Nephrology Drugs in the Treatment of Chronic Kidney Disease

Nephrology Drugs encompass a diverse group of pharmaceuticals used to prevent, manage, and treat kidney-related disorders, including chronic kidney disease (CKD), acute kidney injury (AKI), glomerular diseases, electrolyte imbalances, hypertension-associated renal damage, and end-stage renal disease (ESRD). These agents target underlying pathophysiology, slow disease progression, manage complications, and support renal replacement therapies like dialysis.

The field has evolved dramatically from basic diuretics and antihypertensives in the mid-20th century to sophisticated targeted therapies today. Landmark developments include ACE inhibitors (1980s), SGLT2 inhibitors (2010s), and non-steroidal mineralocorticoid receptor antagonists (2020s). As of 2025, the global nephrology drugs market is valued at approximately USD 35-45 billion, driven by rising CKD prevalence (affecting over 850 million people worldwide), diabetes/hypertension epidemics, and innovative therapies delaying dialysis. Major players include AstraZeneca, Bayer, Boehringer Ingelheim, Johnson & Johnson, and Novo Nordisk.

Classification of Nephrology Drugs

Drugs are categorized by indication or mechanism:

Renoprotective Agents Slow CKD progression and reduce proteinuria.
- ACE Inhibitors (e.g., ramipril, lisinopril): Block angiotensin II, reducing intraglomerular pressure.
- Angiotensin Receptor Blockers (ARBs) (e.g., losartan, valsartan): Similar mechanism, better tolerability.
- SGLT2 Inhibitors (e.g., dapagliflozin, empagliflozin): Originally antidiabetic; reduce glomerular hyperfiltration, with landmark cardiorenal benefits (DAPA-CKD, EMPA-KIDNEY trials).
- Non-Steroidal MRA (finerenone): Reduces fibrosis/inflammation in diabetic kidney disease (FIDELIO-DKD, FIGARO-DKD).
Diuretics Manage fluid overload and hypertension.
- Loop (furosemide, bumetanide): Potent, used in advanced CKD/edema.
- Thiazide/Thiazide-like (hydrochlorothiazide, chlorthalidone): Early CKD.
- Potassium-sparing (spironolactone, eplerenone): With caution due to hyperkalemia risk.
Phosphate Binders Control hyperphosphatemia in CKD-mineral bone disorder.
- Calcium-based (calcium acetate).
- Non-calcium (sevelamer, lanthanum carbonate, sucroferric oxyhydroxide).
- Iron-based emerging for dual anemia/phosphate control.
Erythropoiesis-Stimulating Agents (ESAs) Treat renal anemia: Epoetin alfa, darbepoetin, biosimilars.
Iron Therapies IV iron (ferric carboxymaltose, iron sucrose) for iron deficiency anemia in CKD.
Calcimimetics and Vitamin D Analogs Secondary hyperparathyroidism: Cinacalcet, etelcalcetide; paricalcitol, calcitriol.
Immunosuppressants Glomerular diseases (lupus nephritis, IgA nephropathy): Corticosteroids, mycophenolate mofetil, cyclophosphamide, rituximab, calcineurin inhibitors.
Emerging Therapies
- Complement inhibitors (e.g., for C3 glomerulopathy).
- HIF prolyl hydroxylase inhibitors (roxadustat) for anemia.
- Endothelin receptor antagonists (aprocitentan) for resistant hypertension/CKD.

Key Disease Targets and Therapeutic Goals

Chronic Kidney Disease (CKD): Delay progression (reduce eGFR decline), manage proteinuria, control cardiovascular risk.
Diabetic Kidney Disease: Glycemic control + renoprotection (SGLT2i, finerenone).
Acute Kidney Injury: Supportive (fluids, avoid nephrotoxins); no specific reversal agents.
Glomerulonephritis: Immunosuppression tailored to histology.
ESRD/Dialysis: Control complications (anemia, bone disease, volume).

Mechanisms of Action Highlights

SGLT2 inhibitors: Tubuloglomerular feedback restoration, reduced oxygen demand, anti-inflammatory effects.
Finerenone: Blocks MR overactivation, reducing fibrosis without hyperkalemia of steroidal MRAs.
ESAs: Stimulate erythropoietin receptor for red cell production.

Clinical Evidence and Guidelines

Major trials:

RENAAL/IDNT: ARBs slow diabetic nephropathy.
CREDENCE/EMPA-REG: SGLT2i cardiorenal protection.
DAPA-CKD: Dapagliflozin benefits non-diabetic CKD.
FIDELIO-DKD: Finerenone reduces progression.

KDIGO guidelines recommend RAAS blockade, SGLT2i, and finerenone as foundational therapies.

Safety and Side Effects

RAAS inhibitors: Hyperkalemia, acute kidney injury risk.
SGLT2i: Genital infections, euglycemic DKA, volume depletion.
Phosphate binders: GI upset, calcium overload.
ESAs: Hypertension, thrombosis risk if Hb >11 g/dL.
Immunosuppressants: Infection, malignancy risk.

Monitoring (eGFR, potassium, Hb) essential.

Market and Future Directions

Combination therapies (SGLT2i + finerenone + GLP-1 agonists) show additive benefits. Pipeline includes:

Novel mineralocorticoid antagonists.
Anti-fibrotic agents.
Gene/cell therapies for genetic kidney diseases.

Biosimilars reduce costs for ESAs and biologics.

Conclusion

Nephrology drugs have transformed kidney disease management from supportive to disease-modifying, significantly delaying dialysis and improving outcomes. The integration of cardiorenal protective agents like SGLT2 inhibitors and finerenone marks a new era in slowing progression across etiologies. Ongoing research promises further personalization and combination strategies, offering hope for millions affected by kidney disorders worldwide.