- Urinalysis

Normal values:
- Amount = 0.5-2L per day
- pH = 6
- Protein = albumin < 30 g per gram of creatinine
Sediment Casts
- Formed only in the DCT & CD
flow rate, salt concentration & pH favour protein cast formation
Azotemia = BUN & creatinine due to GFR
Uremia = Azotemia + clinical findings
- Results in metabolic acidosis
acid excretion & bicarbonate reabsorption
Retention of water, phosphate, Na & K
Loss of Ca due to loss of kidney parenchyma > Vit. D
- If BUN:Creatinine ratio is >20:1 > think pre-renal ARF
Renal Syndromes
- Pre-Renal ARF > caused by loss of blood, CO or blood flow obstruction
- Chronic Renal Failure (ie. prolonged uremia)
Caused by DM, HTN or GN
Presents with azotemia/uremua & GFR
Labs show metabolic acidosis, Ca, salt retention & broad waxy casts
Complications include
- HTN & CHF due to water retention
- Renal osteodystrophy due to phosphate & Ca retention > PTH
- Normocytic anemia due to EPO
- Hemorrhagic diathesis
- Nephritic Syndrome (ie. hematuria due to glomerular disease)
Hematuria due to GBM damage > dysmorphic RBCs & RBC casts
Mild proteinuria (<3g / day) due to GBM damage > edema
renal perfusion > oliguria & HTN
Acute Nephritic Syndrome
- MCC is post-strep GN
- Nephrotic Syndrome
Severe proteinuria (>3.5g / day) > hypoalbuminemia > severe edema
Liver compensates > hyperlipidemia > lipiduria > lipid casts (maltese cross)
Loss of gammaglobulins > risk of infection
Loss of antithrombin-III > thromboembolisms
- Urinary Tract Infection
Pyuria w/ WBC casts
Bacteruria >105 colonies / mL of cultured urine
- Plate cultures on both blood agar & MacConkey agar
Count # of colonies on blood agar after 18-24h & multiple by dilution factor
- E. coli
Nitrite +ve
Pink on MacConkey
- Proteus
Nitrite & Urease +ve urease may lead to kidney stones
Lactose -ve
Swarming motility concentric rings on agar
- Staph. saprophyticus & Enterococcus faecalis
Nitrite -ve

- Glomerulonephritis
Glomerular barrier is composed of 3 layers
- Endothelial cells w/ fenestrations

- Glomerular Basement Membrane of collagen T4 & GAGs

- Epithelial podocyte foot processes w/ slit diaphragms
Classifying glomerular pathology
- Diffuse = >50% of all glomeruli are involved
- Focal = <50% of all glomeruli are involved
- Of the glomeruli that are involved
Global = entire glomerulus effected
Segmental = part of glomerulus effected
Mesangial = only mesangial cells effected
Immune Complex Deposition
- Subepithelial b/w epithelium and GBM
- Subendothelial b/w endothelium and GBM
- Mesangial within mesangium
Chronic GN
- End-stage scarred kidneys from several types of GN
- If presenting at this stage, may not be able to make specific diagnosis
- Renal Disease Secondary to Systemic Disease
HTN and the Kidney
- Arteriolonephrosclerosis
Medial & intimal thickening in response to BP
- Endothelial damage > protein extraversion > BM deposition > vessel narrowing
Patchy ischemia > tubular atrophy, interstitial fibrosis & glomerular sclerosis
- Malignant HTN
Accelerated nephrosclerosis
- Gross = flea-bitten kidney
- Micro = fibrinoid necrosis of arterioles & hyperplastic arteriolitis (onion-skin appearance)
Thrombotic Microangiopathies
- HUS
Caused by Shigella-like toxins damaging endothelial cells
- MCC is ground beef containing E. coli O157-H7
Presents with diarrhea & renal damage w/o any CNS symptoms
- Atypical HUS
Most have immune defect with deficiency of complement regulatory proteins (ex. Factor H)
- Inability to turn off immune system > results in endothelial injury
Not associated with diarrhea
Complication of pregnancy, vascular disease, & cancer treatment
- TTP
Caused by deficiency of ADAMTS13 (vWF protease)
- Results in PLT aggregation > microscopic microangiopathic hemolytic anemia
Renal damage due to infarction & ischemia
Presents with CNS symptoms
- Tubulointerstitial Diseases
Acute Tubular Necrosis
- Due to ischemia or toxin & MCC of acute renal failure
Ischemic
- Micro patchy necrosis but entire tubule
- Gross pale swollen cortex
Toxic
- Micro extensive necrosis but mainly PCT
- Gross red swollen cortex
- Differentiate from pre-renal ARF by looking at BUN:creatinine ratio
- 2 pathways of ATN
Ischemia > RAAS > vasoconstriction > GFR > oliguria
Ischemia > tubular cell injury > obstruction & tubular leak back > oliguria

