week 5- Renal 1 Flashcards
• Basic renal/GU fxns:
o Filtration, excretion (emunctory)
o water & electrolyte balance, ions in ECF
o acid/base balance- HCO3, H (N urine pH 4.5-6)
o BP reg- renin
o RBC production- EPO
o Bone metabolism- activate vit D3, ↑ Ca abs
o Gluconeogenesis- during fast
o Reproduction (testicles)- sperm, storage
o Production of hormones (testicles)- T
• Normal fluids in and out:
o Min urine: 0.5-1 ml/kg/hr daily
o Optimal: ~2500 ml urine/day = 250+mL water/hr
o Freq: N every 1-2 hrs awake; 0-1 x/ night
• Kidney position:
o R lower than L dt position of liver (T10-T12)
o descend ~4-5 cm w respiration
• bladder and urethra specs:
o B: Adult capacity ~ 350-450 ml (12-16 oz)
o U: F 4-8 cm long, M 15-22 cm
• Hx for renal cc:
o Pain: renal pain in flank or lower back
o PMHx: lupus, DM, HTN (2nd affects on KDs)
o FHx: PKD, AI nephropathies, renal calculi
o Exposures: heavy metals, chems, radiographic contrast media
o Meds: analgesics, abx, NSAID’s, diuretics
o ROS: assoc sx of renal dz; general: fever, ↓wt, fatigue; CV: SOB, chest pn, edema; GI: anorexia, N/V, crampy abd pn (shared plexi, concomitant sx); LUTS: polyuria, dysuria, hematuria; MS: jot pn, swelling; Skin: rash, pruritis
• PE for renal cc:
o Complete PE required
o Observation: severely ill w renal dz, pale, sallow (urochrome), Drowsiness, slurred speech may suggest acute RF; Deep breathing suggests met acidosis
o Lung/Heart: ↑BP, heart failure, pericardial rub, pleural rub, edema
o Neuro: encephalopathy (any brain dysfxn), stupor to coma dt azotemia/uremia, asterixis (hand tremor hand in flexor direction. Dt various dzs - hepatic failure, CO2 narcosis, chronic KD dz
o Fundoscopi: Retinal changes dt DM, HTN
o Abd: renal mass; renal a bruit, ascites, CVA tenderness: inflam kidney, mb ureter
o Skin: xerosis, pallor, petechiae, ecchymosis
• Hx for GU cc:
o Pain: Ureters: R or L side spasms (eg stone), may radiate to thigh or genitalia; Bladder: suprapubic pn (retention, inflam, irritation; Urethral: dysuria dt inflam, irritation, foreign body
o Voiding sxs: Irritative (dysuria, freq, urgency), Obstructive (hesitancy, straining, ↓caliber); Incontinence, Enuresis
o D/c: Amount, color, consistency, fever, chills, rash, assoc sxs, hematuria, dysuria
• PE for GU cc:
o CVA tenderness: pyelonephritis, calculi, UTI
o Abd: Dullness in suprapubic area mb bladder distention (urge to urinate when pressing), may see distention
o Gyn exam
o Male genitalia exam
• Urinary Frequency:
o need to urinate many x during day; often w Urgency (urgent need, w only small amt of urine)
o ask: Fluid consumption, Flow sxs (pain, hesitancy, sensation of incomplete voiding, nocturia), Fever, hematuria, sexual activity, Missed menses, breast swelling, morning sickness (pg)
o DDX: UTI, pg, compression/prolapsed uterus, foreign bodies, stones, ↑fluid intake, substances (coffee, alcohol, diuretics), DM, food sensitivity, BPH, prostatitis, spinal cord injury, urethral stricture, incontinence
o RED FLAGS: Fever, back pain, LE weakness
• Dysuria:
o painful or uncomfortable urination (burning, aching). From irritation, inflam, infx (eg cystitis, urethritis/STI), perineal lesions exposed to urine
o ask: D/c, chills/fever, hematuria, sexual activity, Timing of pain in relation to urination; Location of pain: urethra, suprapubic (bladder), flank (renal), abd (ureter)
o DDX: cervicitis, cystitis, epididymitis, prostatitis, urethritis, contact irritant/allergen, foreign body, interstitial cystitis, ReA, atrophic vaginitis
