A Research Guide for
Facing Chronic Kidney Disease

FDA-APPROVED The DAPA-CKD trial was a landmark study showing that dapagliflozin reduced the risk of a sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from kidney or cardiovascular causes by 39% compared to placebo. This benefit occurred in patients with and without type 2 diabetes. The trial was stopped early because the benefit was so clear. Dapagliflozin is now recommended by KDIGO for essentially all CKD patients with eGFR 20–45, or eGFR 45–90 with a UACR of 200 mg/g or higher.

FDA-APPROVED The EMPA-KIDNEY trial confirmed and extended the DAPA-CKD findings. Empagliflozin reduced the risk of kidney disease progression or cardiovascular death by 28%. Importantly, this trial included patients with lower levels of proteinuria and a wider range of CKD causes, demonstrating that the kidney-protective effect of SGLT2 inhibitors extends beyond just diabetic kidney disease.

FDA-APPROVED Finerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA) that reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD. The FIDELIO-DKD trial showed an 18% reduction in kidney disease progression, and the FIGARO-DKD trial showed a 13% reduction in cardiovascular events. Finerenone has a lower risk of hyperkalemia compared to older MRAs like spironolactone, though potassium monitoring is still required.

FDA-APPROVED for CKD in type 2 diabetes (Jan 2025) The FLOW trial demonstrated that semaglutide (a GLP-1 receptor agonist) reduced the risk of major kidney disease events by 24% in patients with type 2 diabetes and CKD. This trial was stopped early due to clear benefit. Semaglutide also reduced cardiovascular death and all-cause mortality. On January 28, 2025 the FDA approved semaglutide (Ozempic) specifically to reduce the risk of worsening kidney disease, kidney failure, and cardiovascular death in adults with type 2 diabetes and CKD — so this is now an approved kidney indication, not just an emerging one.

ESTABLISHED STANDARD ACE inhibitors (e.g., lisinopril, ramipril) and ARBs (e.g., losartan, valsartan) have been the backbone of CKD treatment for decades. These drugs lower blood pressure, reduce protein leaking into urine (proteinuria), and slow kidney function decline. They are first-line therapy for any CKD patient with proteinuria (UACR above 30 mg/g). The new therapies (SGLT2 inhibitors, finerenone) are used in addition to, not instead of, ACE/ARBs.

IgA nephropathy is the most common form of glomerulonephritis worldwide and a frequent cause of CKD in younger adults. Beyond the standard kidney-protective drugs above, there are now four FDA-approved disease-modifying therapies for people with IgA nephropathy at risk of progression (used under a kidney specialist's care):

• Targeted-release budesonide (Tarpeyo) FDA-APPROVED — a gut-targeted corticosteroid; the first approved IgA nephropathy therapy (full approval Dec 2023).
• Sparsentan (Filspari) FDA-APPROVED — a dual endothelin/angiotensin receptor blocker; full approval to slow kidney decline in IgA nephropathy (Sep 2024).
• Atrasentan (Vanrafia) FDA-APPROVED — a selective endothelin blocker that lowers protein in the urine (accelerated approval Apr 2025).
• Iptacopan (Fabhalta) FDA-APPROVED — the first oral complement (factor B) inhibitor for IgA nephropathy (accelerated approval Aug 2024); also approved for C3 glomerulopathy.

Questions to ask your doctor: Is my CKD caused by IgA nephropathy, confirmed by biopsy? Am I a candidate for one of these targeted therapies in addition to standard care? What are the risks (including the strict need to avoid pregnancy on endothelin blockers like sparsentan and atrasentan)?

• What is my current eGFR and UACR, and what stage of CKD does that represent?
• How fast is my kidney function declining? What is the trend over the past 1–2 years?
• What is causing my CKD?
• Am I on an ACE inhibitor or ARB? If not, why?
• Should I be on an SGLT2 inhibitor (dapagliflozin or empagliflozin)?
• Should I be referred to a nephrologist?
• What medications should I avoid because of my kidneys?
• How often should I have my kidney function tested?

