Recommendations for Screening, Risk Stratification, and Targeted Treatment for Diabetic Kidney Disease in the UAE

Abstract

Background

Diabetes remains the leading cause of diabetic kidney disease (DKD) and end-stage renal disease (ESRD), posing a significant health care burden both globally and in the United Arab Emirates. The coexistence of DKD and cardiovascular risk factors increases morbidity and mortality, necessitating the need for an integrated, evidence-based approach in management.

Methods

In response, a panel of endocrinologists and nephrologists from the United Arab Emirates collaborated to develop regional consensus recommendations focusing on the local clinical needs.

Results

This article focuses on DKD stage 1 to 4, providing practical guidance on screening, diagnosis, referral, glycemic control, and risk factor management to help delay DKD progression and reduce complications. Given the complexity of DKD, additional recommendations covering advanced stages, dialysis, and transplantation will be presented as a forthcoming part of this consensus.

Conclusion

These recommendations support a proactive and comprehensive approach to improve renal–metabolic outcomes and address the escalating burden of DKD in the United Arab Emirates.

Keywords

chronic kidney disease - diabetes mellitus - diabetic kidney disease - end-stage renal disease - reno-metabolic - type 2 diabetes

Introduction

Diabetic kidney disease (DKD), a specific type of chronic kidney disease (CKD) prevalent in people with a history of diabetes, is clinically defined as excessive albuminuria (≥30 mg/g) and/or a progressive decline in kidney function to below 60 mL/min/1.73m² estimated glomerular filtration rate (eGFR).[1] If untreated, kidney function may continue to decline, leading to end-stage renal disease (ESRD). DKD affects approximately 30% of individuals with type 1 diabetes (T1D) and 40% of those with type 2 diabetes (T2D).[2] In T1D, DKD typically develops after 10 years of diabetes diagnosis, and it is rare for people with T1D to develop kidney disease without retinopathy. In T2D, DKD may already be present at the time of diagnosis, and retinopathy is typically only moderately sensitive and specific for CKD caused by diabetes, as confirmed by a kidney biopsy.[3]

People with DKD also have elevated cardiovascular (CV) risk due to albuminuria, or a decline in eGFR without albuminuria, and high blood pressure (BP) associated with the condition.[4]

DKD can be categorized into two distinct phenotypes: The classical albuminuric phenotype and the non-albuminuric phenotype.[2] Patients with albuminuric DKD may have a higher risk of DKD progression and ESRD incidence compared with those with non-albuminuric DKD.[5] Today, non-albuminuric renal impairment is the prevailing DKD phenotype in patients with T2D who have decreased eGFR.[6] Non-albuminuric DKD presents with reduced kidney function, without albuminuria, suggesting that both the onset and progression of the decline in renal function may also occur independently from the development of albuminuria ([Supplementary Fig. S1] [available in the online version only]).[7] [8]

Prevalence of Diabetic Kidney Disease in the United Arab Emirates

Diabetes

With an overall prevalence of 16% and up to 40% of patients developing DKD each year, diabetes contributes significantly to the United Arab Emirates' annual health care burden. The United Arab Emirates' per-person diabetes expenditure currently exceeds USD 2,000 and is estimated to reach USD 2,099 by 2045.[9]

The Weqaya Program in Abu Dhabi, which screened over 50,000 individuals, reported a diabetes prevalence of 18%. Similarly, the Dubai Health Survey found a prevalence of 19% among Emiratis and 12% among expatriates.[8] Another study reported a diabetes prevalence of 47% among adults aged over 40 years.[10]

Diabetic Kidney Disease

The prevalence of DKD mirrors that of diabetes. Almost one in two United Arab Emirates nationals with T2D has moderately increased albuminuria (formerly microalbuminuria),[11] a key biomarker indicating early DKD.[8] A recent retrospective cross-sectional study in Abu Dhabi identified CKD in 24% of individuals, including 4% in stages 3 to 5 and 2% in stage 1, based on albuminuria alone.[12] A 2017 retrospective study[10] found DKD to be the leading cause of ESRD, accounting for 57% of dialysis patients at the Dubai Hospital HD unit, with 64% among United Arab Emirates nationals and 38% among non-nationals. Another study found DKD in 17% of T2D patients across two diabetes centers in Dubai,[13] while a recent real-world analysis reported a prevalence of CKD ranging from 4% to 20% in various T2D cohorts.[14]

