Key points
- ▪
The presence of chronic or acute kidney disease has significant negative effects on surgical outcomes. Knowledge of key pathophysiologic aspects of glomerular and tubular disorders is a key component to optimal perioperative management of renal patients.
- ▪
Coexisting renal disease greatly affects management of other systems. Kidney disorders can result from systemic illness and invariably compromise other organ systems; renal patients are at especially high risk for cardiovascular complications.
- ▪
Simplified criteria for acute kidney injury emphasize changes in serum creatinine and urine output and reliably predict patient outcomes.
- ▪
Patients with pre-existing chronic kidney disease are at increased risk for acute perioperative deterioration; even mild perioperative changes in renal function can have significant outcome implications.
- ▪
Perioperative management of patients with (or at risk for) kidney injury relies on hemodynamic management and reducing adverse effects; no specific renal protection strategy has yet improved outcomes.
The kidneys are highly vascular and metabolic organs that ultrafilter the blood, excrete byproducts of metabolism, and control water and electrolyte balance. Injuries to the kidneys may involve the vasculature or the renal tissue (or both) and may be primary diseases of the kidneys or part of a multisystem disease complex, such as vasculitis, Wegener’s granulomatosis, or systemic lupus erythematosus (see also renal-related discussion in other chapters).
The three major anatomic demarcations in the kidney are the cortex, the medulla, and the renal pelvis. The cortex receives most of the blood flow and is mainly concerned with reabsorbing filtered material. The medulla is a highly metabolically active area that serves to concentrate the urine. The pelvis collects urine for excretion. Injury to any of these anatomic sites may precipitate acute kidney injury (AKI; acute renal failure), which, if persistent, may result in end-stage renal disease.
This chapter highlights specific renal diseases, including glomerular disease (e.g., nephritic syndrome) and tubulointerstitial disorders (e.g., nephritis), as well as renal effects of systemic disease and vascular involvement of the kidney. Renal replacement therapy and renal transplantation are addressed, along with perioperative management of the kidney transplant patient and general intraoperative and specific anesthetic considerations for renal patients.
Specific renal diseases
Depending on the structures involved, renal diseases are either glomerular or tubular in origin. In glomerular diseases the glomerular structures are damaged, and deposits of antigen, antibodies, and complement can be detected by microscopy. These patients typically present with various degrees of hematuria, proteinuria, and salt and water retention. In tubular diseases the tubular cell structure or the peritubular interstitium is damaged more than the glomerulus, characterized by abnormal handling of fluid and electrolytes.
Glomerular Disease
Glomerulonephritis
Glomerulonephritis accounts for approximately 7% of patients diagnosed with end-stage renal disease (ESRD) in the United States, and its importance relative to diabetes and hypertension has decreased since the 1980s. Glomerulonephritides are characterized by intraglomerular inflammation and cellular proliferation associated with hematuria with secondary renal impairment over days to weeks. Hematuria in patients with glomerulonephritis is characterized by the presence of dysmorphic red blood cells (RBCs) or RBC casts in the urine, findings that differentiate hematuria of glomerular origin from extraglomerular bleeding. Glomerulonephritis may be a primary process, with disease almost entirely restricted to the kidneys (e.g., poststreptococcal glomerulonephritis), or a secondary process occurring in association with more diffuse inflammation (e.g., systemic lupus erythematosus). Patients with glomerulonephritis generally present with one of five clinical syndromes: asymptomatic hematuria, acute glomerulonephritis, rapidly progressive glomerulonephritis, nephrotic syndrome, or chronic glomerulonephritis.
Asymptomatic hematuria refers to macroscopically or microscopically detected blood in the urine of patients who have normal glomerular filtration rate (GFR) and no evidence of a systemic disease known to affect the kidneys. Immunoglobulin A (IgA) nephropathy (mesangioproliferative glomerulonephritis) is a common cause of asymptomatic hematuria often associated with simultaneous respiratory or gastrointestinal (GI) tract infection. IgA nephropathy occurs in all age groups, with a peak incidence in the second and third decades. , Despite a mild clinical presentation with benign hematuria, ESRD ultimately develops in 20% to 40% of patients within 5 to 25 years after diagnosis. There is no cure for IgA nephropathy. In patients with proteinuria but minimal renal insufficiency, angiotensin-converting enzyme (ACE) inhibitors appear effective in preventing progressive renal functional loss. Patients at high risk of ESRD have received glucocorticoids with or without adjunctive cytotoxic agents, although efficacy remains unclear.
The renal lesion of Henoch-Schönlein purpura (HSP) is almost identical to that of the more severe variants of IgA nephropathy. However, as a small-vessel vasculitis, HSP also presents with a purpuric rash largely affecting the lower limbs, arthritis or arthralgia, and abdominal pain with or without rectal bleeding. The disease is most common in those younger than 20 years. Renal involvement can also occur in adults, who are thought to have a worse prognosis. Although the classic renal presentation is hematuria and mild proteinuria, 28% of patients in a multicenter study had nephrotic-range proteinuria at renal biopsy.
Acute glomerulonephritis is a syndrome characterized by the abrupt onset of macroscopic hematuria, oliguria, and acute renal failure (ARF/AKI). It manifests with a sudden decrease in the GFR and with fluid retention, resulting in generalized edema and hypertension. Urinary protein excretion varies widely in this syndrome, but the rate is generally less than 3 g of protein per day. Edema probably results from renal sodium retention caused by the sudden decrease in the GFR.
Poststreptococcal glomerulonephritis (PSGN) is the best known example of acute glomerulonephritis, occurring 1 to 12 weeks after streptococcal pharyngitis. It is representative of a larger group of postinfectious glomerulonephritides, such as that associated with endocarditis, in which acute glomerular injury results from immune events triggered by bacterial, viral, or protozoal infection. Glomerular injury results from an inflammatory response to glomerular deposits of IgG and C3. It remains unclear whether these deposits arise from circulating immune complexes or complexes formed in situ, or both. PSGN is an acute, reversible disease, presenting initially with gross hematuria, sharp increase in creatinine, and edema. Spontaneous resolution, seen in the vast majority of patients, is generally rapid; diuresis usually ensues within 1 to 2 weeks, and serum creatinine concentration returns to baseline within 4 weeks. PSGN predominantly affects children age 2 to 10 years, but almost 10% of patients are older then 40. , Although most patients eventually have a complete recovery, some develop hypertension, recurrent or persistent proteinuria, and chronic renal insufficiency. The long-term prognosis of patients with PSGN has been controversial. The reported incidence of chronic renal insufficiency can be as high as 20%. ,
Rapidly progressive glomerulonephritis (RPGN) is an uncommon clinical syndrome characterized by signs of glomerulonephritis (hematuria, proteinuria, and RBC casts) and a rapid decline in renal function that can lead to ESRD within days to weeks. It accounts for only 2% to 4% of all the glomerulonephritides. Although causes are heterogeneous, the pathologic hallmark of this syndrome is the presence of extensive cellular crescents surrounding most glomeruli. Crescents result from the proliferation of parietal epithelial cells and mononuclear phagocytes within Bowman’s capsule. RPGN is divided into three types: anti–glomerular basement membrane (anti-GBM), immune complex, and pauci-immune, distinguished pathologically according to the presence and character of glomerular immune deposits. Anti-GBM antibody disease is characterized by linear deposition of immunoglobulin along the glomerular basement membrane. Such deposition is the result of circulating antibodies to type IV collagen. This type of RPGN has two peaks of onset age: in the third decade, with a male preponderance, and in the sixth and seventh decades, affecting both genders equally. Associated pulmonary capillaritis (Goodpasture’s syndrome), seen in approximately one half of cases, is more common in young men, whereas isolated damage to the kidneys is more common in older patients. Lung hemorrhage is the most common cause of death during early disease and should be suspected with hemoptysis or alveolar opacities on chest radiography with coincident hemoglobin decrease.
