Intrinsic renal AKI Any of the possible causes of acute renal dysfunction can be encountere d in pregnancy but the following are some of the more common causes: \200 acute tubular n ecrosis; \200 bilateral cortical necrosis; \200 microangiopathy; \200 acute interstit ial nephritis; \200 de novo glomerulonephritis. Each will be discussed separately below. Post-renal AKI This is an uncommon cause of AKI in pregnancy. The uri- nary tract undergoes physiological dilatation in pregnancy especially on the right side in later pregnancy. How ever, pathological obstruction can occur. Rarely women can develop an exaggeration of the n ormal physiological dilatation in the urinary tract in pregnancy. This is called \200\230t he overdistention syndrome \200\231. Very rarely this syndrome may lead to rupture of the d ilated urinary tract. Urinary tract obstruction is dif \201 cult to assess in pregnancy. I f the dilatation is gross or there are associated symptoms of \202 ank pain, urinary trac t infection or impaired renal func- tion then further investigation and drainage may be req uired. The pregnant uterus can rarely be the cause of obstruc- tion. This may be more commo n in presence of extreme polyhydramnios or with twin pregnancies. In later pregnancy obstru ction is relieved by delivery, in earlier pregnancy stenting and amniotomy (for polyhydram- nios) have been reported to delay delivery by 5 \200\22315 weeks. Epidemiology Over the last 20 years the incidence of AKI has reduced in developed but less so in developing countries. In the 1960s the incidence was reported as 1 in 3000 preg- nanc ies but now the rate is almost ten times lower in Europe and North America. AKI requiring d ialysis now occurs in 1 in 20 000 pregnancies in Europe and North America. In the develope d nations there has been little overall change in mortality which is reported to be 0 \200 \22330%. In developing countries AKI in pregnancy continues to cause 20% of the total cases of AKI and mortality is as high as 50%. Traditionally, early pregnancy AKI cases were main ly due to septic abortion and later cases due to obstetric complica- tions including hemorr hage and pre-eclampsia (PeT). The legalization of abortion and improvements in antenatal ca re with early detection of antenatal complications of pregnancy are the two main factors th at have led to a reduction in AKI in pregnancy. CHAPTER 10.12 Acute kidney injury in pregnancy 379 Acute fatty liver of pregnancy This is part of the spectrum of the maternal systemic PeT di sease process. It is a rare but potentially fatal complication of the third trimester. Inci dence ranges from 1 in 10 000 to 1 in 15 000 deliveries. It usually presents mid \200\223la te pregnancy (27 \200\22340 weeks), or occasionally postpartum. Symptoms are usually of mal aise, nausea, vomiting, neuro- logical symptoms, upper abdominal pain and jaundice. The cli nical picture is similar to PeT and HELLP syndrome with hypertension, and with abnormalitie s in coagulation which are due to liver dysfunction rather than abnormal platelet consumpti on. 40% of patients develop AKI. 100 e s a e r c n ERPF 50 GFR i % 0 Non pregnant 16 26 Weeks of pregnancy 36 Fig. 10.12.1 Effect of pregnancy on glomerular \201 ltration rate (GFR) and effective ren al plasma \202 ow (EFPF). (Redrawn from: Davison, 1987.) Septicemia This is a rare complication of pregnancy in developed countries. It is one of th e \201 ve leading causes of maternal death world- wide. A decline in the number of cases of sepsis in pregnancy has been reported in the USA over last 25 years (from 0.6% to 0.3%). Prevalence of bacteremia in pregnancy is 7.5 per 1000 admissions but most do not develop s epticemia. One in 8500 deliveries is complicated by septic shock. Death from septic shock i s uncommon in developed coun- tries and outcome is good compared with nonobstetric patients . Mortality rates vary widely \200\223 one recent study reported a mortality rate of 12.5% . Mortality in developing (mainly African countries) was reported to be >1000 per 100 000 l ive births compared to < 20 per 100 000 live births in European countries. Septicemia may a rise from any cause in pregnancy, e.g. cholecystitis, ruptured appendix, etc. However, comm on causes in pregnancy are: Renal calculi The incidence of renal stone disease is the same as non- pregnant women. Typi cal symptoms of loin pain, hematuria and urinary infection may occur but the diagnosis can be dif \201 cult in heavily pregnant women. Suspected cases should be referred to urologis ts for investigation and may require a ureteric stent or nephrostomy. Clinical presentation This will depend largely on the precipitating cause of AKI (Table 10. 