC KIDNEY DISEASE IN AMBULATORY CARE

Cardiovascular and nephrological risk in patients with chronic kidney disease in ambulatory care. Kuryata O., Semenov V. Patients with chronic kidney disease (CKD) have higher than in general population all-cause and cardiovascular mortality. Arterial hypertension (HTN) is a powerful potentially modifiable risk factor that affects the majority of patients with chronic kidney disease and one of the main causes of end stage renal disease worldwide. Existing tools for assessment of risk of CKD progression do not take into account arterial hypertension. The aim – to investigate the association between cardiovascular and nephrological risk factors in patients with CKD in ambulatory practice. The study was carried out in the Center of Nephrology Care in Mechnikov Dnipropetrovsk Regional Hospital, Dnipro, Ukraine. 278 patients (114 males and 164 women, aged 41 [31;61] years) with CKD (stages 1-3) who were followed-up in ambulatory care, but required diagnosis or treatment revision were enrolled to the study. All patients were examined and followed-up according to local and European standards. Females slightly prevailed in our study, gender distribution varied insufficiently in groups by CKD progression risk. Elevation of risk of CKD progression was accompanied by rise of prevalence of diabetes mellitus, left ventricle hypertrophy, proteinuria and HTN. Risk of CKD progression correlated with age, systolic and diastolic blood pressure, erythrocyte sedimentation rate, total cholesterol, glomerular filtration rate, albumin excretion rate, duration of HTN and body mass index. Rise of cardiovascular risk was accompanied by rise of proportion of patients with high risk of CKD progression. Increase in risk of CKD progression is associated with rise of burden of cardiovascular risk factors. HTN and blood pressure values should be accounted for assessment of risk of CKD progression. Реферат. Серцево-судинний та нефрологічний ризик у пацієнтів з хронічною хворобою нирок в амбулаторній практиці. Курята О., Семенов В. Пацієнти з хронічною хворобою нирок (ХХН) мають вищу, ніж у загальній популяції, загальну та серцево-судинну смертність. Артеріальна гіпертензія (АГ) є потужним фактором ризику, що піддається модифікації, та зустрічається в переважної більшості пацієнтів з ХХН. АГ є однією з основних причин термінальної ХХН. Наявні інструменти для оцінки ризику прогресії ХХН не враховують АГ. Мета – дослідити асоціацію між кардіоваскулярними та нефрологічними факторами ризику в пацієнтів з ХХН в амбулаторній практиці. Дослідження було проведене в Центрі надання нефрологічної допомоги в КЗ “Дніпропетровська обласна клінічна лікарня ім. І.І. Мечникова”, Дніпро, Україна. 278 пацієнтів (114 чоловіків і 164 жінки, віком 41 [31;61] рік) з ХХН (стадії 1-3), що лікувалися амбулаторно, але потребували перегляду діагнозу або лікування в умовах стаціонару, були включені в дослідження. Діагностика та лікування ХХН у всіх пацієнтів проводилася згідно з локальними та Європейськими протоколами. Серед пацієнтів у дослідженні переважали жінки, але гендерний розподіл у групах за ризиком прогресії ХХН не змінювався. Зростання ризику прогресування ХХН супроводжувалося збільшенням частки пацієнтів з цукровим діабетом, гіпертрофією лівого шлуночка та АГ. Ризик прогресування ХХН корелював з віком, систолічним та діастолічним артеріальним тиском, швидкістю зсідання еритроцитів, загальним холестерином, швидкістю клубочкової фільтрації, добовою протеїнурією, тривалістю АГ та індексом маси тіла. Зростання серцевосудинного ризику супроводжувалося збільшенням частки пацієнтів з високи ризиком прогресії ХХН. Збільшення ризику прогресії ХХН асоціюється зі зростанням поширеності факторів ризику серцево-судинних ускладнень. АГ та показники артеріального тиску повинні враховуватися при оцінці ризику прогресії ХХН.


MATERIALS AND METHODS OF RESEARCH
The study was carried out in the Center of Nephrology Care in Mechnikov Dnipropetrovsk Regional Hospital, Dnipro, Ukraine. Our aim was to select patients with CKD who were treated ambulatory by primary care physicians (PCPs), but required nephrologist's consultation. From 4540 patients, who were referred to the Center by PCPs in 2017 we selected 278 patients for the analysis who were followed-up in ambulatory care, but required diagnosis or treatment revision. Independent experts provided patient selection in order to exclude patients that required multidisciplinary approach or patients with stable course of CKD. Exclusion criteria: type 1 diabetes mellitus (DM), polycystic renal disease, hereditary renal diseases, operations on kidneys or urinary tract, patients with GFR <30 ml/min. All patients were examined and followed-up according to local and European standards and gave informed written consent on data collection. The study was approved by the Ethics Committee at the Mechnikov Dnipropetrovsk Regional Hospital, Dnipro, Ukraine.
Diagnosis of HTN was based on previous medical records or systolic BP (SBP)≥140 mmHg or diastolic BP≥90 mmHg revealed during examination. Grade  Statistical analysis Type of data distribution was assessed using Shapiro-Wilk test. As more than 50% of the data were distributed non-parametrically, values were presented as median and interquartile range. Categorical data are presented as n (valid %) to avoid confounding true proportion by missing data. Mann-Whitney and Kruskal-Wallis test were used to compare continuous data, Chi-square test was used to compare categorical data. For correlation analysis we used Spearman's correlation coefficient (ρ). The effect size measurement of linear trend between several groups was performed using Kendall's correlation coefficient (τ). In most cases critical value of p was <0.05. In cases of multiple comparisons we used Bonferroni correction and critical value of p equaled to 0.05/(number of possible comparisons). Data processing and analysis were performed using Libre Office and R [9,11,17].

