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Pathophysiology and progression

TL;DR — Progression is the convergent result of nephron loss, single-nephron hyperfiltration, glomerular pressure, protein trafficking, inflammation, tubular injury and fibrosis. The remnant-nephron model generated the hypothesis that compensatory hyperfiltration can itself become injurious: micropuncture in five-sixths-nephrectomized rats found higher single-nephron GFR, transcapillary pressure and plasma flow alongside epithelial protein-reabsorption droplets, foot-process fusion and mesangial expansion, all largely attenuated by a low-protein diet, and the authors concluded only that sustained hyperfiltration may be maladaptive (Hostetter 1981, PMID 7246778). Fibrosis is a shared final pathway rather than a single disease mechanism (Wynn 2008, PMID 18161745). Albuminuria and eGFR trajectory remain the most practical integrators of these processes (CKD Prognosis Consortium 2023, PMID 37787795). AKI accelerates later CKD risk, but AKI diagnosis and management remain outside this condition's border.

Adaptive physiology becomes injury

After nephron loss, remaining nephrons increase filtration. Sustained intraglomerular pressure can enlarge workload while promoting albumin leakage and sclerosis. The evidence for this is animal micropuncture data — the structural lesions and their attenuation by protein restriction were shown in rats, not humans, and the paper is hypothesis-generating rather than confirmatory (Hostetter 1981, PMID 7246778).

Proteinuria as marker and mediator

Filtered proteins signal glomerular barrier injury and expose tubules to inflammatory and profibrotic stimuli. Lowering albuminuria is informative but not automatically proof of preserved GFR.

Fibrosis

Myofibroblast activation, extracellular-matrix deposition, capillary rarefaction and tubular atrophy integrate multiple initiating diseases (Wynn 2008, PMID 18161745). Human disease is heterogeneous, limiting inference from any single pathway.

Haemodynamic treatment signatures

RAS and SGLT2 inhibitors may cause an early eGFR dip while improving chronic slope; separating acute from chronic slope prevents misclassifying expected haemodynamics as toxicity (Heerspink 2021, PMID 34619108) (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371).

AKI-to-CKD border

An acute creatinine rise can reveal low reserve, cause incomplete recovery or accelerate fibrosis. This page owns the transition and surveillance consequence, not the acute syndrome itself.

Defining progression

Slope, sustained percentage decline, kidney failure and replacement therapy capture different horizons. Competing death and informative dropout complicate every endpoint (Tangri 2016, PMID 26757465).

Progression chain and measurable signatures

Process Observable signature Main inferential limit
Nephron loss and hyperfiltration High single-nephron workload; albuminuria Evidence is rat micropuncture; human single-nephron function is rarely measured (Hostetter 1981, PMID 7246778)
Glomerular barrier injury Albuminuria/proteinuria Marker and mediator roles are hard to separate
Tubular stress Injury markers, impaired concentrating or acid handling Many markers lack outcome validation
Inflammation Cytokine and cellular signatures Cause, consequence and comorbidity confounding
Fibrogenesis Matrix deposition, tubular atrophy, imaging or biopsy fibrosis Existing scar may not identify active reversible biology (Wynn 2008, PMID 18161745)
Haemodynamic therapy response Early eGFR dip Must separate acute from chronic slope (Heerspink 2021, PMID 34619108)
Progressive loss Sustained GFR decline, chronic slope, kidney failure Death and treatment change are competing/intercurrent events

What a nephron actually does, measured in humans

The remnant-nephron hypothesis was built on rat micropuncture; the human counterpart arrived much later and constrains it. Among 1,388 living kidney donors with iothalamate-measured GFR, contrast CT cortical volumetry and biopsy-determined glomerular density, mean GFR was 115 ± 24 mL/min, mean nephron number 860,000 ± 370,000 per kidney and mean single-nephron GFR 80 ± 40 nL/min (Denic 2017, PMID 28614683). Single-nephron GFR was essentially flat across age (below 70), sex and height (up to 190 cm) — meaning that the well-known fall in total GFR with age is driven by nephron loss, not by per-nephron decline. A higher single-nephron GFR was independently associated with larger nephrons, more glomerulosclerosis and arteriosclerosis than expected for age, height over 190 cm, obesity and a family history of ESKD (Denic 2017, PMID 28614683). This is the closest human evidence that hyperfiltration tracks with CKD risk factors and with structural injury — but it is cross-sectional and in donors, so it establishes association, not the causal direction that the rat model asserts.

