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Red flags and safety concerns

TL;DR — CKD is often silent, so the major safety failure is omission of testing in a high-risk person; the major diagnostic red flags are rapid eGFR loss, active sediment, abrupt heavy proteinuria, systemic illness, obstruction and unexplained electrolyte disorders (KDIGO CKD Work Group 2024, PMID 38490803). Medication safety requires reconciliation, kidney-function-aware dosing, sick-day context and potassium monitoring. Dual RAS blockade, high haemoglobin targets, dialysis-era statin extrapolation, veverimer assumptions and bardoxolone all show that favourable intermediate markers can coexist with null or harmful clinical outcomes (Fried 2013, PMID 24206457) (Singh 2006, PMID 17108343) (Tangri 2024, PMID 38261535) (de Zeeuw 2013, PMID 24206459). Contrast risk should be framed against both patient risk and harm from withholding indicated imaging (Macdonald 2022, PMID 35646375).

Diagnostic red flags

Rapid decline, haematuria with proteinuria, nephrotic syndrome, systemic inflammation, recurrent stones, obstruction, inherited clues or refractory complications warrant cause-directed assessment.

Medication reconciliation

NSAIDs, over-the-counter products, supplements, renally cleared drugs and interacting potassium-raising agents should be explicitly elicited.

Haemodynamic change versus injury

RAS and SGLT2 therapy can cause expected early eGFR shifts; volume depletion, sepsis, obstruction and nephrotoxins change the interpretation (Heerspink 2021, PMID 34619108) (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371).

Hyperkalaemia

Potassium should be repeated when unexpected and interpreted with sampling quality, acid-base status and medication changes. Binder enablement is not proof of long-term outcome benefit (Huang 2025, PMID 40542996).

Contrast

Modern guidance stratifies by eGFR and acute illness and discourages indiscriminate delay of necessary imaging (Macdonald 2022, PMID 35646375).

Surrogate traps

Dual blockade improved albuminuria but harmed safety; bardoxolone raised eGFR but increased heart failure; FSGS proteinuria response did not improve slope (Fried 2013, PMID 24206457) (de Zeeuw 2013, PMID 24206459) (Rheault 2023, PMID 37921461).

Safety traps exposed by outcomes

Apparent signal Clinical outcome Lesson
More albuminuria reduction with dual RAS blockade More AKI/hyperkalaemia; no overall kidney benefit Do not equate stronger surrogate change with safer therapy (Fried 2013, PMID 24206457)
Higher haemoglobin with more ESA More composite events or stroke Treat outcomes and symptoms, not normalization (Singh 2006, PMID 17108343; Pfeffer 2009, PMID 19880844)
Higher eGFR with bardoxolone Excess heart failure; trial terminated eGFR can reflect haemodynamics/fluid effects (de Zeeuw 2013, PMID 24206459)
Better FSGS proteinuria remission Neutral 108-week eGFR slope Disease/drug-specific surrogate validation required (Rheault 2023, PMID 37921461)
Corrected bicarbonate hypothesis VALOR-CKD HR 0.99 (0.80–1.20) A small achieved separation limits mechanistic inference (Tangri 2024, PMID 38261535)
Avoided contrast imaging Delayed diagnosis can itself cause harm Balance imaging benefit with eGFR/AKI risk (Macdonald 2022, PMID 35646375)

Contrast: the risk that shrank, and the prophylaxis that failed

Prophylaxis. PRESERVE randomly assigned 5,177 patients at high risk of renal complications scheduled for angiography, in a 2×2 factorial design, to intravenous 1.26% sodium bicarbonate or 0.9% sodium chloride, and to five days of oral acetylcysteine or placebo (4,993 in the modified intention-to-treat analysis). The primary composite of death, dialysis, or a persistent ≥50% rise in serum creatinine at 90 days occurred in 110/2,511 (4.4%) with bicarbonate versus 116/2,482 (4.7%) with saline (OR 0.93, 95% CI 0.72–1.22; p = 0.62), and in 114/2,495 (4.6%) with acetylcysteine versus 112/2,498 (4.5%) with placebo (OR 1.02, 0.78–1.33; p = 0.88), with no difference in contrast-associated AKI and no interaction between the two interventions (p = 0.33) (Weisbord 2018, PMID 29130810). Two widely used prophylactic strategies do nothing, and the sponsor stopped the trial early.

Magnitude of the hazard. Within the same 4,418-participant cohort with prospective outcome ascertainment, contrast-associated AKI carried a large relative risk for the 90-day composite of death, dialysis or persistent kidney impairment (OR 3.93, 95% CI 2.82–5.49; p < 0.0001), but the incidence of clinically significant contrast-associated AKI — patients who both developed it and reached the 90-day outcome — was 1.2% (53/4,418). Contrast-associated AKI did not mediate the association between pre-angiography eGFR and the outcome (Weisbord 2020, PMID 32192658). The correct reading is that low baseline eGFR predicts bad outcomes for reasons that are largely independent of the contrast exposure, and that withholding indicated angiography on the basis of a 3.93 odds ratio misrepresents an absolute risk near 1%.