Diabetic kidney disease (DKD) is the single most common cause of CKD and ESKD worldwide. Chronically elevated blood sugar damages the tiny blood vessels in the kidney’s filtering units (glomeruli). Key points:

• Present in both type 1 and type 2 diabetes
• Risk increases with duration of diabetes and poor blood sugar control
• HbA1c target for most CKD patients with diabetes: below 7.0% (individualized)
• SGLT2 inhibitors, finerenone, and GLP-1 RAs all provide additional kidney protection in DKD beyond blood sugar control

Hypertension both causes and accelerates CKD. High pressure damages the kidney’s filtering units over time. Conversely, damaged kidneys cannot regulate blood pressure properly, creating a dangerous cycle. Blood pressure targets in CKD:

• KDIGO 2024: systolic target below 120 mmHg when tolerated (based on SPRINT trial)
• ACE inhibitors and ARBs are first-line for CKD with proteinuria
• Avoid dual ACE/ARB therapy (increased harm without benefit)

• Glomerulonephritis: Inflammation of the kidney’s filters. Includes IgA nephropathy (the most common form worldwide), lupus nephritis, ANCA-associated vasculitis, and others. May require immunosuppressive treatment.
• Polycystic kidney disease (PKD): An inherited condition where cysts grow in the kidneys. Tolvaptan (Jynarque) can slow cyst growth in autosomal dominant PKD.
• Obstructive uropathy: Blockage of urine flow (e.g., kidney stones, enlarged prostate) that backs up pressure into the kidneys.
• Drug-induced: Long-term use of NSAIDs (ibuprofen, naproxen), certain antibiotics, lithium, and other drugs can damage kidneys. Always check kidney safety of medications.
• Congenital/genetic: Abnormal kidney development, Alport syndrome, Fabry disease.

• Target: Systolic blood pressure below 120 mmHg when tolerated (KDIGO 2024, based on SPRINT trial)
• First-line: ACE inhibitor (lisinopril, ramipril, enalapril) or ARB (losartan, valsartan, irbesartan) for all CKD patients with proteinuria
• Titrate to maximum tolerated dose of ACE/ARB before adding other medications
• Monitor potassium and creatinine within 2–4 weeks of starting or increasing dose
• A small rise in creatinine (up to 30%) after starting ACE/ARB is expected and acceptable — do not stop the medication for this

• Recommended for: CKD patients with eGFR 20–45, or eGFR 45–90 with UACR 200+ mg/g (KDIGO 2024)
• Drugs: Dapagliflozin 10 mg daily or empagliflozin 10 mg daily
• Benefits seen regardless of diabetes status
• Can be initiated down to eGFR 20 and continued until dialysis or transplant
• Expect a small, reversible dip in eGFR of 3–5 mL/min when starting — this is protective, not harmful
• Side effects: increased urinary tract infections and genital yeast infections (especially in women with diabetes); rare diabetic ketoacidosis

• Target HbA1c: Generally below 7.0%, but individualized (6.5–8.0% range)
• Metformin: First-line glucose-lowering agent. Can be used down to eGFR 30 (with dose reduction). Stop below eGFR 30.
• SGLT2 inhibitors: Provide kidney protection beyond glucose lowering
• GLP-1 receptor agonists: Semaglutide, liraglutide, dulaglutide — kidney and cardiovascular benefits (FLOW trial)
• Avoid: Sulfonylureas (hypoglycemia risk increases as eGFR declines); certain insulin regimens need dose reduction in CKD

• Recommended for: Type 2 diabetes with CKD, already on maximized ACE/ARB, with UACR 30+ mg/g and potassium below 5.0
• Drug: Finerenone 10–20 mg daily
• Reduces kidney disease progression (18%, FIDELIO-DKD) and cardiovascular events (13%, FIGARO-DKD)
• Non-steroidal MRA — less hyperkalemia risk than spironolactone, but potassium monitoring every 4 weeks initially is still required
• Can be combined with SGLT2 inhibitors (complementary mechanisms)