Cell states, not cell types

Human kidney injury has now been mapped at single-cell resolution. Applying single-cell and single-nucleus assays to more than 400,000 nuclei or cells from 45 reference and 48 diseased kidneys, with spatial transcriptomics and roughly 1.2 million 3D imaging neighbourhoods, produced an atlas of 51 main cell types and — more importantly for progression — 28 cellular states across nephron segments and interstitium that are altered in injury: cycling, adaptive (successful or maladaptive repair), transitioning and degenerative (Lake 2023, PMID 37468583). Epithelial-repair signatures predicted maladaptive states associated with subsequent decline in kidney function (Lake 2023, PMID 37468583). The conceptual shift matters: fibrosis is not merely accumulated matrix but a stable disease-associated epithelial state that can be identified before scar is visible.

The mechanism most clearly worked out for that state is cell-cycle arrest. Proximal tubular cells arrested in G2–M form TOR–autophagy spatial coupling compartments (TASCCs) that secrete profibrotic factors, cyclin G1 promotes both the arrest and TASCC formation, TASCCs are present in proximal tubule cells of humans with CKD, and tubule-specific deletion of a key TASCC component slowed fibrosis progression in mice (Canaud 2019, PMID 30674655). This gives a concrete target class for antifibrotic therapy and a concrete explanation for why an injury that is over can still drive progression years later.

The hypoxia circuit

Interstitial fibrosis increases oxygen diffusion distance while peritubular capillaries rarefy, so tubular cells become hypoxic; hypoxia drives apoptosis and further fibrosis, closing a self-sustaining loop that operates across aetiologies. Efferent arteriolar vasoconstriction reduces post-glomerular capillary flow, angiotensin II impairs efficient tubular oxygen utilisation through oxidative stress, increased tubular metabolic demand raises consumption, and renal anaemia reduces delivery — several of these act before overt vascular pathology is visible (Nangaku 2006, PMID 16291837). This circuit is why anaemia correction, RAS blockade and HIF-prolyl-hydroxylase inhibition were all proposed as antifibrotic rather than merely symptomatic interventions, and it is the mechanistic bridge between the anaemia page and this one.

Local complement

Complement is classically a circulating, liver-derived system, but kidney cells synthesise complement components locally in both acute and chronic inflammation. Animal models of glomerular and tubulointerstitial disease show increased intrarenal complement expression; knockout of complement components and receptors, and pharmacological complement inhibition, reduce inflammation and fibrosis; single-cell RNA-sequencing, spatial transcriptomics and proteomics localise the change to the fibrotic microenvironment; and human biopsies show rising intracellular complement expression with disease progression (Portilla 2025, PMID 40519169). The evidence chain is currently strongest in animals and descriptive in humans — no complement inhibitor has a CKD-progression outcome trial outside specific glomerular diseases.

The AKI→CKD transition, quantified

The transition is asserted often and quantified rarely. Pooling 13 cohort studies, AKI carried an adjusted HR of 8.8 (95% CI 3.1–25.5) for incident CKD, 3.1 (1.9–5.0) for ESKD and 2.0 (1.3–3.1) for death, with pooled incidences of 25.8 and 8.6 per 100 person-years for CKD and ESKD; the association was graded by AKI severity and attenuated by lower baseline GFR (Coca 2012, PMID 22113526). The larger and methodologically stricter synthesis — 82 studies and 2,017,437 participants restricted to consensus AKI definitions with a non-exposed comparator and ≥1 year follow-up — gives more conservative estimates: new or progressive CKD HR 2.67 (1.99–3.58; 17.76 vs 7.59 per 100 person-years), ESKD HR 4.81 (3.04–7.62; 0.47 vs 0.08 per 100 person-years) and death HR 1.80 (1.61–2.02; 13.19 vs 7.26 per 100 person-years), again graded across AKI stages (See 2019, PMID 30473140).