o RED FLAGS: fever, flank pain, recent instrumentation, immunocomp, recurrence
• Nocturia:
o Etio: excessive fluid late in evening, urine retention, BPH, interstitial cystitis, GU allergies
• Nocturnal enuresis:
o involuntary bedwetting > 5 yo o M > F, w FHx (70% if both parents) o Normally prevented by: ADH secretion at sunset; Ability to wake up when bladder full o Normally uncommon > 4 (under 30%) o 1st and 2nd
• Etio 1st enuresis:
o ~90% of cases, child never achieved continence for > 6mos
o neuro-developmental delay
o genetics
• etio 2nd enuresis:
o incontinence develops > 6 mos of achieving urinary control
o neuro-developmental issues (eg autism, Down’s)
o DM, DI, hypoglycemia, sickle cell dz
o functionally small bladder
o sleep apnea, sleep walking
o bladder irritability (UTI, constipation)
o ADHD
o Psycho stress: sex abuse, bullying, birth of sibling, social isolation, divorce/separation, loss of parent/grandparent or pet
o food allergy/sensitivity (dairy, wheat, apples, oranges)
o parasites (pinworms)
• Urinary incontinence:
o Inability to hold urine; 3 types:
o Overflow: distended bladder from obstruction (BPH, pelvic tumor, fecal impaction, urethra stricture, chronic constipation, unable to completely empty bladder; frequency, dribbling common
o Stress: sudden ↑ intra-abd P from cough, sneeze, exercise → P to bladder →urine leak from sphincter control: childbirth, obesity, aging
o Urge: freq, sudden urge to urinate w little control; ↓parasymp inhib → detrusor mm hyperreflexia, stroke, MS, PD, tumors
o Mixed causes (eg stress and overflow)
• Polyuria:
o ↑output urine (> 3000 ml/day)
o lost fluids and solutes must be replaced (hypotension and CV collapse)
o must distinguish from urinary freq
o ask: Fluid consumption, abrupt/gradual onset, Polyphagia, polydipsia, Dry eyes/mouth, ↓wt/night sweats, drug Hx, FHx
o RED FLAGS: abrupt onset, night sweats, cough, ↓wt, psych do
• Etio of polyuria:
o appropriate response to osmolar, Na or fluid loads; mb 2nd to diuretics, ↑Na intake, ↑water and Na thru IV feedings or rapid resorption of edema fluid
o inappropriate response to pathological state:
o DI: HTH-pit do dt def ADH → polydipsia, polyuria
o nephrogenic DI: urinary concentrating defect unresponsive to ADH. Mb dt chronic RF (nephrons can’t conc urine), recovery from acute RF or acute pyelonephritis, ↑Ca, ↓K, congenital tubular dos, drug-induced dz
o compulsive drinking ↑ fluid: psychogenic polydypspia; overdose of lithium → ADH resistance → polyuria, polydipsia
o osmolar load: glucose osmotically active, spilling → Na & H20 excretion
• Oliguria and Anuria:
o oliguria: ↓ urine output (↓ 400-500 ml/24 hr)
o anuria: ↓ 100 ml/ 24 hours
o etio: Pre-renal (↓ blood to KD), renal, post-renal
o !! refer for immediate eval and tx (catheter)
• Hematuria:
o Microscopic: > 3 RBC/hpf in centrifuged urine or gross; usu renal cause; presence of any RBCs > 1 occasion should be investigated
o Gross: usu uroepithelial (if painless, R/O tumor); Peds: consider GN, child abuse; Geriatric: suspect UTI, st occult
• Ask pt about hematuria:
o Habits: smoking, drug use
o Meds (analgesics, Coumadin)
o Occupational exposures
o Obstructive sxs (incomplete emptying, difficulty starting/stopping stream)
o Irritative sxs (irritation, urgency, frequency, dysuria)
o Recent infx, FHx, drug hx
o Painless urination: consider tumors of Bl, Ki, Prostate until proven otherwise! staghorn calculi, polycystic Ki, sickle cell, hydronephrosis, acute GN
o Dysuria: consider infx
