Further reading D \200\231Amico G, Bazzi C. Urinary protein and enzyme excretion as markers of tubular damage. Curr Opin Nephrol Hypertens 2003; 12: 639 \200\223643. Filler G, Bokenkamp A, Hofmann W, Le Bricon T, Martinez-Bru C, Grubb A. Cystatin C as a mar ker of GFR \200\223 history, indications, and future research. Clin Biochem 2005; 38: 1 \200\2238. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classi \201 ca tion, and strati \201 cation. Am J Kidney Dis 2002; 39: 1 \200\223266. Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new insigh ts into old concepts. Clin Chem 1992; 38: 1933 \200\2231953. Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular \201 ltration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 2004; 141: 929 \200\223937. N-Acetyl-b-glucosaminidase (NAG) NAG is a hydrolytic enzyme with activity in the whole neph ron, particularly in the proximal tubule. With a molec- ular weight of 130 kDa it is not \201 ltered by the glomerulus, so NAG measured in the urine mainly derives from the tubule s. Tubular damage, e.g. in tubulointerstitial nephritis or renal transplant rejection, resu lts in an increase in urinary NAG Stevens LA, Levey AS. Measurement of kidney function. Med Clin North Am 2005; 89: 457 \200\223473. See also The aging kidney, p. 18 Urinalysis and microscopy, p. 8 Nephrogenic diabetes insip idus, p. 220 This page intentionally left blank C. JONES 16 Renal function in the newborn infant Sodium homeostasis Neonates have a limited capacity to excrete a Na+ load or to conserve Na + if there is Na+ restriction. In the \201 rst week of life fractional Na+ excretion is h igh and this is greater in the more immature neonates. Early hyponatremia (occurring shortl y after birth) can be caused by: \200 excessive \202 uid given to the mother; \200 re lease of antidiuretic hormone secondary to neonatal The neonatal kidney can adapt to the usual physiological processes occurring after birth. I t is less able to adapt to endogenous and exogenous stress such as hypotension, hypoxia and \202 uid overload and this is more pronounced in the more immature infants. The understa nding of renal function in the neonate will aid the clinician in the appro- priate manageme nt of \202 uid, electrolytes, nutrition and acid \200\223base in either the sick or prete rm neonate. It helps in the interpretation of biochemical investigations and drug handling in the neonate. Normative biochemical data for newborn infants are listed in Table 1.4.1. pathology such as asphyxia; inadequate Na+ content of feed/ \202 uid. Late hyponatremia can be caused by: \200 inade quate Na+ content of feed/ \202 uid; \200 deranged renal tubular function; \200 Na+ lo sses from the gastrointestinal tract. Prolonged hyponatremia is associated with a reduction in brain function and growth. Hypernatremia can be caused by: \200 sodium bicarbonate in fusions for acidosis; \200 insuf \201 cient free water administration when insensible Table 1.4.1 Normative biochemical data for newborn infants Age Reference range Serum Bicarbonate <1 month 17 \200\22326 mmol/L Base excess Newborn \200\22310 to \200\2232 mmol/L Calcium (total) Premature \211 2 weeks 1.5 \200\2232.5 mmol/L 1.9 \200\2232.8 mmol/L water losses are high. Phosphate 1 month 1.4 \200\2232.8 mmol/L Hypernatremia induces a \202 uid shift from the intracellular compartment causing cell sh rinkage and tearing of the cer- ebral capillaries. This mechanism reduces the physiologic c ontraction of the ECF, increasing the risk of patent ductus arteriosus, cardiac failure, br onchopulmonary dysplasia and intracranial hemorrhage. Potassium 1 month 3.5 \200\2236.0 mmol/L Sodium <1 month 130 \200\223145 mmol/L Creatinine 1 week 2 weeks 40 \200\223125 mol/L 35 \200\223105 mol/L 3 weeks 25 \200\22390 mol/L Potassium homeostasis In the neonate the rate of K+ excretion is low. This reduc- tion in K + excretion is partly explained by the low activity of the Na+K+-ATPase in the K+ secreting epithelium, and a reduction in the number of K+ channels. Plasma K+ in term infants falls in the \201 rst week of life. In preterm infants plasma K+ reaches its maximum in the 3rd or 4th week of life as a result of metabolic acidosis, oliguric renal failure and cataboli c activity. 