QW07-9-24 – Nephro Critical Care Society

QW07-October 2024

Question 1: Select each option to validate with explanations

Question 1

A 58-year-old woman with a history of hypertension arrived at the Emergency Department with symptoms including fever, nausea, vomiting, and confusion. Her vital signs were as follows; temperature: 39.3°C, heart rate: 98/min, blood pressure: 132/64 mm Hg, respiratory rate: 26/min, and oxygen saturation (SaO2): 92% on room air. During the physical examination, she exhibited renal angle tenderness. Laboratory tests revealed a white blood cell count of 22,000/mm³, serum creatinine of 2.3 mg/dL (baseline 0.7 mg/dL), and more than 50 white blood cells per high power field on urine microscopy. A non-contrast CT scan of the abdomen and pelvis showed right perinephric stranding without stones or hydronephrosis. Blood and urine cultures were taken, ceftriaxone was administered, and she was admitted to the ICU.

Question: Which of the following statements about this patient’s acute kidney injury (AKI) is most accurate?

A. AKI is likely due to ischemic acute tubular necrosis (ATN) caused by decreased blood flow.

B. AKI is unlikely to be due to sepsis as she does not meet the current consensus definition of sepsis.

C. AKI is unlikely to be due to sepsis given her normal blood pressure.

D. AKI increases her risk for secondary infections during her hospitalization.

E. Given her stage 3 AKI in the setting of sepsis, she would likely benefit from pre-emptive renal replacement therapy (RRT) before the development of an urgent indication.

Wrong Answer: A. AKI is likely due to ischemic acute tubular necrosis (ATN) caused by decreased blood flow.
Explanation:
This statement is incorrect. Although ATN is a common cause of AKI, especially in the context of ischemia (decreased blood flow), recent evidence suggests that sepsis-associated AKI (SA-AKI) is not primarily due to ischemic injury. Studies have shown that renal blood flow may remain unchanged or even increase during sepsis, and post-mortem analyses often reveal well-preserved renal histology without clear evidence of ATN. SA-AKI appears to result from complex mechanisms, including microvascular dysfunction, inflammation, oxidative stress, and endothelial dysfunction. Therefore, attributing her AKI to ischemic ATN is likely incorrect.

Wrong Answer: B. AKI is unlikely to be due to sepsis as she does not meet the current consensus definition of sepsis.
Explanation:
This statement is incorrect. The Sepsis-3 criteria define sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, with organ dysfunction indicated by a Sequential Organ Failure Assessment (SOFA) score increase of 2 or more points. The quick SOFA (qSOFA) screening tool, which includes respiratory rate ≥22 breaths/min, altered mental status, and systolic blood pressure ≤100 mmHg, can suggest sepsis when two of these criteria are met. Although this patient has normal blood pressure, she exhibits other signs of severe infection, including elevated respiratory rate and altered mental status, making sepsis a likely diagnosis. Therefore, It is highly probable that the patient's AKI is a result of sepsis. .

Wrong Answer: C. AKI is unlikely to be due to sepsis given her normal blood pressure.
Explanation:
This statement is incorrect. Sepsis can lead to AKI even in the absence of hypotension. While hypotension is a common feature of septic shock, sepsis can cause AKI through multiple other mechanisms, including systemic inflammation, microvascular injury, and endothelial dysfunction, which do not necessarily require a drop in blood pressure. The presence of normal blood pressure does not exclude the possibility of sepsis-induced AKI.

Right Answer:D. AKI increases her risk for secondary infections during her hospitalization.
Explanation:
This statement is correct. There is a well-documented bidirectional relationship between AKI and infections. Patients with AKI, particularly SA-AKI, are at a higher risk of developing subsequent infections during their hospitalization. For example, a secondary analysis of the PICARD study showed that more than half of ICU patients with non-septic AKI developed sepsis later during their stay. Another study of cardiac surgery patients found that post-operative AKI was associated with a significantly increased risk of infection. This increased risk is likely due to the impaired immune response and other systemic effects associated with AKI.