o Flank pain: consider Ki/ureteral stone, PN, trauma, tumor
• Timing of gross blood seen:
o Start of micturation: anterior urethral lesions (urethritis, stricture, meatal stenosis)
o End: bladder trigone, prostate, bladder neck, posterior urethra
o Throughout: Bl, ureteral or renal pathology
o Cyclically with menes: endometriosis of urinary tract
o Blood bw voidings (on underwear): bleeding on either end of urethra
• Common etiologies of hematuria:
o Inflammatory: UTI (mc), STI (esp in F), GN, PN, radiation nephritis/cystitis, IC, TB, endocarditis
o Trauma: Exercise-induced: jarring from running, weight-lifting; Abd/pelvic trauma w renal or ureteral injury; Iatrogenic: post-catheterization, surgery; Foreign body (mb physical/sexual abuse)
o Neoplasms: Prostate, Urethra, Bladder, Ureter, KD
o Metabolic: Calculus dz (85% have hemuturia)
o Congenital: PKD
o Hematologic: Bleeding dyscrasias: hemophilia; H-S purpura; sickle cell
o Vascular: AVM, Renal vein thrombosis, Arterial emboli to KD
o Chem: Nephrotoxins, aminoglycosides, cyclosporin
o Obstruction: Hydronephrosis, BPH
• DDX of hematuria, red flags:
o “look-alikes”
o Pseudohematuria: dehydration, dyes (sudan red), foods (beets, rhubarb, berries}, vag bleed, genital/perineal trauma, rifampin
o RF: Gross hematuria, persistent microscopic hematuria in elderly, Age >50, HTN, edema
• Renal colic:
o Usu dt passage of renal calculi
o usu. UL, severe crescendo-decrescendo pain, origin in flank, radiates from CVA to abd, along ureter, to genitalia region and inner thigh
o concomitants: N/V, chills/fever (if infx), gross hematuria suggests stone or bleeding cysts, frequency
o RED FLAGS: fever, oliguria or anuria
• Edema:
o ↑interstitial fluid volume
o Pitting
o non-pitting: Usu dt coagulation of fibrinogen. Trauma creates coagulation of protein, entraps fluid in gel form
o SSX: unexplained ↑wt, tight rings and shoes, puffy face, swollen extremities, abd distention, pitting on digital pressure
• Some Etiologies of generalized edema:
o heart dz: CHF, pericarditis
o liver dz: jaundice, ascities, spider nevi, red nose, palmar erythema, nausea/ vomiting, enlarged & tender liver, history. of heavy alcohol use
o KD dz: nephrotic syndrome, GN, any other cause chronic RF (DM, HTN)
o myxedema (hypothyroid): periorbital edema dt infiltration of mucopolysacch. hyaluronic acid & chrondroitin sulfate, pretibial-swelling on anterior leg, non-pitting, firm
o lymph edema: e.g. mastectomy, removed LNs → swollen arm
• some labs for renal/GU cc:
o urine eosinophils (Wright’s stain): AIN, RPGN, acute prostatitis, Renal atheroembolism
o CBC: anemia (↓ RBC dt ↓ EPO, blood loss), infx
o Urine cytology: Screen and test for uroepithelial/bladder CA: at-risk population, painless hematuria
o Work up for refractory HTN: plasma renin, aldosterone, cortisol, ACTH
o PSA: ↑ w age, BPH, Prostate CA. Used to screen and monitor CaP
o STI testing: Urine NAAT PCR, gram stain, etc
• Imaging for renal/GU cc:
o X-ray (KUB), plain film (for size, shape, position), radiopaque renal calculi (KUB)
o US: masses, cysts, hydronephrosis, aid w bx; PKD, cystic from solid mass. Doppler for renal a, prostate, testicular, penile blood flow
o IVU/P (dye inj, some people react, replaced by CT): visualize kidney & lower UT. if recurrent UTI, obstruction w hydronephrosis, VUR, HTN, renal calculi
o Retrograde urography: detailed exam of lumen of ureters, bladder
o Cystourethrography: incontinence, strictures, reflux
o CT: CA, stones (helical w/o contrast), after US for masses