4 weeks 20 \200\22380 mol/L 26 \200\22360 mL/min/1.73 m2 28 \200\22368 mL/min/1.73 m2 GFR 1 week 1 month Urine Maximal osmolality 1 \200\22314 days 2 \200\2234 weeks 210 \200\223650 mosm/kg 780 \200\2231100 mosm/kg Acid \200\223base balance Following birth, neonates have a mixed respiratory/ metabolic aci dosis as a result of changes in the cardiopul- monary circulation and the effects of the bi rthing process. Later they develop a self-limited metabolic acidosis which is in \202 uenc ed by the protein load, weight gain, ability of the renal tubules to excrete an acid load, and the renal thresh- old for bicarbonate reabsorption. This has usually resolved by the en d of the fourth week. Water homeostasis In early postnatal life there is a reduction in total body water, extrace llular water, and extracellular sodium (Na+) and chloride (Cl \200\223). There is an increa se in intracellular water and its main components protein, magnesium and potassium (K+). To tal body water as a percentage of body weight is 75% and the extracellular \202 uid (ECF ) is 35 \200\22340% of total body water. The reduction in total body water is re \202 ecte d in the weight loss observed in early postnatal life. This is greater in low birth weight premature infants where a weight loss of up to 10% can occur. Fluid prescriptions need to b e adjusted for increased insen- sible water loss because of: \200 increased relative body surface area; \200 increased metabolic rate; \200 increased transepidermal water loss, particularly in the premature infant exposed to phototherapy and over- head heaters. Glomerular \201 ltration rate The glomerular filtration rate is low after birth and is cl osely correlated to gestational age. It is 5 mL/m2 in neonates of 28 weeks gestation and 1 2 mL/m2 in term infants. Postnatally there is a rapid increase in GFR with a two-fold incre ase in GFR occurring in the \201 rst 2 weeks of life. Adult values are achieved between 1 and 2 years of age. Factors involved in the maturation of GFR include: \200 increase in renal blood \202 ow as a consequence of an increase in BP and a fall in intravascular resistance; CHAPTER 1.4 Renal function in the newborn infant 17 increase in the number of super \201 cial nephrons involved The location of angiotensin receptors within the kidney changes during development and the observation that the use of angiotensin-II receptor blockers and angiotensin- converting en zyme inhibitors in the mother cause renal dysplasia in the neonate indicates that the renin \200\223angiotensin system has a role in nephrogenesis. in \201 ltration; increase in the surface area of the glomerular basement membrane. Creatinine is usually used as a measure of renal function as [51Cr]EDTA GFR measurements ar e invasive and expensive. This may underestimate GFR if the patient has a high bilirubin le vel and the analyzer does not correct for noncreatinine cromogens. Creatinine in the \201 rst few days after birth is a measure- ment of maternal plasma creatinine. Plasma creatini ne is usually higher in more immature infants and does not fall steadily from birth, but ri ses in the \201 rst few days of life, reaching a peak and then falling to reach an equili brium level. In more immature infants the rise in cre- atinine is higher and the decrease i s much slower. This trend is the result of slower maturation of glomerular func- tion and i ncreased tubular reabsorption and may not indi- cate renal insuf \201 ciency. The Schwartz formula (eGFR = \227 height/creatinine) can be used to estimate GFR once the plasma cr eatinine has stabilized with the constant k = 33 for full term infants and 24 for low birth weight infants. Neonatal renal handling of drugs Listed below are a few pharmacologic agents commonly used in the neonate. Furosemide Furosemide is excreted by both glomerular \201 ltration and secretion in the t ubules by an organic acid tubular trans- port mechanism. These mechanisms are both immature and reduced in the neonatal kidney. The half-life of furo- semide may be >24 h in the neon ate and therefore if given more frequently it will accumulate in the plasma and exceed the threshold for ototoxicity. Indomethacin Indomethacin is typically used in preterm infants to close the ductus arterios us. Indomethacin inhibits prostaglandin synthesis and consequently reduces renal perfusion and induces acute renal failure in approximately a fourth of neonates <30 weeks gestation. These effects are usually transient and reverse after the drug has been stopped. This effec t is also observed with ibuprofen. Severe and irreversible renal insufficiency has been rep orted in neonates after prenatal exposure to NSAIDs. Tubular function Neonates have a lower urinary concentrating capacity but an obligatory wat er loss even when water-depleted. Normal urinary volume is 1 \200\2233 mL/kg/h and it is us ually dilute. Urinary concentrating ability matures rapidly after birth and by 8 weeks of a ge maximal urine osmolality is 1000 \200\223 1200 mosm/kg H2O. Glycosuria is common in neon ates and is greatest in pre- term infants. Urinary amino acid loss is higher in the neonate as a result of reduced tubular reabsorption. The maturity of renal rea- bsorption varies b etween different amino acids and these factors need to be considered when intrepreting urin ary amino acid pro \201 les for metabolic conditions. Urinalysis may be positive for prote in and does not always indicate renal disease. This decreases with increasing matu- rity