• Am I on the maximum tolerated dose of my ACE inhibitor or ARB?
• Am I a candidate for an SGLT2 inhibitor? If not, why?
• If I have diabetes, should finerenone be added?
• What is my blood pressure target?
• Are there any medications I should stop or avoid because of my kidney function?
• Am I taking any NSAIDs (ibuprofen, naproxen) that could harm my kidneys?
• How often should my kidney function be monitored?
• Should I be referred to a nephrologist?
• Is there a clinical trial I should consider?

Kidneys produce erythropoietin (EPO), which stimulates red blood cell production. As kidneys fail, EPO production drops, causing anemia. Symptoms include fatigue, weakness, pale skin, shortness of breath, and dizziness.

• Iron supplementation: First step. Many CKD patients are iron-deficient. Oral iron often poorly absorbed — IV iron (ferric carboxymaltose, iron sucrose) may be needed.
• Erythropoiesis-stimulating agents (ESAs): Epoetin alfa, darbepoetin alfa. Used when hemoglobin drops below 10 g/dL and iron stores are replete. Target hemoglobin 10–11.5 g/dL — do NOT aim for normal (increased cardiovascular risk per TREAT and CHOIR trials).
• HIF-PHI (new class): Roxadustat, daprodustat — oral pills that stimulate natural EPO production. FDA-approved for dialysis patients. An alternative for patients who do not respond to ESAs.

Failing kidneys cannot activate vitamin D or properly excrete phosphorus. This leads to a cascade: high phosphorus, low calcium, elevated parathyroid hormone (PTH), and weakened bones.

• Phosphate binders: Sevelamer (Renvela), lanthanum (Fosrenol), calcium acetate (PhosLo) — taken with meals to bind dietary phosphorus and prevent absorption. Dietary phosphorus restriction alone is usually insufficient.
• Active vitamin D: Calcitriol or paricalcitol to suppress elevated PTH and maintain calcium levels.
• Calcimimetics: Cinacalcet (Sensipar) or etelcalcetide (Parsabiv, IV) for dialysis patients with uncontrolled secondary hyperparathyroidism.
• Dietary phosphorus restriction: Limit processed foods (phosphate additives are highly absorbed), dark colas, dairy, and organ meats.

Kidneys normally excrete acid. As function declines, acid builds up in the blood (serum bicarbonate drops below 22 mEq/L). Untreated acidosis accelerates muscle wasting, bone loss, and kidney function decline.

• Sodium bicarbonate supplementation: Oral tablets (typically 650 mg 2–3 times daily) to raise serum bicarbonate above 22 mEq/L
• Emerging evidence suggests correcting acidosis may slow CKD progression itself
• Monitor for fluid retention (sodium load) in heart failure patients

Kidneys are the primary route for potassium excretion. High potassium (above 5.5 mEq/L) is dangerous because it can cause fatal heart rhythm disturbances. ACE/ARBs, finerenone, and SGLT2 inhibitors can all raise potassium in CKD patients.

• Dietary restriction: Limit high-potassium foods (bananas, oranges, potatoes, tomatoes, salt substitutes)
• Potassium binders: Patiromer (Veltassa) or sodium zirconium cyclosilicate (Lokelma) — oral medications that bind potassium in the gut, allowing continued use of kidney-protective drugs
• Do NOT stop ACE/ARBs or SGLT2 inhibitors solely for mild hyperkalemia — use binders to enable continued kidney protection

Heart disease is the leading cause of death in CKD patients — more patients die of cardiovascular events than progress to dialysis. CKD is itself a major cardiovascular risk factor.