Clinical pearls: Sepsis Associated AKI(CA-AKI)
Pathophysiology:
1. SA-AKI results from a complex interplay of factors including inflammation, hemodynamic instability, and direct cellular injury.
2. The kidneys are often one of the first organs to be affected during sepsis due to their high blood flow and sensitivity to changes in blood pressure and oxygenation.
Epidemiology:
3. Approximately 40-50% of patients with sepsis develop AKI.
4. The incidence is higher in patients with septic shock, where up to two-thirds may develop AKI.
5. The risk factors include severe sepsis or septic shock, older age, pre-existing conditions like CKD, diabetes, hypertension, heart failure, genetic predispositions, nephrotoxic medications, hypotension, hypoperfusion, heightened inflammatory response, and fluid overload.
Diagnosis:
6. Diagnosis is based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, which include changes in serum creatinine levels and urine output.
7. Biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are being studied for early detection.
Management:
8. Management focuses on treating the underlying sepsis, maintaining hemodynamic stability, and avoiding nephrotoxic agents.
9. Renal replacement therapy (RRT) may be necessary in severe cases.
Prognosis:
10. SA-AKI is associated with a high in-hospital mortality rate, especially in patients requiring RRT.
11. Long-term outcomes include an increased risk of chronic kidney disease (CKD) and major adverse cardiovascular events.

Wrong Answer: E. Given her stage 3 AKI in the setting of sepsis, she would likely benefit from pre-emptive renal replacement therapy (RRT) before the development of an urgent indication.
Explanation:
This statement is incorrect. While pre-emptive renal replacement therapy (RRT) might seem beneficial in severe AKI, recent large multicentre trials have not shown a significant benefit from pre-emptive RRT in SA-AKI patients. Earlier small-scale studies suggested potential benefits, but larger trials, including one specifically focused on SA-AKI, failed to demonstrate an improvement in outcomes with pre-emptive RRT. The current standard of care is to reserve RRT for patients with clear indications, such as refractory hyperkalemia, metabolic acidosis, or fluid overload.

Reference:

[1] Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810.

[2] Uchino S, Bellomo R, Kellum JA, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813-818.

[3] Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2(3):431-439.

[4] Gaudry S, Hajage D, Schortgen F, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122-133.

[5] Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423.

Question 2 - Select each option to validate with explanations

Question 2: Which of the following statements regarding acute graft-versus-host disease (GVHD) after renal transplantation is TRUE?

A. Acute GVHD is more common in renal transplantation compared to bone marrow transplantation.

B. Acute GVHD occurs when donor T cells attack the recipient's tissues.

C. Acute GVHD primarily affects the kidneys in renal transplant recipients.

D. Acute GVHD after renal transplantation does not involve the skin or gastrointestinal tract.

Wrong Answer:A. Acute GVHD is more common in renal transplantation compared to bone marrow transplantation.
Statement is incorrect. Acute GVHD is more commonly associated with bone marrow transplants but can rarely occur after solid organ transplants, including renal transplants.

Right Answer:B. Acute GVHD occurs when donor T cells attack the recipient's tissues. Statement is True. Acute GVHD occurs when donor T cells recognize the recipient's tissues as foreign and mount an immune response.

Clinical Pearls: Acute GVHD
Incidence and Timing: Acute GVHD typically develops within 2 to 12 weeks post-transplant. Symptoms: Common symptoms include skin rashes, gastrointestinal issues (like nausea and diarrhea), liver dysfunction, and bone marrow suppression leading to cytopenias.
Diagnosis: GVHD can be difficult to diagnose because its symptoms are often attributed to other causes. A diagnosis is usually made after a thorough work-up that excludes other potential causes. Diagnosis is often confirmed through a biopsy of the affected organ and evidence of donor chimerism in blood or marrow.
Treatment: Initial treatment usually involves systemic corticosteroids. If GVHD is limited to the skin or oral mucosa, maintenance immunosuppression may be reduced to help the recipient reject the donor immune cells. For more severe cases, additional immunosuppressive therapies may be required.

Wrong Answer: C) Acute GVHD primarily affects the kidneys in renal transplant recipients. Statement is incorrect. Kidney is rarely involved.

Wrong Answer:D) Acute GVHD after renal transplantation does not involve the skin or gastrointestinal tract. Statement is incorrect. Organs rich in immunocompetent cells such as the skin, liver, and gastrointestinal tract are the primary organs affected, rather than the kidney itself.

Reference:

• Bayraktar, U.D. (2019). Graft Versus Host Disease (GHVD) in Critically Ill Oncologic Patients. In: Nates, J., Price, K. (eds) Oncologic Critical Care. Springer, Cham. https://doi.org/10.1007/978-3-319-74698-2_31-1

• Malard, F., Holler, E., Sandmaier, B.M. et al. Acute graft-versus-host disease. Nat Rev Dis Primers 9, 27 (2023). https://doi.org/10.1038/s41572-023-00438-1