Failure to respond to medical therapy Intestinal obstruction from strictures Intestinal per foration Local complications (fistulae, abscesses) 242 \212 \212 \212 \212 \212 \212 \212 \212 Treat rectal disease, if present, with rectal steroids twice daily. Antibiotics can be usef ul if abscess, fistulae, or perforation are identified. Monitor T , pulse, BP, and record stool frequency/character. Perform physical examination twice daily. Obtain daily CBC, ESR, CRP, BMP, and plain abdominal x-ray. Consider need for transfusion (if Hb <10 g/dL) and pa renteral nutrition. If improving after 5 d, transition to oral steroid for taper. If no res ponse (or deterioration) during IV therapy, seek surgical advice. Irritable bowel syndrome IBS is used to describe a heterogeneous group of abdominal symptom s for which no organic cause can be found. IBS patients show an exaggerated response to sti muli like meals, distension, stress, etc. Clinical features Patients are usually 20 \200 \22340 yrs old, and females are more frequently affected than males. Symptoms: Classic pati ent symptoms: A (abdominal pain), B (bloating or abdominal discomfort), C (change in bowel habit) present and stable for at least 6 months. Diagnostic criteria (modified from R ome criteria) IBS is likely if: \212 y g o o r e t n e o r t s a G Pain or discomfort is either \212 Relieved by defecation or \212 Associated with alternat ing stool form (loose and hard) and (need to have at least two of the following): \212 \212 \212 \212 Nausea, dyspareunia; pain in the back, thigh, or chest; urinary frequency; depression can also support the diagnosis. Symptoms are chronic (>3 months over 12-month p eriod), and may be exacerbated by stress, menstruation, or gastroenteritis. l \212 Altered stool passage (straining, urgency, incomplete evacuation), Abdominal bloating, dist ension, tension or hardness, Symptoms worse with eating, Passage of mucus \212 \212 Table 7.20 Management of IBS 6 , 7 Confirm diagnosis : 1) Take a good history and physical with a thorough examination. Exclude symptoms of other illnesses. 2) Elicit history to exclude any red-flag symptoms. 3) May perform testing For all: Celiac panel (anti-TTG Ab, antiendomysial Ab) For IBS with no red flags: No other testing For IBS with red flags: CBC, ESR, CRP, Thyroid studies, ova and parasites. Refer to gastroenterology. Colonoscopy and imaging. (British guidelines also recommend CBC, ESR, an d CRP if symptoms of diarrhea are predominant without red flags; American guidelines recomm end against further testing without red flags and also recom- mend against celiac testing f or those with IBS \200\223constipation.) 243 Management: For typical IBS (no red flags) dietary and lifestyle changes (adjust diet to av oid trigger foods, reduce or increase fiber as appropriate, increase exercise as tolerated, provide reassurance and follow-up care) and initi- ate medications (antispasmodics, antimo tility, laxatives, TCA or SSRI.) For those with IBS and red flags, may also consider furthe r investigation: If diarrhea is prominent, check: LFT; stool culture and testing, fecal fat ; \212 B 12 /folate; antiendomysial ab; TSH; colonoscopy should include ran- dom biopsies. If constipation is prominent, consider rectal exam, anorectal motility testing, gut transi t testing. Further investigation should be guided by severity of symptoms and can also incl ude: Upper GI endoscopy (dyspepsia, reflux) Duodenal biopsy (celiac disease); e.g., if anti -endomysial antibodies +ve. Giardia tests (p. 544) (it often triggers IBS) Small bowel radi ology (Crohn \200\231s disease) MRCP or EUS (chronic pancreatitis) Transit studies and anor ectal physiological studies are rarely used. \212 \212 \212 \212 \212 \212 \212 \212 6 Drossman, D, Camilleri M, Mayer EA, Whitehead WE. AGA Technical Review on Irritable Bowel Syndrome. Gastroenterology. 2002;123 (6): 2108 \200\2232131. 7 Khan S, Chang, L. Diagnosis and management of IBS. Nat Rev Gastroenterol Hepatol. 