Asymptomatic Stones may be identi \201 ed on imaging studies that are under- taken for oth er indications. Clinical assessment and investigation The evaluation of acute colic and chronic loin pain s hould include: The assessment of vital signs for evidence of fever, septi- cemia, and shock . Dipstick urinalysis for the urine pH, the presence of hema- turia, and evidence of infect ion (leukocyte esterase and nitrite). Measurement of full blood count, renal function, seru m calcium and uric acid. Culture of a midstream urine sample. Diagnostic imaging. The diagn osis of a ureteric stone can only be made by imaging. \200 Treatment of the stone The options available are: \200 conservative management with observation and analgesia; extracorporeal shock wave lithotrip sy; ureteroscopy and in situ fragmentation extraction of fragments usually using holmium laser energy; percutaneous nephrolithotomy for larger renal stones or stones in the proxim al ureter; open surgery; this is now rarely required, but the open techniques may now be re plicated by laparo scopic sur- geons and the future may see a growing role for laparo- scop ic ureterolithotomy and pyeloli thotomy. \200 Plain X-ray of the abdomen. This has little role in establishing the initial diagnosis. Uri c acid stones P. BUTTERWORTH 276 Stones \211 5 mm in diameter will pass in 68% of cases, and stones 5 \200\22310 mm in dia meter will pass in only 47% of cases. Treatment of stones in the pelvicalyceal system Chemical dissolution therapy for uric acid stones This can be achieved noninvasively using a combination of: \200 \200 Medical expulsive therapy -adrenoceptor blockers have recently been shown to increase the proportion of patients with ureteric stones who pass their stone spontaneously. The increa se in stone passage rate is 29%. Some studies also show a decrease in both the number of h ospital readmissions and interventions that are required. Most studies have restricted them selves to distal ureteric stones and it should be noted that the use of -blockers for thi s indication is not licensed. Patients who elect conservative observation or medical expuls ive therapy should have well-controlled pain and no evidence of sepsis. These patients shou ld be monitored with periodic imaging studies to monitor stone position, and to identify de velop- ing hydronephrosis or obstruction. high \202 uid intake (>2 \200\2232.5 L/day); urine alkalinization using potassium citrate 6 \200\22310 mmol 2 \200\2233 times a day to achieve a urine pH of >6.5; allopurinol 300 m g/day (particularly if urinary urate excretion is >1000 mg (6 mmol)/day). Alternatively percutaneous dissolution can be achieved by the infusion of an alkaline solut ion (e.g. trihydroxymethyl aminomethan (THAM)) through a percutaneous nephros- tomy. To pre vent either the chemolysis solution draining into the bladder, or an increase in intrarenal pressure, a second nephrostomy tube is usually required for drainage of the irrigation \202 uid. Extracorporeal shock wave lithotripsy (ESWL) Fragmentation of stones needs to be followed b y clearance of the fragments. The likelihood of fragment clearance is determined by the pel vicalyceal anatomy. A dependent calyx with a long infundibulum may retain fragments which t hen form a nidus for further stone for- mation. The passage of multiple large fragments may obstruct the ureter as a Steinstrasse or \200\230stone street \200\231. For stones >2 cm diameter a ureteric stent should be placed prior to ESWL to prevent this complication. Management of ureteric obstruction Persistent or marked obstruction with gross hydronephro- sis warrants intervention. Obstruction may be relieved by insertion of a percutane- ous ne phrostomy under radiological guidance, or by inser- tion of a ureteric stent. The nephrosto my drains an obstructed system more reli- ably, but necessitates an external drainage bag. Ureteric stents drain internally but give rise to lower uri- nary symptoms of frequency and urgency. Flexible ureterorenoscopy and in situ laser lithotripsy The \202 exible ureteroscope can carry a \202 exible laser \201 ber to a stone in any part of the collecting system. Lit hotripsy by contact with holmium laser energy is very effective but the technique is limite d by the very small size of the instruments (200 m diameter laser \201 ber) and the vie w down the ureteroscope which is obscured by even trivial bleeding. Ureteric stone removal This is indicated in the presence of persistent obstruction, failure of stone progression, or recurrent or uncontrolled pain. ESWL and ureteroscopy are both ac ceptable \201 rst-line treatments for ureteric stones. The success rates for each treatme nt modality are listed in Table 8.2.2. Ureteroscopy is associated with a higher stone-free rate after a single treatment in all cases except for larger stones in the proximal one-thi rd of the ureter. However, this