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Introduction
The natural history or clinical course of chronic kidney disease (CKD) is characterized by a progressive decrease in glomerular filtration rate (GFR) decreases over time towards more advanced stages of kidney failure (1). The speed of progression towards kidney failure is variable. Possible factors associated with progression have been identified as the etiology of kidney failure, proteinuria, metabolic control of diabetes, hypertension, smoking, dyslipidemia, calcium, phosphorus, uric acid, and use of nephrotoxics, among others (2)
Some of these factors are associated with rapid progression such as diabetic nephropathy, chronic glomerulonephritis and polycystic kidney disease of the adult. Hypertensive vascular disease and tubulointerstitial nephropathies are associated with slow progression (1, 2). Proteinuria, in addition to being a marker of kidney damage, is a factor associated with rapid progression and is a cardiovascular risk factor (3, 4). The evidence for the effect of the correction of these factors to reduce the speed of progression or the correction of CKD is contradictory, although its benefit on cardiovascular risk has been demonstrated at other levels (1, 2). The objective of the present prospective study was to determine the factors associated with the progression of CKD in a population of adults over 65 years of age.
Methods
Study population
We included 200 patients older than 65 years belonging to a nephroprotection program in a primary health care institution in Colombia and were followed for 12 months. The criteria for admission to the nephroprotection program include patients with a confirmed diagnosis of chronic kidney disease according to international definitions, mainly captured from the follow-up of patients with diagnoses of high blood pressure and confirmed diabetes mellitus, where clinical parameters and progression are monitored. of pathologies of specific underlying risk.
History of Chronic Kidney Disease
Data on history of chronic kidney disease (CKD) was collected by study investigators at including patients with ICD-10 diagnosis of CKD, or with a personal history of CKD; or with eGFR measured using the Cockcroft - Gault formula of <60 mL/min/1.73 m2 ((140 - age (years)) x actual body weight (kg) x (0-85 if female)) / (72 x creatinine (mg/dL)); or patients in follow-up at nephrology clinics. Patients with CKD in renal replacement therapy, including kidney transplant history were excluded.
Definitions of CKD and stages of the disease
We defined as CKD case the presence of structural abnormalities (markers of renal damage: albuminuria, urinary sediment abnormalities, hydroelectrolytic disorders and other anomalies secondary to tubulointerstitial disorders, abnormalities detected by histology or radiological studies, and functional decrease in eGRF <60 ml/min/1.73 m2) present for more than three months, with health implications (5). CKD was classified based on the cause, category according to eGFR,and level of proteinuria/albuminuria.
The variables of interest were recorded (age, sex, history of diabetes mellitus, serum creatinine at baseline and at 12-month follow-up, high blood pressure (>140/90 mmHg), altered high density lipoprotein (HDL) and low density lipoprotein (LDL), cholesterol levels, proteinuria/albuminuria, use of antihypertensive drugs, use of antidiabetics, allopurinol, proton pump inhibitors, antiplatelet agents, and folic acid). The eGFR was measured at baseline and at 12- month follow-up and the progression of CKD were established. A decrease of > 25 % of the initial GFR was defined as a global progression of CKD. Rapid progression of the CKD was defined as the decrease > 5mL/min/1.73m2 /year of the initial GFR (5).
Statistical analysis
Descriptive analysis was performed using proportions (%) or means with standard deviations. We used Pearson Chi-square and Student’s t-test for the comparisons between variables. To establish the association between the variables of interest and global or rapid progression of CKD, a Multivariate Logistic Regression model was used. All statistical analyses were conducted using the Stata version 14.2 software (StataCorp, College Station, TX) and R version 3.4.3 (R Core Team, R Foundation for Statistical Computing), p value <0.05 was considered statistically significant for all test.
Results
Baseline characteristics
200 patients were included with an average age of 78.9 + 0.5 years, 51 % (102) of females, 33.5 % (66) with a history of diabetes mellitus, with a mean initial eGFR 38.8 + 12.1 mL/min/1.73 m2. The mean of the final GFR was 36.4 + 11.0 mL/min/1.73 m2. Baseline characteristics are shown in Table 1. The changes in the CKD stage are shown in Table 2.
Progression of CKD
17.5 % (35) presented a decrease > 25 % of the initial GFR (global progression) and 37.5 % (75) showed a decrease > 5ml/min/1.73m2 /year (rapid progression).
Factors associated with the progression of CKD
Global progression (Table 3 ) was significantly associated with age (p = 0.004) and male sex (p <0.001). There were no significant associations with other variables of interest.
Rapid progression (Table 4) was significantly associated with age (p = 0.003), male sex (p < 0.00), proteinuria (p =0.03) and angiotensin receptor antagonist-II (ARA-II) (p = 0.03). There were no significant associations with other variables of interest.
Discussion
The factors associated with progression of CKD may be classified as modifiable and not modifiable (1,2). Among the non-modifiable factors, we have the initial kidney function, race, sex, age, birth weight and specific genetic factors. Advanced kidney failure at the time of diagnosis of CKD is a factor of poor prognosis (6). A faster CKD progression has been observed in the black race associated with socioeconomic, dietary and environmental factors (7).
In men, prognosis seems to be worse compared to women, and in the elderly there is a greater frequency of structural abnormalities that increases with the years (8).
In our study, the progression of CKD was significantly associated with the increase in age and male gender.
Among the modifiable factors are proteinuria, high blood pressure, poor glycemic control in diabetes, dyslipidemia, uric acid, use of nephrotoxic-medication, among others (1, 2). Proteinuria is an independent risk factor most important in the progression of CKD (7, 9, 10). ACE-I and ARA-II are recommended in the guidelines for the management of arterial hypertension, due to their effectiveness in the control of proteinuria (11,12). In our study, the rapid progression of CKD was significantly associated with the presence of proteinuria and the blocking drugs of the renin angiotensin aldosterone system.
Although the evidence is contradictory, long-term treatment with allopurinol may slow the rate of progression of kidney disease (13,14). The association between the use of proton pump inhibitors and the deterioration of CKD has been reported in clinical trials and observational studies (15, 16). The reports of the association between the use of folic acid and decrease in the progression of CKD are also contradictory (17,18). In our study, no significant association was found between the progression of CKD and the use of allopurinol, proton pump inhibitors and folic acid.
The absence of data on the specific race, the use of other specific nephrotoxic drugs and the short duration of follow-up are the main limitations of our study.
In conclusion, the progression of CKD in those older than 65 years in a nephroprotection program in Colombia was significantly associated with the increase in age, male sex, and presence of proteinuria.