Immune complex crescentic glomerulonephritis has a variety of causes, including PSGN, HSP, membranoproliferative glomerulonephritis, and lupus nephritis. The immune complex form of RPGN accounts for one third to one half of cases in children and young adults, but is much less common in patients older than 60. Pauci-immune RPGN, accounting for more than 50% of cases, is characterized pathologically by minimal glomerular immunoglobulin deposition. Serologically, however, these diseases are linked in about 90% of cases by the finding of antineutrophil cytoplasmic antibodies. This category is represented by microscopic polyangiitis, granulomatosis with polyangiitis (GPA, also called Wegener’s granulomatosis), and idiopathic crescentic glomerulonephritis. Microscopic polyangiitis is associated with cutaneous (purpura), neurologic (mononeuritis multiplex), or gastrointestinal vasculitis together with renal failure. Pulmonary symptoms, caused by nongranulomatous arteriolar vasculitis and capillaritis, are present in only 50% of patients. By contrast, GPA is dominated by sinopulmonary manifestations, including sinusitis, airway lesions, and nodular or cavitating lung lesions.
Unless complicated by systemic disease, RPGN typically has an insidious onset, with nonspecific symptoms such as malaise and lethargy. Urinalysis invariably demonstrates hematuria, usually dysmorphic RBCs, and moderate proteinuria; nephrotic-range proteinuria occurs in less than 30% of patients. RPGN should be treated aggressively. A delay in the diagnosis and initiation of therapy increases the risk of ESRD, and the likelihood of renal recovery is poor without therapy. Glucocorticoids and cyclophosphamide are the traditional therapeutic agents, although recent study has shown rituximab may be at least as effective as cyclophosphamide. Plasma exchange is typically used to remove circulating pathogenic autoantibodies in patients with anti-GBM antibody disease.
Chronic glomerulonephritis is a syndrome manifest by progressive renal insufficiency in patients with glomerular inflammation, hematuria, and often, hypertension. The disease may be idiopathic or associated with one of several systemic diseases, including hepatitis B or C, cryoglobulinemia, and systemic lupus erythematosus (SLE). The kidney is the organ most often affected by SLE, and lupus nephritis is one of the most serious manifestations of this autoimmune disease. The clinical spectrum of lupus nephritis ranges from mild urinary abnormalities to AKI and chronic kidney disease (CKD; chronic renal failure). This affects patients in the 20s and 30s, with black women especially predisposed. Patients complain of lethargy, arthralgia or arthritis, rashes, and symptoms of pleurisy and pericarditis in the months before presentation. Clinically significant nephritis develops most frequently within 3 years after diagnosis and rarely develops after 5 years. Asymptomatic hematuria or nonnephrotic proteinuria may be the only clues to renal involvement and should prompt further tests for other evidence of glomerular disease. Although tubulointerstitial nephritis can be a prominent component of lupus nephritis, immune complex glomerulonephritis is the primary histopathologic finding.
Nephrotic syndrome
Nephrotic syndrome presents as “heavy” proteinuria (protein excretion > 3 g/day), hypoalbuminemia, edema, and varying degrees of hyperlipidemia and lipiduria. The most common histologic lesions associated with primary nephrotic syndrome are focal segmental glomerulosclerosis, membranous glomerulopathy, minimal change disease, and membranoproliferative glomerulonephritis (MPGN). Diabetes is the most common cause of nephrosis ( Box 7-1 ). Among the nondiabetic glomerulopathies, minimal change disease accounts for the majority of the cases of nephrosis in children, whereas membranous glomerulopathy causes most of the adult cases. MPGN is a histologic finding with several etiologies and may present with nephrotic syndrome or as an acute or chronic glomerulonephritis (see earlier). Idiopathic MPGN generally affects persons between ages 5 and 30 years and has a slight female predominance. With the recognition of a causal relation between hepatitis C virus (HCV) infection and MPGN, diagnoses of idiopathic MPGN are now uncommon. Patients with HCV-associated MPGN present 10 to 15 years after infection in middle age and have subclinical liver disease with mild biochemical abnormalities. HCV is also a common cause of cryoglobulinemia. This systemic disorder has a range of renal manifestations, including nephrotic syndrome, and is characterized by malaise, anemia, peripheral neuropathy, polyarthralgia, and a purpuric rash, together with lower limb ulceration and Raynaud’s disease.
Depending on the causative disease, nephrotic syndrome may be reversible or may eventually result in renal failure, whereas other patients may respond to treatment of an underlying systemic disease or to corticosteroid and immunosuppressant therapy. ACE inhibitors are often used in both hypertensive and nonhypertensive patients because these agents are known to limit urinary protein loss.
Fluid management can be particularly difficult in patients with nephrotic syndrome, and assessment of volume status may require invasive monitoring. Low plasma oncotic pressure causes diffuse interstitial edema because of fluid leakage from the intravascular space and may result in low intravascular volume, particularly in patients undergoing aggressive diuretic treatment. In cases of reduced GFR and less severe hypoalbuminemia (e.g., > 2 g/dL), however, volume overload caused by enhanced sodium and water reabsorption at the tubular level may be the primary driver of edema. In these patients, diuretic therapy may be necessary. However, patients with nephrotic syndrome tend to respond poorly to diuretics, perhaps because protein binding of drug is decreased in plasma, resulting in increased volume of distribution. Therefore, higher and more frequent diuretic doses, or the combined use of loop and thiazide diuretics, may be needed. limited data suggest that coadministration of intravenous (IV) albumin and loop diuretics may improve diuresis compared with diuretics alone.
The pharmacokinetics of other drugs with high protein binding, including most anesthetic drugs, are also affected by the low proteinemia of nephrotic syndrome, and doses should be reduced accordingly.
Patients with nephrotic syndrome have a particularly high frequency of cardiovascular disease and should undergo a thorough cardiac evaluation before higher-risk surgeries. In fact, altered apolipoprotein metabolism causes hyperlipidemia, whereas loss of anticoagulant plasma proteins leads to a hypercoagulable state. One study of nephrotic syndrome patients estimated a 1%/yr risk of venous thromboembolic events and a 1.5%/yr risk of arterial thromboembolic events, with the greatest risk concentrated in the first 6 months after diagnosis (~ 5% and ~ 3%, respectively). These patients require diligent prophylactic anticoagulation with heparin and compressive devices in the perioperative period ( Box 7-2 ).