advantage comes at the cost of greater risks of ureteric in jury and sepsis, and the requirement for anesthesia. Use of ESWL for stones in the middle t hird of the ureter may be restricted by the bones of the pelvis which prevent penetration o f the shock wave. Percutaneous nephrolithotomy A sheath is delivered into the pelvicalyceal system through th e skin of the loin via the renal parenchyma. The stone is removed under direct vision using instruments passed down the sheath. The main complications relate to the puncture and incl ude hemorrhage, which rarely requires embolization of the kidney or even emergency nephrect omy, and septicemia. Excellent stone-free rates are achievable, but other less invasive tec hniques may subsequently be required to treat residual fragments ( \200\230sandwich therapy \200\231). Ureterolithotomy Open ureterolithotomy should be required only rarely. A small number of se ries describe good results when laparoscopic ureterolithotomy is used to treat large impact ed stones in the proximal ureter. Treatment of ureteric stones In ureteric colic, encouraging patients to drink plenty of \202 uid to induce a forced diuresis is of no bene \201 t. An increased urine output reduc es the rate of ureteric peristalsis, which is the mechanism by which stones are expelled. A s obstruction of the ureter becomes chronic (>18 h), afferent arteriolar vasoconstriction c auses a decrease in glomerular \201 ltration and effectively diverts urine produc- tion t o the contralateral kidney. Table 8.2.2 Stone-free rate after single treatment for ureteric stone ESWL Ureteroscopy Proximal Mid-ureter Distal ureter 82% 73% 74% 87% 86% 94% Conservative, observational management Many ureteric stones may be safely left to pass spon taneously. CHAPTER 8.2 Surgical management of stone disease 277 Prevention of recurrence In high risk patients or recurrent stone-formers a formal metaboli c screen may be useful. Identi \201 cation of the likely stone composition can facilitate targeted therapy. This involves analysis of a 24 h urine collection for volume, and the qua ntity of calcium, oxalate, phosphate, uric acid and sodium (and citrate if available). A sp ot urine test for the presence of cystine (followed by a 24 h collection for cystine excret ion if the spot urine is positive) should also be undertaken. The composition of the stone should also be analyzed when possible. In all cases and irrespective of the stone subtypes, mainte- nance of a large output of dilute urine (minimum 2 L, ide- ally more) is the most important intervention. This should also include drinking at bed-time to induce nocturia. Maintain a large urine output, ideally 3 L per day. Uric acid stones may be dissolved by al kalinization of the urine to a pH of 6.5 \200\2237.0. Potassium citrate is the preferred al kalinizing agent, but many patients are intolerant of the taste. Allopurinol is useful if t he patient is hyperuricemic or if the urinary uric acid excretion is >1000 mg (6 mmol)/day. Cystine stones The risk of forming recurrent cystine stones can be mini- mized by the follo wing approach. Forced diuresis is essential. Patients should aim for a urine output >3 L pe r 24 h and this requires the patient to wake at night to drink. Alkalinization of the urine to a pH of 7 \200\2238. Use of cystine complexing agents: cystine forms soluble complexes with D-penicillamine, tiopronin or captopril. These oral agents reduce urinary cystine excr etion but many patients experience intolerable side-effects. Calcium oxalate stones Following an initial stone episode 50% of patients will have anothe r episode within 10 years. After a second epi- sode the risk rises to \211 75%. The risk o f further stone formation can be minimized with the following approach. Maintain a large ur ine output. Treat hypercalcemia if present. Restrict dietary sodium intake to <100 mmol/day . Restrict dietary oxalate by avoidance of oxalate-rich foods (coffee, chocolate, nuts, str awberries, green leafy vegetable). Avoid purine gluttony to decrease uric acid excretion. I ncrease citrus fruit consumption to increase urinary cit- rate excretion. It is well-establ ished that calcium restriction is not helpful. Indeed a calcium-rich diet may bind dietary oxalate in the gut and thereby reduce urinary oxalate excretion. Consider thiazide diuretic s. Thiazides stimulate calcium reabsorption from the distal tubule and so decrease cal- ciu m excretion. However, there is little evidence of bene \201 t compared with placebo and si de-effects mean long-term compliance is poor. Consider the administration of allopurinol to patients with recurrent calcium oxalate stones and hyperuricosuria. Further reading Auge BK, Preminger GM. Surgical management of urolithiasis. Endocrinol Metab Clin North Am 2002; 31: 1065 \200\2231082. Miller NL, Lingeman JE. Management of kidney stones. Br Med J 2007; 334: 468 \200\223472. Teichman