Diabetic kidney disease (DKD) represents one of the most pressing challenges in global nephrology today. As diabetes mellitus continues its rise as one of the most prevalent chronic conditions on the planet, its impact on the kidneys has become impossible to ignore. DKD is now the single most common cause of both chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide — conditions that reduce quality of life dramatically and carry enormous individual and societal costs.
For decades, managing DKD meant controlling blood sugar and blood pressure and hoping for the best. Today, the picture is far more nuanced and, importantly, far more hopeful. A new generation of evidence-based therapies has transformed the treatment landscape. The International Society of Nephrology has played a central role in translating this evidence into practical guidance — advocating for patients, educating clinicians, and promoting equitable access to life-changing medications across all regions of the world.
This article provides a comprehensive overview of DKD: what it is, how it progresses, how it is diagnosed and staged, and what modern treatment looks like — with particular attention to the advances that the ISN (International Society of Nephrology) has championed in recent years.
What Is Diabetic Kidney Disease?
Diabetic kidney disease is a form of chronic kidney damage that develops as a complication of both type 1 and type 2 diabetes mellitus. It occurs when persistently elevated blood glucose levels damage the small blood vessels within the kidneys — particularly the intricate network of capillaries that make up the glomeruli, the kidney’s primary filtering units.
Over time, this damage disrupts the delicate filtration barrier of the kidney, allowing proteins — especially albumin — to leak into the urine. This leakage, measured as albuminuria or proteinuria, is one of the earliest and most important signs that the kidneys are under stress. Simultaneously, the kidneys’ overall filtering efficiency, measured by the estimated glomerular filtration rate (eGFR), begins to decline. When left unmanaged, DKD can progress relentlessly toward kidney failure requiring dialysis or transplantation.
What makes DKD particularly dangerous is that it rarely acts alone. Patients with diabetic kidney disease carry a substantially elevated risk of cardiovascular events — heart attack, stroke, and heart failure — often before they ever reach advanced stages of kidney impairment. This dual burden of kidney and cardiovascular disease underscores why managing DKD requires a comprehensive, multi-system approach rather than a narrow focus on glucose control alone.
The Global Burden: Why This Matters
The numbers are sobering. Approximately 40 percent of people with diabetes will develop some form of kidney disease during their lifetime. Given that more than 500 million adults worldwide are currently living with diabetes, the downstream burden on kidney health is enormous. In many high-income countries, DKD is responsible for 30 to 50 percent of all new cases of kidney failure requiring renal replacement therapy. In low- and middle-income countries, where both diabetes and CKD often go undetected for years, the situation is frequently even more severe.
The economic consequences are equally significant. Dialysis and transplantation are among the most resource-intensive interventions in all of medicine. Preventing or delaying the progression of DKD therefore represents not only a clinical imperative but also a critical public health and health-system priority. This is a key reason why the International Society of Nephrology has made DKD awareness and access to treatment a cornerstone of its global advocacy work.
Recognizing and Staging Diabetic Kidney Disease
Key Diagnostic Markers
Diagnosis of DKD relies primarily on two measurements that clinicians use together to paint a complete picture of kidney health:
- Estimated Glomerular Filtration Rate (eGFR): This reflects how efficiently the kidneys are filtering waste from the blood. It is calculated from serum creatinine, age, and sex. A normal eGFR is above 60 mL/min/1.73m², and values below this threshold — sustained over at least three months — indicate CKD.
- Urine Albumin-to-Creatinine Ratio (UACR): This measures how much albumin is spilling into the urine. Normal values are below 30 mg/g. Levels between 30 and 300 mg/g indicate moderately increased albuminuria (formerly called microalbuminuria); levels above 300 mg/g indicate severely increased albuminuria (formerly macroalbuminuria or proteinuria).
Together, eGFR and UACR form the basis of the KDIGO risk stratification system — often visualized as a color-coded “heat map” — which the ISN has widely promoted as a practical framework for primary care providers and nephrologists alike. This system guides not only the frequency of monitoring but also when to refer patients to specialist nephrology care.
KDIGO eGFR Categories and Clinical Actions
| eGFR Category | eGFR (mL/min/1.73m²) | Stage Description | Recommended Clinical Action |
|---|---|---|---|
| G1 | ≥ 90 | Normal or high | Treat risk factors; annual monitoring if albuminuria present |
| G2 | 60–89 | Mildly decreased | Treat risk factors; optimize glycemia and blood pressure |
| G3a | 45–59 | Mildly to moderately decreased | Nephrology consultation; intensify treatment |
| G3b | 30–44 | Moderately to severely decreased | Nephrology co-management; prepare for advanced CKD |
| G4 | 15–29 | Severely decreased | Renal replacement therapy planning |
| G5 | < 15 | Kidney failure | Dialysis or transplantation |
The Pillars of Modern DKD Treatment
The 2022 KDIGO Clinical Practice Guideline for Diabetes Management in CKD — produced with the endorsement of the International Society of Nephrology and published in the journal Kidney International — represents the most comprehensive evidence-based framework for managing DKD to date. It brings together decades of trial data into a unified, practical treatment algorithm covering glycemic targets, renin-angiotensin system inhibition, SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone. The following sections outline each major treatment pillar.
