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Open research questions in Chronic Kidney Disease and Diabetes

126 unresolved questions extracted from the limitations and future-work sections of 804 Chronic Kidney Disease and Diabetes papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Our study population was ethnically homogenous (> 98% Caucasian/white) and therefore our findings may not be generalizable to other ethnicities.

    Examining commonly used equations for estimating the glomerular filtration rate (GFR) in a healthy cohort of children and adolescents · 2026 · DOI

  • 4 Strengths and limitations This study is among the first to evaluate u-PDX in a South Asian population and includes internal validation of diagnostic performance. specificity or require complex assays, which limits routine use, and head-to-head comparative data remain scarce.

    Urinary podocalyxin as an early biomarker for diabetic nephropathy · 2026 · DOI

  • The landscape of diabetes management in chronic kidney disease is shifting from a singular focus on achieving a target HbA1c to a more holistic appreciation of glycemic stability. Substantial evidence from observational studies and emerging data from CGM research converge on a central theme: long-term visit-to-visit HbA1c variability is a robust, independent correlate of adverse renal outcomes, cardiovascular events, and mortality in patients with diabetes and CKD (Table 1). This variability likely reflects a confluence of factors, including treatment adherence, therapeutic efficacy, underlying metabolic instability, and susceptibility to complications. The clinical implications are clear. Risk stratification in diabetic kidney disease should incorporate an assessment of glycemic variability, in addition to traditional markers like albuminuria and eGFR. Therapeutic strategies should prioritize treatment regimens that minimize wide glucose fluctuations and hypoglycemia, particularly in advanced CKD where the margin for error is narrow. The integration of CGM into the management toolkit offers an unprecedented opportunity to visualize and address glycemic instability in real-time, moving towards truly personalized care. However, important knowledge gaps persist. Much of the evidence is observational, and causality is not fully established. There is a pressing need for randomized controlled trials to determine whether interventions specifically designed to reduce glycemic variability (guided by CGM or sophisticated analytics of serial HbA1c) can improve hard renal and cardiovascular outcomes. The optimal frequency and mode of CGM use in dialysis patients, its cost-effectiveness, and long-term impact on patient- reported outcomes require further investigation. Similarly, the efficacy and safety of automated insulin delivery systems in this complex population are promising but require rigorous evaluation. Future research should also explore the biological mechanisms linking glucose fluctuations to tissue injury, particularly in the context of uremia. Furthermore, the development and validation of integrated risk scores that ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT combine variability in HbA1c, blood pressure, and other parameters could enhance bedside prognostication. Ultimately, advancing the care of patients with diabetes and CKD will depend on embracing the complexity of glycemic control, leveraging technology for better assessment, and individualizing therapy to achieve not just a lower average glucose, but a safer and more stable glycemic journey.

    Glycemic instability in renal decline: a review of HbA1c variability and outcomes in chronic kidney disease · 2026 · DOI

  • FABP1 linked to DKD has been suggested to be a predictor for progression to microalbuminuria (A2) in patients with type 1 diabetes; whether FABP1 would be a more sensi- tive marker of DKD than albumin excretion rate is not well understood [21].

    Evaluation of FABP1 as a biomarker of diabetic kidney disease in children with type 1 diabetes · 2026 · DOI

  • Background: Non-canonical transforming growth factor beta (TGF-β) signaling plays a critical role in the progression of chronic kidney disease (CKD), but the pathological contributions of its downstream mitogen-activated protein kinases signaling such as extracellular signal-regulated kinase (ERK), p38α, and c-Jun N-terminal kinase (JNK) remain unclear.

    Selective JNK3 Inhibition Ameliorates TGF-β–Mediated Glomerular Injury and Fibrosis in the Kidneys · 2026 · DOI

  • Introduction Adropin is an energy homeostasis–related peptide implicated in metabolic and vascular regulation, but its relationship with diabetic kidney disease (DKD) remains unclear.

    Serum adropin as a potential renoprotective factor in diabetic kidney disease: evidence from a Chinese elderly cohort and an experimental mouse model · 2026 · DOI

  • L-Ergothioneine (EGT), a diet-derived antioxidant concentrated in renal tissue via the OCTN1 transporter, has shown renoprotective potential preclinically, but human interventional data are sparse.

    Effects of Ergothioneine Supplementation on Glomerular Filtration and Patient-Reported Urological Symptoms in Adults with Early Renal Function Decline: A Single-Center, Open-Label, Self-Controlled Trial · 2026 · DOI

  • Diabetic nephropathy (DN) is the leading cause of kidney failure in the developed world, but the genetic architecture of DN susceptibility is not well characterised.