JM. Acute renal colic from ureteral calculus. N Engl J Med 2004; 350: 684 \200\223693. Wen CC, Nakada SY. Treatment selection and outcomes: renal cal- culi. Urol Clin North Am 2007; 34: 409 \200\223419. Internet resources Detailed guidelines on the management of stone disease from the European Association of Urology: http://www.uroweb.org/fileadmin/user_upload/ Guidelines/Urolithiasis.pdf General stone info rmation for patients: http://www.kidney.niddk.nih.gov/kudiseases/ pubs/stonesadults National Kidney Foundation in formation on stone disease: www.kidney.org/atoz/atozTopic.cfm?topic=13 See also Imaging in renal disease, p. 20 Lower and upper urinary tract infection in adults, p. 244 Medical management of stone disease, p. 270 Renal and urinary tract stone disease i n children, p. 282 Uric acid stones Recurrent uric acid stones may be prevented by the fol- lowing approach. R. AL JAYYOUSI 278 Nephrocalcinosis Nephrocalcinosis is de \201 ned as calci \201 cation within the renal parenchyma. This ca n be microscopic or macroscopic and be in a corti- cal or medullary distribution. Medullary nephrocalcinosis is the commonest form. The prevalence of nephrocalcinosis is not known bu t a small study of nephrectomy specimens (removed for renal tumors) found that interstitial calci \201 cation is a common \201 nding. Microscopic nephrocalcinosis is sometimes det ected inci- dentally on renal biopsy. It is caused predominantly by metabolic disorders aff ecting calcium metabolism such as Bartter \200\231s syndrome, distal renal tubular acidosis , primary hyperoxaluria, and second- ary hyperparathyroidism. The clinical implication of m icroscopic nephro- calcinosis has not been extensively studied in man but is likely to be s imilar to that seen with macroscopic nephro- calcinosis. This chapter will focus on macrosc opic nephrocalcinosis that is detectable on imaging as discussed below. 75% of patients with Dent \200\231s disease develop nephrocalci- nosis but the extent of th is does not correlate with the progression of the renal impairment. Type 1 renal tubular ac idosis. Hypomagnesemia \200\223hypercalciuria syndrome. Bartter \200\231s syndrome. Ameloge nesis imperfecta. Congenital hypothyroidism. Primary hyperoxaluria (cortical nephrocalcinos is in this setting carries a worse renal outcome than medullary nephrocalcinosis). X-linked hypophosphatemic rickets. \200 \200 \200 \200 \200 Structural kidney disease Medullary sponge kidney. Calci \201 ed deposits form in the malf ormed collecting ducts in the pericalyceal region of the medullary pyramids. Medullary spon ge kidney disease generally follows a benign course and rarely causes progressive CKD. \200 Papillary necrosis (e.g. caused by NSAIDs) can lead to nephrocalcinosis in the damaged papi llae and gives a characteristic radiological appearance. Drugs \200 Etiology Cortical nephrocalcinosis Cortical nephrocalcinosis generally follows tissue destr uc- tion and tends to have an asymmetric distribution. Underlying causes include: \200 \200 \200 \200 \200 \200 \200 \200 \200 Acetazolamide (probably by interfering with urinary acidi \201 cation). Furosemide. This i nhibits the sodium \200\223potassium \200\223 chloride channel in the ascending loop of Hen le. This leads to reduction in the luminal electropositivity and reduces the paracellular r eabsorbtion of calcium leading to hypercalciuria. Furosemide is particularly implicated in the nephrocalcinosis seen in severely premature babies. NSAIDs (as discussed above). Oral s odium phosphate solution used as bowel prepara- tion. Several case reports have described w idespread calcium phosphate deposition in the renal medulla on renal biopsy. This is seen p articularly in patients with pre- existing renal disease. In some reports the renal biopsy \201 ndings included acute tubular necrosis but whether this is caused by the calcium pho sphate deposition or by intercurrent volume depletion is not clear. Amphotericin. This caus es renal tubular injury and may lead to a clinical picture similar to that seen in distal R TA including nephrocalcinosis. Lipid and colloidal prepara- tions of amphotericin B appear to have a less nephro- toxic pro \201 le. Total parenteral nutrition (TPN). The mechanism of this is unclear but is probably related to the calcium:phos- phate ratio required for ma intaining a neutral or positive calcium balance to prevent bone disease. This may be compou nded by the acidosis which results from a cata- bolic state. trauma (e.g. following lithotripsy); renal infarction; renal neoplasms; chronic pyelonephri tis; vesicoureteric re \202 ux; renal transplant rejection; granulomatous disease; chronic glomerulonephritis; acute cortical necrosis (e.g. following severe postpartum hemorrhage); oxalosis. \200 Medullary nephrocalcinosis Medullary nephrocalcinosis is usually symmetrical and bilateral in its distribution. The list of