CME INDIA Presentation by Dr. Dinesh Agarwal, MD (Med), Diabetologist, Course Director – Advance Certificate Course in Diabetology, Dean – Academics and Research at Marwari Hospital, Guwahati, Assam, India.

Based on a presentation at ICDM-2023 at Vadodara.

What does a UACR > 300 indicate in a patient with diabetes and other comorbidities?

• UACR level greater than 300 indicates significant albuminuria or proteinuria in a patient with diabetes and other comorbidities. It suggests the presence of diabetic kidney disease (also known as diabetic nephropathy) which is a common complication of diabetes. It signifies a higher risk of progressive kidney damage and may require further evaluation and management.

What can be the differentials of UACR >300

• Uncontrolled hypertension
• Active UTI
• Diabetic nephropathy
• Non glomerular pathologies like glomerulonephritis

What should be the initial approach to a patient with UACR > 300 and diabetes with other comorbidities?

• The initial approach to a patient with UACR > 300 and diabetes with other comorbidities should involve the following steps:

What further investigations may be necessary for a patient with UACR > 300 and diabetes with other comorbidities?

• Renal ultrasound: A renal ultrasound can assess the structure and size of the kidneys and detect any abnormalities, such as kidney stones or cysts Kidney biopsy: In some cases, a kidney biopsy may be recommended to determine the underlying cause of kidney disease, especially if there are atypical features or treatment is not progressing as expected.
• Lipid profile: Assessing lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) can help identify dyslipidemia, a common cardiovascular risk factor in patients with diabetes and kidney disease.
• Hemoglobin A1c (HbA1c): Measure HbA1c levels to assess long-term blood glucose control.
• Serum electrolytes and blood urea nitrogen (BUN): Evaluate electrolyte levels (sodium, potassium, calcium, phosphorus) and BUN to assess kidney function and potential imbalances.
• Complete blood count (CBC): Check the CBC to assess red and white blood cell counts, hemoglobin levels, and platelet counts.
• Additional specific tests: Depending on the patient’s medical history and physical examination, additional tests may be ordered to evaluate specific comorbidities, such as cardiac stress testing, ophthalmologic examination, or peripheral vascular assessment.

Importance of increase UACR

• Increase risk of progression to CKD
• Increased CVS morbidity

What are the potential complications of diabetic kidney disease (DKD)?

• Chronic kidney disease (CKD)
• Cardiovascular disease
• Hypertension
• Fluid retention and edema
• Electrolyte imbalances
• Anemia
• Bone and mineral disorders
• Increased infections

How to Manage?

• Long-term management of a patient with UACR > 300 and diabetes with other comorbidities should focus on the following aspects: Glycemic control: Optimize blood glucose control through regular monitoring, lifestyle modifications (diet, exercise, weight management), and appropriate diabetes medications (oral hypoglycemic agents and/or insulin).
• Blood pressure management: Maintain blood pressure at recommended targets (<130/80 mmHg) through lifestyle changes (salt restriction, weight loss, exercise) and antihypertensive medications (including ACE inhibitors or ARBs as first-line agents for kidney protection). Protein intake management: Restrict dietary protein intake, usually through consultation with a registered dietitian, to reduce the workload on the kidneys. The exact amount should be individualized based on the patient’s specific needs.
• Lipid management: Control dyslipidemia with lifestyle modifications (lowfat diet, exercise) and lipid-lowering medications (statins) to reduce the risk of cardiovascular complications. Regular follow-up: Schedule regular visits with healthcare providers to monitor kidney function, blood pressure, UACR levels, blood glucose control, and adjust medications as needed. Multidisciplinary approach: Collaborate with a healthcare team including primary care physicians, endocrinologists, nephrologists, dietitians, and other specialists as necessary to address the various aspects of the patient’s comorbidities.
• Patient education and self-care: Educate the patient about their condition, emphasizing the importance of medication adherence, lifestyle modifications, regular monitoring, and early reporting of any concerning symptoms. When To Refer to a Nephrologists’: Consider referral to a nephrologist or other specialists for further evaluation and management if the patient’s kidney function continues to decline or if additional complications arise.

Treatment

• ACEi/ARB
• SGLT2 Inhibitor
• Finerenone
• GLP 1- RA

How do we combine or initiate agents like ARB/SGLT2i/MRA in patient with DKD and albuminuria?