Gadolinium. Systematic review and meta-analysis of 16 studies including 4,931 patients with stage 4 or 5 CKD receiving an American College of Radiology group II gadolinium-based agent found zero unconfounded cases of nephrogenic systemic fibrosis: pooled incidence 0/4,931 (0%; upper bound of the two-sided 95% CI 0.07%), with agent-specific upper bounds of 0.12% for gadobenate dimeglumine (0/3,167), 0.31% for gadoterate meglumine (0/1,204), 1.11% for gadobutrol (0/330) and 1.59% for gadoteridol (0/230). The authors conclude that the diagnostic harm of withholding an indicated group II agent may exceed the NSF risk (Woolen 2020, PMID 31816007).

These three results share a structure worth naming: each is a case where a real historical hazard has been so substantially mitigated that the residual danger has shifted from the exposure to the avoidance of the exposure.

NSAIDs: a modest hazard that concentrates in the people already affected

Systematic review and meta-analysis of 40 studies (39 in the meta-analysis) covering 1,757,118 participants found chronic NSAID use associated with CKD occurrence or progression: pooled OR 1.24 (95% CI 1.11–1.39; p < 0.001; I² = 91.21%) and pooled HR 1.50 (1.31–1.70; p < 0.001; I² = 90.77%). Stratified, the hazard ratio was 1.31 (1.26–1.40) in people without baseline CKD and 1.67 (1.38–2.02) in those with pre-existing CKD; 1.35 (1.27–1.43) in populations with diabetes and/or hypertension and 1.36 (0.88–2.10) in rheumatic disease (Soliman 2025, PMID 39412516). Heterogeneity above 90% means these pooled estimates should be treated as a direction and rough magnitude rather than a precise risk, and every included study is observational with confounding by indication.

Metformin below the label threshold

The relaxation of metformin contraindications has been driven by evidence in mild-to-moderate CKD; the advanced-CKD data point the other way. In a Taiwanese national cohort of 12,350 patients with type 2 diabetes and serum creatinine above 530 µmol/L (approximately stage G5), 813 metformin users propensity-matched 1:3 to 2,439 non-users on 30 baseline clinical and socioeconomic variables, all-cause mortality over median 2.1 years occurred in 434 (53%) of users versus 1,012 (41%) of non-users, giving an adjusted HR of 1.35 (95% CI 1.20–1.51; p < 0.0001), dose-dependent and consistent across subgroups (Hung 2015, PMID 26094107). This is observational, and confounding by indication in the opposite direction (sicker patients having metformin stopped) would bias against the observed harm — which strengthens rather than weakens the signal, though it cannot establish causation.

Exposure Absolute risk Relative risk Practical implication
Iodinated contrast at angiography Clinically significant CA-AKI 1.2% (53/4,418) OR 3.93 (2.82–5.49) for 90-day death/dialysis/persistent impairment Relative risk large, absolute risk small; eGFR predicts outcome independently (PMID 32192658)
Bicarbonate or acetylcysteine prophylaxis Composite 4.4% vs 4.7%; 4.6% vs 4.5% OR 0.93 (0.72–1.22); 1.02 (0.78–1.33) Neither works (PMID 29130810)
Group II gadolinium in G4–G5 0 of 4,931 NSF cases Upper 95% bound 0.07% Withholding indicated imaging is the larger harm (PMID 31816007)
Chronic NSAID use Not estimable from pooled data HR 1.50 (1.31–1.70) overall; 1.67 (1.38–2.02) with pre-existing CKD I² >90%; direction reliable, magnitude not (PMID 39412516)
Metformin at creatinine >530 µmol/L Mortality 53% vs 41% over median 2.1 years Adjusted HR 1.35 (1.20–1.51), dose-dependent Observational; the plausible confounding runs against the finding (PMID 26094107)

Vaccination: reduced response is a reason to vaccinate earlier, not less

Infection is a major cause of morbidity and mortality across CKD stages, including on dialysis and after transplantation, and vaccine responses are impaired in all three settings. Guidance concentrates on hepatitis B, influenza and pneumococcal vaccination in addition to age-appropriate immunisation, and the review of this literature makes two points that change timing rather than indication: seroconversion rates are generally higher in earlier-stage CKD, so there is a benefit to immunising before dialysis or transplantation; and data on clinical efficacy, optimal dosing and optimal timing in this population remain insufficient (Krueger 2020, PMID 31585683).

