Diabetes Care Volume 48, Supplement 1, January 2025 S239

11. Chronic Kidney Disease and American Diabetes Association

Professional Practice Committee*
Risk Management: Standards of
Care in Diabetes—2025
Diabetes Care 2025;48(Suppl. 1):S239–S251 | https://doi.org/10.2337/dc25-S011

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11. CHRONIC KIDNEY DISEASE AND RISK MANAGEMENT
The American Diabetes Association (ADA) “Standards of Care in Diabetes” in-
cludes the ADA’s current clinical practice recommendations and is intended to
provide the components of diabetes care, general treatment goals and guide-
lines, and tools to evaluate quality of care. Members of the ADA Professional
Practice Committee, an interprofessional expert committee, are responsible for
updating the Standards of Care annually, or more frequently as warranted. For a
detailed description of ADA standards, statements, and reports, as well as the
evidence-grading system for ADA’s clinical practice recommendations and a full
list of Professional Practice Committee members, please refer to Introduction
and Methodology. Readers who wish to comment on the Standards of Care are
invited to do so at professional.diabetes.org/SOC.

For prevention and management of diabetes complications in children and adoles-

cents, please refer to Section 14, “Children and Adolescents.”

CHRONIC KIDNEY DISEASE

Screening

Recommendations
11.1a Assess kidney function (i.e., spot urine albumin-to-creatinine ratio [UACR])
and estimated glomerular filtration rate [eGFR] in people with type 1 diabetes
with duration of $5 years and in all people with type 2 diabetes regardless of
treatment. B
11.1b In people with established chronic kidney disease (CKD), monitor uri-
nary albumin (e.g., spot UACR) and eGFR 1–4 times per year depending on
the stage of the kidney disease (Fig. 11.1). B
*A complete list of members of the American
Diabetes Association Professional Practice Committee
can be found at https://doi.org/10.2337/dc25-SINT.
Treatment Duality of interest information for each author is
available at https://doi.org/10.2337/dc25-SDIS.
Recommendations
11.2 Optimize glucose management to reduce the risk or slow the progression Suggested citation: American Diabetes Association
Professional Practice Committee. 11. Chronic
of CKD (Fig. 9.3). A kidney disease and risk management: Standards
11.3 Optimize blood pressure management (aim for <130/80 mmHg [Fig. of Care in Diabetes—2025. Diabetes Care 2025;
10.2]) and reduce blood pressure variability to reduce the risk or slow the 48(Suppl. 1):S239–S251
progression of CKD and reduce cardiovascular risk. A © 2024 by the American Diabetes Association.
11.4a In nonpregnant people with diabetes and hypertension, either an ACE in- Readers may use this article as long as the
hibitor or an angiotensin receptor blocker (ARB) is recommended for those with work is properly cited, the use is educational
moderately increased albuminuria (UACR 30–299 mg/g creatinine) B and is and not for profit, and the work is not altered.
strongly recommended for those with severely increased albuminuria (UACR More information is available at https://www
.diabetesjournals.org/journals/pages/license.
S240 Chronic Kidney Disease and Risk Management Diabetes Care Volume 48, Supplement 1, January 2025

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Figure 11.1—Risk of CKD progression, cardiovascular disease risk, and mortality; frequency of visits; and referral to nephrology according to GFR
and albuminuria. The numbers in the boxes are a guide to the frequency of screening or monitoring (number of times per year). Green reflects no
evidence of CKD by estimated GFR or albuminuria, with screening indicated once per year. For monitoring of prevalent CKD, suggested monitoring
varies from once per year (yellow) to four times or more per year (i.e., every 1–3 months [deep red]) according to risks of CKD progression and
CKD complications (e.g., cardiovascular disease, anemia, and hyperparathyroidism). These are general parameters based only on expert opinion
and underlying comorbid conditions, and disease state must be taken into account, as should the likelihood of impacting a change in management
for any individual. CKD, chronic kidney disease; GFR, glomerular filtration rate. Adapted from de Boer et al. (1).

$300 mg/g creatinine) and/or eGFR 11.5a For people with type 2 diabetes if used, should be switched prior
<60 mL/min/1.73 m2 to maximally tol- and CKD, use of a sodium–glucose co- to conception to antihypertensive
erated dose to prevent the progression transporter 2 (SGLT2) inhibitor with medications considered safer dur-
of kidney disease and reduce cardiovas- demonstrated benefit is recommended ing pregnancy. B
cular events. A to reduce CKD progression and car- 11.7 Aim to reduce urinary albumin
11.4b Monitor for increased serum diovascular events in individuals with by $30% in people with CKD and al-
creatinine and for increased serum eGFR $20 mL/min/1.73 m2. A buminuria $300 mg/g to slow CKD
potassium levels when ACE inhibi- 11.5b To reduce cardiovascular risk progression. B
tors, ARBs, and mineralocorticoid re- and kidney disease progression in 11.8 For people with non–dialysis-
ceptor antagonists (MRAs) are used, people with type 2 diabetes and dependent stage G3 or higher CKD,
or for hypokalemia when diuretics are CKD, a glucagon-like peptide 1 ago- protein intake should be 0.8 g/kg
used at routine visits and 7–14 days af- nist with demonstrated benefit in body weight per day, as for the gen-
ter initiation or after a dose change. B this population is recommended. A eral population. A For individuals on
11.4c An ACE inhibitor or an ARB is 11.5c To reduce cardiovascular events dialysis, protein intake of 1.0–1.2
not recommended for the primary and CKD progression in people with
g/kg/day should be considered since
prevention of CKD in people with CKD and albuminuria, a nonsteroidal
protein energy wasting is a major
diabetes who have normal blood MRA that has been shown to be effec-
pressure, normal UACR (<30 mg/g problem for some individuals on dial-
tive in clinical trials is recommended
ysis. B
creatinine), and normal eGFR. A (if eGFR is $25 mL/min/1.73 m2). Po-
11.4d Continue renin-angiotensin sys- 11.9 Individuals should be referred for
tassium levels should be monitored. A
tem blockade for mild to moderate evaluation by a nephrologist if they
11.6 Potentially harmful antihyperten-
increases in serum creatinine (#30%) sive medications in pregnancy should have continuously increasing urinary
in individuals who have no signs of be avoided in sexually active individu- albumin levels and/or continuously
extracellular fluid volume deple- als of childbearing potential who are decreasing eGFR and/or if the eGFR is
tion. A not using reliable contraception and, <30 mL/min/1.73 m2. A
diabetesjournals.org/care Chronic Kidney Disease and Risk Management S241

