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Diabetic kidney disease

TL;DR — Diabetic kidney disease is a clinical phenotype rather than proof that every kidney lesion in a person with diabetes is diabetic nephropathy. RAS blockade established kidney protection in albuminuric type 2 diabetes (Brenner 2001, PMID 11565518); CREDENCE then reduced its kidney/cardiovascular composite by 30% (Perkovic 2019, PMID 30990260); finerenone reduced CKD progression (Bakris 2020, PMID 33264825); and FLOW added a dedicated semaglutide kidney-outcome result (Perkovic 2024, PMID 38785209). The kidney regimen is now layered. One pair of layers has been randomized head-to-head: CONFIDENCE compared finerenone, empagliflozin and both, and combination therapy lowered uACR 29% more than finerenone alone and 32% more than empagliflozin alone at 180 days (Agarwal 2025, PMID 40470996) — but on albuminuria, not kidney failure. Randomized evidence for the full four-class combination and for sequence on hard outcomes is still absent; the lifetime estimates are modelled (Neuen 2024, PMID 37952217). Glycaemic targets and glucose-lowering strategy belong to the diabetes conditions; this page owns albuminuria, eGFR and kidney failure.

Phenotyping

Long duration, retinopathy and progressive albuminuria support attribution, while active sediment, abrupt decline, systemic features or atypical chronology raise alternative disease.

RAS foundation

Losartan reduced doubling of creatinine, kidney failure or death in overt nephropathy (Brenner 2001, PMID 11565518). Dual blockade later proved harmful (Fried 2013, PMID 24206457).

SGLT2 layer

CREDENCE enrolled uACR above 300 mg/g on RAS blockade and reduced the primary outcome (HR 0.70, 95% CI 0.59–0.82) (Perkovic 2019, PMID 30990260).

Finerenone layer

FIDELIO-DKD reduced the kidney composite (17.8% vs 21.1%; HR 0.82, 95% CI 0.73–0.93) in 5,734 patients, with hyperkalaemia-related discontinuation 2.3% versus 0.9% (Bakris 2020, PMID 33264825). Finerenone's evidence base no longer stops at type 2 diabetes: FIND-CKD covered non-diabetic CKD and FINE-ONE covered type 1 diabetes, the latter on a six-month albuminuria endpoint in 242 participants (Heerspink 2026, PMID 42246672) (Heerspink 2026, PMID 41780000).

GLP-1 layer

FLOW reduced major kidney events in type 2 diabetes and CKD (HR 0.76, 95% CI 0.66–0.88) (Perkovic 2024, PMID 38785209).

Combination gap

The four-class lifetime model is not a randomized outcome trial of the combination; sequence, interaction, adherence and cost remain open (Neuen 2024, PMID 37952217). As of this audit (2026-09-02) the only randomized combination evidence is CONFIDENCE's 180-day albuminuria comparison of finerenone, empagliflozin and both (Agarwal 2025, PMID 40470996), whose secondary analysis showed combination therapy did not reduce hyperkalaemia relative to finerenone alone (Agarwal 2026, PMID 41493296). Glycaemic targets and treatment belong to type 2 diabetes and type 1 diabetes; this page owns the kidney endpoint.

Kidney-outcome platform

Layer Pivotal evidence Kidney effect Principal boundary
ARB RENAAL / IDNT Hard kidney-outcome reduction Proteinuric T2D nephropathy (PMIDs: 11565518, 11565517)
SGLT2 inhibitor CREDENCE Primary HR 0.70 (0.59–0.82) uACR >300 mg/g on RAS blockade (Perkovic 2019, PMID 30990260)
Non-steroidal MRA FIDELIO-DKD Kidney HR 0.82 (0.73–0.93) Potassium monitoring; T2D in this trial, but non-diabetic and type 1 evidence now exists (Bakris 2020, PMID 33264825; Heerspink 2026, PMIDs: 42246672, 41780000)
GLP-1 receptor agonist FLOW Kidney/CV composite HR 0.76 (0.66–0.88) Albuminuric T2D CKD (Perkovic 2024, PMID 38785209)
Full combination Lifetime model Estimated event-free survival gain Not randomized for outcomes; only the finerenone+empagliflozin pair has randomized albuminuria data (Neuen 2024, PMID 37952217; Agarwal 2025, PMID 40470996)

