What is warm ischaemia (ischemia) in the context of kidney transplant?

Warm Ischemia Time Definition in Kidney Transplantation

Warm ischemia time in kidney transplantation refers to the period when the kidney is at body temperature (or above the metabolic threshold of 15-18°C) without adequate blood supply, and should not exceed 45-60 minutes total to prevent significant organ dysfunction. 1

Key Time Periods and Definitions

Warm ischemia in kidney transplantation encompasses two distinct phases that must be understood separately:

First (Donor) Warm Ischemia Time

• Begins when systolic blood pressure drops below 50 mmHg (or when SpO₂ falls below 70%) in donation after circulatory death (DCD) donors 2
• Ends at the time of cold flush/cross-clamp or initiation of normothermic regional perfusion 2
• The American Society of Transplant Surgeons mandates documentation of the first minute when sBP drops to <50 mmHg as a critical time point 2, 1
• For uncontrolled DCD donors (out-of-hospital cardiac arrest), total warm ischemia can range from 120-150 minutes when appropriate preservation techniques are employed, though this represents a substantially longer acceptable window than controlled DCD 2, 1

Second (Recipient) Warm Ischemia Time

• Occurs during vascular anastomosis when the kidney is removed from cold storage and exposed to temperatures exceeding 15-18°C (the metabolic threshold where hypothermic protection is lost) before reperfusion 3
• This anastomotic time represents the only surgically modifiable period to minimize warm ischemic injury 4
• Even brief periods matter: warm ischemia times of 30-40 minutes are associated with a 17% increased risk of death/graft failure compared to 10-20 minutes 5

Critical Time Thresholds

The total warm ischemia time for kidney transplantation should remain ≤45-60 minutes to prevent significant complications 1. This recommendation comes from the American Society of Transplant Surgeons and represents the upper acceptable limit.

Functional Impact by Duration

• 10-20 minutes: Reference baseline risk 5
• 30-40 minutes: 17% increased hazard of death/graft failure 5
• 40-50 minutes: 20% increased hazard 5
• ≥60 minutes: 23% increased hazard and exponential losses in kidney function 2, 5
• >60 minutes: Leads to significant exponential losses in kidney function, with warm ischemia beyond this threshold causing severe functional compromise 2, 6

Surgical Timing Requirements

The American Society of Transplant Surgeons provides specific operative benchmarks to minimize warm ischemia:

• Kidney extraction time should be ≤60 minutes from flush/cross-clamp until the kidneys are placed in hypothermic solution 2
• Mandatory "no-touch" time after circulatory arrest declaration should be ≤5 minutes to avoid unnecessary warm ischemic injury 2, 1
• Blood pressure, heart rate, and oxygenation must be monitored and recorded every minute during the agonal phase to accurately determine functional donor warm ischemia time 2

Strategies to Minimize Warm Ischemia

Donor Management

• Preferentially perform withdrawal of life support in the operating room after prepping and draping 1
• Administer heparin before withdrawal rather than waiting for the onset of the agonal phase 1
• Use experienced DCD procurement teams familiar with rapid surgical techniques 2, 1

Recipient Surgery

• Surface cooling techniques during anastomosis (such as ice bag technique) significantly reduce detrimental events including delayed graft function and acute rejection 7
• Elimination of second warm ischemia through kidney surface cooling shows a 65% reduction in detrimental events (delayed graft function and/or acute rejection) and higher glomerular filtration rate at day 14 post-transplant 7
• Various cooling methods exist ranging from simple surface cooling to organ immersion in ice slush to specialized cooling jackets 3

Important Clinical Caveats

Warm ischemia time impacts both short-term and long-term outcomes, with associations persisting regardless of donor type (living vs. deceased) or delayed graft function status 5. The combination of prolonged warm ischemia with other risk factors—such as donor age ≥65 years, cold ischemia time >8 hours, or hepatic steatosis—significantly compounds the risk of graft failure 1.

Cold ischemia time for kidney transplantation should be kept ≤24 hours to optimize outcomes, as this interacts synergistically with warm ischemia time 1. The goal in clinical practice should be achieving the shortest possible total ischemia time 8.

Prolonged warm ischemia causes severe decrements in creatinine clearance, urine output, and fractional excretion of sodium, though it may not immediately result in tissue necrosis—meaning kidneys can appear viable histologically despite significant functional compromise 6.