• In patients with diabetes, hypertension, and albuminuria, it is recommended to commence treatment with either an Angiotensin-Converting Enzyme Inhibitor (ACEi) or an Angiotensin II Receptor Blocker (ARB), and to gradually adjust the dosage to the highest approved level that can be tolerated.
• In cases where diabetes and albuminuria coexist with normal blood pressure, the option of initiating treatment with an ACEi or ARB can be considered.
• If symptomatic hypotension or uncontrolled hyperkalemia persists despite medical intervention, or if there is a need to alleviate uremic symptoms while managing kidney failure (estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2), it may be necessary to reduce the dosage or discontinue ACEi or ARB therapy.
• It is essential to administer only one agent at a time for renin-angiotensin system (RAS) blockade. Combining an ACEi with an ARB, or pairing an ACEi or ARB with a direct renin inhibitor, carries potential risks and should be avoided.

SGLT2i

• KIDGO recommends initiating treatment with an SGLT2 inhibitor (SGLT2i) in patients diagnosed with type 2 diabetes (T2D), chronic kidney disease (CKD), and an estimated glomerular filtration rate (eGFR) of 20 ml/min per 1.73 m2 or higher.
• When selecting an SGLT2i, prioritize agents that have demonstrated kidney or cardiovascular benefits, and consider the patient’s eGFR as a determining factor.
• It is advisable to temporarily withhold SGLT2i treatment during extended periods of fasting, surgical procedures, or instances of critical medical illness, particularly when there is an increased risk of ketosis.
• In patients at risk of hypovolemia, consider reducing thiazide or loop diuretic dosages before initiating SGLT2i therapy. Additionally, educate patients about the symptoms of volume depletion and low blood pressure, and monitor their volume status after starting the medication.
• It’s important to note that a reversible decrease in eGFR may occur when beginning SGLT2i treatment, and this alone is not typically a reason to discontinue the therapy.
• Once an SGLT2i is initiated, it is reasonable to continue its use even if the eGFR falls below 20 ml/min per 1.73 m2, unless it is not well-tolerated or the patient undergoes kidney replacement therapy.

MRAs

• For patients diagnosed with type 2 diabetes (T2D), an estimated glomerular filtration rate (eGFR) of ≥25 ml/min per 1.73 m2, normal serum potassium levels, and albuminuria (≥30 mg/g [≥3 mg/mmol]) despite receiving the maximum tolerated dose of renin-angiotensin system inhibitor (RASi), we recommend considering a nonsteroidal mineralocorticoid receptor antagonist (MRA) that has demonstrated benefits for kidney or cardiovascular health.
• Nonsteroidal MRAs are most suitable for individuals with T2D who face a high risk of both chronic kidney disease (CKD) progression and cardiovascular events, as evidenced by persistent albuminuria despite adhering to other standard-of-care treatments.
• Combining a nonsteroidal MRA with a RASi and an SGLT2 inhibitor (SGLT2i) can be a beneficial approach for managing T2D and CKD.
• To minimize the risk of hyperkalemia, it is advisable to select patients with consistently normal serum potassium levels and closely monitor their potassium levels after initiating treatment with a nonsteroidal MRA.
• Steroidal MRAs are more appropriate for addressing heart failure, hyperaldosteronism, or refractory hypertension but can potentially lead to hyperkalemia or a temporary decline in glomerular filtration, especially in patients with a low GFR.

What are the practical considerations when initiating SGLT2 inhibitors or MRAs and monitoring patients with DKD?

• SGLT2 inhibitors (SGLT2i) are recommended for their protective effects on the kidneys and cardiovascular system. They have demonstrated safety and benefits in patients with chronic kidney disease (CKD), even in the absence of type 2 diabetes (T2D). Therefore, if patients are already receiving treatment with other glucose-lowering agents, the addition of an SGLT2i to their current regimen is a viable option.
• When selecting an SGLT2i, prioritize agents with established benefits for kidney and cardiovascular health, taking the estimated glomerular filtration rate (eGFR) into consideration.
• It is advisable to temporarily suspend SGLT2i therapy during periods of prolonged fasting, surgical procedures, or critical medical illness when there may be an elevated risk of developing ketosis.
• For patients with T2D, it’s important to note that there is a slight but increased risk of euglycemic diabetic ketoacidosis associated with SGLT2i use.
• In cases where a patient is susceptible to hypovolemia, consider reducing thiazide or loop diuretic dosages before initiating SGLT2i treatment. Provide patients with guidance on recognizing symptoms of volume depletion and low blood pressure, and monitor their volume status after starting the medication.
• A reversible decrease in eGFR may occur when initiating SGLT2i treatment, but this alone is generally not a reason to discontinue the therapy.
• Once SGLT2i therapy is initiated, it is reasonable to continue it even if the eGFR falls below 20 ml/min per 1.73 m2, unless the patient experiences intolerance or initiates kidney replacement therapy.