2010;7: 565 \200\223581. Table 7.20 (Continued) When to Refer: Just because one meets criteria for IBS, it doesn \200\231t mean the patient will never have another disease or disorder. If symptoms change or intensify, if depressio n becomes severe, if red-flag symptoms are evoked, if pain is found to be cyclical and coin cide with menstrual cycle, continue investi- gation as appropriate. Treatment Be honest wit h patients. They have a disorder, it will not cause malignancy, but it may cause symptoms. Careful explanation and reassurance are vital. Create a good relationship with your patient . Food intolerance: Can experiment with limited exclusion diets (difficult to maintain). E ncourage patient to keep a food diary. Constipation (p. 200): Increase fiber intake gradual ly; can lead to bloating Diarrhea: Bulking agent loperamide 2 mg after each loose stool; max 16 mg/d; se: Colic, nausea, dizziness, constipation, bloating, ileus Dyspeptic symptom s: May respond to metoclopramide or antacids Psychological : Emphasize positive aspects and prognosis: In 50%, symp- toms go away or improve after 1 yr; <5% worsen. Symptoms are stil l troublesome in the rest at 5 yrs. Tricyclic antidepressants (low dose) are often helpful; as are psychotherapy , cognitive-behavioral therapy . Explain that all forms of stress (se xual, physical, or verbal abuse) perpetuate IBS. Signs: Examination is often unremarkable although generalized abdominal tenderness is commo n. Insufflation of air during endoscopy may reproduce the pain. Markers of organic disease : Referral and further workup for anyone >50 with new onset symptoms; anyone with red-flag symptoms (rectal bleeding, nocturnal diarrhea, weight loss, family history of cancer, anemi a, masses, fistulae, markers, or history suggestive of IBD) (i.e., it may well not be IBS). Age >40 yrs; history <6 months; anorexia; weight \206\223 ; waking at night with pain/dia rrhea; mouth ulcers; rectal bleeding; abnormal investigations. Management : See Table 7.20. 244 Carcinoma of the pancreas Epidemiology: Fourth most common cause of cancer-related death in the United States; highly lethal; 36,800 deaths in United States in 2010. Typical patient: >60 yrs old. Risk factors: Smoking, alcohol, DM, family history. Pathology: Most are ducta l adenocarcinoma (metastasize early; late presen- tation). 60% arise in the pancreas head, 15% the tail, and 25% in the body. A minority arise from the ampulla of Vater (ampullary tu mor) or pancre- atic islet cells (insulinoma, gastrinoma, glucagonomas, somatostatinomas, V IPomas); these have a better prognosis. Symptoms and signs Tumors in the head of the pancre as classically pres- ent with painless obstructive jaundice. Tumors in the body and tail pr es- ent with epigastric pain, which typically radiates to the back and may be relieved by s itting forward. Either may cause anorexia, weight loss, DM, or acute pancreatitis. Rare fea tures include thrombophlebitis migrans, maran- tic endocarditis, hypercalcemia, Cushing \200\231s syndrome, ascites (peritoneal metastases), portal hypertension (splenic vein thrombosis), nephrotic syndrome (renal vein metastases). Signs: Jaundice + palpable gallbladder (Courvoisier \200\231s \200\234law \200\235: Painless jaundice + palpable GB implies a diagnosis other than gallstones), epiga stric mass, hepatomegaly, splenomegaly, lymph- adenopathy, ascites. Tests Blood: Cholestati c jaundice. CA 19 \200\2239 is elevated in pancreatic cancer but is nonspecific and not ind icated as a screening test. Imaging: Ultrasound or CT scan show a pancreatic mass dilate d biliary tree hepatic metas- tases. Staging CT or endoscopic ultrasound. ERCP can delin eate the bil- iary tree anatomy and localize the site of obstruction if necessary. MRI is h elpful Histology: Obtainable by endoscopic ultrasound with fine-needle aspiration (FNA), ul trasound- or CT-guided percutaneous biopsy. Treatment Most ductal carcinomas present with m etastatic disease; <10% are suitable for radical surgery. Surgery: Consider pancreatoduoden ectomy if patient is able to tolerate surgery and the tumor is <3 cm and with- out metastas es. Postop morbidity is high (mortality <5% in experienced hands). Postop chemotherapy dela ys disease progression. Palliation of jaun- dice: Endoscopic (ERCP) or percutaneous stent i nsertion if symptoms of cholangitis, severe symptoms of hyperbilirubinemia, or if unresecta ble dis- ease. Plan for chemo or palliation; otherwise discuss options with surgeons. Rarel y, palliative bypass surgery is indicated for duodenal obstruction or unsuccessful ERCP. Pa in relief: Disabling pain may be relieved by opiates or radiotherapy. Celiac plexus infiltr ation with alcohol may be done at the time of palliative surgery, percutaneously or via end oscopic ultrasound. Prognosis Mean survival <6 months. 