an d by 2 weeks of life is usually <50 mg/L. Fractional reabsorption of phosphate is greater i n the neonate to allow bone accretion of phosphate. Neonates have a lower ability to secret e anions and this is more pro- nounced in the preterm infant. Drugs used in the neonate tha t are organic anions include folic acid, benzylpenicillin, methotrexate and phenobarbitone. Timed urines to measure tubular function require urethral catheterization and are not prac tical for routine use. Spot urines to look at tubular function expressed as a ratio of crea tinine are also unreliable because of the variation in urinary creatinine and the unreliabl e normative data. Contrast agents Hypertonic radiographic contrast material is associated with renal artery t hrombosis, medullary necrosis and ischemia. These high osmolar agents increase plasma osmol ality and may also cause intravascular hemorrhage. The risk of nephrogenic systemic \201 brosis (nephrogenic \201 brosing dermopathy) following the use of gadolinium- containing contrast agents in neonates with borderline renal function has not been quanti \201 ed. Aminoglycosides Aminoglycosides are eliminated by glomerular \201 ltration and therefore the dose needs to be adjusted with increas- ing conceptional age. Changes in tubular and gl omerular function as a result of aminoglycoside nephrotoxicity are usually reversible. Further reading Arant BS. Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 1978; 92: 705 \200\223712. Brion LP, Fleischman AR, McCarron C, Schwartz GJ. A simple estimate of glomerular \201 ltration rate in low birth weight in fants during the \201 rst year of life: non-invasive assessments of body composition and growth. J Pediatr 1986; 109: 698 \200\223707. Guignard JP, Drukker A. Why do newborn infants have a high plasma creatinine? Pediatrics 1999;103:e49 \200\22352. Guignard JP, Torrado A, Cunha OD, Gautier E. Glomerular \201 ltration rate in the \201 rst three weeks of life. J Pediatr 1975; 87: 268 \200\223272. Karlsson FA, Hardell LI, Hell sing K. A prospective study of urinary proteins in early infancy. Acta Paediatr Scand 1979; 68: 663 \200\223667. Schwartz GJ, Feld LG, Langdorf DJ. A simple estimate of glomerular \201 ltration rate in full-term infants during the \201 rst year of life. J Pediatr 1984; 104: 849 \200\223854 Renin \200\223angiotensin system Renal renin activity is higher in the neonate than in the adult and falls after birth reaching adult levels between ages 6 and 9 years. Neonates have a highly activated renin \200\223 angiotensin \200\223aldosterone system but the decline i n plasma Na+ and rise in plasma K+ re \202 ect a relative unresponsive- ness to aldosteron e. Simmons MA, Adock EW, Bard H. Hypernatraemia and intracranial hemorrhage in neonates. N Engl J Med 1974; 291: 6 \200\22310. J. FLOEGE AND J. KANNMACHER 18 The aging kidney Aging is a physiological process which incorporates degen- erative changes in many organs. The involvement of the kidney is accompanied by a decrease in renal function asso- ciated w ith certain structural and functional alterations. A wide variety of mechanisms promoting r enal change with age have been proposed, such as elevated angiotensin II levels, reduced ni tric oxide production by endothelial cells or chronic hyperuricemia (see Table 1.5.1). decrease is greater for the renal cortex than for the medulla. Capillary permeability In elderly people a higher prevalence of microalbuminuria and albumi nuria has been detected. Microalbuminuria is regarded as an independent risk factor for car diovascular events. Electrolyte problems Sodium. In aging there is impaired sodium excretion follow- ing a salt load, and the ability to conserve salt during sodium restriction is also reduced. In devel oped countries very sodium-rich diets are common, leading to the risk of sodium excess in e lderly people. The trend to increased total body sodium may promote the development of hype rtension with aging, in addition to other factors, such as endothelial dysfunction. This mi ght explain why, in most elderly patients, sodium restriction results in a signi \201 cant fall in blood pressure. Potassium. As a result of impaired potassium excretion and reduced aldosterone levels elderly people are more likely develop hyperkalemia than younger subjec ts. Impaired distal tubular acidi \201 cation in elderly patients contributes to the tende ncy to develop acid \200\223base disturbances. Structural changes The maximum size of the kidneys is reached at the age of 40 years, foll owed by a decrease of 10% per decade. In males this trend seems to be greater than in fema les. The renal cortex becomes thinner and the number of neph- rons declines. Some anatomica l alterations that affect the glomeruli can be identi \201 ed. \200 The preserved glomer uli often hypertrophy. \200 There is a thickening of the glomerular