11.10 Refer to a nephrologist for albumin-to-creatinine ratio because it will DIAGNOSIS OF CHRONIC KIDNEY
ultimately need to be done. DISEASE IN PEOPLE WITH
uncertainty about the etiology of
Normal level of urine albumin excre- DIABETES
kidney disease, difficult management
issues, and rapidly progressing kidney tion is defined as <30 mg/g creatinine, CKD in people with diabetes is usually a
disease. B moderately elevated albuminuria is de- clinical diagnosis made based on the pres-
fined as $30–300 mg/g creatinine, and ence of albuminuria and/or reduced eGFR
severely elevated albuminuria is defined as in the absence of signs or symptoms of
$300 mg/g creatinine. However, UACR is a other primary causes of kidney damage.
EPIDEMIOLOGY OF DIABETES AND continuous measurement, and differences The typical presentation of CKD in people
CHRONIC KIDNEY DISEASE within the normal and abnormal ranges are with diabetes is considered to include
Chronic kidney disease (CKD) is diag- associated with kidney and cardiovascular long-standing duration of diabetes, reti-
nosed by the persistent elevation of uri- outcomes (6,10,11). Furthermore, because nopathy, albuminuria without gross he-
nary albumin excretion (albuminuria), of high biological variability of >20% be- maturia, and gradually progressive loss of

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low estimated glomerular filtration rate tween measurements in urinary albumin ex- eGFR. However, signs of CKD may be pre-
(eGFR), or other manifestations of kid- cretion, two of three specimens of UACR sent at diagnosis or without retinopathy
ney damage (1). In this section, the fo- collected within a 3-to 6-month period in type 2 diabetes. Reduced eGFR without
cus is on CKD attributed to diabetes in should be abnormal before considering albuminuria has been frequently reported
adults, which occurs in 20–40% of peo- an individual to have moderately or se- in type 1 and type 2 diabetes and is be-
ple with diabetes (1–4). CKD in people verely elevated albuminuria (1,12,13). Ex- coming more common over time as the
with diabetes typically develops after a ercise within 24 h, infection, fever, heart prevalence of diabetes increases in the
duration of 10 years in type 1 diabetes failure, marked hyperglycemia, menstrua- U.S. (2,3,16,19–21). An active urinary sedi-
(the most common presentation is 5–15 tion, and marked hypertension may ele- ment (containing red or white blood cells
years after the diagnosis of type 1 dia- or cellular casts), rapidly increasing albu-
vate UACR independently of kidney
betes) but may be present at diagnosis minuria or total proteinuria, the presence
damage (14). Moreover, a recent analysis
of type 2 diabetes. CKD can progress to of nephrotic syndrome, rapidly decreasing
showed variability in the measurement
kidney failure requiring dialysis or kid- eGFR, or the absence of retinopathy (in
of UACR when measured weekly over a
ney transplantation and is the leading type 1 diabetes) suggests alternative or
1-month period. Thus, repeated meas-
cause of end-stage kidney disease additional causes of kidney disease. For in-
urements and tracking of trending over
(ESKD) in the U.S. (5). In addition, dividuals with these features, referral to a
time are needed to properly follow
among people with type 1 or type 2 di- nephrologist for further diagnosis, includ-
changes in UACR (12). ing the possibility of kidney biopsy, should
abetes, the presence of CKD markedly
Traditionally, eGFR is calculated from be considered. It is rare for people with
increases cardiovascular risk and health
serum creatinine using a validated for- type 1 diabetes to develop kidney disease
care costs (6). For details on the man-
agement of CKD in children with diabe- mula (15). eGFR is routinely reported by without retinopathy. In type 2 diabetes,
tes, please see Section 14, “Children laboratories along with serum creati- retinopathy is only moderately sensitive
and Adolescents.” nine, and eGFR calculators are available and specific for CKD caused by diabetes,
online at nkdep.nih.gov. An eGFR persis- as confirmed by kidney biopsy (22). It can-
ASSESSMENT OF ALBUMINURIA tently <60 mL/min/1.73 m2 and/or an not be definitively stated that a person
AND ESTIMATED GLOMERULAR urinary albumin value of >30 mg/g creat- with diabetes and CKD has CKD related to
FILTRATION RATE inine is considered abnormal, though op- diabetes unless the person has a kidney
timal thresholds for clinical diagnosis are biopsy, as there may be another cause or
Screening for albuminuria can be most
debated in older adults over age 70 years multiple causes. Hence, without a biopsy, it
easily performed by urine albumin-to-
creatinine ratio (UACR) in a random spot (1,16). Historically, a correction factor for is recommended to state that the individual
urine collection (1). Timed or 24-h collec- muscle mass was included in a modified has CKD in a person with diabetes. In most
tions are more burdensome and add little equation for African American people; people, there is no need for a kidney bi-
to prediction or accuracy. Measurement however, race is a social and not a bio- opsy, as the other possible diagnoses would
of a spot urine sample for albumin alone logic construct, making it problematic to not change treatment. Referral to a ne-
(whether by immunoassay or by using a apply race to clinical algorithms. Hence, phrologist should be done if there are any
sensitive dipstick test specific for albu- the Chronic Kidney Disease Epidemiology reasons to consider another cause of CKD
minuria) without simultaneously mea- Collaboration (CKD-EPI) creatinine equa- in a person with diabetes (Table 11.1).
suring urine creatinine is less expensive tion was refit without the race variable
but susceptible to false-negative and false- and should be used for everyone (17,18). STAGING OF CHRONIC KIDNEY
positive determinations as a result of vari- Additionally, increased use of cystatin DISEASE
ation in urine concentration due to hydra- C (another marker of eGFR) is suggested Stage G1 and stage G2 CKD are defined
tion (7). Thus, semiquantitative or in combination with serum creatinine be- by evidence of high albuminuria with
qualitative (dipstick) screening will need to cause combining filtration markers (creati- eGFR $60 mL/min/1.73 m2, and stages
be confirmed by UACR values in an accred- nine and cystatin C) is more accurate and G3-G5 CKD are defined by progressively
ited laboratory (8,9). Hence, it is better to would support better clinical decisions lower ranges of eGFR (23) (Fig. 11.1). At
simply collect a spot urine sample for than either marker alone. any eGFR, the degree of albuminuria is
S242 Chronic Kidney Disease and Risk Management Diabetes Care Volume 48, Supplement 1, January 2025

kidney disease, albuminuria and eGFR may

Table 11.1—Reasons to consider nondiabetic kidney diseases in a person with
chronic kidney disease and diabetes change due to progression of CKD, develop-
ment of a separate superimposed cause of
• Type 1 diabetes duration <5 years kidney disease, AKI, or other effects of med-
• Active urine sediment (e.g., containing red blood cells or cellular casts) ications, as noted above. Serum potassium
• Chronically well-managed blood glucose
should also be monitored in individuals
• Rapidly declining eGFR
• Rapidly increasing or very high UACR or urine protein/creatinine level treated with diuretics because these medi-
• No retinopathy in a person with type 1 diabetes cations can cause hypokalemia, which is as-
sociated with cardiovascular risk and
Information adapted from Liang et al. (129). eGFR, estimated glomerular filtration rate;
UACR, urine albumin-to-creatinine ratio.
mortality (38–40). Individuals with eGFR
<60 mL/min/1.73 m2 receiving ACE inhibi-
tors, ARBs, or MRAs should have serum po-
associated with risk of cardiovascular dis- glomerular filtration. There was concern tassium measured periodically. Additionally,