The gap between HR 8.8 and HR 2.67 for incident CKD is itself the finding: the larger estimate came from studies with looser exposure definitions and less adjustment, and both reviews name incomplete outcome reporting, missing biochemistry and residual confounding by baseline kidney function as the dominant biases. Whether AKI causes subsequent CKD or reveals kidneys that were already losing reserve remains unsettled, and the effect size a clinician should assume differs roughly three-fold depending on which synthesis is used.

Exposure/mechanism Best human quantification What is still animal-only or associational
Nephron endowment and single-nephron GFR 860,000 ± 370,000 nephrons/kidney; snGFR 80 ± 40 nL/min (Denic 2017, PMID 28614683) Causal direction between high snGFR and later CKD
Maladaptive epithelial repair 28 injury-associated cell states; repair signatures predict function decline (Lake 2023, PMID 37468583) Whether states are reversible by any available drug
G2–M arrest and TASCC secretion TASCCs present in human CKD proximal tubule (Canaud 2019, PMID 30674655) Fibrosis reduction shown by knockout in mice only
Chronic tubulointerstitial hypoxia Framework supported by anaemia, RAS and HIF pharmacology (Nangaku 2006, PMID 16291837) No trial has used tissue oxygenation as an endpoint
Local complement activation Rising intrarenal complement expression on human biopsy with progression (Portilla 2025, PMID 40519169) Outcome trials confined to specific glomerular diseases
AKI as an accelerant CKD HR 2.67 (1.99–3.58), ESKD HR 4.81 (3.04–7.62) (See 2019, PMID 30473140) Causation versus revealed low reserve

The urate hypothesis, tested and failed twice

Elevated serum urate is strongly and consistently associated with CKD progression, which made urate lowering one of the most attractive mechanistic targets in the field. Two randomized trials published simultaneously in 2020 tested whether allopurinol slows progression in high-risk CKD and type 1 diabetic kidney disease.

CKD-FIX randomized adults with stage 3–4 CKD, no history of gout, and either uACR ≥265 mg/g or an eGFR fall of at least 3.0 mL/min/1.73 m² in the preceding year, to allopurinol 100–300 mg daily or placebo. Enrolment stopped early for slow recruitment at 369 of 620 intended patients; 363 (mean eGFR 31.7, median uACR 716.9, mean urate 8.2 mg/dL) contributed to the primary outcome. eGFR change at week 104 was −3.33 mL/min/1.73 m²/year (95% CI −4.11 to −2.55) with allopurinol and −3.23 (−3.98 to −2.47) with placebo — mean difference −0.10 (95% CI −1.18 to 0.97; p = 0.85). Serious adverse events occurred in 46% versus 44% (Badve 2020, PMID 32579811).

PERL randomized 530 people with type 1 diabetes, serum urate ≥4.5 mg/dL, eGFR 40.0–99.9 and evidence of diabetic kidney disease to allopurinol or placebo, with iohexol-measured GFR after 3 years plus a 2-month washout as the primary outcome. Serum urate fell from 6.1 to 3.9 mg/dL with allopurinol and stayed at 6.1 with placebo — an unambiguous target engagement. The between-group difference in measured GFR after washout was 0.001 mL/min/1.73 m² (95% CI −1.9 to 1.9; p = 0.99), and the annual measured-GFR decline was −3.0 versus −2.5 mL/min/1.73 m²/year (difference −0.6; 95% CI −1.5 to 0.4) (Doria 2020, PMID 32579810).

PERL is the more decisive of the two because it used measured rather than estimated GFR, achieved a large biochemical effect, and completed enrolment. Together the trials show that allopurinol did not slow progression in their enrolled populations despite successful urate lowering; they do not prove that every urate association in every CKD population is non-causal.

