Addressing Dyslipidaemia in Advanced CKD: Insights from a Secondary Care Cohort

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a very thoughtful retrospective analysis of a single center cohort of advanced CKD patients undergoing dialysis which investigates LDL-C levels, adequacy of LDL control, as well as a summary of therapies used in this population. This is a highly relevant field given the paucity of adequate LDL control in CKD patients who carry a high burden of cardiovascular risk factors and co-morbid conditions such as CAD, diabetes, and hypertension. The authors present a nice introduction highlighting the gaps in knowledge, and set the stage well for their analysis. In terms of methods, they are sound and limited by a small sample size and a single center retrospective design which limits the generalizability of the findings, this should be outlined in the limitations section. The discussion is interesting, I would supplement the discussion by highlighting the practice variation in prescribing statins to patients on hemodialysis. Many practitioners would refrain from prescribing statins to dialysis patients, and other agents such as PCSK9 inhibitors often exclude patients with CKD from randomized trials for obvious reasons. This leaves an important gap in the management of patients with CKD and dyslipidemia or those with other indication for statin (known CAD, diabetic patients over 40 etc). The authors should comment on the type of dialysis and the regional practice patterns regarding safety and pattern of statin use in hemodialysis patients specifically. Despite these limitations, this is a thoughtful and well done paper that sheds light on an important issue where clinical equipoise and practice variations exist. 

Author Response

Comment 1:

This is a very thoughtful retrospective analysis of a single center cohort of advanced CKD patients undergoing dialysis which investigates LDL-C levels, adequacy of LDL control, as well as a summary of therapies used in this population. This is a highly relevant field given the paucity of adequate LDL control in CKD patients who carry a high burden of cardiovascular risk factors and co-morbid conditions such as CAD, diabetes, and hypertension. The authors present a nice introduction highlighting the gaps in knowledge, and set the stage well for their analysis. In terms of methods, they are sound and limited by a small sample size and a single center retrospective design which limits the generalizability of the findings, this should be outlined in the limitations section. The discussion is interesting, I would supplement the discussion by highlighting the practice variation in prescribing statins to patients on hemodialysis.

Response 1: Although study cohort was pre dialysis, we have added a section on the importance of this cohort and also the evidence behind LLT use in dialysis patients with references – Line 245

 

Comment 2: Many practitioners would refrain from prescribing statins to dialysis patients, and other agents such as PCSK9 inhibitors often exclude patients with CKD from randomized trials for obvious reasons.

Response 2: This has been added to the above-mentioned section – these agents are offered to non-dialysis patients in our centre based on their safety data - Line 254.

 

Comment 3: This leaves an important gap in the management of patients with CKD and dyslipidemia or those with other indication for statin (known CAD, diabetic patients over 40 etc). The authors should comment on the type of dialysis and the regional practice patterns regarding safety and pattern of statin use in hemodialysis patients specifically.

Response 3: Practice recommendations are is in accordance with  the JBS-3 and NICE guidelines in patients on dialysis (both haemodialysis and CAPD) – this is expanded in the discussion – Line 254

 

Comment 4: Despite these limitations, this is a thoughtful and well done paper that sheds light on an important issue where clinical equipoise and practice variations exist. 

 

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors This paper aims to audit lipid management practices, particularly LDL-C levels and lipid-lowering therapy (LLT) usage, among advanced chronic kidney disease (CKD) patients (eGFR < 30 mL/min/1.73 m²) in a UK pre-dialysis clinic and assess adherence to national and international LDL-C targets using both the Friedewald and Sampson algorithms. This paper noted that there is significant underachievement of LDL-C targets among advanced CKD patients. Increased clinician awareness and expanded use of combination therapies are needed, along with the adoption of more accurate LDL-C calculation methods like Sampson’s equation. However, some concerns have been raised. 1. As a retrospective audit without prospective outcomes or interventional data, the study provides limited actionable insights for a broad readership. While the topic is clinically important, the audit format restricts its generalizability and impact. 2. Only a small fraction of patients were treated with newer therapies like ezetimibe, inclisiran, or PCSK9 inhibitors, which limits the strength of the conclusions regarding underutilization. 3. The absence of cardiovascular outcomes, stroke, renal function decrease, or hospitalization data reduces the paper’s applicability to clinical decision-making. 4. Not hypothesis-driven; does not present novel mechanisms or breakthroughs. 5. The daily dose of statin used or other lipid-lowering therapy (LLT) used was not found or discussed in this paper. 6. Other factors that affect the lipid levels were not found or discussed in this study.