basement membrane. Focal and segmental glomerulosclerosis can be found affecting an increasing number of glome ruli. This is asso- ciated with the expansion of the mesangial matrix and a loss of capilla ry loops. Both tubules and interstitium also undergo structural changes. \200 Tubular dilatation an d atrophy particularly appear in the Water balance In older patients urine-concentrating and -diluting abilities are impaired. T here may be a predisposition to develop dehydration, due to production of urine with an ina ppro- priately reduced urine osmolality and a weaker thirst response to an increasing plasm a osmolality. As excretion following a water load also is impaired, there may be a ten- den cy to hyponatremia. outer medulla. Interstitial \201 brosis occurs due to collagen deposition and is accompanied by intersti tial in \201 ltration of macrophages and myo \201 broblasts. Small tubular diverticuli may be detectable, which possi- bly promote the development of re current pyelonephri- tis by constituting reservoirs for bacteria. Clinical implications The treatment of elderly patients requires some general consideration s. \200 The \202 uid, electrolyte and acid \200\223base balances of elderly patients ar e more likely to become abnormal in response to disease. In particular this must be taken i nto consider- ation in, for example, patients with diarrhea, those receiv- ing intravenous \202 uids or those suffering from hypoxemia. \200 Due to comorbidity, renal disease in elderly patients is often the result of more than one pathology. For exam- ple diabetic or hypertensive nephropathy often coexists with other lesions such as glomerulonephritis. Furthermore several vascular changes occur with aging. \200 In patients with hypertension thickening of the arterioles can frequently be seen. Arteriolar hyalinosis is typical for elderly people. The development of vascular shunts from afferent to efferent arterioles may result in bypas sing of glomeruli. Functional changes Glomerular \201 ltration rate (GFR) In elderly patients serum creatini ne is of limited use as a marker of renal function, because of a reduction in muscle mass w ith aging. Whereas normal daily creatinine excre- tion is 20 \200\22325 mg/kg body weight f or males and 15 \200\22320 mg/ kg body weight for females, this value progressively decline s after the 6th decade of life. In spite of a decrease in creati- nine clearance the serum level of creatinine may remain stable due to reduced muscle mass. Both the MDRD equa- tion and Cockcroft \200\223Gault formula underestimate GFR in patients aged >65 years. With adva ncing age there may be a reduction in the so-called renal reserve, which describes the abil ity of the kidneys to increase GFR following a protein load or food intake. The prevalence of many diseases differs between young and old people. This must be consider ed when establish- ing a diagnosis. Table 1.5.2 provides examples for dis- eases, which exh ibit signi \201 cant differences in prevalence with aging. The clinical manifestations of certain diseases may be atypical compared to younger patient s. For example a considerable number of elderly patients with IgA neph- ropathy present wit h acute renal failure, whereas this is less common in younger patients. Older persons are more prone to the nephrotoxic effects of many drugs, such as NSAIDs, amin oglycosides, COX-2 inhibitors and chemotherapy. Renal plasma \202 ow (RPF) There is a decrease in RPF with age, measured by para-aminohip purate clearance, from 650 mL/min in the 4th decade to 300 mL/min in the 9th decade. This The incidence and prevalence of end-stage renal disease is higher for elderly people. CHAPTER 1.5 The aging kidney 19 Table 1.5.1 Possible mechanisms causing renal affects of aging Cumulative injury to all kinds of tissue over time Free oxygen-derived radicals General senescence due to impaired replication capacity Telomere shortening of chromosomal DNA Hypertrophy of remaining glomeruli due to hyper \201 ltration, subsequent scarring Decrease in the number of glomeruli Glomerular hypertension, nonhemodynamic effects (podocyte injury) Intrarenal activation of the renin \200\223angiotensin system Impaired renal autoregulation and ischemia due to reduced nitric oxide production Endothelial dysfunction Renal overexpression of transforming growth factor-B Chronic hyperuricemia Mediation of renal \201 brosis Inhibition of nitric oxide availability, activation of the renin \200\223angiotensin system Further reading Epstein M. Aging and the kidney. J Am Soc Nephrol 1996; 7: Table 1.5.2 Diseases more/less frequent with aging Increase in incidence with aging Membranous glomerulonephritis Malignancy-associated glomer ular disease Acute renal failure (e.g. following cardiovascular surgery) Acute-on-chronic r enal failure Renovascular disease Urinary calculi Malignancies