    A Cross-Species Systems Genetics Framework Identifies Causal Genes in Diabetic Nephropathy · 2026 · DOI

  • However, sCysC in cats presented moderate elevations in CKD and, crucially, its clinical validation is limited by the scarcity of comparative studies between nephropathic animals and those with other non-renal pathologies.

    Beyond traditional biomarkers: do serum cystatin C and urinary cystatin B improve diagnostic precision in feline and canine renal disease? A systematic review and meta-analysis · 2026 · DOI

  • These inconsistent findings may stem from the dynamic nature of SUA levels during disease progression; single SUA measurements used in these studies may be insufficient to capture longitudinal changes and the cumulative burden of elevated SUA expo- sure.

    Association Between Time-Averaged Serum Uric Acid and Renal Outcomes in Patients with Type 2 Diabetes Mellitus with Chronic Kidney Disease: A Multicenter Retrospective Cohort Study · 2026 · DOI

  • Although the distribution of sex did not differ signifi- cantly across CKM stages in the present cohort, the potential impact of sex on PTX3-associated inflammatory pathways warrants further investigation in future studies. Validation in larger, multi- center, and ethnically diverse cohorts including both outpa- tient and inpatient CKM populations is warranted to further corroborate our findings. Prospective studies are warranted to determine whether PTX3 predicts subsequent CKM stage transitions or adverse cardiorenal outcomes.

    Pentraxin 3 is an inflammation-related biomarker that distinguishes early-stage from mid-advanced cardiovascular-kidney-metabolic syndrome · 2026 · DOI

  • In general, the results of this study confirm the necessity of conducting further studies on the application of nephron structural changes as diagnostic indicators of CKD that may eventually result in better diagnostic and treatment plans and minimise the impact of the development of kidney diseases.

    Structural Anatomy of the Nephron and Its Clinical Implications in Early Kidney Disease Detection · 2026 · DOI

  • To change the current status of CKD in the world, equal access to proven biomarkers and predictive instruments will be needed, especially in the low- and middlethe disease burden income nations where is large. Major multinational disproportionately partnerships are necessary to guarantee the validation of biomarkers in different populations and health care systems. Even smaller projects such as the Global Kidney Health Atlas show that there is a necessity to organize research methods, data repositories, and policy-level engagement in improving kidney care infrastructures at a global scale. The combination of these interventions will contribute to transforming CKD management into an inclusive, predictive, and preventative, and globally precision medicine system. One of the notable future directions of precision nephrology is incorporation of multi-omics information and transcriptomic, like metabolomic layers. High-frequency and pathwaybased techniques add strength to prognostic gene signatures, which can be applied in the personalized risk prediction and target therapeutic platforms in CKD populations. Optimal computation models also result in the practical examination of heterogeneous omics information, that is, the recognition of molecular pathways involving the development of diseases. AI and machine learning are highly likely to become even more central to the process of biomarker discovery and clinical risk stratification of chronic kidney disease. Big-data analytics can be used to work with the analysis of complex, high-dimensional clinical data, enhancing the modeling of disease and facilitating data-driven decision-making in nephrology care.

    Novel Biomarkers for Early Detection and Risk Stratification in Chronic Kidney Disease · 2026 · DOI

  • for managing hemolyzed samples in clinical chemistry testing. Clinical Chemistry and Laboratory Medicine (CCLM). 2018 Apr 25;56(5):718-27. (WG-PRE).

    Pre-Analytical Errors in Renal Diagnostics: Implications for Kidney Disease Evaluation, Patient Safety, and Clinical Decision-Making · 2026 · DOI

  • Quality indicators are an essential tool that will assist in ascertainment of the weak points of the pre-analytical phase and improving the quality of the renal diagnostics. Laboratory diagnostics is gaining popularity as an inherent goal in clinical decision making, and there is a suggestion of the need to standardize performance monitoring. International programs also promote standardized pre-analytical quality measures to reduce the number of errors that can be avoided and improve patient safety. The secret behind the regular application of such recommendations in the nephrology sector where the determination of the CKD staging is made by the utilization of biomarkers such as creatinine. efficacy of the diagnostic procedures to support the important stakes clinical decisions. Standard practices, in their turn, increase inter-laboratory and in the provision of evidence-based nephrology care in the healthcare sectors, it also increases comparability of outcome aids.