Glycemic Control: Necessary but Not Sufficient
Blood glucose management remains foundational in DKD care. The landmark Diabetes Control and Complications Trial (DCCT) demonstrated clearly that intensive glycemic control in patients with type 1 diabetes significantly reduces the onset of microalbuminuria — an early marker of DKD. The United Kingdom Prospective Diabetes Study (UKPDS) established comparable findings for patients with type 2 diabetes.
However, subsequent large trials including ACCORD, ADVANCE, and VADT introduced important nuance: in patients who already have established cardiovascular or renal disease, overly aggressive glucose lowering may not confer additional benefit and can increase the risk of hypoglycemia. Today, glycemic targets are individualized, typically aiming for an HbA1c of approximately 7 percent (53 mmol/mol), with less stringent targets appropriate for older or more frail patients with significant comorbidities.
Renin-Angiotensin System Inhibition
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been the cornerstone of DKD management for over two decades. By blocking the renin-angiotensin-aldosterone system (RAAS), these drugs reduce intraglomerular pressure, decrease proteinuria, and slow the progression of kidney disease — independently of their blood pressure-lowering effects. They remain first-line therapy for most patients with DKD who have significant albuminuria, and the ISN continues to advocate for their widespread availability across all health systems.
SGLT2 Inhibitors: A Paradigm Shift in Kidney Protection
Perhaps the most transformative development in DKD management over the past decade has been the emergence of sodium-glucose cotransporter-2 (SGLT2) inhibitors. These agents, originally developed as glucose-lowering drugs, were found to have profound kidney-protective effects that extend well beyond glycemic control.
SGLT2 inhibitors work in part by reducing hyperfiltration at the glomerular level — a key early driver of kidney damage in diabetes. They also attenuate albuminuria across a wide spectrum of DKD severity and appear to protect kidney structure through multiple complementary mechanisms. Three major clinical trials have firmly established their role in nephroprotection:
- CREDENCE (canagliflozin): Demonstrated a significant relative risk reduction in the primary composite kidney outcome in patients with type 2 diabetes and CKD.
- DAPA-CKD (dapagliflozin): Showed kidney and survival benefits even in patients without diabetes, broadening the evidence base beyond DKD specifically.
- EMPA-KIDNEY (empagliflozin): Confirmed robust kidney protection across a wide range of eGFR levels and albuminuria categories, including patients with relatively low eGFR values.
The ISN (International Society of Nephrology) has actively advocated for the inclusion of SGLT2 inhibitors on national essential medicines lists — particularly in low- and middle-income countries — recognizing that cost and access remain the primary barriers to their use where the burden of DKD is often greatest and least addressed.
GLP-1 Receptor Agonists
Glucagon-like peptide-1 (GLP-1) receptor agonists represent another important class of agents now integrated into DKD management guidelines. In addition to their well-established effects on blood glucose, body weight, and cardiovascular risk, GLP-1 receptor agonists have demonstrated meaningful reductions in albuminuria and may slow kidney disease progression over time. Their cardiovascular benefits are particularly relevant given the high rate of cardiovascular events in the DKD population. Current guidelines position them as valuable options, especially when SGLT2 inhibitors cannot be used or as add-on therapy in patients who require further risk reduction.
Finerenone: A Significant New Addition
One of the most significant recent additions to DKD therapy is finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA). Unlike older steroidal MRAs such as spironolactone, finerenone has a more selective mechanism of action with a more favorable safety profile, particularly regarding the risk of hyperkalemia and hormonal side effects. Its action on the mineralocorticoid receptor helps reduce kidney inflammation and fibrosis — two processes that drive the progression of DKD independently of blood pressure and glucose levels.
Two landmark randomized controlled trials established finerenone’s clinical role:
- FIDELIO-DKD (Bakris et al., New England Journal of Medicine, 2020): Demonstrated significant reductions in the composite kidney outcome — including sustained decline in eGFR, kidney failure, and kidney-related death — in patients with type 2 diabetes and CKD.
- FIGARO-DKD (Pitt et al., New England Journal of Medicine, 2021): Showed significant cardiovascular benefits alongside kidney protection, particularly in patients with less advanced CKD and high albuminuria.
Pooled analysis from both trials — conducted under the FIDELITY program — provided sufficient statistical power to confirm a meaningful reduction in all-cause mortality, reinforcing finerenone’s place as a substantive new pillar of the DKD treatment armamentarium alongside RAAS inhibitors and SGLT2 inhibitors.