What glycaemic control does and does not buy

The kidney effect of glucose lowering is real, modest and slow. Individual-participant meta-analysis of ACCORD, ADVANCE, UKPDS and VADT (27,049 participants, median 5.0 years, IQR 4.5–5.0) found that more intensive control achieved a mean HbA1c difference of −0.90% (95% CI −1.22 to −0.58) and reduced kidney events — a composite of ESKD, renal death, eGFR falling below 30, or development of overt diabetic nephropathy — by 20% (HR 0.80, 95% CI 0.72–0.88; p < 0.0001), with 1,626 kidney events recorded. Eye events fell 13% (0.87, 0.76–1.00; p = 0.04) and nerve events were not reduced (Zoungas 2017, PMID 28365411). Cross-trial comparisons with SGLT2 inhibitors or finerenone are not valid measures of benefit per unit of treatment burden because populations, endpoints and follow-up differ.

In type 1 diabetes the same intervention has a longer shadow. Over EDIC years 1–18 following DCCT, 191 new cases of microalbuminuria occurred — 71 in the former intensive group and 120 in the former conventional group — despite mean HbA1c converging between the groups after the trial ended (DCCT/EDIC Research Group 2014, PMID 25043685). The persistence of divergence after exposure equalises is the clearest human evidence for metabolic memory, and it argues that early glycaemic control has value that a contemporaneous HbA1c cannot represent.

Non-albuminuric diabetic kidney disease

The albuminuria-first model of diabetic nephropathy no longer describes the majority phenotype. In RIACE, 15,773 people with type 2 diabetes enrolled in 2006–2008 with vital status retrieved for 15,656 (99.26%), adjusted mortality risk relative to no kidney disease was 1.45 (95% CI 1.33–1.58) for albuminuria alone, 1.58 (1.43–1.75) for reduced eGFR alone, and 2.08 (1.88–2.30) for both. Normoalbuminuric individuals with eGFR below 45 — particularly those with low-range albuminuria of 10–29 mg/day — carried risk exceeding that of microalbuminuric individuals and similar to macroalbuminuric individuals with preserved eGFR (Penno 2018, PMID 30032426).

Two things follow. Reduced eGFR without albuminuria is not a benign phenotype, and the classical "microvascular signature" correlates — glycaemic exposure and retinopathy — predicted mortality only in the albuminuric phenotypes, while prevalent cardiovascular disease and low HDL cholesterol predicted it in all of them (Penno 2018, PMID 30032426). This is consistent with non-albuminuric diabetic kidney disease being predominantly vascular rather than glomerular in origin, which would explain why glycaemic interventions perform worse in that group — but the causal claim has not been tested directly.

Weight as an intervention on the kidney

Bariatric surgery has the largest observed effect on kidney trajectory of any non-pharmacological intervention in this population. Matching 985 surgical patients to 985 non-surgical controls on demographics, baseline BMI, eGFR, comorbidity and prior nutrition-clinic use (mean age 45, 80% female, 33% with baseline eGFR <90), mean 1-year weight loss was 40.4 kg versus 1.4 kg. Over median 4.4 and 3.8 years respectively, 85 versus 177 patients had an eGFR decline ≥30% and 22 versus 50 had doubled creatinine or ESRD, giving adjusted hazard ratios of 0.42 (95% CI 0.32–0.55) and 0.43 (0.26–0.71), with consistency across subgroups defined by baseline eGFR, hypertension and diabetes (Chang 2016, PMID 27181999).