5-yr survival rate: <2%. Overall 5-y r survival after Whipple procedure 5 \200\22314% (see Figure 7.3). Patients with the rarer ampullary or islet cell tumors have a better prognosis. y g o o r e t n e o r t s a G l 245 Nutritional disorders Scurvy is due to lack of vitamin C in the diet. Is the patient poor, pregnant, or on an odd diet? Signs: (1) Listlessness, anorexia, cachexia. (2) Gingivitis, l oose teeth, and foul-smelling breath (halitosis). (3) Bleeding from gums, nose, hair follic les, or into joints, bladder, gut. Diagnosis: No test is completely satisfactory. Treatment : Dietary education; ascorbic acid 250 mg/d PO. Beriberi presents with heart failure with g eneralized edema (wet beriberi) or neuropathies (dry beriberi) due to lack of vitamin B 1 ( thiamine). Pellagra (lack of niacin). Classical triad: Diarrhea, dementia, dermatitis ( n europathy, depression, insomnia, tremor, rigidity, ataxia, fits). It may occur in carcinoid syndrome and anti-tuberculosis (TB) treatment. It is endemic in China and Africa. Treatmen t: Education, electrolyte replacement, nicotin- amide. Look for other vitamin deficiencies. Xerophthalmia This vitamin A deficiency is a major cause of blindness in the tropics. Conj unctivae become dry and develop oval or triangular spots (Bitot \200\231s spots). Corneas b ecome cloudy and soft. Give vitamin A 200,000 IU stat PO, repeat in 24 h and a week later ( halve dose if <1 yr old; fourth if <6 months old); get special help if pregnant; vitamin A embryopathy must be avoided. Re-educate and monitor diet. Carcinoid tumors A diverse group of tumors of argentaffin cell origin (neuroendocrine tumor s), by definition capable of producing 5HT. Common site : Appendix (25%) or rectum. They al so occur elsewhere in the GI tract, ovary, testis, and bronchi. Tumors may be benign but 80 % >2 cm will metastasize. Symptoms and signs: Initially few. GI tumors can cause appendicit is, intussusception, or obstruc- tion. Hepatic metastases may cause RUQ pain. Carcinoid tum ors may secrete adrenocorticotropic hormone (ACTH; Cushing \200\231s syndrome); 10% are par t of multiple endocrine neoplasia (MEN)-1 syndrome and 10% occur with other neuroendocrine tumors. Carcinoid syndrome occurs in 10%. Carcinoid syndrome usually Signs: Paroxysmal flus hing ( migrating wheals \200\224bright red color on the face, chest, trunk, and extremiti es lasting 10 \200\22330 min), abdominal pain, diarrhea, tricus- pid incompetence, and pulm onary stenosis. CNS effects: Numerous (e.g., enhanced ability to learn new stimulus \200 \223response associations). Carcinoid crisis occurs when a tumor outgrows its blood supply and mediators flood into vasculature; this is life-threatening. Diagnosis Useful tests: 24 h urine 5-hydroxyindoleacetic acid \206\221 (5HIAA, a 5HT metabolite; levels change with d rugs and diet: Discuss with lab). If liver metastases are not found, try to find the primar y (CXR; chest/pelvis MRI/ CT) as curative resection may be possible. Plasma chromogranin A, which is present in chromaffin granules of neuroendocrine cells, is suggested as primary b iomarker for diagnosis of neuroendocrine tumors (reflects tumor implies hepatic involvement. 246 y g o o r e t n e o r t s a G Figure 7.3 Whipple procedure l Liver Liver Stomach Stomach A B A B C D B B A D A C Pancreas Roux loop Duodenu Pancreas m C C D D (a) Areas of reflection of different parts (b) Postoperation Whipple procedure may be used for removing masses in the head of the pancreas \200\224typically from pancreatic carcinoma , or, less com- monly, a carcinoid tumor. 247 mass, can follow treatment response); CT and MRI scans, 111 Indium oct- reotide scintigraph y (OctreoScan); positron emission tomography (PET) or PET-CT. Treatment Carcinoid syndrome: Octreotide and lanreotide (somatosta- tin analogs) block release of tumor mediators and co unters peripheral effects. Effects lessen over time. Other options : Loperamide or cyprohep ta- dine for diarrhea; ketanserin (experimental 5HT 2 antagonist) for flushing; interferon- . Tumor therapy: Surgical debulking (e.g., enucleation) or embo- lization of hepatic me tastases can decrease symptoms. These must be done with octreotide on-board to avoid precip itating a massive carcinoid crisis. Crisis is treated with high-dose octreotide and careful management of fluid balance. Median survival: 5 \200\2238 yrs; 38 months if metastases are present, but may be much longer ( 20 yrs); two-thirds of patients with neuroendocrine tumo rs have stable disease for up to 5 years. Gastrointestinal malabsorption Symptoms Diarrhea, \206\223 weight, steatorrhea (fatty stoo ls, difficult to flush). Deficiency signs: Anemia ( \206\223 Fe, B 12 , folate), bleeding ( \206\223 vitamin K), edema ( \206\223 