Fibrinous thromboemboli within arteries, with in \202 ammation of the adja- cent renal tis sue, may also occur as a consequence of septic emboli \200\224 renal abscesses can form at these sites. Thrombotic microangiopathy with cortical necrosis can complicate severe sepsi s. Acute tubular injury is a consequence of haemodynamic compromise (as well as nephrotoxic drugs (aminoglycosides or others). Treatment \200 If GN, cure IE, using appropriate antibiotics. There is no role for adjunctive treatments, even if crescentic change on biopsy. If ATN, tailor aminoglycoside doses to levels or change antibiotic. \200 IF AIN, change a ntibiotic. No role for steroids. \200 Valve surgery may be required. MRSA glomerulonephritis MRSA glomerulonephritis presents either as rapidly progressive glo- merulonephritis (RPGN) and/or as nephrotic syndrome with various degrees of proteinuria, u sually in the context of a severe MRSA infec- tion. Normal complement levels and polyclonal elevation of serum IgG and IgA are often seen. Histological changes are described in Table 8.12. CHAPTER 8 The kidney in systemic disease 694 e r a c h t i h t i h t i h t i w s e v o r p m w s e v o r p m w s e v o r p m w s n e s r o W e v i t r o p p u s e m o c t u O s c i t o b i t n a s c i t o b i t n a s c i t o b i t n a e b a i r a V l i i i I I I i l o b m e o b m o r h t s i t i r h p e n o u r e m o l g s a n o i t a r t l \201 n s i t i r h p e n y r a l l i l r e d r o s i d s i t i r h p e n o u r e m o l g p a c o d n e / l a g n a s e M i l a i t i t s e t n o u b u t s t n e c s e r c l a i t i t s r e t n o u b u T s u o n i r b \201 e s u f f i s i t i d r a c o d n e 7 0 1 e v i t a r e f i l e h t y g o o t s i H d . i p l r o i i l a i r e t r A l e b b f l o t r a p l l a c o F y a M e e S o r p e v i t c e f n s n i l i u b o l g o n u m m h t i M g I M g I w d e t a c o s s a , , A g I A g I A g I , , , G g I i G g I i G g I i i n n I t n e m e l p m o C e s a e s i d l a n e r n n n n d f o s e r u t a e f s t s a c e g n a r s t s a c a i r u s t s a c l l e c a i r u t a m e a H a i r u n e t o r p s i s y l a n i r U c i t o r h p e N l i h p o n i s o E r a l u n a r G l a i l l a c g o o h t a p o c n l l e c e h t i p E i i d e R l n o i t c r a f n N G x e p m o c - e n u m m y r u n i s i t i r h p e n o u r e m o l g i l j l a i t i t s r e t n C ) l i i N A r a l u b u t l a n e r 2 1 8 I ( . l s i t i r h p e n c i l i e l b a T A S R M e t u c A e t u c A o b m E I THE KIDNEY IN INFECTIVE ENDOCARDITIS 695 Table 8.13 Bacterial infection-related glomerular disease Mycobacterium leprae Amyloidosis (AA): \210\222 Glomerulonephritis \210\222 Diffuse proli ferative GN \210\222 Focal proliferative GN \210\222 MCGN \210\222 Mesangial proliferati ve GN Mycobacterium tuberculosis Amyloidosis (AA) MCGN type II Treponema pallidum Congenital syphilis: \210\222 Membranous nephropathy Acquired syphilis: \210\222 Membranous nephropathy \210\222 Diffuse endocapillary GN \210\222 MCGN \210 \222 Mesangial proliferative GN \210\222 Amyloidosis (AA) Salmonella typhi Mesangial proliferative GN IgA nephropathy Streptococcus pneumoniae Mesangial proliferative GN Diffuse proliferative GN Others reported in association with GN Brucella melitensis E. coli Klebsiella pneumoniae Yersinia enterocolitica Mycoplasma pneumoniae Legionella Bartonella henselae Reproduced from Oxford Desk Reference: Nephrology, Jonathan Barratt, Kevin Harris, and Pete r Topham (2008), with permission of Oxford University Press. CHAPTER 8 The kidney in systemic disease 696 Renal tuberculosis Introduction Tuberculosis is caused by Mycobacterium tuberculosis and af fects 8 \200\223 10 mil- lion people every year, usually presenting as pulmonary disease. The global burden of TB has risen sharply as a result of HIV infection and the increased nu mber of patients with solid organ transplants taking long-term immu- nosuppressive medicati on. (cid:2) Data from the World Health Organization (2010) suggests that one-third of the w orld population has been exposed to TB and has at least latent disease. After lymph node involvement, the most common site of extrapulmo- nary TB is the genitourin ary system (15 \200\223 30% all cases). Renal dysfunction can occur through a variety of m echanisms, including direct infection of the kidney or lower urinary tract, obstructive uro pathy, tubulointerstitial nephritis, and secondary amyloidosis. Genitourinary TB (GUTB) Pathogenesis Mycobacterium tuberculosis bacilli are inhaled into th e alveoli. Initially, the bacilli are locally contained by leucocytes and macrophages, but, over time, they are carried to regional lymph nodes and the thoracic duct before delivery into venous blood and seeding of distant organs. In the kidneys, multiple granuloma form at the site of metastatic foci. These are typically bilateral, cortical, and