• Statin therapy: Recommended for all CKD patients (non-dialysis) aged 50+ per KDIGO. SHARP trial showed simvastatin/ezetimibe reduced major atherosclerotic events by 17% in CKD.
• Blood pressure control: Below 120 mmHg systolic when tolerated
• SGLT2 inhibitors: Provide cardiovascular protection in addition to kidney protection
• Heart failure management: CKD patients are at high risk for heart failure; SGLT2 inhibitors benefit both conditions

• Is my hemoglobin being monitored for anemia? Do I need EPO or iron?
• What are my phosphorus, calcium, and PTH levels?
• Do I need phosphate binders or vitamin D?
• Is my potassium safe? Am I on a potassium binder to allow continued kidney-protective medications?
• What is my serum bicarbonate level? Do I need sodium bicarbonate?
• Am I on a statin for cardiovascular protection?
• When should we start discussing dialysis or transplant planning?
• Should I be referred for vascular access (fistula) creation?
• Are there clinical trials I should consider at this stage?

• Sodium: Limit to less than 2,000 mg (2 grams) daily in all CKD stages. Reduces blood pressure, fluid retention, and proteinuria. This is the single most impactful dietary change.
• Protein: Stage 1–3: moderate restriction (0.8 g/kg/day). Stages 4–5 (not on dialysis): may benefit from lower intake (0.6–0.8 g/kg/day) under dietitian guidance. On dialysis: protein needs INCREASE (1.0–1.2 g/kg/day) to replace dialysis losses.
• Potassium: Restrict only if blood levels are elevated. Many CKD patients are advised to limit high-potassium foods, but some with normal potassium on newer drugs (SGLT2 inhibitors tend to lower potassium) may not need strict restriction.
• Phosphorus: Avoid processed foods with phosphate additives (read labels for ingredients containing “phos”). Organic/natural phosphorus in whole foods is absorbed less.
• Fluid: Generally unrestricted until stage 5 or when on dialysis. Some patients with fluid retention may need limits.

• Exercise: 150 minutes per week of moderate activity (walking, cycling, swimming). Exercise improves blood pressure, blood sugar, cardiovascular fitness, and quality of life in CKD.
• Smoking cessation: Smoking accelerates CKD progression and dramatically increases cardiovascular risk. Quitting is one of the highest-yield interventions.
• Weight management: Obesity worsens CKD progression. Weight loss through diet and exercise (or GLP-1 RAs in appropriate patients) reduces proteinuria and slows decline.
• Avoid nephrotoxic drugs: No NSAIDs (ibuprofen, naproxen), minimize contrast dye exposure, avoid herbal supplements with unknown kidney effects, use acetaminophen (Tylenol) for pain instead of NSAIDs.
• Renal dietitian: Ask your nephrologist for a referral to a renal dietitian. Individualized dietary counseling is far more effective than generic advice.

Blood is pumped through a machine that filters waste, removes excess fluid, and returns the cleaned blood to the body.

• In-center hemodialysis: Typically 3 sessions per week, each 3–5 hours, at a dialysis center. Staff-assisted. Most common modality in the US (~88% of dialysis patients).
• Home hemodialysis (HHD): Performed at home by the patient (often with a care partner). Can be done more frequently (daily or nocturnal), which provides better fluid and toxin removal and improved outcomes.
• Vascular access: Requires an arteriovenous (AV) fistula (preferred — lasts longest), AV graft, or central venous catheter (temporary, higher infection risk). Fistula creation should be planned 6+ months before dialysis is needed.
• Side effects: Fatigue after sessions, muscle cramps, low blood pressure, access-related infections

Uses the lining of the abdomen (peritoneum) as a natural filter. A catheter is placed in the abdomen, and a special fluid (dialysate) is infused, absorbs waste, and is drained.

