Patients Hospitalized with COVID-19 Face Risk of Kidney Damage
Human prospective observational epidemiological studies have reported associations between CKD and most often defined as development of reduced eGFR and high LDL-C, low high-density lipoprotein cholesterol, and high triglyceride and triglyceride-rich lipoproteins in the general population. A recent analysis found a 2.92- and 2.32-fold higher risk of CKD, respectively, among individuals with possible and probable/definite familial hypercholesterolemia compared with those unlikely to have familial hypercholesterolemia.
In these observational studies, investigators were careful to exclude individuals with overt CKD at baseline. However, reduced eGFR is not a marker of early kidney disease. Such epidemiological studies are likely best interpreted as showing an association of dyslipidemia with the progression of the renal disease rather than showing an association with incident renal injury.
Consistent with the current results, prior metaanalyses of randomized trials of statin therapy in patients with CKD demonstrated no benefit on progression to end-stage renal disease, but less progress in proteinuria/albuminuria and lesser declines in eGFR, especially among those treated with high-intensity statins. Kidney regeneration treatment randomization overcomes several limitations of traditional observational epidemiology and relationships are shown between genetic traits and outcomes are generally interpreted as causal.
So, how do we reconcile the lack of reproducibility of the LDL-C/CKD relationship which showed only univariate associations between LDL-C and CKD that became nonsignificant in multivariable randomization?Heterogeneity in results can occur because of randomization analyses can be affected by the type and composition of the underlying population, availability of individual participant-level data versus summary-level data, follow-up time, and phenotyping of the outcome, among others, as well as differences in randomization methodologies.
More research on the link between LDL-C and CKD is needed. Importantly, we need better markers for early stages of renal dysfunction and noninvasive methods to better classify the etiology and stage of renal diseases in population-level studies and future clinical trials. Given the available data, it is premature to recommend pharmacological treatment of LDL-C for the sole purpose of CKD prevention.
However, when faced with a patient with high LDL-C, clinicians should not only think about the risk of cardiovascular disease, but also consider the risk of CKD, especially in patients with other concomitant CKD risk factors.
Patients should be counseled to avoid potential nephrotoxins (e.g., nonsteroidal anti-inflammatory medications) and instructed in a healthy lifestyle to mitigate the LDL-C elevation and concurrent CKD risk factors such as obesity, hypertension, and diabetes. In patients with non–dialysis-requiring CKD and LDL-C between 71 and 269 mg/dl, current guidelines recommend moderate-intensity statin therapy. Whether newer lipid-lowering agents will favorably affect renal function is currently unknown.
