CKD, Glomerular Disease & Renal Innovation
A comprehensive analysis of the nephrology clinical trial landscape — from estimated GFR-based endpoint design and kidney biopsy infrastructure to novel biomarker integration and pipeline dynamics across CKD progression, IgA nephropathy, and emerging renal therapies.
The Nephrology Trial Landscape in 2026
Nephrology has undergone a remarkable transformation in the clinical trial landscape over the past several years. Once considered a therapeutic area with limited pipeline activity and few disease-modifying options beyond renin-angiotensin system (RAS) blockade, nephrology now stands at the forefront of metabolic and immunologic drug development. Within the Clinitiative network, nephrology encompasses 10 active studies spanning chronic kidney disease (CKD) at all stages, IgA nephropathy (IgAN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), polycystic kidney disease (PKD), and dialysis innovation studies. This portfolio reflects the accelerating pace of renal therapeutic development and the growing recognition of kidney disease as a global public health priority.
The approval and widespread adoption of SGLT2 inhibitors — initially developed for type 2 diabetes but now established as cornerstone CKD therapy regardless of diabetes status — has fundamentally reshaped the nephrology trial landscape. Every new CKD study must now account for background SGLT2 inhibitor use, either as a required co-therapy or as a stratification factor. Similarly, finerenone's emergence as a complementary agent for diabetic kidney disease has added another layer of background therapy complexity. These advances have raised the bar for new agents, which must demonstrate incremental benefit on top of optimized standard of care rather than against placebo alone.
Perhaps the most consequential regulatory development in nephrology has been the acceptance of eGFR slope as a reasonably likely surrogate endpoint for accelerated approval. Traditional renal outcome trials required years of follow-up to capture doubling of serum creatinine, end-stage kidney disease, or renal death. The eGFR slope approach — measuring the rate of kidney function decline over shorter time horizons — has compressed development timelines and attracted sponsors who previously considered nephrology trials impractical due to their duration and cost. This shift has catalyzed a surge in glomerular disease programs targeting IgAN, FSGS, and complement-mediated nephropathies, creating new opportunities and operational demands across our research network.
Key Performance Metrics
Network-wide benchmarks from our nephrology portfolio provide critical reference points for study planning and site performance evaluation across the spectrum of renal indications.
Across all renal indications, our network sites achieve a median enrollment rate of 1.4 patients per site per month. Broad CKD studies perform best at 1.8 patients per site per month, benefiting from large eligible populations identified through routine eGFR screening in primary care and diabetes clinics. IgA nephropathy studies average 0.6 patients per site per month, requiring nephrology referral networks and biopsy-confirmed diagnosis. FSGS studies are the most challenging at 0.3 patients per site per month, reflecting the rarity of the condition and the stringent histopathologic eligibility criteria that narrow the recruitable population considerably.
Screen failure rates across the nephrology portfolio average 34%, driven primarily by eGFR range criteria that exclude patients with kidney function either too preserved or too advanced for the study population, proteinuria thresholds that require confirmed quantification via urine protein-to-creatinine ratio (UPCR) or urine albumin-to-creatinine ratio (UACR), and concomitant medication requirements including mandatory RAS blockade at stable doses. Glomerular disease studies requiring diagnostic biopsy confirmation carry higher screen failure rates approaching 42%, as historical biopsies may not meet protocol-specified pathologic criteria.
From contract execution to first patient enrolled, nephrology sites within the network achieve a median startup time of 14.6 weeks. This moderate timeline reflects the specialized infrastructure requirements including nephrology investigator credentialing, kidney biopsy suite validation, renal function laboratory certification, and dialysis center research agreements for studies involving hemodialysis or peritoneal dialysis populations. Sites with established nephrology research programs and pre-existing biopsy capabilities consistently achieve startup 2-3 weeks faster than sites requiring new procedural agreements.