Practical approach to initiating sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes and chronic kidney disease (CKD). Courtesy: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S): S1–S127.

• Steroidal mineralocorticoid receptor antagonists (MRAs), like spironolactone and eplerenone, have established cardiovascular benefits for individuals with heart failure and are effective in the treatment of primary hyperaldosteronism and refractory hypertension. Additionally, steroidal MRAs have been found to reduce albuminuria. However, their impact on the progression of kidney disease, including declines in estimated glomerular filtration rate (eGFR) or the development of kidney failure, has not been extensively studied in large-scale trials. Consequently, their precise benefits regarding clinical kidney outcomes remain uncertain.
• It’s important to note that the use of steroidal MRAs comes with an increased risk of hyperkalemia, approximately 2 to 3 times greater than baseline levels, and a twofold increased risk of acute kidney injury. Moreover, spironolactone usage may lead to gynecomastia, a side effect characterized by breast tissue enlargement in males.
• Due to these adverse effects and reports of a higher incidence of hyperkalemia after the publication of the Randomized Aldactone Evaluation Study, the utilization of steroidal MRAs has been limited, particularly in populations at high risk for these side effects.
• Novel nonsteroidal MRAs, such as finerenone and esaxerenone, exhibit greater selectivity for mineralocorticoid receptors and have been observed to achieve similar reductions in albuminuria while carrying a lower risk of hyperkalemia.

What are the adverse events associated with CKD therapies and how are they best managed?

• Blood Pressure (BP) Management and Renin-Angiotensin-Aldosterone System (RAAS) Interruption – It is advisable to personalize BP targets and the selection of BP-lowering agents based on factors such as age, the presence of concurrent cardiovascular disease, other underlying medical conditions, the risk of chronic kidney disease (CKD) progression, the existence of retinopathy (particularly in CKD patients with diabetes), and the patient’s tolerance to the prescribed treatment.
• When treating CKD patients with BP-lowering medications, routinely inquire about symptoms of postural dizziness and regularly assess for postural hypotension.
• Tailor BP treatment plans for elderly individuals with CKD by taking into careful consideration their age, comorbidities, and other ongoing therapies. Gradually adjust the treatment regimen and closely monitor for adverse events related to BP management, which may include electrolyte imbalances, acute deterioration in kidney function, orthostatic hypotension, and medication side effects.
• In both diabetic and non-diabetic adults with CKD and urine albumin excretion levels ≥30 mg/24 hours (or equivalent*), it is recommended to initiate treatment with BP-lowering medications when their office BP consistently exceeds 140 mm Hg systolic or 90 mm Hg diastolic. The objective is to maintain BP levels consistently below 140 mm Hg systolic and 90 mm Hg diastolic.

 Serum potassium monitoring during treatment with finerenone. Courtsey: Kidney International (2022) 102 (Suppl 5S), S1–S127.

It is advisable that in both diabetic and non-diabetic adults with chronic kidney disease (CKD) and urine albumin excretion levels of ≥30 mg/24 hours (or equivalent*), treatment with BP-lowering medications be initiated when their office BP consistently registers above 130 mm Hg systolic or 80 mm Hg diastolic. The goal is to maintain BP levels consistently below 130 mm Hg systolic and 80 mm Hg diastolic.

• In diabetic adults with CKD and urine albumin excretion levels between 30 and 300 mg/24 hours (or equivalent*), it is recommended to use an Angiotensin Receptor Blocker (ARB) or Angiotensin-Converting Enzyme Inhibitor (ACE-I).
• For both diabetic and non-diabetic adults with CKD and urine albumin excretion levels exceeding 300 mg/24 hours (or equivalent*), it is strongly advised to employ an ARB or ACE-I as part of the treatment regimen.

