AKI
ACT trial: Acetylcysteine for AKI protection
| Article Name: Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography |
| URL: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.111.038943 |
| Journal and year of publication: Circulation, 2011 |
| Trial Design: Randomized clinical trial |
| Population: 2308 patients Key inclusion criteria: – Patients undergoing diagnostic intravascular angiography or PCI – At least 1 risk factor for contrast-induced AKI Key exclusion criteria: – On dialysis – ST-segment elevation myocardial infarction for primary angioplasty |
| Intervention Studied: Acetylcysteine |
| Control: Placebo |
| Outcomes: – Incidence of contrast-induced AKI: Acetylcysteine: 12.7% vs Placebo: 12.7% (P=0.97) The authors concluded that “In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.” |
| Citation: ACT Investigators. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT). Circulation. 2011 Sep 13;124(11):1250-9. doi: 10.1161/CIRCULATIONAHA.111.038943. Epub 2011 Aug 22. PMID: 21859972. |
SALT-ED trial: IV fluid types for non-critically ill patients
| Article Name: Balanced Crystalloids versus Saline in Noncritically Ill Adults |
| URL: https://www.nejm.org/doi/full/10.1056/NEJMoa1711586 |
| Journal and year of publication: NEJM, 2018 |
| Trial Design: Randomized clinical trial |
| Population: 13,347 patients Key inclusion criteria: – Adults who received at least 500 ml of IV isotonic crystalloids in ED and were subsequently hospitalized outside an ICU Key exclusion criteria: |
| Intervention Studied: Balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) |
| Control: Saline |
| Outcomes: – Incidence of major adverse kidney events (within 30 days): Balanced crystalloids: 4.7% vs Saline: 5.6% (P=0.01) – No difference in hospital-free days The authors concluded that “Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline.” |
| Citation: Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828. doi: 10.1056/NEJMoa1711586. Epub 2018 Feb 27. PMID: 29485926; PMCID: PMC5846618. |
IDEAL-ICU trial: Timing of dialysis for critically ill patients
| Article Name: Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis |
| URL: https://www.nejm.org/doi/full/10.1056/NEJMoa1803213 |
| Journal and year of publication: NEJM, 2018 |
| Trial Design: Randomized clinical trial |
| Population: 488 patients Key inclusion criteria: – Adults admitted to ICU in the early phase of septic shock (within 48 hours) – AKI meeting at least one of the criteria for the failure stage of RIFLE classification: Oliguria, anuria for 12 hours or more, or serum creatinine level 3 times the baseline level Key exclusion criteria: – End stage kidney disease on chronic RRT – Obstructive etiology for AKI |
| Intervention Studied: Early-strategy group (renal-replacement therapy within 12 hours) |
| Control: Delayed-strategy group (delay of 48 hours if renal recovery had not occurred) |
| Outcomes: – Death (within 90 days): Early-strategy group: 58% vs Delayed-strategy group: 54% (P=0.38) The authors concluded that “Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy.” |
| Citation: Barbar SD, Clere-Jehl R, Bourredjem A, Hernu R, Montini F, Bruyère R, Lebert C, Bohé J, Badie J, Eraldi JP, Rigaud JP, Levy B, Siami S, Louis G, Bouadma L, Constantin JM, Mercier E, Klouche K, du Cheyron D, Piton G, Annane D, Jaber S, van der Linden T, Blasco G, Mira JP, Schwebel C, Chimot L, Guiot P, Nay MA, Meziani F, Helms J, Roger C, Louart B, Trusson R, Dargent A, Binquet C, Quenot JP; IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med. 2018 Oct 11;379(15):1431-1442. doi: 10.1056/NEJMoa1803213. PMID: 30304656. |
CKD/ESRD
IDEAL trial: Timing of dialysis initiation
| Article Name: A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis |
| URL: https://www.nejm.org/doi/full/10.1056/NEJMoa1000552 |
| Journal and year of publication: NEJM, 2010 |
| Trial Design: Randomized clinical trial |
| Population: 828 patients Key inclusion criteria: – Progressive CKD – eGFR between 10.0 and 15.0 ml/min/1.73 m2 of BSA Key exclusion criteria: – eGFR <10.0 ml/min – Plans to receive a kidney transplant from a live donor within 12 months |
| Intervention Studied: Early initiation of dialysis (median time to initiation: 1.80 months) |
| Control: Late initiation of dialysis (Median time to initiation: 7.40 months) |
| Outcomes: – Death: Early-start group: 37.6% vs Late-start group: 36.6% (P=0.75) – Adverse events: No significant difference in the frequency between groups The authors concluded that “In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes.” |
| Citation: Cooper BA, Branley P, Bulfone L, Collins JF, Craig JC, Fraenkel MB, Harris A, Johnson DW, Kesselhut J, Li JJ, Luxton G, Pilmore A, Tiller DJ, Harris DC, Pollock CA; IDEAL Study. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010 Aug 12;363(7):609-19. doi: 10.1056/NEJMoa1000552. Epub 2010 Jun 27. PMID: 20581422. |