The overall patient retention rate across nephrology studies is 84%, reflecting strong patient motivation to slow CKD progression and avoid or delay dialysis initiation. CKD patients who understand the connection between trial participation and kidney preservation demonstrate high engagement with study visits and protocol compliance. Dialysis studies benefit from inherent retention advantages, as patients attend regular treatment sessions 3-4 times per week, enabling study procedures to be integrated into routine dialysis visits. Retention is lowest in early-stage CKD studies where patients may feel asymptomatic and less motivated to continue long-duration protocols.
Network Capabilities
Executing nephrology trials at the complexity required by modern protocols demands specialized renal assessment infrastructure, biopsy capabilities, dialysis research integration, and cardiorenal monitoring expertise. Our network has been intentionally developed to ensure deep nephrology-specific capabilities across every participating site.
Renal Function Assessment
Accurate measurement of kidney function is the foundation of every nephrology clinical trial. Our network sites maintain capabilities for both estimated and measured glomerular filtration rate (GFR) assessment, including iothalamate and iohexol clearance protocols for studies requiring gold-standard measured GFR rather than creatinine-based estimates. Sites are equipped for standardized 24-hour urine collections with validated specimen integrity verification, spot urine protein-to-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) measurement using calibrated laboratory assays, and serial serum creatinine and cystatin C monitoring for eGFR slope calculations that form the basis of accelerated approval endpoints.
For studies utilizing the eGFR slope as a primary or key secondary endpoint, our sites follow standardized sample collection protocols that minimize pre-analytical variability — including fasting requirements, hydration status documentation, and time-of-day consistency across visits. This rigor ensures that eGFR measurements reflect true changes in kidney function rather than collection artifacts, supporting regulatory-quality data submissions.
Kidney Biopsy & Pathology
Glomerular disease trials frequently require kidney biopsy for diagnostic confirmation, baseline histopathologic scoring, or on-treatment assessment of disease activity and chronicity. Our network sites offer percutaneous renal biopsy performed by interventional radiologists or nephrologists under ultrasound guidance, with established post-biopsy observation protocols that include serial hemoglobin monitoring, imaging surveillance for bleeding complications, and standardized discharge criteria. Biopsy specimens are processed for light microscopy, immunofluorescence, and electron microscopy — the full triad required for accurate glomerular disease classification.
For IgA nephropathy studies, sites maintain expertise in Oxford classification (MEST-C) scoring and IgA/complement staining interpretation. FSGS studies require podocyte assessment and segmental sclerosis grading. All biopsy specimens are processed according to sponsor-specified protocols with tissue allocation for central pathology review, ensuring consistency across multi-site studies and supporting histopathologic endpoints.
Dialysis Research Integration
Clinical trials involving patients on dialysis present unique logistical requirements that demand close coordination between research operations and dialysis care delivery. Our network includes partnerships with both hospital-based and free-standing dialysis centers that provide research access to hemodialysis and peritoneal dialysis populations. Sites can perform intradialytic study procedures — including blood sampling at specific time points relative to dialysis sessions, drug administration during or between treatments, and hemodynamic monitoring during fluid removal — without disrupting standard dialysis schedules.
For studies evaluating novel dialysis technologies, improved membrane compositions, or dialysis adequacy interventions, our sites maintain standardized Kt/V measurement protocols, ultrafiltration documentation, and vascular access assessment capabilities. Research coordinators embedded in dialysis units facilitate patient identification, consent processes, and study visit scheduling that aligns with the thrice-weekly hemodialysis rhythm.
Cardiorenal Monitoring
The growing recognition of cardiorenal syndrome — the bidirectional relationship between heart and kidney disease — has made cardiovascular monitoring an essential component of nephrology trials. Many CKD studies now include cardiovascular outcome endpoints or require cardiac safety assessments as secondary measures. Our network sites offer NT-proBNP and high-sensitivity troponin monitoring, comprehensive fluid balance assessment including bioimpedance analysis, ambulatory blood pressure monitoring (ABPM) for studies evaluating agents with hemodynamic effects, and echocardiography for left ventricular structure and function assessment.