- UA shows eosinophilic dirty granular casts of epithelial cells

Obstructive Uropathy
- Hydronephrosis = dilation of renal pelvis & calyces from urine buildup leading to atrophy
Reflux Nephropathy
- Retrograde flow during bladder contraction causing recurrent UTIs
- 2 causes:
Malformed ureter insertion into bladder
Malformed, blunted renal papillae
- Seen as polar scarring
Acute Pyelonephritis
- Caused by PEEKS > Proteus, E. coli, Enterobacter, Klebsiella & Serratia
- Complications > Papillary necrosis, Pyonephrosis, Perinephric abscess & Pyelonephritic scar
Papillary necrosis can be seen w/o pyelonephritis in Analgesic Nephropathy
- Analgesic Nephropathy > usually seen w/ excessive phenacetin intake
Chronic Pyelonephritis
- Gross irregular scarring w/ broad cortical fibrosis, blunted calyx & flattened papillae
- Histo interstitial fibrosis, mononuclear infiltration & Thyroidization (dilated tubules with hyaline)
- Xanthogranulomatous Pyelonephritis
Associated with Proteus infection > yellow nodules due to foamy M
Acute Drug-Induced Allergic Interstitial Nephritis
- Hypersensitivity reaction beginning 2 weeks after exposure to drug
Commonly antibiotics, diuretics & NSAIDS
- Visible as mononuclear interstitial infiltration w/ E, N & possible granulomas
- UA shows E & E casts (stain with Hansels stain)
Urate Nephropathy
- Uric acid crystals in tubules/collecting ducts obstructing flow
- MC in patients receiving lymphoma/leukemia chemotherapy due to massive cell death
- Prevent w/ hydration & by urine pH
- Chronic urate nephropathy seen in moonshine drinkers due to amount of lead exposure
Myeloma Kidney
- Light chain nephropathy due to light chains combining with urinary glycoproteins to form casts
These casts obstruct tubules
- Light chains can also cause amyloidosis
- Hematuria
3 RBC per high powered field in 2/3 centrifuged urine sample
MCC are UTI, stones or malignancy
Evaluation of a patient with hematuria
- Pyuria or dysuria UTI
- Recent URI post-strep GN
- Unilateral flank pain ureteral obstruction or renal infarction
- Cyclical hematuria in women endometriosis of urinary tract
- African American sickle cell trait
Glomerular vs. Extraglomerular Hematuria
- Glomerular
Dysmorphic RBCs & RBC casts
Proteinuria >500mg/dL
Dark brown coloured urine
- Extraglomerular
Clotted blood
Bright red blood
Glomerular Hematuria Causes
- IgA Nephropathy
MCC of GN in Europe & Asia
MCC of GN in children
MCC of mono symptomatic hematuria

