I was a healthy young man, and I thought I was invincible before I was diagnosed with kidney disease.
Postoperative renal complications are frequent in the elderly; this is essentially due to a combination of aging processes that affect the kidney, causing reduction in renal reserves and associated conditions, that frequently occur with aging and further deteriorate renal function. Acute kidney insufficiency (AKI) is the most common. AKI is an independent risk factor for mortality, chronic kidney disease (CKD), end-stage renal disease (ESRD) and cardiovascular comorbidity.
Despite advancements in its understanding, definition and diagnosis that have occurred in recent years, AKI remains a frequent complication in geriatric surgery, mostly after cardiovascular, major non-cardiac procedures and femur fracture repair. Consequences are serious for both patients (who are exposed to increased mortality or may experience the burden of renal replacement therapy) and society, as treatment of CKD causes a significant increase in the use of healthcare services. With the recent expansion registered in geriatric surgery, it can be expected that the rate of postoperative renal complications will increase proportionally.
Acute Kidney Insufficiency
Definition and Incidence
Acute kidney injury (AKI) has been defined as “an abrupt decrease in kidney function” (Kellum and Lameire 2013). AKI globally affects 30% of hospitalized patients with a mortality rate of 60% when renal replacement therapy (RRT) is needed (Haase et al. 2011).
Two main classifications, both strongly associated with prognosis, are available for AKI: RIFLE and AKIN (Table 40.1; Kellum and Lameire 2013). They are both based on plasma creatinine and urinary output measures and are more precise than the rough practical criterium identifying AKI as urine output <200 ml in 12 h and urea levels >30 mml/l; however, they can be of limited usefulness for a prompt diagnosis in the immediate postoperative phase, mostly in cases of emergent surgery. In fact, baseline creatinine may not have been evaluated or fluid accumulation can lead to serum creatinine dilution, causing the condition to be underestimated (Haase et al. 2011).
|Classification||Stages||Serum creatinine||Urine output|
|RIFLE||Risk||1.5–1.9 times baseline||<0.5 ml/kg/hour for ≥6 hours|
|Injury||2–2.9 times baseline||<0.5 ml/kg/hour for ≥12 hours|
|Failure||≥3 times baseline or creatinine ≥4 mg/dl (≥353.6 μmol/l) with acute rise of ≥0.5mg/dl (≥44 µmol/L)||<0.3 ml/kg/hour for ≥24 hours|
|Loss||Complete loss of kidney function for >4 weeks|
|End-stage renal disease||Complete loss of kidney function for >3 months|
|AKIN||1||1.5–1.9 times baseline or ≥0.3 mg/dl (≥26.5 μmol/l) increase||<0.5 ml/kg/hour for ≥6 hours|
|2||2.0–2.9 times baseline||<0.5 ml/kg/hour for ≥12 hours|
|3||≥3.0 times baseline or ≥4.0 mg/dl (≥353.6 μmol/l) increase or initiation of renal replacement therapy||<0.3 ml/kg/hour for ≥24 hours or anuria for ≥12 hours|
An important area of research is currently aimed at identifying early biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin, not yet introduced in clinical practice (Mårtensson and Bellomo 2015, Elmendany et al. 2017).
The global incidence of postoperative AKI in the elderly population is high, particularly after cardiac surgery, where it is reported to be up to 30% (Mao et al. 2013). After major non-cardiac surgery, a 20% incidence was found (Chao et al. 2013), whereas after hip fracture repair it was reported to be 15.3% (Cagatay et al. 2012). Prognosis is severe: in-hospital mortality after postsurgical AKI in the elderly is higher than 50% (Uchino et al. 2005) and the percentage of survivors who develop CKD within two years is almost 70%. In such cases, the risk of developing ESRD is increased 40-fold, compared to elderly subjects without AKI (Ishani et al. 2009).
With aging, renal function declines progressively (see Chapters 1 and 2). A decrease in glomerular filtration rate (GFR) of 0.75–1 ml/min/year after the age of 40 has been reported. However, this decrease seems quite heterogeneously distributed among elderly people (Glassock and Winearls 2009). Many patients show a gradual decrease in GFR and renal blood flow (RBF), that are the main determinants of kidney filtration function. GFR decreases due to reduced glomerular capillary flow and reduced afferent arteriolar resistance, together with an increased glomerular capillary pressure. Together with these hemodynamic changes, structural changes also occur, consisting of loss of renal mass, hyalinization of glomerulosclerosis, tubular atrophy and interstitial fibrosis (Glassock and Rule 2012). Moreover, with aging vasoactive response to vasoconstriction becomes more intense, whereas vasodilator response is often impaired. The renin-angiotensin system is also affected by aging, predisposing to hypertension and hyperkaliemia. A decline in renal ability to concentrate and dilute sodium also occurs, leading to a higher risk of hypo or hypernatremia (Epstein 1996).