For studies in advanced CKD and dialysis populations where cardiovascular events represent the leading cause of mortality, sites maintain adjudication-quality event documentation and established relationships with cardiology subspecialists for event classification. This cardiorenal monitoring infrastructure supports the increasing number of trials designed to demonstrate both renal and cardiovascular benefit simultaneously.
Enrollment Dynamics
Nephrology enrollment patterns are shaped by the intersection of disease prevalence, diagnostic requirements, and the evolving standard of care landscape. Understanding these dynamics is essential for realistic enrollment planning and site management across the spectrum of renal indications.
CKD patients represent the largest recruitable population in nephrology, with identification increasingly driven by eGFR screening integrated into routine primary care and diabetes clinic workflows. Electronic health record (EHR) alerts for declining eGFR or elevated albuminuria serve as powerful pre-screening tools, enabling research coordinators to identify eligible patients before they are seen by nephrologists. Our network leverages these EHR-based identification strategies across primary care, endocrinology, and cardiology referral channels, capturing CKD patients at earlier stages when intervention may have the greatest impact on long-term kidney outcomes.
IgA nephropathy recruitment relies heavily on nephrology referral networks and academic medical center glomerulonephritis clinics where biopsy-confirmed patients are concentrated. FSGS enrollment is among the most challenging in all of nephrology due to the disease's rarity, the requirement for histopathologic confirmation, and the heterogeneous nature of the condition with multiple underlying etiologies. Our network addresses FSGS recruitment through relationships with transplant centers and academic nephrology programs where FSGS patients are followed longitudinally. Dialysis patients are identified through dialysis center partnerships, with the advantage that this population attends regular treatments multiple times per week, facilitating both identification and ongoing study participation.
The high comorbidity burden in the CKD population — particularly the co-occurrence of diabetes, hypertension, cardiovascular disease, and anemia — creates both opportunities and challenges for enrollment. While these comorbidities increase the likelihood of patients being seen regularly by healthcare providers (improving identification), they also introduce concomitant medication complexity, competing trial eligibility conflicts, and safety monitoring requirements that can slow screening and enrollment workflows. Careful protocol design that accounts for real-world CKD comorbidity patterns is essential for achievable enrollment targets.
Key Challenges in Nephrology Trial Execution
The unique characteristics of kidney disease and the evolving standard of care present operational challenges that require specialized strategies and infrastructure.
Long-Duration Outcome Trials
Traditional renal outcome endpoints — including sustained 40% or 57% decline in eGFR, end-stage kidney disease (ESKD), and renal death — require extended follow-up periods of 2-4 years to accumulate sufficient events for statistical powering. This duration creates significant operational challenges including site staff turnover, patient fatigue, and protocol amendment complexity. The adoption of eGFR slope as a surrogate endpoint for accelerated approval has partially mitigated this challenge, with some programs achieving regulatory submissions based on 6-9 month slope data. However, confirmatory outcome trials remain necessary, and sponsors must plan for the operational and financial commitment of multi-year nephrology studies. Our network supports long-duration study execution through dedicated site retention programs, longitudinal patient engagement strategies, and experienced coordinators who maintain study continuity across extended timelines.
Background Therapy Optimization
The rapid evolution of CKD standard of care — with SGLT2 inhibitors now recommended for all CKD patients with eGFR above 20 ml/min and finerenone established for diabetic kidney disease — creates complex trial design considerations. New investigational agents must demonstrate benefit on top of optimized background therapy that may already include ACE inhibitors or ARBs, SGLT2 inhibitors, and potentially finerenone. This triple or quadruple background therapy creates challenges for demonstrating incremental efficacy, requires run-in periods to stabilize background medications, and complicates safety monitoring as adverse events may be attributable to multiple concurrent agents. Protocol designs must carefully define required versus permitted background therapies, establish washout or optimization periods, and implement stratification factors that account for the variable background treatment landscape across the enrolled population.