protein). Common causes: Celiac disease, Crohn \200\231s, chronic pancreatitis. Others causes include: \206\223 Bile (primary biliary cir rhosis); ileal resection; biliary obstruction. Treatment : E.g., cholestyramine. Pancreatic insufficiency: Chronic pancreatitis, pancreas cancer, cystic fibrosis. Small bowel mucosa: Celiac and Whipple diseases, tropical sprue, radia- tion enteritis, small bowel resection, brush border enzyme deficiencies (e.g., lactase insufficiency), drugs (metformin, neomycin , alcohol), amyloid. Bacterial overgrowth: Spontaneous (especially in elderly), in jejunal diver- ticula, postop blind loops. Try fluoroquinolones, Bactrim. Infection: Giardiasis, di phyllobothriasis (B 12 malabsorption), strongyloidiasis. Intestinal post-vagotomy, hurry: g astrojejunostomy. Tests CBC (MCV \206\223 , macrocytosis), \206\223 Ca 2+ ( \206\223 vit amin D due to fat malabsorp- tion), \206\223 Fe, \206\223 folate, \206\221 PT ( \206 \223 vitamin K), celiac serology (below). Stool: Sudan stain for fat globules, stool micros copy for infestation. Ba follow-through: Diverticula, Crohn \200\231s, radiation enteritis. Breath hydrogen analysis: Bacterial overgrowth; take samples of end-expired air; give gluc ose; take more sam- ples at half-hour intervals. If there is overgrowth, there is increased exhaled hydrogen. Small bowel biopsy: Use endoscopy; MRCP biliary obstruction, chronic pan creatitis. intestinalis, Typical Tropical malabsorption Cryptosporidium parvum, Isospora be lli, Cyclospora cayetanensis, and the microsporidia. Tropical sprue: Villous atrophy and ma labsorption occurring in the Far and Middle East and Caribbean (rare in Africa); the etiolo gy is unknown. Tetracycline and folic acid may be helpful. Celiac disease is a T-cell media ted autoimmune disease of the small bowel in which gluten (alcohol-soluble proteins in whea t, barley, rye, oats) intol- erance causes villous atrophy and malabsorption. Associatio ns: HLA DQ2 in 95%; the rest are DQ8; autoimmune disease; dermatitis herpetiformis. Present ation: Steatorrhea/offensive stools, other abdominal pain, bloat- ing, nausea/vomiting, aph thous ulcers, angular stomatitis, weight \206\223 , fatigue, weakness, iron-deficiency ane mia, osteomalacia, poor growth (children). One-third are asymptomatic, so have a low thresh old for evaluating patients for celiac disease. Occurs at any age (peaks in infancy and 50 \200\22360 yrs). 248 Postgastrectomy dumping, causes: Giardia Diagnosis: Antibodies: ( anti-gliaden , transglutaminase, antiendomysial \200\224an IgA ant ibody; 95% specific, unless the patient is IgA-deficient). Duodenal biopsies done at endosc opy (as good as jejunal biopsy if >4 samples taken). Villous atrophy, reversing on gluten-f ree diet (along with \206\223 symptoms and antibodies). Treatment: Lifelong gluten-free di et. Rice, maize, soya, potatoes, +/ oats , and sugar are OK. Gluten-free biscuits, flour, bread, and pasta are available. Verify diet by endomysial antibody tests. Refer to a nutri tionist. Complications: Anemia, secondary lactose-intolerance, GI T-cell lymphoma (rare, su spect if worsening despite diet), malignancy (gastric, esopha- geal, bladder, breast, brain ), myopathies, neuropathies, hyposplenism, osteoporosis. Chronic pancreatitis Epigastric pa in \200\234bores \200\235 through to back; bloating, steatorrhea, \206\223 weight, DM. Ca uses: Autoimmune, Recurrent and severe acute pancreatitis, Obstruction. More specific: ANNA HEIM criteria: Alcohol consumption (excessive, increased, or moderate); Nicotine (pack-year s of smoking); Nutritional fac- tors (hyperlipidemia or high-fat diet); Hereditary factors (hereditary pan- creatitis, familial pancreatitis, early \200\223onset idiopathic, late-ons et idiopathic, tropical pancreatitis, possible gene mutations PRSS1, CFTR, or SPINK 1); Eff erent duct factors (pancreatic divisum, annular pancreas, pancreatic duct obstruction [tumo r], post-traumatic pancreatic duct scars, sphinc- ter of Oddi dysfunction); Immunologic fac tors (autoimmune pancreatitis, Sj gren-associated, IBD-associated, chronic pancreatitis with PSC or PBC, and miscellaneous factors (hypercalcemia, hyperparathyroidism, chronic ren al failure, drugs, toxins). Tests: Ultrasound (dilated biliary tree; stones); if normal con sider CT/MRCP or EUS [>6 criteria of chronic pancreatitis on EUS had a positive predictive value of 85%]. Plain movie: Speckled pancreatic calcification; glucose \206\221 ; breath t ests (above). Drugs : Recommend stopping smoking and