Given the growing burden of DKD in the United Arab Emirates, there is an urgent need for practical and locally relevant guidance to support early detection and management. While international guidelines provide valuable frameworks, they may not fully account for the unique epidemiological patterns, health care infrastructure, and referral dynamics within the United Arab Emirates. To address this gap, a multidisciplinary panel of United Arab Emirates-based endocrinologists and nephrologists came together to develop consensus-driven recommendations. This initiative aimed to standardize the screening, diagnosis, referral, and management of DKD across stages 1 to 4, and ultimately improve the quality of life for people living with diabetes and kidney disease in the United Arab Emirates.

Materials and Methods

In September 2024, a United Arab Emirates-based initiative was launched. A mini-Delphi method was used to achieve consensus among 14 national experts in endocrinology and nephrology. Draft recommendations were developed based on international guidelines (American Diabetes Association, Kidney Disease: Improving Global Outcomes [KDIGO], NICE, UAE Cardiometabolic) and covered key topics, including definitions, screening, treatment, and referral. Experts provided feedback via an online survey, followed by a virtual meeting to review and vote on each statement. Consensus was defined as ≥80% agreement; statements with borderline agreement (∼70%) were revised and re-voted on after further discussion. [Supplementary Material S1] and [S2] (available in the online version only) highlights the salient points (S1) and provides more detailed supporting evidence (S2). Recommendations are presented in the Text Boxes 1 to 15.

Results

Screening and Diagnosis

Screening should involve both assessment of eGFR and measurement of UACR. Confirmation of albuminuria, even at levels of 30 to 300 mg/g, requires detection on at least two occasions within a 3- to 6-month period to rule out transient causes, such as fever or uncontrolled hypertension.[15] In high-risk patients, such as those with metabolic syndrome, obesity, hypertension, or CV disease (CVD), more frequent monitoring may be necessary to detect early kidney damage and intervene appropriately.

In adults at risk for CKD, we recommend using creatinine-based eGFR ([Fig. 1]). If cystatin C is available, the GFR category should be estimated from the combination of creatinine and cystatin C (creatinine and cystatin C-based estimated glomerular filtration rate).[15] Annual CKD screening is recommended for all patients with diabetes, with earlier and more frequent screening for those with additional risk factors such as hypertension, obesity, or established CVD.[16] The incorporation of cardiovascular risk markers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin, is recommended to better identify the risk of cardiorenal syndrome.[17] While the wide-reaching benefits of renal screening in people with diabetes are difficult to quantify, screening for CKD in people with diabetes is cost-effective.[18] This evidence aligns with KDIGO recommendations, which support early identification of CKD in at-risk asymptomatic people, particularly when results are used to guide clinical decisions.[15] [19]

Fig. 1 Stages of stratifying CKD based on eGFR and albuminuria. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

Risk Factors for Diabetic Kidney Disease

A variety of metabolic risk factors result in the onset and progression of DKD. Effective management of these risks is crucial for mitigating their contribution to disease progression, identifying patients at risk of progression, and enabling physicians to implement more targeted approaches to managing DKD.[15] [20] Baseline glycated hemoglobin (HbA1c), systolic blood pressure (SBP), proteinuria, serum uric acid, vascular comorbidities, and obesity are significant and independent factors associated with a rapid DKD progression.[21] Elevated body mass index (BMI), waist circumference, and waist-to-height ratio are recognized as independent risk factors for eGFR decline in individuals with normal or reduced eGFR levels.[22] Furthermore, smoking significantly contributes to renal impairment, especially in people with hypertension and T2D, where it increases the risk of developing diabetic nephropathy.[23] [Table 1] summarizes a comparison of key recommendations for managing modifiable DKD risk factors. It has been demonstrated that lower BP levels, as well as lower levels of total cholesterol and triglycerides, are associated with regression from moderate albuminuria to normal UACR, particularly in patients with T2D,[24] while also reducing the risk of progression to severe albuminuria and ESRD.[25] [Supplementary Figure S1] (available in the online version only) demonstrates the acute kidney injury (AKI) induced by medications (adapted from Izzedine et al, 2013[26], and Shahrbaf et al, 2015[27]).