Establish cardiac risk stratification.
Measure albumin concentration.
Assess volume status, and consider invasive monitoring.
Reduce doses of drugs with high protein binding.
Provide venous thromboembolism prophylaxis.
Tubulointerstitial Disease
Nephritis
Acute interstitial nephritis is characterized by a peritubular inflammation causing renal insufficiency, sterile pyuria, and leukocyte casts ( Table 7-1 ). Hematuria and proteinuria are also observed but are of lower degree than in glomerular diseases. Altered sodium reabsorption and reduced urine-concentrating ability are more frequently seen than edema and hypertension. Systemic manifestations such as rash, fever, and peripheral eosinophilia are often observed. Acute interstitial nephritis is caused by drugs, particularly antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), but can also be caused by infectious and autoimmune diseases. Discontinuation of the inciting agent usually results in renal recovery, but corticosteroids may be necessary in some patients.
| Type | Signs |
|---|---|
| Acute interstitial nephritis | Sterile pyuria Leukocyte casts Eosinophiluria Eosinophilia |
| Chronic tubulointerstitial nephropathy | Polyuria Acidosis Hyperkalemia |
| Pyelonephritis | Pyuria, bacteriuria Signs of infection Flank pain |
Pyelonephritis is an acute interstitial inflammation caused by a bacterial infection. Fever and signs of acute infection are usually observed, although the inflammatory response can be blunted in elderly and immunosuppressed patients. Pyelonephritis can be a cause of septic shock, particularly in hospitalized patients.
Nephropathy
Chronic tubulointerstitial nephropathy is a slowly evolving interstitial inflammation and is a relatively common cause of chronic kidney disease (renal failure). Patients usually have pyuria, mild proteinuria, and minimal or no hematuria. Tubular dysfunction characterizes this disease, with hyperkalemia, nongap metabolic acidosis, and polyuria. Chronic tubulointerstitial nephropathy can be caused by chronic ingestion of NSAIDs and acetaminophen, as well as by other drugs (e.g., cyclosporine, tacrolimus), toxins, autoimmune disease, and neoplastic disorders.
Disorders of Tubular Function
Bartter’s syndrome (juxtaglomerular cell hyperplasia) is characterized by sodium (Na + ), chloride (Cl − ), and potassium (K + ) ion wasting. It is caused by a rare autosomal recessive genetic defect of the Na + , K + , 2Cl − transporter in the thick ascending limb of the loop of Henle. The two forms of Bartter’s syndrome are neonatal, characterized by polyhydramnios, and classic, with onset at age 2 to 3 years and characterized by polyuria, failure to thrive, and vomiting. Patients present with findings similar to loop diuretic effects, with hypokalemia, hypochloremic metabolic alkalosis, and increased urinary Na, K, and Cl concentrations. Patients are not hypertensive, although renin, angiotensin, and aldosterone levels are elevated; renal prostaglandin production is typically increased. Patients with Bartter’s syndrome are treated acutely with saline infusion and potassium supplementation. The syndrome responds to chronic inhibition of prostaglandin synthesis, probably because cortical blood flow is reduced.
Gitelman’s syndrome is an autosomal recessive disorder of the Na + , Cl − transporter in the distal convoluted tubule that mimics the effect of thiazide diuretic use. It has similar features to Bartter’s syndrome, but Gitelman’s has a later onset and is characterized by hypocalciuria and hypomagnesemia.
Liddle’s syndrome is an autosomal dominant disorder characterized by constant activation of the epithelial sodium channel in the collecting tubule despite low aldosterone levels, resulting in excess sodium reuptake and potassium wasting. Patients present in their teenage years with symptoms similar to those caused by mineralocorticoid excess, including hypertension, polyuria, failure to thrive, and hypokalemia. Treatment includes salt restriction, potassium supplementation, and lifelong administration of triamterene or amiloride.
Pseudohypoaldosteronism type I (PHA-I) is an autosomal dominant resistance to the action of aldosterone, characterized by renal sodium loss and decreased sodium concentrations in sweat and saliva. The levels of aldosterone and its metabolites are typically increased, distinguishing it from true hypoaldosteronism. The onset of PHA-I is in early life, with failure to thrive, vomiting, and hyponatremia. Respiratory tract infections are common and resemble cystic fibrosis. Treatment mainly consists of sodium supplementation and is particularly important during periods of stress, such as illness or surgery.
Fanconi’s syndrome is a global dysfunction of the proximal tubules, resulting in urinary loss of amino acids, glucose, bicarbonate, Na, K, and phosphate. The main clinical manifestations are growth retardation, rickets, hyperchloremic type II renal tubular acidosis, polyuria, dehydration, and symptomatic hypokalemia. Fanconi’s syndrome has multiple causes leading to dysfunction of different tubular channels. Etiology may be genetic (cystinosis, Wilson’s disease, galactosemia, glycogenosis) or acquired (heavy-metal poisoning, tetracycline, chemotherapeutics). Treatment involves sodium and fluid replacement, correction of acidosis and hypokalemia, vitamin D and phosphate supplementation, and correction of the underlying causes when possible. Cystinosis usually evolves to ESRD within 10 years of diagnosis. The early use of cysteamine decreases lysosomal cystine and delays the evolution of renal failure, avoiding renal transplant in some patients.
Renal tubular acidosis (RTA) represents a group of differing renal tubular defects that share abnormalities of Na and Cl handling. Normal renal function, and indeed control of acid-base balance, requires the kidney to excrete a net load of Cl − over Na + because dietary intake of these ions is similar. In RTA the nephron excretes insufficient Cl − , reducing the strong ion difference and resulting in nongap metabolic acidosis.
Proximal renal tubular acidosis (type II) is a problem of Na and Cl handling in the proximal tubule, leading to hypokalemic nongap metabolic acidosis. The most common cause is urinary excretion of light chains associated with multiple myeloma (occult or overt), but it can also be caused by carbonic anhydrase inhibitors or occur as part of Fanconi’s syndrome. Proximal RTA is defined by the inability to acidify the urine below a pH of 5.5. In some cases there is excess urinary elimination of sodium and its companion anion bicarbonate because of mutations in the gene SLC4A4, encoding the Na + /HCO 3 − cotransporter NBC-1, resulting in limited ability to excrete chloride. The diagnosis of RTA-II can be confirmed by urine alkalinization to more than 7.5 after an IV sodium bicarbonate load. Treatment is by Na administration as sodium acetate or sodium bicarbonate. In adults, if mild, acidosis may not require treatment because it is naturally self-limiting; as the plasma bicarbonate concentration falls, the mid- and distal nephron can reabsorb enough of the reduced filtered bicarbonate load to maintain acid-base balance.
