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Open research questions in Chronic Kidney Disease and Diabetes

1,214 gap statements mined from Chronic Kidney Disease and Diabetes papers in our 7.9M-paper local library, which holds 4,810 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • One challenge is the complexity of peritoneal membrane biology and the multiple molecular pathways involved in fibrogenesis. Another challenge is the need to identify genetic markers that can predict baseline peritoneal transport rates and tailor dialysis prescriptions accordingly. The paper also highlights the challenge of developing personalized dialysis therapy based on genetic discoveries.

    From Genes to Membrane Failure: Genetic Determinants of Peritoneal Dialysis Physiology and Outcomes · 2026 · DOI

  • There is a need to understand the genetic factors that influence peritoneal dialysis outcomes. The current literature lacks a comprehensive review of the genetic determinants of peritoneal membrane transport and fibrosis.

    From Genes to Membrane Failure: Genetic Determinants of Peritoneal Dialysis Physiology and Outcomes · 2026 · DOI

  • The lack of early diagnosis and intervention for CKD, as many patients remain asymptomatic until advanced stages. The need for additional CKD biomarkers and risk stratification models. The potential of CT-based perirenal structural characteristics to improve CKD diagnosis and risk assessment.

    Association of CT-based perirenal structural characteristics with chronic kidney disease risk categories: the additional value of imaging · 2026 · DOI

  • Current therapies are not sufficient to prevent disease progression. Conventional parameters such as albuminuria and estimated glomerular filtration rate are not accurate enough to predict disease progression. There is a need for biomarkers that can predict disease progression earlier and more accurately.

    Predictive value of kynurenine pathway metabolites in patients with diabetic kidney disease · 2026 · DOI

  • There is a need to clarify the clinical determinants and prognostic significance of the HALP score in DKD. Prior studies have not investigated the relationship between the HALP score and renal progression in a homogeneous cohort of patients with stage 3-4 CKD secondary to type 2 DM.

    HALP score and risk of renal progression in diabetic kidney disease · 2026 · DOI

  • The lack of understanding of the effects of Retatrutide on diabetes-associated renal injury. The need to investigate the modulation of inflammatory cytokines and HIF-1 gene expression in kidney tissue.

    Retatrutide treatment in streptozotocin-induced diabetic rats: renal inflammatory cytokines, HIF‑1α expression, and histopathological injury profile · 2026 · DOI

  • Longitudinal studies are needed to establish the temporal relationship between urinary succinate and kidney injury. Studies are needed to investigate the mechanisms by which urinary succinate is associated with kidney injury. Research is needed to develop and validate urinary succinate as a clinical biomarker for kidney injury.

    Urinary succinate is associated with kidney injury in type 2 diabetes mellitus: a cross-sectional analysis · 2026 · DOI

  • There is a lack of comprehensive evidence on the use of novel non-steroidal mineralocorticoid receptor antagonists in DKD. Prior studies have shown inconsistent results on the efficacy and safety of these antagonists. There is a need for a systematic review and meta-analysis to provide a clear overview of the current evidence.

    Efficacy and safety of novel non-steroidal mineralocorticoid receptor antagonists in diabetic kidney disease: an updated systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

  • The specific mechanistic contributions of microRNAs to exercise-mediated renoprotection remain to be established. Exercise intensity and duration are important determinants of the renal response, making it challenging to interpret renal miRNA responses.

    Exercise-mediated renoprotection across kidney diseases: emerging roles of microRNAs · 2026 · DOI

  • Limitations in interpreting the results due to the lack of an independently measured GFR using an exogenous filtration marker.

    Comparison of Established and Emerging Biomarkers Across Estimated GFR · 2026 · DOI

  • The relationships between established and emerging kidney biomarkers and eGFR are not well characterized. There is a need to evaluate the diagnostic accuracy of these biomarkers for true glomerular filtration. Prior studies have not systematically compared the relationships between these biomarkers and eGFR using multiple CKD-EPI equations.

    Comparison of Established and Emerging Biomarkers Across Estimated GFR · 2026 · DOI

  • Further research should focus on discovering the most efficient combined therapy to fully restore the inflammatory regulation ability. Research in severely metabolically challenged models is required to understand the potential synergy of renal function preservation and partial tapering of inflammatory activity.

    Atorvastatin Confers Renoprotection and Modulates Inflammation in Diabetic Rats on a High-Fat Diet · 2025 · DOI

  • The need to investigate the effects of atorvastatin treatment in diabetic-and-obese rats. The lack of understanding of atorvastatin's pleiotropic activities.

    Atorvastatin Confers Renoprotection and Modulates Inflammation in Diabetic Rats on a High-Fat Diet · 2025 · DOI

  • The need for a portable and user-friendly device for monitoring CKD progression. The limitations of current methods for measuring uACR, such as requiring laboratory equipment and trained personnel. The lack of a device that can provide seamless data transmission for efficient data management and patient monitoring.

