Renal physiology Flashcards
Which of the following statements do not correspond to the definition of AKI
- Increase in serum creatinine to less than 2 times baseline, which is known or presumed to have occurred within the prior 7 days
- Urine volume >0.5 ml/kg/h for 12 hour
- Increased urine protein levels more than 30 mg/dl
Which of the following statements correspond to the definition of AKI stages?
- Increase of Cr ≥1.5-1.9 times baseline or urine output (UO) <0.5 ml/kg/h for >6 consecutive hours
- Increase of Cr ≥2-2.9 times baseline or UO <0.5 ml/kg/hours for ≥12 hours
- Increase of Cr ≥3 times baseline or UO <0.3 ml/kg/h for ≥24 hours or anuria for ≥12 hours
- Initiation of RRT is defined as AKI stage 3
What period of time do not correspond to AKI?
- Up to 24 hours,
- More than 72 hours,
- More than 7 days,
- More than 90 days
What are the factors leading to mis-diagnosis of AKI?
- High level of ADH,
- Obesity,
- Diabetes mellitus,
- Muscle mass loss
A 42-year-old man has been in intensive care for 108 days after contracting COVID. He has had a tracheostomy and is slowly weaning from the ventilator. He required renal replacement therapy 10 days after admission, although he is now off haemodiafiltration, passing good volumes of urine. His baseline serum creatinine was 95 µmol/L and his current serum creatinine is 178 µmol/L. His serum creatinine peaked at 398 µmol/L prior to renal replacement therapy. The following statement is true regarding his renal function?
B is the correct answer -
The definition of acute kidney disease is the criteria for AKI persisting for more than 7 days but less than 90 days. After 90 days, ongoing renal impairment is considered chronic and staged accordingly. This man developed AKI 10 days after admission and still has renal impairment 98 days later
a.
He has stage 1 acute kidney injury .
b.
He is now classed as having chronic kidney disease.
c.
Although he has developed acute kidney disease, he has a good chance of return to normal renal function.
d.
His acute kidney injury is ongoing with an increased risk of developing acute kidney disease and later chronic kidney disease.
e.
He is now classed as having acute kidney disease, with an increased risk of developing chronic kidney disease.
A 58-year-old man with type 2 diabetes mellitus, obesity, hypertension and chronic kidney disease has been admitted to the intensive care unit after open surgery for an abdominal aortic aneurysm. His weight is estimated at 130 kg. His baseline creatinine is 278 µmol/L and the following day he has a serum creatinine of 341 µmol/L. His urine output averages between 30 and 60 mL/h. The following is true about his renal function?
Patient has stage 1 AKI
A 72-year-old man has had an elective knee replacement. His has a significant past medical history of ischaemic heart disease, type-2 diabetes mellitus, chronic renal disease (CKD stage 3) and sleep apnoea secondary to obesity. His pre-operative serum creatinine was 172 µmol/L. His serum creatinine has increased to 220 µmol/L but he is in considerable pain and you have been asked to review his drug chart. His current medications include; ramipril, bisoprolol, furosemide, atorvastatin and doxazocin (usual medications) and ibuprofen, oral morphine, ondansetron, omeprazole and dalteparin (started since surgery). The following would be the best course of action.?
Continue the bisoprolol, stop ramipril and furosemide and review need for doxazocin. Stop the ibuprofen, change the morphine to oral oxycodone, continue the omeprazole and continue the dalteparin but with anti-Xa monitoring.
Feedback:
Reviews of drug charts can be complicated when considering acute problems on the background of chronic disease. Bisoprolol should be continued if possible because of the risk of tachyarrhythmias secondary to acute withdrawal. Ramipril should be temporarily stopped because of its potential impact on AKI although it had an overall protective effect in many cases of CKD. The need for doxazocin in the immediate post-operative period is very much dictated by the patient’s cardiac status and furosemide should be held until the patient’s fluid status is optimised peri-operatively. Its use should then be guided by the clinical status of the patient. Furosemide does not protect the kidneys from AKI.
Ibuprofen is a potent nephrotoxin and should be avoided in the peri-operative patient with additional risks of AKI (e.g. diabetes mellitus, CKD). Omeprazole is a potential nephrotoxin although most nephrotoxicity is observed after long term use. Its advantages, protecting against stress ulcers, outweigh the risk of AKI in most major peri-operative patients. Morphine has a potent renally excreted metabolite which may accumulate in renal impairment. Oxycodone is less effected by kidney injury. Low molecular weight heparins may accumulate in AKI but they can be safely used if anti-Xa measurements are used to check for accumulation.