Kidney Biopsy Requirements & Risks
Many glomerular disease trials require kidney biopsy for diagnostic confirmation, baseline disease characterization, or on-treatment histopathologic assessment. While percutaneous renal biopsy is generally safe, it carries inherent risks including hemorrhage (occurring in approximately 5-10% of procedures, with clinically significant bleeding in 1-2%), post-procedural pain, and rare but serious complications requiring intervention. Patient reluctance to undergo biopsy — particularly repeat biopsies for on-treatment assessment — is a meaningful source of screen failure and study discontinuation. Our network addresses this through experienced biopsy operators who maintain complication rates below national benchmarks, thorough patient education regarding biopsy risk-benefit ratios, and protocol consultation that helps sponsors optimize biopsy requirements to minimize patient burden while preserving essential histopathologic data.
Dialysis Population Complexity
Conducting clinical trials in dialysis patients introduces a unique set of operational challenges that distinguish this population from pre-dialysis CKD. Hemodialysis patients carry a high comorbidity burden including cardiovascular disease, diabetes, anemia, bone mineral disorder, and malnutrition, creating complex eligibility assessments and elevated safety monitoring requirements. Vascular access challenges — including arteriovenous fistula or graft complications and central venous catheter-related issues — can limit blood sampling and intravenous drug administration capabilities. Study visit scheduling must accommodate the thrice-weekly hemodialysis rhythm, with consideration for interdialytic versus intradialytic procedures and the physiologic variability that occurs across the dialysis cycle. Our network sites with dialysis research experience have developed specialized workflows that integrate study procedures seamlessly into dialysis sessions, reducing patient burden while maintaining protocol compliance and data quality.
Pipeline Analysis
The nephrology development pipeline has expanded dramatically, driven by regulatory pathway innovations, validated surrogate endpoints, and the commercial success of SGLT2 inhibitors that demonstrated the viability of kidney-focused drug development. Several therapeutic modalities are driving significant shifts in trial design and site requirements.
Novel CKD Progression Inhibitors
Beyond SGLT2 inhibitors and finerenone, the next wave of CKD therapeutics targets multiple pathogenic pathways driving kidney fibrosis and progression. Endothelin receptor antagonists (ERAs) are in advanced development for diabetic kidney disease and proteinuric CKD, with atrasentan leading the class following positive Phase III results demonstrating significant proteinuria reduction. Aldosterone synthase inhibitors offer an alternative approach to mineralocorticoid pathway blockade with potentially fewer hyperkalemia-related side effects than mineralocorticoid receptor antagonists. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), already approved for renal anemia in some markets, are being investigated for potential renoprotective effects beyond erythropoiesis. These programs require careful background therapy documentation, hyperkalemia monitoring protocols, and fluid balance assessment capabilities at participating sites.
Glomerular Disease Targeted Therapies
Glomerular diseases represent the most dynamic segment of the nephrology pipeline, with precision medicine approaches replacing the broad immunosuppression that historically defined treatment. Complement inhibitors targeting the alternative and lectin pathways are advancing rapidly for IgA nephropathy and C3 glomerulopathy (C3G), with iptacopan and other factor B and factor D inhibitors in Phase II and III development. Anti-CD20 therapies are being evaluated for treatment-resistant FSGS, targeting B-cell mediated circulating factor production. Anti-BAFF and anti-APRIL agents represent a novel approach to IgA nephropathy by targeting the mucosal immune pathway that drives galactose-deficient IgA1 production. Lupus nephritis programs utilizing anti-BAFF, calcineurin inhibitors, and Type I interferon receptor antibodies continue to expand. These targeted therapies require biopsy infrastructure for patient selection, complement and immunoglobulin level monitoring, and infectious disease screening protocols given the immunosuppressive nature of many agents.