alcohol . Can give analgesia ( celia c-plexus block). Pancrelipase; e.g., Creon ; fat-soluble vitamins (e.g., Multivite ), and vitamin D (1,000 units daily). Diet: Low fat (+ no alcohol) may help. Surgery: For unremit ting pain; narcotic abuse (beware of this); weight \206\223 ; pancreatectomy or pancreatic ojejunostomy, some research cen- ters investigating total pancreatectomy with autoislet cel l transplant. y g o o r e t n e o r t s a G l in general: TIGAR-0 : Toxic metabolic, Idiopathic, Genetic, 249 Renal medicine Matthew Foy , M.D. and Sumeska Thavarajah , M. D. e n i c i d e m Contents Introduction to nephrology 250 Urine 252 Urinary tract imaging 254 Renal biopsy 256 Urinary tract infection 257 Renal calculi (nephrolithiasis) 258 Urinary tract obstruction 260 Retr operitoneal fibrosis 261 Glomerulonephritis 261 The nephrotic syndrome 266 Acute kidney inj ury: Diagnosis 268 Acute kidney injury: Management 269 Chronic kidney disease 271 Renal rep lacement therapy 274 Renal transplantation 275 Interstitial nephritis and nephrotoxins 276 Nephrotoxins 278 Renal vascular diseases/secondary hypertension 278 Renal tubular disease 2 80 Inherited kidney diseases 282 Renal manifestations of systemic disease 282 l a n e R 8 Introduction to nephrology Web links for estimating glomerular filtration rate (GFR) The fo ur-variable Modification of Diet in Renal Disease (MDRD) equa- tion estimates GFR based on age, sex, race, and serum creatinine (www. nephron.com). Another estimate of creatinine cle arance uses serum crea- tinine (SCr), sex, and ideal body weight (IBW; muscle bulk is impor tant). See www.globalrph.com/crcl.htm. It is based on the Cockcroft-Gault equation: CrCl (140 \200\223 age) \227 IBW/(SCr \227 72) ( \227 0.85 for females). IBW in (kg) is 50 kg + 2.3 kg for each inch of height over 5 ft for men. IBW is 45.5 kg + 2.3 kg for each inc h over 5 ft for women. Units: SCr (mcmol/ L)/8.4 = SCr (mg/dL). Example : A 70-yr-old white woman with a serum creatinine of 1.3 mg/dL has an estimated GFR of 43 mL/min/1.73 m 2 by t he four-variable MDRD equation. For Cockcroft-Gault, the same woman standing at 5 feet, 4 i nches would have an estimated GFR of 41 mL/min. 250 e n i c i d e m Renal disease typically presents with one or more of a short list of clinical syndromes, li sted below. One underlying pathology may have a variety of clinical presentations. 1 Protei nuria and nephrotic syndrome: Normal protein excretion is <150 mg/d. Nonpathologic increase s to 300 mg/d can be seen in orthos- tatic proteinuria (related to posture); during fever, during pregnancy, or after exercise. Proteinuria (excessive urine protein excretion) is a sign of glomerular or tubular disease. Nephrotic syndrome is the triad of proteinuria (>3 g /d [p.248]), hypoalbuminemia (albumin <3.5 g/ dL), and edema. Hyperlipidemia is often seen. l a n e R 2 Hematuria and nephritic syndrome: Hematuria (blood in the urine) may arise from anywhere in the renal tract. It may be macroscopic , microscopic , or detected as hemoglobinuria . N ephritic syndrome com- prises hematuria and proteinuria, although often in subnephrotic ran ge. It may be associated with hypertension (HTN), peripheral edema, oliguria, and acute kid ney injury (AKI) (ARF) . The question of who to refer hematuria patients to (urologist or n ephrologist) is discussed on p. 236. 3 Oliguria and polyuria: Oliguria is a urine output of <400 ml/d. It is a normal response t o severe fluid restriction. Pathologic causes : Reduced renal perfusion, renal parenchymal disease, urinary tract obstruction. Polyuria is the excretion of larger than normal volumes of urine (generally >3 L/d), usually from high fluid or solute intake. Pathological causes include diabetes mellitus (DM), diabetes insipi- dus (p. 306), disorders of the renal medu lla (urinary concentrating defect), and supraventricular tachycardia. 4 Flank pain and dysuria: Flank pain is usually due to postrenal obstruc- tion, acute pyelo nephritis, polycystic kidneys, or renal infarction. Severe flank pain (aka renal colic) may be associated with fever and vomiting and may radiate to the abdomen, groin, or upper thig h. It is usually caused by a renal calculus, clot, or sloughed papilla. Urinary frequency a nd dysuria (pain on passing urine) are symptoms of cystitis. 251 5 Acute renal failure (ARF)/AKI is significant decline in renal function occurring over hou rs to days, detected by a rising serum creati- nine and urea nitrogen, with or without olig uria. AKI usually occurs secondary to reduced blood flow to the kidneys (hypotension, hypov olemia, sepsis, abdominal compartment syndrome), urinary obstruction, or intrinsic renal di sease. 