12.1). It is important to establish the presence of: \200 \200 \200 fever and other systemic symptoms of sepsis; symptoms of bleeding or other obstetric compli cations; speci \201 c disease associated symptoms e.g. rash in SLE, joint pains, vasculiti c rash. BP may be low in prerenal AKI or raised in the presence of glomerulonephritis or PeT. Jugul ar venous pressure/volume status \200\223 may be low due to volume depletion or high when there is established renal impairment indicating hypervolemia and \202 uid over- load, of ten associated with peripheral and pulmonary edema. It is always important to ask the obste trician to assess the fetal viability and growth and exclude antepartum hemor- rhage and ot her intrauterine complications. Septic abortion This remains common in developing countries, but uncom- mon in developed co untries following the introduction of antibiotics, oral contraception and legalized abortio n. It is usually caused by infection with Clostridium spp. Patients present with systemic f eatures of septicemic shock and may have evidence of gas formation in the uterus or abdomen . Acute pyelonephritis Patients may complain of fever, loin pain, lower urinary tract sympt oms including dysuria, etc. In addition, if the infection is severe there may be symptoms a nd signs of systemic infection and septic shock, decline in renal func- tion and multiple o rgan failure. Acute tubular necrosis in pregnancy This occurs most commonly due to prolonged volume deple tion, hypotension and vasoconstriction. ATN can occur secondarily to a number of underlying pathologies in pregnancy: Pre-eclampsia, HELLP syndrome PeT is accompanied by volume contraction and vasocon- stricti on and patients are more at risk of developing estab- lished ATN following any further volu me depletion. PeT is often associated with intravascular coagulation and gener- alized \200\230endothelial activation \200\231, further compromising renal blood \202 ow and lea ding to multiple organ dysfunction. Other causes of ATN in pregnancy Other complications of pregnancy that may result in preren al AKI and established ATN include prolonged intra- uterine death and amniotic \202 uid e mbolism. S.J. CARR 380 \200 Table 10.12.1 Causes of acute kidney injury in pregnancy neurological symptoms; hypertension. Prerenal causes of AKI Volume contraction, hypotension and vasoconstriction due to: Laboratory investigations \200 thrombocytopenia; \200 anemia; \200 schistocytes/fragm ented red blood cells on blood \201 lm; \200 elevated serum lactate dehydrogenase; \200 reduced haptoglobin; \200 impaired renal function. water and electrolyte depletion persistent vomiting, diarrhea, or overdiuresis edema-forming states pre-eclampsia, nephrotic syndrome hemorrhage antepartum and postpartum hemorrhage Pre-eclampsia Renal causes of AKI Acute tubular necrosis Pathogenesis In normal individuals, endothelial cell-derived von Willebrand factor multimer s are cleaved by a metallopro- teinase enzyme (ADAMTS13). In patients with acquired TTP the ADAMTS13 activity is reduced, leading to aggregation and systemic circulation of excess vo n Willebrand factor multimers which cause endothelial cell damage, activation of the coagul ation cascade and microangiopathy in the kidney and other organs. Secondary to prolonged volume depletion, hypotension and vasoconstriction of any cause, e.g . pre-eclampsia, HELLP syndrome, hemorrhage Septicemia Bilateral cortical necrosis Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome Acute interstitial nephritis De novo glomerulonephritis Amniotic \202 uid embolism Hemolytic uremic syndrome (HUS) This is a very rare complication of pregnancy. It may occur at any stage of pregnancy but most typically occurs postpartum (few hours to 8 \200\22310 weeks postpartum, but may be delayed several months). The pregnancy and delivery in most ca ses have been unremarkable. The resultant microangiopathy mainly affects the kidneys. Clini cal features It frequently begins with \202 u-like symptoms, hypertension, edema and olig oanuria. Hypertension is present in half of cases. HUS can be very dif \201 cult to differ entiate from PeT in the later stages of pregnancy. If renal failure is progres- sive a rena l biopsy may be considered but is dif \201 cult if thrombocytopenia is present. Postrenal causes of AKI Physiological dilatation of pregnancy (hydronephrosis and/or hydroureter) Renal calculi Obstruction by gravid uterus Tubular obstruction Bilateral cortical necrosis Any cause of sustained hypovolemia, hypotension or pro- found vasoconstriction can result i n this condition. Pregnant women may be more susceptible than nonpregnant patients. The inc idence is reported to be 20% following septic abortion whereas the incidence is only 2% fo llowing other causes of AKI in pregnancy. It most commonly occurs following severe PeT or a ntepar- tum hemorrhage. Laboratory investigations These are similar to TTP. Management of microangiopathy in pregnancy This requires close liaison between hematologist , nephrol- ogist and obstetric team. Microangiopathic syndromes in pregnancy These