Prevalence of the stages of chronic kidney disease (CKD) according to simplified MDRD formula in patients from ambulatory settings

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1 PRACE ORYGINALNE Marcin KRZANOWSKI Rafał JANUSZEK Katarzyna KRZANOWSKA Marek KUŹNIEWSKI Jerzy KOPEĆ Eve CHOWANIEC Władysław SUŁOWICZ Prevalence of the stages of chronic kidney disease (CKD) according to simplified MDRD formula in patients from ambulatory settings Stadia przewlekłej choroby nerek (PChN) uzyskane w oparciu o uproszczony wzór MDRD u pacjentów poradni nefrologicznej Chair and Department of Nephrology Jagiellonian University, Krakow, Poland Head: Prof. dr. hab. med. Władysław Sułowicz Additional key words: chronic kidney disease (CKD) estimated GFR simplified MDRD formula Dodatkowe słowa kluczowe: przewlekła choroba nerek (PChN) szacowany GFR uproszczony wzór MDRD Adres do korespondencji: Dr med. Marcin Krzanowski Chair and Department of Nephrology Jagiellonian University, Kraków ul. Kopernika 15c Tel: Fax: mkrzanowski@op.pl Background. The staging system of chronic kidney disease (CKD) classification plays an important role in patients stratification according to disease activity. The aim of the study was to evaluate the frequency of appearance of consecutive stages of chronic kidney disease based on simplified MDRD formula in patients with diagnosed CKD. Additionally, relationship between egfr values and selected biochemical parameters and comorbidities were analyzed. Methods. The study was performed retrospectively in the group of 1176 patients (636 males and 540 females) aged between years (mean 64.7) with creatinine level >120 µmol/l and/or creatinine clearance <90 ml/min/1.73 m 2. Results. The highest percentage of patients were designated to the 3 rd CKD stage. There were positive correlations between egfr and Hb, Ht, Fe, LDL-Ch, AspAT, HbA1c and negative correlations between egfr and age, mean and systolic blood pressure, as well as with P, K, ipth, and uric acid concentration. Patients with cardiovascular diseases had significalntly lower egfr values as compare with patients without such complications, respectively: atrial fibrillation, arterial hypertension, chronic heart failure, ischaemic heart disease (p < 0.01), and myocardial infarction (p < 0.04). Conclusions. The highest percentage of patients with diagnosed CKD belong to the 3 rd stage of disease. Patients with cardiovascular complications have significantly lower egfr as compared with those without such disturbances. Wprowadzenie: System klasyfikacji przewlekłej choroby nerek (PChN) odgrywa ważną rolę w stratyfikacji pacjentów według aktywności choroby. Celem badania była ocena częstotliwości występowania kolejnych stadiów przewlekłej choroby nerek w oparciu o uproszczony wzór MDRD u pacjentów, u których zdiagnozowano przewlekłą chorobą nerek. Ponadto analizowano związek pomiędzy wartościami egfr a wybranymi parametrami biochemicznymi oraz chorobami współistniejącymi. Materiał i Metodyka: Badanie przeprowadzono retrospektywnie w grupie 1176 pacjentów (636 mężczyzn i 540 kobiet) w wieku lat (średnia 64,7), ze stężeniem kreatyniny > 120 µmol/l i / lub klirensem kreatyniny <90 ml/min/1,73 m2. Wyniki: Najwyższy odsetek pacjentów przynależał do 3 stadium PChN. Obserwowano dodatnie korelacje pomiędzy egfr a Hb, Ht, Fe, LDL- Ch, AspAT, HbA1c i ujemne między egfr a wiekiem, średnim i skurczowym ciśnieniem tętniczym, jak również z P, K, ipth oraz stężeniem kwasu moczowego. Chorzy z powikłaniami sercowo-naczyniowymi mieli istotnie niższą wartość egfr w porównaniu z pacjentami bez tych schorzeń, odpowiednio: migotanie przedsionków, nadciśnienie tętnicze, przewlekła niewydolność serca, choroba niedokrwienna serca (p < 