o Angiography: most invasive; for vascular lesions (aneurysm, tumors)
o MRI: staging, hemorrhagic vs infx cyst, KD vasculature
o Renal scan (radionucleotide scan): renal emboli, renal parenchymal scarring
• Procedures for renal cc:
o Catheterization: urinary retention
o Cystoscopy: visualize bladder wall (bladder CA, interstitial cystitis), bx
o Bx (renal, bladder, prostate)
o Urethral dilation for strictures
• General info on UTIs:
o Mb asx, esp kids and elderly
o Lower: urethritis, cystitis, prostatitis. Sx: dysuria, urgency, frequency, suprapubic pain, cloudy urine, strong odor to urine, hematuria
o Upper: pyelonephritis, ureteritis. Sx: mb fever ( ≥103° F), chills, flank pain, tender CVA, GI sx (D, N/V), mb dysuria
• Pathophysiology of UTI:
o Ascending infections from perineal area/urethra
o Hematogenous: blood borne infections from abscess, IV drugs users
o Direct extension and spread from neighboring organs
• UTI Causative organisms:
o E. coli: 80-90% of cystitis cases; Serotypes 01, 2, 4, 6, 18, 75; Several virulence factors
o Klebsiella, enterobacter: mc kids
o Pseudomonas, Staph: Nosocomial
o Staphylococcus saprophyticus: in young F, (-) nitrite
o Chlamydia trachomatis: Urethritis, prostatitis, epididymitis can mimic cystitis. Routine cultures (-) since intracellular
• Host defenses in the urinary tract:
o WBC’s in bladder mucosa
o acidity of urine
o mechanical action: unobstructed urine flow flushes organisms
o local Abs (IgA) in uroepithelium
o Tamm-Horsfall glycoproteins in uroepithelium and renal tubules
• Risk factors for UTI:
o Anatomical/congenital malf (esp M)
o DM, ↑ CHO diet
o Pg: compression of GU structures → obstruction
o Vag intercourse (“honeymoon cystitis”)
o Hygiene (F): wiping from back to front introduces E. coli to urethra; anal intercourse preceding vaginal intercourse
o prior abx use
o catheterization
o ↓ water intake (infrequent urination/flushing
o use of tampons, spermacides
• Associated pain with the GU tract:
o dull pain at CVA = kidney
o colicky, sudden, severe, radiating from CVA to ureter, scrotum, vulva = ureteral pain (mb R/LLQ pain)
o suprapubic or urethral area pain on urination, better after emptying = bladder, urethra
o fullness or dull perineal or low back pain = prostate
• Associated symptoms with UTI:
o Nocturia: cystitis, incomplete emptying, CHF, mobilization of edema, DM, GU allergies
o Nocturnal enuresis- consider bladder size, hypoglycemia
o Incontinence: usu elderly or post partum (esp. multipara). meds (sedatives, alpha adrenergic blockers, Ca channel blockers), cystitis, CNS dysfxn, pelvic laxity (local trauma from childbirth, surgery), B12 def, DM (peripheral neuropathy)
• Urethritis types:
o Gonocccal: 50%
o NGU: 50%, of these
o most are Chlamydia trachamotis (obligate intracellular organism)
o ureaplasma urealyticum:
o trichomonas vaginalis - rare in males but consider if F partner has persistent infx
o E coli: mc F who practice anal sex
• Urethritis ssx
o Ssx: urgency, frequency, tingling with urination, urethral itching → burning on urination, purulent yellow, green d/c (GC) or whitish-mucoid (NGU)
o NOTE: in female, GC has mild sxs (dysuria, freq, vag d/c) after 7 – 21d incubation; often asx mb carrier of GC & spread to partner, get PID
• Urethritis labs, ddx:
o Lab: UA, urine culture, gram stain, urine NAT; Confirmed cases of GC/CT reportable to public health system
o DDX recurrent UTI’s: Congenital abn (VUR), Bladder CA, Prostatic obstruction, DM, Bladder Calculus
• Cystits, ssx:
o Often asx in elderly and kids
o F: ascending infx from vag, perineal area
o M: ascending from urethra or prostate; chronic bacterial prostatitis mc cause of relapsing cystitis
o SSX- burning or painful urination, frequency, urgency, nocturia, suprapubic pain
o Usu NO fever or back/flank pain
• Cystitis labs, work-up, ddx:
o UA: pyuria, bacteriuria, hematuria (gross or microscopic), (+) leukocyte esterase, Nitrite usu (+) unless amicrobic. Protein (trace or 1+). NO casts (unless KD involve)
o Urine C&S: if UA findings or sx severe, concomitant risk factors
o Mb urther work-up (U/S, CT, CMP): if M under 50; ssx KD involve, recurrent infx, diabetic, immunocompromised, nosocomial source
o DDX for dysuria, urgency, frequency: Vulvovaginitis, STI w urethritis, IC, HSV, trauma cystitis, eosinophilic cystitis (food allergens, drugs, eos in urine)
o Hematuria from neoplasia or calculi, PID, PN
• Acute Pyelonephritis (PN), etio, ssx:
o =acute, U/BL, pyogenic infx of kidney tubules and interstitium
o Etio: ascending from urethra, catheterization (uncommon in M w/o anatomic abn)
o Organisms: E coli (75%), Klebsiella, Proteus, Enterobacter, Pseudomonas, staphylococci
o SSX: Hx LUTI, rapid onset chills, fever (101+), tachycardic (appear ill/toxic); flank pain; tender, enlarged kidney(s); CVA tenderness, N/V, anorexia
o 33% have frequency and urgency
o Mb abd guarding (r/o IP dz)
• Acute PN labs, work-up:
o CBC: ↑ WBC wi left shift
o UA: numerous WBC, (+) LE, nitrites
o Protein usu (-); presence is ominous sign suggesting nephron destruction
o Glitter cells=PMN’s w cyto granules in state of Brownian motion
o Hematuria, bacteriuria, WBC casts, mb bacterial casts
o Urine C&S
o Mb Preg test
o Imaging: if no response to tx; boys, older men (also check prostate); diabetics; hx stones; hx urologic surgery; previous episodes of PN, immunosuppressed
• Acute PN complication, ddx:
o Renal Abscess: If renal infx does not improve in 5 d, consider; =walled off pocket of infx in KD; Fever/chills, flank pain, N/V, malaise, CVA and abd tenderness; seen on CT, treated with draining
o DDX: PID (+CMT); Nephrolithiasis (blood, no fever, ↑ pain); appendicitis (+McBurney’s, +psoas); Acute GN (RBC casts, protein); Perinephritic abscess; endometriosis (cyclic nature); acute abdomen (peritonitis, +rebound tend)
• Chronic PN, risks factors , path:
o Usu BL pyogenic KD infx or congenital reflux nephropathy → renal parenchymal scarring and atrophy of calyces. Course over 20+ yrs
o Risks: Elderly, DM, chronic urolithiasis, ↓water intake/infreq urination, urine reflux, sedentary lifestyle, BPH w obstruction, chronic analgesic use, recurrent bacterial UTI
o Path: unclear; Renal scarring from type 1 fimbriated E. coli is extremely common outcome of PN; histo: patchy interstitial fibrosis, inflam infiltrate. The tubules are dilated or contracted and atrophied
• Ssx, work-up, ddx for chronic PN:
o Ssx: usu asx, found incidentally; may → HTN and RF; oliguria late
o UA: Bacteriuria and pyuria if active infx; Min proteinuria until glomerular involvement; ↓SG and urine osm may be 1st clue; Late: granular, waxy, broad casts
o KUB: small KDs, irregular outline
o Ddx: KD fibrosis, bladder CA, RCC, BPH, chronic prostatitis, CaP, nephrolithiasis
• Nephropathies:
o Glomerular (nephritic, nephrotic), Tubular, Interstitial, both
• Glomerular dos:
o Consider glomerular involvement if:
o family hx, edema,
o urine findings: hematuria (dysmorphic), RBC casts, lipiduria, proteinuria (of variable amts), ↑serum creatinine.