The design limit is unavoidable and should be stated: patients selected for and completing bariatric surgery differ from matched controls in ways that propensity matching on the listed covariates cannot fully capture, and no randomized trial has used kidney endpoints. Its effect estimate should not be compared directly with randomized drug effects.

Measuring glycaemia when the kidney distorts every marker

HbA1c is known to be unreliable in CKD, and glycated albumin and fructosamine have been proposed as replacements. A prospective study directly tested all three against continuous glucose monitoring in 104 participants with type 2 diabetes — 80 with eGFR below 60 (not on dialysis) and 24 frequency-matched controls with eGFR ≥60 — each wearing a blinded CGM for two 6-day periods separated by two weeks, with blood and urine sampled at the end of each period.

Within-person biomarker values were highly reproducible between periods (r = 0.92–0.95), and all three markers correlated similarly with mean CGM glucose (r = 0.71–0.77) — but none captured within-person variability in mean glucose. Compared with mean CGM glucose, glycated albumin and fructosamine were significantly biased by age, BMI, serum iron, transferrin saturation and albuminuria, while HbA1c was underestimated only in the presence of albuminuria (Zelnick 2020, PMID 32788282).

The conclusion runs against the usual recommendation: the proposed alternatives were not less variable than HbA1c at a given mean glucose and carried more sources of bias, so HbA1c remains the marker of choice for trends below an eGFR of 60, while any question about short-term variability or hypoglycaemia requires direct glucose measurement rather than a different integrated marker.

When to biopsy a person with diabetes

The assumption that kidney disease in a person with diabetes is diabetic nephropathy is contradicted by the largest available biopsy series. Retrospective analysis of clinical and pathological parameters from 49,075 biopsied patients with diabetes (2001–2024), linked to United States Renal Data System outcomes, found non-diabetic kidney disease (NDKD) in 58.8% — 35.9% without concurrent diabetic nephropathy, and 22.9% as a second diagnosis alongside it (Caza 2026, PMID 42034202).

The predictors are usable. Acute kidney injury and acute nephritic syndrome as biopsy indications carried greater odds of finding NDKD in patients who also had diabetic nephropathy. Prevalence of NDKD was higher at both age extremes — under 30 and 60 or over — and higher chronicity on biopsy was associated with lower NDKD prevalence. Most consequentially for prognosis, patients with NDKD were 2.56-fold less likely to progress to end-stage kidney disease than those with diabetic nephropathy alone (Caza 2026, PMID 42034202).

The selection caveat is severe and unavoidable: these are people who were biopsied, which means a clinician already suspected something atypical, so 58.8% is the yield in a selected population and not the prevalence of NDKD among all people with diabetes and kidney disease. Within that constraint, the direction of the finding — that a second diagnosis is common, predictable from the indication, and associated with substantially better kidney prognosis — is an argument for a lower biopsy threshold than current practice applies, and it stands against the older view that biopsy rarely changes management in diabetes.