of the urinary tract Obstruc tive uropathy Urinary incontinence 1106 \200\2231122. Fliser D, Franek E, Joest M, Block S, Mutschler E, Ritz E. Renal func- tion in the elderly: impact of hypertension and cardiac function. Kidney Int 1997; 51: 1196 \200\2231204. Lindeman, RD, Goldman R. Anatomic and physiologic age changes in the kidney. Exp Gerontol 1986; 21: 379 \200\223406. See also Clinical assessment of renal function, p. 12 Decrease in incidence with aging Systemic lupus erythematosus Wegener \200\231s granulomato sis Y. REES 20 Imaging in renal disease Imaging of the renal tract has changed dramatically over recent years with advances in the technology of all imaging modalities. The basic underlying principle of renal imaging remai ns obtaining the diagnosis by the quickest and safest route possible. The causes of abnormally sized kidneys are listed in Table 1.6.1. To look for renal cortical scarring. To demonstrate interstitial renal disease. \200 As t he severity of intrinsic renal disease increases, the echogenicity of the kidneys tends also to increase. Plain X-ray KUB (kidney, ureters, bladder) This is a plain radiograph of the abdomen, cente red on the umbilicus, that includes the upper poles of the kidneys and the pubic symphysis (Fig. 1.6.1). It provides only limited information. The main value of plain radiography is: \200 Identification of calcification and its relationship to the renal tract. Approximat ely 85% of renal calculi are radio-opaque. To demonstrate and characterize renal masses. \200 Cystic lesions: simple cysts are anech oic; complex cysts may contain multiple internal septae and abnormal soft tissue. Solid lesions: renal tumors cannot be characterized further except for angiomyolipomas whic h are increased in echogenicity due to the fat content. CT or MRI is required for further e valuation. Although CT is used for the staging of renal tumors, USS may be used to demonstrate metasta ses in the liver, enlarged retroperitoneal lymph nodes and tumor throm- bus in the renal ve ins. Assessment of the renal outlines which can be identi \201 ed due to the contrasting densit y of the kidneys with the perirenal fat. This may be dif \201 cult due to overlying bowel gas obscuring the outlines. Table 1.6.1 Causes of abnormally sized kidneys Identi \201 cation of bone abnormalities that may be associ- ated with renal tract disease , e.g. renal osteodystrophy, and sclerotic bone metastases in prostate cancer. Large kidneys Bilateral Unilateral Compensatory hypertrophy Hydronephrosis Renal vein thrombosis Tumor Cysts Polycystic kidney disease In \201 ltration (lymphoma, oedema) HIV-associated nephropathy R enal vein thrombosis Small kidneys Bilateral Unilateral Congenital hypoplasia/ dysplasia Renal artery stenosis Chronic intrinsic renal disease (glo merulonephritis, interstitial nephritis) Re \202 ux nephropathy Renal tuberculosis Congenital hypoplasia/dysplasia Renal artery stenosis Chronic intrinsic renal disease (glom erulonephritis, interstitial nephritis) Re \202 ux nephropathy Renal tuberculosis Fig. 1.6.1 Plain X-ray in renal tract disease. Plain X-ray showing (a) a triangular calculu s overlying the pelvis of the left kidney, and (b) renal outline. Ultrasound is poor at demonstrating transitional cell carci- nomas of the kidney as they me rge into the fat of the renal sinus. These may, however, be identi \201 ed because of sec- ondary effects of the tumor, e.g. obstruction, especially in high risk patients. \200 To demonstrate bladder abnormalities. Ultrasound scanning (USS) Ultrasound is the \201 rst-line investigation for most renal di seases (Fig. 1.6.2). It is relatively quick to perform, requires minimal patient preparatio n, and does not involve the use of ionizing radia- tion or contrast agents. However, it is operator dependent, gives no functional information, and offers little in the assessment of pelviuret- eric abnormalities. Bladder tumors may be diagnosed on USS but cystos- copy remains the gold standard for diagn osis. USS is also useful for the assessment of bladder emptying. To provide evidence of renal tract obstruction. Obstruction rarely occurs without dilatatio n of the col- lecting system but dilatation may occur without obstruc- tion. The level and cause of the obstruction may also be identi \201 ed on USS. Indications for USS in native kidneys To assess the size and position of the kidneys. \200 To demonstrate renal calci \201 cation. The normal renal size range is 9.0 \200\22312 cm and cortical thickness is normally >1.5 cm . USS gives very good anatomical detail. The demonstra- tion of small shrunken kidneys impl ies advanced CKD. Calci \201 cation including calculi can be demonstrated but the sensitivity is dependent o n the size of the stone. Other techniques (e.g. CT scanning) are more sensitive. CHAPTER 1.6 Imaging in renal disease 21 1 2 a a b b 4 a 3 a a 5 a Fig. 1.6.2 Ultrasound in renal tract disease. 