6 Chronic kidney disease (CKD): Kidney damage >3 months as defined by structural or functio nal abnormalities of the kidney, with or with- out | GFR or a GFR <60 mL/min/1.73 m 2 body surface area. It is classified according to GFR into five categories: Stage 1 (kidney dam- age with normal GFR >90 mL/min), stage 2 (60 \200\22389 mL/min), stage 3 (30 \200\22359 mL/ min), stage 4 (15 \200\22329 mL/min), and stage 5 (<15 mL/min). There is poor correlation b etween symptoms and signs of CKD. Progression may be so insidious that patients attribute s ymptoms to age or other illnesses. Severe CKD may not present with any symp- toms. End-stag e renal failure is a degree of renal failure that, without renal replacement therapy, would result in death. 7 Microalbuminuria is a silent harbinger of serious renal (and cardiovas- cular) risk. In o ne study, 30% of those with type 2 DM died within 5 yrs of developing microalbuminuria. Urine Examine fresh urine (<1 h old) whenever you suspect renal disease. Dipsticks \212Hem aturia: Causes: Infections (cystitis, either bacterial or BK and JC virus; pyelonephritis, prostatitis; tuberculosis (TB); schistosomiasis; urethritis), calculi, neoplasia (kidney, b ladder, prostate, urethra), trauma (commonly from Foley placement in a hospitalized patient ), glomerulonephritis, inter- stitial nephritis, polycystic kidney disease, papillary necro sis (sickle-cell disease, NSAIDs), medullary sponge kidney, vasculitis, vascular malforma- tion, cyclophosphamide, hemophilia. Anticoagulation should not cause hematuria at usual the rapeutic goal levels. Tests: Urine dipstick and micro- scopic exam, culture, 24 h urine col lection (protein, creatinine clearance); CBC, erythrocyte sedimentation rate (ESR), c-react ive protein (CRP), blood urea nitrogen (BUN), creatinine. Others: Clotting factors, hemo- g lobin (Hb) electrophoresis; computed tomography (CT) pyelogram with and without IV contrast or renal ultrasound renal biopsy. Management plan: Usually refer to urologist for uroth elial malignancy evaluation if >40 yrs or other high risk (smoker, cyclophosphamide, dye wo rker). Refer to nephrologist if risk of urothelial malignancy is low and risk of glomeru- l onephritis is not negligible (e.g., <40 yrs old, \206\221 serum creatinine, \206\221 BP, proteinuria, systemic symptoms, family history of renal disease). False +ve dipstick hematu ria: Free Hb, myoglobin, bacterial peroxidase False negative: Ascorbic acid, old dipsticks. NB: Urine concentration can affect detection rates. Red urine: Beets, porphyria, rifampin, phenazopyridine, phenolphthalein (found in some laxatives). \212Proteinuria: Normal protein excretion is <150 mg/d (may rise >300 mg/d in fever, or wi th exercise). Causes: Urinary tract infection (UTI), ortho- static proteinuria, primary and secondary glomerular disease (systemic lupus erythematosus [SLE], amyloidosis, DM, pregnan cy), interstitial dis- ease, hemolytic-uremic syndrome, multiple myeloma. Tests: Blood pres - sure (BP), urine dipstick (only detects albumin , not other proteins, such as light chain s; in this instance, use the sulfosalicylic acid test) and micro- scopic exam; 24 h urine c ollection (protein excretion, creatinine clear- ance). Spot urine protein-to-creatinine rat io (ratio of 1 \211\210 urine protein excretion of 1 g/24 h if patient has 1 g urine crea tinine excretion), renal ultrasound, serum complement, or others (antinuclear antibodies [A NA]; rapid plasma reagin [RPR]; hepatitis C, hepatitis B, HIV, protein electro- phoresis [S PEP, UPEP]). If abnormal, consider renal biopsy. 252 \212Microalbuminuria: Albumin excretion 30 \200\223300 mg/24 h or spot urine sam- ple value of 30 \200\223300 mcg/ mg creatinine. Causes : DM, \206\221 BP. \212Other substances Glucose : DM (serum glucose levels >200 mg/dL), preg- nancy, Fanconi \200\231s syndrome, proximal tubule damage. Ketones: Starvation, ketoacidosis. Leukocytes : UTI, vaginal discharge, interstitial nephri- tis. Nitrites : Enterobacteriaceae infection, high-protein meal. Bilirubin: Obstructive jaundice. Urobilinogen: Prehepatic jaundice. Spe cific gravity: Normal range: 1.000 \200\2231.030 (dilution and concentration). Fixed range of 1.010 is isosthenuria and indicative of interstitial renal disease process, such as sic kle cell anemia, severe CKD. PH: Normal range: 4.5 \200\2238 (acid \200\223 base