Hypokalemic distal renal tubular acidosis (type I) is caused by an abnormality of chloride excretion in the distal tubule. There is a parallel reduction in the excretion of NH 4 . In its autosomal dominant form, distal RTA is associated with mutations in the gene encoding the Cl − /HCO 3 − exchanger AE1 or band 3 protein. In adults, it is most often seen in association with autoimmune diseases, classically Sjögren’s syndrome. Patients with RTA-I have severe metabolic acidosis with serum bicarbonate levels close to 10 mmol/L and are unable to acidify urine to less than a pH of 5.5. Several mechanisms for hypokalemia have been postulated, but the underlying cause has not been established. Patients frequently present with kidney stones caused by hypercalciuria, which is caused by increased calcium mobilization from bone buffers. Compared with proximal RTA, patients with distal RTA require a much lower dose of alkali replacement because treatment does not result in a substantial bicarbonate diuresis.
Hyperkalemic distal renal tubular acidosis (type IV) is caused by impaired excretion of both Cl − and K + in the distal tubule, leading to nongap acidosis and hyperkalemia. The underlying cause is either aldosterone deficiency or tubular resistance to aldosterone. The former occurs in chronic renal insufficiency, especially diabetic nephropathy, from inadequate renin secretion. Other notable causes of RTA-IV include primary adrenal insufficiency, congenital adrenal hyperplasia, and several medications (e.g., NSAIDs, cyclosporine, trimethoprim, potassium-sparing diuretics).The acidosis is usually mild, with serum bicarbonate concentrations above 17 meq/L. Urine pH is usually lower than 5.5, unlike RTA types I and II. Patients with RTA-IV need treatment when the hyperkalemia is significant. Use of fludrocortisone, thiazides, and sodium bicarbonate can be considered.
Renal Cystic Disease
Renal cysts can be observed in a significant percentage of the population and are usually asymptomatic. Polycystic kidney is a severe inherited disease that can be transmitted in an autosomal recessive or dominant manner. The recessive form has an incidence of 1 in 20,000 live births and usually results in perinatal death from extreme renal enlargement causing pulmonary compression and hypoplasia. The dominant form occurs in 1 of 800 live births and results in significant disease by adult age. The pathogenesis involves alteration in the synthesis of the tubuloepithelial membrane receptor polycistin. At age of presentation, the kidneys are massively enlarged, and patients complain of flank pain, hypertension, hematuria, and recurrent pyelonephritis. This disease leads to ESRD in 50% of cases. About 10% of patients also have cerebral arterial aneurysms, and cysts may form in other organs as well. Therapy includes management of hypertension, prevention of kidney infections, and renal transplantation. Some patients may require nephrectomy because of recurrent severe pyelonephritis or discomfort from the megakidney.
Renal Involvement in Systemic Disease
Hypertension and diabetes
Long-standing, poorly controlled hypertension frequently causes renal dysfunction and accounts for about 20% of ESRD cases. African American ethnicity is a particular risk factor for this complication. Hypertension initially causes functional alterations in the renal circulation, with rightward displacement of the autoregulatory curve ( Fig. 7-1 ), followed by permanent histologic changes at the arteriolar level. When autoregulation is completely lost, both systemic hypotension and hypertension may result in worsening renal function. High glomerular intravascular pressures cause increased capillary permeability and proteinuria, whereas low blood pressure (BP) results in renal cell ischemia.
Accelerated hypertension is a particular condition in which an extremely elevated BP causes significant acute kidney injury characterized by marked proteinuria. The goal in the management of these patients is to obtain an acute reduction in mean arterial pressure of approximately 25%, followed by further reductions over weeks. In patients who present with accelerated hypertension, excessively rapid correction of BP can lead to renal ischemic injury.
Diabetes mellitus is the most important cause of ESRD. Although type 1 diabetes is more frequently associated with renal involvement, the prevalence of patients with type 2 diabetes and renal disease has increased, probably because of their longer survival. Diabetic nephropathy is characterized by proteinuria, the extent of which predicts the onset and the outcome of renal insufficiency. Proteinuria not only is a marker of renal disease but also contributes to causing further renal damage. In fact, in animal models, excessive tubular reabsorption of protein may cause interstitial inflammation, scarring, and fibrosis.
Poorly controlled BP, hyperglycemia, and hypercholesterolemia are risk factors for the development of diabetic nephropathy and therefore must be controlled to prevent or limit diabetic kidney disease. Improved glycemic control has been shown to reduce the incidence of diabetic nephropathy. Strict BP control has beneficial effects on the kidney in diabetic patients, and its benefit is probably higher for those patients with significant proteinuria.
Although the BP goal can be reached with any agent, ACE inhibitors are more effective in slowing nephropathy than other classes of antihypertensive drugs, both in diabetic and in nondiabetic patients. This effect of ACE inhibitors is probably related to their ability to reduce or prevent proteinuria. Similar renoprotective effects are seen with angiotensin receptor blockers. The use of ACE inhibitors in patients with compromised renal function is often associated with a moderate increase in serum creatinine and potassium levels. This effect should be seen as a normal response to decreased BP and a marker of drug effectiveness rather than a sign of deterioration of renal function and an indication to discontinue ACE inhibitor therapy. Calcium channel blockers also have beneficial effects on renal function, although they do not appear to be as renoprotective as ACE inhibitors in African Americans with hypertensive nephropathy. Additional measures proposed to slow the progression of chronic diabetic and nondiabetic nephropathy are dietary protein intake restriction, smoking cessation, and lipid-lowering medications.
Sickle cell disease
Sickle cell disease is the cause of a significant nephropathy with hematuria, papillary necrosis from occlusion of vasa recta, AKI from renal hypoperfusion or rhabdomyolysis, and CKD from glomerulosclerosis. Proteinuria is detected in a high percentage of patients. An inability to concentrate urine is the hallmark of sickle cell nephropathy, resulting from loss of the countercurrent exchange mechanism caused by loss of perfusion to the vasa recta. The intraoperative management of patients with sickle cell nephropathy should follow the general recommendations on sickle cell management, with additional care to avoid renal hypoperfusion.
Vascular Disease of Kidney
Chronic atherosclerotic stenosis of the renal arteries is a relatively common condition in the older population with extrarenal atherosclerosis on angiographic studies. Renal artery stenosis can cause progressive ischemic nephropathy and, when bilateral, results in significant renal dysfunction. However, this condition is often underdiagnosed, mainly because specific chemical markers of renal ischemic disease are lacking. Most often, the diagnosis is made by radiologic investigations such as duplex ultrasonography, angiography, computed tomography (CT), or magnetic resonance imaging (MRI) angiography. Although renal artery atherosclerosis is often associated with systemic hypertension, correction of the stenosis does not always result in BP normalization, because hypertension is more likely to be essential in the majority of cases. Thrombosis of the renal artery may complicate pre-existing stenosis or may be caused by hypercoagulability, trauma, or aortic dissection; and it can precipitate AKI/ARF. Fibromuscular dysplasia of the renal artery, a noninflammatory nonatherosclerotic stenotic condition, occurs mainly in young women and still has no known causes. Unlike atherosclerotic stenosis, this condition rarely causes renal failure, and hypertension in these patients is most likely of renovascular etiology.