include: \200 \200 \200 Cryoprecipitate-poor fresh frozen plasma Treatment is similar to nonpregnant cases. Cryopre cipitate- poor fresh frozen plasma is used to replace the de \201 cient metalloproteinases . This treatment is often effective alone in nonoliguric patients (60%). PeT/HELLP syndrome; thrombotic thrombocytopenic purpura; hemolytic uremic syndrome. PeT/HELLP is discussed in detail in Chapter 9.5. Plasma exchange Oliguric or severely affected patients will require plasma exchange which a lso removes excess von Willebrand fac- tor multimers and autoantibodies against the metallo pro- teinase ADAMTS13. Treatment is given daily and response to treatment is accompanied by reduced schistocytes on a blood \201 lm, increased platelet counts and reduction in LDH levels. Thrombotic thrombocytopenic purpura A rare complication of pregnancy. Both acquired idiopat hic TTP and familial TTP can occur in pregnancy. Pregnancy is a predisposing factor for de novo disease or relapse of the condition. It often occurs in the 2nd or 3rd trimester with mean onset at 23 weeks. Clinical features \200 \200 \200 \200 Platelet and blood transfusions Platelet transfusions should be avoided given the potential risk of increased microvascular thrombosis unless there is risk of life-threatening bleedi ng. Blood transfusion can be given if required. thrombocytopenia; microangiopathic hemolytic anemia; fever; renal dysfunction; CHAPTER 10.12 Acute kidney injury in pregnancy 381 it can be dif \201 cult to distinguish between new onset of lupus nephritis and PeT. It is important to consider the extrarenal manifestations of SLE and the effects on pregnancy. 3 0% patients with SLE have antiphospholipid antibodies. Increased risk of thrombotic microan giopathy can result in hypertension, proteinuria and renal impairment which are dif \201 c ult to distinguish from PeT. For other manifestations of thromboembolic disease, anti- coag ulation needs to be considered with obstetric and hematology teams. Some patients with SLE have anti-Ro/La antibodies which have been linked to neonatal cardiac problems with brady- cardia and heart block. It is therefore important to discuss the need for fetal cardiac mon itoring with the obstetricians. In general, the outcome of SLE is good in pregnancy but dep ends on the severity and extent of organ involvement. There is a high incidence of early-on set PeT. One series reported that PeT occurred in 15% of patients with SLE. Complications a re more severe in the presence of antiphospholipid antibodies. Renal replacement therapy Patients with significant renal dysfunction will require hemodial ysis (see below). Continuance of the pregnancy Unlike severe PeT, HELLP syndrome or acute fatty liver of preg nancy \200\223 when the condition occurs in the early stages of gestation the pregnancy ca n be continued in patients with TTP/HUS. The mother may require ongoing treat- ment during pregnancy with plasma infusion/exchange and dialysis. In addition, the fetus needs to be cl osely moni- tored for signs of compromise to regularly determine whether the outcome of ear ly delivery would be better than continuing pregnancy. Outcome HUS and TTP in pregnancy are associated with increased maternal morbidity and morta lity. Recent case series report a reduction in maternal mortality with a rate of 0 \200\223 10% (previously 40 \200\22350%). Similarly, fetal outcomes have improved with recent report s of 20% fetal loss (previous 80%). Most cases result in early delivery (average 26 weeks). Acute interstitial nephritis The pregnant patient may develop acute interstitial nephri- ti s (AIN) which is often due to medication in pregnancy as in the nonpregnant patient. In 1st and early 2nd trimesters a renal biopsy may be per- formed to establish the cause of susta ined deterioration in renal function. Drugs considered a potential cause of AIN should be d is- continued and avoided. Steroid therapy can be adminis- tered in pregnancy if necessary. Diagnosis is more dif \201 cult in mid/later pregnancy as it is technically dif \201 cul t to perform a safe renal biopsy (see renal biopsy in pregnancy). Associated clinical \201 ndings (rash, etc.) may indicate possi- ble AIN and potentially nephrotoxic drugs shou ld be discontinued. In later pregnancy it is again necessary to consider the relative merit s and disadvantages to mother and fetus of continuing with the pregnancy in utero or consid ering an early delivery. Management of glomerulonephritis in pregnancy This depends on the type of glomerulonephriti s and the severity of the initial presentation. In pregnancy, treatment for active SLE usua lly includes: \200 \200 \200 corticosteroids; low dose aspirin; immunosuppressive medication (azathioprine or cyclo- pho sphamide); hydroxychloroquine; antihypertensive medications (nifedipine, methyldopa and/or labetaolol); low molecular weight heparin (if antiphospholipid