An 82 year old woman has been admitted to intensive care with biliary sepsis. She has been in inten-sive care for 24 hours. Although she is frail with a weight of 48 kg, she has minimal past medical his-tory and no known chronic kidney disease and no further information about her is available. She has been given 4.5g piperacillin-tazobactam and has been fluid resuscitated. She is requiring norepinephrine at 0.1 µg/kg/min to maintain a mean arterial pressure of > 65 mmHg. Her urine output over the last 12 hours has averaged 20 mL/hour and her serum creatinine is 88 88 µmol l/L. The following is true regarding her renal function?
She has AKI stage 2 based on her urine output over 12 hours.
Feedback:
The urine output is low and consistent with AKI. Although the serum creatinine is only 88 µmol/L, the woman’s fragility and low weight suggest, in the absence of a past medical history of chronic kidney disease, that her baseline creatinine is likely to be low and an increase of x1.5 or of > 26.5 µmol/L is certainly possible, if not likely.
What is the definition of AKD?
AKD occurs in any patient in whom an AKI persist for more than 7 days and less than 90 days. It is not dependent on the stage of AKI observed nor on the severity of the renal impairment ongoing.
Cytochrome P450 inhibitors?
- Macrolides
Antibiotics associated with an increased risk of acute kidney injury include:
- Penicillin
- Fluoroquinolones
- Aminoglycosides
Certain co-morbidities are associated with an increased risk of developing AKI in hospital. These include?
CCF, COPD , Obesity, HTN
20% of patients admitted to hospital with heart failure will develop an AKI and the development of AKI is associated with an increased risk of mortality. COPD is an independent risk factor for the development of both CKD and AKI. Obesity may increase the risk of AKI through changes to venous blood flow and pressures and through systemic inflammation. Hypertension is an independent risk factor for AKI.
Modifiable risk factors for developing AKI include:?
- High fluid volume resuscitation
- NSAIDs
- PPI
Recovery from sepsis related AKI or AKD?
Is associated with an increased risk of mortality even if renal recovery is complete
Feedback:
Serum creatinine is a poor measure of renal function in AKI. Either SCr may be slow to recover despite improving renal function, or SCr may be falsely low, especially in longer term ICU patients in whom muscle wasting has occurred.
Approximately 50% of patients with sepsis related AKD will not have renal function return to baseline by the time they leave hospital.
Patients who have an AKI which recovers have a higher mortality than patients with no AKI.
Patients with any severity of underlying CKD are more likely to progress to more severe CKD or end stage renal failure if they suffer AKI.
The following may be considered non-modifiable risk factors for developing an acute kidney injury?
- Increasing Age
- COPD
- Afro-Caribbean
- Male gender
Feedback:
Two recent meta-analyses including one with over 6 million patients, found that men are more likely to develop HA-AKI with an odds ratio of 1.23 [1.11, 1.36] Neugarten 2018, Grams 2015)
Older age, Afro-American descent and certain chronic medical conditions increase the risk of developing AKI. Other conditions include, hypertension, diabetes mellitus, cardiac failure, ischaemic heart disease, chronic kidney disease, obesity and some forms of malignancy.
The following statements are true regarding disease related acute kidney injury?
Feedback:
The incidence of AKI sharply increases if urine output rather than serum creatinine criteria are used post major surgery. It is unclear which criteria are best for assessing peri-operative renal function since both methods are flawed.
The impact of contrast media on the progression of AKI is probably overstated in most situa-tions. The exception may be cardiac procedures where large volumes of contrast media are used but in most other cases the benefits of a proper diagnostic scan outweigh the risks to kidney function.
Anaemia is an independent risk factor for AKI but there is no evidence to support a liberal transfusion target in most patients in order to avoid AKI.
Outcome from sepsis related AKI is poorer than non-sepsis related AKI.
The following statements are true regarding renal recovery after AKI:?
- Patients who have a recurrence of AKI during their hospital admission have an increased risk of mortality at 1 year
- Patients who develop AKI and recover within 24 – 48 hours remain at increased risk of renal morbidity
- The development of both AKI and AKD, regardless of initial recovery is associated with increased risk of CKD
Feedback:
Recurrent AKI that occurred before discharge is associated with significantly increased 1- year mortality.
Patients with AKI who have a sustained recovery within 1 week of it developing have im-proved outcome compared with AKD which even if it recovers is associated with an increased risk of progression to CKD and an increased 1-year mortality.
All episodes of AKI are associated with increased risk of CKD. Patient who recover quickly most likely to do well but nevertheless risk of relapse and progression may persist.
Patients who develop AKI and AKD remain at increased risk of CKD even if their measured renal function returns to their apparent baseline.
When assessing renal recovery from AKI or AKD, the following statements are true?