CHOIR trial: Epoetin and target hemoglobin for anemia of CKD
| Article Name: Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease |
| URL: https://www.nejm.org/doi/full/10.1056/NEJMoa065485 |
| Journal and year of publication: NEJM, 2006 |
| Trial Design: Randomized clinical trial |
| Population: 1,432 patients Key inclusion criteria: – Adult with CKD and hemoglobin level <11.0 g/dL Key exclusion criteria: – Uncontrolled hypertension – Active GI bleeding – Iron-overload state OR refractory iron-deficiency anemia |
| Intervention Studied: Epoetin Alfa (Target hemoglobin 13.5 g/dL) |
| Control: Epoetin Alfa (Target hemoglobin 11.3 g/dL) |
| Outcomes: – The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke: – High-hemoglobin group: 125 out 715 patient – Low-hemoglobin group:occurred: 97 out of 717 patient – Hazard ratio for high-hemoglobin: 1.34 (95% CI: 1.03 to 1.74) (P=0.03) The authors concluded that “The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life.” |
| Citation: Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98. doi: 10.1056/NEJMoa065485. PMID: 17108343. |
RENAAL trial: Losartan for diabetic nephropathy
| Article Name: Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy |
| URL: https://www.nejm.org/doi/full/10.1056/nejmoa011161 |
| Journal and year of publication: NEJM, 2001 |
| Trial Design: Randomized clinical trial |
| Population: 1,513 patients Key inclusion criteria: – Adult with T2DM and nephropathy (Ratio of urinary albumin to creatinine of at least 300 (or a rate of urinary protein excretion of at least 0.5 g/day) and serum creatinine values between 1.3 and 3.0 mg/dL) Key exclusion criteria: – Type 1 DM or nondiabetic renal disease, including renal-artery stenosis |
| Intervention Studied: Losartan (50 to 100 mg once daily) |
| Control: Placebo |
| Outcomes: – Occurrence of primary endpoint (composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death): Losartan group: 327 patients (43.5%) vs Placebo group: 359 patients (47.1%). Risk reduction: 16%, P=0.02 The authors concluded that “Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.” |
| Citation: Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9. doi: 10.1056/NEJMoa011161. PMID: 11565518. |
DAPA CKD trial: Dapagliflozin for CKD
| Article Name: Dapagliflozin in Patients with Chronic Kidney Disease |
| URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2024816 |
| Journal and year of publication: NEJM, 2020 |
| Trial Design: Randomized, double-blind, placebo-controlled, clinical trial |
| Population: 4,304 patients Key inclusion criteria: – Estimated GFR of 25 to 75 ml per minute per 1.73 m2 of body-surface area – Urinary albumin-to-creatinine ratio of 200 to 5000 – Receiving a stable dose of an ACE inhibitor or ARB for at least 4 weeks – With or without T2DM Key exclusion criteria: – Type 1 diabetes – Polycystic kidney disease – Lupus nephritis – Antineutrophil cytoplasmic antibody–associated vasculitis |
| Intervention Studied: Dapagliflozin (10 mg once daily) |
| Control: Placebo |
| Outcomes: – A primary outcome event (composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes) occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% CI 0.51 to 0.72; P<0.001). – The known safety profile of dapagliflozin was confirmed. The authors concluded that “Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.” |
| Citation: Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. PMID: 32970396. |
EMPA-KIDNEY trial: Empagliflozin for CKD
| Article Name: Empagliflozin in Patients with Chronic Kidney Disease |
| URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2204233 |
| Journal and year of publication: NEJM, 2023 |
| Trial Design: Randomized, double-blind, placebo-controlled, clinical trial |
| Population: 6,609 patients Key inclusion criteria: – eGFR 20 – 45 ml per minute per 1.73 m2, regardless of the level of albuminuria, or with an eGFR 45 – 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio of at least 200 – With or without T2DM – Taking a clinically appropriate dose of a single-agent RAS inhibitor Key exclusion criteria: – Polycystic kidney disease – Kidney transplant recipients |
| Intervention Studied: Empagliflozin (10 mg once daily) |
| Control: Placebo |
| Outcomes: – Primary outcome (composite of progression of kidney disease or death from renal or cardiovascular causes) occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% CI 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. – The rates of serious adverse events were similar in the two groups. The authors concluded that “Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo.” |
| Citation: The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4. PMID: 36331190; PMCID: PMC7614055. |
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