antibodies/signi \201 cant proteinuria). \200 Mycophenolate mofetil is contraindicated in pregnancy. The renal and obstetric teams need t o liaise closely and determine issues regarding continuation of the pregnancy in consultati on with the mother. The remainder of the management is as outlined below. De novo glomerulonephritis Any acute glomerulonephritis can present in pregnancy. Hypertens ion and urinary abnormalities are often detected during routine antenatal care. Glomerulone phritis can present at any stage of pregnancy and it may be dif \201 cult to distinguish a new presentation of glomerulonephritis in later pregnancy from PeT. Clinical presentation of glomerulonephritis may be mild with hypertension, urinary abnormalities including micro- scopic hematuria and proteinuria with or without impaired renal function; or severe with r enal failure, thrombocyto- penia, edema and hypertension. There may be associated clinical symptoms and signs which aid diagnosis as in the nonpregnant patient, e.g. symptoms and sig ns of other organ involvement: skin lesions and joint symptoms in systemic lupus erythemato sis (SLE), purpuric rash in vasculitis. Investigations These are essentially the same as for nonpregnant patients, but with particu lar emphasis on identi \201 cation of speci \201 c causes related to pregnancy (Table 10. 12.2). Biochemistry \200 \200 \200 urea and electrolytes; liver function tests; quanti \201 cation of urinary protein excreti on. Blood \201 lm, LDH, haptoglobin and platelet count \200 to exclude schistocytes and microangiopathic hemolytic anemia. Urate \200 raised in patients with diagnosis of PeT. Immunology screen \200 \200 \200 \200 dsDNA antibodies; complement levels C3, C4; lupus anticoagulant and anticardiolipin antibod ies; ANCA. Lupus nephritis in pregnancy Pregnancy may exacerbate activity in SLE, especially if dis- e ase is active at the time of conception. In later pregnancy S.J. CARR 382 Table 10.12.2 Investigation of AKI in pregnancy Renal ultrasound scan \200 diagnosis of urinary tract obstruction may be dif \201 cult as dilatation of ureter and re nal pelvis (especially on right) is a feature of normal pregnancy. Urine urine stick testing (blood, protein, leukocytes and nitrites) \200 quanti \201 cation of proteinuria (24 h urine collection or urine Renal biopsy \200 protein:creatinine ratio) urine culture \200 microscopy/cytology Consider in certain cases if, for example, GN is suspected and results of a biopsy are like ly to lead to speci \201 c therapy. Biochemistry urea and electrolytes \200 bone chemistry \200 liver function tests \200 lactate dehy drogenase and haptoglobin \200 glucose \200 urate \200 C-reactive protein Renal biopsy in pregnancy Rarely, when AKI of unknown cause or symptomatic de novo renal di sease presents in a pregnant women, renal biopsy will need to be considered (Table 10.12.3) . Recent studies have reported the complication rate to be the same as in nonpregnant patie nts. In all cases USS should be performed to exclude obstruction and a urine culture to exc lude infection before proceeding to a renal biopsy. In addition, platelet count, coagulatio n screen should be normal and BP well-controlled. If possible a renal biopsy should be defe rred until after pregnancy is completed. Although pregnancy confers no additional risk, the positioning of the patient may be more dif \201 cult and it may be uncomfortable for a wo man to lie on her stomach, in which case the biopsy can be performed sitting. It is wise to liaise with the radiologists. When a biopsy is performed in pregnancy there should be an e xpectation that the histological \201 ndings may lead to immediate treatment which would improve the outcome of pregnancy for the mother and fetus. Investigation of newly identi \201 ed urinary sediment abnor- malities in pregnancy with normal renal function should be deferred until postpartum. Hematology full blood count \200 blood \201 lm \200 coagulation studies (include lupus anticoagu lant in SLE) Immunology autoantibodies (dsDNA, anticardiolipin antibodies and anti-Ro/La antibodies in SLE) complement Microbiology blood cultures \200 speci \201 c infections and virology as required Radiology renal ultrasound (to exclude obstruction and assess renal size) Renal biopsy see Table 10.12.3 Obstetric liaison arrange for obstetric monitoring of the fetus Treatment The following are required: \200 prompt identi \201 cation and correction of volume depletion and electrolyte disturbances; prompt identi \201 cation of sepsis with supportive treat- ment and commencement of broad spectrum and then speci \201 c antibiotics; prompt investigation and relief of urinary tr act obstruction; discontinuation of medication likely to cause acute interstitial nephritis . speci \201 c therapy for some pathologies, e.g. SLE, may require immunosuppressive thera py; HUS may require fresh frozen