Summary of Evidence-Based Drug Classes in DKD Management
| Drug Class | Key Agents | Primary Kidney Benefit | Key Supporting Trials |
|---|---|---|---|
| RAAS inhibitors | ACE inhibitors, ARBs | Reduced albuminuria; slowed GFR decline | RENAAL, IDNT, IRMA-2 |
| SGLT2 inhibitors | Canagliflozin, Dapagliflozin, Empagliflozin | Glomerular hyperfiltration reduction; nephroprotection across CKD spectrum | CREDENCE, DAPA-CKD, EMPA-KIDNEY |
| GLP-1 receptor agonists | Semaglutide, Liraglutide, Dulaglutide | Albuminuria reduction; cardiovascular and renal risk reduction | LEADER, SUSTAIN-6, FLOW |
| Non-steroidal MRAs | Finerenone | Composite kidney and cardiovascular outcome reduction; anti-fibrotic effect | FIDELIO-DKD, FIGARO-DKD, FIDELITY |
Beyond Medication: The Role of Multidisciplinary Care
The management of DKD has grown considerably more complex in recent years. Patients now have access to multiple drug classes acting through different but complementary mechanisms, and the challenge lies in deploying these tools strategically, safely, and equitably. The International Society of Nephrology has consistently emphasized that optimizing DKD care requires close collaboration across medical specialties and cannot rest on the shoulders of any single clinician.
An effective multidisciplinary team for a patient with DKD typically includes:
- A nephrologist to oversee CKD staging, guide specialist treatment decisions, and monitor for complications including electrolyte imbalances, anemia, and bone-mineral disease
- An endocrinologist or diabetologist to optimize glycemic management and navigate complex diabetes pharmacotherapy
- A cardiologist when significant cardiovascular disease is present or when cardiovascular risk requires dedicated management
- A dietitian specializing in kidney disease nutrition to provide individualized guidance on protein, sodium, potassium, and phosphate intake
- A diabetes educator and clinical pharmacist to support medication adherence, patient empowerment, and safe polypharmacy
- A primary care physician to coordinate routine monitoring, manage comorbidities, and facilitate timely referrals
This kind of integrated, team-based approach is particularly important given the dual kidney-cardiovascular burden carried by most DKD patients. Treatment decisions that benefit one organ system may have implications for another, and careful cross-specialty communication reduces both the risk of under-treatment and the risk of harmful drug interactions in an already complex patient population.
ISN’s Global Advocacy: Bridging the Gap Between Evidence and Access
The clinical evidence for modern DKD treatment is compelling. Yet evidence alone does not improve patient outcomes — access to effective medications does. This is where the ISN (International Society of Nephrology) has focused a significant portion of its global advocacy effort.
In many low- and middle-income countries, the majority of patients with DKD have no reliable access to SGLT2 inhibitors, finerenone, or even adequate blood pressure management. Kidney disease frequently goes undiagnosed until it is already advanced, and patients who do receive a diagnosis may have no pathway to evidence-based treatment. The ISN has engaged with national governments, health ministries, and international health organizations to advocate for inclusion of SGLT2 inhibitors and other key DKD therapies on national essential medicines lists. These efforts rest on a clear moral and scientific foundation: the greatest burden of untreated CKD falls disproportionately on populations least able to afford the treatments that could help them most.
Education is equally central to ISN’s mission. By disseminating the updated
KDIGO heat map — which combines eGFR and UACR categories to stratify risk and guide clinical decision-making — the International Society of Nephrology has helped primary care providers in resource-limited settings make better-informed decisions about when to initiate treatment, when to refer, and how frequently to monitor their patients with DKD. This practical, visual framework has been widely adopted across ISN member countries as a tool that bridges the gap between guideline complexity and real-world clinical practice.
Conclusion: A Transformative Era for Diabetic Kidney Disease
The management of diabetic kidney disease has undergone a remarkable transformation over the past two decades. From the foundational work of the DCCT and UKPDS trials through to the cardio-renal protection now demonstrated with SGLT2 inhibitors and finerenone, the evidence base for DKD management has never been stronger or more comprehensive. Patients today can benefit from a layered treatment approach that simultaneously protects kidney function, reduces cardiovascular risk, attenuates inflammation and fibrosis, and — where access allows — significantly delays or prevents kidney failure.
Yet the clinical advances of recent years will only fulfill their promise if they reach every patient who needs them. Diabetes does not respect geographic boundaries, and neither should effective kidney care. The updated KDIGO guideline framework, endorsed by the International Society of Nephrology, provides a unified treatment algorithm that clinicians across all practice settings can apply. But guidelines require delivery systems, trained clinicians, affordable medications, and engaged patients to translate into real-world benefit.
Understanding DKD — its mechanisms, its progression, and the expanding toolkit now available to manage it — is essential for every clinician who cares for patients with diabetes. The ISN remains committed to bridging the gap between evidence and practice through guideline development, clinician education, patient advocacy, and sustained engagement with health systems around the world. In doing so, it works toward a future where a diagnosis of diabetic kidney disease no longer means an inevitable journey toward kidney failure, but rather the beginning of a well-supported, evidence-guided path toward preserved kidney health.