Table 1 Recommendations on modifiable diabetic kidney disease risk factors

Risk factor	NICE	KDIGO	The present consensus
Glycemic control	Target blood glucose to reduce HbA1c	HbA1c ≈7%, individualized	HbA1c ≈7%, individualized
Hypertension	BP <140/90 (or 130/80 with kidney/CV risks)	BP < 120/80 without albuminuria; <130/80 with albuminuria	BP <120/80 or lower if tolerated
Albuminuria/Proteinuria	Monitor microalbuminuria (>30 mg/day)	Routine screening is essential	Monitor microalbuminuria (>30 mg/day)
Dyslipidemia	Manage LDL cholesterol	Statin therapy to reduce risk	LDL <55 mg/dL for very high risk; ≥50% reduction with high-intensity statin
Obesity	Manage weight to lower risk	Emphasize weight control in T2D	Weight management
Smoking	Smoking cessation	Smoking cessation	Smoking cessation
Nephrotoxic drugs	Avoid nephrotoxics	Avoid nephrotoxics; monitor meds	Avoid nephrotoxics (e.g., NSAIDs, COX2i)[a]

Abbreviations: BP, blood pressure; CV, cardiovascular; HbA1c, glycated hemoglobin; T2D, type 2 diabetes; LDL: low density lipoprotein, NSAID: non-steroidal anti-inflamatory drug, COX2i: cyclooxygenase-2 inhibitors.

Findings based on international renal guidelines[15] [29] [83] [85] and opinions of the authors of this consensus document.

^a Refer to the [Supplementary Fig. S1] (available in the online version only) for more information on nephrotoxic medications and medications to avoid during acute kidney injury.

According to expert consensus, key non-modifiable risk factors include the patient's duration of diabetes, their family history of kidney disease, and potential ethnicity. The risk of DKD rises significantly after 10 to 15 years of diabetes, particularly in individuals with T1D, though both T1D and T2D carry substantial risk. Additionally, experts highlight that South Asians, African-Caribbeans, and Hispanics face a higher risk of developing DKD, an important consideration in regions like the United Arab Emirates, where these ethnic groups form a large proportion of the expatriate population.

Referral to Nephrology

Prompt detection and referral to nephrology services offer the potential to halt or slow the progression of DKD.[18] Conversely, delayed referrals to a nephrology center for renal replacement therapy (RRT) can worsen the outcomes among CKD patients and increase treatment expenses.[28] [29] [Figure 2] demonstrates the goals of early identification and referral. Several studies have shown that while nephrology referrals increase before dialysis initiation, over half are referred late, typically within 90 days of starting hemodialysis.[29] Similarly, delayed referral to a nephrologist is associated with rising mortality from CKD stages 1 to 4 and an exponential increase in ESRD after CKD stage 3a.[30] Early referrals made 6 to 12 months prior to RRT can potentially delay progression and improve prognosis in CKD patients.[31] [32] An active urinary sediment (containing red or white blood cells or cellular casts) suggests an alternative or additional cause of kidney disease. Patients with refractory hypertension, or those with persistent potassium abnormalities, may benefit from referral to a nephrologist and an endocrinologist. The criteria for referral to nephrology are summarized in [Fig. 3].[15]

Fig. 2 The goals of early identification and referral. CKD, chronic kidney disease; DKD, diabetic kidney disease.

Fig. 3 Criteria for referral to nephrology in diabetic kidney disease. DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease.

Glycemic Management

Glycemic control has been shown to delay the development of albuminuria, CVD, and DKD progression in patients with diabetes and kidney disease.[33] [34] [35] [36] [37] Glycemic control has been shown to delay the development of albuminuria, CVD, and DKD progression in patients with diabetes and kidney disease.[35] Intensive glycemic control reduces the risk and progression of DKD in both T1D and T2D. The DCCT/EDIC (T1D) and the Kumamoto, UKPDS, VADT, ADVANCE, and ACCORD (T2D) studies reported delayed onset and progression of nephropathy, as well as an association between lower HbA1c levels and reduced albuminuria with intensive glycemic management.[38] [39] [40] [41] [42] [43] [44]

Glycemic Targets

HbA1c should be used as the primary measure of glycemia in patients with diabetes and DKD, except in cases where HbA1c reliability may be limited, such as in advanced renal disease, severe anemia, or concurrent hemoglobinopathies.[40]