causes is extensive. Excess urinary constituents that may precipitate (calcium, phosphate, oxalate): \200 \200 \200 \200 \200 \200 \200 \200 primary hyperparathyroidism; milk-alkali syndrome; vitamin D toxicity; sarcoidosis; idiopat hic hypercalciuria; oxalosis; type 1 renal tubular acidosis (RTA); rapidly progressive oste oporosis. Other conditions associated with medullary nephrocalcinosis \200 Hyperaldosteronism and a pparent mineralocorticoid ex- cess syndromes. This is likely related to chronic hypoka- lem ia in \202 uencing calcium handling by the kidney. Recurrent pyelonephritis. Severe premat urity (see below). Hereditary and congenital disorders \200 Dent \200\231s disease. This is an X-linked recessive disorder caused by a mutation in volt age-gated chloride channels with a Fanconi syndrome phenotype, hypercalciuria, medullary ne phrocalcinosis, renal impairment and varia- ble urinary acidi \201 cation defects. \200 CHAPTER 8.3 Nephrocalcinosis 279 \200 \200 \200 \200 \200 \200 \200 Clinical presentation \200 oxalate; sodium; protein; creatinine (to con \201 rm complete collection). Spot urine samp le to measure: pH; amino acids; 2-Microglobulin (as a measure of low molecular weight pro teinuria); glucose; bacterial culture (in \202 ammatory pyuria is common). The extent of calci \201 cation does not correlate with dis- ease activity. Medullary calc i \201 cation is more likely to have clinically relevant consequences than cortical calci \201 cation. The symptoms and signs are caused by several mecha- nisms: \200 damage to the tubular epithelium leading to loss of concentrating ability and therefore pol yuria and thirst; erosion of the papillary epithelium causing symptoms and signs of nephrol ithiasis; distal tubular dysfunction leading to salt wasting and hypovolemia; erythrocytosi s: the mechanism is unclear but may be related to capillary damage and hyperreninism caused by salt wasting. \200 Natural history and management Potential long-term complications \200 Distal RTA can develop secondary to medullary nephro- calcinosis. It is therefore dif \201 cult to diagnose primary dRTA in patients with nephrocalcinosis in the absence of a family history of the disease. Progressive CKD can occur and is more likely to be associated with metabolic disorders such as primary hyperoxaluria and Dent \200\231s disease than with med ullary sponge kidney. Reports of the likelihood of progression vary. In one series 15% of p atients evaluated for nephrocalcinosis had a creatinine clearance of <50 mL/min. Osteopenia was reported in 15 of 23 patients with neph- rocalcinosis in a small study. This may be re lated to an underlying calcium metabolism disorder rather than to nephrocalcinosis per se. Investigations To con \201 rm the diagnosis of nephrocalcinosis Imaging Macroscopic nephro calcinosis can be detected by plain KUB radiography, ultrasonography and noncontrast enhanc ed helical CT. The speci \201 city and sensitivity are increased if two imaging techniques are used one of which is a noncontrast enhanced helical CT. Intravenous urography has a hi gher sensitivity for demon- strating medullary sponge kidney. Pharmacological management Management of the underlying cause may halt the precipi- tation of further deposits. Nephrocalcinosis lesions are no longer visible radiologi- cally in mos t severely premature infants by the age of 7 years. In adults resolution of established les ions is not widely described but thiazides have been reported to arrest progression. Anothe r report suggests that sodium thiosulphate could play a role in halting or reversing progre ssion. The bene \201 - cial effect may be mediated by generation of calcium thio- sulfate that is a soluble compound, and/or stabilization of glutathione which may protect the renal parenchyma from free radical-induced injury. Renal biopsy As proteinuria is not commonly present in nephrocalcino- sis unless the underl ying cause produces Fanconi \200\231s syn- drome, renal biopsy is not usually performed as part of the diagnostic evaluation. When nephrocalcinosis is suspected, imaging and meta- bo lic evaluation are commonly used to con \201 rm the diag- nosis. Nephrocalcinosis can be s een on biopsies performed for other indications, however, and has been reported in asso- ci ation with focal segmental glomerulosclerosis. To identify the causes and complications of nephrocalcinosis Detailed family and drug histo ry. History of skeletal disease. Nonpharmacological management In patients with hypercalciuria, salt and animal protein rest riction may reduce progression and the risk of nephro- lithiasis. Depending on the underlyi ng cause, metabolic derange- ments may occur and dietary supplementation may become necessa ry such as in hypomagnesemia \200\223hypercal- ciuria syndrome. Serum metabolic evaluation: \200 calcium (if elevated investigate as described in Chapter 