The practical corollary is that vaccination status belongs in the same review as the CKD staging that predicts declining response — a point that follows from the biology and is not covered by the guideline documents indexed on the guidelines page. Because nephrologists frequently function as the effective primary care physician for people with advanced CKD, an omission here is unlikely to be corrected elsewhere.

AKI on a background of CKD: the acute insult dominates

The pathophysiology page treats AKI as a long-term accelerant of CKD. In the acute setting the relationship inverts: it is the features of the acute episode, not the pre-existing CKD stage, that determine short-term outcome. In a retrospective cohort of 327 patients with CKD and hospital-acquired superimposed AKI (mean age 68.6 ± 11.4, mostly men, mean creatinine 1.85 ± 0.74 mg/dL; hypertension 81.7%, cardiovascular disease 61.5%; most common CKD aetiology undetermined at 26.6%; most common AKI aetiology septic at 45.3%), overall mortality was 29.1% and 35.2% required kidney support therapy. Among those admitted to intensive care, 73.2% required dialysis and 74.4% died, rising to 85.7% in those who received kidney support therapy.

CKD staging was not associated with either primary outcome. Risk factors for kidney support therapy were obesity, the ATN-ISS severity score and a creatinine rise greater than three times baseline; risk factors for death were the ATN-ISS score, undetermined CKD aetiology, septic AKI, ICU admission and receipt of kidney support therapy (Chagas 2026, PMID 41523706).

The practical implication for a red-flag page is direct: when someone with CKD develops AKI, the baseline eGFR category is the wrong variable to triage on. Sepsis as the precipitant, the magnitude of the creatinine rise, and ICU-level illness carry the prognosis. This is a single-centre retrospective cohort of modest size, so the specific hazard estimates should not be transported, but the negative finding — that CKD stage did not predict either outcome — is the one that changes a triage heuristic.

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
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.
24206457 Combined angiotensin inhibition for the treatment of diabetic nephropathy. (Fried 2013, PMID 24206457) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
17108343 Correction of anemia with epoetin alfa in chronic kidney disease. (Singh 2006, PMID 17108343) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38261535 VALOR-CKD trial of veverimer in CKD with metabolic acidosis. (Tangri 2024, PMID 38261535) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
24206459 Bardoxolone methyl in type 2 diabetes and stage 4 CKD. (de Zeeuw 2013, PMID 24206459) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
35646375 Canadian guidance on contrast-associated acute kidney injury. (Macdonald 2022, PMID 35646375) Guideline or commentary; recommendation evidence depends on its review.
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.
40542996 Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. (Huang 2025, PMID 40542996) Synthesis; heterogeneity and included-study definitions constrain transport.
37921461 Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. (Rheault 2023, PMID 37921461) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
19880844 A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. (Pfeffer 2009, PMID 19880844) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
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.
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.
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.
26757465 Multinational assessment of equations predicting kidney failure. (Tangri 2016, PMID 26757465) Synthesis; heterogeneity and included-study definitions constrain transport.
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.
17108342 Normalization of hemoglobin level in patients with chronic kidney disease and anemia. (Drüeke 2006, PMID 17108342) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
23121374 Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. (EVOLVE Trial Investigators 2012, PMID 23121374) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
19332456 Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. (Fellstrom 2009, PMID 19332456) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
16034009 Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. (Wanner 2005, PMID 16034009) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
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.
38622759 Sodium zirconium cyclosilicate in CKD, hyperkalemia, and metabolic acidosis: NEUTRALIZE. (Ash 2024, PMID 38622759) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
32588430 Potassium binders for chronic hyperkalaemia in people with CKD. (Natale 2020, PMID 32588430) Synthesis; heterogeneity and included-study definitions constrain transport.

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

  • Which combination of surveillance interval and trigger detects rapid progression early enough to change its course? Red flags are enumerable; their yield as a screening rule is not established.
  • Does structured sick-day guidance for RAS, SGLT2 and MRA therapy reduce acute kidney injury without reducing long-term persistence on protective drugs?
  • How should an eGFR rise be interpreted after bardoxolone showed that filtration gain can accompany a heart-failure excess (HR 1.83, 1.32–2.55) (de Zeeuw 2013, PMID 24206459)?

  • What is the net harm of contrast avoidance — deferred diagnosis versus acute kidney injury — under current low-risk contrast guidance (Macdonald 2022, PMID 35646375)?

  • How should a relative risk of 3.93 for contrast-associated AKI be communicated alongside an absolute clinically significant incidence of 1.2%, when the same patients' baseline eGFR predicts the outcome independently of contrast exposure (Weisbord 2020, PMID 32192658)?

  • Is any contrast prophylaxis effective? Bicarbonate and acetylcysteine both failed in a 5,177-patient factorial trial (Weisbord 2018, PMID 29130810), and no alternative has been tested at that scale.
  • Is the NSAID–CKD association causal? Pooled estimates have I² above 90% and every included study is observational (Soliman 2025, PMID 39412516).