 Can present with gross hematuria during viral illness & microscopic between episodes
- Alports Hereditary Nephritis
Recurrent or persistant microscopic hematuria
- Proteinuria
Normal urine contains Tamm-Horshfall protein (mucoprotein)
Categories
- Microalbuminuria is 30-300 mg/day
Consider early diabetes, HTN or early GN
- Macroalbuminuria is 300-3500 mg/day
Consider Myeloma-associated kidney disease
- Nephrotic is >3500 mg/day
Transient proteinuria > fever, exercise, CHF & seizure related
Orthostatic proteinuria > first morning sample should have normal protein:creatinine ratio
Quantitation
- Creatinine Index: 20-25 mg/kg/day for men
15-20mg/kg/day for women
- Protein:Creatinine radio: 0.2
- 1+ (30mg/dL) 2+ (100mg/dL) 3+ (300mg/dL) 4+ (2g/dL)
- Urinary Tract Infections
Usually occur in sexually active women of reproductive age
- Male patients are usually >50 and have enlarged prostates
Usually caused by retrograde ascent of microbes up urethra to bladder or kidneys
- MCC is E. coli
Type 1 fimbriae bind mannose
P fimbriae bind kidney cells
Upper UTI vs. Lower UTI
- Upper UTI (ie. pyelonephritis)
Presents with fever, chills, sweats, N+V
Flank pain or abdominal discomfort
UA shows pyuria, WBC casts & bacteria
- Lower UTI (ie. cystitis)
Presents with dysuria, frequency & urgency
Suprapubic pain
UA shows hematuria, pyuria & bacteriuria
In males, can be prostatitis
- Presents with fever, pelvic pain, back pain & urinary retention
Tender prostate on DRE
- Caused by E. coli & Staph. aureus
Bacterial Causes
E. coli leading cause of HA & CA UTIs
Staph. saprophyticus 2 to E. coli in young, sexually active females Honeymoon Cystitis
Enterococcus faecalis more common in patients with BPH
Proteus more common in HA & institutionalized elderly
Viral Causes
- Only seen in IC patients (ex. transplant recipients)
- MCC are Adenovirus & BK Virus
Adenovirus
- Acute hemorrhagic cystitis in boys
- Transmitted by respiratory droplets, feces & swimming pools
BK Virus
- Cystitis, hemorrhagic cystitis & ureteral stenosis in children
- Transmitted by respiratory droplets

 Helminth Causes
- Schistosoma hematobium
Usually in Africa, Asia & Mediterranean
Snails are intermediate host & release larvae into water
Presents with hematuria & dysuria
- Acid Base Balance
Formulas
- Metabolic Acidosis Winters Formula > pCO2 = 1.5 x HCO3 + 8
- Metabolic Alkalosis Winters Formula > pCO2 = 0.8 x HCO3 + 15
Compensation
- Acute Hypercapnia HCO3 1 meq/L for each 10 mmHg in PaCO2
- Chronic Hypercapnia HCO3 3.5 meq/L for each 10 mmHg in PaCO2
- Acute Hypocapnia HCO3 2 meq/L for each 10 mmHg in PaCO2
- Acute Hypercapnia HCO3 5 meq/L for each 10 mmHg in PaCO2
Anion Gap
- AG = Na - [Cl + HCO3]
normally 12-14
- Causes of anion gap acidosis:
Causes of non-anion gap acidosis:
M methanol
H hyperalimentation
U uremia
A Addison disease
D DKA
R renal tubular acidosis
P propylene glycol
D diarrhea
I ingestions [cocaine]
A acetozolamide
L lactate
S spirnolactone
E ethanol
S saline infusion
S salicylates
- Pathology of Renal Development
Renal Hypoplasia 6 renal pyramids
Renal Dysplasia
- Enlarged & cystic kidney
- MCC of cystic disease in children
- Micro immature glomeruli, tubules & cartilage surrounded by mesenchymal tissue
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- Massive kidneys w/ expanding cysts that destroy renal parenchyma > CRF
- Always bilateral > if unilateral, think renal cell carcinoma
- 2 causes
PKD1 mutation of Polycystin-1 has 70% progression to renal failure
PKD2 mutation of Polycystin-2 has 15% progression to renal failure
- Associated complications
Berry Aneurysm in the Circle of Willis (esp. anterior communicating artery)
Hepatic & splenic cysts
Mitral valve prolapse
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
- Bilateral cystic dilation of only the collecting duct
- Caused by PKHD1 mutation of Fibrocystin
- Gross multiple small cysts within cortex & medulla > Spongiform Kidney
- Associated with liver cysts > Congenital Hepatic Fibrosis
Acquired Cysts
- Simple Cyst benign, subcapsular cortical cysts that rarely produce symptoms
- Dialysis-Associated Cyst cortical & medullary cysts that can progress to renal cell carcinoma
Alports Syndrome
- X-linked mutation causing defective assembly of collagen type IV
- Visible as irregular thinning of the GBM with a split lamina densa
- Presents with hematuria & possible nephrotic syndrome
- Associated with deafness & ocular disorders

