11. ADA 2022差異: 11. Chronic Kidney Disease and Risk Management:

diabetes kidney disease


2021 vs 2021
11.1b 糖尿病和尿蛋白 ≥300 mg/g  和/或 eGFR 30-60  的患者應每年監測兩次以指導治療。 B
11.1b Patients with diabetes and urinary albumin >300 ≥300 mg/g (2022 修正)creatinine and/or an estimated glomerular filtration rate 30–60 mL/min/1.73 m2 should be monitored twice annually to guide therapy. B
2021 vs 2022
11.3a 對於 2 型糖尿病和糖尿病腎病患者,在 eGFR  ≥30 eGFR ≥25 (2022 修) 和尿蛋白 >300 mg/g 的患者中,考慮 (2022刪) 使用 SGLT 2 抑製劑以減少慢性腎臟疾病進展和心血管事件 (2022 新增) A
11.3a For patients with type 2 diabetes and diabetic kidney disease,consider (2022 刪)use of a sodium–glucose cotransporter 2 inhibitor in patients with an estimated glomerular filtration rate ≥30≥25 mL/min/1.73 m2 and urinary albumin >300 mg/g creatinine.is recommended to reduce chronic kidney disease progression and cardiovascular events. (2022新增)  A
2021 vs 2022
11.3b 在患有 2 型糖尿病和糖尿病 慢性腎病的患者中,當 eGFR 和尿白蛋白肌酐≥30 ≥25mL/min/1.73 m2 或 >300 mg/時,考慮額外使用 SGLT 2 抑製劑以降低心血管風險 。 A
11.3b In patients with type 2 diabetes and diabetic chronic kidney disease, consider use of sodium–glucose cotransporter 2 inhibitors additionally for cardiovascular risk reduction when estimated glomerular filtration rate and urinary albumin creatinine are ≥30 ≥25mL/min/1.73 m2 or >300 mg/g, respectively. A
11.3c 在心血管事件風險增加的慢性腎病患者中,使用GLP-1 RA 可降低腎臟終點,主要是白蛋白尿、白蛋白尿進展和心血管事件(表 9.1)。 A
11.3c In patients with chronic kidney disease who are at increased risk for cardiovascular events, use of a glucagon-like peptide 1 receptor agonist reduces renal end point, primarily albuminuria, progression of albuminuria, and cardiovascular events (Table 9.1). A
2022 修正 新增 (CKD  2022 -> favor fenerenone > GLP-1 RA)
11.3c 對於心血管事件或慢性腎病進展風險增加或無法使用 SGLT 2 抑製劑的慢性腎病患者,建議使用 finerenone 來減少慢性腎病進展 和心血管事件(表 9.2)。 A
11.3c In patients with chronic kidney disease who are at increased risk for cardiovascular events or chronic kidney disease progression or are unable to use a sodium–glucose cotransporter 2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce chronic kidney disease progressionand cardiovascular events (Table 9.2). A
2022  新增: 要 MACR reduction > 30%
11.3d  對於尿白蛋白≥300 mg/g 的慢性腎病患者,建議將尿白蛋白減少 30% 或更多,以減緩慢性腎病的進展。 B
11.3d In patients with chronic kidney disease who have ≥300 mg/g urinary albumin, a reduction of 30% or greater in mg/g urinary albumin is recommended to slow chronic kidney disease progression. B
2021 vs 2022:
11.4 優化血壓控制降低血壓變異性以降低慢性腎病的風險或減緩其進展。 A
11.4 Optimize blood pressure control and reduction in blood pressure variability (2022 新增)to reduce the risk or slow the progression of chronic kidney disease. A
2021 vs 2022: stage 3 or higher 遵守 <0.8/kg /day protein
對於非透析依賴性3 期或以上慢性腎病患者,膳食蛋白質攝入量應約為 (應不超過)每天 0.8 g/kg 體重(推薦的每日攝入量)。 A 
對於透析患者,應考慮更高水平的膳食蛋白質攝入量,因為營養不良是一些透析患者的主要問題。 B
11.6 For people with nondialysis-dependent stage 3 or highers(2022 新增)chronic kidney disease, dietary protein intake should be approximatelya maximum of (2022 修正) 0.8 g/kg body weight per day (the recommended daily allowance). A 
For patients on dialysis, higher levels of dietary protein intake should be considered, since malnutrition is a major problem in some dialysis patients. B
2021 vs 2022:
11.11 如果不確定腎臟病的病因、難以處理的問題和快速進展的腎臟疾病,請立即轉診給腎臟科醫師。 A
11.11 Promptly refer to a physician experienced in the care of kidney disease nephrologist (2022 修正)for uncertainty about the etiology of kidney disease, difficult management issues, and rapidly progressing kidney disease. A