- Measured creatinine clearance may be useful in determining renal recovery, particularly in patients with prolonged ICU admission
Feedback:
Although serum creatinine remains the most convenient biomarker of renal function its interpretation can be very problematic. In defining AKI and recovery a patient’s baseline serum creatinine is required. If a patient has not presented to the hospital before or if they are out of region, this information may not be available. The baseline serum creatinine for an individual may not be known and ‘normal’ serum creatinine has a wide range depending on fac-tors such as gender, body habitus, age and ethnicity. Prolonged ICU admission is associated with decreased muscle mass and an associated decline in serum creatinine. In the acute clinical setting serum creatinine does not follow renal function reliably. Interventions (e.g. fluid resuscitation) may dilute the true creatinine or increase it (e.g. trimethoprim therapy). During recovery, renal clearance may improve faster than serum creatinine decreases by several hours.
Fractional excretions of sodium and urea have not proved useful in defining renal recovery.
Urine collection and measurement of creatinine clearance may be useful in determining renal function and recovery. Collection time can be over any time period between 1 and 24 hours. 24- hour urine collections are not considered best practice in assessing AKI as renal function may change within such a period. 24-hour creatinine clearance is more suitable for assessing stable renal function. The choice of timing is dependent in part on local skills and facilities. The shorter the collection time, more accurate timing of the collection is required and more precise measurement of serum creatinine. For these reasons 4 or 8-hour urine collections are probably the optimum for clinical use outside of research.
A 66-year-old man is admitted to the ICU after a hybrid repair of a complex aortic aneurysm. He has a history of type 2 DM with stage 3b chronic kidney disease (CKD). The following are risk factors for developing an AKI:
Advanced age, the presence of CKD, radiocontrast agents, major non-cardiac surgery are all risk factors for AKI including duration of surgery
Regarding sepsis mediated AKI, which one of the following statements is most appropriate?
The inflammatory processes involved in sepsis mediated AKI are mediated by Toll-like receptors expressed on tubular and endothelial cells. Receptor activation triggers local release of additional pro-inflammatory mediators and the recruitment of infiltrating peritubular inflammatory cells.
Sepsis is characterized by systemic vasodilation, profound alterations in the macro- and micro-circulation with heterogeneity of regional blood flow distribution with decrease in functional capillary density. Despite an increase in renal blood flow, oliguria occurs and AKI can develop within hours, a dissociation between GFR and renal blood flow. Many mechanisms are responsible for septic AKI.
The correct answer is: Toll-like receptors play an important role in the pathophysiology of injury
AKI diagnosis and underlying renal pathology can poorly correlate as:
- Tubular injury in AKI is indirectly related to changes in GFR
- Urine output can be preserved or increased in moderate AKI
- In most forms of AKI in the ICU tubular necrosis is rare and cellular changes on light microscopy are subtle
feedback:
a. While the hallmark of a clinical AKI diagnosis is a rapid decline in GFR, the cellular pathology of sustained AKI is predominantly related to the renal tubule
b. Urine output may indeed persist until renal function almost ceases
c. The pathology of most AKI occurring as a component of multi-organ dysfunction thus appears to involve tubular cell injury and dysfunction more often than frank tubular necrosis
d. The leading causes of AKI in the ICU are septic shock, major surgery and cardiogenic shock
Regarding nephrotoxic AKI, which of the following are true?
- Tubular toxicity is increased by filtration and concentration of circulating toxins
- > 20% of the 100 drugs most frequently administered to adult ICU patients are classified as nephrotoxic
Feedback:
a. Nephrotoxic renal injury may recapitulate AKI pathophysiology seen in other settings, particular inflammatory pathways
b. Tubular epithelial cells are especially prone to toxic injury, as they concentrate filtered toxins along the nephron and express specific transporters that result in high intracellular uptake of toxins and their metabolites
c. The risk of contrast-“induced” AKI is smaller than previously suggested
d. Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 2002;39:930-6. PMID:11979336
Regarding the pathophysiology of AKI, which of the following are true?
- Increased afferent arteriolar resistance links tubular injury to loss of GFR
Feedback:
a. The pathology of most AKI occurring as a component of multi-organ dysfunction thus appears to involve tubular cell injury and dysfunction more often than frank tubular necrosis.
b. Established AKI: low RBF, high capsular pressure, and low/no GFR
c. The distal proximal tubules and thick ascending limb are at highest risk for ischaemic injury and tubular necrosis.
d. Afferent arteriole constriction reduces both RBF and glomerular capillary pressure in parallel and as a result GFR decreases markedly.
Regarding the pathophysiology of AKI, which of the following is true?
- Similar local inflammatory mechanism can mediate tubular injury in septic, post-surgical, ischaemic and nephrotoxic AKI
Feedback:
Inflammatory responses substantially contribute to the overall renal damage in AKI. Both innate and adaptive immune systems are involved in the inflammatory process occurring in post-ischaemic AKI. Immune cells of both the innate and adaptive immune systems contribute to the pathogenesis of renal injury after Ischaemia-reperfusion injury. These immune cells are also involved in the pathogenesis of nephrotoxic AKI