*Note: The term “equivalent” likely refers to alternative measurements of urine albumin excretion, such as albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio (PCR), which are commonly used in clinical practice as substitutes for 24-hour urine collections. The specific thresholds mentioned here may vary depending on clinical guidelines and the units used for these measurements.

Protein intake

• KIDGO suggests lowering protein intake to 0.8 g/kg/day in adults with diabetes or without diabetes and GFR 30 ml/min/ 1.73 m2 (GFR categories G4-G5), with appropriate education.
• We suggest avoiding high protein intake (<1.3 g/kg/day) in adults with CKD at risk of progression.

Glycemic control

• KIDGO recommends a target hemoglobin A1c (HbA1c) of 7.0% (53 mmol/mol) to prevent or delay progression of the microvascular complications of diabetes, including diabetic kidney disease. (1A)
• KIDGO recommends not treating to an HbA1c target of <7.0% (<53 mmol/mol) in patients at risk of hypoglycemia. (1B)
• KIDGO suggests that target HbA1c be extended above 7.0% (53 mmol/mol) in individuals with comorbidities or limited life expectancy and risk of hypoglycemia. (2C)
• KIDGO recommends that metformin be continued in people with GFR Z45ml/min/1.73 m2 (GFR categories G1-G3a); its use should be reviewed in those with GFR 30–44ml/min/1.73 m2 (GFR category G3b); and it should be discontinued in people with GFR o30 ml/min/1.73 m2 (GFR categories G4-G5).
• In people with CKD and diabetes, glycemic control should be part of a multifactorial intervention strategy addressing blood pressure control and cardiovascular risk, promoting the use of angiotensin-converting enzyme inhibition or angiotensin receptor blockade, statins, and antiplatelet therapy where clinically indicated.

Salt intake

• It is strongly recommended to reduce salt intake to less than 90 mmol (equivalent to less than 2 grams) per day of sodium (equivalent to 5 grams of sodium chloride, common table salt) in adults, unless there are specific contraindications.
• For children with chronic kidney disease (CKD) who have hypertension (systolic and/or diastolic blood pressure above the 95th percentile) or prehypertension (systolic and/or diastolic blood pressure between the 90th and 95th percentiles), it is advisable to restrict sodium intake according to age-specific Recommended Daily Intake guidelines.
• In the case of children with CKD experiencing polyuria, it is recommended to provide supplemental free water and sodium supplements to prevent chronic intravascular depletion and support optimal growth. This helps maintain adequate hydration and electrolyte balance.

Hyperuricemia

• There is currently insufficient evidence to support or refute the use of agents to lower serum uric acid levels in individuals with chronic kidney disease (CKD) who have either symptomatic or asymptomatic hyperuricemia for the purpose of delaying the progression of CKD.
• Individuals with CKD are strongly recommended to engage in physical activity that is consistent with cardiovascular health and their individual tolerance, with the aim of achieving at least 30 minutes of physical activity five times per week. Additionally, it is advisable for them to attain a healthy weight, typically defined as having a BMI (Body Mass Index) within the range of 20 to 25, while considering country-specific demographics. Smoking cessation is also highly recommended for those with CKD to support overall health.
• Individuals with CKD should receive expert dietary guidance and information as part of an education program. This dietary advice should be tailored to the severity of CKD and address specific needs related to salt, phosphate, potassium, and protein intake as indicated by their condition.

Anaemia

• Work-up for anemia in CKD should include assessment of secondary causes including iron deficiency.
• Iron replacement is often effective in anemia of CKD as initial therapy and routes of administration (intravenous or oral) will be determined by clinicians, patient preferences, and local available resources.
• ESA therapy is not recommended in those with active malignancy, or recent history of malignancy.
• In most people with CKD, ESAs should not be used to intentionally increase the Hb concentration above 11.5 g/dl (115 g/l)

CKD Metabolic Bone Disease

• It is recommended to measure serum levels of calcium, phosphate, PTH, and alkaline phosphatase activity at least once in adults with GFR <45 ml/min/ 1.73 m2 (GFR categories G3b-G5) in order to determine baseline values and inform prediction equations if used.
• In people with GFR <45 ml/min/1.73m2 (GFR categories G3b-G5), we suggest maintaining serum phosphate concentrations in the normal range according to local laboratory reference values.
• In people with GFR <45 ml/min/1.73m2 (GFR categories G3b-G5) the optimal PTH level is not known. We suggest that people with levels of intact PTH above the upper normal limit of the assay are first evaluated for hyperphosphatemia, hypocalcemia, and vitamin D deficiency.