1. Transverse image of kidney showing (a) a r enal tumor, and (b) the kidney. 2. Longitudinal image of kidney showing (a) a renal tumor, and (b) the kidney. 3. Longitudinal and transverse images of bladder showing (a) bladder tu mors. 4. Longitudinal image of kidney showing (a) a collection of calculi. 5. Longitudinal image of kidney showing hydronephrosis. (a) Renal parenchyma and (b) dilated pelvis. RI of up to 0.8 is normal. A value above this indicates graft dysfunction, but this is a no nspeci \201 c \201 nding and does not differentiate between the different causes of graf t dysfunction. Minimal dilatation of the collecting system in renal trans- plants is normal . Care must therefore be taken to dif- ferentiate dilatation due to reflux from that due to obstruction. Ultrasound is also useful in identifying perinephric collec- tions that may s ubsequently be drained percutaneously. Indications for USS in renal transplants Renal transplants are very amenable to ultrasound scan- ning because: \200 there is little respiratory movement; \200 the renal artery is well positioned for accurate assess- ment of flow velocities to investigate renal artery s tenosis. Doppler ultrasound is valuable in the assessment of the patency of the renal vessels and ov erall \202 ow velocity. Measurement of the resistive index (RI), which is an indica- tion of the resistance to arterial \202 ow in the renal vascular bed, is useful in the assess ment of graft dysfunction. (peak systolic velocity \200\223 end diastolic velocity) peak s ystolic velocity RI = Y. REES 22 May cause ureteric trauma with perforation and/or Intravenous urography (IVU) The role of IVU in renal imaging is declining as other modaliti es take its place. Indications \200 Can provide good anatomical detail of the urinary tra ct. \200 Useful particularly for the diagnosis of conditions involv- stricture formation. Infection may be introduced into the upper urinary tract. Antegrade pyelography This is the visualization of the upper urinary tract by direct inject ion of contrast media into the renal pelvis. This is rarely done apart from as a prelude to an interventional procedure. The renal pelvis or preferably a calyx is percutaneously punc tured using a narrow gauge needle under USS or \202 uor- oscopic (after an IV injection o f contrast media) guidance. ing the urothelium. Effective in the evaluation of patients with ureteral colic but this role has been supersed ed by CT (Fig. 1.6.3). Disadvantages \200 Involves the use of iodinated contrast media. \200 Involves a radiat ion dose. \200 May fail to identify some calculi. \200 Masses, especially those lying a nteriorly or posteriorly, may be missed. Unable to differentiate solid from cystic masses. Procedure After a plain KUB radiograph is performed, iodinated con- trast medium is injected IV. As the contrast is excreted, a seri es of images of the abdomen are taken: 5 min post injection: an X-ray of the renal area is obtained to visualize the renal parenchyma (nephrogram). Delayed nephrograms may be seen wi th: \200 obstruction; \200 ATN; \200 reduced renal perfusion; \200 renal vein throm bosis. Renal scars may also be identi \201 ed. Abdominal compression is then applied to im pede the pas- sage of contrast into the bladder. 15 min post injection: an X-ray of the ren al area is obtained to visualize the calyces, pelves, and proximal ureters (pyelo- grams). Immediately after abdominal compression is released, a radiograph is obtained to visualize the ureters and the bladder. The study is completed by obtaining a post-void radiograph. Other contrast radiography Retrograde pyelography This is the visualization of the ureter a nd pelvicalyceal sys- tem using a direct retrograde injection of contrast medium introduced via a catheter placed in the ureter during cystoscopy. Indications \200 To investigate possible transitional cell carcinoma in the ureters or re nal pelvis, when other imaging modali- ties either have failed to identify a lesion, or are contraindicated. To further evaluate defects seen on other investigations. Advantages \200 Provides excell ent anatomical detail of the ureters and Fig. 1.6.3 Intravenous urography. 1. Control image showing (a) outline of left kidney and ( b) a small opacity in the left side of the pelvis. 