balance: U rease producing bacteria and distal RTA may cause alka- line urine). Microscopy Collect a fresh urine specimen via clean catch or from Foley catheter. Centrifug e 10 mL for 5 min at 2,000 \200\2233,000 rpm. Invert tube, emp- tying most of urine, then r esuspend pellet in few drops of urine. Put a drop of centrifuged urine sediment on a micros cope slide, cover with a coverslip, and examine under low (100 \227 ) and high (400 \227 ) power for leukocytes, rbcs, bacteria, crystals, and casts. Leukocytes: >10/mm 3 in an unspun urine specimen is abnormal. Causes : Cystitis, urethritis , prostatitis, pyelonephritis, interstitial nephritis, TB, renal calculi, glomerulonephriti s. Red cells: >3 \200\2235 red blood cells (RBCS)/high-powered field in two-thirds of morni ng specimens. Causes: See hematuria. Casts are cylindrical bodies formed in the lumen of di stal tubules as cells or other elements and are embedded in Tamm \200\223Horsfall protein. Finely granular and hyaline casts (clear, colorless) are found in concen- trated urine, fev er, after exercise, or with loop diuretics and pathologic conditions. Densely granular cast s: Acute tubular necrosis (ATN), GN, or interstitial nephritis. Fatty casts: Heavy proteinu ria. Under polarized light, show Maltese-cross appearance. Red cell casts are a hallmark of glomerulonephritis (GN). May be seen with interstitial nephritis or vasculitis. White cell casts occur in pyelonephritis, interstitial nephritis, atheroembolic disease, and rarely p roliferative glomerulonephritis. Epithelial cell casts occur in ATN. Crystals are common in old or refrigerated urine and may not signify pathology. Cystine crystals are diagnostic o f cystinuria. Oxalate crystals in fresh urine may indicate ethylene glycol poisoning in pat ients with severe metabolic acidosis (see Figure 8.1). Medications (sulfonamides, indinavir , acyclovir). 24 h urine for creatinine protein excretion. Take blood creatinine simul- taneously to calculate creatinine clearance. Can check 24 h urine for Na + , K + , for elec trolyte disorders, or stone risk profile for recurrent stones. e n i c i d e m l a n e R 253 Figure 8.1 Urine microscopy 254 Principle source: M. Longmore An Atlas of Microscopy rcgp . When you find red cells, consider their morphology to understand where in the GU tract they come from. If >80% of RBCs are dysmorphic G1 cells, suspect glomerular bleeding and look h ard for red cell casts. Acanthocytes are RBCs with donut shapes, target configurations, and membrane protrusions or blebs. Acanthocyturia of >5% is considered indicative of glomerula r hematuria. www.uninet.edu/cin2003/conf/nguyen/nguyen.html Urinary tract imaging Kidney, ureters, bladder (KUB) x-ray Look at kidneys, path of the ure ters, and bladder. Abnormal calcification may be related to calculi (only 80% of stones are visible on plain films: See CT below), dystrophic calcifica- tion; e.g., in carcinomas or TB (uncommon) and nephrocalcinosis. Note: Plain abdominal movie focuses more on bowel, not urinary system, and may miss stones. Ultrasound is the usual initial image in renal medicin e. May be performed with Doppler. Abnormal parenchyma if echogenicity is greater than that of the liver. It shows: \212Renal size . S mall (<9 cm) implies CKD; large in renal masses , benign cysts 1 ; hypertrophy if other kidney missing, polycystic kidney disease, amyloido sis, diabetes, and lymphomatous infiltration 1 Cysts may be inherited, developmental, or acquired; e.g., polycystic kidney disease, medu llary sponge kidney, multicystic dysplastic kidney, medullary cystic disease, tuberous scle rosis, renal sinus cysts, von Hippel \200\223Lindau \200\231s disease. \212Hydronephrosis , which indicate renal obstruction or reflux \212Perinephric collectio ns (trauma, postrenal biopsy) \212Transplanted kidneys (collections, obstruction; color Do ppler indicates e n i c i d e m perfusion) \212Bladder residual volume \212Power Doppler ultrasound evaluates for renal artery steno sis. Advantages: Fast, cheap, independent of renal function, no IV contrast or radiation ri sk. Disadvantages : Intraluminal masses, such as transitional cell carcinomas (TCC) in the upper tracts, may not be seen; not a functional study; only suggests obstruction when there is dilatation of the collecting system ( 1 \200\2232% of obstructed kidneys have nondilate d systems). Disadvantages : May miss obstruction and hydroureter early on in the disease. H elical noncontrast/CT is gold standard for diagnosis of renal