plasma and plasma exchange; close monitoring of all bioche mical parameters including urea and electrolytes, acidosis; when AKI occurs in pregnancy on e of the most impor- tant treatment decisions is whether the outcome would be improved by i mmediate delivery. pregnancy may be lost if immediate delivery takes place. In this situation if the maternal condition is stable and fetus is viable, a patient with AKI may be given dialysis during pr egnancy. When renal impairment is present but not requiring dialysis then a decision may ne ed to be taken regarding maximizing the viability of the fetus versus continuing the pregna ncy and risking further deterioration in renal function. This requires close liaison betwee n renal and obstetric teams. Indications for dialysis in pregnancy \200 \200 \200 \200 volume overload; hyperkalemia; metabolic acidosis; uremia (urea >20 mmol/L). There is no clear evidence to indicate the correct time to start dialysis in pregnancy; how ever, most nephrologists aim to keep the serum urea level <20 mmol/L in a pregnant patient. Early delivery of the baby The decision to deliver the baby depends upon: 1. Whether the ca use of AKI is presumed to be PeT, HELLP or acute fatty liver of pregnancy where delivery is often the only way to stop the disease process or when the presence of an ongoing pregnanc y prevents administration of ade- quate treatment to the mother. 2. The stage of pregnancy. Facilitating delivery is relatively easy in later pregnancy >28 \200\22332 weeks when the fetus is likely to be viable, but below this level of gestation the Dialysis modality Both peritoneal dialysis and hemodialysis have been suc- cessfully used in pregnancy. Hemod ialysis is used most frequently and needs to be performed approximately daily to minimize u remia and intradialytic weight gain. Generally, 6 treatments per week (20 h) are recommende d. Care needs to be taken to avoid hypokalemia and excessive \202 uid removal because hyp otension and wide variations in vol- ume status may affect placental perfusion. CHAPTER 10.12 Acute kidney injury in pregnancy 383 Table 10.12.3 Indications for renal biopsy in pregnancy Sudden deterioration in renal function before 28 weeks gestation of unknown cause In this s ituation a biopsy may identify an important reversible pathology and lead to immediate trea tment, e.g. SLE with lupus nephritis, renal vasculitis. Symptomatic nephrotic syndrome before 28 weeks Renal biopsy may identify a pathology which is treatable such as minimal change disease, SLE or a pathology for which you would not initiate further therapy during pregnancy, e.g. mesangiocapillary glomerulonephritis. In this way a renal biopsy can also be useful to prevent initiation of potentially toxic em pirical treatment with steroids during pregnancy. All other situations Generally, investigation by renal biopsy should be deferred until afte r delivery but may sometimes be considered in 1st trimester if the result would inform futu re management decisions: \200 isolated proteinuria >3 g/24 h; \200 previously diagnosed systemic disease associated with urinary abnormalities or renal impairment; \200 unexpla ined chronic renal impairment. Patients may also be anemic; hemoglobin should be main- tained >10 g/dL units. Erythropoiet in therapy appears safe in pregnancy. Dwyer PL, O \200\231Reilly M. Recurrent urinary tract infection in the female. Curr Opin Obstet Gynaecol 2002; 14: 537 \200\223543. Evans R, Fernandez-Perez, Salman S, et al. Sepsis during pregnancy. Crit Care Med 2005; 33(10, Suppl): S286 \200\223293. Prognosis Outcome depends on the cause of AKI. When the cause of AKI is reversible, renal f unction often recovers in 3 \200\2234 weeks. Some patients will require dialysis and other intensive care measures. Unfortunately, bilateral cortical necrosis may also be a consequen ce and recovery of renal function may then be limited. Full renal recovery is reported in 6 0 \200\22390% cases of AKI in pregnancy. Gammill HS, Jeyabalan A. Acute renal failure in pregnancy. Crit Care Med 2005; 33(10, Suppl): S372 \200\223384. Hou S, Firanek C. Management of the pregnant dialysis patient. Adv Renal Replacement Therapy 1998; 5: 24 \200\22330. Johnson RJ, Feehally J (eds). Renal Complications in the Normal Pregnancy. Comprehensive cl inical nephrology, 2nd edn. London: Mosby; 2003. Chapter 44, pp. 567 \200\223581. Karumanchi SA, Epstein FH. Renal complications in pregnancy. In: Feehally J, Floege J, John son RJ (eds) Comprehensive clinical nephrology, 3rd edn. Philadelphia, PA: Mosby; 2007; Cha pter 41, pp 483 \200\223494. Follow-up Postpartum follow-up of women with AKI in pregnancy is essential. The urgency and duration of follow-up depends on the nature of the AKI. All women in the UK have a 6 week postnatal check but women with AKI may need early nephrological review to consider further investigation, i.e. renal biopsy and man- agement