adjacent to the glomeruli. They can remain inactive for decades. Active granulomas may grow to invade the calyceal systems, resulting in the spread of bacil li to the renal pelvis, ureters, bladder, and other genitourinary organs, including the epi didymis and prostate. The renal medulla is preferentially affected, but subsequent papillary and pelvic involveme nt causes progressive scarring, calci \201 cation, \201 brosis, and chronic abscess form ation. Extensive lesions will result in ESRD. Ureteral TB may cause strictures (can be extensive), hydronephrosis, and obstruction. Often unilateral. Symptoms and signs Classical TB symptoms, e.g. fever, weight loss, and night sweats, are un common. Pulmonary symptoms may be absent (although 7 30% will have an abnormal CXR). Sympto ms are often non-speci \201 c, with >25% asympto- matic. It is 6 essential to maintain a h igh index of suspicion in those at risk. Abdominal (particularly back and \202 ank) pain, LUTS, recurrent UTIs that are poorly antibiotic-responsive, macro- and microscopic haematu ria, incontinence (bladder \201 brosis), infertility in both sexes. Investigation \200 Sterile pyuria (WCC on microscopy but negative culture) is characteristic ( b p. 24). Three consecutive early morning urine samples (EMUs). Microscopy for acid-fast bacilli on centrifuged urine (Ziehl \200\223 Neelsen stain) and c ulture on L wenstein \200\223 Jensen media (takes 2 \200\223 6 weeks). RENAL TUBERCULOSIS 697 EMUs for AFBs have a sensitivity of only 65% (although speci \201 city is 7 100%). More rapid results (<1 week) with a radiometric culture system (BACTEC). PCR for mycobacterial DNA can be helpful when available. It is a rapid test with high sensitivity and speci \201 city. U&E ( d Na + s to SIADH), SCr, LFTs, CRP, FBC, ESR. \200 2 Consider HIV testing. \200 T uberculin skin testing is usually undertaken; however, beware false positives in those pati ent vaccinated with BCG and false negatives in those on immune suppression. \200 Plain KU B may show calci \201 cation. \200 IVU or CT-IVU: abnormal (70 \200\223 90%), with caly ceal tip erosions ( \200\230 moth-eaten \200\231 calyx), pelvic distortion (e.g. the \200\230 hiked-up \200\231 appearance), strictures, \201 lling defects, and calci \201 cation. \200 Rena l tract USS if obstruction suspected. CHAPTER 8 The kidney in systemic disease 698 Renal tuberculosis: TB-TIN and TB in patients with ESRD Tuberculous interstitial nephritis (TB-TIN) Pathogenesis A presumed immune-mediated process. TB causes a parenchymal reaction character ized by giant cells, tubulointerstitial in \202 ammation, and caseating granuloma formatio n. TB-TIN is a more insidious and less well-recognized form of renal involvement but is tho ught to be an underestimated world- wide cause of renal failure (e.g. in Asian patients pre senting with advanced CKD and small kidneys on imaging). Symptoms and signs Usually presents as CKD in at-risk populations (esp. South Asians). Urin alysis is bland. USS shows normal or decreased renal sizes, usually with a smooth contour. EMU for AFBs are usually negative. CXR may demonstrate prior or active pulmonary TB. Skin t uberculin testing is often positive. Diagnosis made on renal biopsy, although this may not under- taken if kidneys are small at presentation. Mycobacterium tuberculosis can be identi \201 ed on tissue stain or paraf \201 n-embedded samples, although detection rates are o ften low. Luciferase and \202 uorescence technique improve sensitivity and can detect low numbers of mycobacteria. Management Anti-TB treatment is associated with improved renal function, and recov- ery fro m even advanced CKD has been reported. Cure requires combina- tion therapy for 6 months. Co mpliance may be problematic and should be reinforced through good patient education. The se nsitivities of cultured M. tuberculosis should be con \201 rmed, but this should not delay initiation of treatment once the diagnosis has been secured. 2 Check local protocols for drug selection and dosing. 2 A dose adjustment is required for most agents if d GFR. Initial phase (2 months) Once-daily rifampicin, isoniazid, pyrazinamide (available in combi nation preparations, e.g. Rifater ). Add-on ethambutol or streptomycin if immu- nocompro mised or previously treated for TB ( (cid:2) isoniazid resistance). Continuation phase (fur ther 4 months) Rifampicin and isoniazid. Notes \200 Add pyridoxine 10 \200\223 20mg daily (prevents the peripheral neuropathy associated with isoniazid). Check LFT before and 3-weekly during initial phase. \200 Check visual acuity if using eth ambutol (risk of irreversible optic neuropathy). If HIV-positive, prolonged multidrug treatment may be necessary. RENAL TUBERCULOSIS: TB-TIN AND TB IN PATIENTS WITH ESRD 699 X Corticosteroids, e.g. prednisolone 0.5mg/kg for 2 months and weaned thereafter. This is poorly