To the best of our knowledge, the present report constitutes the first study comparing echocardiographic parameters between populations with different CKD aetiologies and a healthy control population. The findings of this large-scale cohort study include significantly impaired diastolic and systolic function, and increased LV mass associated with DN and CKDu compared with healthy controls. Hypertensive or renovascular nephropathy was associated with impaired systolic and diastolic function, while glomerulonephritis or vasculitis was associated with slightly increased LV mass. In contrast, PKD was associated with better systolic function than the control population. Thus, tubulointerstitial nephritis and PKD showed no adverse associations, while glomerulonephritis or vasculitis was only associated with slight structural differences. Conversely, DN, CKDu and hypertensive or renovascular nephropathy were associated with adverse findings in all or most of the examined measures of cardiac structure and function.

Several aetiologies discussed in this report are results of systemic underlying diseases, such as diabetes mellitus or hypertension. Myocardial dysfunction is a common finding in relation to diabetes mellitus [11, 12]. The systemic effects of diabetes mellitus are believed to result from hemodynamic, metabolic, and inflammatory abnormalities leading to vascular complications, including atherosclerosis, retinopathy, nephropathy, and likely also myocardial dysfunction [13, 14]. A previous echocardiographic study found increased LVMi and decreased LV systolic shortening in patients with DN compared with normoalbuminuric patients [15], suggesting increased cardiovascular effects of diabetes mellitus with renal involvement. We believe that there are three possible explanations for the increased extent of these cardiac effects in DN compared with diabetes mellitus. The first possibility is the additive cardiovascular effects of diabetes mellitus coupled with the known adverse effects of declining renal function. The second possibility is that diabetes mellitus drives both the renal and cardiac insult, and the renal involvement thus is a passive comorbidity of CVD rather than a cause of it. The third and most likely explanation is a combination of the first two, as the kidneys are intrinsically linked with the cardiovascular system. Similar to diabetes, hypertension is a common cause of both CKD and CVD. Additionally, increasing renal involvement in hypertension, assessed by UACR, has also been linked with increasingly impaired LV diastolic and systolic function, and with increasing LVMi [16, 17]. In this study, we found associations between hypertensive or renovascular nephropathy, and decreased LV diastolic and systolic function. As with DN, it is difficult to establish the extent to which the adverse cardiac findings in hypertensive nephropathy can be explained by the underlying affliction, hypertension. In continuation of this, it is of interest that even though the prevalence of hypertension in the PKD group was almost as high as that of the hypertensive or renovascular nephropathy group, LVMi in patients with PKD was the lowest amongst patients. This might be due to earlier onset of antihypertensive treatment within this patient group, while individuals from the hypertensive or renovascular nephropathy group might have been afflicted with undetected or uncontrolled hypertension for longer periods of time leading to renal and perhaps also cardiac damage.

CKDu also showed similar associations with DN. Since this group likely contains cases of both DN and hypertensive or renovascular nephropathy, which were not verified through renal biopsy, the similarities in results between CKDu and these groups might be explained by common aetiologies.

Future longitudinal studies following the development and progress of adverse cardiac manifestations in patients with DN and hypertensive or renovascular nephropathy are warranted to elucidate the respective roles of the underlying systemic diseases and the consequential renal involvement. Furthermore, it could be of interest for future studies to take into account the severity and duration of the underlying disease.

This study found that PKD and tubulointerstitial nephritis were not associated with adverse cardiac findings compared with controls. Additionally, the study found only slightly increased LV mass in patients with glomerulonephritis or vasculitis. This is interesting for two main reasons. Firstly, because it is well established, that CKD is associated with numerous cardiac abnormalities, including LV hypertrophy and reduced LV diastolic and systolic function [18,19,20,21]. Our findings could suggest that these adverse associations are, at least in part, dependent upon the underlying aetiologies in addition to the impaired renal function.

Secondly, it is interesting because markers of renal function, eGFR and albuminuria, are also directly correlated with adverse cardiac alterations in CKD [7, 18, 22, 23]. Albuminuria has been linked with impaired systolic function in different populations, including in heart failure with preserved ejection fraction [24], and in type 1 diabetes mellitus [12]. In this study, patients with glomerulonephritis or vasculitis exhibited the highest prevalence of severe albuminuria, but did not differ significantly from the control group in LV function. This could indicate that the context in which albuminuria occurs might influence the association with cardiac structure and function. While not conclusive evidence, this might serve as a potential hypothesis for future studies. Similarly, tubulointerstitial nephritis was associated with the lowest eGFR, but did not differ from the control group with regards to cardiac structure or function either, albeit this finding is weakened by the small sample size of the patient group.

Compared with controls, we found that DN and hypertensive or renovascular nephropathy were related to more adverse cardiac findings than other aetiologies of CKD, even after adjustment for traditional risk factors and eGFR and albuminuria. Contrarily, glomerulonephritis/vasculitis, tubulointerstitial nephritis, and especially PKD did not differ significantly from healthy controls. Several of the echocardiographic parameters addressed in this report are prognostic of adverse outcomes in the general population and in populations with CKD, including cardiovascular morbidity and mortality [22, 25,26,27]. While eGFR and albuminuria are often regarded in relation to the assessment of cardiovascular risk of patients with CKD, the findings of this study might indicate a potential prognostic benefit of further considering aetiology in addition to eGFR and albuminuria. This might be the subject of future longitudinal works.

The results of this study should be interpreted within the context of its limitations. These include the unequal sample sizes of the patient groups, which may have influenced the results of statistical analyses. In addition, the aetiology was not confirmed through biopsy in all cases, and the prevalence of biopsy-verified cases differed between groups, in part also due to less relevance with some aetiologies, for example PKD. Our population size unfortunately did not allow for stratification according to both aetiology, eGFR and albuminuria, which could have supported the association between certain aetiologies and adverse cardiac findings independent of the extent of kidney disease. In addition, information regarding duration of kidney disease was not available. The ethnicity of the study population was relatively uniform, and therefore not necessarily representative of all ethnicities. Similarly, due to the multiple visits and tests related to the study, the population might be slightly affected by volunteer bias. The cross-sectional design of the study precludes the possibility of establishing causality between aetiologies and echocardiographic findings, and merely serves to demonstrate associations. Thus, it is possible that these patients already exhibited impaired cardiac function or structure prior to the development or time of diagnosis of their CKD. Future longitudinal studies are warranted to monitor potential decline or alterations in cardiac function and mass concurrently with the development and progress of the specific chronic kidney diseases.