Glycemic Monitoring

Self-monitoring of blood glucose or continuous glucose monitoring (CGM) is advised for all those with DKD to prevent hypoglycemia and improve glycemic variability. Maintaining time in range above 70% is particularly crucial, especially in those with DKD. Intermittent monitoring may suffice for patients with stable DKD and a low risk of hypoglycemia. In contrast, more frequent monitoring is advised for those with advanced DKD or on hypoglycemia-prone therapies, such as insulin or sulfonylureas. HbA1c testing is recommended every 3 months for both early and advanced CKD. However, its reliability decreases in advanced CKD (eGFR <30), and CGM is often beneficial. [Table 2] lists the factors influencing HbA1c measurement in CKD. Findings based on expert opinion are listed as authors of this consensus document.[41]

Table 2 Factors influencing glycated hemoglobin measurement in chronic kidney disease

Factor	Impact on HbA1c measurement	Influence on HbA1c measurement
Iron or vitamin B12 deficiency[42]	Overestimation	Decreased RBC turnover leads to longer glycation periods and higher HbA1c
Erythropoietin administration[42]	Underestimation	Increased RBC production reduces HbA1c as glycosylation time shortens
Hemodialysis[42]	Underestimation	Shortened RBC lifespan in dialysis patients lowers HbA1c levels
Blood urea nitrogen[42]	Overestimation	Carbamylated Hb mimics glycated Hb, falsely raising HbA1c

Abbreviation: HbA1c, glycated hemoglobin.

Findings based on opinion of the authors of this consensus document.

Managing Hypoglycemia Risk by Diabetic Kidney Disease Stage

An expert panel recommends avoiding intensive glucose-lowering strategies in the later stages of DKD (G3b and above) to reduce the risk of hypoglycemia. Instead, prioritize safer glucose-lowering options, such as sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which provide CV and renal benefits with a lower risk of hypoglycemia. Use medications requiring renal dose adjustments (e.g., insulin, sulfonylureas) with caution in advanced DKD.[42]

Targeted Therapy for Diabetic Kidney Disease

Effective DKD management requires a multifaceted approach, including lifestyle modifications, glycemic control, cardiovascular risk mitigation, and BP regulation with the use of a renin–angiotensin–aldosterone system (RAAS) inhibitor.[43] [44] These foundational strategies represent the established pillars of DKD therapy, along with a fourth emerging pillar—the GLP-1 RAs, which play a significant role in individuals with T2D[45] [46] as illustrated in [Fig. 4].

Fig. 4 Four pillars of pharmacotherapy. CKD, chronic kidney disease; GLP-1 RA, glucagon-like peptide-1 receptor agonist; nsMRA, non-steroidal mineralocorticoid receptor antagonist; SGLT2i, sodium–glucose cotransporter 2 inhibitor; T2D, type 2 diabetes.

Sodium–Glucose Cotransporter 2 Inhibitors

SGLT2i were originally approved for use in patients with T2D to improve glycemic control. However, large outcome trials designed to test its cardiovascular safety showed cardiorenal protective benefits.[46] This benefit was subsequently confirmed in landmark trials conducted in patients with albuminuric CKD and T2D. Canagliflozin showed a 30% reduction in the primary outcomes, including ESRD, doubling of serum creatinine, and death from cardiovascular or renal causes, as demonstrated in the CREDENCE trial. A 39% reduction in the primary composite kidney failure outcome was observed with dapagliflozin.[47] Furthermore, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo, in a broad range of CKD patients at lower risk of disease progression.[48] [49]

In a collaborative meta-analysis comprising 13 trials with over 90,000 participants, those allocated to an SGLT2i experienced a 37% reduction in the risk of kidney disease progression and a 23% reduction in the risk of AKI, irrespective of diabetes status, compared with placebo.[50] Another meta-analysis highlighted that SGLT2i use in CKD patients was associated with a lower incidence of cardiovascular death, a lower risk of AKI, and treatment discontinuation compared with placebo.[46]

In patients with CKD stage 4 (eGFR 20–29 mL/min/1.73 m²), SGLT2i have minimal glycemic effects and are primarily used for kidney and cardiovascular protection rather than glycemic control.[51] Additionally, it is important to withhold SGLT2i therapy during prolonged fasting, surgery, or critical medical illness when the risk of ketosis may be elevated.[42] In the EMPA-KIDNEY study, 20% of participants had non-albuminuric DKD and still demonstrated significant benefits from SGLT2i therapy.[49]