evidence-based. Theory: granulomatous in \202 ammati on heals by \201 brosis so reduce in \202 ammation to prevent secondary scarring. Genera lly reserved for those with severe 9 rapidly progressive CKD. TB in patients with ESRD \200 Dialysis patients have a signi \201 cantly increased (6 \200\223 25-fold) risk of TB. \200 ESRD is considered a state of relative immune compromi se, mainly s to disruption of cell-mediated immune (CMI) responses. CMI response is primari ly mediated by T cells, whose functions include the identi \201 cation and killing of intr acellular pathogens, such as M. tuberculosis . Nosocomial transmission of TB in dialysis units has also been reported. Risk factors include: older age, Asian race, smoking, malnutrition, and anemia. The diagnosis in this population is dif \201 cult because disease is often non-pulmonary and symptoms may be non-speci \201 c. Diagnosis \200 Tuberculin skin test consists of intradermal injection of tuberculin. In p ositive cases, a T cell-mediated delayed type hypersensitivity reaction causes a variable d egree of induration within 48 \200\223 72 hours. However, a high prevalence of anergy in d ialysis patients means that response rates are poor, so false positives are common. Interferon gamma release assays (IGRAs) appear more sensitive and speci \201 c in this population. \200 T cells from patients exposed to TB become sensiti zed to two proteins termed ESAT-6 and CFP-10. When these T cells are exposed to these antig ens in the assay, they produce IFN- G , and the strength of this response can be quanti \201 ed. Note: IGRAs do not distinguish between latent and active disease. Examples include the T-SPOT TB test and the QuantiFERON-TB Gold In-Tube test (QFT-GIT)). IGRAs have now been included in the guidelines for the detection of latent TB infection in many countries, including the USA and UK. CHAPTER 8 The kidney in systemic disease 700 Schistosomiasis Introduction Schistosomal infestation (a water-borne trematode) affects as many as 200 million people worldwide and may lead to urinary tract disease or glomeruloneph ritis. S. haematobium is endemic in most of Africa and the Middle East. It preferentially m igrates to the venous plexus surrounding the bladder, causing lower urinary tract disease. S. mansoni (additionally found in Latin America) and S. japonicum (found in Asia alone) mig rate to the mesenteric vessels or portal tree, causing hepatosplenic disease Pathogenesis Acute infestation tends to occur in childhood in residents of endemic areas bu t can affect travelers of any age. It is characterized by dermal invasion ( \200\230 swimm er \200\231 s itch \200\231 ) and a subsequent systemic serum sickness-like syndrome ( \200\230 Katayama fever \200\231 ) with eventual maturation of a trematode in blood vessel s. Eggs released from mature worms cause delayed type hypersensitivity and granulomatous in \202 ammation in local tissues. Urinary schistosomiasis Caused by S. haematobium infestation. Presents with terminal haemat uria (frank blood at the end of micturition), dysuria, and frequency as a result of an in \202 ammatory cystitis. A quiescent, asymptomatic period follows that can last for decades. Late schistosomiasis occurs in 10 \200\223 40% and may lead to progressive bladder \201 brosis and detrusor failure. Ureteric stricture formation with obstruction is common ( 7 1 0%). Complications: recurrent bacterial infection, bladder calculi, CKD (and ESRD) s to obs tructive nephropathy, and an increased risk of bladder cancer. Investigations \200 Typical live ova on urine microscopy (centrifuge sample to improve yield). FBC (eosinophilia), U&E, SCr, eGFR, LFTS. \200 Serology: anti-schistosomal antibodies may be positive 4 \200\223 8 weeks after exposure. They will not differentiate between past a nd active disease. However, a positive test in an individual who does not live in an endemi c area can be helpful. PCR for schistosome DNA is highly sensitive and speci \201 c on stool and urine samples, if available. Plain KUB may demonstrate calci \201 cation. \200 USS to exclude obstruction \200\224 t reatment will often improve anatomical abnormalities in schistosomiasis, unlike GUTB ( b p. 696). Cystoscopy may show a nodular or polypoid lesions 9 ulcerating haemorrhagic cystitis. Schistosomal glomerulonephritis Complicates hepatosplenic disease in 7 10% patients with S. mansoni (less common with other species). Although the worms have developed strate- gies t o evade immune recognition, if these are incomplete, an antibody response may result in cir culating immune complex formation. These SCHISTOSOMIASIS 701 become trapped in glomeruli (esp. if liver \201 brosis has caused poor immune complex cle arance), causing in \202 ammation and glomerulonephritis. Presents as proteinuria (often nephrotic range), haematuria, and impaired renal function. S