2.3); phosphate; magnesium; bicarb onate; sodium; potassium; chloride; thyroid function tests. \200 \200 \200 \200 \200 \200 Surveillance If a familial disease is suspected, family members should be counseled and eva luated. Regular monitoring should include: \200 renal function and proteinuria; \200 se rum and urinary electrolytes; \200 bone chemistry; \200 bone density. Urine metabolic evaluation: 24 h urine collection (refer to Chapter 8.1 for details) to mea sure: \200 \200 calcium; phosphate; R. AL JAYYOUSI 280 Further reading Beyea A, Block A, Schned A. Acute phosphate nephropathy follow- ing oral so dium phosphate solution to cleanse the bowel for colonoscopy. Am J Kidney Dis 2007; 50: 151 \200\223154. Seikaly MG, Baum M. Thiazide diuretics arrest the progression of nephrocalcinosis in childr en with X-linked hypophosphatemia. Pediatrics 2001; 108: E6. Wrong, O. Nephrocalcinosis. In: Davison AM, Cameron JS, Grunfeld J-P, Kerr DNS, Ritz E, Win earls CG (eds), The Oxford textbook of nephrology, 3rd edn. Oxford: Oxford University Press ; 2005. pp. 1257 \200\2231280. Cheidde L, Ajzen SA, Tamer Langen CH, Christophalo D, Pfeferman, Heilberg I. A critical app raisal of the radiological evaluation of nephrocalcinosis. Nephron Clin Pract 2007; 106: c1 19 \200\223124. Kummeling MT, de Jong BW, Laffeber C, et al. Tubular and intersti- See also Medical management of stone disease, p. 270 Renal and urinary tract stone disease in children, p. 282 Hypo-/hypercalcemia, p. 52 Hypo-/hyperphosphatemia, p. 56 Fanconi syndr ome, p. 204 Renal tubular acidosis, p. 208 tial nephrocalcinosis. J Urol 2007; 178(3 Pt 1): 1097 \200\2231103. Manley P, Somer \201 eld J, Simpson I, Barber A, Zwi J. Bilateral uraemic optic neuritis c omplicating acute nephrocalcinosis. Nephrol Dial Transplant 2006; 21: 2957 \200\2232958. Monk R, Bushinsky D. Nephrolithiasis and nephrocalcinosis. In: Johnson and Feehally (eds), Comprehensive clinical nephrology, 2nd edn. Amsterdam: Elsevier; 2003. pp. 731 \200\223741. M ller D, Eggert P, Krawinkel M. Hypercalciuria and nephrocalcino- sis in a patient receiv ing long-term parenteral nutrition: the effect of intravenous chlorothiazide. J Pediatr Gas troenterol Nutr 1998; 27: 106 \200\223110. Porter E, McKie A, Beattie TJ, McColl JH, Aladangady N, Watt A, White MP. Neonatal nephroca lcinosis: long term follow up. 2007. Arch Dis Child Fetal Neonatal Ed 2006; 91: F333 \200 \223336. This page intentionally left blank W. VAN T HOFF 282 Renal stone disease in children Groups at higher risk for stone formation include ex-pre- mature infants and children with severe neurological disa- bility. Renal stones are still very rare in children. However, as the age of onset of stone disease in adults reduces, there is an increasing number of young people, especially females, with stones. The presentation and etiology of stone disease differs con- siderably from adults, with a greater burden of inherited metabolic stone disorders. Similarly, the management of stones, especially in infants, re \202 ects the technical limits of lithotripsy and minim ally invasive techniques. Management Initial management After analgesia, rehydration and treatment of infection, the \201 rst aim is to con \201 rm the stone burden and plan for stone removal (delay metabo lic evaluation until stones are cleared). Ultrasound is the \201 rst-line investigation i n children (it is much more sensitive than in adults). Obtain a plain radiograph of the abd omen (KUB) to check for the presence of ureteric stones (ultrasound will miss these due to overlying bowel gas). Following diagnosis, it is essential to liaise with clinicians with s peci \201 c expertise in the management of renal stones in the pediatric age group (for ex ample a regional pediatric stone service). Usually further imaging is required to de \201 ne split renal function and identify pre-existing renal damage (e.g. DMSA renogram), and ca lyceal anatomy to plan stone removal (e.g. limited IVU). This may be undertaken at a specia list unit. Metabolic evaluation should usually be postponed until after stone clearance is achieved. Pathogenesis In the UK and developed countries, 25% of cases are related to previous urina ry tract infection (UTI), 50% have an underlying metabolic abnormality, and in 25% no cause is identi \201 ed. However, such a de \201 nition of abnormality (e.g. higher than 95% c entile for age-related normal ranges) is scienti \201 cally not useful since there is over whelming evidence in adult stone-formers that the risk of stone formation increases steadil y with increasing urinary oxalate and calcium excre- tion (even within the \200\230normal range \200\231). Infective stones are commonest in young children, espe- cially in uncircum cized boys. Infection with urea-splitting bacteria produces ammonium ions, alkalinizes the urine and leads to supersaturation of magnesium ammonium phosphate. Most children with