Vitamin D supplementation and bisphosphonates in people with CKD

• KIDGO suggests not to routinely prescribe vitamin D supplements or vitamin D analogs, in the absence of suspected or documented deficiency, to suppress elevated PTH concentrations in people with CKD not on dialysis.
• It is suggested not to prescribe bisphosphonate treatment in people with GFR <30 ml/min/1.73 m2 (GFR categories G4-G5) without a strong clinical rationale.

Acidosis

• KIDGO suggests that in people with CKD and serum bicarbonate concentrations <22 mmol/l treatment with oral bicarbonate supplementation be given to maintain serum bicarbonate within the normal range, unless contraindicated.

BNP/N-terminal-proBNP (NT-proBNP)

• In people with GFR <60 ml/min/1.73 m2 (GFR categories G3a-G5), we recommend that serum concentrations of BNP/NT-proBNP be interpreted with caution and in relation to GFR with respect to diagnosis of heart failure and assessment of volume status.
• Troponins: In people with GFRo60 ml/min/1.73 m2 (GFR categories G3a-G5), we recommend that serum concentrations of troponin be interpreted with caution with respect to diagnosis of acute coronary syndrome.

• People with CKD presenting with chest pain should be investigated for underlying cardiac disease and other disorders according to the same local practice for people without CKD (and subsequent treatment should be initiated similarly).
• KIDGO suggests that clinicians are familiar with the limitations of non-invasive cardiac tests (e.g., exercise electrocardiography [ECG], nuclear imaging, echocardiography, etc.) in adults with CKD and interpret the results accordingly.

CME INDIA Learning Points

(Dr. Dinesh Agarwal)

• Patients with diabetes should be routinely screened for DKD with assessments of urinary albumin and kidney function.
• Patients with DKD should be treated to achieve targets for A1C, following current guidelines. Patients with DKD should be treated to achieve a target BP.
• Patients with DKD should be treated with a RAAS inhibitor (either an ARB or ACEi).
• For patients with DKD and eGFR > 20 mL/min/1.73 m2, treatment with an SGLT2 inhibitor can be initiated as part of the standard of care along with ACEi/ARB use, BP control, and A1C control. ➢For patients who progress to ESKD requiring dialysis, SGLT2 inhibitors should be discontinued. ➢In patients with a history of heart failure, SGLT2 inhibitors should be initiated to reduce the risk of CV death or hospitalization for heart failure.
• In high-risk patients with T2D (i.e., those with ASCVD and/or CKD), SGLT2 inhibitors should be initiated to reduce the risk of cardiovascular events.
• In patients with DKD, finerenone should be considered in combination with ACEi or ARB medications to reduce the risk of CV events and CKD progression.
• In patients with DKD, finerenone may be used with or without an SGLT2 inhibitor to reduce the risk of CV events and CKD progression.
• Patients with confirmed DKD should have measures of UACR and eGFR taken every year, with more frequent measurements in patients with higher disease severity.
• Initiate SGLT2 inhibitors for DKD at the dose with evidence of cardiorenal benefit (ie, canagliflozin 100 mg daily, dapagliflozin 10 mg daily, empagliflozin 10 mg daily).
• In patients with DKD or heart failure, RAAS inhibitor and SGLT2 inhibitor initiation and maintenance should be prioritized over other medications with antihypertensive effects.
• Routine eGFR and electrolyte measurements after the initiation of SGLT2 inhibitors are recommended only in cases where there is clinical concern about volume status (e.g., BP >120/70 mm Hg, sign/symptoms of volume depletion, high-dose diuretics, elderly, eGFR
• When initiating finerenone, check serum potassium levels 2 to 4 weeks after initiation and regularly thereafter.
• RAAS inhibitors should be titrated to the highest approved, tolerated dose. Lowering of the dose or discontinuing RAAS inhibitors to lower potassium levels or prevent additional episodes of clinically significant hyperkalemia should only be undertaken after attempting measures to maintain the evidencebased dose of RAAS inhibitor.
• Patients with diabetes prescribed SGLT2 inhibitors should be educated about the signs and symptoms of GMI and DKA.
• Patients should be counselled on sick day medications (SADMANS) and when they should be avoided.
• Treatment decisions should be individualized based on risks and benefits, patient needs and preferences, access and cost, and the degree of glucose lowering needed.
• For most patients with DKD who need additional glycemic control or who are at high CV risk, a GLP1-RA should be considered.
• Primary-care practitioners should screen adult patients for diabetes.
• Primary-care practitioners should follow screening guidelines for DKD including measurement of both eGFR and albuminuria.
• Primary-care practitioners should prescribe SGLT2is for appropriate patients with DKD, following the evidence.
• For patients who may benefit from finerenone therapy.
• Primary-care physicians should consider consulting with a specialist to determine individual patient suitability.