Inflammation: a positive signal that was never followed up

CANTOS randomized stable post-myocardial-infarction patients with hs-CRP ≥2 mg/L to placebo or canakinumab (IL-1β monoclonal antibody) at 50, 150 or 300 mg subcutaneously every three months, following 10,061 participants for a median 3.7 years. Of these, 1,875 (18.6%) had baseline eGFR below 60 and had substantially higher major adverse vascular event rates than those above (6.92 versus 4.13 per 100 person-years; p < 0.0001). Canakinumab reduced major adverse cardiovascular events in the CKD subgroup (HR 0.82, 95% CI 0.68–1.00; p = 0.05), with the largest benefit among those achieving on-treatment hs-CRP below 2 mg/L (HR 0.68, 0.53–0.86; p = 0.0015) (Ridker 2018, PMID 29793629).

This is direct randomized evidence that targeting the IL-1β pathway reduces cardiovascular events in CKD, and it has not been followed by a dedicated CKD trial. The result sits awkwardly with the negative urate trials: both targets were justified by inflammation-related mechanism, and the one that worked was tested only as a subgroup.

Klotho: the marker that did not survive adjustment

Klotho deficiency is central to the mechanistic account of CKD-MBD and vascular calcification. In 1,088 CRIC participants with eGFR 20–70 (mean 42; median plasma Klotho 0.31 ng/mL, IQR 0.10–3.27), comparing the highest with the lowest of six Klotho groups gave 5-year hazard ratios of 0.77 (95% CI 0.32–1.89) for mortality, 1.10 (0.38–3.17) for heart-failure hospitalisation, 1.19 (0.57–2.52) for atherosclerotic events and 1.05 (0.58–1.91) for the composite kidney endpoint — none significant. FGF23, by contrast, was significantly associated with mortality and heart-failure hospitalisation independently of Klotho (Edmonston 2024, PMID 38583756).

Circulating Klotho assay performance and sample storage are acknowledged limitations, so this is evidence against measured circulating Klotho as a biomarker rather than against the Klotho biology. The asymmetry with FGF23 in the same cohort and the same samples is nonetheless the strongest available data point.

Decision and interpretation matrix

Dimension Question Guardrail
Diagnostic axis Cause + G category + A category Avoid treating eGFR as the diagnosis
Time axis Chronicity and trajectory Separate acute change from persistent disease
Risk axis Kidney failure + cardiovascular events + death Show competing events
Treatment axis Eligibility, absolute benefit, harm, burden Do not rank drugs by relative effect alone
Measurement axis Assay, equation, repeatability State what was actually measured
Equity axis Testing, referral, access, affordability Audit downstream care, not labels only
Patient axis Symptoms, function, life participation Include outcomes patients prioritize
Evidence axis RCT, cohort, model, guideline Do not collapse designs

Evidence ledger

This ledger makes the page’s evidentiary mix inspectable. It does not imply that every source answers every question.