2. Postmicturition image showing (a) a n ormal right collecting system, (b) a dense nephrogram on the left, (c) a dilated pelvicalyc eal system on the left, and (d) a dilated ureter down to the level of the opacity demonstra ted in image 1. collecting system. Disadvantages \200 Invasive, requiring a catheter to be placed up the ureter and into the collecting system. Indications \200 To identify the cause of upper tract obstruction when IV urography/CT ur ography or retrograde pyelography is unsatisfactory or cannot be undertaken. Requires iodinated contrast. However, the contrast is extravascular unless extravasation occurs. Requires radiation. CHAPTER 1.6 Imaging in renal disease 23 To determine in a renal transplant whether a dilated col- lecting system represents obstruc tion in the face of deteriorating function. It is part of upper tract urodynamic testing (Whitaker test). Disadvantages \200 Relative contra-indications are an uncorrected bleeding diathesis, cut aneous infection, or anatomy that precludes safe renal puncture. Can be complicated by puncture of adjacent structures (renal vein, liver, spleen, colon) al though these are rarely signi \201 cant given the small needle size. In an obstructed system some contrast extravasation Fig. 1.6.5 Urethrogram. (a) Catheter, (b) penile urethra, and (c) a stricture in the membra nous urethra. may occur post procedure. It is time-consuming and may be unsuccessful if the collecting system is nondilated. Computed tomography CT without contrast enhancement This is now the gold standard for the d iagnosis of renal calculi especially in the setting of acute ureteral colic (Fig. 1.6.6). N oncontrasted CT has a sensitivity and speci \201 city of >95% for the detection of stone d isease. Contrast is not usually required since almost all calculi, even those traditionally considered radiolucent on plain imaging, are seen as high density structures (the only exc eption is stones caused by indinavir sulfate). Contrast may be required to differentiate ph leboliths from calculi in the pelvis. It involves a signi \201 cant radiation dose especia lly in those patients requiring repeated examinations. In up to 30% of cases another cause for \202 ank or abdominal pain may be demonstrated. The site of renal tract obstruction c an be determined. Cystography Contrast is introduced via a bladder catheter to \201 ll up the bladder and X -ray images are then taken of the bladder (Fig. 1.6.4). The patient can then be asked to mi cturate to obtain further information (micturating cystography). Indications Cystography is used to demonstrate: \200 bladder anatomy; \200 urinary leak s (which are usually iatrogenic); \200 vesico-enteric \201 stulae; \200 ureteric re \202 ux; \200 urethral anatomy. Primary signs of stone disease \200 Calculus within the ureteric lumen. Secondary signs o f stone disease \200 Hydronephrosis. \200 Perinephric or periureteric stranding. \200 Ureteric dilatation. \200 Blurring of the sinus fat. \200 Enlarged kidney. CT with int ravenous contrast enhancement Scanning is performed after the intravenous injection of cont rast media (Fig. 1.6.6). The acquisition of images at dif- ferent times after injection pro vides additional information: Arterial: This is used to image renal arteries primarily for evidence of renal artery stenosis. To optimize the visualiza- tion of the arteries, bolus t racking is done \201 rst so that the scan can be performed at the time of peak enhancemen t of the aorta. Corticomedullary phase: 25 \200\22380 s post injection. During this phase t he cortex is enhanced while the (hypovascular) medulla remains relatively unenhanced. It is useful for evaluating the vascularity of tumors and in \202 ammatory lesions. Hypovascula r medullary tumors or hypervascular cortical tumors may, however, be missed during this pha se. Nephrographic phase: 85 \200\223100 s post injection. The renal parenchyma should appea r homogeneous during this phase. This is the best phase for detecting and evaluating renal lesions. Fig. 1.6.4 Cystogram. (a) Bladder, and (b) urinary re \202 ux into the collecting system o f a transplant kidney. Ascending urethrography Contrast is introduced into the urethra through a narrow- bore cath eter and X-ray images are obtained (Fig. 1.6.5). It provides good anatomical detail of the urethra and can be performed by ultrasound or \202 uoroscopy. Indications \200 Following trauma it is used to demonstrate continuity of the urethra and urethral leaks. To evaluate penile strictures prior to intervention. Y. REES 24 Fig. 1.6.6 CT scanning in renal disease. 1. Abdominal CT scan without contrast showing a ca lculus in the mid-ureter with stranding around it (arrow). 2. CT scan without contrast show ing (a) a dilated pelvis and (b) peri-renal stranding. 3. CT scan without contrast demonstr ating a small solid lesion (arrow) containing fat (low attenuation), therefore most likely to be an angiomyolipoma. 4. CT scan with contrast demonstrating (a) a normal right kidney, (b) a left renal tumor, and (c) remaining normal renal parenchyma on the left. 5. Reconstru cted CT scan with contrast demonstrating (a) a normal right kidney, (b) a renal tumor in th e left upper pole, (c) normal lower pole of the left kidney, (d) normal liver, and (e) sple en. 6. CT scan demonstrating multiple bladder tumors (arrowheads). 