of persisting problems. Many medications are changed or omitted during preg- nancy e.g. ACEIs. A full medication review is required post- partum to consider reintroduction of medications discontinued antenatally. It is impo rtant to consider the safety of medications in women who are breastfeeding and advice may b e needed from a pharmacist. Moroni G, Ponticelli C. The risk of pregnancy with lupus nephritis. J Nephrol 2003; 16: 161 \200\223167. Sturgiss SN, Dunlop W, Davison JM. Renal haemodynamics and tubular function in human pregna ncy. Balli res Clin Obstet Gynecol 1994; 8: 209 \200\223234. Internet resources SafeFoetus.com, useful site to assess safety of prescribing in pregnancy : http://www.safefoetus.com/ Pregnancy as a test of renal function: a streamed lecture held o n the RCP Edinburgh website: http://rcpe.ac.uk/education/education/ streamed_lectures/renal-med.php Lupus UK, patient fr iendly information on planning preg- nancy in patients with SLE: Future prospects The majority of the available data on renal disease and pregnancy dates fr om the 1970s and 1980s. There is a need for contemporary data to improve the advice we are able to give to pregnant mothers with renal disease. It will be important that future colla borative studies are established and funded and that information regarding renal disease in pregnancy is accumulated by the National Obstetric and Renal registries \200\223 for exam ple UK CORD (Collaboration in Renal disease in Pregnancy) and the UK Transplant Pregnancy R egistry. The Royal College of Obsterics and Gynecology and NICE are currently reviewing the evidence for treatment of hypertension in pregnancy and will publish their recom- mendatio ns within the next 12 months. http://www.lupusuk.com Royal College of Obstetricians and Gynecologists: http://www.rcog.org.uk National Collaborating Center for Women \200\231s and Children \200 \231s Health: http://www.ncc-wch.org.uk/ See also CKD in pregnancy, p. 476 Hypertensive disorders in pregnancy p. 310 Clinical appro ach to acute kidney injury, p. 318 Renal replacement therapies in acute kidney injury, p. 3 28 Further reading Davison JM. Overview: kidney function in pregnant women. Am Kidney Dis 1987; 9: 248. R. WESTACOTT 384 Acute kidney injury in the elderly blunted response to sodium depletion due to reduced tubular reabsorption capacity (salt was ting); blunted response to sodium loading, due to a reduced natriuretic response; reduced u rinary concentrating ability; reduced urinary diluting ability; reduced sensation of thirst despite raised plasma osmolality; loss of renal blood \202 ow autoregulation in response to a reduction in perfusion pressure (increased vascular tone and reduced vasodilatory res ponse); Introduction Acute kidney injury (AKI) is more common in the elderly population resulting f rom a combination of physiological changes within the aging kidney, a higher frequency of a sso- ciated comorbidities and differences in the etiological spectrum of AKI in the elderly population. The \200\230biological age \200\231 of patients is likely to be of more rele- vance than chronological age, but is much more dif \201 cult to de \201 ne. In studies o f AKI, therefore, it is chronological age that is most widely used to de \201 ne an elderl y population. Despite this, there is considerable variation in the age used to de \201 ne \200\230elderly \200\231 in the published literature. The age demography of the developed world is that of an increasingly elderly population, a trend that is likely to continue as life expectancy rises. The age at which one is considered elderly also varies between count ries with an average life expectancy in India of 62.5 years compared with 77.7 years in the UK (data from the US Census Bureau International Database 2000). \200 \200 In addition to these functional changes, there is also an increased use of drugs interferin g with autoregulation of blood \202 ow (ACEIs, loop diuretics, NSAIDs, etc.). As a conseq uence of these changes, the elderly patient is at increased risk of developing: \200 dehydration and hypernatremia due to a reduction in maximal concentrating ability combined with reduced thirst perception; hyponatremia and \202 uid overload due to a reduction in maximal diluting ability combined with impaired ability to conserve sodium; hyperkalemic (t ype IV) renal tubular acidosis due to a reduction in basal renin and aldosterone activity. This increases the risk of hyperkalemia following a GI bleed and with drugs inhibiting the renin \200\223angiotensin system (ACEIs, ARBs, heparin, tacrolimus, ciclosporin, NSAIDs) or those blocking sodium channels (trimethoprim, pentamidine, K+-sparing diuretics). Epidemiology The incidence of AKI in the elderly is dif \201 cult to quantify as the de \201 nitions of both \200\230elderly \200\231 and \200\230AKI \200\231 differ widely in t he literature. Studies also vary in