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A novel test identifies patients at high risk for kidney damage.



New Urology biomarkers can predict the risk of acute kidney damage after cardiac surgery and predict future decline in renal function, new research shows.

"Dickkopf-3 [DKK3] Specific modulators of the proinflammatory pathway used to communicate in coronary cells, "said Dr. Danilo Fliser of Saarland University Medical Center in Homburg, Germany.

"Stress in these cells creates stress and produces a measurable DKK3 in the urine." Medscape Medical News.

The high preoperative level of urinary DKK3 significantly increased the risk of acute kidney injury after surgery, he said.

In the validation cohort of this study, including participants who underwent remote ischemic preconditioning after induction of anesthesia in the RenalRIP clinical trialJama. 2015; 313: 2133-2141) – Despite the high preoperative value of DDK3, the risk of acute kidney damage did not increase.

"Thus, we not only identify patients at high risk of acute kidney injury, but have shown that high levels of DKK3 can prevent and prevent remote ischemic preconditioning," Fliser said.

The results of the study were discussed at a press conference at the 56th General Assembly of the European Renal Association (European Renal Association – European Transition and Transplant Association) lanceIt will be presented at a session on how to prevent acute kidney damage.

In a derived cohort of 733 non-selected patients scheduled for cardiac surgery, the risk of acute renal failure was 65% higher than those of more than 65% in patients with prostate-urinary DKK3 / creatinine concentrations greater than 471 pg / mg. ratio [OR], 1.65: blood = .015).

This association was independent of the baseline estimated glomerular filtration rate (eGFR).

In a mean follow-up of 820 days, the eGFR concentration was lower in patients with a baseline urinary tract DKK3 / creatinine concentration above the reference level (63.1 versus 67.0 mL / min, 1.73 m²; blood = .0060).

Likewise, patients with high urinary DKK3 / creatinine concentrations were twice as likely to exhibit consistently low eGFR during follow-up at concentrations below the 471 pg / mg baseline (<60 mL / min per 1.73 m²) OR, 2.01; blood = 0.0015).

Patients with increased DKK3 / creatinine levels before surgery were more likely to experience progression of chronic kidney disease.

Verification cohort of RenalRIP trial

Participants in the RenalRIP trial had a score of 6 or higher on the Cleveland Clinic Foundation and were at high risk for acute kidney injury and were randomly drawn into a remote ischemic precondition or a fake procedure.

In RenalRIP, "After multivariable control with renal function at admission, the urogenital DKK3, which is higher than 471 pg / mg creatinine, significantly increased the risk of AKI," Fliser and his colleagues report.

However, remote ischemic angiography of RenalRIP essentially halved the risk of acute renal failure after cardiac surgery (OR, 0.53; blood = .016). The small group had a high DKK3 / creatinine concentration and a high risk of acute kidney damageblood = .31), there is a continuing renal dysfunction after 90 days of kidney function control at admission.

Results from participants with RenalRIP: Concentrations below the pre-operative DKK3 / creatinine level of 471 pg / mg or greater
resultOdds ratio blood value
Acute renal injury risk1.94.026
Continuous kidney dysfunction risk at 90 days6.67.0072
The risk of kidney replacement therapy is 90 days.13.57.020
Fake Procedure Subgroups
Acute renal injury risk2.79.0022
Continuous kidney dysfunction risk at 90 days3.82.014

In the remote ischemic preconditioning protocol evaluated in the RenalRIP test, the systolic pressure was increased by 15 mmHg for 5 minutes, followed by contraction for 5 minutes, and the blood pressure cuff was placed on the patient's upper arm. The protocol was repeated three times.

Fliser pointed out that it is necessary to induce pretreatment after anesthesia has begun.

The reason why the protocol helps protect against kidney damage is not well understood, but Fliser speculated that a short cut of ischemia may seem to protect the heart from myocardial ischemia.

So far, we have not had any definitive intervention in the prevention of AKI, but all sorts of drugs and interventions were under development. DKK3 analysis is "a kind of precise medicine because you can only see results if you are at high risk for AKI."

Separate process

According to Dr. Andreas Kribben of Essen University Hospital, Chairman of the German Kidney Society, two courses of acute kidney damage, acute renal failure and kidney damage,

"The problem of acute kidney damage is defined only by functional loss," said Kribben. "This DKK3 is indeed an indicator of acute kidney damage that we need." Medscape Medical News.

This is especially true in the context of heart surgery because current clinical parameters do not predict acute kidney damage, he explained. Identifying people at risk for a kidney injury in this setting will allow the clinician to change tactics, such as changing the operation from an on-pump to an off-pump procedure to reduce risk.

"While care should be taken to limit this outcome to patients with acute kidney damage during cardiac surgery," Kribben said.

"Acute kidney damage is associated with an increased risk of death over a long period of time," he said.

Fliser is currently co-founder of DiaRen, which sells the DKK3 ELISA assay. Kribben served as an adviser to Ablynx, Alexion, Alexion, Astellas, Chiesi, Novartis, Otsuka, Shire.

European Kidney Association – European Dialysis and Transplant Association (ERA-EDTA) 56th General Assembly: Abstract Sa0038. Awarded June 15, 2019.

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