Medical management of renal artery stenosis centers on control of hypertension, with ACE inhibitors the drugs of choice, although inhibition of angiotensin-mediated efferent tone may precipitate renal failure in patients with bilateral renal artery stenosis and should be carefully monitored in these patients, especially if used with a diuretic. Surgical correction of renal artery stenosis is aggravated by a significant rate of complications, particularly in patients with coexisting aortic disease, and is probably not indicated in patients with advanced nephropathy. The use of percutaneous angioplasty and stenting has emerged as an attractive alternative to the surgical corrective approach.
Renal Failure
The terms acute renal failure (ARF) and chronic renal failure (CRF) are classified here as, respectively, chronic kidney disease and acute kidney injury.
Chronic Kidney Disease
Chronic kidney disease has become increasingly frequent in the western world ; the population of patients with ESRD requiring dialysis has tripled over the past 19 years and is projected to increase to more than 500,000 by 2020 ( Fig. 7-2 ). These patients’ prevalent mortality has been steadily declining but is still approximately 200 deaths per 1000 patient-years. , The prevalence is higher in advanced ages and in certain ethnic groups (e.g., African American, Native American). Recent studies have detected an extremely high rate of mild to moderate renal dysfunction in the U.S. population, particularly in elderly persons ( Fig. 7-3 ). These patients are at risk for progression to CKD if further kidney damage is superimposed.
A significant number of patients with CKD undergo surgery for reasons that may or may not be related to kidney disease; therefore, understanding the pathophysiology and the clinical management of these patients is crucial for the anesthesiologist. In fact, CKD significantly complicates perioperative management and impacts surgical outcomes. In patients with CKD necessitating dialysis, mortality rates of 4% after general surgery and of 10% after cardiac surgery have been reported, with morbidity rates approaching 50%. This increased rate of complications probably results from the low renal reserve of patients with CKD and their reduced ability to respond to the stress, fluid load, and tissue trauma caused by surgery. However, morbidity increases with the organ dysfunction and coexisting disease often found in these patients.
Pathophysiology
Many different renal and extrarenal pathologic conditions result in the loss of glomerular function as their “final common pathway.” Renal dysfunction is progressive and usually divided in stages according to the GFR ( Table 7-2 ). Proteinuria is also used as an index of the severity of kidney disease and can be used to predict renal survival. The loss of GFR can be accelerated by events such as intercurrent diseases, nephrotoxins, and surgery. Eventually, ESRD is reached when the GFR decreases below a critical point and the kidney is unable to maintain homeostasis unless renal replacement therapy is initiated.
| Stage | Description | Creatinine Clearance * | Metabolic Consequences |
|---|---|---|---|
| 1 | Normal or increased GFR— people at increased risk or with early renal damage | >90 | |
| 2 | Early renal insufficiency | 60-89 † | Concentration of parathyroid hormone starts to rise (GFR ~ 60-80) |
| 3 | Moderate renal failure (chronic renal failure) | 30-59 | Decrease in calcium absorption (GFR <50) Lipoprotein activity falls Malnutrition Onset of left ventricular hypertrophy Onset of anemia (erythropoietin deficiency) |
| 4 | Severe renal failure (pre–end-stage renal disease) | 15-29 | Triglyceride concentrations start to rise Hyperphosphatemia Metabolic acidosis Tendency to hyperkalemia |
| 5 | End-stage renal disease (ESRD, uremia) | <15 | Azotemia develops |
* Approximate glomerular filtration rate ( ∼︀ GFR); mL/min/1.73 m 2 .
When renal tissue is lost, surviving nephrons undergo adaptive changes, with tubular hypertrophy, afferent vessel vasodilation, and increased glomerular blood flow. By increasing tubular excretion or reabsorption of water and solutes, these changes allow the remaining nephrons to compensate for lost tissue and to maintain near-normal handling of the glomerular ultrafiltrate. On the other side, these same changes seem to accelerate the progression of kidney disease. Glomerular capillary hypertension from afferent vasodilation causes glomerulosclerosis, increased endothelial permeability, and proteinuria, which probably promotes further renal damage; 43,61 excessive tubular reabsorption of urinary protein may cause peritubular inflammation, scarring, and fibrosis.
A progressive inability to maintain tight control of body fluid composition follows the exhaustion of renal compensatory mechanisms. Patients with low GFR are prone to sodium accumulation and hypervolemia because they may not be able to excrete the equivalent of their sodium intake. When the regulation of urine osmolality and free-water excretion is impaired, changes in water intake may cause sodium concentration abnormalities. Inability to excrete potassium by the distal tubule results in K + accumulation. Patients with CKD usually tolerate significant hyperkalemia, partly from increased intestinal excretion. However, acute processes such as acidosis, surgery, and tissue necrosis can trigger rapid increases in serum potassium and cause life-threatening arrhythmias. Decreased phosphate excretion causes accumulation of this electrolyte and its precipitation in tissues, together with calcium. Hypocalcemia is also caused by deficient renal production of vitamin D and by lower intestinal absorption of calcium, and it results in secondary hyperparathyroidism, bone resorption, and renal osteodystrophy.
Patients with CKD develop a metabolic acidosis that is initially associated with hyperchloremia and normal anion gap. When renal failure becomes severe, inability to excrete titratable acids causes an increased anion gap.
The uremic syndrome characterizes renal decompensation and is caused by accumulation of catabolic byproducts. Although the severity of uremia is usually quantified from blood urea nitrogen (BUN) levels, uremic syndrome is caused by accumulation of different substances and several hormonal and metabolic defects. Central nervous system (CNS) manifestations may range from personality changes to coma and seizures, with onset related more to the rapidity of the onset of azotemia than to its absolute level. Peripheral and autonomic neuropathies are relatively common and cause sensory loss, gastroparesis, and sympathetic dysregulation. Uremia causes gastric mucosal irritation and gastric ulcers in a significant fraction of patients who have uncompensated CKD. Uremic patients have a bleeding diathesis even when coagulation times are normal. This bleeding tendency is caused by a platelet dysfunction resulting from inadequate release of von Willebrand factor and factor VIII by the endothelial cells. Renal failure may also cause a predisposition to thrombosis from hyperfibrinogenemia, antiphospholipid antibodies, hyperhomocysteinemia, and anticoagulatory protein C deficiency. Patients with CKD typically have significant anemia, mainly caused by deficient production of erythropoietin, although GI bleeding and iron deficiency may contribute.
Multiple cardiovascular derangements are associated with CKD. Hypertension usually results from fluid overload but also neuroendocrine imbalance. Patients with CKD often have significant left ventricular (LV) hypertrophy and enlargement, associated with systolic and diastolic dysfunction, and are prone to heart failure. Anemia significantly contributes to the adverse effects of CKD on the cardiovascular system, by increasing cardiac output and myocardial oxygen demand and by causing LV hypertrophy and enlargement. Uremic pericarditis occurs infrequently in dialysis patients but should be considered because its presence can be complicated by pericardial hemorrhage and tamponade.