their clinical setting (community, general hospital, IT U, etc.) making generalizations and comparisons between sets of data impossible. The freque ncy of AKI increases with advancing age which- ever de \201 nition is chosen. A UK communi ty-based study found that the incidence of AKI was: \200 \200 Other factors As well as physiological changes within the aging kidney, there are other fac tors which increase the risk of AKI amongst elderly populations: 17 pmp/year in <50-year-olds; 949 pmp/year in 80 \200\22389-year-olds. From the same study: 72% cases of AKI occurred in patients aged >70 years. More recently, a nother smaller UK study found the incidence of severe AKI to be: \200 \200 Chronic comorbidity Chronic conditions that lead to CKD, such as hypertension and diabetes mellitus, are more p revalent in the elderly. Polypharmacy The use of multiple medications is much greater among the elderly and often in cludes potentially nephrotoxic drugs (ACEIs, ARBs and NSAIDs). 68 pmp/year in <65-year-olds; 351 pmp/year in >65-year-olds. In general, the incidence of AKI also appears to be increas- ing over time although some of this rise re \202 ects the chang- ing criteria for AKI and indications for treatment. A S cottish study found the incidence of AKI requiring renal replacement therapy (RRT) to be 50 pmp/year in 1989 \200\2231990 and 297 pmp/year in 2002. Radiological tests and surgical interventions More aggressive investigation and treatment h as led to an increase in radiological tests and surgical interventions being performed on e lderly patients with the attendant risk of contrast nephropathy and postoperative AKI. Predisposing factors The elderly are at increased risk of developing AKI through a combinat ion of physiological changes within the kidney and other demographic factors. Clinical features As in other populations, AKI in the elderly is often multifac- torial, ma king precise etiological classi \201 cation dif \201 cult. Although the overall etiologic al spectrum in the elderly is similar to other populations, certain causes are more prevale nt in older populations (Table 10.13.1). The clinical features, investigation and managemen t of speci \201 c causes are dealed with elsewhere in this book. The text below details sp eci \201 c features pertaining to the elderly. Structural and functional changes in the aging kidney Under normal circumstances, the elder ly kidney is capable of maintaining \202 uid and electrolyte balance and the physi- ologi cal changes associated with age are clinically silent. However, the capacity to adapt is re duced and the response rate to change is slower, thus making the elderly kidney more suscep tible to developing AKI. Being less able to adapt to sudden changes in blood \202 ow or s alt and water balance leads to: CHAPTER 10.13 Acute kidney injury in the elderly 385 Glomerulonephritis There is an increased incidence of rapidly progressive glomerulonephriti s (RPGN) due to small vessel vasculitis in patients aged >60 years. RPGN consistently accou nts for approximately a third of cases in renal biopsy series in the elderly. Lupus nephrit is is very rarely found in renal biopsies in older populations. Table 10.13.1 Causes of AKI occuring more frequently in the elderly Prerenal AKI (all forms more common in the elderly) True hypovolemia Reduced intravascular volume (functional hypovolemia) NSAID- or ACEI/ARB-induced hemodynamic changes Renal artery thrombosis Cholesterol embolization Acute tubular necrosis Acute tubular necrosis (ATN) is the commonest cause of AKI in both y oung and elderly populations, particularly for those patients who require ITU admission. Al though a distinction is frequently made between ischemic, nephrotoxic and septic ATN, in re ality, ATN com- monly results from a mixture of insults. The elderly also have an increased prevalence of comorbid conditions predisposing them to develop ATN (diabetes mellitus, hyp ertension, CKD and heart failure). Ischemic ATN is more common in elderly populations where approximately one-third of cases are the conse- quence of surgical intervention. Raised se rum creatinine or urea preoperatively strongly predict the likelihood of developing worseni ng renal function postoperatively. Cardiac and vascular surgery are most likely to result i n postoperative AKI. Septic ATN is common in younger adults as well as the elderly. Multipl e organ failure in the elderly most frequently results from infection, and the development of AKI is a strong predictor of mortality in this age group. The interaction of nephrotoxin s and renal hypoperfusion is at least additive in the development of AKI and may be synergi stic. Risk factors for the development of nephro- toxic ATN in the elderly are: \200 Intrinsic renal AKI Rapidly progressive glomerulonephritis Focal segmental glomeruloscleros is Ischemic ATN Nephrotoxic ATN Myeloma Postrenal AKI Benign prostatic