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ease (CVD), CKD progression, and mortal- that sodium–glucose cotransporter 2 people with this lower range of eGFR
ity (6). Therefore, there is an additional (SGLT2) inhibitors may promote AKI should have their medication dosing veri-
subclassification by level of urine albumin through volume depletion, particularly fied, their exposure to nephrotoxins (e.g.,
(Fig. 11.1). Furthermore, Kidney Disease: when combined with diuretics or other nonsteroidal anti-inflammatory drugs and
Improving Global Outcomes (KDIGO) rec- medications that reduce glomerular filtra- iodinated contrast) should be minimized,
ommends a more comprehensive CKD tion; however, this has not been found to and they should be evaluated for potential
staging that incorporates albuminuria at be true in randomized controlled trials of CKD complications (Table 11.2).
all stages of eGFR; this system is more advanced kidney disease (29) or high CVD There is a clear need for annual quanti-
closely associated with risk but is also more risk with normal kidney function (30–32). It tative assessment of UACR. This is espe-
complex (1). Thus, based on the current is also noteworthy that the nonsteroidal cially true after a diagnosis of albuminuria,
classification system, both eGFR and albu- mineralocorticoid receptor antagonists institution of ACE inhibitors or ARB ther-
minuria must be quantified to guide treat- (MRAs) do not increase the risk of AKI when apy to maximum tolerated doses, and
ment decisions. Quantification of eGFR used to slow kidney disease progression achievement of blood pressure goals. Early
levels is essential for modifications of medi- (33). Timely identification and treatment of changes in kidney function may be de-
cation dosages or restrictions of use (Fig. AKI is important because AKI is associated tected by increases in albuminuria before
11.1) (23,24), and the degree of albumin- with increased risks of progressive CKD and changes in eGFR (41), and this also signifi-
uria should influence the choice of antihy- other poor health outcomes (34). cantly affects cardiovascular risk. Contin-
pertensive medications (see Section 10, Elevations in serum creatinine (up to ued surveillance can assess both response
“Cardiovascular Disease and Risk 30% from baseline) with renin-angiotensin to therapy and disease progression and
Management”) or glucose-lowering medi- system (RAS) blockers (such as ACE inhibi- may aid in assessing participation in ACE
cations (see below). Observed history of tors and ARBs) must not be confused inhibitor or ARB therapy. In addition, in
eGFR loss (which is also associated with risk with AKI (35). An analysis of the Action to clinical trials of ACE inhibitor or ARB
of CKD progression and other adverse Control Cardiovascular Risk in Diabetes therapy in people with type 2 diabetes,
reducing albuminuria to levels <300 mg/g
health outcomes) and cause of kidney dam- Blood Pressure (ACCORD BP) trial demon-
creatinine or by >30% from baseline has
age (including possible causes other than di- strated that participants randomized to in-
been associated with improved kidney
abetes) may also affect these decisions (25). tensive blood pressure lowering with up
and cardiovascular outcomes, leading
to a 30% increase in serum creatinine did
to the recommendation that medica-
ACUTE KIDNEY INJURY not have any increase in mortality or pro-
tions should be titrated to maximize re-
Acute kidney injury (AKI) is diagnosed gressive kidney disease (36,37). Moreover,
duction in UACR (8). See Table 11.3 for
by a sustained increase in serum creati- a measure of markers for AKI showed no
interventions that lower albuminuria.
nine over a short period of time, which significant increase of any markers with
Data from post hoc analyses demon-
is also reflected as a rapid decrease in increased creatinine (37).
strate less benefit on cardiorenal out-
eGFR (26,27). People with diabetes are at Accordingly, ACE inhibitors and ARBs
comes at half doses of RAS blockade (42).
higher risk of AKI than those without diabe- should not be discontinued for increases
In type 1 diabetes, remission of albumin-
tes (28). Other risk factors for AKI include in serum creatinine (<30%) in the ab-
uria may occur spontaneously, and cohort
preexisting CKD, the use of medications sence of volume depletion.
studies evaluating associations of change
that cause kidney injury (e.g., nonsteroidal in albuminuria with clinical outcomes have
anti-inflammatory drugs), certain intrave- SURVEILLANCE reported inconsistent results (43,44).
nous dyes (e.g., iodinated radiocontrast Both albuminuria and eGFR should be The prevalence of CKD complications
agents) and the use of medications that monitored annually to enable timely di- correlates with eGFR (40). When eGFR is
alter renal blood flow and intrarenal he- agnosis of CKD, monitor progression of <60 mL/min/1.73 m2, screening for com-
modynamics. In particular, many antihy- CKD, detect superimposed kidney diseases plications of CKD is indicated (Table 11.2).
pertensive medications (e.g., diuretics, including AKI, assess risk of CKD complica- Early vaccination against hepatitis B virus
ACE inhibitors, and angiotensin receptor tions, dose medications appropriately, and is indicated in individuals likely to progress
blockers [ARBs]) can reduce intravascular determine whether nephrology referral is to ESKD (see Section 4, “Comprehensive
volume, renal blood flow, and/or needed. Among people with existing Medical Evaluation and Assessment of
diabetesjournals.org/care Chronic Kidney Disease and Risk Management S243

0.8 g/kg/day is not recommended because

Table 11.2—Screening for selected complications of chronic kidney disease
it does not alter blood glucose levels, car-
Complication Physical and laboratory evaluation
diovascular risk measures, or the course of
Blood pressure >130/80 mmHg Blood pressure, weight, BMI GFR decline (46). Some organizations rec-
Volume overload History, physical examination, weight ommend a lower protein intake (0.6–0.8 g/
Electrolyte abnormalities Serum electrolytes
kg/day). In particular, guidelines from the
National Kidney Foundation Kidney Dis-
Metabolic acidosis Serum electrolytes ease Outcomes Quality Initiative (NKF
Anemia Hemoglobin; iron, iron saturation, ferritin testing KDOQI) (47) and the International Soci-
if indicated ety of Renal Nutrition and Metabolism
Metabolic bone disease Serum calcium, phosphate, PTH, vitamin 25(OH)D (48) recommend a lower protein intake
level for reno-protection and state that
Complications of chronic kidney disease (CKD) generally become prevalent when estimated
this lower level is relatively safe. How-
glomerular filtration rate falls below 60 mL/min/1.73 m2 (stage G3 CKD or greater) and be-