CME INDIA Pearls from ESC, 2023

• Combining an SGLT2 inhibitor with either an ACE inhibitor (ACE-I) or an ARB has demonstrated clear beneficial effects in reducing the risk of kidney failure and hospitalization for heart failure (HF) in patients with both chronic kidney disease (CKD) and type 2 diabetes (T2DM).
• Mineralocorticoid receptor antagonists (MRAs) effectively reduce both blood pressure (BP) and albuminuria in patients with chronic kidney disease (CKD).
• There is limited information available regarding the safety and efficacy of combining Mineralocorticoid Receptor Antagonists (MRAs) with Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2 inhibitors) in chronic kidney disease (CKD) patients. This is primarily due to the fact that only a small percentage of participants in major clinical trials, such as FIDELIO-DKD, FIGARO-DKD, DAPA-CKD, and CREDENCE, were prescribed this combination therapy.
  • In FIDELIO-DKD, approximately 4% of participants received a combination of MRAs and SGLT2 inhibitors.
  • In FIGARO-DKD, around 8% of participants were on this combination therapy.
  • In DAPA-CKD, about 5% of participants were prescribed both MRAs and SGLT2 inhibitors.
  • In the CREDENCE trial, no participants were receiving this combination therapy.
• Because of the limited data available, the safety and efficacy of combining MRAs and SGLT2 inhibitors in CKD patients should be carefully considered on an individual basis, taking into account the patient’s specific medical history, risk factors, and potential interactions between these medications. Close monitoring and consultation with healthcare professionals are essential when contemplating such combination therapy
• Both the FIDELIO-DKD and FIGARO-DKD trials excluded individuals with potassium levels exceeding 4.8 mmol/L, as Mineralocorticoid Receptor Antagonists (MRAs) are known to induce hyperkalemia. Interestingly, combining Renin-Angiotensin System (RAS) and Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors does not seem to elevate the risk of hyperkalemia. There is even a hypothesis suggesting that SGLT2 inhibitors may reduce the likelihood of severe hyperkalemia among MRA users with heart failure.
• As a result, the use of finerenone, in addition to an RAS inhibitor, is recommended for patients with type 2 diabetes (T2DM) who have an estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m2 and a urinary albumin-to-creatinine ratio (UACR) equal to or exceeding 34 mg/mmol (or 300 mg/g), or an eGFR ranging from 25 to 60 mL/min/1.73 m2 with a UACR of 3 mg/mmol (or 30 mg/g) or higher. This should be accompanied by appropriate monitoring of potassium levels to ensure safety.

CME INDIA Tail-Piece:

References:

1. de Boer IH, Khunti K, Sadusky T, Tuttle KR, Neumiller JJ, Rhee CM, Rosas SE, Rossing P, Bakris G. Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022 Dec 1;45(12):3075-3090. doi: 10.2337/dci22-0027. PMID: 36189689; PMCID: PMC9870667.
2. Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1–S127.
3. Nikolaus Marx, Massimo Federici, Katharina Schütt, Dirk Müller-Wieland, Ramzi A Ajjan, Manuel J Antunes, Ruxandra M Christodorescu, Carolyn Crawford, Emanuele Di Angelantonio, Björn Eliasson, Christine Espinola-Klein, Laurent Fauchier, Martin Halle, William G Herrington, Alexandra Kautzky-Willer, Ekaterini Lambrinou, Maciej Lesiak, Maddalena Lettino, Darren K McGuire, Wilfried Mullens, Bianca Rocca, Naveed Sattar, ESC Scientific Document Group , 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC), European Heart Journal, 2023;, ehad192, https://doi.org/10.1093/eurheartj/ehad192

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