Glucagon-Like-Peptide-1 Receptor Agonists

GLP-1 RAs have evolved from promising antihyperglycemic agents to becoming crucial cardiometabolic therapies with notable CV benefits. The SUSTAIN-6 study, which investigated once-weekly semaglutide in patients with eGFR >30 mL/min/1.73 m², reported improvements in persistent macroalbuminuria, doubling of serum creatinine, and a reduction in creatinine clearance to <45 mL/min or continuous RRT.[52] [53] Additionally, in the REWIND study, dulaglutide therapy in patients with an eGFR greater than 15 mL/min/1.73 m² resulted in improvements in the incidence of new macroalbuminuria, a sustained decline in eGFR of 30% or more, or the need for chronic RRT.[53] [54] Furthermore, the recent FLOW trial, conducted in individuals with T2D and DKD, suggests that GLP-1 RAs can slow the progression of CKD. It demonstrated a 24% lower risk of the composite primary outcome, which included kidney disease progression, cardiovascular events, and kidney death.[55] Liraglutide, lixisenatide, dulaglutide, and semaglutide have been shown to reduce the development of macroalbuminuria, indicating a renal protective effect.[53] [56] [57]

Renin–Angiotensin–Aldosterone System Blockers

Activation of the RAAS, driven by the bioactive metabolites angiotensin II and aldosterone, may lead to glomerular injury and proteinuria. Additionally, it contributes to systemic inflammation, generation of reactive oxygen species, and fibrosis in the renal and CV organ systems.[44] Two types of RAAS inhibitors, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), are recommended for delaying DKD progression in patients with albuminuria and hypertension.[58]

In a large meta-analysis of 119 randomized controlled trials involving patients with CKD (eGFR <60 mL/min/1.73 m²), the use of RAAS blockade was associated with a reduced risk of progression to ESRD, major adverse cardiovascular events (MACE), and all-cause mortality.[59] [60] The RENAAL trial and the Irbesartan Diabetic Nephropathy trial demonstrated that the use of losartan and irbesartan, respectively, can slow DKD progression.[61] [62] Additionally, the RENAAL also demonstrated a 28% relative reduction in the risk of ESRD.

ACEi or ARB therapy should be continued unless there is a 30% or greater increase in serum creatinine within 4 weeks of starting or increasing the dose. These medications can be maintained in patients with DKD even if the eGFR falls below 30 mL/min/1.73 m².

Hyperkalemia associated with RAAS blockers is often manageable through interventions to lower serum potassium levels, rather than reducing the dose or discontinuing the RAAS blocker. A recent individual patient-level data meta-analysis showed a benefit in delaying KRT in patients with eGFR <30 mL/min/1.73 m².[63] Additionally, two observational studies found poorer outcomes among participants who discontinued RAAS blockers after reaching an eGFR of <30 mL/min/1.73 m², compared with those who continued the treatment.[64] [65] [Figure 5] depicts the strategy for monitoring of serum creatinine and potassium during ACEi or ARB treatment in DKD.[15] [66]

Fig. 5 Monitoring of serum creatinine and potassium during ACEi or ARB treatment in DKD. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; DKD, diabetic kidney disease.

Non-Steroidal Mineralocorticoid Receptor Antagonists

Non-steroidal mineralocorticoid receptor antagonists (nsMRAs) are recommended in patients with T2D and DKD receiving RAAS inhibition for their potential cardiorenal benefits.[68] [69] They are particularly appropriate for adults who are also at high risk of DKD progression or CV events, as evidenced by persistent albuminuria despite other standard-of-care therapies.[15] To date, two nsMRAs have been approved for clinical use: Finerenone, approved by the U.S. Food and Drug Administration (FDA) in 2021, and esaxerenone, which is approved in Japan.[69] Finerenone is a bulky molecule that acts as an inverse agonist to the mineralocorticoid receptor (MR) by reducing cofactor recruitment, even in the absence of aldosterone. Finerenone exhibits higher selectivity for the MR compared with eplerenone, while retaining potency equivalent to spironolactone.[68]