Assessment of Albuminuria and Estimated Glomerular Filtration Rate

2022 新增
白蛋白尿篩查最容易通過隨機現場尿液收集中的尿白蛋白肌酐比 (UACR) 進行 (1,2)。 定時或 24 小時收集更繁重,對預測或準確性的影響很小。 在不同時測量尿肌酐 (Cr) 的情況下,單獨測量尿樣中的白蛋白(無論是通過免疫測定還是通過使用專門針對白蛋白尿的靈敏試紙測試)成本較低,但由於以下原因容易出現假陰性和假陽性測定 水合導致的尿液濃度變化 (8)
因此,為了對患者篩查有用,半定量或定性(試紙)篩查試驗在白蛋白尿中度升高(≥30 mg/g)的患者中應 >85% 陽性,並在認可實驗室通過白蛋白與肌酐值進行確認 (9,10)。 因此,最好簡單地收集尿樣以測定白蛋白與肌酐的比值,因為最終需要這樣做。(2022 新增)
Screening for albuminuria can be most easily performed by urinary albumin-to-creatinine ratio (UACR) in a random spot urine collection (1,2). Timed or 24-h collections are more burdensome and add little to prediction or accuracy. Measurement of a spot urine sample for albumin alone (whether by immunoassay or by using a sensitive dipstick test specific for albuminuria) without simultaneously measuring urine creatinine (Cr) is less expensive but susceptible to false-negative and false-positive determinations as a result of variation in urine concentration due to hydration (8)
Thus, to be useful for patient screening, semiquantitative or qualitative (dipstick) screening tests should be >85% positive in those with moderately increased albuminuria (≥30 mg/g) and be confirmed by albumin-to-creatinine values in an accredited laboratory (9,10). Hence, it is better to simply collect a spot urine sample for albumin-to-creatinine ratio because it will ultimately need to be done.
2022 新增:
應使用經過驗證的公式從血清肌酐計算 eGFR。 慢性腎臟病流行病學協作 (CKD-EPI) 方程通常是首選 (2)。 eGFR 由實驗室定期報告血清肌酐,並且 eGFR 計算器可在 nkdep.nih.gov 在線獲得。 eGFR 持續 <60 mL/min/1.73 m2 被認為是異常的,儘管在老年人中對臨床診斷的最佳閾值存在爭議 (2,16)。 當前的 GFR 估計方程中存在不公平現象,經過深思熟慮,召集了一個特別小組,提出了一個新的、更公平的涉及 Cystatin C 的方程; 結果即將到來。2022 新增
eGFR should be calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is generally preferred (2). eGFR is routinely reported by laboratories with serum creatinine, and eGFR calculators are available online at nkdep.nih.gov. An eGFR persistently <60 mL/min/1.73 m2 is considered abnormal, though optimal thresholds for clinical diagnosis are debated in older adults (2,16). There were inequities noted in the current GFR estimating equation, and after much deliberation a special panel was convened to put forth a new, more equitable equation involving cystatin C; results are forthcoming.2022 新增