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come more common and severe as CKD progresses. Evaluation of elevated blood pressure ever, for CKD in diabetes, the expert
and volume overload should occur at every clinical contact possible; laboratory evaluations are grade is “opinion” only. The guidelines
generally indicated every 6–12 months for stage G3 CKD, every 3–5 months for stage G4 CKD, note that the evidence for lower protein
and every 1–3 months for stage G5 CKD, or as indicated to evaluate symptoms or changes in intake in people with CKD has been pub-
therapy. 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone. lished for only those without diabetes,
which is graded Level 1A. Low-protein
Comorbidities,” for further information on 5 years. Almost all participants did not eating patterns should only be followed
immunization). have signs of kidney disease at the time alongside guidance from a health care
of enrollment. No differences between professional experienced in managing nu-
Prevention the examined medications were observed, trition for people with CKD.
The only proven primary prevention inter- which suggests that there were no unique Restriction of dietary sodium (to
ventions for CKD in people with diabetes reno-protective effects among these medi- <2,300 mg/day) may be useful to manage
are blood glucose (A1C goal of 7%) and cations for prevention. Of note, SGLT2 in- blood pressure and reduce cardiovascular
blood pressure management. There is no hibitors were not included in the study, as risk (49,50), and individualization of dietary
evidence that renin-angiotensin-aldosterone potassium may be necessary to manage se-
these medications were not routinely
system inhibitors or any other interventions rum potassium concentrations (28,38–40).
available at the time the study started.
prevent the development of CKD in the ab- These interventions may be most important
sence of hypertension or albuminuria. Thus, for individuals with reduced eGFR, for whom
INTERVENTIONS
the American Diabetes Association does not urinary excretion of sodium and potassium
Nutrition may be impaired. For individuals on dialysis,
recommend routine use of these medica-
For people with stages 3–5 non–dialysis- higher levels of dietary protein intake should
tions solely for the purpose of prevention
dependent CKD, dietary protein intake be considered since protein-energy wasting
of the development of CKD. In 2023, the
Glycemia Reduction Approaches in Dia- should be 0.8 g/kg body weight per day is a major problem for some individuals
betes: A Comparative Effectiveness Study (the recommended daily allowance) (1). on dialysis (51). Recommendations for
(GRADE) was published (45). This large Compared with higher levels of dietary dietary sodium and potassium intake
prospective study compared liraglutide, protein intake, this level slowed GFR de- should be individualized based on comorbid
sitagliptin, glimeperide, and insulin glar- cline with evidence of a greater effect conditions, medication use, blood pressure,
gine with respect to achieving and main- over time. Higher levels of dietary protein and laboratory data.
taining A1C goals in people with type 2 intake (>20% of daily calories from protein
diabetes treated with metformin mono- or >1.3 g/kg/day) have been associated Glycemic Goals
therapy; kidney and cardiovascular end with increased albuminuria, more rapid Intensive lowering of blood glucose with
points were examined as secondary out- kidney function loss, and CVD mortality the goal of achieving near-normoglycemia
comes. A total of 5,047 participants were and therefore should be avoided. Reduc- has been shown in large, randomized stud-
enrolled from July 2013 to August 2017 ing the amount of dietary protein below ies to delay the onset and progression of al-
and were followed for an average of the recommended daily allowance of buminuria and reduce eGFR in people with
type 1 diabetes (52,53) and type 2 diabetes
Table 11.3—Interventions that lower albuminuria (1,54–59). Insulin alone was used to lower
blood glucose in the Diabetes Control and
• Blood glucose management Complications Trial (DCCT)/Epidemiology of
• Blood pressure management Diabetes Interventions and Complications
• Treatment with ACE inhibitors or ARBs
(EDIC) study of type 1 diabetes, while a vari-
• Smoking cessation
• Weight loss ety of agents were used in clinical trials of
• Changes in eating patterns (decreased salt intake and/or protein intake) type 2 diabetes, supporting the conclusion
• Treatment with SGLT2 inhibitors, MRAs, or GLP-1 RAs that lowering blood glucose itself helps pre-
ARB, angiotensin receptor blocker; GLP-1 RA, glucagon-like peptide 1 receptor agonist; MRA,
vent CKD and its progression. The effects of
mineralocorticoid receptor antagonist. glucose-lowering therapies on CKD have
helped define A1C goals.
S244 Chronic Kidney Disease and Risk Management Diabetes Care Volume 48, Supplement 1, January 2025

The presence of CKD affects the risks ACE inhibitors or ARBs are the pre- period or a <21% decline in a 1-month
and benefits of intensive lowering of ferred first-line agents for blood pressure period was associated with better long-
blood glucose and a number of specific treatment among people with diabetes, term kidney outcomes. Hattori et al.
glucose-lowering medications. Adverse hypertension, eGFR <60 mL/min/1.73 m2, (83) evaluated 6,065 participants be-
effects of intensive management of and UACR $300 mg/g creatinine because tween 2005 and 2021 (approximately
blood glucose levels (hypoglycemia and of their proven benefits for prevention of 40% had diabetes) with eGFR ranging
mortality) were increased among people CKD progression (71,72,74). ACE inhibitors from 10 to 60 mL/min/1.73 m2 who
with kidney disease at baseline (60). and ARBs are considered to have similar had ACE inhibitors or ARBs stopped
Moreover, there is a lag time of at least 2 benefits (75,76) and risks. In the setting (usually due to hyperkalemia or AKI)
years in type 2 diabetes to over 10 years of lower levels of albuminuria (30–299 and found that those who restarted the
in type 1 diabetes for the effects of in- mg/g creatinine), ACE inhibitor or ARB ACE inhibitor or ARB had better long-term
tensive glucose control to manifest as therapy at maximum tolerated doses in kidney outcomes and lower mortality
improved eGFR outcomes (57,61,62). trials has reduced progression to more (there was no significant difference in hy-