 Thin Basement Membrane Lesion (Benign Familial Hematuria)

- Mutation of collagen type IV causes thin GBM
- Presents with hematuria but requires no treatment
Renal Organ Rejection
- Hyperacute
Preformed Ab attack transplant kidney
- Acute
2 phases
- Cellular Rejection lymphocytes invade
- Humoral Rejection Ab cause necrotizing vasculitis & C4d depostion
- Chronic
Interstitial fibrosis, tubular atrophy, thickened GBM
Marked intimal blood vessel fibrosis
- Renal Failure
Acute Renal Failure:
- creatinine of >0.5 mg/dl in 72h
- BUN & creatinine
- GFR
- urinary output
5 stages of ARF (Rifle)
- Risk serum creatinine 1.5x or GFR by 25%
- Injury serum creatinine 2x or GFR by 50%
- Failure serum creatinine 3x or GFR by 75%
- Loss loss of kidney function for >4w but reversible
- End Stage loss of kidney function for >3m not reversible
Contrast-Induced ARF
- Esp. a risk for patients with diabetes
- Caused by contract used in angiography
- Prevent with NAC or saline
Chronic Renal Failure (CKD)
- Renal osteodystrophy
plasma calcitriol fall when GFR is less than 30mL/min
- Stages:
Stage 1 GFR >90 (normal but at risk)
Stage 2 GFR 60-89 (mild)
Stage 3 GFR 30-59 (moderate)
Stage 4 GFR 15-29 (severe)
Stage 5 GFR <15 (renal failure)
- Dialysis indications (A E I O U)
A acidosis pH 7.2
E electrolyte abnormality (hyperkalemia)
I intoxication (methanol, ethylene glycol, theophylline)
O overload of volume (CHF, pulmonary edema)
U uremia (pericarditis, seizures, neuropathy or encephalopathy
- Geriatrics
Skin
- Seborrheic Keratosis benign dark lesions on skin
- Cutaneous Horn pre-malignant
- Basal Cell Carcinoma malignant
Sarcopenia loss of muscle mass & strength w/ no underlying cause other than aging
Geriatric Giants
- Postural Instability (ex. falls)
- Immobility
- Cognitive impairment (ex. dementia, delirium)

- Urinary Incontinence
Functional Incontinence cannot get to and/or use the toilet
Urge Incontinence detrussor muscle overactivity
Stress Incontinence weak pelvic floor muscles allows for urine leaks
Overflow Incontinence atonny & overfilling of bladder (seen w/ BPH)
- Urolithiasis
Formation of stones in renal collecting system from crystals contained in urine
2 pathogenesis
- Supersaturation of urine causing crystals to precipitate out [ex. Dehydration]
- Deficiency of urinary stone formation inhibitors
Presents with renal colic & gross hematuria with no casts
- Paroxysmal flank pain radiating to groin
Obstructions can lead to hydronephrosis, recurrent UTIs & pyelonephritis
Stone Type