PKD Disease-Modifying Approaches
Autosomal dominant polycystic kidney disease (ADPKD) remains an area of significant unmet need despite the approval of tolvaptan, which is limited by aquaretic side effects, hepatotoxicity monitoring requirements, and the need for strict water intake management. Next-generation vasopressin V2 receptor antagonists with improved tolerability profiles are in development, alongside entirely novel mechanisms targeting cyst growth and proliferation. These include mTOR pathway modulators with kidney-specific targeting, somatostatin analogs, CFTR modulators to reduce cyst fluid secretion, and early-stage gene therapy approaches targeting PKD1 and PKD2 mutations. PKD studies require total kidney volume (TKV) measurement via MRI as a key endpoint, necessitating standardized imaging protocols, central radiology review, and volumetric analysis capabilities at participating sites.
Kidney Regeneration & Dialysis Innovation
The most forward-looking segment of the nephrology pipeline addresses the fundamental challenge of kidney replacement for patients with end-stage kidney disease. Artificial kidney development programs aim to create wearable or implantable devices that replicate glomerular filtration and tubular reabsorption, potentially freeing patients from facility-based dialysis. Bioartificial kidney constructs incorporating living renal tubular cells on biocompatible scaffolds are advancing through early feasibility studies. Regenerative medicine approaches — including renal progenitor cell therapy, organoid-based kidney tissue engineering, and xenotransplantation research — represent longer-term opportunities that are generating early-phase clinical data. In the nearer term, improved dialysis membrane technologies, sorbent-based portable dialysis systems, and enhanced peritoneal dialysis solutions are in clinical testing with more immediate translational potential. These programs require specialized engineering and biocompatibility assessment capabilities alongside traditional clinical trial infrastructure.
Site Requirements for Nephrology Excellence
The infrastructure, staffing, and operational processes required to execute modern nephrology protocols at the highest level of quality and regulatory compliance.
Certified laboratory capabilities for serum creatinine, cystatin C, BUN, and electrolyte panels with same-day turnaround. Standardized 24-hour urine collection and processing for proteinuria quantification, creatinine clearance, and electrolyte excretion. Capacity for iothalamate or iohexol measured GFR protocols when required by study design. Central laboratory specimen processing and shipping infrastructure for PK/PD and biomarker samples.
Ultrasound-guided percutaneous renal biopsy capability performed by credentialed interventional radiologists or nephrologists. Post-biopsy observation area with serial monitoring protocols. Specimen processing for light microscopy, immunofluorescence, and electron microscopy. Tissue allocation procedures for central pathology review and biobanking per sponsor specifications.
Established partnerships with hemodialysis and peritoneal dialysis centers enabling research access to dialysis populations. Capability for intradialytic study procedures including blood sampling, hemodynamic monitoring, and investigational product administration. Standardized Kt/V and dialysis adequacy measurement protocols. Vascular access documentation and assessment capabilities.
Comprehensive cardiorenal assessment including NT-proBNP and high-sensitivity troponin, ambulatory blood pressure monitoring (ABPM), echocardiography, ECG with central reading capabilities, and bioimpedance analysis for fluid volume assessment. Established cardiology referral pathways for cardiovascular event adjudication and subspecialty consultation in the CKD population.
Dedicated research pharmacy with temperature-controlled storage for investigational products, including specialized handling for biologic agents and complement inhibitors. Drug accountability systems, randomization management through interactive response technology (IRT), and dispensing protocols for oral and injectable study medications. Potassium binder and rescue medication inventory for hyperkalemia management protocols.
Dedicated nephrology clinical research coordinators with experience in renal function assessment, biopsy coordination, and dialysis research workflows. Research nurses trained in infusion administration and adverse event monitoring specific to nephrology agents. Data managers proficient in EDC systems and eGFR slope calculation methodologies. Regulatory coordinators managing IRB submissions and protocol amendments across multi-study nephrology portfolios.
Discuss Your Nephrology Program
Connect with our team to explore site capabilities, enrollment strategies, and renal assessment infrastructure for your nephrology clinical development program.