o Definitive dx by renal bx
• Nephritis syndromes:
o Glomerular inflam process causing renal dysfunction:
o Structural changes: cellular and leukocyte proliferation, GBM thickens and scleroses, deposits
o Functional: ↓GFR, HTN, RBCs, protein passes membrane
o Classic presentation: PHAROH- Proteinuria, Hematuria, Azotemia, RBC casts, Oliguria, HTN
o Other ssx: edema (peripheral, periorbital, pulmonary), mb rash, heart murmur
o PIGN, RPGN, Berger’s (IgA), Alport’s,
• PIGN, path:
o Type III hypersensitivity rxn: Ag-Ab complexes lodged in GBM podcytes → C activation
o Common in kids 5-15
o Organisms: mc nephritogenic strain of group A beta hemolytic strep; or others (bacteria, viruses, parasites)
o Path: Ags bind GBM, activate C → focal or diffuse glomerular damage
• PIGN ssx, work-up:
o SSX: Prior GAS infx; Latent period 1-3 wks post pharyngitis; 3-6 wks after skin infx; Fever, confusion, HTN, periorbital edema, hematuria, HA, N/V, malaise
o UA: cola-colored urine, oliguria, RBCs, RBC casts (pathognomonic, but not always present)
o 24 hr urine protein: Proteinuria
• RPGN, 3 types:
o Conds that → glomerular cresents (bx), can → ESRF in wks-mos. 20-50yo
o type 1, a-GBM dz; eg Goodpasture’s syndrome: Assoc w influenza A, H-C solvent exposure or HLA-DR2 Ag. a-collagen Abs in alveoli capillaries cross-react w GBM, trigger Type II hypersensitivity rxn; Concomitant pulm hemorrhage (dyspnea, hemoptysis, crackles), renal sxs (edema, HTN).
o type 2, immune complex: eg Henoch-Schönlein purpura: IgA immune complexes in CT as and GBM. Renal dz (hematuria, proteinuria), purpura on arms, legs, buttocks, arthralgia, GI sxs. Mc M ↓15
o type 3, Pauci-immune: eg Wegener’s granulomatosis (ANCA-assoc): → necrotizing GN. Renal dz (hematuria and proteinuria), bleeding respiratory tract nodules (hemoptysis, crackles)
• Berger’s dz (IgA Nephropathy ), ssx:
o IgA deposition in mesangium, mesangial proliferation
o M > F (6:1), peak teens & 20s
o Mc cause GN worldwide. Unknown etio
o SSX: Episodic gross hematuria ↓5 d after viral/bacterial URI (flu-like sx) or GE; persistent microscopic hematuria, mild persistent proteinuria, HTN; RF rare; 30-40% asx
• Berger’s work-up:
o UA: mild proteinuria, RBCs and casts, WBCs
o Serum creatinine usu N
o ↑ Serum IgA in 50% (not so useful)
o KD bx: (on pts with persistent proteinuria >1g/d) ; IgA deposits on mesangium
• Alport’s Syndrome (Hereditary Nephritis):
o Gene mutation of type IV collagen. X-linked
o →GBM scarring and interstitial fibrosis
o SSX: hematuria, impaired renal fxn, sensorineural hearing loss, cataracts
o Px: st acute GN → Chronic GN: irreversible and progressive glomerular and tubular fibrosis, ↓GFR, retention of toxins → chronic KD dz, ESRF
• Nephrotic syndromes:
o end result of a variety of dz that damage (immune or other) GBM →protein wasting (altered GBM charge), ↑permeability of glomerular capillaries
o Severe proteinuria (>3.5 g/1.73 m2/24 hr) → systematic edema: ↓oncotic P → ↑fluid in interstitial spaces
o “Foamy” urine: albumin has soap-like effect that ↓ surface tension
o Lipids pass as well (lipiduria, lipidemia)
• Primary nephrotic syndromes (non-proliferative??):
o Minimal change dz: Kids and adults, Sudden onset proteinuria w/o renal dysfxn; Pattern: T-cell cytokine injury to epithelial foot process, no deposits
o FSGS: Young adults, black men; Assoc w drugs, obesity, HIV; Pattern: focal and segmental hyalinization of GBM, sclerosis
o Membraneous nephropathy: adults; Assoc w drugs, Hep B, syphilis, Lupus, malaria; Pattern: IgG deposits on thickened glomerular capillary walls
