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10 marksDrNB 2025NephrologyTransplant Nephrology

a) Role of Nephrologists to promote DBD (Donation after brain death) programme. [7] b) Role of innate immune system in renal allograft injury. [3]

Definition

Donation after Brain Death (DBD) refers to organ donation from patients who have been declared brain dead, allowing procurement of organs like kidneys for transplantation (Harrison's 21e, Ch. 278).

Etiopathogenesis

Brain death results in irreversible cessation of all brain functions, while circulation is maintained artificially. This state permits organ viability for transplantation. Nephrologists’ involvement enhances utilization of kidneys from DBD donors by ensuring prompt diagnosis, maintenance, and counseling.

Clinical Features

N/A — pertains to donor management and program promotion, not a clinical syndrome.

Diagnosis

Brain death diagnosis follows standardized criteria including:

CriteriaDetails
Clinical ExaminationComa, absent brainstem reflexes
Apnea TestNo spontaneous respiration despite hypercarbia
Confirmatory Tests*EEG, cerebral blood flow studies (optional)

*Varies per institutional protocols (Bradley's Neurology in Clinical Practice, 8e).

Management

Role of Nephrologist in DBD Programme:

DomainSpecific Role
Early IdentificationRecognize potential brain dead patients with suitable kidneys
Donor MaintenanceOptimize hemodynamics, fluid balance, electrolytes to preserve renal function
Family CounselingParticipate in communication to address concerns, explain donation benefits
CoordinationLiaise with transplant teams and organ donation coordinators
Training & AdvocacyEducate healthcare workers on DBD protocols and ethical aspects
Data CollectionMaintain and audit donor outcomes to improve programme quality

Effective donor kidney management reduces delayed graft function and improves transplant outcomes (Brenner & Rector’s The Kidney, 11e).

Recent Advances

  • Use of nociception monitors to support donor hemodynamic stability
  • Structured training modules for nephrologists on brain death protocols
  • AI-based tools for donor-recipient matching improving allograft survival (Harrison's 21e)

Key Points for Exam

  • Brain death mandates irreversible loss of all brain function with maintained circulation.
  • Nephrologists optimize donor kidney function by maintaining hemodynamics and electrolytes.
  • Counseling families is critical for consent and public awareness.
  • Coordination with transplant teams facilitates timely organ retrieval.
  • Audit and quality improvement enhance donor pool and transplant outcomes.

Definition

Innate immunity triggers early inflammatory responses leading to renal allograft injury via recognition of donor antigens and ischemia-reperfusion injury (Brenner & Rector’s The Kidney, 11e).

Etiopathogenesis

Innate immune cells recognize damage-associated molecular patterns (DAMPs) released during transplantation:

Innate Immune ComponentRole in Allograft Injury
Dendritic Cells (DCs)Antigen presentation, cytokine release
MacrophagesPhagocytosis, secretion of proinflammatory cytokines (TNF-α, IL-1)
Natural Killer (NK) CellsKill stressed donor endothelial cells, amplify inflammation
Complement SystemActivation causes endothelial injury, recruits leukocytes

Ischemia-reperfusion injury (IRI) upregulates toll-like receptors (TLRs), amplifying cytokine storms that exacerbate tissue damage (Harrison's 21e, Ch. 279).

Clinical Features

Manifest as early graft dysfunction:

  • Delayed graft function
  • Acute tubular necrosis
  • Elevation of serum creatinine soon post-transplant

Diagnosis

Monitoring includes:

  • Serum creatinine, urine output trends
  • Kidney biopsy demonstrating innate immune cell infiltration and complement deposition

Management

  • Use of immunosuppressants targeting innate pathways (e.g., C1 esterase inhibitors)
  • Minimizing ischemic times during transplant
  • Emerging TLR antagonists under research (Brenner & Rector’s The Kidney, 11e)

Recent Advances

  • Development of complement inhibitors (eculizumab) to prevent antibody-mediated injury
  • Novel TLR blockers to reduce innate immune activation post-transplant

Key Points for Exam

  • Innate immunity triggers initial allograft injury post-transplant.
  • DAMPs activate dendritic cells, macrophages, NK cells, and complement.
  • Ischemia-reperfusion injury worsens innate immune-mediated damage.
  • Targeting innate immunity is a therapeutic strategy to improve graft survival.

Mnemonic for Nephrologist’s Role in DBD: “F-A-C-T-C”

  • Find brain dead donors
  • Assess and maintain donor kidney function
  • Counsel families effectively
  • Team coordination
  • Continuous audit and training

References:

  • Harrison's Principles of Internal Medicine, 21st edition
  • Brenner & Rector's The Kidney, 11th edition
  • Bradley's Neurology in Clinical Practice, 8th edition

References

Bradley's Neurology in Clinical Practice, 8eBrenner & Rector’s The Kidney, 11eHarrison's 21eHarrison's 21e, Ch. 278Harrison's 21e, Ch. 279