PMID Record used Role and boundary
7246778 Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. (Hostetter 1981, PMID 7246778) Observational or conceptual evidence; association is not treatment effect.
18161745 Cellular and molecular mechanisms of fibrosis. (Wynn 2008, PMID 18161745) Observational or conceptual evidence; association is not treatment effect.
37787795 Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. (CKD Prognosis Consortium 2023, PMID 37787795) Synthesis; heterogeneity and included-study definitions constrain transport.
34619108 Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. (Heerspink 2021, PMID 34619108) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38061371 Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the EMPA-KIDNEY trial. (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
26757465 Multinational assessment of equations predicting kidney failure. (Tangri 2016, PMID 26757465) Synthesis; heterogeneity and included-study definitions constrain transport.
38490803 KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. (KDIGO CKD Work Group 2024, PMID 38490803) Guideline or commentary; recommendation evidence depends on its review.
38519239 Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. (Levin 2024, PMID 38519239) Guideline or commentary; recommendation evidence depends on its review.
32061315 Global, regional, and national burden of chronic kidney disease, 1990-2017. (GBD CKD Collaboration 2020, PMID 32061315) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
22038337 A population-based approach for the definition of chronic kidney disease: CKD Prognosis Consortium. (Cirillo 2012, PMID 22038337) Synthesis; heterogeneity and included-study definitions constrain transport.
23243116 Cohort profile: the chronic kidney disease prognosis consortium. (Matsushita 2013, PMID 23243116) Observational or conceptual evidence; association is not treatment effect.
30348535 Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities. (Inker 2019, PMID 30348535) Synthesis; heterogeneity and included-study definitions constrain transport.
34554658 New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. (Inker 2021, PMID 34554658) Observational or conceptual evidence; association is not treatment effect.
34563581 A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. (Delgado 2022, PMID 34563581) Guideline or commentary; recommendation evidence depends on its review.
36857500 Kidney Failure Risk Equation evaluation with novel inputs in 59 cohorts. (Grams 2023, PMID 36857500) Observational or conceptual evidence; association is not treatment effect.
26028594 eGFR and albuminuria for prediction of cardiovascular outcomes: individual-participant meta-analysis. (Matsushita 2015, PMID 26028594) Synthesis; heterogeneity and included-study definitions constrain transport.
32970396 Dapagliflozin in Patients with Chronic Kidney Disease. (Heerspink 2020, PMID 32970396) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
36331190 Empagliflozin in Patients with Chronic Kidney Disease. (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
30990260 Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. (Perkovic 2019, PMID 30990260) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
41205219 Chronic Kidney Disease Prevalence and Awareness Among US Adults. (Gong 2026, PMID 41205219) Observational or conceptual evidence; association is not treatment effect.
38213490 Cost-effectiveness of screening for chronic kidney disease: evidence and gaps. (van Mil 2024, PMID 38213490) Guideline or commentary; recommendation evidence depends on its review.
39137037 Screening for chronic kidney disease: change of perspective and novel developments. (van Mil 2024, PMID 39137037) Observational or conceptual evidence; association is not treatment effect.
38186904 Cost-effectiveness of screening for CKD in the general adult population: systematic review. (Yeo 2024, PMID 38186904) Synthesis; heterogeneity and included-study definitions constrain transport.
40227684 Balancing Efficiency and Equity in Population-Wide CKD Screening. (Cusick 2025, PMID 40227684) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
37403003 Chronic kidney disease of unknown aetiology: a global review. (Rao 2023, PMID 37403003) Observational or conceptual evidence; association is not treatment effect.
33116757 Mesoamerican Nephropathy: What We Know so Far. (Sanchez Polo 2020, PMID 33116757) Observational or conceptual evidence; association is not treatment effect.
24522492 Relative risks of CKD for mortality and end-stage renal disease across races are similar. (Wen 2014, PMID 24522492) Observational or conceptual evidence; association is not treatment effect.
37921461 Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis (DUPLEX). (Rheault 2023, PMID 37921461) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.

What can and cannot be concluded

  • Risk associations do not by themselves establish that changing the marker changes risk.
  • A relative effect must be paired with baseline risk, follow-up and the exact endpoint.
  • Albuminuria, acute eGFR change, chronic eGFR slope and kidney failure are not interchangeable.
  • Subgroup consistency is not evidence that every subgroup had adequate power.
  • Guideline recommendations combine evidence with values, feasibility, cost and service capacity.
  • Older adults require competing-mortality and treatment-burden framing.
  • Dialysis and transplantation comparisons are vulnerable to eligibility and immortal-time bias.
  • Modelled lifetime benefit is not a randomized observed benefit.
  • A biochemical response without a patient-important outcome remains a surrogate result.
  • This page is research synthesis, not individualized medical advice.

Research-design checklist

  • Define CKD cause, G category, A category and chronicity at baseline.
  • Report the creatinine or cystatin C equation and laboratory calibration.
  • Prespecify acute and chronic eGFR slopes when haemodynamic effects are expected.
  • Keep sustained GFR decline, kidney failure and replacement therapy separable.
  • Report absolute event risks, follow-up and confidence intervals with relative effects.
  • Treat death as a competing event where it can preclude kidney failure.
  • Measure hyperkalaemia, acute kidney injury and treatment discontinuation consistently.
  • Include symptoms, function, life participation and treatment burden.
  • Describe background RAS, SGLT2, MRA and GLP-1 therapy explicitly.
  • Prespecify albuminuria and cause strata without over-reading underpowered interactions.
  • Record screening, prescribing, persistence and monitoring as separate implementation steps.
  • Report representation, access and affordability variables needed for equity analysis.