everal histological variants are recognized on kidney biopsy, including mesangioproliferati ve, MCGN-like, and FSGS. Co-infection with Salmonella may lead to a diffuse proliferative l esion (presents as the acute nephritic syndrome). Cryoglobulinaemia (usually concomitant he p C) and secondary AA amyloidosis are also possibilities. Treatment African Association of Nephrology (AFRAN) classi \201 cation (classes I \200\223 V): \200 Classes I and II respond to anti-helminthic therapy. \200 Classes III \200\223 V progress to ESRD in spite of therapy (75% progress to advanced CKD or RRT over 4 \200\223 6 years). Praziquantel 40mg/kg PO stat (80 \200\223 90% cure rate). \200 If S. japonicum , i dose to 60mg/kg in two divided doses. \200 There may be some resolution of urinary tract lesio ns in urinary schistosomiasis (esp. if little \201 brosis). However, strictures may require urological intervention. Schistosomal glomerulonephritis responds poorly. CHAPTER 8 The kidney in systemic disease 702 Malaria Introduction Malaria is caused by Plasmodium parasites transmitted via Anopheles mo s- quitoes. It is endemic in many parts of the world, affecting 300 \200\223 500 mil- lion people annually and causing 1 \200\223 3 million deaths/year. Previously only P. falcipar um and P. malariae were associated with renal disease, but AKI and glomerulopathy are now r ecognized with P. vivax . AKI due to malaria can occur as part of multi-organ failure or as an iso- lated complicatio n. The causes of AKI in malaria are complex and multiple. Histological \201 ndings includ e ATN (most frequent), interstitial nephritis, and a proliferative glomerulonephritis. Glomerulopathy s to malaria is most common in childhood and ado- lescence, with glomerular lesions found post-mortem in 7 20% of patients with falciparum malaria. AKI 2 to malaria AKI complicates P. falciparum malaria in 1 \200\223 4% cases but is mor e com- mon in non-immune travelers ( 7 25%). If severe, >50% will require renal support, an d mortality is 7 10% (partly due to non-availability of RRT). Although P. vivax is usually considered a benign parasite with a low mor- tality rate, it can rarely cause severe diseas e with AKI. Pathogenesis Proposed mechanisms include immune-mediated glomerular injury, hyperbilirubina emia ( l ATN), alterations in the renal and systemic haemodynamics, cytoadherence of infect ed RBCs ( l capillary obstruc- tion), mononuclear cell in \201 ltration ( l in \202 ammat ory cytokine release), and increased release of both reactive oxygen species and nitric oxi de. In addition, dehydration, haemolysis ( l haemoglobinuria), DIC, and rhabdomyolysis may all contribute. Signs and symptoms Nausea, vomiting, diarrhea, malaise, headache, confusion, fevers, myalgi a, jaundice ( 7 75%), and haemoglobinuria (blackwater fever). d BP, peripheral vasodilatati on, anemia, and hepatosplenomegaly. Investigations Urinalysis and uPCR (proteinuria usually <1g/24h). FBC (haemolytic anae- mia ), d Plt (70%). Thick and thin blood \201 lm for parasitaemia (usually >5%). Haptoglobins . DIC (APTT, INR, D-dimers). U&E ( d Na + in >50%), SCr, CK, LFTs (hepatitis in 7 20%), and serum lactate (acidosis common). Management \200 Manage patients with AKI in high depend ency environment. \200 RRT may need early initiation, as patients are highly catabolic. I n addition, i K + can be severe ( s to haemolysis, rhabdomyolysis, and acidosis). Supportive blood products, as required. \200 Culture blood, and consider empirical broad- spectrum antibiotics (bacterial superinfection is not uncommon). MALARIA 703 IV quinine loading dose as 20mg/kg (max 1.4g) over 4h, then 10mg/kg (max 700mg) IV over 4h qds for 7 days, with cardiac monitoring. \200 Artemisinin derivatives clear parasitaemia more rapidly, act against more stages of the parasitic life cycle, and reduce mortality, in comparison to quinine, but are not widely available. Artesunate 2.4mg/ kg IV \201 rst do se, followed by 2.4mg/kg at 12 and 24h, followed by 2.4mg/kg once daily for 3 days, then or al therapy, as necessary. Doxycycline may be added. \200 If the patient has G6PD de \201 ciency, seek expert help. \200 X The role of exchange transfusion is controversial and reserved for high-burden pa rasitaemia. Potential bene \201 ts are quicker reduction of parasitaemia and a decreased r isk of severe intravascular haemolysis. The Centers for Disease Control (CDC) suggests it s hould be considered if parasite density is >10%, with evidence of end-organ complications. Glomerular involvement in malaria Transient nephrotic and nephritic illnesses may be seen d uring infection with P. falciparum and P. vivax . These glomerulopathies are reversible \200\224 usually resolving within 2 \200\223 6 weeks of treatment. The histological lesion is typically mesangial hypercellularity with mesangial and subendothelial deposition of