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Therefore, in some people with prevalent advanced albuminuria ($300 mg/g creati- perkalemia in those who restarted ACE in-
CKD and substantial comorbidity, treat- nine), slowed CKD progression, and re- hibitors or ARBs). There is also an accom-
ment may be less intensive (i.e., A1C duced cardiovascular events but has not panying editorial that details the strengths
goals may be higher) to decrease the risk reduced progression to ESKD (74,77). and weaknesses of the studies (84).
of hypoglycemia (1,63). A1C levels are While ACE inhibitors or ARBs are often In the absence of kidney disease, ACE
also less reliable at advanced CKD stages prescribed for moderately increased albu- inhibitors or ARBs are useful to manage
(64,65). minuria (30–299 mg/g creatinine) without blood pressure but have not proven supe-
hypertension, outcome trials have not been rior to alternative classes of antihyperten-
Blood Pressure and Use of ACE performed in this setting to determine sive therapy, including thiazide-like diuretics
Inhibitors and Angiotensin Receptor whether they improve kidney outcomes. and dihydropyridine calcium channel
Blockers Moreover, two long-term, double-blind blockers (85). In a trial of people with
ACE inhibitors and ARBs remain a main- studies demonstrated no renoprotective type 2 diabetes and normal urinary al-
stay of management for people with effect of either ACE inhibitors or ARBs bumin excretion, an ARB reduced or
CKD with albuminuria and for the treat- among people with type 1 and type 2 dia- suppressed the development of albu-
ment of hypertension in people with di- betes who were normotensive with or minuria but increased the rate of car-
abetes (with or without CKD in people without high albuminuria (formerly microal- diovascular events (86). In a trial of
with diabetes). Indeed, all the trials that buminuria, 30–299 mg/g creatinine) (78,79). people with type 1 diabetes exhibiting
evaluated the benefits of SGLT2 inhibition It should be noted that ACE inhibitors neither albuminuria nor hypertension,
or nonsteroidal MRA effects were done in and ARBs are commonly not dosed at ACE inhibitors or ARBs did not prevent
individuals who were being treated with maximum tolerated doses because of the development of glomerulopathy as-
an ACE inhibitor or ARB, in some trials up concerns that serum creatinine will rise. sessed by kidney biopsy (78). This was
to maximum tolerated doses. As previously noted, not maximizing further supported by a similar trial in
Hypertension is a strong risk factor these therapies for this reason would people with type 2 diabetes (79).
for the development and progression of be considered suboptimal care. Note Two clinical trials studied the combi-
CKD (66). Antihypertensive therapy re- that in all clinical trials demonstrating nations of ACE inhibitors and ARBs and
duces the risk of albuminuria (67–70), efficacy of ACE inhibitors and ARBs in found no benefits on CVD or CKD, and
and among people with type 1 or 2 di- slowing kidney disease progression, the the medication combination had higher
abetes with established CKD (eGFR maximum tolerated doses were used— adverse event rates (hyperkalemia and/or
<60 mL/min/1.73 m2 and UACR $300 not very low doses that do not provide AKI) (87,88). Therefore, the combined use
mg/g creatinine), ACE inhibitor or ARB benefit. Moreover, there are now stud- of ACE inhibitors and ARBs should be
therapy reduces the risk of progres- ies demonstrating outcome benefits on avoided.
sion to ESKD (71–80). Moreover, anti- both mortality and slowed CKD progres-
hypertensive therapy reduces the risk sion in people with diabetes who have Direct Kidney Effects of
of cardiovascular events (67). an eGFR <30 mL/min/1.73 m2 (80). Ad- Glucose-Lowering Medications
A blood pressure level <130/80 mmHg ditionally, when increases in serum cre- Some glucose-lowering medications also
is recommended to reduce CVD mortality atinine reach 30% without associated have effects on the kidney that are direct,
and slow CKD progression among all peo- hyperkalemia, RAS blockade should be i.e., not mediated through glycemia. For
ple with diabetes. Lower blood pressure continued (36,81). example, SGLT2 inhibitors reduce renal tu-
goals (e.g., <130/80 mmHg) should be Two recent large retrospective analy- bular glucose reabsorption, weight, systemic
considered based on individual anticipated ses provide additional support for the blood pressure, intraglomerular pressure,
benefits and risks. People with CKD are at aggressive use of ACE inhibitors and and albuminuria and slow GFR loss through
increased risk of CKD progression (particu- ARBs in individuals with CKD. Ku et al. mechanisms that appear independent of
larly those with albuminuria) and CVD; (82) reviewed 17 trials that included glycemia (31,89–92). Moreover, recent
therefore, lower blood pressure goals may 11,800 individuals with CKD (defined as data support the notion that SGLT2 inhib-
be suitable in some cases, especially in in- eGFR <60 mL/min/1.73 m2); 82% had itors reduce oxidative stress in the kidney by
dividuals with severely elevated albumin- diabetes. The authors reported that a >50% and blunt increases in angiotensino-
uria ($300 mg/g creatinine). <13% decline in eGFR over a 3-month gen as well as reduce NLRP3 inflammasome
diabetesjournals.org/care Chronic Kidney Disease and Risk Management S245

activity (92–94). Glucagon-like peptide 1 KDIGO consensus recommendation al- A number of recent studies have shown
(GLP-1) receptor agonists (RAs) have gorithm for medications in people with cardiovascular protection from SGLT2 in-
also been shown to improve kidney out- diabetes and CKD. hibitors and GLP-1 RAs as well as kidney
comes (95–100). Kidney effects should The FDA revised its guidance for the protection from SGLT2 inhibitors and from
be considered when selecting agents use of metformin in CKD in 2016 (103), GLP-1 RAs. Selection of which glucose-low-
for glucose lowering (see Section 9, recommending use of eGFR instead of se- ering medications to use should be based
“Pharmacologic Approaches to Glycemic rum creatinine to guide treatment and ex- on the usual criteria of an individual’s risks
Treatment”). panding the pool of people with kidney (cardiovascular and kidney in addition to
disease for whom metformin treatment glucose management) as well as considera-
Selection of Glucose-Lowering should be considered. The revised FDA tions of effects on weight, other adverse ef-
Medications for People With Chronic guidance states that 1) metformin is con- fects, individual preferences, and cost.
Kidney Disease traindicated in individuals with an eGFR SGLT2 inhibitors are recommended for
For people with type 2 diabetes and es- <30 mL/min/1.73 m2, 2) eGFR should be people with eGFR $20 mL/min/1.73 m2

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tablished CKD, special considerations for monitored while taking metformin, 3) the and type 2 diabetes, as they slow CKD
the selection of glucose-lowering medi- benefits and risks of continuing treatment progression and reduce heart failure
cations include limitations to available should be reassessed when eGFR falls to risk independent of glucose management
medications when eGFR is diminished <45 mL/min/1.73 m2 (104,105), 4) met- (106). GLP-1 RAs are suggested for cardio-
and a desire to mitigate risks of CKD formin should not be initiated for individu- vascular risk reduction if such risk is a pre-
progression, CVD, and hypoglycemia als with an eGFR <45 mL/min/1.73 m2, dominant problem, as they reduce risks
(101,102). Medication dosing may require and 5) metformin should be temporarily dis- of CVD events and hypoglycemia and
modification with eGFR <60 mL/min/ continued at the time of or before iodinated slow progression of CKD (100,107–110).
1.73 m2 (1). Figure 11.2 shows the contrast imaging procedures in individuals A number of large cardiovascular out-
American Diabetes Association and with eGFR 30–60 mL/min/1.73 m2. comes trials in people with type 2 diabetes