7. CT urogram demonstrat ing (a) contrast in the right collecting system, and (b) a \201 lling defect in the colle cting system consistent with a transitional cell carcinoma. CHAPTER 1.6 Imaging in renal disease 25 Excretory phase: 3 \200\2235 min post injection. The collecting sys- tem is enhanced and th is is primarily useful in detecting urothelial lesions (see \200\230CT urography \200\231 below). Nephrotoxic contrast agents are avoided. The risk of neph- rogenic systemic \201 brosis n eeds to be considered in those with impaired renal function. Indications \200 To stage urogenital cancers: may be used in conjunction with MRI. To demonstrate obstruction, the level of obstruction, and its cause. If contrast is given, calculi may be more dif \201 cult to identify. To demonstrate collections associated with the renal tract, e.g. perinephric collections. To demonstrate soft tissue abnormalities related to the renal tract, e.g. retroperitoneal \201 brosis. To demonstrate mass lesions in the renal tract. \200 To differentiate cystic from solid t umors. \200 To characterize the vast majority of angiomyolipomas so that they do not require tissue con \201 rmation. To aid in the diagnosis of infection, including tuberculosis. \200 To evaluate the renal tract after trauma to demonstrate: the anatomy of the renal tract and any pre-existing anom alies; the type and severity of parenchymal injury; the extent of perinephric hemorrhage; u rinary extravasation/leaks; injuries to the vascular pedicle. \200 \200 \200 CT urography The patient \201 rst undergoes a noncontrast enhanced scan to exclude calci \201 cation. This is followed by an arterial phase scan to demonstrate enhancing tumors in cluding transitional cell carcinomas. A \201 nal scan is undertaken 5 \200\2237 min after the IV injection of contrast media, by which time contrast has accumulated in the collecti ng system (Fig. 1.6.6). It is undertaken mainly to diagnose congenital abnormali- ties of t he urinary tract, and to detect and evaluate urothe- lial lesions (e.g. transitional cell c arcinomas). Magnetic resonance imaging Indications \200 To characterize renal mass lesions (Fig. 1.6. 7). Noncontrasted and gadolinium-enhanced T1-weighted scans are undertaken during the phase s described under contrasted CT. To stage bladder and prostate carcinomas. \200 To assess tumor thrombus in renal tumors. MRI does not require iodinated contrast media but the risk of nephrogenic systemic \201 b rosis if gadolinium-based MR contrast agents are used in patients with reduced GFR must be considered. There is no cross-sensitivity between iodinated contrast agents and MR contrast agents. The risk of anaphylaxis with MR contrast agents is 0.04%. MRI may be used in earl y pregnancy. Fig. 1.6.7 MRI of the renal tract. 1. MRI demonstrating multiple bladder tumors (arrowheads ). 2. MR angiography demonstrating (a) left ostial renal artery stenosis, (b) normal right renal artery, (c) aorta, and (d) iliac artery. 3. MR urogram demonstrating (a) left hydrone phrosis, (b) dilated left ureter, (c) a ureteric \201 lling defect, and (d) the bladder. MR angiography This is an effective and noninvasive method to evaluate renovascular disease in native kidneys (Fig. 1.6.7). For the diagnosis of renal artery stenosis the sensitivity is >93% and the speci \201 city >83%. No radiation is required. MR urography This can be an effective method for imaging the urinary tract (Fig. 1.6.7). It provides good anatomical detail but the resolution is not as good as CT. It can be underta ken in two ways: \200 Heavily T2-weighted image acquisition provides good detail of stati c \202 uid in the collecting system, particularly Y. REES 26 when it is obstructed and dilated. IV contrast is not required, therefore this method is us eful even in the absence of urine production. T1-weighted images can be obtained during the excre- tory phase following IV gadolinium inj ection. This is analogous to CT urography. Nuclear medicine Nuclear medicine techniques can provide both functional and structural inf ormation in the investigation of renal disease. There are broadly three types of nuclear me dicine study: \200 GFR estimation (this is discussed in Chapter 1.3). \200 Dynamic: ser ial scans are obtained to determine uptake, transit and excretion of the tracer. Static: tracer is taken up and retained in the kidney. Scanning is performed in multiple pr ojections to identify structural abnormalities. The four most widely used radiopharmaceuticals are: \200 [51Cr]Ethylenediamine tetra-acet ic acid ([51Cr]EDTA). It is excreted exclusively by glomerular \201 ltration and is used for the accurate estimation of GFR. It is not used for imaging. [ 99mTc]Diethylenetriamine penta-acetic acid ([99mTc]DTPA). Again this is excreted by glome rular \201 ltration. It is used in dynamic imaging studies. This has fallen out of favor and is being replaced by [99mTc]MAG3.