Creatinine clearance (CrCl) diminishes with aging; however, it is accompanied by a parallel reduction in total muscle mass. Accordingly, GFR may be reduced in the elderly despite normal serum creatinine values, and CrCl measurement should only be considered as an index of renal function in this population.
Age is also a risk factor for AKI because aging is accompanied by comorbidities, of which hypertension and diabetes are the most common. Both contribute to deteriorating renal function, mostly due to induced microcirculation alterations. Cardiac insufficiency may cause reduced cardiac output and renal hypoperfusion. Ischemic heart disease, anemia, inflammation, sepsis, hypovolemia and fluid overload are also associated with deterioration in renal function.
Poly-pharmacy is frequent in these patients and predisposes them to iatrogenic AKI, the main triggers of which are non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, radiocontrast media and nephrotoxic antibiotics.
When defined as an eGFR (estimated GFR) <60 ml/min/1.73 m² or as albuminuria >30 mg/g, chronic kidney disease (CKD) affects almost 50% of subjects aged 70 years or more and its prevalence is reported to increase with age (Bowling and Muntner 2012). Some authors suggest that CKD might be overdiagnosed in the elderly and that, in many patients, a moderate degree of chronic renal insufficiency (defined by an eGFR between 30 and 60 ml/min/1.73 m²) is simply due to “normal” kidney senescence (Mangione and Canton 2010). According to these authors, the thresholds defining chronic renal insufficiency should be adjusted with age. However, as in young adults, even moderate chronic renal insufficiency is associated with adverse events in the elderly, such as mortality, ESRD, cardiovascular events, AKI, infection or cognitive decline (Taal 2015).
Several factors may intervene before, during and after surgery that cause functional challenges to the kidney, such as changes in systemic blood pressure, hypo or hypervolemia, overload of kidney-eliminated drug metabolites, inflammatory response to surgical aggression, side effects of blood transfusion and others. Among all of them, hemodynamic equilibrium plays a pivotal role. In fact, “the driving force for GFR” (Mårtensson and Bellomo 2015) is the glomerular hydrostatic pressure (GHP). GHP itself is determined by both the systemic blood pressure and the tone in afferent and efferent arterioles, and is opposed to the plasma oncotic pressure on one side, and to the hydrostatic pressure in Bowman’s capsule on the other. Renal auto-regulation is also reduced in elderly patients and this exposes them to increased risk of renal damage after hypotension. These concepts offer the key to understanding the pivotal role played by hypotension in the development of AKI.
Together with age >75 years, baseline renal function was found to be an independent predictor of AKI in many studies conducted in both cardiac and non-cardiac surgery (Cagatay et al. 2012, Teixeira et al. 2014). Other risk factors are diabetes, obesity, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease and chronic renal disease. Studies also found male gender, previous coronary surgery and multimorbidity to be significantly associated with increased risk for AKI.
Prediction models based on clinical risk factors have been proposed: the Cleveland Clinic Foundation Score has been validated and is reported to be the better performer (Thakar et al. 2005, see Table 40.2).
|Clinical risk factors||Score|
|Congestive heart failure||1|
|Left ventricle ejection fraction <35%||1|
|Preopertive use of IABP||2|
|Previous cardiac surgery||1|
|Valve surgery only||1|
|Valve surgery + CABG||2|
|Other cardiac surgeries||2|
|Preoperative serum creatinine: 1.2 to 2.1 mg/dl||2|
Lowest AKI risk: sum of scored points = 0
Highest AKI risk: sum of scored points = 17
Estimating GFR in the elderly can be difficult. A valid eGFR allows accurate diagnosis of chronic renal insufficiency and appropriate drug dose adjustments. Until recently, two main creatinine-based equations were available: the Cockcroft–Gault equation and the MDRD (Modification of Diet in Renal Disease Study; Levey et al. 1999). formula. The former widely underestimates GFR in the elderly, whereas the latter is more precise (Lamb et al. 2007). Two novel creatinine-based equations are now available: the CKD EPI (Chronic Kidney Disease Epidemiology Collaboration) formula and the BIS (Berlin Initiative Sudy) equation, the latter specifically developed in an elderly population (Schaeffner et al. 2012). Other versions of these two formulae include both creatinine and cystatin C. Cystatin C is produced by all nucleated cells and is not influenced by muscle mass, which is particularly interesting in elderly subjects in whom protein-energy wasting is highly prevalent.
Presently, creatinine- and cystatin-based CKD EPI seems to offer the most accurate estimation of GFR in the elderly (Fan et al. 2015).