hyperplasia or prostate cancer Abdominal/pelvic malignancy Prerenal AKI Prerenal AKI is more common in the elderly and also more common in community-a cquired AKI. It may result from a number of causes. Hypovolemia The elderly are more susceptible to true hypovolemia due to reduced maximal con centrating ability, reduced sodium reabsorption capacity, a reduced thirst impulse and an i ncreased prevalence of diuretic usage. Functional hypovolemia (interpreted by the kidney as a reduction in intravascular volume) from pre-existing conditions such as heart failure is also more common in the elderly. radiocontrast use (prevalence increasing as more inter- ventions carried out); an increased prevalence of polypharmacy; injudicious use of nephrotoxic drugs especially when dosage is not adjusted for the reduction in GFR. Aminoglycosides in particular are associated with a n increased incidence of AKI amongst the elderly and should be avoided unless absolutely ne cessary where- upon monitoring of drug levels is essential. Hemodynamic Impaired renal blood flow autoregulation leaves the elderly kidney at increased risk from superadded hemo- dynamic effects from drug therapy. Age alone, however, has not been shown to be a risk factor for AKI following either NSAIDs or ACEIs/ARBs. Risk factors for NSAID-induced AKI include patient aged >60 years with concomitant cardiovascular diseas e, CKD and renal hypoperfusion. Risk factors for ACEI/ARB-induced AKI include the pres- enc e of renal artery stenosis, severe chronic heart failure, polycystic kidney disease and int ra-renal nephrosclerosis (often undiagnosed). \200 Acute interstitial nephritis The overall incidence of acute interstitial nephritis is not h igher in the elderly, but theoretically they are more at risk due to the higher prevalence of polypharmacy. If diagnosis is suspected, renal biopsy should be performed promptly as ea rly treatment with corticosteroids may improve renal recovery. Renovascular disease Both renal artery thrombosis and cholesterol embolism are more common in the elderly. Cholesterol embolization is an important cause of AKI in the elderly. It mo st commonly occurs after vascular inter- ventions with AKI, generally occuring up to 2 \200 \2234 weeks after the procedure. It is thought to be responsible for a third of cases of AK I following AAA repair. Cholesterol emboliza- tion can also arise spontaneously in an indiv idual with severe atherosclerotic disease, or following anticoagula- tion or thrombolysis. Intratubular obstruction This is less common than urethral/ureteric obstruction. Intratubul ar obstruction due to myeloma (light chain precipitation) is more common in the elderly. Ot herwise the causes of intratubular obstruction are similar to the general population. Postrenal AKI Obstructive renal failure is more common in the elderly than in younger adult s. The incidence in the general population is quoted as 1 \200\22310% but in elderly popula tions the incidence is increased to 9 \200\22322%. Intrinsic renal AKI Rapidly progressive glomerulonephritis, renovascular disease and myelom a are all seen more frequently in the elderly. R. WESTACOTT 386 AKI only develops where there is bilateral obstruction or obstruction to a single functioni ng kidney. CT scan An enhanced CT scan should be considered if renal artery occlusion is suspected. Urethral/ureteric obstruction This is an important cause of AKI in the elderly and is often amenable to treatment. Important causes to consider in the elderly patient are: \200 Renal biopsy There is no excess risk in performing a renal biopsy in the elderly patient an d much potentially to be gained if a treat- able condition is diagnosed. A biopsy should th erefore be performed if clinically indicated. Interpretation of the biopsy can sometimes be more dif \201 cult due to the presence of age-related changes such as glomerulosclerosis. However, this should not be used as a reason for not per- forming a biopsy if it is otherw ise indicated. The most common diagnoses seen in renal biopsy series in elderly patients wi th AKI are: \200 \200 \200 \200 prostatic disease (benign prostatic hyperplasia and pros- tate cancer); intra-abdominal mal ignancy; retroperitoneal malignancy. \200 Presentation of AKI The presentation of AKI in the elderly as in the general population is often nonspeci \201 c. However, the elderly are more likely to have an atypical presentati on of AKI such as an acute confusional state. Physical signs can also be misleading in the elderly. In particular: \200 RPGN (one-third of all renal biopsies in the elderly); ATN; renovascular disease; acute int erstitial nephritis. loss of skin turgor is a common \201 nding in the elderly and may be a re \202 ection of aging rather than hydration status; orthostatic hypotension may occur in elderly patients without hypovolemia; edema may occur in the absence of \202 uid overload.