Ig G, IgM, and C3. Serum complement components may be reduced s to immune complex formation. Chronic malarial nephropathy (or quartan malarial nephropathy) is a different entity. It is the most common form of secondary glomerular disease in the tropics, causing nephrotic syn drome, mainly in children and adolescents. It is usually associated with P. malariae , occa sionally P. vivax . The histological lesion is an MCGN-type pattern of injury, with subendo thelial immune complex deposits containing IgG, C3, and (rarely) malarial antigens. Pathoge nesis, particularly the role of the malarial parasite, is still a matter of signi \201 can t debate. is steroid-resistant and generally does not improve with successful eradi- cation of the ma larial infection. Progression to ESRD occurs within 5 years. The renal prognosis is poor. The nephrotic syndrome 705 Chapter 9 Essential urology Urinary tract infection: introduction 706 Urinary tract infection: investigations and treat ment 708 Urinary tract infection: miscellaneous 710 Re \202 ux nephropathy 712 Congenital abnormalities of the kidney and urinary tract 714 Nephrolithiasis 716 Stone disease: evalua tion 720 Stone disease: management 722 Acute renal colic 724 Obstruction: overview 726 Obst ruction: pathophysiology 728 How to approach obstruction 730 Obstruction: imaging 732 Obstr uction: treatment 734 Pelvi-ureteric (PUJ) obstruction 736 Retroperitoneal \201 brosis: o verview 738 Retroperitoneal \201 brosis: management 740 Investigation of a renal mass 742 Renal cell carcinoma: general 744 Renal cell carcinoma: diagnosis 746 Renal carcinoma: man agement and follow-up 748 Tumors of the bladder: overview 750 Tumors of the bladder: pathol ogy and management 752 Tumors of the renal pelvis and ureter 756 Benign prostatic enlargeme nt: general 758 Benign prostatic enlargement: investigation and management 760 Prostate cancer: general 766 Prostate cancer: investigation 768 Prostate cancer: screening 772 Prostate cancer: management 774 CHAPTER 9 Essential urology 706 Urinary tract infection: introduction Introduction The incidence of UTI (including infectio ns of the bladder and kidneys) is 7 50,000 pmp, making it, by far, the most common disorder of the renal tract. 50% of \231\200 will experience UTI in their lifetime, predominantly cystitis (usually occurring in a normal urinary tract). 7 10% of post-menopausal \231\200 and 7 0.5% of younger sexually active \231\200 will have a UTI each year. A second infection is common in women who have had one UTI, but only 3 \200\223 5% will de velop recurrent UTIs ( b p. 710). In men and children, UTI is rare and almost always associ ated with urinary tract abnormalities that require further investigation ( b p. 708). Altho ugh serious morbidity from UTI is usually low, renal scarring can result from sporadic or r ecur- rent infections. Bacteraemia from a UTI can be a life-threatening medical emergency. UTI in pregnancy is discussed on b p. 842. De \201 nitions Asymptomatic bacteriuria is the isolation of a signi \201 cant bacterial count in an asymptomatic patient ( b p. 710). Uncomplicated UTI is a symptomatic bladder in fection (cystitis) in a \231\200 with a normal urinary tract. Complicated UTI is a symptom atic infection of any part of the urinary tract in a \231\200 with a functional or structu ral urinary abnormality. Re-infection is a recurrent UTI with the same or different organis m, following clearance of the original UTI. Relapse refers to a recurrent UTI with the same organism that has not been adequately cleared. Pathogenesis In \231\200 , the pathogens responsible for UTI are found in the colonic \202 ora. Subsequent UTI is usually ascending, i.e. after perivaginal, perineal, and transu rethral colonization, often triggered by intercourse. Lactobacilli, found as commensals in the vagina, prevent urinary pathogens from colo- nizing the perineum \200\224 changes in t he vaginal pH, use of spermicides, or antibiotic treatment may lead to failure of this defe nse mechanism. Host factors predisposing to UTI \200 Female sex. \200 Sexual intercourse. \200 Use o f spermicides. \200 Urinary stasis or incomplete bladder emptying. \200 Comorbidities, esp. diabetes mellitus. \200 Institutionalized patient. \200 i Age ( l d estrogen + vag inal pH). \200 Eradication of vaginal commensal organisms (see \200\230Pathogenesis \200 \231). \200 Urinary tract stones. \200 Urinary catheter. \200 Highly concentrated uri ne (>800mOsmol/kg) or failed urinary acidi \201 cation (pH >5). Non-secretion of certain blood group antigens (allows bacteria with speci \201 c adhesins to recognize urothelial cells). URINARY TRACT INFECTION: INTRODUCTION 707 Some women express an inherited and unique receptor on the urothelium that aids the binding of E. coli . Also, E. coli that expresses type P \201 mbriae (pili), an adhesin that pro motes