• Secondary nephrotic syndromes (proliferative??), ssx:
o Poorly controlled DM (diabetic nephropathy), Primary KD dz and nephritic conditions, SLE, amyloidosis, HIV, pre-eclampsia, drugs (penicillamine, NSAIDs, lithium, heroin, gold compounds), Snake bite, CA (lymphomas and leukemias), FH of congenital kidney dz
o Ssx: HTN: ↓ renal flow, renin secretion, ↑BP to ↑GFR
o ↓urine output: renin-angiotensin → vasoconstriction; aldosterone → Na and H2O retention
o Edema, ascites, ↑wt, “moon facies” (periorbital edema)
o Foamy urine, Muscle wasting, weakness, malaise
o Cough, DOE
o Risk infx dt loss of Ig’s; risk bleeding dt loss coagulation factors
• Work-up for 2nd NS:
o Proteinuria >2g/m2/day (or >3.5 g/d), microalbuminuria (>30 mg/24 hr)
o hematuria, lipiduria (oval fat bodies)
o Hypoalbuminemia, dyslipidemia, azotemia
o Renal US
o Electron or light microscopy: characteristic lesions
o Other: (+)ANA, ↓C3, C4 in SLE; ANCA, a-GBM Abs
o Renal bx to dx, always indicated if cause is apparent
• Diabetic Nephropathy, risks factors, ssx:
o mc cause NS and ESRD in US
o Glomerular sclerosis and fibrosis from glycosylation of GBM proteins, cytokines, mesangial deposits, vascular endothelial damage (course of yrs)
o Suspected w DM who develop proteinuria
o IDDM: 40% → RF; NIDDM 20-30%
o Risk: ethnicity (blacks, Latinos, Polynesians), duration/degree of hyperglycemia, HTN, dyslipidemia, smoking
o SSX: early asx, HTN, dependent edema, uremia (N/V, anorexia), Diabetic neuropathy, retinopathy
• DN lab, management, ddx:
o Lab: Microalbuminuria 30-300 mg/d → proteinuria →NS, ESRF
o Manage: control glucose levels, control BP, screen urine proteins (microalbumin), HgA1c, retinal exams, diabetic foot testing
o Also watch for: infx (glucose in urine feeds bacteria, PN risk), neurogenic bladder (retention or incontinence dt neuro damage)
o Ddx (other edema states): CHF, LV failure, PN, ATN, malignant HTN, multiple myeloma
• Mixed nephritic/otic syndromes:
o Membranoproliferative glomerulonephritis: kids & adults; Assoc w SLE, HIV, Hep B/C, CA, pattern: diffuse thickening of GBM
o Systemic Lupus: specific “wire loop” lesions, with several histologic patterns; Type III hypersensitivity rxn; Recurrent hematuria, proteinuria, HTN, rash, jt problems
• Tubule-interstitial dzs:
o Injury to renal tubules, interstitium or both; extent of damage → RF o ATN (acute tubular necrosis) o ATIN (acute tubule-interstitial nephritis) o CTIN
• Acute Tubular Necrosis (ATN)
o “Toxic Nephropathy”; Damage to renal tubular epithelial (RTE) cells from:
o 1) ischemia: shock (sepsis, anaphylaxis, hemorrhage), trauma, surgery, DIC
o 2) nephrotoxins: eg. aminoglycosides, amphotericin B, lithium, cisplatin, radiographic dyes, solvents, heavy metals, toxic mushrooms, NSAIDs
o Histo: Patchy focal necrosis of tubule. Lumens fill with casts, cellular debris
o SSX: depends on cause, course is variable. May → ARF. mb: uremic pruritis, pericardial friction rub, asterixis, HTN, edema. Oliguria depending on severity and extent of tubular damage
o UA: mild proteinuria, hematuria, RTE/casts w tubular fragments
o CMP: ↑ BUN/creatinine ratio, ↓ GFR
• Acute Tubulointerstitial Nephritis (ATIN), categories:
o “Hypersensitivity Nephropathy”; Inflam renal interstitium, from cell-mediated immune response binding to interstitial proteins → ↓ renal function. Interstitial compartment infiltrated by T-cells, mono, plasma cells