Clinical Presentation
Patients with CKD often present with a history of a known kidney disease that has been medically managed along its evolution and that has relatively controlled manifestations. Therefore, many patients with CKD present in a compensated state and with relatively mild symptoms. Vague malaise or nocturia may be the only complaints. However, some patients may present with the signs and symptoms of acute renal decompensation and uremic emergency ( Table 7-3 ), a condition that should be rapidly addressed by a nephrologist and that often requires emergent initiation of hemodialysis. This is more likely in patients with rapidly progressing or unrecognized renal disease. In other patients, an acute event or illness may overcome the residual renal reserve or cause further kidney damage, precipitating acute kidney injury on CKD ( Box 7-3 ).
| Emergency | Signs |
|---|---|
| Fluid overload | Hypertension, pulmonary edema, peripheral edema |
| Electrolyte imbalance | Hyperkalemia, hyponatremia, hypocalcemia |
| Acid-base abnormalities | Increased anion gap, hyperchloremia, low plasma CO 2 , hyperventilation |
| Encephalopathy | Seizures, coma, decreased airway reflexes, obtundation |
| Systemic hypoperfusion | Congestive heart failure, cardiac tamponade |
| Bleeding diathesis | Normal platelet count and coagulation times, increased bleeding times |
- ▪
Dehydration
- ▪
Infection
- ▪
Uncontrolled hypertension
- ▪
Renal disease exacerbation
- ▪
Heart failure
- ▪
Nephrotoxins
- ▪
Urinary obstruction
- ▪
Major surgery
Patients receiving chronic dialysis usually present in a relatively compensated state, but they may have signs of hypovolemia if fluid removal has been overzealous. When either the dose or the timing of dialysis is inadequate ( Box 7-4 ), some of the clinical manifestations of uremia resurface. Pericardial effusions caused by uremic pericarditis are slow to evolve and rarely result in tamponade, but they should be suspected in the presence of hypotension, pulsus paradoxus, and jugular vein enlargement.
Anorexia, nausea, vomiting, diarrhea
Peripheral neuropathy
Weakness, poor functional status
Decreased alertness
Ascites, pericarditis
Hypertension, fluid overload
Persistent anemia despite erythropoietin
Minimal urea reduction with dialysis
Anemia accounts for many of the symptoms and signs observed in CKD patients, such as malaise, low exercise ability, decreased mental acuity, LV dilation, and hypertrophy. Improvement in such symptoms has been reported if anemia is corrected by erythropoietin administration. A major clinical trial in patients with CKD, however, demonstrated that normalizing hemoglobin levels (> 13 g/dL) with erythropoietin versus a rescue approach (treating only when level < 9 g/dL) only modestly improved symptoms while significantly increasing the risk of stroke. As such, the risks of erythropoietin for mild anemia in this population may outweigh the benefits.
Patients who are not receiving dialysis are typically undernourished because of anorexia and hypercatabolism associated to CKD. Additionally, some patients may be receiving a low-protein diet as an attempt to delay the need for dialysis and to limit the progression of renal disease. The protein weight loss is often masked by the increase in body water content. Patients who do receive dialysis should be fed an adequate amount of protein, because currently available dialysis systems afford efficient solute-clearing capabilities, and protein intake limitation is unnecessary. The clinical manifestations of renal osteodystrophy are usually evident only when bone and renal disease are advanced and include bone and joint pain, lytic lesions on radiographs, and occasionally, spontaneous bone fractures. Growth retardation and bone deformities are common in children. Pruritus is common in patients with severe kidney disease, particularly in those on dialysis, and is probably caused by calcium precipitation in the skin.
Patients receiving hemodialysis have a surgically created access that can consist of a native arteriovenous (AV) fistula or a synthetic graft. Some patients may present with a hemodialysis catheter placed in a central or femoral vein. Dialysis access sites are at high risk of clotting and infection and should be inspected for patency and local irritation. Long-term dialysis patients have a long history of peripheral and central cannulation and may present a challenge for central access.
Differential Diagnosis
Any diseases that damage the kidney at the glomerular or tubular level may progress to CKD. Diabetes and hypertension are by far the most important causes of ESRD in the United States, accounting together for more than 60% of cases. Glomerular diseases and tubulointerstitial diseases cause 18% and 7% of cases, respectively, followed by cystic kidney disease (5%).
The differential diagnosis is usually straightforward and based on history, imaging, and laboratory analysis ( Box 7-5 ). Renal biopsy is indicated in patients with unexplained CKD who do not have atrophic kidneys on ultrasound and in patients with nondiabetic nephritic syndrome. Establishing a differential diagnosis is important, especially when the condition causing renal failure can be controlled and further renal damage can be prevented, such as with vasculitis, drug-induced nephropathy, autoimmune disease, renal ischemia, and infectious diseases.
Diabetes
Hypertension
Glomerulonephritis
Cystic kidney disease
Ischemic renal disease
Pyelonephritis
Analgesic nephropathy
Hereditary diseases
Autoimmune diseases
Vasculitis
Given the high prevalence of diabetes and hypertension in patients with CKD, it is not surprising that the most important comorbidities associated with CKD involve the cardiovascular system ( Box 7-6 ). Cardiac disease is the most important cause of death in patients with ESRD. Congestive heart failure is present in 40% of patients receiving dialysis and is an important predictor of death. About 75% of CKD patients have LV hypertrophy and diastolic dysfunction at initiation of dialysis. LV dysfunction improves with dialysis, correction of anemia, and renal transplant. Coronary artery disease (CAD) is common in patients with CKD, with a reported prevalence of 40%, and is an important cause of LV dysfunction and mortality. The “classic” risk factors contribute to prevalence of CAD, but CKD itself might be an independent risk factor; significant CAD is also observed in CKD patients who are neither hypertensive nor diabetic.
- ▪
Hypertension
- ▪
Diabetes
- ▪
Coronary artery disease
- ▪
Congestive heart failure
- ▪
Dyslipidemia
- ▪
Peripheral vascular disease
- ▪
Immune depression
Hypertension is almost universal in renal failure, whether a pre-existing causative factor or secondary manifestation of fluid overload and endocrine dysregulation. Hyperlipidemia is highly prevalent in CKD patients, manifesting with increases in triglycerides (TGs) and very-low-density lipoproteins (VLDLs) and decreased high-density lipoproteins (HDLs). Patients with nephrotic syndrome have a 90% prevalence of hypercholesterolemia. Control of hyperlipidemia is important not only to decrease CAD risk but also to reduce proteinuria and help preserve glomerular function.
Patients with advanced kidney disease are particularly prone to infections and delayed wound healing and may not respond to certain immunizations, such as hepatitis B. This is partly caused by malnutrition but also by specific deficiencies in humoral and cell-mediated immunity, such as impaired phagocytosis, defective lymphocyte function, and impaired antibody response. Hemodialysis does not completely correct this immunodeficiency and adds risk of infection.