Finerenone was associated with significantly lower increases in serum/plasma potassium compared with spironolactone, as well as lower incidences of hyperkalemia (serum potassium ≥5.6 mmol/L) or worsening renal function in individuals with T2D.[70] To mitigate the risk of hyperkalemia, it is essential to select individuals with consistently normal serum potassium levels and to monitor potassium levels regularly after initiating an nsMRA.[71] However, a recent post hoc analysis (for 24-hour ambulatory BP) in a subset of patients (n = 240) showed significant reductions in 24-hour, daytime, and night-time SBP with finerenone versus placebo beyond 2 months of treatment.[72]

Patients with mild kidney dysfunction (eGFR ≥60 mL/min/1.73 m²) should initiate treatment with the 20 mg/day dose, whereas those with moderate kidney dysfunction (eGFR 25–59 mL/min/1.73 m²) should start with 10 mg/day. Finerenone is not recommended for initiation in patients with severe kidney dysfunction (eGFR <25 mL/min/1.73 m²).[74] Finerenone is also contraindicated in patients receiving a strong cytochrome P450 3A4 inhibitor or those who have adrenal insufficiency.

A sustained decrease of ≥40% in eGFR from baseline, or death from renal causes, was significantly lower with finerenone compared with placebo.[74] Similarly, the primary composite outcome of CVD-related death, non-fatal MI, non-fatal stroke, or heart failure (HF)-related hospitalization was significantly lower with finerenone versus placebo.[70] A significant relative risk reduction of 23% in the composite kidney endpoint was reported for finerenone versus placebo, and of 14% in the composite cardiovascular endpoint, including a 22% relative risk reduction in HF-related hospitalizations, from a prespecified pooled analysis.[75] The ongoing Phase 2 CONFIDENCE study will be important in further defining the role of finerenone in the treatment algorithm for CKD and T2D relative to the SGLT2i.[76]

Recent advancements in DKD treatment options have shown promising results in clinical trials; however, DKD progression remains a continuous challenge.[77] It is reported that combination therapy may delay the progression of CKD by 5.5 years (95% CI, 4.0–6.7) and increase the MACE-free survival by 3.2 years (95% CI, 2.1–4.3) compared with conventional care. Additionally, this approach could improve survival by delaying mortality by 2.4 years (95% CI, 1.4–3).[78] The management of DKD is summarized in a consensus-driven algorithm, as shown in [Fig. 6]. In addition, [Supplementary Table S1] (available in the online version only) provides a summary of the primary outcomes across finerenone, empagliflozin, dapagliflozin, canagliflozin, and semaglutide clinical trials.

Fig. 6 Algorithm for management of DKD based on consensus recommendations by the experts. Adapted from KDIGO 2022, KDIGO 2024 Guidelines, and modified with expert recommendations. ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide-1 receptor agonist; nsMRA, Non-steroidal mineralocorticoid receptor antagonist; SGLT2, sodium–glucose cotransporter 2.

Glucose-Lowering Therapies for Use in Patients with Type 2 Diabetes and Diabetic Kidney Disease

In individuals with T2D and established chronic kidney disease (CKD), the selection of glucose-lowering therapies requires careful consideration.[79] As kidney function declines, particularly when eGFR falls below 60 mL/min/1.73 m², certain medications may become less effective or contraindicated, and dose adjustments are often necessary. [Table 3] summarizes the consensus recommendations for glucose-lowering therapy for use in people with T2D and DKD.

Table 3 Consensus recommendations for glucose-lowering therapy in use with type 2 diabetes and diabetic kidney disease patients

