Modular Strategies for Nephron Replacement and Clinical Translation Original paper
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Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Clinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
What was reviewed
This review examined modular nephron replacement strategies, highlighting how emerging bioengineered systems aim to reconstruct filtration, reabsorption, endocrine signaling, and microvascular exchange in a segment-specific manner. Drawing on perspectives, experimental data, and platform comparisons, the paper integrates insights from organoids, implantable bioartificial kidneys, 3D-bioprinted tissues, and decellularized scaffolds. It synthesizes their capabilities across glomerular filtration, proximal tubular solute handling, countercurrent concentration, distal regulation, and collecting-duct water balance while mapping each technology to native nephron functions.
Who was reviewed
The review draws from multidisciplinary work spanning stem-cell biology, tissue engineering, microfluidics, and device design. Study populations are models, not patients—human iPSC-derived organoids, bioprinted constructs, large-animal studies for iBK devices, and recellularized porcine or human kidney scaffolds. The paper integrates over 80 referenced studies, focusing on experimental systems that approximate nephron segments. It is inherently preclinical, describing how glomerular podocytes, proximal tubular epithelia, endothelial networks, and interstitial fibroblast-like cells behave in engineered environments. By evaluating cellular maturity, transporter expression, vascular integration, and endocrine activity, the review emphasizes readiness across biological and hybrid systems without involving clinical cohorts.
Most important findings
Across platforms, the review identifies filtration and proximal-tubule reabsorption as the segments best replicated to date, with organoids and bioprinted proximal tubules showing transporter activity and shear-responsive polarity. The nephron-platform table outlines precise cellular and molecular requirements, while the readiness matrix shows that vascular integration and hormonal responsiveness remain the major barriers. Organoids lack fully perfused vasculature and drainage; iBK devices provide physiologic filtration but minimal endocrine or tubular complexity; 3D bioprinting offers architectural precision but poor vascular scaling; scaffolds preserve ECM cues but face reseeding and immune-compatibility challenges. Critically, endocrine structures (JGA), countercurrent systems (loop of Henle), and peritubular capillaries remain unresolved bottlenecks for replicating dynamic nephron physiology.
| Key Area | Summary |
|---|---|
| Filtration | iBK membranes = most advanced; biological glomeruli still immature |
| Reabsorption | Proximal tubule models show robust transport but limited integration |
| Endocrine signaling | JGA recreation minimal; renin cells present but not functional |
| Vascularization | Largest unmet need across all biological platforms |
Key implications
The review argues that no single technology can replicate full nephron function; hybrid modular assemblies will be required. Device-based glomerular filtration may pair with biologically derived tubular segments, and scaffolds may provide structural “backbones” for multi-segment assembly. Clinical translation will hinge on vascular integration, immune compatibility, and interoperable design standards that allow plug-and-play nephron modules. Regulatory pathways must evolve to evaluate mixed living-cell and mechanical devices. Ultimately, modular nephron systems may supplement dialysis, delay progression of chronic kidney disease, or serve as bridge therapies long before whole-organ engineering becomes feasible.
Citation
Stepanova N, Tamazenko Y. Modular Strategies for Nephron Replacement and Clinical Translation. Kidney Dial. 2025;5:41. doi:10.3390/kidneydial5030041