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Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study.

Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Fondelli C, Gruden G, Cavalot F, Lamacchia O, Trevisan R, Vedovato M, Penno G, RIACE Study Gro - Cardiovasc Diabetol (2014)

Bottom Line: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories.The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification.However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical and Molecular Medicine, "La Sapienza" University, Via di Grottarossa, 1035-1039, 00189 Rome, Italy. giuseppe.pugliese@uniroma1.it.

ABSTRACT

Background: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification.

Methods: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.

Results: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped into AKDN and KDIGO risk category 1 and moderate, respectively, and to a lesser extent into higher risk categories.

Conclusions: Though the new systems perform better than the NKF's KDOQI in grading complications and identifying diabetic subjects without complications, they might underestimate CVD burden in patients assigned to lower risk categories and should be tested in large prospective studies.

Trial registration: ClinicalTrials.gov; NCT00715481.

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Prevalence (% of cases, number of subjects on top of columns) of any coronary event (A), AMI (B), any cerebrovascular event (C), stroke (D), any peripheral event (E), and ulcer/gangrene (F) according to CKD NFK’s KDOQI stage (left), AKDN risk category (middle), and KDIGO risk category (right). NFK’s KDOQI classification: stage 0 (green), 1 (yellow), 2 (orange), 3 (red), 4 (brown), and 5 (blue); AKDN alternate system: risk category 0 (green), 1 (yellow), 2 (orange), 3 (red), and 4 (brown); KDIGO classification: risk category low (green), moderate (yellow), high (orange), and very high (red).
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Figure 3: Prevalence (% of cases, number of subjects on top of columns) of any coronary event (A), AMI (B), any cerebrovascular event (C), stroke (D), any peripheral event (E), and ulcer/gangrene (F) according to CKD NFK’s KDOQI stage (left), AKDN risk category (middle), and KDIGO risk category (right). NFK’s KDOQI classification: stage 0 (green), 1 (yellow), 2 (orange), 3 (red), 4 (brown), and 5 (blue); AKDN alternate system: risk category 0 (green), 1 (yellow), 2 (orange), 3 (red), and 4 (brown); KDIGO classification: risk category low (green), moderate (yellow), high (orange), and very high (red).

Mentions: Though prevalence of complications increased with increasing CKD severity with all systems (P for trend <0.0001), it differed significantly between NKF’s KDOQI stages and AKDN or KDIGO risk categories (Figures 2 and 3). In fact, since prevalence of CVD, but not DR, was higher in patients with nonalbuminuric renal impairment (NKF’s KDOQI stages 3-5) than in micro and macroalbuminuric subjects with normal-to-high or mildly reduced eGFR (NKF’s KDOQI stages 1-2) (Table 1) [8,25], prevalence of any CVD, any coronary events, and myocardial infarction was significantly higher in risk category 1 or moderate than in stage 1 (P at least <0.001) as well as in risk category 2 (P < 0.0001) or high (P at least <0.005) than in stage 2, whereas prevalence of advanced DR was higher in risk category 3 or very high than in stage 3 (P < 0.0001). Moreover, since CVD prevalence was relatively low in macroalbuminuric subjects with non-reduced eGFR (included in AKDN and KDIGO risk category 3 and high, respectively) [8], it tended to plateau between AKDN risk categories 2 and 3, whereas they increased markedly from KDIGO risk category high to very high (Figures 2 and 3). However, a higher number of subjects without CVD (2,788) or DR (2,808) were appropriately classified in the lowest risk categories of the new systems (i.e. 1 and moderate, respectively) than in NKF’s KDOQI stage 1 (820 and 757, respectively). Logistic regression analysis showed that the strength of association of complications, independent of confounders, increased more progressively with AKDN and particularly KDIGO risk categories than with NKF’s KDOQI stages, except for cerebrovascular and peripheral events. In addition, NKF’s KDOQI stage 1 was not significantly associated with any CVD event and CVD events by vascular bed, except ulcer/gangrene, whereas stage 2 did not correlate with any CVD and coronary events. Finally, the odd ratios for CVD, except cerebrovascular events, tended to plateau between AKDN risk categories 3 and 4 or even 2 and 4 (Figure 4).


Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study.

Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Fondelli C, Gruden G, Cavalot F, Lamacchia O, Trevisan R, Vedovato M, Penno G, RIACE Study Gro - Cardiovasc Diabetol (2014)

Prevalence (% of cases, number of subjects on top of columns) of any coronary event (A), AMI (B), any cerebrovascular event (C), stroke (D), any peripheral event (E), and ulcer/gangrene (F) according to CKD NFK’s KDOQI stage (left), AKDN risk category (middle), and KDIGO risk category (right). NFK’s KDOQI classification: stage 0 (green), 1 (yellow), 2 (orange), 3 (red), 4 (brown), and 5 (blue); AKDN alternate system: risk category 0 (green), 1 (yellow), 2 (orange), 3 (red), and 4 (brown); KDIGO classification: risk category low (green), moderate (yellow), high (orange), and very high (red).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4008155&req=5

Figure 3: Prevalence (% of cases, number of subjects on top of columns) of any coronary event (A), AMI (B), any cerebrovascular event (C), stroke (D), any peripheral event (E), and ulcer/gangrene (F) according to CKD NFK’s KDOQI stage (left), AKDN risk category (middle), and KDIGO risk category (right). NFK’s KDOQI classification: stage 0 (green), 1 (yellow), 2 (orange), 3 (red), 4 (brown), and 5 (blue); AKDN alternate system: risk category 0 (green), 1 (yellow), 2 (orange), 3 (red), and 4 (brown); KDIGO classification: risk category low (green), moderate (yellow), high (orange), and very high (red).
Mentions: Though prevalence of complications increased with increasing CKD severity with all systems (P for trend <0.0001), it differed significantly between NKF’s KDOQI stages and AKDN or KDIGO risk categories (Figures 2 and 3). In fact, since prevalence of CVD, but not DR, was higher in patients with nonalbuminuric renal impairment (NKF’s KDOQI stages 3-5) than in micro and macroalbuminuric subjects with normal-to-high or mildly reduced eGFR (NKF’s KDOQI stages 1-2) (Table 1) [8,25], prevalence of any CVD, any coronary events, and myocardial infarction was significantly higher in risk category 1 or moderate than in stage 1 (P at least <0.001) as well as in risk category 2 (P < 0.0001) or high (P at least <0.005) than in stage 2, whereas prevalence of advanced DR was higher in risk category 3 or very high than in stage 3 (P < 0.0001). Moreover, since CVD prevalence was relatively low in macroalbuminuric subjects with non-reduced eGFR (included in AKDN and KDIGO risk category 3 and high, respectively) [8], it tended to plateau between AKDN risk categories 2 and 3, whereas they increased markedly from KDIGO risk category high to very high (Figures 2 and 3). However, a higher number of subjects without CVD (2,788) or DR (2,808) were appropriately classified in the lowest risk categories of the new systems (i.e. 1 and moderate, respectively) than in NKF’s KDOQI stage 1 (820 and 757, respectively). Logistic regression analysis showed that the strength of association of complications, independent of confounders, increased more progressively with AKDN and particularly KDIGO risk categories than with NKF’s KDOQI stages, except for cerebrovascular and peripheral events. In addition, NKF’s KDOQI stage 1 was not significantly associated with any CVD event and CVD events by vascular bed, except ulcer/gangrene, whereas stage 2 did not correlate with any CVD and coronary events. Finally, the odd ratios for CVD, except cerebrovascular events, tended to plateau between AKDN risk categories 3 and 4 or even 2 and 4 (Figure 4).

Bottom Line: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories.The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification.However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical and Molecular Medicine, "La Sapienza" University, Via di Grottarossa, 1035-1039, 00189 Rome, Italy. giuseppe.pugliese@uniroma1.it.

ABSTRACT

Background: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification.

Methods: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.

Results: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped into AKDN and KDIGO risk category 1 and moderate, respectively, and to a lesser extent into higher risk categories.

Conclusions: Though the new systems perform better than the NKF's KDOQI in grading complications and identifying diabetic subjects without complications, they might underestimate CVD burden in patients assigned to lower risk categories and should be tested in large prospective studies.

Trial registration: ClinicalTrials.gov; NCT00715481.

Show MeSH
Related in: MedlinePlus