  • Does metformin cause the excess mortality observed at creatinine above 530 µmol/L, or does prescribing selection explain it? The likely direction of confounding by indication runs against the observed harm (Hung 2015, PMID 26094107).

  • What are the clinically effective vaccine schedules and doses in CKD, as opposed to seroconversion rates? The evidence supports earlier immunisation but does not define dosing or timing (Krueger 2020, PMID 31585683).

  • Why did CKD stage fail to predict death or need for kidney support therapy in hospital-acquired AKI superimposed on CKD, when acute-episode features did (Chagas 2026, PMID 41523706)? If replicated in larger cohorts, triage tools built on baseline eGFR category would need revision.

References

  1. 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
  2. Fried et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892-1903. PMID 24206457
  3. Singh et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355(20):2085-2098. PMID 17108343
  4. Tangri et al. VALOR-CKD trial of veverimer in CKD with metabolic acidosis. J Am Soc Nephrol. 2024;35(3):311-320. PMID 38261535
  5. de Zeeuw et al. Bardoxolone methyl in type 2 diabetes and stage 4 CKD. N Engl J Med. 2013;369(26):2492-2503. PMID 24206459
  6. Macdonald et al. Canadian guidance on contrast-associated acute kidney injury. Can J Kidney Health Dis. 2022;9:20543581221097455. PMID 35646375
  7. 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
  8. 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
  9. Huang et al. Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. Drugs. 2025;85(8):1013-1031. PMID 40542996
  10. Rheault et al. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023;389(26):2436-2445. PMID 37921461
  11. Pfeffer et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361(21):2019-2032. PMID 19880844
  12. 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
  13. GBD CKD Collaboration et al. Global, regional, and national burden of chronic kidney disease, 1990-2017. Lancet. 2020;395(10225):709-733. PMID 32061315
  14. Cirillo et al. A population-based approach for the definition of chronic kidney disease: CKD Prognosis Consortium. J Nephrol. 2012;25(1):7-12. PMID 22038337
  15. Matsushita et al. Cohort profile: the chronic kidney disease prognosis consortium. Int J Epidemiol. 2013;42(6):1660-1668. PMID 23243116
  16. CKD Prognosis Consortium et al. Estimated GFR, Albuminuria, and Adverse Outcomes: individual-participant data meta-analysis. JAMA. 2023;330(13):1266-1277. PMID 37787795
  17. Inker et al. Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities. Am J Kidney Dis. 2019;73(2):206-217. PMID 30348535
  18. 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
  19. Delgado et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis. 2022;79(2):268-288.e1. PMID 34563581
  20. Tangri et al. Multinational assessment of equations predicting kidney failure. JAMA. 2016;315(2):164-174. PMID 26757465
  21. 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
  22. Drüeke et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071-2084. PMID 17108342
  23. EVOLVE Trial Investigators et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482-2494. PMID 23121374
  24. Fellstrom et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395-1407. PMID 19332456
  25. Wanner et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238-248. PMID 16034009
  26. Agarwal et al. Patiromer to enable spironolactone in resistant hypertension and CKD: AMBER. Lancet. 2019;394(10208):1540-1550. PMID 31533906
  27. Ash et al. Sodium zirconium cyclosilicate in CKD, hyperkalemia, and metabolic acidosis: NEUTRALIZE. Kidney360. 2024;5(6):812-820. PMID 38622759
  28. Natale et al. Potassium binders for chronic hyperkalaemia in people with CKD. Cochrane Database Syst Rev. 2020;6(6):CD013165. PMID 32588430
  29. Weisbord SD, et al. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018;378(7):603-614. PMID 29130810
  30. Weisbord SD, et al. Contrast-Associated Acute Kidney Injury and Serious Adverse Outcomes Following Angiography. J Am Coll Cardiol. 2020;75(11):1311-1320. PMID 32192658
  31. Woolen SA, et al. Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis. JAMA Intern Med. 2020;180(2):223-230. PMID 31816007
  32. Soliman S, et al. Non-steroidal anti-inflammatory drugs: what is the actual risk of chronic kidney disease? A systematic review and meta-analysis. Rom J Intern Med. 2025;63(1):3-27. PMID 39412516
  33. Hung SC, et al. Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study. Lancet Diabetes Endocrinol. 2015;3(8):605-614. PMID 26094107
  34. Krueger KM, et al. Practical Guide to Vaccination in All Stages of CKD, Including Patients Treated by Dialysis or Kidney Transplantation. Am J Kidney Dis. 2020;75(3):417-425. PMID 31585683
  35. Chagas MW, et al. Chronic Kidney Disease and Superimposed Acute Kidney Injury: Greater Impact of Acute Insults on Outcomes. Int J Nephrol. 2026;2026:1353892. PMID 41523706