    Pre-Analytical Errors in Renal Diagnostics: Implications for Kidney Disease Evaluation, Patient Safety, and Clinical Decision-Making · 2026 · DOI

  • to Special Populations and Pediatrics: Special population studies, such as the elderly with frailty, the malnourished, pregnancy and postpartum, and pediatric populations, are necessary to determine the changes in thresholds and management with the use of cystatin C, as emphasized in the Contexts sections regarding the development of guidelines for special populations. REFERENCES 1. Bolton, G. R., Deen, W. M., & Daniels, B. S. (1998b). Assessment of the charge selectivity of glomerular basement membrane using Ficoll sulfate. American Journal of Physiology-Renal Physiology, F889–F896. 274(5): https://doi.org/10.1152/ajprenal.1998.274.5.f889 2. Vollenbröker, B., George, B., Wolfgart, M., Saleem, M. A., Pavenstädt, H., & Weide, T. (2008). mTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes. American Journal of Physiology-Renal Physiology, 296(2): F418–F426. https://doi.org/10.1152/ajprenal.90319.2008 3. Wilkie, M. (2015).

    SHRUNKEN PORE SYNDROME: AN OVERLOOKED ENTITY WITH MAJOR CLINICAL CONSEQUENCES · 2026 · DOI

  • While our findings provide novel insights into dapagliflozin's molecular effects beyond its primary SGLT-2 inhibition, the lack of correlation between miRNA alterations and microalbuminuria reduction warrants further investigation. More comprehensive, long-term studies with larger patient cohorts are warranted to elucidate the precise relationship between dapagliflozin's beneficial effects on miRNA alterations and clinical outcomes in DN.

    Effects of Dapagliflozin on miRNA Expression and Microalbuminuria in Diabetic Nephropathy · 2026 · DOI

  • Nevertheless, multinational validation studies incorporating ethnically ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT ARTICLE IN PRESS diverse populations are warranted to corroborate these findings and strengthen their clinical applicability across varying genetic and environmental backgrounds.

    Non-insulin-dependent insulin resistance surrogate indexes for predicting chronic kidney disease in diabetic individuals: a prospective cohort study · 2026 · DOI

  • Despite the rising burden of T2DM in Indonesia, the fifth largest diabetic population worldwide, population-specific evidence on DN risk factors from geographically distinct Indonesian regions remains scarce, limiting the development of locally relevant prevention strategies.

    Modifiable Risk Factors for Diabetic Nephropathy in Type 2 Diabetes Patients: A Case-Control Study from South Kalimantan, Indonesia · 2026 · DOI

  • Despite sharing a common origin, the UTs studied follow distinct metabolic pathways with different effects, highlighting the need for further investigation of the tryptophan pathway on CI in CKD.

    Association of Tryptophan Metabolites with Cognitive Impairment in Chronic Kidney Disease · 2026 · DOI

  • BACKGROUND While glycated hemoglobin (HbA1c) remains the clinical cornerstone for monitoring type 2 diabetes (T2D), the prognostic value of the cumulative glycemic burden and its dynamic trajectories for predicting incident diabetic kidney disease (DKD) remains insufficiently characterized.

    Dynamic glycemic exposure and trajectory profiling for incident diabetic kidney disease: A longitudinal cohort study · 2026 · DOI

  • Abstract Background The influence of life-course body size on the progression of cardio-renal-metabolic multimorbidity (CRMM) is insufficiently understood.

    Life-course body size trajectories and the progression of cardio-renal-metabolic multimorbidity: a prospective UK biobank study · 2026 · DOI

  • Druggable genes (DGGs) present a promising avenue, yet their causal prioritization in DN and their connections to gut microbiota-metabolite mechanisms remain underexplored.

    Therapeutic targets for diabetic nephropathy identified by druggable genome mendelian randomization: the role of the gut microbiota-metabolite axis · 2026 · DOI

  • Most participants (61%) showed high levels of adherence to DKD guidelines, but they presented a substantial gap in knowledge regarding the optimum screening time of DKD in patients with type 1 diabetes, the ideal screening test for albuminuria, the recommended interval for the routine surveillance, the annual screening tests, the therapeutic target of hemoglobin A1c (HbA1c), the indications of Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) and the timing of referral to a nephrologist.

    Determinants of primary healthcare physicians’ knowledge of diabetic kidney disease · 2026 · DOI

  • Background: Albuminuria reflects systemic endothelial dysfunction and cardiorenal interaction in heart failure (HF), yet its short-term prognostic value in acute decompensated HF (ADHF) remains incompletely characterized.

    Urinary Albumin-to-Creatinine Ratio as an Independent Predictor of 90-Day Outcomes in Patients Hospitalized for Acute Decompensated Heart Failure · 2026 · DOI

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126 open questions have been extracted from the limitations and future-work passages of 804 Chronic Kidney Disease and Diabetes papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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