Intraoperative hypotension has been shown to be independently associated with increased risk of AKI in many studies, and should be avoided by careful hemodynamic management. However, the critical level of hypotension for renal damage has not been determined.
Fluid overload and venous congestion have also been recognized to be related to increased risk of AKI. In fact, high levels of central venous pressure may reduce renal perfusion and hamper ultrafiltration through increased intratubular pressure (Rajendram and Prowle 2014), especially in patients presenting with decompensated heart failure.
To reduce the consequences of hemodynamic imbalance, optimization of oxygen delivery and use of goal-directed therapy algorithms in fluid administration have been introduced in recent years (see Chapter 21). Even though several reports confirm that these strategies are effective in reducing postoperative complications, there is presently no convincing evidence that they specifically improve renal function after major surgery, compared to good standard clinical care (Schmidt et al. 2016).
In case of cardiac surgery, there may be an increased risk for AKI associated with red blood cell transfusion with hemoglobin >8 g/dl (Kinnunen et al. 2017).
In the early postoperative period, prerenal AKI and acute tubular necrosis are the most common form of AKI. However, in the days after surgery, the etiology should be precisely known, in order to provide specific treatment. Sediment examination, urinary biology and renal ultrasound are required, as shown in Figure 40.1 (Abdel-Kader and Palevsky 2009; Mårtensson and Bellomo 2015).
An important cause of relative hypovolemia in the perioperative setting is intra-abdominal hypertension (IAH). IAH occurs when intra-abdominal pressure increases to values >12 mmHg (normal range 5–7 mmHg). The elevated abdominal pressure alters renal vascularization, predisposing to AKI. Risk factors for IAH include diminished abdominal wall compliance (abdominal surgery, major trauma/burns), increased intraluminal contents (gastric distention, ileus), increased intra-abdominal contents (hemo/pneumoperitoneum, intraperitoneal fluid collections, infection, tumors, laparoscopy with excessive insufflation pressures), massive fluid resuscitation, polytransfusion, mechanical ventilation, obesity and age. If intra-abdominal pressure exceeds 20–25 mmHg, abdominal compartment syndrome may result, with multiorgan dysfunction.
A modern approach to AKI secondary to tubular necrosis should aim to avoid emergency dialysis and plan a praecox, prophylactic treatment, aimed to avoid uremic consequences. However, no specific treatment is presently available.
Indications for RRT are severe hyperkalemia, severe acidosis or fluid overload irresponsive to diuretics. The optimal timing for starting RRT is still under debate; however, instead of serum urea or creatinine cut-off values, fluid accumulation should be considered for starting RRT, as fluid overload at dialysis initiation is associated with increased mortality risk (Mårtensson and Bellomo 2015).
In cases of abdominal compartment syndrome, decompressive surgery, optimal sedation and analgesia, neuromuscular blockade and fluid restriction strategies should be considered.
Regardless of the etiology, the following basic principles should be respected:
nephrotoxic drugs should be avoided whenever possible
avoiding both dehydration and fluid overload is a major issue
hemodynamic parameters, serum creatinine and urine output should be closely monitored
dosing of renal-eliminated drugs should be adjusted (Kellum and Lameire 2013).
In prerenal AKI, volume expansion is required, except in the case of congestive heart failure or liver disease. In acute renal vascular disease affecting large vessels, anticoagulation should be started (Abdel-Kader and Palevsky 2009).
Treatment of postrenal AKI consists of urinary drainage according to the level of the obstacle. An important postobstructive diuresis frequently occurs and should be monitored to avoid development of volume depletion and serious electrolyte disorders.
It is important to preoperatively identify subjects at higher risk of AKI, with the aim of applying both optimization strategies and perioperative monitoring of renal function. ACE inhibitors and ARBs should be stopped one day before surgery and reintroduced postoperatively, according to renal function and the persistence of AKI risk factors (Haase et al. 2011).
Using hemodynamic parameters to guide intraoperative fluid administration is associated with decreased mortality and, probably, a reduced rate of postoperative AKI. The use of hydroxyethyl starch and large doses of hyperchloremic solutions promote AKI and should be avoided.
Perioperative management of patients at risk should aim to reduce all the causative factors for renal damage mentioned above, with preservation of hemodynamic stability as a priority.
High-risk patients should have serum creatinine measurements taken at least daily. In the intensive care unit, bladder catheterization is required in many cases (Kellum and Lameire 2013). When risk factors for intra-abdominal hypertension exist, intra-abdominal pressure should be monitored by the trans-bladder technique.
Several pharmacological interventions have been proposed to reduce the risk of AKI. The use of statins, aspirin and intensive glycemic control have not proven to be effective (Mårtensson and Bellomo 2014). Atrial natriuretic peptide seems promising in preventing AKI after cardiac and emergency gastrointestinal surgery, as does levosimendan, a calcium sensitizer, in cardiac surgery. However, their effectiveness needs to be assessed in large randomized control trials.