bacterial attachment to the urothelium, is particularly likely to cause pyelonephriti s. There are many other factors that have been suggested to contribute to bacterial virulen ce. Bacteriology Uncomplicated UTI \200 Escherichia coli (70 \200\223 90%). \200 Coagulase-negative sta phylococci ( S. saprophyticus ) (5 \200\223 20%). \200 Klebsiella spp. (1 \200\223 2%). \200 Enterococci (1 \200\223 2%). \200 Proteus mirabilis (1 \200\223 2%). \200 Cit robacter spp., Enterobacter spp., Pseudomonas aeruginosa , Staphylococcus aureus , group B streptococci (all <1% each). Complicated UTI \200 E. coli remains the most common, but Proteus , Klebsiella , Citrobac ter spp., enterococci, Pseudomonas aeruginosa , Staphylococcus aureus , and group B streptococc i account for a higher proportion. Symptoms and signs Cystitis or lower UTI Dysuria, frequency, urgency, nocturia, suprapubic pain, or tenderness. Offensive urine or frank haematuria. Ask about previous episodes of UT I, recent antibiotic use, pre-existing LUTS ( b p.78), and, sensitively, about new sexual p artners and spermicidal use. Vaginal irritation 9 discharge makes UTI less likely (vaginiti s more so). 2 In the elderly, UTI may present as confusion 9 incontinence. Pyelonephritis o r upper UTI Fever, chills, night sweats, rigors. Nausea, vomiting. Loin pain, costoverte- b ral (renal) angle tenderness. May be systemically unwell, with progression to SIRS and shoc k a possibility. 2 In immunocompromised (and children), all of the listed symptoms/signs may be absent \200 \224 so maintain a high index of suspicion, esp. if unexplained fever. Diagnosis \200 A pure growth of a urinary pathogen: \211 10 5 cfu/mL urine remains the standard. However , at this cut-off, 30 \200\223 50% of UTI will escape diagnosis. So, in addition, consider: \200 \211 10 2 \200\2235 cfu/mL: in young women with suspected unco mplicated cystitis, children, \231\202 , or if pyelonephritis possible. \200 Bacteriuria \211 10 2 cfu/mL associated with signi \201 cant pyuria ( 9 symptoms) is usually signi \201 cant. Bacteriuria in the absence of pyuria almost always represents contamination. CHAPTER 9 Essential urology 708 Urinary tract infection: investigations and treatment Investigations \200 Dipstick urine: positive leucocyte esterase 9 nitrite reductase. Positive predictive value of 7 66% and a negative predictive value of 7 90%. May be modest haematuri a or proteinuria. In low-risk cases, no further investigation is needed if positive dipstic k with characteristic symptoms . Clean-catch MSU for microscopy at x 40 magni \201 cation (i.e. high-powered \201 eld), pyuria (>10 4 WCC per mL urine) 9 organisms (see b p. 707). WCC c asts strongly suggest pyelonephritis. \200 Culture: sample should be cultured within 2h o f sampling. If not possible, store at 4 * (for <48h). Repeat urine culture to con \201 rm eradication post-treatment is not recommended. A pregnancy test should be undertaken if appropriate. \200 If suspected pyelonephritis: i WCC, i CRP, SCr, U&E. \200 Imaging is only required in complicated cases, e.g. fever per sists >48h despite therapy, clinical deterioration, poorly controlled diabetes, immune comp romised, systemic sepsis, recurrent episodes, stone former. \200 CT with contrast has bec ome the investigation of choice and has superseded IVU. Stones should be excluded on the no n-contrast images. CT will identify changes on renal parenchymal perfusion, obstruction, pe rinephric collections or \202 uid, and abscesses. \200 USS is also useful and preferred by many clinicians as an initial investigation, as it does not involve radiation or contrast, and it will exclude obstructio n with hydronephrosis. However, a negative USS does not exclude pyelonephritis, and ureteri c abnormalities will be missed. Pre- and post-micturition images of the bladder to exclude incomplete bladder emptying should be performed. 99m Tc-DMSA \201 ndings are non-speci \201 c, but it has a role in children. \200 In \231\202 , assess the prostate size and bladder emptying with urodynamic \202 ow studies ( b p. 760). Cystoscopy may be indicated in those at risk for bladder or prostate cancer, as well as tho se with evidence of impaired bladder emptying who may bene \201 t from urethral dilatation . Who needs closer attention? \200 Symptoms >14 days. \200 Recurrent UTI. \200 \231 \202. \200 Children. \200 Pregnant \231\200 ( b p. 842). \200 Diabetic patients. \200 The immune compromised (for renal transplant patients, see b p. 438). Proteus UTI \200\224 ? associated stones. \200 Known abnormal urinary tract. \200 Ston es. \200 Indwelling catheter or ureteric stent. URINARY TRACT INFECTION: INVESTIGATIONS AND TREATMENT 709 Treatment Antibiotic selection and duration of therapy varies widely. Prescribing choice sh ould always be informed by local antimicrobial resistance pat- terns. In general, broad-spe