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
11565518 Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. (Brenner 2001, PMID 11565518) 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.
33264825 Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. (Bakris 2020, PMID 33264825) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38785209 Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. (Perkovic 2024, PMID 38785209) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
37952217 Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. (Neuen 2024, PMID 37952217) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
24206457 Combined angiotensin inhibition for the treatment of diabetic nephropathy. (Fried 2013, PMID 24206457) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
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.
11565517 Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. (Lewis 2001, PMID 11565517) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
11565519 The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. (Parving 2001, PMID 11565519) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
18707986 Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. (Mann 2008, PMID 18707986) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
32970396 Dapagliflozin in Patients with Chronic Kidney Disease. (Heerspink 2020, PMID 32970396) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
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.
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.
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.
35023547 Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. (Agarwal 2022, PMID 35023547) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38914124 Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. (Mann 2024, PMID 38914124) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
30697905 SGLT2 inhibitors and cardiovascular, renal and safety outcomes in T2D and CKD: meta-analysis. (Toyama 2019, PMID 30697905) Synthesis; heterogeneity and included-study definitions constrain transport.
36316605 SGLT2 inhibitors in advanced CKD: systematic review and meta-analysis. (Cao 2023, PMID 36316605) Synthesis; heterogeneity and included-study definitions constrain transport.
36927680 Finerenone outcomes in stage 4 CKD and type 2 diabetes. (Sarafidis 2023, PMID 36927680) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
36272755 Executive summary of KDIGO 2022 Diabetes Management in CKD guideline. (Rossing 2022, PMID 36272755) Guideline or commentary; recommendation evidence depends on its review.
33637203 Executive summary of KDIGO 2021 Blood Pressure in CKD guideline. (Cheung 2021, PMID 33637203) Guideline or commentary; recommendation evidence depends on its review.
31533906 Patiromer to enable spironolactone in resistant hypertension and CKD: AMBER. (Agarwal 2019, PMID 31533906) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
40542996 Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. (Huang 2025, PMID 40542996) Synthesis; heterogeneity and included-study definitions constrain transport.
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.
40470996 Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes (CONFIDENCE). (Agarwal 2025, PMID 40470996) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
41493296 Hyperkalaemia with empagliflozin, finerenone or both: CONFIDENCE secondary analysis. (Agarwal 2026, PMID 41493296) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
42246672 Finerenone in Persons with Chronic Kidney Disease without Diabetes (FIND-CKD). (Heerspink 2026, PMID 42246672) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
41780000 Finerenone in Type 1 Diabetes and Chronic Kidney Disease (FINE-ONE). (Heerspink 2026, PMID 41780000) 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

  • In what order should the four classes be started, and does order matter for adherence, potassium and cost? Only the finerenone–empagliflozin pair has been randomized, on albuminuria over 180 days (Agarwal 2025, PMID 40470996) (Neuen 2024, PMID 37952217). → OQ-1
  • How reliably does the clinical phenotype of diabetic kidney disease correspond to diabetic nephropathy on biopsy, and does the mismatch change treatment?
  • Does finerenone's type 1 diabetes albuminuria effect extend to kidney outcomes? FINE-ONE randomized 242 participants for six months (Heerspink 2026, PMID 41780000).

  • Which patients gain enough from a fourth agent to justify the pill, cost and monitoring burden? Absolute benefit at the margin has not been characterised.

  • Is non-albuminuric diabetic kidney disease a vascular rather than glomerular process? Its risk-factor correlates differ from the albuminuric phenotypes — glycaemia and retinopathy predict mortality only when albuminuria is present (Penno 2018, PMID 30032426) — but no mechanistic study has tested the distinction directly.

  • How much of the bariatric-surgery kidney benefit (HR 0.42, 0.32–0.55 for ≥30% eGFR decline) survives the selection that propensity matching cannot capture, and would a randomized trial with kidney endpoints be feasible (Chang 2016, PMID 27181999)?
  • Why does metabolic memory persist for 18 years after HbA1c converges in type 1 diabetes (DCCT/EDIC 2014, PMID 25043685), and does an equivalent memory exist for the newer kidney-protective classes?

  • Given that a 0.9% HbA1c difference yields a 20% kidney-event reduction over five years (Zoungas 2017, PMID 28365411), how should glycaemic intensity be traded against the burden of a four-drug kidney-protective regimen in an individual patient?

  • If glycated albumin and fructosamine carry more covariate bias than HbA1c in CKD (Zelnick 2020, PMID 32788282), why do they continue to be recommended as HbA1c substitutes, and what would displace HbA1c?

  • How should glycaemic targets be set at eGFR below 60 when no integrated marker captures within-person glucose variability and hypoglycaemia risk is elevated (Zelnick 2020, PMID 32788282)?

  • What is the prevalence of non-diabetic kidney disease among all people with diabetes and CKD, rather than among the biopsied 58.8% (Caza 2026, PMID 42034202)? The selection into biopsy cannot be undone by any analysis of biopsied patients.