Figure 11.2—Holistic approach for improving outcomes in people with diabetes and CKD. Icons presented indicate the following benefits: BP cuff, BP
lowering; glucose meter, glucose lowering; heart, cardioprotection; kidney, kidney protection; scale, weight management. eGFR is presented in units
of mL/min/1.73 m2. *ACEi or ARB (at maximal tolerated doses) should be first-line therapy for hypertension when albuminuria is present. Otherwise, di-
hydropyridine calcium channel blocker or diuretic can also be considered; all three classes are often needed to attain BP targets. †Finerenone is currently
the only ns-MRA with proven clinical kidney and cardiovascular benefits. ‡Semaglutide can be used as another first-line agent for people with CKD. ACEi,
angiotensin-converting enzyme inhibitor; ACR, albumin-to creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular dis-
ease; BP, blood pressure; CCB, calcium channel blocker; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like
peptide 1 receptor agonist; HTN, hypertension; MRA, mineralocorticoid receptor antagonist; ns-MRA, nonsteroidal mineralocorticoid receptor antago-
nist; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RAS, renin-angiotensin system; SGLT2i, sodium–glucose cotransporter 2 inhibitor;
T1D, type 1 diabetes; T2D, type 2 diabetes. Adapted from de Boer et al. (1).
S246 Chronic Kidney Disease and Risk Management Diabetes Care Volume 48, Supplement 1, January 2025

at high risk for CVD or with existing CVD assessment, doubling from the baseline se- with kidney disease with an eGFR of at
examined kidney effects as secondary out- rum creatinine average sustained for $30 least 20 but less than 45 mL/min/1.73 m2
comes. These trials include EMPA-REG days by central laboratory assessment, or or who had an eGFR of at least 45 but
OUTCOME [BI 10773 (Empagliflozin) Car- renal death or cardiovascular death, was re- less than 90 mL/min/1.73 m2 with a
diovascular Outcome Event Trial in Type 2 duced by 30%. This benefit was on back- UACR of at least 200 mg/g creatinine. Ap-
Diabetes Mellitus Patients], CANVAS ground ACE inhibitor or ARB therapy in proximately one-half of the 6,609 partici-
(Canagliflozin Cardiovascular Assessment >99% of the participants (29). More- pants had diabetes. The empagliflozin-
Study), LEADER (Liraglutide Effect and Ac- over, in this advanced CKD group, there treated participants had lower risk of pro-
tion in Diabetes: Evaluation of Cardiovas- were clear benefits on cardiovascular out- gression of kidney disease and lower risk
cular Outcome Results), and SUSTAIN-6 comes demonstrating a 31% reduction in of death from cardiovascular causes (HR
(Trial to Evaluate Cardiovascular and cardiovascular death or heart failure hospi- 0.72 [95% CI 0.64–0.82]; P < 0.001).
Other Long-term Outcomes With Sema- talization and a 20% reduction in cardiovas- With respect to cardiovascular outcomes,
glutide in Subjects With Type 2 Diabetes) cular death, nonfatal myocardial infarction, SGLT2 inhibitors have demonstrated re-

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(91,95,98,111). Specifically, compared with or nonfatal stroke (29,110,113). duced risk of heart failure hospitalizations
placebo, empagliflozin reduced the risk A second trial in advanced CKD in peo- and some also demonstrated cardiovascular
of incident or worsening nephropathy ple with diabetes was the Dapagliflozin risk reduction. GLP-1 RAs have clearly
(a composite of progression to UACR and Prevention of Adverse Outcomes in demonstrated cardiovascular benefits.
>300 mg/g creatinine, doubling of se- Chronic Kidney Disease (DAPA-CKD) study (See Section 10, “Cardiovascular Disease
rum creatinine, ESKD, or death from (114). This trial examined a cohort similar and Risk Management,” for further de-
ESKD) by 39% and the risk of doubling of to that in CREDENCE except 67.5% of the tailed discussion.)
serum creatinine accompanied by eGFR participants had type 2 diabetes and CKD Of note, while the glucose-lowering ef-
#45 mL/min/1.73 m2 by 44%; canagliflo- (the other one-third had CKD without fects of SGLT2 inhibitors are blunted with
zin reduced the risk of progression of al- type 2 diabetes), and the end points eGFR <45 mL/min/1.73 m2, the renal and
buminuria by 27% and the risk of were slightly different. The primary out- cardiovascular benefits were still seen at
reduction in eGFR, ESKD, or death from come was time to the first occurrence of eGFR levels as low as 20 mL/min/1.73 m2
ESKD by 40%; liraglutide reduced the risk any of the components of the composite, even with no significant change in glucose
of new or worsening nephropathy (a including $50% sustained decline in eGFR (29,31,52,63,98,111,114–116). Most par-
composite of persistent macroalbuminu- or reaching ESKD or cardiovascular death, ticipants with CKD in these trials also had
ria, doubling of serum creatinine, ESKD, or or renal death. Secondary outcome meas- diagnosed atherosclerotic cardiovascular
death from ESKD) by 22%; and semaglutide ures included time to the first occurrence disease (ASCVD) at baseline, although
reduced the risk of new or worsening ne- of any of the components of the compos- 28% of CANVAS participants with CKD
phropathy (a composite of persistent UACR ite kidney outcome ($50% sustained de- did not have diagnosed ASCVD (32).
>300 mg/g creatinine, doubling of serum cline in eGFR or reaching ESKD or renal Based on evidence from the CREDENCE,
creatinine, or ESKD) by 36% (each P < death), time to the first occurrence of ei- DAPA-CKD, and EMPA-KIDNEY trials, as
0.01). These analyses were limited by evalu- ther of the components of the cardiovas- well as secondary analyses of cardiovascu-
ation of study populations not selected pri- cular composite (cardiovascular death or lar outcomes trials with SGLT2 inhibitors,
marily for CKD and examination of kidney hospitalization for heart failure), and time cardiovascular and renal events are re-
effects as secondary outcomes. to death from any cause. The trial had duced with SGLT2 inhibitor use in individu-
Three large clinical trials of SGLT2 inhibi- 4,304 participants with a mean eGFR at als with an eGFR of 20 mL/min/1.73 m2,
tors have focused on people with CKD and baseline of 43.1 ± 12.4 mL/min/1.73 m2 independent of glucose-lowering effects
assessment of primary kidney outcomes. (range 25–75 mL/min/1.73 m2) and a (110,113).
Canagliflozin and Renal Events in Diabetes median UACR of 949 mg/g (range 200– The recently published FLOW study
with Established Nephropathy Clinical Evalu- 5,000 mg/g). There was a significant bene- demonstrated that the GLP-1 RA sema-
ation (CREDENCE), a placebo-controlled trial fit by dapagliflozin for the primary end glutide had reno-protective effects in
of canagliflozin among 4,401 adults with point (hazard ratio [HR] 0.61 [95% CI people with CKD (100). The study en-
type 2 diabetes, UACR $300–5,000 mg/g 0.51–0.72]; P < 0.001) (114). The HR for rolled 3,533 participants with significant
creatinine, and eGFR range 30–90 mL/min/ the kidney composite of a sustained de- kidney disease defined by level of eGFR
1.73 m2 (mean eGFR 56 mL/min/1.73 m2 cline in eGFR of $50%, ESKD, or death and/or by level of albuminuria (of note,
with a mean albuminuria level of >900 from renal causes was 0.56 (95% CI all participants had an albuminuria level
mg/day), had a primary composite end 0.45–0.68; P < 0.001). The HR for the of at least 100 mg/g). The primary out-
point of ESKD, doubling of serum creati- composite of death from cardiovascular come was defined as the first major kid-
nine, or renal or cardiovascular death causes or hospitalization for heart failure ney disease event (onset of >50% in
(29,112). It was stopped early due to was 0.71 (95% CI 0.55–0.92; P = 0.009). Fi- eGFR, onset of persistent eGFR of
positive efficacy and showed a 32% risk nally, all-cause mortality was decreased in <15 mL/min/1.73 m2, initiation of dialy-
reduction for development of ESKD over the dapagliflozin group compared with the sis or transplant, renal death, and cardio-
control (29). Additionally, the development placebo group (P < 0.004). vascular death). The study was stopped
of the primary end point, which included di- The most recently published clinical early due to reaching a prespecified out-
alysis for $30 days, kidney transplantation trial was EMPA-KIDNEY (Study of Heart come. There was a 24% lower HR for those
or eGFR <15 mL/min/1.73 m2 sustained and Kidney Protection with Empagliflozin) taking semaglutide compared with the pla-
for $30 days by central laboratory (115). This study enrolled participants cebo group. Of note, cardiovascular deaths
diabetesjournals.org/care Chronic Kidney Disease and Risk Management S247