infe ctive stones do not have under- lying congenital urological abnormalities but children with reconstructed bladders, ileal conduits, urinary stasis or obstructive lesions are at incre ased risk of stone formation. The commonest type of stone is calcium oxalate, usually as di hydrate and often with a minor component of calcium phosphate. Hypercalciuria is a common f inding in such situations although usually this is unrelated to renal tubulopathy (such as distal RTA or hypomagnesemia \200\223hypercalciuria syndrome) or hypercalcemia. Primary hyp erparathyroidism is extremely rare in children. Hypocitraturia is a common \201 nding. Ch ildren with hyperoxaluria (either primary or secondary) will produce calcium oxalate stones . The \201 nding of mono- hydrate crystals suggests a need to exclude hyperoxaluria. Cyst ine stones are diagnostic of cystinuria. Uric acid stones require further investigation to exclude speci \201 c metabolic disorders. Stone clearance Single stones may require one or two treatments with the newer minimally in vasive techniques. Clearance rates are comparable to those in adults, with clearance rates of 85 \200\22390% for each of the modalities listed below. Children with a signi \201 cant stone burden (e.g. bilateral and multiple stones) will need several sessions over a number of months to clear the calculi. Lithotripsy \200 Very successful for many pediatric stones but it usually requires a general anesthetic, and may need several ses- sions for complex (staghorn or multiple) stones. Less successful for lower pole stones and cystine calculi. Associated with transient renal \200\230injury \200\231 e.g. enzymuria, but there is currently no evidence of long-term compli- cations. Percutaneous nephrolithotomy \200 Very good success rate. \200 Technically very demandi ng in small children. \200 Main complications are bleeding, infection and urine leakage. Presentation Stones can develop at any age, and as young as the \201 rst weeks of life (g rit or \200\230putty-like \200\231 material in nappies). Typical symptoms (pain, hematuria , persistent UTI) may be present but pain is not reported in 50% of children with stones. N onspeci \201 c symptoms may occur in infants: poor feeding, vomiting, poor weight gain (me an weight and height of chil- dren presenting with stones are below 50% centile). A family history is common ( 20% of \201 rst degree and 40% of second degree relatives have stones ). Ureteroscopy and laser disintegration of stones \200 Useful for ureteric and mobile renal stones. \200 Main complications are infection and ureteric damage. Open surgery \200 This is rarely required but still has a limited role. CHAPTER 8.4 Renal stone disease in children 283 Cystinuria \200 Metabolic evaluation Stone analysis. This may suggest the etiology: \200 Children with cystinuria should all receive a high \202 uid intake (>1.5 L/m2/day), salt restriction and potassium cit- rate. Urinary cystine concentrations should be maintained at <1000 mol/L. Tiopronin or penicillamine act as sulfhydryl-chelating agents and are effec tive but have signi \201 cant adverse effects (rash, bone marrow suppression, nephropathy and other systemic effects). They are therefore reserved for those with recurrent stones or kidney damage. Magnesium ammonium phosphate/calcium apatite (stru- vite). This suggests urinary infection. Calcium oxalate dihydrate (weddellite) and monohy- drate (whewellite). This is suggestive of idiopathic stone formation, and is also seen in hyperoxaluria (primary or secondary). Ca lcium phosphate (usually hydroxyapatite, rarely brus- hite, tricalcium phosphate (whitlocki te) or octocalcium phosphate). It is often a minor component of other cal- cium or struvite stones. It suggests alkaline urine and hypercalciuria, so if it is a major component of th e stone consider distal renal tubular acidosis and primary hyper- parathyroidism. Cystine. This indicates cystinuria. Uric acid. Magnesium ammonium phosphate is seen in endemic stone areas; other uric acid stones are rare (see below) Hyperoxaluria and purine disorders \200 The speci \201 c management of hyperoxaluria and purine disorders is detailed in later Cha pters 15.13 and 15.14. \200 Prognosis Most children have a single stone episode but a signi \201 - cant number have a potential biochemical abnormality that increases stone risk and a small number have mono- g enic metabolic disorders that cause recurrent stones and can lead to CKD. All children ther efore should receive prompt stone clearance and thereafter undergo a metabolic evaluation. Plasma biochemistry (including bicarbonate, urate). Urine biochemistry. Measure urine speci \201 c gravity, calcium, oxalate, citrate, urate and cystine excretion: \200 \200 \200 \200 Screen with spot urine samples in young children. Con \201 rm results with 24 h urine coll ections. Specialist laboratory analysis. Reference