0,01), a przebyty zawał serca (p < 0,04). Wnioski: Najwyższy odsetek pacjentów z rozpoznaną PChN należy do 3 stadium choroby. Pacjenci z powikłaniami sercowo-naczyniowymi mają istotnie niższą wartość egfr w porównaniu z tymi, którzy nie mają tych zaburzeń. Introduction During the last years, incidence of chronic kidney disease (CKD) is steadily increasing and has become a global social and economical problem in the World, as well as in Poland [1-4]. The staging system of CKD classification introduced in 2002 by the National Kidney Foundation, plays an important role in patients stratification according to disease activity [5]. NKF-KDOQI evidence-based guidelines facilitate optimal patients management respective to disease stage and related complications. Many data indicate 277

2 that patients with CKD (even in the early stages), have increased cardiovascular morbidity and mortality [6-9]. The aim of the study was to evaluate based on retrospective analysis of medical records of patients with renal failure the frequency of appearance of consecutive stages of CKD based on the abbreviated MDRD formula and relationships between egfr values and selected biochemical parameters, as well as comorbidities. Patients and methods The study was performed in the group of 1176 patients (636 males and 540 females) aged between 17 and 98 years (mean 64.7) with serum creatinine concentration >120 µmol/l and/or creatinine clearance <90 ml/ min/1.73m 2, while being under supervision of the Outpatient Clinic, Department of Nephrology, University Hospital. The estimated GFR were calculated based on the abbreviated MDRD formula. The serum concentration of selected biochemical parameters: creatinine, urea, total protein, albumin, P, Ca, Mg, K, Na, ipth, total-cholesterol (Ch), HDL-Ch and LDL-Ch, triglicerydes, glucose, uric acid, HbA1c, bilirubin, Fe, AlAT, AspAT, TSH and blood morphology were estimated based on routine laboratory procedures. The obtained results were presented as mean and standard deviations. Results It was shown that the percentage of consecutive stages of CKD based on the abbreviated MDRD formula, were designated as follows: 1 st stage of CKD - 0.2%, 2 nd stage - 7.9%, 3 rd stage %, 4 th stage %, and to the 5 th stage - 5.1%. After calculation, we obtained in the whole study group mean GFR values according MDRD formula: 38.4 ± ml/min/1.73m 2. The highest percentage of patients were designated to the 3 rd CKD stage. GFR value distribution according to patients sex, indicates that males predominate in the 1 st, 2 nd, and 3 rd CKD stages, while females in the 4 th and 5 th stages (Fig. 1). The correlations between egfr obta- Table I Correlations between egfr value obtained based on simplified MDRD formula and tested parameters. Korelacje pomiędzy wartością egfr otrzymaną w oparciu o uproszczony wzór MDRD a badanymi parametrami. Number of patients Mean SD r 2 p Mean clearence Albumin (g/l) Total protein (g/l) BMI (kg/m 2 ) Hb (g/dl) < Hct (%) < Fe (μmol/l) < MCV (fl) P (mmol/l) < Ca (mmol/l) ipth (pg/ml) < AF (IU/l) LDL (mmol/l) < HDL (mmol/l) Total cholesterol (mmol/l) Triglicerydes (mmol/l) Diastolic blood preassure Systolic blood preassure Mean blood preassure < < Age (years) < AlAT (IU/l) < AspAT (IU/l) Glucose (mmol/l) HbA1 (%) < K + (mmol/l) < Uric acid (μmol/l) < Mg ++ (mmol/l) Na + (mmol/l) Bilirubin (μmol/l) TSH (uiu/ml) SD Figure 1 Distribution of egfr values obtained based on abbreviated MDRD formula according to sex in the studied patients group. Rozmieszczenie w badanej grupie chorych wartości egfr uzyskanych w oparciu o uproszczony wzór MDRD w zależności od płci. Figure 2 and hemoglobin concentration (p<0.01). a stężeniem hemoglobiny (p<0,01). 278 M. Krzanowski i wsp.