comprised about 38% of the events. When participants (119); enrollment criteria in- decrease in eGFR of $57% from baseline
the cardiovascular deaths are removed cluded eGFR >60 mL/min/1.73 m2, but over at least 4 weeks, or renal death.
from the analysis, the HR for kidney spe- efficacy was seen at eGFR >20 mL/min/ The double-blind, placebo-controlled
cific events was 21% lower in those taking 1.73 m2 in people with heart failure. Most trial randomized 5,734 people with CKD
semaglutide. Thus, the study supports a recently, the EMPA-KIDNEY trial showed and type 2 diabetes to receive finere-
beneficial effect of semaglutide in slowing efficacy in participants with eGFR as low none, a nonsteroidal MRA, or placebo.
decline in kidney function as well as being as 20 mL/min/1.73 m2 (115). Hence, the Eligible participants had a UACR of 30 to
cardioprotective in people with CKD and new recommendation is to use SGLT2 in- <300 mg/g, an eGFR of 25 to <60 mL/min/
type 2 diabetes. Of note, the participants hibitors in individuals with eGFR as low as 1.73 m2, and diabetic retinopathy, or a
who took semaglutide had lower A1C, 20 mL/min/1.73 m2. In addition, the DE- UACR of 300–5,000 mg/g and an eGFR of
lower blood pressure, and more weight CLARE-TIMI 58 trial suggested effective- 25 to <75 mL/min/1.73 m2. The potassium
loss—all of which are beneficial for ness in participants with normal urinary level had to be #4.8 mmol/L. The mean
slowing decline in kidney function and albumin levels (120). In sum, for people age of participants was 65.6 years, and