Author Response

This paper aims to audit lipid management practices, particularly LDL-C levels and lipid-lowering therapy (LLT) usage, among advanced chronic kidney disease (CKD) patients (eGFR < 30 mL/min/1.73 m²) in a UK pre-dialysis clinic and assess adherence to national and international LDL-C targets using both the Friedewald and Sampson algorithms. This paper noted that there is significant underachievement of LDL-C targets among advanced CKD patients. Increased clinician awareness and expanded use of combination therapies are needed, along with the adoption of more accurate LDL-C calculation methods like Sampson’s equation.

However, some concerns have been raised.

Comment 1: As a retrospective audit without prospective outcomes or interventional data, the study provides limited actionable insights for a broad readership.

Response 1:This is included in the limitations section and the potential findings of a well-designed longitudinal study in this cohort described – Line 245 and Line 278. We have updated the manuscript and uploaded the updated manuscript.

 

Comment 2: While the topic is clinically important, the audit format restricts its generalizability and impact.

Response 2: This is acknowledged under limitations. We also add that our poor results in a secondary care renal unit should encourage similar units to evaluate their lipid lowering performance – Line 264.

 

Comment 3: Only a small fraction of patients were treated with newer therapies like ezetimibe, inclisiran, or PCSK9 inhibitors, which limits the strength of the conclusions regarding underutilization.

Response 3: These agents have been available in our secondary care centre for a long period of time; ezetimibe (since 2002), bempedoic acid (since 2020), PCSK9 inhibitors (since 2016) and inclisiran (since 2021). Hence, we were surprised that greater utilisation of these post-statin therapies was not evident. We have added this to the discussion – Line 205 and Line 254.

 

Comment 4: The absence of cardiovascular outcomes, stroke, renal function decrease, or hospitalization data reduces the paper’s applicability to clinical decision-making.

Response 4: This has been acknowledged and included under limitations – Line 245

 

Comment 5: Not hypothesis-driven; does not present novel mechanisms or breakthroughs.

Response 5: This has been acknowledged under limitations – Line 254

 

Comment 6: The daily dose of statin used or other lipid-lowering therapy (LLT) used was not found or discussed in this paper.

Response 6: This has been acknowledged – the data was collected, but would have led to numerous subgroups with few patients would have made it difficult to draw conclusions, As very few patients were on combination therapy, which is on offer in our centre, our conclusion that LLT use was suboptimal appears valid - Line 275.

 

Comment 7: Other factors that affect the lipid levels were not found or discussed in this study.

Response 7: Although we do not collect data on other factors affecting the LDL-C values such as thyroid function, checking secondary causes of dyslipidaemia is part of the treatment pathway prior to LLT initiation – this is acknowledged under limitations – Line 278.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Although the authors acknowledge the limitations of this retrospective audit design, they have addressed these transparently in the revised manuscript. This study's findings reveal a significant underachievement of LDL-C targets in a high-risk, pre-dialysis CKD population, despite long-standing availability of lipid-lowering therapies. By comparing the Friedewald and Sampson equations, it also highlights how the calculation method may influence perceived target attainment—an under-recognized issue in practice. Furthermore, the unexpectedly low uptake of non-statin therapies such as ezetimibe and PCSK9 inhibitors underscores a gap between guideline recommendations and real-world treatment patterns. These insights provide a valuable foundation for future quality improvement initiatives and prospective studies aimed at optimizing lipid management in advanced CKD.