ctrum agents, such as co-amoxiclav, quinolo- nes, and cephalosporins, should be avoided, as they increase the risk of antibiotic resistance (as well as Clostridium dif \201 cile ). Uncomplicated lower UTI (cystitis) For empirical therapy: \200 Either : short-course (3 d ays) therapy: Trimethoprim 200mg bd (or co-trimoxazole 960mg bd). Or : longer-course (7 \200\223 10 days) therapy: Nitrofurantoin 100mg bd (not in renal impairment). If second-line treatment is necessary, e.g. hypersensitivity reaction, side effects, failur e of \201 rst-line treatment, then urine culture with sensitivity testing is recommended. Options: Fluoroquinolones, such as cipro \202 oxacin 500mg bd or levo \202 oxacin 250mg od. Oral cephalosporins often offer a useful alternative. \200 Fosfomycin 3g single dose. Ampicillin/amoxicillin are less effective at eradicating vaginal and peri-urethral colonization. Encourage high \202 uid intake, e.g. >2L/day. Complicated lower UTI \200 2 At-risk patients: \231\202 , recent urinary tract instrumen tation, recent antibiotics, diabetes mellitus, immunosuppressed, obstruction, structural ab normalities, functional abnormality (e.g. neurogenic bladder, re \202 ux), foreign body, r enal failure. \200 Empirical therapy should be started immediately (e.g. \202 uoroquinolones for 7 \200\223 10 days), but antibiotic therapy should always be tai lored against urine culture and sensitivity results. Pregnant \231\200 ( b p. 842). \200 In the immunocompromised, consider additional single -dose aminoglycoside (e.g. gentamicin 3 \200\223 5mg/kg IVI or IMI). For UTI in renal transplant recipients, see b p. 438. 2 Acute pyelonephritis \200 Initial assessment will need to determine if treatment can be outpatient-based or whether admission is necessary ( l nausea and vomiting, systemically un well). Suggestions (tailor against culture results): Fluoroquinolones (e.g. cipro \202 oxacin 250 \200\223 500mg bd PO) or levo \202 oxacin 250mg od for 14 days. Alternatives include co-amoxiclav IVI, then PO, or a third-generation cephalosporin IVI, then PO for 14 days. \200 Consider additional single- dose gentamicin 3 \200\223 5mg/kg IVI. Rehydration with 0.9% NaCl. \200 Appropriate analgesia and antiemetics. CHAPTER 9 Essential urology 710 Urinary tract infection: miscellaneous Asymptomatic bacteriuria \200 Common (1% in young \231\200 vs 7 20% in \231\200 aged >80. Rare in \231\202 ). \200 De \201 nition ( \231\200 ): isolation of the same organism ( \211 105 cfu/mL) in two consecutive urine samples. Patient has no symptoms attributable to the urinary tract (by de \201 nition!). Associated with: sexual activity, diabetes, institutionalization, impaired urinary voiding, indwelling device (e.g. catheter or stent). 2 Important in: Pregnancy ( b p. 842). \200 Those about to undergo urinary tract instrumentation ( l muco sal bleeding, overt UTI, and bacteraemia). These are the only two groups where screening is appropriate, and treatment is not advocated outside these circumstances. Recurrent UTIs De \201 ned as >4 culture-proven UTIs in a year. A recurrence is not the sa me as a relapse (de \201 ned as return of symptoms with a culture of the same organism, fo llowing an initial UTI). Relapse can be treated with a pro- longed (e.g. 2 \200\223 4 week s \200\231 ) course of antibiotics. \200 Establish whether related to intercourse. \200 Advise to increase \202 uid intake >2L/day, with frequent voiding. \200 Double voidin g may help bladder emptying. \200 Spermicides or spermicide-coated condoms should be disc ouraged. \200 Consider topical estrogen creams (per vagina) in post-menopausal \231\200 . \200 Cranberry juice: in vitro data con \201 rm cranberry juice inhibits adherence of uropathogens to urothelial cells. Con \202 icting results in clinical studies (may be depe ndent on \200\230dose \200\231 and mode of administration (tablet vs drink). X Probiotics: alter vaginal \202 ora to inhibit colonization by uropathogens. Results from clinical trials to date have been disappointing. Consider investigations for an abnormal urinary tract: imaging (including bladder emptying), cystoscopy. For prophylaxis, see Box 9.1 . The following do not predispose to UTI: wiping patterns, voiding after intercourse, persona l hygiene, showering, hot baths or saunas, pantyhose or synthetic fabrics. Catheter-related UTI \200 Bacteriuria occurs in 3 \200\223 10% of patients with an indwe lling catheter/per day catheterized. There is no role for screening asymptomatic patients. Treatment is generally only required if signi \201 cant local symptoms or systemic upset. If required, continue antimicrobials for a minimum of 7 days, and remove the catheter, if p ossible, as a surface bio \201 lm will otherwise act as a reservoir of infection. Diagnosis: cultures positive for >10 5 cfu/mL and heavy pyuria (although pyuria is not always