data for children rather than adults. Further reading Coward RJM, Peters CJ, Duffy PG, et al. Epidemiology of pediatric renal sto ne disease in the UK. Arch Dis Child 2003; 88: 962 \200\223965. Rizvi SA, Naqvi SA, Hussain Z, et al. Pediatric urolithiasis: developing Further metabolic studies as indicated. nation perspectives. J Urol 2002; 168: 1522 \200\2231525. VanDervoort K et al. Urolithiasis in pediatric patients: a single center study of incidence , clinical presentation and outcome. J Urol 2007; 177: 2300 \200\2232305. Ongoing management and prevention The principles of medical management are similar to those in adult stone disease. van \200\231t Hoff W. Renal and urinary tract stone disease in children. In: Davison AM, Ca meron S, Grunfeld J-P, Ponticelli C, Ritz E, Winearls C, van Ypersele C (eds), Oxford textb ook of clinical neph- rology, 3rd edn. Oxford: Oxford University Press. Chapter 8.3, pp. 12 81 \200\2231291. Hydration \200 The mainstay of stone prevention is good hydration to maintain high urine \202 ow rates. Diet \200 Internet resources Information on kidney stones aimed at teenagers: Dietary review is useful but in general protein and calo- rie intake should be maintained t o permit good growth. In contrast to adult stone disease where a signi \201 cant pro- port ion of patients are overweight, growth parameters are below average in children with stones . Sodium intake should be reviewed but restriction of cal- cium intake is counterproductive (as well as impractical in young children). http://www.childrenfirstforhealth.co.uk/teens/ health/conditions/k/kidney_stones.html Infor mation on childhood stone disease: http://www.pediatriconcall.com/forpatients/ CommonChild/Urinary_renal.asp See also Primary hyperoxalurias, p. 632 Inherited disorders of purine metabolism and transp ortation, p. 636 Isolated defects of tubular function, p. 200 Medical management of stone d isease, p. 270 Surgical management of stone disease, p. 274 Hypercalciuria \200 This alone is not necessarily an indication for speci \201 c therapy other than increased \202 uid intake and salt restric- tion. The risk of further stone formation in hypercalci u- ric children is low. In those with a signi \201 cantly damaged kidneys, or recur- rent symptoms or stones, consider \201 rstly potassium cit- rate, and then a thiazide diuretic . This page intentionally left blank 285 Chapter 9 Hypertension Chapter Contents Clinical approach to hypertension 286 Renovascular disease 292 Malignant hypertension 300 H ypertensive children 304 Hypertensive disorders in pregnancy 310 A. STANLEY 286 Clinical approach to hypertension Introduction Hypertension (HTN) is one of the most common condi- tions encountered in medic al practice. For the majority of patients, the etiology is unknown and the treatment is str aightforward. This chapter provides an overview of the clinical assessment of a hypertensiv e patient with particu- lar reference to the less common etiologies, its complica- tions an d initial treatment options. Renovascular HTN is a relatively uncommon cause of HTN (<1% of newly diagnosed patients) an d can present as \201 bromuscular dysplasia in the young or atherosclerotic renal artery stenosis in older people. Endocrine disease This is the cause of HTN in 5% of cases. Hyperaldosteronism (e.g. Conn \200\231s syndrome, adrenal hyperplasia) accounts for the majority of cases. The combined o ral contraceptive pill increases BP by an average of 5/3 mmHg; in 1% of women, severe HTN may be seen. De \201 nition British, European and WHO guidelines de \201 ne the catego- ries of HTN ba sed on clinic blood pressure (BP): Blood pressure Other causes Other causes are rare and combined account for 1% of all HTN. Single gene dis orders affecting renal tubular function are very rare and usually present in childhood. Pre gnancy-induced HTN affects 8 \200\22310% of pregnancies and pre-eclampsia affects a further 8% of pregnancies. Blood pressure returns to normal in most women with pregnancy-related H TN after 3 \200\2236 months, but is a risk factor for the development of HTN later in the w oman \200\231s life. Optimum: Normal: High \200\223normal: <120/80 mmHg <130/85 mmHg 130 \200\223139/85 \200\22389 mmHg. Hypertension Mild (grade 1): Moderate (grade 2): Severe (grade 3): 140 \200\223159/90 \200\22399 mmHg 160 \200\223179/100 \200\223109 mmHg >180/110 mmHg. Isolated systolic hypertension Grade 1: Grade 2: 140 \200\223159/<90 mmHg >160/<90 mmHg. Assessment of the patient History Hypertension is often asymptomatic, hence its description as the \200\230silent killer \200\231. The history from a hypertensive patient should: \200 \200 \200 Epidemiology The prevalence of HTN increases with age. Data from the Health Survey for Engl and 1998 revealed 72% of men and 68% of women aged >75 years had HTN (de \201 ned by a BP >140/90 mmHg). This compares to 17% and 4% in men and women