UQ PATH: RENAL MODULE

RENAL WEEK 1:
URINARY 3: Urinary Tract Infections Cystitis (bladder); Pyelonephritis (kidney; acute or chronic)
UTI: usually G-ve bacilli, usually living in intestinal tract (S. faecalis); fungi, viruses, other infectious agents
Pyelonephritis pathogenesis: ascending infection, haematogenous infection (immunocompromised, usually
not enteric)
o Ascending: colonization of distal urethra; infection urethra to bladder (especially F); urinary stasis
facilitates bacterial growth (BPH, obstruction); VUR, IRR (intra-rental reflex)APN

Vesicouteral reflex = scarring on the poles of the kidney (see lots of neutrophils)
o Hematogenous: septicaemia (from infective endocarditis)
Acute Pyelonephritis: Clinical Features: Pain at CV angle, systemic infection, dysuria/frequency/urgency,
urine contains leukocytes, neutrophil casts (because means kidney tubules involved)
o Associated conditions: UT obstruction, cath, VUR, pregnancy, DM, immunosuppression/age (until 40;
F>M; after = males because of prostate) and sex
o Outcome: appropriate antibiotics resolve within few days; histologically healing when
neutrophils and debris removed by macrophages

Severe infection: extensive necrosis fibrosis deformation of underlying calyx/pelvis

o Complications: papillary necrosis (DM/obstruction coagulative necrosis can become ARF);
pyonephrosis (almost complete obstruction; cant drain & fills calyx filtering system); perinephric
abscess (infection spread through capsule)

Polyoma virus latent in urine; widespread; immunosuppression of allograft recipients

nephropathyallograft failure in up to 5% of kidney transplant patients
Chronic Pyelonephritis: tubulointerstitial renal disease with involvement of calyces and pelvis 2 forms:
o 1. Reflux nephropathy more common form; renal involvement in childhood due to congenial VUR
causing intrarenal reflux (doesnt need infection, just obstruction causes damage) repeated urinary
infection

Can be uni/bilateral; bilateral chronic renal insufficiency

o 2. Chronic obstructive pyelonephritis: obstruction infections scarring renal insufficiency
(uni/bilateral)

Hallmark = corticomedullary scar; blunted/deformed calyx; microtubules show atrophy and

hypertrophy in others (thyroidisation of kidney); interstitial contains inflammation/scarring in
cortex/medulla

Xanthomatous pyelonephritis: special type where there is large aggregates of

macrophages mixed w/ chronic inflammatory cells (looks like RCC; usually due to proteus
infection
o Clinical features: insidious onset of chronic renal disease, HTN, polyuria/nocturia, asymmetrically
scarred contracted kidneys, recurrent acute PN, proteinuria/nephrotic syndrome from FSGS
Urinary Tract Obstruction occur anywhere; usually pain but symptoms are usually due to cause of
obstruction (renal colic from calculi, irritative bladder symptoms from BPH); may not have symptoms for a
long time
Tumours of the kidney: Divide by epithelial, stromal, lymphoid and then benign, malignant
o Papillary adenoma: common, papillary epithelial neoplasms < 5 mm in diameter, no nuclear atypia
o Angiomyolipoma: happen in association to tuberous sclerosis, but can occur spontaneously
o Oncocytoma: produce encapsulated tumor with central scar, packed with large eosinophilic cells
because packed with mitochondria, can be any size
o Prognosis: 25% have metastases at presentation, no Tx, overall 5 year survival 45%, 5 year survival
in absence of mets at time of nephrectomy 70%

Depends on histological subtype, Fuhrman nuclear grade, pathologic stage, vascular invasion,
necrosis, tumour size

5 year survival chromophobe = 100%, papillary 86%, clear cell 76%, unclassivied 24 %

RCC: T1 7cm or less; T2 >7 cm, T4 beyond Gerota fascia spread

o RCC: >90% of renal malignancy, M>F in older age (but can also occur in children), associated with
tobacco, exposure to chemicals (asbestosis), obesity, estrogenic exposure

Characterized by: CV pain, palpable mass, hematuria, generalized constitutional systems, found
incidentally

Paraneoplastic: EPO, PTHrP, ACTH, haptic dysfunction, feminization, eosinophilia, amyloidosis,

leukemoid reactions

Categorized into specific types:

1. Clear Cell RCC (Conventional Type): 70% renal tumors, usually solitary (multicentric in
4%), bilateral in approximately 3%
o Deletion of short arm of chromosome 3; loss of tumor suppressor gene deletion
RCC
o Multilocular Cystic Renal Cell Carcinoma: 5% of clear cell renal cell carcinomas; well
differentiated, excellent prognosis

2. Papillary Renal Cell Carcinoma: 15% of renal tumours; bilateral in 4% of cases;

multifocal in 20-25% of cases; most common type occurring in renal cystic disease
o Trisomy of chromosome 16 and 17; trisomy or tetrasomy of chromosome 7