• CAPD (Continuous Ambulatory PD): Manual exchanges 4–5 times daily. No machine needed. Highly portable.
• APD (Automated PD): A machine (cycler) performs exchanges overnight while you sleep. Frees up daytime hours.
• Advantages: More independence, done at home, gentler on the heart, preserves remaining kidney function longer, more flexible schedule, allows travel more easily
• Disadvantages: Risk of peritonitis (abdominal infection), weight gain from glucose in dialysate, requires storage space for supplies, less effective in very large patients
• Globally: PD is more common in Mexico, Hong Kong, and several developing countries due to lower infrastructure requirements

Some patients — particularly elderly patients with multiple serious illnesses — may choose not to start dialysis. This is a valid choice. Conservative management focuses on maximizing quality of life through symptom control, dietary management, and palliative care. Life expectancy without dialysis in ESKD is typically weeks to months, but varies. This decision should be made with full understanding of the alternatives and in consultation with the patient’s family and medical team.

• Living donor transplant: A kidney from a living person (family member, friend, or altruistic donor). Best outcomes. Shorter wait time. The donor lives normally with one kidney.
• Deceased donor transplant: A kidney from someone who has died. Requires placement on the national waiting list (UNOS in the US). Median wait time varies by blood type and region: 3–5 years average, longer in some areas.
• Preemptive transplant: Transplant before starting dialysis. Best outcomes of all transplant types. Requires early referral and evaluation.
• Paired kidney exchange: If your willing living donor is not a match for you, you can swap donors with another incompatible pair. Greatly expands living donor options.

• Graft survival: Living donor kidney: ~95% at 1 year, ~85% at 5 years. Deceased donor: ~92% at 1 year, ~75% at 5 years.
• Patient survival: Transplant recipients live 10–15 years longer on average than patients who remain on dialysis
• Quality of life: Dramatic improvement. Most transplant recipients return to normal activities, work, and travel.
• Immunosuppression: Required for life. Standard regimen: tacrolimus + mycophenolate + prednisone. Increases risk of infection and certain cancers (skin cancer, lymphoma). Regular monitoring of drug levels is essential.

Most ESKD patients are eligible for transplant evaluation. There is no absolute age cutoff — patients in their 70s and occasionally 80s receive transplants. Factors that may exclude someone include:

• Active cancer (must be cancer-free for a period, usually 2–5 years depending on cancer type)
• Active infection
• Severe heart or lung disease that makes surgery too risky
• Active substance abuse
• Inability to adhere to immunosuppressive medications

Referral should happen early. KDIGO recommends transplant evaluation beginning at stage 4 (eGFR below 30) for all patients who are interested and potentially eligible.

• Am I a candidate for kidney transplant? When should I be referred for evaluation?
• Should I consider a living donor? How does paired exchange work?
• What type of dialysis is best for my situation?
• When should I get my AV fistula or PD catheter placed?
• Can I get a preemptive transplant (before starting dialysis)?
• How long is the deceased donor waiting list in my area?
• What immunosuppressive medications will I need after transplant?
• What are the risks of transplant surgery?
• Is conservative management (no dialysis) an appropriate option for my situation?

• US FDA, EMA, PMDA (Japan), Health Canada: Dapagliflozin and empagliflozin approved for CKD regardless of diabetes status
• NICE (UK): Dapagliflozin recommended by NICE for CKD (TA775). Empagliflozin also assessed.
• LMIC (low- and middle-income countries): Access remains limited due to cost, though generic SGLT2 inhibitors are becoming available in some countries. WHO Essential Medicines List consideration ongoing.
• KDIGO 2024: SGLT2 inhibitors recommended as standard of care globally. Implementation varies by local resources and drug availability.

• United States: ~88% hemodialysis, ~12% peritoneal dialysis. Home dialysis growing but still minority.
• Hong Kong: ~80% peritoneal dialysis (PD-first policy). One of the highest PD utilization rates globally.
• Mexico: Peritoneal dialysis more common than HD due to infrastructure constraints.
• Japan: Highest dialysis rate per capita globally. Nearly all in-center hemodialysis. Very low transplant rate due to cultural factors.
• Taiwan: Second-highest dialysis rate per capita. Government-funded universal coverage for dialysis.
• Australia/New Zealand: High home dialysis utilization (~25% PD). Pioneer in patient-centered dialysis care.