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reducing cardiovascular adverse events. with type 2 diabetes and CKD, use of an 30% were female. The mean eGFR was
Whether this beneficial combination of ef- SGLT2 inhibitor is recommended to reduce 44.3 mL/min/1.73 m2, and the mean albu-
fects was the primary cause for the reno- CKD progression and cardiovascular events minuria was 852 mg/g (interquartile range
protective outcomes or whether there is a in people with an eGFR $20 mL/min/ 446–1,634 mg/g). The primary end point
unique reno-protective effect of semaglu- 1.73 m2. was reduced with finerenone compared
tide remains to be determined. Of note, GLP-1 RAs may also be used with placebo (HR 0.82 [95% CI 0.73–0.93];
Adverse event profiles of these agents at low eGFR for cardiovascular protec- P = 0.001), as was the key secondary com-
also must be considered. Please refer to tion but may require dose adjustment
Table 9.2 for medication-specific factors, posite of cardiovascular outcomes (HR 0.86
(121). [95% CI 0.75–0.99]; P = 0.03). Hyperkale-
including adverse event information, for
these agents. Additional clinical trials fo- mia resulted in 2.3% discontinuation in the
Renal and Cardiovascular Outcomes study group compared with 0.9% in the
cusing on CKD and cardiovascular out-
of Mineralocorticoid Receptor
comes in people with CKD are ongoing placebo group. However, the study was
Antagonists in Chronic Kidney Disease
and will be reported in the next few years. completed, and there were no deaths re-
MRAs historically have not been well
For people with type 2 diabetes and lated to hyperkalemia. Of note, 4.5% of the
studied in people with diabetes and
CKD, the selection of specific agents may total group were being treated with SGLT2
CKD because of the risk of hyperkalemia
depend on comorbidity and CKD stage. inhibitors.
(122,123). However, data that do exist
SGLT2 inhibitors are recommended for The Finerenone in Reducing Cardio-
suggest sustained benefit on albumin-
individuals at high risk of CKD progres- vascular Mortality and Morbidity in Dia-
uria reduction. There are two different
sion (i.e., with albuminuria or a history betic Kidney Disease (FIGARO-DKD) trial
classes of MRAs, steroidal and nonste-
of documented eGFR loss) (Fig. 9.3). For assessed the safety and efficacy of finer-
roidal, with one group not extrapolat-
people with type 2 diabetes and CKD, enone in reducing cardiovascular events
able to the other (124). Late in 2020,
use of an SGLT2 inhibitor in individuals among people with type 2 diabetes and
the results of the first of two trials, the
with eGFR $20 mL/min/1.73 m2 is rec- CKD with elevated UACR (30 to <300 mg/g
Finerenone in Reducing Kidney Failure and
ommended to reduce CKD progression creatinine) and eGFR 25–90 mL/min/1.73
Disease Progression in Diabetic Kidney Dis-
and cardiovascular events. The reason m2 (126). The potassium level had to be
ease (FIDELIO-DKD) trial, which examined #4.8 mmol/L The study randomized eligi-
for the limit of eGFR is as follows. The
major clinical trials for SGLT2 inhibitors the kidney effects of finerenone, demon- ble subjects to either finerenone (n =
that showed benefit for CKD in people strated a significant reduction in CKD 3,686) or placebo (n = 3,666). Participants
with diabetes are CREDENCE, DAPA-CKD, progression and cardiovascular events in with an eGFR of 25–60 mL/min/1.73 m2
and EMPA-KIDNEY. CREDENCE enrollment people with diabetes and advanced CKD at the screening visit received an initial
criteria included eGFR >30 mL/min/1.73 m2 (33,125). This trial had a primary end point dose at baseline of 10 mg once daily, and
and UACR >300 mg/g (29,110). DAPA- of time to first occurrence of the compos- if eGFR at screening was $60 mL/min/
CKD enrolled individuals with eGFR ite end point of onset of kidney failure, a 1.73 m2, the initial dose was 20 mg once
>25 mL/min/1.73 m2 and UACR >200 mg/g. sustained decrease of eGFR >40% from daily. An increase in the dose from 10 to
Subgroup analyses from DAPA-CKD (117) baseline over at least 4 weeks, or renal 20 mg once daily was encouraged after 1
and analyses from the EMPEROR heart death. A prespecified secondary outcome month, provided the serum potassium
failure trials suggest that SGLT2 inhibitors was time to first occurrence of the com- level was #4.8 mmol/L and eGFR was
are safe and effective at eGFR levels of posite end point of cardiovascular death or stable. The mean age of participants was
>20 mL/min/1.73 m2. The Empagliflozin nonfatal cardiovascular events (myocardial 64.1 years (31% were female), and the
Outcome Trial in Patients With Chronic infarction, stroke, or hospitalization for median follow-up duration was 3.4 years.
Heart Failure With Preserved Ejection Frac- heart failure). Other secondary outcomes The median A1C was 7.7%, the mean sys-
tion (EMPEROR-Preserved) enrolled 5,998 included all-cause mortality, time to all- tolic blood pressure was 136 mmHg, and
participants (118), and the Empagliflozin cause hospitalizations, and change in UACR the mean GFR was 67.8 mL/min/1.73 m2.
Outcome Trial in Patients With Chronic from baseline to month 4, and time to first People with heart failure with a reduced
Heart Failure and a Reduced Ejection Frac- occurrence of the following composite end ejection fraction and uncontrolled hyper-
tion (EMPEROR-Reduced) enrolled 3,730 point: onset of kidney failure, a sustained tension were excluded.
S248 Chronic Kidney Disease and Risk Management Diabetes Care Volume 48, Supplement 1, January 2025

The primary composite outcome was participants taking either an ACE inhibitor mortality and end-stage renal disease in individuals
cardiovascular death, myocardial infarc- or an ARB, often at maximally tolerated with and without diabetes: a meta-analysis. Lancet
2012;380:1662–1673
tion, stroke, and hospitalization for heart doses. 7. Yarnoff BO, Hoerger TJ, Simpson SK, et al.;
failure. The finerenone group showed a Centers for Disease Control and Prevention CKD
13% reduction in the primary end point REFERRAL TO A NEPHROLOGIST Initiative. The cost-effectiveness of using chronic
compared with the placebo group (12.4% Health care professionals should consider
kidney disease risk scores to screen for early-
vs. 14.2%; HR 0.87 [95% CI 0.76–0.98]; stage chronic kidney disease. BMC Nephrol
referral to a nephrologist if the individual 2017;18:85
P = 0.03). This benefit was primarily with diabetes has continuously rising UACR 8. Coresh J, Heerspink HJL, Sang Y, et al.; Chronic
driven by a reduction in heart failure hos- levels and/or continuously declining eGFR, Kidney Disease Prognosis Consortium and Chronic
pitalizations: 3.2% vs. 4.4% in the placebo if there is uncertainty about the etiology of Kidney Disease Epidemiology Collaboration.
group (HR 0.71 [95% CI 0.56–0.90]). kidney disease, for difficult management Change in albuminuria and subsequent risk of end-
Of the secondary outcomes, the most stage kidney disease: an individual participant-level
issues (anemia, secondary hyperpara- consortium meta-analysis of observational studies.
noteworthy was a 36% reduction in thyroidism, significant increases in albu-

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Lancet Diabetes Endocrinol 2019;7:115–127
ESKD: 0.9% vs. 1.3% in the placebo minuria despite good blood pressure 9. Levey AS, Gansevoort RT, Coresh J, et al.
group (HR 0.64 [95% CI 0.41–0.995]). management, metabolic bone disease, Change in albuminuria and GFR as end points for
There was a higher incidence of hyper- resistant hypertension, or electrolyte dis- clinical trials in early stages of CKD: a scientific
kalemia in the finerenone group, 10.8% turbances), or when there is advanced kid-
workshop sponsored by the National Kidney
vs. 5.3%, although only 1.2% of the Foundation in collaboration with the US Food and
ney disease (eGFR <30 mL/min/1.73 m2) Drug Administration and European Medicines
3,686 individuals on finerenone stopped requiring discussion of renal replacement Agency. Am J Kidney Dis 2020;75:84–104
the study due to hyperkalemia. therapy for ESKD (1). The threshold for 10. Afkarian M, Sachs MC, Kestenbaum B, et al.
The FIDELITY prespecified pooled effi- Kidney disease and increased mortality risk in
referral may vary depending on the fre-
cacy and safety analysis incorporated in- type 2 diabetes. J Am Soc Nephrol 2013;24:
quency with which a health care profes-
dividuals from both the FIGARO-DKD 302–308
sional encounters people with diabetes 11. Groop P-H, Thomas MC, Moran JL, et al.;
and FIDELIO-DKD trials (N = 13,171) to al-
and kidney disease. Consultation with a FinnDiane Study Group. The presence and
low for evaluation across the spectrum of
nephrologist when stage 4 CKD develops severity of chronic kidney disease predicts all-
severity of CKD, since the populations
(eGFR <30 mL/min/1.73 m2) has been cause mortality in type 1 diabetes. Diabetes
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