3 Figure 3 and hematocrite (p<0.01). a wartością hematokrytu (p<0,01). Figure 4 and LDL-Ch (p<0.02). and LDL-Ch (p<0,02). Figure 5 and age (p<0.01). a wiekiem (p<0,01). Figure 6 and serum phosphate concentration (p<0.01). a stężeniem fosforanów w surowicy (p<0,01). Figure 7 and serum potassium concentration (p<0.03). a stężeniem potasu w surowicy (p<0,03). Figure 8 and serum uric acid concentration (p<0.01). a stężeniem kwasu moczowego w surowicy (p<0,01). ined based on MDRD formula and tested parameters were shown in Table I. There were positive correlations between egfr obtained based on simplified MDRD formula and Hb (Fig. 2), Ht (Fig. 3), LDL-Ch, (Fig. 4), Fe, AspAT, HbA1c and negative correlations between egfr and age (Fig. 5), P (Fig. 6), K (Fig. 7), uric acid (Fig. 8) as well as with mean and systolic blood pressure and ipth (Tab. I). It was shown that a high percentages of patients from the studied group had one 279

4 Table II Comparison of egfr values obtained based on simplified MDRD formula between patients group with and without observed comorbidities (test T). Porównanie wartości egfr otrzymanych w oparciu o uproszczony wzór MDRD pomiędzy pacjentami z i bez współchorobowości (T test). Group of patients without comorbidity or more comorbidities. The most important were: hypertension 64.5%, ischaemic heart disease 31.3%, diabetes mellitus 25.2%, previous nephrectomy 10.6%, history of myocardial infarction 10.6%, heart insufficiency 9.8%, urinary tract stones 7.7%, atrial fibrillation - 6.7%, previous CABG procedure 2.2%, and PTCA 1.9%. Statistically significant differences between values of egfr were observed in the group of patients with such complications as: atrial fibrillation, arterial hypertension, history of myocardial infarction, heart failure, and ischaemic heart disease when compared with patients without these complications (Tab. II). Discussion Generally introduced calculations of egfr have allowed for more accurate identification of patients with kidney damage and have thrown a new light on incidence of CKD in the general population [10-13]. Attention has been drawn of other medical specialists to the existence of the problem of CKD and has permitted for earlier referral of these patients to the nephrologist [14-17]. Earlier medical attention to patients with CKD has also introduced prescription of nephroprotection, which in itself may delay disease progression to terminal renal failure [18,19]. The presented data has revealed that the highest percentage of studied patients were designated to the 3 rd stage of CKD. The abbreviated MDRD formula seems to be the most suitable method of egfr estimation. It has been recommended by the Australian Creatinine Consensus Working Group in 2005; and in the last years in our country by the Polish Society of Nephrology as a basic method of egfr calculation [9,20]. We observed egfr values calculated N Group of patients with comorbidity GFR (ml/min) GFR (ml/min) N Mean SD Mean SD Overcome CABG Diabetes Dyslipidemia Atrial fibrilation <0.01 Hypercholesterolemia Arterial hypertension <0.01 Overcome myocardial infarction <0.04 Heart insufficiency <0.01 Urinary Stones Ischemic heart disease <0.01 Overcome nephrectomy Overcome PTCA based on the abbreviated MDRD formula distribution according to patients sex. It was found that males predominate in the 1 st, 2 nd, and 3 rd CKD stages, while females in the 4 th and 5 th stages. We expect that ongoing longterm observation of the studied population will give us information about the influence of sex on CKD progression. The metaanalysis of 68 studies, that contained a total of 11,345 patients indicate that men with CKD of various etiologies show a more rapid decline in renal function with time than women [21]. We observed positive correlations between egfr and Hb, Ht, Fe, LDL-Ch, AspAT, HbA1c and negative correlations between egfr and mean as well as systolic blood pressure, age, P, K, uric acid serum concentrations. It is a well known fact that patients with more advanced renal failure have more severe anemia, frequently present with hypertension, are older and have higher P, K, and uric acid concentrations, as well as increased mortality [22,23]. In our study, patients with comorbidities such as: atrial fibrillation, arterial hypertension, history of myocardial infarction, heart failure and ischeamic heart disease had significantly lower egfr values when compared to patients without such complications. There are many data indicating that advanced CKD, substantially increases the risk of cardiovascular complications and mortality [6,22]. Patients with cardiovascular disease have a higher prevalence of CKD and high rate of progression to end stage renal disease, while the time required for progression to ESRD depends upon many factors [8,20]. In comparison with other egfr estimation methods simplified MDRD formula is very useful and accurate in identification of CKD patients with different stages of disease [24-27]. T p Conclusions The highest percentage of patients with diagnosed CKD are belonging to the 3 rd stage of disease. Patients with cardiovascular complications have significantly lower egfr as compared with those without such disturbances. References 1. Coresh J, Astor B, Greene T, Eknoyan G, Levey A: Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. 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