• United States: Median wait 3–5 years (varies dramatically by region, blood type, and race)
• Spain: Among the highest deceased donor rates globally due to opt-out consent system
• Iran: Unique regulated living-donor compensation system; virtually no wait for living donor kidneys
• India: Very long waits for deceased donors; living donor transplant is primary mode
• UK: Median wait 2.5–3 years; National Kidney Sharing Scheme for paired exchange

HARMFUL The ONTARGET trial showed that combining an ACE inhibitor with an ARB increased acute kidney injury, hyperkalemia, and dialysis risk without improving outcomes. The VA NEPHRON-D trial in diabetic CKD was stopped early for safety concerns. Do not take both an ACE inhibitor and an ARB.

FAILED The ALTITUDE trial tested aliskiren added to ACE/ARB in diabetic patients. It was terminated early due to excess adverse events (stroke, hyperkalemia, hypotension) without kidney benefit. Aliskiren should not be combined with ACE/ARBs in CKD.

HARMFUL The TREAT (darbepoetin) and CHOIR (epoetin alfa) trials showed that using ESAs to target hemoglobin above 13 g/dL increased stroke, cardiovascular events, and death. Current guidelines recommend a conservative hemoglobin target of 10–11.5 g/dL. Higher is not better for EPO therapy.

FAILED The BEACON trial tested bardoxolone methyl in advanced diabetic CKD. Despite early-phase data showing eGFR improvements, the phase 3 trial was terminated due to excess heart failure and cardiovascular death. The eGFR rise was likely a hemodynamic artifact, not true kidney function improvement. Development in diabetic CKD stopped, though some trials in other kidney diseases (Alport, ADPKD) continue.

FAILED Both drugs showed promise in early studies for reducing proteinuria in diabetic kidney disease but failed to demonstrate meaningful clinical endpoints in larger trials. Sulodexide (Sun-MACRO trial) showed no significant reduction in serum creatinine doubling or ESKD. Pirfenidone antifibrotic trials in CKD were underpowered and results inconclusive.

• Help manage medications. CKD patients often take 10+ medications daily, including phosphate binders that must be taken with meals. Pill organizers, phone reminders, and medication lists are essential.
• Support dietary changes. Cooking kidney-friendly meals is one of the most valuable things a caregiver can do. A renal dietitian can provide meal plans tailored to the patient’s stage and lab values.
• Track lab values. Keep a log of eGFR, UACR, hemoglobin, potassium, phosphorus, and PTH over time. Trends matter more than single values.
• Attend appointments. Nephrology visits involve complex information. Having a second person to listen, take notes, and ask questions is invaluable.

• Home dialysis: If peritoneal dialysis or home hemodialysis is chosen, caregivers may need training on setup, troubleshooting, and emergency procedures.
• Transportation: In-center hemodialysis requires 3 trips per week. Many dialysis centers have early morning or evening shifts; plan transportation accordingly.
• Post-dialysis fatigue: Many patients feel drained for hours after hemodialysis sessions. Plan rest periods and light meals.
• Fluid and diet monitoring: Between dialysis sessions, fluid and potassium intake must be carefully managed. Help with meal preparation and monitoring fluid intake.

• CKD is a marathon, not a sprint. Unlike many acute illnesses, CKD management is measured in years and decades. Pace yourself.
• Advance care planning: Discuss goals of care, advance directives, and preferences for dialysis vs. conservative management when the patient is well enough to participate.
• Caregiver support: The National Kidney Foundation (1-855-NKF-CARES) and American Kidney Fund (1-866-300-2900) offer caregiver resources, financial assistance, and peer support.
• Mental health: Depression is common in CKD patients and caregivers. Seek professional help if needed. Social workers at dialysis centers can provide referrals.