RESULTS AND DISCUSSION
Females were more prevalent in our study, gender distribution varied insufficiently in groups by CKD progression risk (

На умовах ліцензії CC BY 4.0
There was a steady decline in proportion of low risk patients and rise of prevalence of high risk patients with rise of grade of HTN (Fig. 1). Low-to-moderate risk patients showed higher proportion of low risk patients of CKD progression, than high-tovery-high risk patients.

Fig. 1. Distribution of risk of CKD progression in patients subdivided by grade of HTN and cardiovascular risk
The majority of normotensive patients were related to low-risk patients -55.5% (Fig. 1). While the greatest proportion of patients with HTN also had low risk of CKD progression (Table 1), they were markedly more prevalent among high-risk patients.
In patients with HTN risk of CKD progression was significantly associated with age, ePWV, ESR, total cholesterol, GFR and AER, while in patients without HTN it was connected only to ESR and AER (Fig. 2).
Our findings support strong interconnection of HTN and risk of CKD progression. Increase of nephrological risk was accompanied by deterioration of the majority of laboratory and instrumental parameters and rise of comorbidities (Table 1). This trend was more expressed in patients with low and moderately increased risk of CKD progression, that may be explained by younger age of low-risk patients. Despite age parity of patients with moderately increased, high and very-high risk of CKD progression (p=0.61), there were steady rises of systolic BP, diastolic BP and ePWV. Control of HTN in patients under our study was poor (<35%), being the worst for patients with high risk of CKD 19/ Том XXIV / 3 progression and ePWV is the novel CV disease risk factor, calculated from age and mean BP [6, 10]. It correlated significantly (p<0.001) with age (ρ=0.84), SBP (ρ=0.65), DBP (ρ=0.56) and may be considered for assessment both cardiovascular and nephrological prognosis. Elevation of ESR may reflect increase of inflammatory activity, that, in turn, may influence the course of atherosclerosis [12]. Notably, that this association was stronger for normotensive patiens (Fig. 2). Lack of statistical significance in models with total cholesterol may be the sequence of high percentage of missing data. Interestingly, that risk of CKD progression was poorly associated with duration of CKD but was related to duration of HTN.

Fig. 2. Correlation analysis of patients' characteristics and risk of CKD progression in patients subdivided by presence of HTN
Hypertensive patients had unfavourable clinical and laboratory characteristics, as compared to normotensive ones. Uncontrolled HTN leads to deterioration of both renal and cardiovascular outcomes, and in our study it significantly affected both cardiovascular and nephrological risk profiles. Results of this section may be confounded by substantial difference in age and DM prevalence between groups. But this fact adds importance to DM and HTN as powerful risk factors of loss of renal function [3]. On the Figure 1 it is shown that the main contributors to high-risk groups of CKD progression were patients with HTN as well as patients with high-to-very-high risk of cardiovascular complications. After the correlation analysis ( Figure 2) we found that in hypertensive patients risk of CKD progression was connected with both cardiovascular and nephrological risk factors, while in patients without HTN it was related only to nephrological ones (mainly to AER).
There is the evidence that one time urine estimation is non-inferior to daily urine protein excretion assessment [5,18]. Only 66% of patients with elevated risk of CKD progression and 78% of patients with AER>30 mg/24 hours had protein loss in first urine void. Thus, assessment of proteinuria in morning void may lead to underestimation of risk of CKD progression. Moreover, only 52% of patients with HTN had proteinuria and there was no difference in AER between patients with and without HTN.
In the meta-analysis of Mahmoodi et al. (2012) risk of the end stage renal disease was associated with GFR and urine albuminuria and was not influenced by HTN status [2]. HTN is a major cause of end stage renal disease and there is poor association between HTN in CKD and urine protein loss [3] this thesis was confirmed in our study. Risk underestimation in usage of conventional charts is a common problem in nephrology [7] and cardiology [8], that may be explained by regional differences of the populations [7]. Correction of proteinuria and GFR has proven beneficial impact on prognosis [1,21], but these treatment targets are difficult to reach. HTN is a powerful factor of prognosis, that is relatively simply corrected. Although HTN does not influence risk estimation [2], it affects outcomes [3], and, thus, should be incorporated to assessment of risk of CKD progression.
На умовах ліцензії CC BY 4.0 CONCLUSIONS 1. Increase in risk of CKD progression is associated with rise of burden of cardiovascular risk factors.
2. HTN and BP values should be accounted in assessment of risk of CKD progression.
Limitations. 1. Significant age difference between patients with and without HTN impedes extrapolation of our results on the whole population of CKD patients.
2. Patients in our study needed nephrologist's consultation due to appearance of new symptoms or deterioration of CKD, and, thus, are not completely representative for patients with CKD in ambulatory practice.
Conflict of interest: the authors declare no conflict of interest.