Preoperative evaluation and preparation
The preoperative evaluation of the patient with CKD should start with a thorough history and physical examination, focusing on the comorbidities associated with kidney diseases and the signs and symptoms of uremia, fluid overload, and inadequate dialysis. Laboratory studies should assess electrolyte concentrations, acid-base status, urea and creatinine levels, hematocrit, platelet count, and coagulation. Electrolytes should not be measured immediately after dialysis because of incomplete equilibration between plasma and intracellular fluids. Platelet dysfunction is not related to a low platelet count and can be detected only with bleeding time, measured as the time to cessation of hemorrhage after a standardized skin incision. However, this test seems to have a limited predictive value for clinical bleeding and is used infrequently. Patients who are receiving adequate dialysis are less likely to have significant platelet dysfunction, and their risk of bleeding should not be excessive. A chest radiograph is usually ordered to rule out fluid overload, although probably not in younger patients who are adequately dialyzed, have good exercise tolerance, and are having lower-risk surgeries. An electrocardiogram (ECG) is obtained to screen for changes caused by myocardial ischemia and by electrolyte abnormalities.
The cardiac risk stratification of patients with CKD is not straightforward. In fact, the sensitivity and specificity of symptoms such as chest pain and reduced exercise tolerance are decreased compared with the population without renal disease. Silent myocardial ischemia is relatively common because of the frequency of diabetes and autonomic neuropathy, whereas dyspnea on exertion may be caused by fluid overload. The classic signs of congestive heart failure may be absent in patients who have ventricular dysfunction but are receiving adequate dialysis. The cardiac evaluation of CKD patients is further complicated by the lesser accuracy of noninvasive evaluation in this population. In renal transplantation candidates, myocardial scintigraphy and dobutamine stress echocardiography had less than75% sensitivity for significant CAD on angiography and had poor predictive power for myocardial events. Therefore, in CKD patients undergoing higher-risk surgeries, the threshold for requesting a cardiac evaluation and for obtaining a coronary angiogram should be lower than in the nonrenal population. One group proposed that renal transplantation candidates who are asymptomatic for myocardial ischemia but have diabetes or are older than 50 undergo noninvasive cardiac evaluation, followed by coronary arteriography and revascularization if indicated. According to this same algorithm, patients who are symptomatic for ischemia or heart failure should receive an invasive evaluation. Although no evidence is available in patients undergoing nontransplant surgeries, it is reasonable to follow a similar approach for procedures with similar and higher risk. The outcomes of revascularization in patients with CKD are worse compared with the remaining population. Percutaneous balloon angioplasty has a higher rate of restenosis in renal than in nonrenal patients, although better results have been obtained with stent placement. Coronary artery bypass graft (CABG) surgery in CKD patients carries higher perioperative morbidity and mortality, but patients may have a lower rate of restenosis and better long-term survival than those with angioplasty.
In preparation for elective surgery, patients with ESRD should receive dialysis the day before surgery. This is essential to achieve a volume status as close to normovolemic as possible, to allow the patient to tolerate fluid loads associated with surgery, and to obtain normal electrolyte concentrations. On the other hand, excessive fluid removal may cause hypovolemia and predispose the patient to intraoperative hemodynamic instability. The dialysis records, when available, can help to assess the adequacy of dialysis. Urea should decrease more than 65% during a dialysis session. Dry weight, defined as the lowest weight tolerated in absence of hypovolemic symptoms, is recorded to monitor the efficacy of fluid removal and ideally should be relatively stable over time, with 3% to 4% weight gain between sessions. Dialysis should not be performed immediately before surgery because of the possibility of rapid fluid shifts and hypokalemia. In the case of emergent surgery, it may be possible to proceed without dialysis if a minimal weight gain between treatments is documented; however, patients with signs of fluid overload or with life-threatening hyperkalemia may need emergent dialysis before the operation if time allows. Otherwise, patients need to be managed medically and receive dialysis after the operation. Significant hyperkalemia, when present, can be temporarily controlled with pharmacologic means. Intraoperative use of ultrafiltration is relatively common during on-pump cardiac surgery, and it also has been reported during noncardiac surgery. Potassium levels above 5.5 mEq/L are usually considered a contraindication to elective surgery because tissue trauma and cell death can cause potassium to increase to life-threatening levels. Hypokalemia should not be treated unless at life-threatening levels.
Blood pressure should be optimized before elective surgery. Current recommendations for long-term CKD management set a BP goal below 130/80 mm Hg. Hypertension in CKD patients is usually volume dependent and responds to adequate dialysis, but most patients also require pharmacologic therapy. Perioperative beta-adrenergic blockers should be considered for patients at increased cardiac risk. Hypertension management is important not only for myocardial protection but also because the use of certain antihypertensive drugs (ACE inhibitors, angiotensin receptor blockers) has been shown to limit the evolution of renal disease.
Control of anemia is important because anemia is an important cause of LV hypertrophy, heart failure, and angina. Hematocrit should be optimized before surgery. For ambulatory ESRD patients, hemoglobin of 11 to 12 g/dL is considered optimal ; this value is also used as a target before surgery, although this practice is not supported by clinical evidence. The target hemoglobin level can be achieved by increasing erythropoietin administration if time allows or by transfusion for urgent surgery. Correction of anemia also helps to improve the platelet dysfunction of renal failure. If platelet dysfunction is suspected or documented, it can be treated by administration of desmopressin or cryoprecipitate, both of which increase the level of von Willebrand factor and improve the interaction between platelets and endothelial cells. Their onset of action is rapid, which renders both drugs useful intraoperatively. However, the prolonged use of desmopressin is limited by induction of tachyphylaxis. Estradiol is also effective in the treatment of platelet dysfunction, but its peak effect is delayed for several days. Common long-term pharmacologic therapies administered to patients with CKD are listed in Table 7-4 .
| Comorbidity | Agents |
|---|---|
| Hypertension | Beta-adrenergic blockers Calcium channel blockers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin antagonists |
| Fluid overload | Thiazides Furosemide |
| Osteodystrophy and hypocalcemia | Calcium supplements Phosphate binders Calcitriol |
| Diabetes | Insulin Oral hypoglycemics |
| Anemia | Erythropoietin, iron |
Acute Kidney Injury
Acute kidney injury, formerly known as acute renal failure, refers to rapid loss of renal function characterized by a dramatic reduction in GFR and inadequate solute excretion. It is caused by hypovolemia (prerenal injury), a medley of intrinsic injuries to the nephron (as previously discussed), and injury to or compression of the renal effluent system (postrenal). AKI manifests as acute reduction in urine output (oliguria) or an increase in the circulating concentration of nitrogenous waste products, which ultimately lead to the syndrome of uremia. In clinical practice, serum urea and creatinine are used as measurable markers of uremia but are not responsible for it. Oliguria is defined as a urine volume less than 400 to 500 mL/24 hr. Oliguria is not necessary for the diagnosis of AKI, although it is often the presenting sign. Until recently, there has been no consensus on an operational definition of AKI.