3. Chromophobe RCC: 5% of RCC; differentiation towards intercalated cells of collecting

ducts
o Hypodiploid; loss of entire chromosomes (1,2,6,10,13,17,21), loss of heterozygosity at
regions (1p,2p,6p,17p,17q)
o 2 types: typical variant versus eosinophilic variant

4. Collecting Duct RCC: <1% of renal tumors; arising from collecting duct epithelium,
predominant in medullar but cortex may in involved, grossly infiltrative
o Loss of chromosome arms 8p and 13q; monosomies for chromosome 1,6,14,22

5. Childhood RCC: incidence increase in papillary and unique subtypes; associated with
syndromes, often high grade, high stage, unusual morphology (nephroblastoma however is
still more common)
o Familial Renal Cell Tumors: VHL, hereditary papillary renal cancer (c-MET), hereditary leiomyomatosis
and RCC (FH), Birt Hogg Dube (BHD), TSC 1 and 2, Constitutional chromosome 3 translocation
Urothelial Carcinoma of Bladder: 5-10% primary renal tumors; present later than with bladder UC; papillary
and exophytic or invasive
o Low grade or high grade; 50% there is concominant bladder UC, will see flank pain and hematuria
o Can be due to: analgesic nephropathy, tobacco, exposure to chemicals, HNPCC
o Poor prognosis, 5 year survival rates varying from 50-70% for low grade, only 10% for infiltrating high
grade cancer
Pediatric Malignant Renal Tumors
o 1. Nephroblastoma (Wilms tumor): malignant embryonal neoplasm derived from nephrogenic
blastemal cells

Most <10 y.o,; rare in adults mutation of WT1 gene (chr 11) or CTNNB1 (gene encoding protooncogene beta catenin); WTX is inactivated in up to 30% of the Wilms tumor cases

Syndromes: 10% will show WAGR, Beckwith-Weidmann, Denys-Drash, Familial nephroblastoma,

hemihypertrophy

Histologically, most are triphasic (undifferentiated blastemal cells + epithelial + stromal)

Clinical features: abdominal mass, hematuria, fever, sometimes vomiting/anorexia

Tumors of the bladder: urothelial neoplasms, squamous cell carcinoma, glandular neoplasms, small cell
carcinoma
o Bladder urothelial carcinoma: 7th most common cancer worldwide, M>F risk factors: tobacco,
chemicals, phenacetin, other drugs, chronic infection

Papillary or invasive; divided to 1. Urothelial papilloma, 2. Non-invasive papillary urothelial

neoplasms of LMP, 3. Non-invasive papillary urothelial carcinoma LG (low grade), 4. Non-invasive
papillary urothelial carcinoma, HG

Symptoms of haematuria, frequency, urgency, incomplete voiding, dysuria/pain occur earlier

with papillary
RENAL WEEK 2: URINARY 2
Three layers of the glomerulus: inner fenestrated layer +GBM +foot process of podocytes/slit membrane
(with negative charge)
Immunological system & kidney: most common injury is antibody mediated antibody production directed
against antigen or cells
o Antigens directed to intrinsic kidney (autoimmune against GBM) or implanted (against antigen
deposited onto GBM)
Acute Renal Injury: affects single anatomic compartment (glomeruli, tubules or vasculature), loss specific
function one compartment
Chronic Renal Injury: ongoing injury that leads to failure of adaptive processes and involves multiple kidney
compartments, GFR 30-50% normal = progression renal failure inevitable
Hematuria (+/- proteinuria): Acute proliferative GN, RPGN, IgA nepthropathy/HSP, Alport/Thin membrane
Disease
Proteinuria (+/- nephrotic syndrome): Membranous glomerulopathy, minimal change, FSGFS,
membranoproliferative GN
In biopsy: proliferative patterns (too many cells) tend to be nephritic, nonproliferative (too much matrix)
tends to be nephrotic
Nephrotic Syndromes:
o Minimal change: when it occurs in adults, more associated with Hodgkins lymphoma and NSAID
usage

Pathogenesis overall: circulating cytokines, directed against glomerular epithelial cell adhesion
molecule
o Membranous glomerulopathy due to: malignancy (breast, lung GI, GU common), can also include
syphilis, DM, thyroiditis

30% rule: spontaneous remission, persistent proteinuria, progressive renal failure acute
complication= renal vein thrombosis
o Focal segmental: 50% primary progress to renal failure in 10 years, high recurrence rate in
transplants

Can be caused by previous healed glomerulonephritis

Nephritic Syndromes:
o APSGN: bacterial: Group A strep/staph/pneumococcus/typhoid; viruses: mumps/ECHO/coxsakie/EBV,
parasites: toxo/ malaria

Occurs 1-4 weeks post original infection; majority children recover in 6-8 weeks, adults only 60%
fully recover
o Membrano-proliferative GN: can be divided into

1. Chronic immune complex-mediated disease:idiopathic, autoimmune (SLE, RA, Sjogren),

infection, chronic liver disease

Idiopathic divided into MPGN 1, 2, 3 based on EM

o MPGN 1: IF - granular reactivity for C3/C1 & IgG in sub endothelial deposits in capillary
loops, EM mesangial cell interposition (between layer GBM extending into capillary
loops, sub endothelial deposits)
o MPGN 2: IF discontinuous linear reactivity for C3 in capillary loops and mesangial
rings, EM linear thick electron deposits in subendothelial location