o Allergic Drug Rexn: (75%) methicillin, sulfonamides, Cipro, NSAIDS, thiazide diuretics, allopurinol, phenytoin, captopril, cimetidine
o Infx: (5-10%) Legionella, Leptospira, Strep, Corynebacterium diptheriae, Rickettsia, Toxoplasma, Salmonella, S.areus, Mycoplasma, TB, HIV, EBV, CMV
o Related to systemic AI dz: (10-15%) SLE, sarcoidosis, Sjogren’s, Wegener’s
o Idiopathic
• ATIN ssx, work-up:
o Ssx: acute onset ↓renal function, d-2 wks post meds or infx; fever, rash, hematuria, oliguria, N/V, malaise
o UA: hematuria, mild-mod proteinuria, ↑WBCs, WBC casts, NO bacteria. Usu Eosinophiluria
o CBC: eosinophilia
o ↑ serum creatinine w ↓ renal fxn
o FENa (fractional Na excretion) > 1% = tubular damage
o Depending on cause: mb PPD skin test, serology
o renal bx if persisting sxs
• CTIN:
o mult causes of chronic damage: fibrotic scar tissue replace cellular infiltrate, tubular atrophy & dysfxn over mos-yrs
o General SSX: nocturia, uremia sx, small kidneys, hyperkalemia, ↓SG
o Hyperchloremic metabolic acidosis from: ↓ammonia production, Inability to acidify distal tubules, Proximal tubule HCO3 wasting
• Causes of CTIN:
o Obstructive uropathy renal stone, prostate dz, cx/colon/bladder CA; if partial obstruction urine output alts from polyuria (ADH insensitivitiy) and oliguria (↓GFR); Late: Azotemia and HTN
o Reflux nephropathy (VUR): incompetent sphincter allows retrograde low; HTN, renal insufficiency, hx recurrent UTI in kids; Renal scarring → proteinuria and CKD.
o Analgesic nephropathy: Common F 50-55. 3-5% all ESRF in US. many asx (found incidentally), polyuria, HTN; hematuria, proteinuria, anemia, ↑serum creatinine; Sloughed papillae in urine
o Lead nephropathy (and other heavy metals, Cd): kids 3-6mos from pica, Environ or occ exposure; Pb: filtered by glomerulus, transported across PTs, accumulates; hyperuricemia, HTN, Multisystem sxs (GI, Neuro, hematologic)
• General Work-up for CTIN:
o UA, BUN, Serum creatinine, electrolytes
o Abd US or IVU to investigate obstruction or reflux
o Analyze hx analgesic use
o CT w/o contrast shows small, calcified, indented kidneys
o EDTA chelation test for heavy metals
• Renal tubular transport abnormalitites:
o Fanconi syn o Liddle syn o Nephrogenic DI o RTA o Wilson’s dz
• Fanconi syndrome:
o Damaged PT → wasting of molecules usu reabsorbed (phosphaturia, glucosuria, albuminuria, uricosuria, bicarb wasting)
o familial or acquired (assoc w multiple myeloma, Pb/Cd toxicity, ARV drugs, tetracycline)
o SSX: osteomalacia in adults, hypophosphatemic rickets in kids, polyuria, polydipsia
• Liddle syndrome:
o = pseudoaldosteronism. Very rare. AD defect in tubules
o Presents as severe / refractory HTN, metabolic alkalosis from hypokalemia, hypoaldosteronism
• Nephrogenic DI:
o Congenital (x-linked) or Acquired (Li, amphotercin-B, PN, PKD) defect to renal tubular responsiveness to ADH
o Ssx: polyuria, polydipsia, failure to thrive, dehydration
o Lab: urine SG ↓1.005, hypernatremia
• RTA:
o →met acidosis, PTs don’t reabsorb HCO3 (type 2), DTs don’t secrete H (type 1), or abn ALD response in DT (type 4)
o Causes: heredity, A (Sjogren’s, Lupus, RA), drugs/toxins (toluene, Li, amphotericin B, Pb), chronic obstruction, DM
o SSX: urinary stones, bone demineralization, hypokalemia in type 1 or 2 (mm weakness, hyporeflexia), hyperkalemia in type 4 (arrhythmias)
• Wilson’s Disease:
o (NOT Wilson’s syndrome- a thyroid dz.)
o Hereditary
o Cu deposited in tubules, liver, brain, RBCs → injury
o May present w Fanconi, hepatitis, Kayser-Fleischer ring (gray-green corneal limbus)