Therapy class/drug	Details
Metformin[15]	• Recommended initial treatment for patients with T2D and DKD (eGFR 60–30 mL/min/1.73 m2) is dual therapy with metformin and an SGLT2i[15] • Metformin dosing should be adjusted when eGFR falls below 45mL/min/1.73 m2 and discontinued when eGFR <30 mL/min/1.73 m2[15] • Use metformin with dose adjustment in impaired kidney[15] • Metformin elimination half-life of 1.5 to 8.7 hours. About 90% of a dose is excreted within 12 to 24 hours via kidneys.
Sulfonylureas[15]	• Avoid first-generation agents (e.g., chlorpropamide, tolazamide) due to prolonged half-life and increased hypoglycemia risk. • Choose second-generation agents such as gliclazide (excluding glyburide), primarily metabolized by the liver. • Gliclazide's inactive or weakly active metabolites are excreted in urine, offering a lower risk of hypoglycemia in DKD.
Glinides[79]	• Repaglinide is preferred due to hepatic metabolism and excretion of inactive metabolites via urine, minimizing hypoglycemia risk. • Can be used with other oral anti-diabetic agents or basal insulin to cover postprandial glucose surges. • Nateglinide is less favored due to active metabolites and higher hypoglycemia risk.[78]
Thiazolidinediones[79]	• Metabolized by the liver with no renal excretion • Use with caution due to risk of fluid retention, edema, and heart failure, especially in non-dialysis patients. • In patients on pioglitazone, monitor fluid retention every 3 months.
DPP-4 inhibitors[15]	• Effective in glycemic control and well-tolerated in patients with DKD, including those with concomitant hypertension. • Generally safe in DKD stages G3 to G4; dose adjustments may be required. • Linagliptin, excreted via bile, requires no dose adjustment in dialysis patients. • Sitagliptin requires dose adjustment (DKD G3B: 50 mg/day; DKD G4: 25 mg/day). • Vildagliptin can be used at 50 mg/day in moderate (eGFR:30–50) to severe DKD (eGFR <30).
Alpha-glucosidase inhibitors[79]	• Take Acarbose and Miglitol at the start of meals to reduce glucose absorption post-meal • Use in stage G3 without dose adjustment • Avoid in stages G4 to G5 due to adverse effect risk. • Miglitol is renally excreted, thus not recommended in patients with significant renal dysfunction.
Insulin[79]	• Insulin therapy is encouraged in dialysis patients for optimal glycemic control. • Rapid-acting (e.g., aspart, lispro) and long-acting (e.g., glargine, detemir) analogs are unaffected by DKD. • No specific regimen is preferred in the DKD setting. • For T1D, standard treatment is a basal–bolus regimen of 3 daily injections of short-acting insulin with meals combined with one or two injections of long-acting insulin

Abbreviations: DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; SGLT2i, sodium–glucose cotransporter 2 inhibitor; T1D, type 1 diabetes; T2D, type 2 diabetes; DPP-4, dipeptidyl peptidase-4.

The consensus was reached, and recommendations were adapted/modified for regional use based on respective evidence from KDIGO guidelines.[15] [42] [79]

Hypertension and Lipid Management

Hypertension is a major independent risk factor for CKD progression and ESRD, affecting 80% to 85% individuals with CKD.[59] [60] Frequent BP monitoring and therapeutic control of hypertension to protect against DKD progression are crucial.[80] [81] [82] [83] [Table 4] summarizes the evidence-based recommendations for antihypertensive therapy in patients with DKD and albuminuria. The consensus was reached and adapted for regional use based on evidence from KDIGO guidelines, and relevant publications for hypertension management in this group of patients.[15] [42] [79] [Supplementary Table S2] (available in the online version only) details the recommendations relevant to hypertension in CKD patients in the 2021 KDIGO and 2023 ESH Guidelines.

Table 4 Recommendations on antihypertensive therapy in diabetic kidney disease patients with albuminuria

Recommendations on antihypertensive therapy in DKD patients with albuminuria

• Use either an ACEi or an ARB, as first choice antihypertensive therapy for DKD patients with albuminuria (G3–G4, A2-A3) at the maximum tolerated approved dose to ensure optimal nephroprotection. • ACEi with ARB or aliskiren, as combination therapy is not recommended due to increased risks of adverse events, as demonstrated by prematurely terminated outcome trials. • ACEi or ARB therapy should be continued unless there is an increase in serum creatinine by more than 30% within 4 weeks of starting or increasing the dose. These medications can be maintained in patients with DKD even if the eGFR falls below 30 mL/min per 1.73 m2. • Investigate for renovascular disease if eGFR drops consistently or significantly (>30%) and discontinue RAS blockers if necessary.[84] • Be cautious of the increased risk of hyperkalemia associated with RASi in DKD patients, as it is a common reason for dose adjustment or discontinuation. • Use novel potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) to effectively normalize and maintain serum potassium levels in DKD patients on ACEis, ARBs, or MRAs. • Target serum potassium levels <5.5 mmol/L to enable continued optimal treatment with RAAS inhibitor or MRA.

Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; MRA, mineralocorticoid receptor antagonist; RAAS, renin–angiotensin–aldosterone system.

The consensus was reached and adapted for regional use based on evidence from KDIGO guidelines, and relevant publications for hypertension management in this group of patients.[15] [42] [85]

DKD exacerbates dyslipidemia and increases the incidence of atherosclerotic CVD.[84] As kidney function declines, lipid abnormalities such as high triglycerides and low density lipoprotein cholesterol (LDL-C), as well as low high density lipoprotein cholesterol (HDL-C), become more pronounced and contribute to atherosclerotic cardiovascular disease (ASCVD) risk.

Statin initiation is recommended for most adults with DKD who are not on dialysis[85]: (a) Adults over 50 years old with eGFR >60 mL/min/1.73 m², and (b) Adults aged 18 to 49 years with known coronary heart disease, a history of ischemic stroke, or an estimated 10-year risk of coronary heart disease death or non-fatal myocardial infarction greater than 10%. The addition of ezetimibe or a PCSK9 inhibitor is advised to achieve target LDL-C levels (<55 mg/dL or at least 50% reduction from baseline).[86]

In patients with high triglycerides or low HDL-C, lifestyle changes and better glycemic control should be prioritized before using icosapent ethyl. Intensive lipid-lowering may also help slow kidney disease progression, especially in early DKD with albuminuria and preserved eGFR.[80]

Hypertension, dyslipidemia, and T2D are highly prevalent and poorly controlled cardiometabolic diseases in the Middle East, and therapeutic inertia is the major contributor to this suboptimal control.[81] Therapeutic inertia arises from both clinician- and patient-related factors, including concerns about drug side effects, lack of awareness of international guidelines recommendations and new therapeutic options, and perceived complexity of treatment regimens.[82] Through these consensus guidelines, we aim to take a proactive step in overcoming barriers to achieving BP and LDL-C targets by promoting timely treatment intensification, structured care pathways, and supporting greater adherence to evidence-based cardiometabolic management across United Arab Emirates clinical practice.

Management of Obesity in Adults with Stages 3 to 4 Diabetic Kidney Disease

Four FDA-approved antiobesity medications or procedures are currently available for use: GLP-1 RAs, SGLT2i, orlistat, and metabolic surgery.[22] The authors recommend using a combination of SGLT2i and GLP-1 agonists when glycemic control is inadequate in individuals with T2D and DKD. [Supplementary Table S3] (available in the online version only) describes the management of obesity in adults with stage 3 to 4 DKD.

Conclusion

In conclusion, this consensus recommendation sets out a standardized approach for managing DKD in the United Arab Emirates. It highlights the critical role of a multidisciplinary team in ensuring comprehensive care and timely referrals, emphasizing the need for collaboration between nephrologists, endocrinologists, dietitians, and other health care professionals. This collaborative effort and coordination are crucial in advancing DKD management across the United Arab Emirates. Primary health care centers (PHCs) serve as the first point of contact for UACR and eGFR screening, optimization of glycemic and BP control, and reinforcement of adherence to medications before referral to nephrology. DKD screening reminders should be incorporated into PHC electronic records, targeted continuous professional development training should be provided for general practitioners, and these initiatives should be integrated into national chronic disease pathways. To facilitate the dissemination of knowledge, a basic MS PowerPoint Slide Deck with all the recommendations is provided ([Supplementary Material S1] [available in the online version only]).

Given the breadth of the topic, recommendations related to advanced DKD, including dialysis, transplantation, and end-stage kidney care, will be addressed in the forthcoming parts of the DKD guidelines, including additional insights discussed during the consensus meeting.

Conflict of Interest

None declared.

Acknowledgments

The authors would like to acknowledge the leadership role of the Emirates Diabetes and Endocrine Society and Emirates Medical Association – Nephrology and Transplant Society in convening the expert group, MEDCON Middle East, for providing medical writing assistance.

Authors' Contributions

A.B. is the principal author for the manuscript. All authors contributed to the drafting and revising of the manuscript. All authors reviewed the final version of the manuscript and take collective responsibility for all of its contents.

Ethical Approval

No prior ethical approval is needed for a review-type article.

Data Availability Statement

All data, views, and recommendations generated for this initiative are included in this article and its supplementary material files. All primary literature is cited in its bibliography.

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Publication History

Article published online:
22 January 2026