The AKI syndromes have traditionally been classified into three major categories on the basis of their pathophysiology: prerenal, renal, and postrenal. Prerenal AKI is associated with a reduction in renal blood flow and glomerular perfusion, secondary to hypotension or hypovolemia. In the initial stages there is no damage to the tubules; if it is sustained, however, ischemic injury results. Postrenal AKI is characterized by acute obstruction to the urinary tract, at any level from the renal pelvis to the urethra. for obstruction proximal to the urinary bladder to result in AKI, however, it must be bilateral or occur in the patient with a single functional kidney. Abdominal compartment syndrome (see later) appears to combine prerenal and postrenal components. Intrinsic ARF is associated with renal parenchymal injury. This results from ischemic or toxic injury to renal tubular epithelial cells (acute tubular necrosis) and from glomerular, vascular, and interstitial inflammatory disease processes ( Box 7-7 ).
Acute Tubular Necrosis
Ischemia
Hypotension
Hypovolemic shock
Sepsis
Cardiac arrest
Cardiopulmonary bypass
Drug-Induced Nephropathy
Aminoglycosides
Radiocontrast agents
Amphotericin
Cisplatinum
Pigment Nephropathy
Intravascular hemolysis
Cryoglobulinemia
Rhabdomyolysis
Acute Interstitial Nephritis
Drug Induced
Penicillins
Cephalosporins
Sulfonamides
Rifampin
Phenytoin
Furosemide
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Infection Related
Bacterial infection
Viral infections
Rickettsial disease
Tuberculosis
Endocarditis
Systemic Diseases
Systemic lupus erythematosus
Multiple myeloma
Diabetes mellitus
Amyloidosis
Acute glomerulonephritis
Poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
Vascular Syndromes
Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Systemic vasculitis
Renal artery thromboembolism
Renal vein thrombosis
Confusion concerning the extent and definitions of kidney injury have been addressed and clarified by the Acute Dialysis Quality Initiative (ADQI; www.adqi.net ) group, who produced a now–universally accepted staging system for kidney injury known as the RIFLE criteria (risk, injury, failure, loss, end stage). This is based on rapid onset of renal injury, which may be oliguric or nonoliguric; thus there are both urine output and GFR criteria ( Table 7-5 ). The RIFLE criteria have been successfully used to predict patient outcomes. Although widely adopted by intensive care specialists, these criteria have been subsequently superseded by two groups. Initially the Acute Kidney Injury Network (AKIN) modified the RIFLE criteria to reflect a simpler staging system for AKI. This approach has been consolidated by the Kidney Disease: Improving Global Outcomes (KDIGO) group. The modifications these staging systems introduced to RIFLE were based on emerging data indicating that a small change in serum creatinine influences outcome. In addition, the “L” and “E” components were thought to be less useful for prognostication. Therefore, we recommend the latest version of these criteria ( Table 7-6 ).
| RIFLE | GFR Criteria | UO Criteria | Sensitivity/ Specificity |
|---|---|---|---|
| R isk | Increased creat × 1.5 or GFR decrease >25% | UO <0.5ml/kg/hr for 6 hours | High sensitivity |
| I njury | Increased creat × 2 or GFR decrease >50% | UO <0.5 mL/kg/hr for 12 hours | High sensitivity |
| F ailure | Increased creat × 3 or GFR decrease >75% or creat >4 mg/dL | UO <0.3 mL/kg/hr for 12 hours or anuria × 12 hours | High sensitivity |
| L oss | Persistent AKI (or ARF) = complete loss of kidney function >4 weeks | High specificity | |
| E nd-stage kidney disease | End-stage kidney disease = loss >3 months | High specificity | |
Stage | Criteria | |
|---|---|---|
| Serum Creatinine (S Cr ) | Urine Output | |
| 1 | Increase ≥26 μmol/L [0.3 mg/dL] within 48 hours or Increase ≥1.5 to 1.9 × reference/baseline S Cr | <0.5 mL/kg/hr >6 hours (consecutive) |
| 2 | Increase ≥2 to 2.9 × reference S Cr | <0.5 mL/kg/hr >12 hours |
| 3 | Increase ≥3 × reference S Cr or Increase ≥354 μmol/L [4 mg/dL] or RRT initiated regardless of stage | <0.3 mL/kg/hr >24 hours or Anuria for 12 hours |
Acute tubular necrosis
Acute tubular necrosis (ATN) results in AKI from a number of processes. Medullary ischemia results from hypoxic injury to the thick limb of the loop of Henle. This leads to sloughing of cells (casts), which block tubular flow. The tubular pressure builds up, and glomerular filtration is inhibited. Ischemic ATN is common in perioperative medicine, resulting from hypovolemia, hypotension, or deliberate ischemia, such as application of suprarenal cross-clamps (in cardiac and aortic surgery). ATN also results from a variety of toxic insults, including aminoglycoside and glycopeptide (vancomycin) antibiotics, NSAIDs, radiographic contrast, pigment (rhabdomyolysis), heavy metals, and solvents.
The clinical course of ATN can be divided into three phases: initiation, maintenance, and recovery. In the initiation phase the kidney is injured, and progression is potentially preventable. When renal failure becomes established, GFR may decrease dramatically and manifest as oliguria, with accumulation of nitrogenous waste products of metabolism and development of uremia, confusion with cognitive decline, pericarditis, and platelet dysfunction. This maintenance phase lasts days to weeks. The recovery phase lasts 4 to 6 weeks and is characterized by poor renal concentrating capacity and polyuria. Cellular repair takes place, and GRF gradually returns to normal.
Renal function tests
A normally functioning kidney is able to conserve salt and water. A sensitive indicator of tubular function is sodium handling because the ability of an injured tubule to reabsorb sodium is impaired, whereas an intact tubule can maintain this reabsorptive capacity against hemodynamic stress. With a prerenal insult, the urinary sodium concentration (U Na ) should be less than 20 mEq, and the calculated fractional excretion of sodium (FENa) should be less than 1% [FENa = (U Na /P Na ) ÷ (U Cr /P Cr ); Cr , creatinine]. Urine osmolality is high in prerenal syndrome. If the patient has tubular damage for any reason, U Na will be greater than expected (> 80 mEq) and urine osmolality low.
There is minimal consensus as to what constitutes AKI/ARF. In clinical practice, urea, a breakdown product of protein that is partially reabsorbed, and creatinine, a metabolic byproduct of muscle metabolism that is partially secreted, are used as markers for renal failure. Serum urea underestimates GFR. Serum creatinine is a better marker, assuming that muscle turnover is constant. Thus, in a trauma victim, who may have significant muscle injury, creatinine may underestimate renal function. Serum creatinine is insensitive to even substantial declines in GFR, which may be reduced by up to 50% before creatinine increases. Creatinine overestimates the GFR, so it is difficult to assess true renal function using the serum creatinine value. Conventional wisdom holds that a doubling of the serum creatinine level is indicative of renal failure. However, this may be misleading in patients with reduced muscle turnover (critically ill or elderly patients). The creatinine clearance (~ GFR) has been used as a method of overcoming these problems. The following method of calculation is most often used:
Creatinine clearance ( mL/min ] = ( 140 − Age ) × Weight ( 72 × Creatinine )
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