    Urinary Albumin-to-Creatinine Ratio (uACR) Point-of-Care (POC) Device with Seamless Data Transmission for Monitoring the Progression of Chronic Kidney Disease · 2025 · DOI

  • Further studies are needed to confirm the findings and to explore the long-term effects of the therapy. Studies with larger sample sizes and control groups are needed to fully understand the effects of the therapy. Research on the mechanisms by which autologous dendritic cells exert their effects on FA and MMP-9 is needed.

    Diffusion Tensor Imaging Magnetic Resonance Imaging Assessment in a Clinical Trial of Autologous Dendritic Cell Transfer for Diabetic Kidney Disease: A Molecular Approach · 2025 · DOI

  • The direct correlation between non-invasive imaging biomarkers and inflammatory biomarkers in the context of immunotherapy remains underexplored. There is a need to evaluate the therapeutic impact of autologous dendritic cell transfer on diabetic kidney disease.

    Diffusion Tensor Imaging Magnetic Resonance Imaging Assessment in a Clinical Trial of Autologous Dendritic Cell Transfer for Diabetic Kidney Disease: A Molecular Approach · 2025 · DOI

  • Investigate the long-term effects of angiotensin on db/db mice. Examine the effects of angiotensin on female db/db mice. Study the mechanisms by which angiotensin exaggerates albuminuria in db/db mice.

    Angiotensin (1–7) exaggerates albuminuria and nephrin gene expression but does not modulate renal function-specific microRNAs expressions in kidneys of db/db mice · 2026 · DOI

  • The study had a cross-sectional design, which limits the ability to establish causality. The study population was limited to patients with T2DM and healthy controls, which may not be representative of other populations. The study relied on a single measurement of urinary succinate, which may not reflect long-term changes in kidney function.

    Urinary succinate is associated with kidney injury in type 2 diabetes mellitus: a cross-sectional analysis · 2026 · DOI

  • A small risk of false negatives remained. The study used a single random urine sample from each patient. The study had a relatively small sample size of 103 patients.

    Urinary Albumin-to-Creatinine Ratio (uACR) Point-of-Care (POC) Device with Seamless Data Transmission for Monitoring the Progression of Chronic Kidney Disease · 2025 · DOI

  • Investigating the underlying mechanisms of CKD, - Examining the potential of CT-based perirenal structural characteristics in other patient populations, - Developing and validating more accurate and reliable models for CKD risk assessment, - Exploring the potential of other imaging modalities in CKD diagnosis…

    Association of CT-based perirenal structural characteristics with chronic kidney disease risk categories: the additional value of imaging · 2026 · DOI

  • Reduced sample size, - Conservative multiple-comparison correction, - The study was limited to molecular and histopathological examinations, - The study did not reevaluate cognitive and metabolic…

    Retatrutide treatment in streptozotocin-induced diabetic rats: renal inflammatory cytokines, HIF‑1α expression, and histopathological injury profile · 2026 · DOI

  • Further studies on the clinical role of albuminuria, - Research on the treatment effects of SGLT2 inhibition and finerenone in selected patients with stable glomerular diseases, - Investigation of the safety boundaries for RASi therapy…

    Albuminuria as a treatment-response biomarker during layered kidney-protective therapy for albuminuric chronic kidney disease · 2026 · DOI

  • Most novel biomarkers remain investigational rather than established for routine clinical use, - Current therapies reduce rather than eliminate risk, - Residual risk remains greatest in patients with persistent albuminuria or advanced…

    Chronic Kidney Disease: Current Insights into Epidemiology, Molecular Mechanisms, Biomarkers and Management · 2026 · DOI

  • Precision prevention strategies that combine genetic risk detection with lifestyle and environmental interventions, - Further research on the role of molecular biomarkers and precision medicine in CKD…

    Chronic Kidney Disease: Current Insights into Epidemiology, Molecular Mechanisms, Biomarkers and Management · 2026 · DOI

  • The certainty of evidence was rated as low for some outcomes - The study had a limited number of trials - The study had heterogeneity in the included…

    Efficacy and safety of novel non-steroidal mineralocorticoid receptor antagonists in diabetic kidney disease: an updated systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

Most-cited papers in Chronic Kidney Disease and Diabetes

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Open questions raised by papers listed on this page include: (1) There is a need to understand the genetic factors that influence peritoneal dialysis outcomes (“From Genes to Membrane Failure: Genetic Determinants of Peritoneal Dialysis…”, 2026); (2) The lack of early diagnosis and intervention for CKD, as many patients remain asymptomatic until advanced stages (“Association of CT-based perirenal structural characteristics with chronic…”, 2026); (3) There is a need for biomarkers that can predict disease progression earlier and more accurately (“Predictive value of kynurenine pathway metabolites in patients with diabetic…”, 2026); (4) There is a need to clarify the clinical determinants and prognostic significance of the HALP score in DKD (“HALP score and risk of renal progression in diabetic kidney disease”, 2026); (5) The lack of understanding of the effects of Retatrutide on diabetes-associated renal injury (“Retatrutide treatment in streptozotocin-induced diabetic rats: renal…”, 2026). 1,214 gap statements have been mined from Chronic Kidney Disease and Diabetes papers in our 7.9M-paper local library, which holds 4,810 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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