Cardiovascular Disease and Mortality in Advanced CKD

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Lankinen R, Hakamäki M, Metsärinne K, Koivuviita NS, Pärkkä JP, Hellman T, Kartiosuo N, Raitakari OT, Järvisalo MJ: Cardiovascular Determinants of Mortality in Advanced Chronic Kidney Disease. American Journal of Nephrology DOI 10.1159/000509582

Little doubt exists that progressive chronic kidney disease (CKD) imposes added risks of mortality, mainly from cardiovascular disease (CVD). This relationship is a very complex one involving a multitude of factors (such as dyslipidemia, microinflammation, hypertension, metabolic disorders, vascular calcification, volume overload, anemia, and others).

Lankinen and coworkers examined some of the “determinants” of CVD and all-cause mortality in an interim report of the findings in a cohort of 210 patients with stage 4 or 5 (non-dialysis) CKD enrolled in a prospective cohort study carried out in Finland. The average age of the enrollees was 61 years, with 43% diabetic and 99% hypertensive. The median eGFR was 12 mL/min. The subjects underwent a number of studies, including measurement of troponin T, NT-proBNP, serum albumin, bicycle ergometry, X-rays for abdominal aortic calcification (AAC), echocardiography, carotid and femoral intima-media thickness, and brachial artery flow-mediated vasodilatation. About 21% of the subjects died during a follow-up of 42 ± 17 months; 80% of the enrollees began dialysis (hemo- or peritoneal dialysis) or received a kidney transplant during the follow-up period. Death was due to CVD in 47%, malignancy in 22%, infection in 14%, and other causes in the remaining 17%. The prediction of all-cause mortality by variable measured was studied in Cox proportional hazards modeling with adjustments for comorbidity, but the validity of the proportional hazards model was not tested by examination of Schoenfeld residuals.

The factors associated with increased mortality risk were increased troponin T, increased NT-proBNP, decreased maximum exercise capacity (determined by the energy expenditure in the last 4 min of graded exercise by bicycle ergometry), degree of AAC, E/e ratio by cardiac electrocardiography, and a low albumin concentration. Carotid and femoral intima-media thickness and brachial artery flow-mediated dilatation did not consistently predict mortality. Interestingly, the left ventricular mass index and left ventricular ejection fraction also did not predict mortality.

These findings could be incorporated into a “scoring system” for mortality prediction, but comparison to other much simpler prognostic tools would be very appropriate. Such tools are readily available and include the powerful “surprise” question incorporated into the QXmd calculator (see and that presented by Schmidt et al. [1]. Whether the variables included in this study will improve the accuracy of prediction of all-cause and cardiovascular mortality in patients with stage 4/5 CKD compared to simpler methods needs to be studied in the future iterations of this cohort analysis, in my opinion.

Richard Glassock

[1] Schmidt RJ, Landry DL, Cohen L, Moss AH, Dalton C, Nathanson BH, Germain MJ. Derivation and validation of a prognostic model to predict mortality in patients with advanced chronic kidney disease. Nephrol Dial Transplant. 2019;34:1517–25

Quoted Karger Article

Cardiovascular Determinants of Mortality in Advanced Chronic Kidney Disease