aged 16 \200\22324 years respec tively. However, the number of patients prescribed treatment for HTN is much less. Data fro m primary care (Key Health Statistics from General Practice 1998) revealed that <2.5% of pa tients aged under 35 years (men: 1.7%; women: 2.4%) and <30% of patients aged \211 85 year s (men: 20.1%; women: 29.1%) were taking antihypertensive drugs. It is not known whether th ese patients were treated to target BP. attempt to establish an etiology; identify complications/end organ damage; put the HTN into the context of overall cardiovascular risk. Baseline features to assess: \200 \200 \200 duration of HTN and BP values; treatment history and concordance with treatment; any advers e drug reactions. Establishing an etiology A family history of HTN. In women a history of pregnancy-related H TN. A history of any recent \200\230over the counter \200\231 and/or prescribed drug thera py: \200 NSAIDS; \200 combined oral contraceptives; \200 corticosteroids; \200 symp athomimetics. Etiology The cause of HTN in the vast majority of cases, even in young people, is not clear . About 90% of people with newly diagnosed HTN are given the diagnosis \200\230primary \200\231 (or \200\230essential \200\231) HTN and the etiol- ogy is likely to re \202 ect a multifactorial genetic predisposi- tion and/or lifestyle factors such as obesity and poor diet. Secondary HTN accounts for the remaining 10% of cases and the causes are listed in T able 9.1.1. A history of renal or urological disease. A pheochromocytoma might be suggested by: \200 \200 \200 \200 episodic palpitations; sweating; chest pain; paroxysmal HTN. Renal disease This is the cause of HTN in 5% of newly diagnosed hyper- tensive subjects. D iabetic renal disease accounts for the majority of cases and this is increasing both in ter ms of absolute numbers and as a proportion of all CKD. Identifying complications/end-organ damage Common complications to speci \201 cally enquir e about: \200 \200 ischemic heart disease; heart failure; CHAPTER 9.1 Clinical approach to hypertension 287 At the initial assessment, the BP should be measured three times, a minute between each rea ding, and in both arms. The BP for each arm should be recorded as the average of the 2nd an d 3rd readings. A standing BP should be recorded in: \200 \200 \200 \200 Table 9.1.1 Causes of secondary hypertension Renal Diabetic renal disease Chronic pyelonephritis Renovascular hypertension Obstructive n ephropathy Renal parenchymal disease Renin-secreting tumors patients with a history of postural hypotension; the elderly; those at risk of autonomic dy sfunction (e.g. diabetics); those taking multiple antihypertensive drugs. Endocrine Mineralocorticoid hypertension Physical examination A full examination with particular reference to the heart and circulat ory system should always be undertaken. The general appearance of the patient may give clue s towards an endocrine diagnosis such as acromegaly or Cushing \200\231s disease. Signs of tar staining on the hands, obesity or hyperlipidemia (e.g. corneal arcus, xanthelasma) woul d suggest additional cardiovascular risk. Radio-femoral delay or weak peripheral pulses may sug- gest a coarctation of the aorta. A palpable kidney would raise the suspicion of hydro neph- rosis or polycystic kidney disease. Abdominal (renal) bruits are rarely heard in pati ents with renovascular disease, but their presence is highly indicative. Complications of H TN may be evident from signs of heart failure, peripheral vascular disease (femoral or caro tid bruits) or a neurological de \201 cit. Conn \200\231s syndrome Bilateral/(unilateral) adrenal hyperplasia Glucocorticoid-remediabl e aldosteronism Adrenal carcinoma Deoxycorticosterone excess Congenital adrenal hyperplasia 11B-Hydroxylase de \201 ciency 17B-Hydroxylase de \201 cie ncy Glucocorticoid receptor resistance Cortisol excess Cushing \200\231s syndrome 11B-Hydroxysteroid dehydrogenase de \201 ciency Apparent mineralocorticoid excess Glycyrrhetinic acid (licorice) Pheochromocytoma Oral contraceptive and estrogen replacement Hypothyroidism/hyperthyroidism Acromegaly Hyperparathyroidism/hypercalcemia Carcinoid Fundoscopy Fundoscopy is useful in assessing for end-organ damage. Type 2 hypertensive reti nopathy (copper wiring, arteriov- enous nipping) is very common in middle-aged/elderly pati ents with longstanding HTN. Patients with recently elevated severe high BP and type 3 hyper tensive retinopathy (hard exudates, \202 ame-shaped hemorrhages), and all patients with t ype 4 hypertensive retinopathy (type 3 abnormalities and papilloedema) are, by de \201 nit ion, hypertensive urgencies and require immedi- ate treatment. Conversely, normal fundoscop y in a patient with a long- standing history of high BP readings would cast doubt on the di agnosis of severe HTN, suggesting an alternative diagnosis of \200\230white-coat HTN \200 \231.