Mechanism

Features

Calcium Oxalate
Calcium Phosphate

Hypercalciuria
Hyperoxaluria

MCC of renal stones

Radiopaque
Seen w/ hyperparathyroidism

Ammonium Magnesium
Phosphate (AMP)

Alkaline urine due to Proteus or

Klebsiella infection

Radiopaque
Seen w/ renal infections
Cause Staghorn Calculi

Uric Acid

Hyperuricosuria
Acidic urine

Radiolucent
Seen w/ gout, leukemia/
lymphoma

Cystine

Hereditary cystinuria

Primarily in children

Renal Adenoma

- renal tubule origin

- potentially malignant

- papillary
- no nuclear atypia or clear cells

- asymptomatic

Angiomyolipoma

- vessel, SM & fat origin

- MC renal tumor in tuberous sclerosis

- proliferation of blood vessels, smooth

muscle cells & lipid cells

- spontaneous
hemorrhage

Medullary Fibroma

- renal medulla origin

- benign

- small white/grey lesion in medulla

Oncoytoma

- collecting duct origin

- benign

- tan color and circumscribed

- central scar
- granular eosinophilic cytoplasm
- abundant mitochondria
- colloidal iron stain -ve

Squamous Cell
Carcinoma

- caused by chronic irritation (ex.

catheter)
- common in areas endemic for
schistosomes

- normal Sq CA appearance:
- keratin pearls & bridges

Wilms Tumor
(Nephroblastoma)

- MC paediatric tumor
- 95% <10 y/o
- preceded by nephrogenic rest lesions
- deletion of WT1 & WT2 genes on
chromosome 11

- solid w/ areas of necrosis/cysts

- triphasic:
- epithelial
- blastema
- myxoid stroma
- primitive tubules, glomeruli &
mesenchymal elements
- may have cartilage, bone & muscle

- poorer prognosis associated with:

- anaplasia (large pleomorphic
hyperchromatic nuclei w/ abnormal
mitosis)

- congenital malformations
WAGR
- Wilms tumor
- Aniridia
- GU malformation
- Retardation
Denys-Drash
- Gonadal dysgen.
- Nephropathy
Beckwith Widman
- Hemihypertrophy
- Macroglosia
- Embryonal tumors

Renal Cell
Carcinoma (RCC)

- MC renal tumor
- males >70 y/o
- smoking risk
- VHL mutation
- MCC of metastatic clear cell
carcinoma
- poorer prognosis associated with:
- sarcomatoid change
- renal vein

Clear Cell RCC

- solid or trabecular
- clear cytoplasm b/c of glycogen &
lipids

Triad
- Hematuria
- Mass
- Dull flank pain

Papillary RCC
- cuboidal or low columnar cells
- interstitial foamy M

Paraneoplastic due to
EPO, Renin, PTH, ACTH
production

Chromophobe RCC
- sheets of eosinophilic cells w/
perinuclear halos
- colloidal iron stain +ve
- abundant cytoplasmic vesicles

Urothelial Tumor
(Transitional Cell)

- urothelium of renal pelvis, ureter,

urethra & bladder
- Males >50 y/o
- smoking risk
- napthylamine dyes risk
- non-invasive is mutation of p16 on
chromosome 9
- invasive is mutation of p53 on
chromosome 17
- prognosis depends on stage:
- superficial 90% 5yr survival
- invasive 50% 5 yr survival
- metastatic 5% 2 yr survival

Exophytic Papilloma
- fibrovascular papillae covered by
urothelium
Inverted Papilloma
- smooth surface with inward growth
Low Malignant Potential
- similar to, but thicker than papilloma
Carcinoma in Situ
- flat red lesion with no mass
- malignant cells within epi.
- many progress to high grade
Low Grade Carcinoma
- mild atypia w/ some mitosis
- rarely invade but often reoccur
High Grade Carcinoma
- solid papillary structure
- nuclear atypia w/ mitosis
- often necrosis & invasion

- painless hematuria