Fluid restriction strategies are not effective. In contrast, fluid overload is a risk factor for AKI (Mårtensson and Bellomo 2015).
In addition to age-related renal changes, several factors predispose elderly patients to electrolyte disorders. The age-related diminution in lean body mass leads to a 10–15% reduction of total body water, causing even smaller water balance disorders to induce greater changes in natremia. The thirst mechanism is less effective in older adults, as compared to young adults, especially in cases of hyperosmolarity. Cognitive impairment and physical disability are other risk factors for dehydration. In many cases, dysnatremia or dyskalemia is related to medical treatment, such as ACE inhibitors, NSAIDs, diuretics, intravenous hypotonic fluids or excessive salt administration. The postoperative period is marked by an increased secretion of antidiuretic hormone (ADH), renin and aldosterone, making the older adult more vulnerable to salt and water retention (El-Sharkawy et al. 2014).
Hyponatremia, defined by a serum sodium concentration <135 mEq/l, is common in older adults. Furthermore, they are more prone than young adults to hospital-acquired hyponatremia. Hyponatremia was found to be associated with gait disturbance and falls, and could be responsible for bone demineralization (Ayus et al. 2012). It was also found to be associated with increased mortality in patients admitted for orthopedic surgery (El-Sharkawy et al. 2014). Clinical manifestations include headache, nausea, vomiting, asthenia, delirium, seizures and coma. Diagnosis and management are summarized in Figure 40.2 (Adrogué and Madias 2000, Reynolds et al. 2006, Ayus et al. 2012). The most common causes in the elderly include syndrome of inappropriate ADH secretion (SIADH) and thiazides. It should be noted that the postoperative period itself can provoke SIADH.
A particular cause of hyponatremia is TURP syndrome, caused by irrigant solutions used during transurethral prostatectomy. Cerebral salt wasting syndrome is defined as a renal loss of sodium after neurosurgery or any intracranial disorders leading to hyponatremia and hypovolemia. Cerebral demyelination can occur with rapid natremia correction and is also more commonly seen in cases of alcoholism, liver disease, malnutrition, hypokalemia and hypoxia. Symptoms – which include dysarthria, dysphagia, paraparesis, seizures and coma – are generally delayed for two to six days after serum sodium elevation and are irreversible. Consequently, sodium correction should not exceed 8–12 mEq/day (Reynolds et al. 2006, Ayus et al. 2012).
Hypernatremia, defined as serum sodium concentration >145 mEq/l is less frequent than hyponatremia, but is also associated with poor prognosis (El-Sharkawy et al. 2014). It reflects an absolute or relative loss of water. Symptoms include intense thirst (that can be absent in elderly patients), anorexia, nausea, vomiting, delirium and coma. Causes leading to hypovolemia include burns, excessive sweating, gastrointestinal losses, use of diuretics, diabetic hyperosmolar state, fever, insufficient water intake and diabetes insipidus.
In cases of hypervolemia, excess hypertonic saline fluids, antibiotics containing sodium and hyperaldosteronism should be evoked.
Non-specific treatment of hypernatremia consists of intravenous hypotonic fluids, or isotonic fluids in cases of extreme hypovolemia. Sodium concentration should be diminished slowly in order to avoid convulsions and cerebral edema (Reynolds et al. 2006).
Other Postoperative Electrolyte Disorders
Potassium alterations have not been widely studied in geriatric patients undergoing surgery. However, hyperkalemia can be related to excessive potassium supplementation, potassium-sparing diuretics, NSAIDs, ACE inhibitors, β-blockers, heparin, digoxin or sulfamethoxazole, whereas hypokalemia is usually related to diuretic treatment (Luckey and Parsa 2003).
Hypocalcemia occurs in approximately 25% of patients after thyroidectomy and is mainly transitory. It is caused by impaired secretion of parathyroid hormone (PTH). A PTH decrease >65% from baseline occurring 6 hours after surgery is highly predictive of hypocalcemia. Preventive calcium and 25-OH vitamin D supplementation should start a week before surgery. Postoperatively, calcium and vitamin D administration should be continued in cases of hypoparathyroidism. The duration of treatment is defined by biological monitoring. Hypomagnesemia should be searched for and treated, as it causes resistance to PTH. Symptomatic hypocalcemia should be urgently treated by intravenous calcium gluconate (Christou and Mathonnet 2013).
Primary hyperparathyroidism is frequent in the elderly and may require surgical treatment. As with thyroidectomy, parathyroidectomy can be complicated by a transient or durable hypocalcemia. Management is identical to that following thyroidectomy (Davies et al. 2002).