Acute Kidney Injury

2022 新增:
急性腎損傷 (AKI) 可通過血清肌酐在短時間內持續升高 50% 或更高來診斷,這也反映為 eGFR 的快速下降 (24,25)。與沒有糖尿病的人相比,患有糖尿病的人患 AKI 的風險更高 (26)。 AKI 的其他危險因素包括先前存在的 CKD、使用導致腎損傷的藥物(例如,NSAID)以及使用改變腎血流和腎內血流動力學的藥物。特別是,許多抗高血壓藥物(例如,利尿劑、ACEI和 ARB)可以減少血管內容量、腎血流量和/或腎小球濾過率。有人擔心SGLT2 抑製劑可能通過容量不足促進 AKI,特別是與利尿劑或其他降低腎小球濾過率的藥物聯合使用時;然而,在晚期腎病 (27) 或腎功能正常的高心血管疾病風險 (28-30) 的隨機臨床結果試驗中並未發現這一點。同樣值得注意的是,新一代的 MRA 在用於減緩腎臟疾病進展時不會增加 AKI 的風險 (31)。
Acute kidney injury (AKI) is diagnosed by a 50% or greater sustained increase in serum creatinine over a short period of time, which is also reflected as a rapid decrease in eGFR (24,25). People with diabetes are at higher risk of AKI than those without diabetes (26). Other risk factors for AKI include preexisting CKD, the use of medications that cause kidney injury (e.g., nonsteroidal anti-inflammatory drugs), and the use of medications that alter renal blood flow and intrarenal hemodynamics. In particular, many antihypertensive medications (e.g., diuretics, ACE inhibitors, and angiotensin receptor blockers [ARBs]) can reduce intravascular volume, renal blood flow, and/or glomerular filtration. There was concern that sodium–glucose cotransporter 2 (SGLT2) inhibitors may promote AKI through volume depletion, particularly when combined with diuretics or other medications that reduce glomerular filtration; however, this has not been found to be true in randomized clinical outcome trials of advanced kidney disease (27) or high cardiovascular disease risk with normal kidney function (28–30). It is also noteworthy that the nonsteroidal mineralocorticoid receptor antagonists (MRAs) fail to increase the risk of AKI when used to slow kidney disease progression (31).
2022 新增: ACEI/ARB max tolerance dose 概念, Cr>30% 沒有高血鉀,持續用!
使用 RAS 阻滯劑(如 ACEI 和 ARB)時血清肌酐的小幅升高(較基線升高 30%)不得與 AKI 混淆 (33)。 一項對糖尿病血壓控制心血管風險行動 (ACCORD BP) 試驗的分析表明,那些隨機接受強化降壓且血清肌酐增加高達 30% 的患者死亡率或進行性腎病沒有任何增加(34 –37)。 此外,AKI 標誌物的測量顯示肌酐升高的任何標誌物均未顯著增加 (36)。 因此,在沒有血容量不足的情況下,不應因血清肌酐輕微升高(<30%)而停用 ACEI和 ARB。
最後,應該注意的是,ACEI 和 ARB 通常不會以最大耐受劑量給藥,因為擔心血清肌酐會升高。 如上所述,這是一個錯誤。 請注意,在所有證明 ACE 抑製劑和 ARB 可延緩腎臟疾病進展的臨床試驗中,都使用了最大耐受劑量,而不是無法提供益處的極低劑量。 此外,現在有研究表明,對於 eGFR <30 mL/min/1.73 m2 的糖尿病患者,死亡率和 CKD 進展減慢都有益處 (37)。 此外,當血清肌酐升高高達 30% 且沒有相關的高鉀血症時,應繼續 RAS 阻斷 (35,38)。2022 新增
Small elevations in serum creatinine (up to 30% from baseline) with renin-angiotensin system (RAS) blockers (such as ACE inhibitors and ARBs) must not be confused with AKI (33). An analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial demonstrates that those randomized to intensive blood pressure lowering with up to a 30% increase in serum creatinine did not have any increase in mortality or progressive kidney disease (34–37). Moreover, a measure of markers for AKI showed no significant increase of any markers with increased creatinine (36). Accordingly, ACE inhibitors and ARBs should not be discontinued for minor increases in serum creatinine (<30%), in the absence of volume depletion.
Lastly, it should be noted that ACE inhibitors and ARBs are commonly not dosed at maximally tolerated doses because of fear that serum creatinine will rise. As noted above, this is an error. Note that in all clinical trials demonstrating efficacy of ACE inhibitors and ARBs in slowing kidney disease progression, the maximally tolerated doses were used—not very low doses that do not provide benefit. Moreover, there are now studies demonstrating outcome benefits on both mortality and slowed CKD progression in people with diabetes who have an eGFR <30 mL/min/1.73 m2 (37). Additionally, when increases in serum creatinine are up to 30% and do not have associated hyperkalemia, RAS blockade should be continued (35,38).2022 新增