a reliable marker of infection in this context). Prevention is best: avoid catheterization or remove as soon as possible. URINARY TRACT INFECTION: MISCELLANEOUS 711 Box 9.1 Prophylaxis Prophylactic antibiotics are an option if no remediable underlying caus e is identi \201 ed and can reduce recurrence rates by 95%. Ensure any current infection i s successfully eradicated \201 rst. The optimum antibiotic regimen has not been establish ed. \200 If UTI related to sexual activity: trimethoprim 200mg, co-trimoxazole 480mg, or nitrofurantoin 50mg after intercourse. For others, offer nightly low-dose prophylaxis in a monthly rotation as: trimethoprim 100mg, then nitrofurantoin 50mg, then cefalexin 250mg. Alternativ es include co-trimoxazole 480mg or amoxicillin 250mg. These may be adapted, according to previous culture results. \200 Give prophylaxis for 1 year initially. \200 Warn against the potential development of oral or vaginal candida and how this may be treated if it occurs. Related disorders 2 Emphysematous pyelonephritis Caused by gas-forming Enterobacteriaceae a nd occurs predominantly in diabetic patients (90%). Presents as severe pyelonephritis. Gas usually vis- ible on KUB or CT. Mortality is high (20 \200\223 60%), but broad-spectrum an tibi- otics and urgent nephrectomy signi \201 cantly improve outcomes. Xanthogranulomatous pyelonephritis A chronic unilateral pyelonephritis associated with rena l calculi or obstruction and causing widespread parenchymal destruction. More common in dia betes mellitus. Presents as fever, nausea, anorexia, weight loss, \202 ank pain, and syst emic upset. The affected kidney is often palpa- ble. Urinalysis and MSU for M,C+S con \201 rm UTI (usually Proteus spp. or other Gram-negative organism). CT con \201 rms diagnosis. Treat initially as for pyelonephritis. Relapse is common. A nephrectomy is often required. May be confused for renal cell carcinoma. Acute bacterial prostatitis Probably caused by re \202 ux of infected urine into the prost atic ducts. Presents with symptoms of lower tract infection, associated with fever and, occ asionally, with urethral obstruction. The prostate is swollen and tender on DRE. Urine cult ure will often demonstrate pyuria and bacteriu- ria. Treatment: \202 uoroquinolones (prol onged \211 4 weeks). Interstitial cystitis A sterile in \202 ammatory cystitis, presenting in \231\200 aged >4 0 (often with a prior history of recurrent UTI). Symptoms include frequency, dysuria, and ( often disabling) suprapubic or pelvic pain. May be associated with sterile pyuria. Sensitiv ity to intravesical potassium solutions may help to con \201 rm the diagnosis. Cystoscopy and bladder biopsy may show characteristic in \202 ammation and ulceration. Treatment can be dif \201 cult. Tricyclic antide- pressants can help with neuropathic pain. Oral (or int ravesical) pentosan polysulfate sodium is ef \201 cacious in some cases. CHAPTER 9 Essential urology 712 Re \202 ux nephropathy Re \202 ux nephropathy (RN) is a progressive lesion caused by repe ated infec- tions in the kidneys and almost always develops in childhood in the con- text o f an abnormal urinary tract. The long-term renal scarring and CKD resulting from this early injury is called RN or chronic pyelonephritis . 5 \200\223 12% of the ESRD population in the developed world is generally considered to have RN (although the diagnosis is often pre sumed in a patient presenting with scarred kidneys). The main anatomical abnormality of the urinary tract is usually vesi- coureteric re \202 u x (VUR), but RN can also occur with incomplete bladder emptying or out \202 ow obstruction . The ureter inserts obliquely through the bladder wall, forming a com- pressible tunnel that acts as a one-way valve to prevent re \202 ux of urine. A short or incompetent tunnel may allow re \202 ux of urine into the ureters, as the bladder contracts during micturition. Superinfection is the norm. By late childhood, the bladder base thickens; the ureteric tunn el elongates, and free re \202 ux generally no longer occurs. Vesicoureteric re \202 ux \200 Genetically heterogeneous but: \200 Affects 0.1 \200 \223 1% of newborns. \200 Underlies 12 \200\223 50% of children with a proven UTI. Is almost always present in children with proven renal scarring. \200 It may be associate d with renal dysplasia and hypoplasia (and 6 childhood i BP, CKD, and ESRD). Unilateral or bilateral (unilateral will not cause signi \201 cant CKD). \200 Ceases aro und puberty when anatomical changes mean that free re \202 ux is no longer possible. Essentially a radiological diagnosis, classi \201 ed grades I \200\223 V by severity (see Table 9.1). Surgical correction of incompetent valves offers no bene \201 t over simple antibiotic prophylaxis and prompt treatment of UTIs in terms of long-term outcome. Table 9.1 Classi \201 cation of VUR Grade I