colic. Noncontrast scans are 97% sensitive for calculi and show other patholo- gies. CT allows detailed characterization of masses (solid or cystic, contrast enhancement, calcification, local/distant extension, renal vein involvement); renal trauma (hemorrhage, devascularization, laceration, urine lea k); retro- peritoneal lesions. CT urogram for hematuria uses IV contrast to visualize colle cting system if noncontrast CT is negative. Intravenous urogram/pyelogram (IVU/IVP) A study for defining anat- omy (especially pelvi-calyceal) and for detecting pathology distorting the collecting system. It yields limited functional information. Abdominal films are taken before and after IV contrast, which is filtered by the kidney, reach- ing the renal tubules at 1 min (nephrogram phase). Later images show contrast in the system (pyelogram), ureter s, and bladder. Detects papillary necrosis, medullary sponge kidney. Side effects (SE) : Fl ushing, nausea, rash, contrast nephropathy (Caution: Risks include preexisting CKD, DM). Re trograde pyelography is good at showing anatomy of the pelvi-calyceal systems and ureters a nd for detecting pathology, such as transitional cell carcinoma (TCC). Contrast is injected via a ureteric catheter. Percutaneous nephrostomy The renal pelvis is punctured with imagi ng guidance. Diagnostic images are obtained following contrast injection. A nephrostomy tub e may then be placed to allow drainage of an obstruction above the bladder. Renal arteriogr aphy Still the gold standard for renal artery stenosis. Can perform pressure monitoring acr oss stenosis for significant pressure change for borderline lesions. Therapeutic indication s include angioplasty, stenting, and selective embolization (bleeding tumor, trauma, or art eriovenous [AV] malformations). Magnetic resonance imaging (MRI) offers improved soft tissu e resolu- tion; it may be used to clarify equivocal noncontrast CT findings. Magnetic reson ance angiography ( MRA ) is useful in imaging renal artery stenosis. Avoid gadolinium in se vere CKD. Radionuclide imaging scans quantify each kidney \200\231s contribution to renal f unction and can detect renal scarring ( 99 TC m DTPA, diethylenetriamine penta-acetic acid) . Radiolabeled metal chelators such as 51 Cr-EDTA (ethyl- enediaminetetraacetic acid), 125 I iothalamate, or 99 Tc m DTPA, can also mea- sure GFR. l a n e R 255 Renal biopsy See Table 8.1. Table 8.1 Renal biopsy Most acute kidney injury is due to prerenal causes or ATN, and recov- ery of renal function typically occurs over the course of a few weeks. Renal biopsy should be performed if knowi ng histology will influence management. Once CKD is long-standing with small kidneys, risks of bleeding from biopsy may be increased and therapy may be limited. Indications for renal biopsy: \212 \212 What is the cause of this acute kidney injury (p. 268)? Investigating func- isolated hematu ria with normal tion and minimal proteinuria to rule out glomerulonephritis is nephrologist -dependent. Is persistent hematuria in this scenario from IgA nephropathy, thin basement me mbrane disease, or hereditary nephropathy? What is the cause of this heavy proteinuria (e.g ., >2 \200\2233 g/d) when diabetic nephropathy is unlikely? Renal dysfunction post-transpla ntation: Is the cause rejection, drug toxicity, or recurrence of renal disease? renal \212 \212 Preprocedure: Check cbc, coagulation profile. Obtain written informed consent. Ultrasound. Hold aspirin, NSAIDs, and anticoagulation at least 7 d prior to procedure if possible. Rela tive contraindications (CI) : 1 One kidney or horseshoe kidney 2 Morbidly obese 3 Uncontrol led HTN (systolic >160 mm Hg) In these instances, consider open procedure or CT-guided biop sy. Procedure: Biopsy may be performed with real-time ultrasound using needle guides, with the patient lying in the prone position and the breath held. May also be performed by radio logy via transjugular approach or surgically via laparoscopic or open techniques for those who are obese or who are at increased risk for bleeding. Samples should be sent to patholog y for routine stains, immunofluorescence, and electron microscopy. A clear indication on th e request form of why the test has been done(e.g., exclude amyloidosis) will help in the se lection of special stains, immunofluorescence, and use of electron microscopy. Postprocedur e: Bed rest for 6 \200\22324 h. Monitor pulse, BP, symptoms, and urine color. Bleeding is t he main complication with nephrectomy and death ( 1/1,000 cases). 256