2021 vs 2022:  2022: ACEI/ARB 只有 eGFR<60 再追縱是否有高血鉀
定期 每年 監測白蛋白尿和 eGFR,以便及時診斷 CKD,監測 CKD 進展,檢測包括 AKI 在內的疊加腎臟疾病,評估 CKD 並發症的風險,適當給藥藥物,並確定是否需要轉診腎臟科。如上所述,在患有腎臟疾病的人中,白蛋白尿和 eGFR 可能會因 CKD 的進展、腎臟疾病、AKI 的單獨疊加原因的發展或藥物的其他影響而發生變化。還應監測接受 ACEI、ARB (2022 刪除)和利尿劑治療的患者的血清鉀,因為這些藥物會導致高鉀血症或低鉀血症,這與心血管風險和死亡率有關 (37-39)。
對於 eGFR <60 mL/min/1.73 m2 的患者,接受 ACEI、ARB 或 MRA 的患者應定期測量血清鉀。(2020增).此外,eGFR 範圍較低的人(2022增)應驗證適當的藥物劑量,應盡量減少腎毒素(如NSAIDs和碘造影劑)的暴露,並應評估潛在的 CKD 並發症(表 11.1) .
腎功能的早期變化可能會在 eGFR 變化之前通過蛋白尿的增加來檢測 (42),這也顯著影響心血管風險。 此外,美國FDA心臟病學和腎臟病學認為,初始降低 > 30% 低於最初測量值,隨後維持至少 2 年,被認為是腎臟益處的有效替代指標。 10)。(2022增)
Early changes in kidney function may be detected by increases in albuminuria before changes in eGFR (42) and this also significantly affects cardiovascular risk. Moreover, an initial reduction of >30% below where it was initially measured, subsequently maintained over at least 2 years, is considered a valid surrogate for renal benefit by the Division of Cardiology and Nephrology of the U.S. Food and Drug Administration (FDA) (10). (2022增)
持續監測可以評估對治療的反應和疾病進展,並可能有助於評估對 ACEI 或 ARB 治療的依從性。 此外,在 2 型糖尿病的 ACE 抑製劑或 ARB 治療的臨床試驗中,將白蛋白尿水平降低   ≥300 mg/g Cr  至 <300 mg/g Cr 水平或從基線水平降低 > 30% (2022修)與改善腎臟和 心血管結果,導致一些人建議應滴定藥物以最大限度地降低 UACR(2022修) 然而,這種方法尚未在前瞻性試驗中得到正式評估。(2022刪) 事後分析的數據表明,半劑量的 RAS 阻滯劑對心腎結果的益處較小 (43)在 1 型糖尿病中,白蛋白尿的緩解可能會自發發生,評估白蛋白尿變化與臨床結果相關性的隊列研究報告的結果不一致 (40,41)。
Continued surveillance can assess both response to therapy and disease progression and may aid in assessing adherence to ACE inhibitor or ARB therapy. In addition, in clinical trials of ACE inhibitors or ARB therapy in type 2 diabetes, reducing albuminuria from levels ≥300 mg/g Crto levels <300 mg/g Cr or by >30% from their baseline has been associated with improved renal and cardiovascular outcomes, leading some to suggest that medications should be titrated to maximize reduction in UACR. minimize UACR. However, this approach has not been formally evaluated in prospective trials.  Data from post hoc analyses demonstrate less benefit on cardiorenal outcomes at half doses of RAS blockade (43).
In type 1 diabetes, remission of albuminuria may occur spontaneously, and cohort studies evaluating associations of change in albuminuria with clinical outcomes have reported inconsistent results (40,41).

Selection of Glucose-Lowering Medications for Patients With Chronic Kidney Disease

2021 vs 2022: DM with CKD metformin 並不是一定是第一線治療。
對於 eGFR 30-60 mL/min/1.73 m2 的患者,metformin 應在碘造影期間或之前暫時停用。 在這些限制條件下,metformin 應被可能視為所有 2 型糖尿病患者(包括 早期 CKD 患者)的一線治療藥物 血糖控制的初始治療
metformin should not be initiated for patients with an eGFR <45 mL/min/1.73 m2; and metformin should be temporarily discontinued at the time of or before iodinated contrast imaging procedures in patients with eGFR 30–60 mL/min/1.73 m2. Within these constraints, metformin should may be considered the first-line treatment as initial treatment of glycemic control for all patients with type 2 diabetes, including those with early CKD.
SGLT2 抑製劑和 GLP-1 RA 應考慮用於需要在metformin 中添加另一種藥物以達到目標 A1C 或不能使用或耐受metformin 的 2 型糖尿病和 CKD 患者。 SGLT2 抑製劑可降低 CKD 進展、CVD 事件和低血糖的風險。 建議使用 GLP-1 RA,因為它們降低了 CVD 事件和低血糖的風險,並且似乎可能減緩 CKD 進展 (77)。
SGLT2 inhibitors and GLP-1 RAs should be considered for patients with type 2 diabetes and CKD who require another drug added to metformin to attain target A1C or cannot use or tolerate metformin. SGLT2 inhibitors reduce risks of CKD progression, CVD events, and hypoglycemia. GLP-1 RAs are suggested because they reduce risks of CVD events and hypoglycemia and appear to possibly slow CKD progression (77).
2022:不以 metfromin 為第一線; SGLT2i, GLP-1RAs分開說明
SGLT2 抑製劑應給予所有患有 3 期或更高期 CKD 和 2 型糖尿病的患者,無論血糖控制如何,因為它們可減緩 CKD 進展並降低獨立於血糖控制的心衰竭風險 (79)。
如果心血管風險是主要問題,則建議 GLP-1 RA 用於降低心血管風險,因為它們降低了 CVD 事件和低血糖的風險,並且似乎可能減緩 CKD 進展 (80-82)。
  • SGLT2 inhibitors should be given to all patients with stage 3 CKD or higher and type 2 diabetes regardless of glycemic control, as they slow CKD progression and reduce heart failure risk independent of glycemic control (79).
  • GLP-1 RAs are suggested for cardiovascular risk reduction if such risk is a predominant problem, as they reduce risks of CVD events and hypoglycemia and appear to possibly slow CKD progression (80–82).