  • Should the biopsy threshold in diabetes be lowered, given that non-diabetic kidney disease carries a 2.56-fold lower risk of end-stage kidney disease and its likelihood is predictable from the clinical indication (Caza 2026, PMID 42034202)?

References

  1. Brenner et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. PMID 11565518
  2. Perkovic et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. PMID 30990260
  3. Bakris et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383(23):2219-2229. PMID 33264825
  4. Perkovic et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. PMID 38785209
  5. Neuen et al. Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. Circulation. 2024;149(6):450-462. PMID 37952217
  6. Fried et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892-1903. PMID 24206457
  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. Lewis et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851-860. PMID 11565517
  10. Parving et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870-878. PMID 11565519
  11. Mann et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. Lancet. 2008;372(9638):547-553. PMID 18707986
  12. Heerspink et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. PMID 32970396
  13. 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
  14. EMPA-KIDNEY Collaborative Group et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. PMID 36331190
  15. 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
  16. Agarwal et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484. PMID 35023547
  17. Mann et al. Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. Nat Med. 2024;30(10):2849-2856. PMID 38914124
  18. Toyama et al. SGLT2 inhibitors and cardiovascular, renal and safety outcomes in T2D and CKD: meta-analysis. Diabetes Obes Metab. 2019;21(5):1237-1250. PMID 30697905
  19. Cao H, et al. Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2023;60(3):325-335. PMID 36316605
  20. Sarafidis et al. Finerenone outcomes in stage 4 CKD and type 2 diabetes. Clin J Am Soc Nephrol. 2023;18(5):602-612. PMID 36927680
  21. Rossing et al. Executive summary of KDIGO 2022 Diabetes Management in CKD guideline. Kidney Int. 2022;102(5):990-999. PMID 36272755
  22. Cheung et al. Executive summary of KDIGO 2021 Blood Pressure in CKD guideline. Kidney Int. 2021;99(3):559-569. PMID 33637203
  23. Agarwal et al. Patiromer to enable spironolactone in resistant hypertension and CKD: AMBER. Lancet. 2019;394(10208):1540-1550. PMID 31533906
  24. Huang et al. Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. Drugs. 2025;85(8):1013-1031. PMID 40542996
  25. GBD CKD Collaboration et al. Global, regional, and national burden of chronic kidney disease, 1990-2017. Lancet. 2020;395(10225):709-733. PMID 32061315
  26. Agarwal R, et al. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes. N Engl J Med. 2025;393(6):533-543. PMID 40470996
  27. Agarwal R, et al. Risk of Hyperkalemia With Empagliflozin, Finerenone, or Both: Secondary Analysis of the CONFIDENCE Randomized Trial. J Am Coll Cardiol. 2026;87(7):772-784. PMID 41493296
  28. Heerspink HJL, et al. Finerenone in Persons with Chronic Kidney Disease without Diabetes. N Engl J Med. 2026;395(6):533-545. PMID 42246672
  29. Heerspink HJL, et al. Finerenone in Type 1 Diabetes and Chronic Kidney Disease. N Engl J Med. 2026;394(10):947-957. PMID 41780000
  30. Zoungas S, et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 2017;5(6):431-437. PMID 28365411
  31. DCCT/EDIC Research Group. Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: long-term follow-up of the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study. Lancet Diabetes Endocrinol. 2014;2(10):793-800. PMID 25043685
  32. Penno G, et al. Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study. Diabetologia. 2018;61(11):2277-2289. PMID 30032426
  33. Chang AR, et al. Bariatric surgery is associated with improvement in kidney outcomes. Kidney Int. 2016;90(1):164-171. PMID 27181999
  34. Zelnick LR, et al. Continuous Glucose Monitoring and Use of Alternative Markers To Assess Glycemia in Chronic Kidney Disease. Diabetes Care. 2020;43(10):2379-2387. PMID 32788282
  35. Caza TN, et al. Clinical and histologic predictors of non-diabetic kidney disease in patients with diabetes mellitus. Kidney Int. 2026;110(2):426-437. PMID 42034202