Open questions

  • Can any marker distinguish active, treatment-responsive fibrogenesis from established scar? Fibrosis is a shared final pathway, but no marker has been validated against outcomes (Wynn 2008, PMID 18161745). → OQ-12
  • Does the rat remnant-nephron mechanism operate at the same magnitude in human CKD? Single-nephron function is rarely measurable in people, so the hyperfiltration model remains inferred rather than demonstrated (Hostetter 1981, PMID 7246778).
  • How should an AKI episode update a long-term CKD risk estimate? Current tools are dominated by eGFR and uACR and have no standardised AKI severity or recovery input (Tangri 2016, PMID 26757465). → OQ-13

  • Is albuminuria a mediator of progression or only a marker of it? Lowering albuminuria does not reliably preserve GFR, as the FSGS result shows (Rheault 2023, PMID 37921461).

  • Does AKI cause subsequent CKD or reveal kidneys that were already losing reserve? Adjusted hazard ratios for incident CKD differ roughly three-fold between the two major syntheses (8.8, 3.1–25.5 versus 2.67, 1.99–3.58) largely because of exposure definition and adjustment (Coca 2012, PMID 22113526) (See 2019, PMID 30473140).

  • Are the maladaptive epithelial cell states identified in the human kidney atlas reversible, and does any existing drug move them (Lake 2023, PMID 37468583)?
  • Is elevated single-nephron GFR a cause of later CKD or a correlate of the same risk factors? The human data are cross-sectional in living donors (Denic 2017, PMID 28614683).

  • Can local intrarenal complement activation be targeted for CKD progression outside specific glomerular diseases (Portilla 2025, PMID 40519169)?

  • Why is urate so consistently associated with CKD progression and so completely without causal effect? Two trials — one with iohexol-measured GFR and unambiguous target engagement — found differences of −0.10 and 0.001 mL/min/1.73 m² (Badve 2020, PMID 32579811) (Doria 2020, PMID 32579810).

  • Should IL-1β blockade be tested prospectively in CKD? A prespecified CKD subgroup of 1,875 participants showed MACE HR 0.82 (0.68–1.00), and 0.68 (0.53–0.86) among hs-CRP responders, with no dedicated follow-up trial since 2018 (Ridker 2018, PMID 29793629).
  • Is circulating Klotho measurable well enough to be a biomarker? It showed no association with any 5-year outcome in CRIC while FGF23 in the same samples did (Edmonston 2024, PMID 38583756).

References

  1. Hostetter et al. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981;241(1):F85-F93. PMID 7246778
  2. Wynn et al. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199-210. PMID 18161745
  3. CKD Prognosis Consortium et al. Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. JAMA. 2023;330(13):1266-1277. PMID 37787795
  4. Heerspink et al. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9(11):743-754. PMID 34619108
  5. EMPA-KIDNEY Collaborative Group et al. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol. 2024;12(1):39-50. PMID 38061371
  6. Tangri et al. Multinational assessment of equations predicting kidney failure. JAMA. 2016;315(2):164-174. PMID 26757465
  7. KDIGO CKD Work Group et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. PMID 38490803
  8. Levin et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684-701. PMID 38519239
  9. GBD CKD Collaboration et al. Global, regional, and national burden of chronic kidney disease, 1990-2017. Lancet. 2020;395(10225):709-733. PMID 32061315
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  13. Inker et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-1749. PMID 34554658
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  19. Perkovic et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. PMID 30990260
  20. Gong et al. Chronic Kidney Disease Prevalence and Awareness Among US Adults. JAMA Cardiol. 2026;11(1):77-81. PMID 41205219
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