2. Thrombotic microangiopathy (Chronic/healed) due to procoagulants, other factors

3. Deposition disease: Waldenstrom, paraprotein deposition

o RPGN: >50% loss in GFR within weeks; usually evidence of downstream tubular injury

Focal segmental necrotising lesions = baby crescents that havent grown up to be classified into
crescent

Classified on IF patterns:

Type 1 = antiglomerular BM disease +ve IF; only 20% will recover, anti-GBM levels =
severity
o IgG antibody against BM glycoprotein found in glomeruli and alveoli; so can be AntiGMB Ab GN or Goodpastures
o IF: strong linear GMB reactivity

Type 2 = immune complex mediated diseases (+ve IF)related to HSP/IgA nephropathy,

SLE, post infection

Type 3 = Pauci-immune disease (-ve IF) associated with small vessel vasculitis
(Wegners, Microscopic polyangitis, Churg Strauss (IF and EM NEGATIVE for deposits)
o Cyclophasphamide + corticosteroids = better
o IgA nephropathy = most common cause of renal insufficiency; SLE has to be excluded because
treatments are different

LM: variable, but usually dominated mesangial expansion (too much) with some increase in
cellularity

Low progression rate but because of prevalence, 10-20% of end stage renal disease (1/3 clinical
remission, 1/3 progressive decline over years)
Diabetic Kidney Disease: 30-40% will have severe or end stage renal insufficiency; microalbuminemia first
then proteinemia
RENAL WEEK 3:
URINARY 1: Max kidney M approx 170 grams, F 150 grams
Hypoplasia: kidneys dont develop into correct size; Ectopic kidneys kidneys develop extremely low in
location, causes urter kinks
Trisomny 18 = more common to have horseshoe kidney
Cystic dysplasia: abnormality in metanephric differentiation ureteropelvic obstruction, U/L urinary tract
anomalies, uni/bilateral
o ADPKD: can also have cysts in liver, spleen, pancreas and lungs
o ARPKD: has 4 categories perinatal, neonatal, infantile, juvenile (most common = perinatal,
neonatal); usually bilateral ; only collecting ducts have cysts
o Can have: liver cysts, portal fibrosis, proliferation of well-differentiation bile ductules, congenital
hepatic fibrosis
o Medullary cystic disease: medullary spong kidney; nephronothisis-medullary cystic disease complex

Medullary sponge kidney: adults, usually discovered incidentally complications include

calcification, hematuria, infection, urinary caliculi however, renal function usually normal and
pathogenesis unknown
o Nephronothisis-Medullary Cystic Disease Complex (HTIN) = progressive renal disoders, often
childhood in onset

Cysts in the medulla (CM junction); distal tubule with BM destruction tubular atrophy,
interstitial fibrosis leading to renal insufficiency = most common genetic cause of end stage
renal disease in children/young adults

4 variants:

1. Sporadic, non-familial (20%)

2. Familial juvenile nephronothisis (40-50%); AR

3. Renal-retinal dysplasia (15%); AR

4. Adult onset medullary cystic disease (15%); AD

Usually present with polyuria/polydipsia due to distal tubular pathologies may also have ocular
motor abnormalities, retinitis pigmentosa, liver fibrosis, cerebellar abnormalities

AR juvenile diseases = NPH1, NPH2, NPH3 affected; 2 genes MCKD1 and MCKD 2 are involved in
AD adult type
Acquired cystic renal disease: occurs after end stage renal disease after prolonged dialysis; lots of
cortical/medullary cysts about 0.5-2 cm in diameter

Most are asymptomatic but some cysts bleed which = hematuria (sudden severe pain); have high risk
of developing RCC
Renal Vascular Supply: end arteries; capillary beds of renal tubules derived from efferent arterioles of
glomeruli
o Renal medulla = most vulnerable to ischemia; low levels oxygen of blood in capillary loops = interfere
with medulla BS = medullary necrosis
Acute Renal Failure
o 1. Prerenal marked hypotention, shock; vascular problems such as atheroembolic disease & renal
vein thrombosis, infection
o 2. Renal - infection, usually sepsis/ toxins/ rhabdomyolysis/ haemolysis/ MM/ Acute GN
o 3. Postrenal medications interfering w/ normal bladder emptying, prostate conditions, kidney stones,
abdominal malignancy
Acute Tubular Necrosis 50% of ARF; either ischemic (PAN, malignant HTN, HUS, hypotention, shock) or
nephrogenic causes (drugs)
o Reversible changes: cellular swelling, loss of brush border/blebbing, loss of polarity, cellular
detachment
o Irreversible changes: necrosis, apoptosis

In toxic ATN, 95% recover when toxin is removed

Chronic Renal Failure: abnormally low GFR (high serum creatinine) leads to end stage kidney disease;
leading COD = CARDIAC
o Causes: Vascular (large vessel bilateral renal artery stenosis; small vessel ischemic nephropathy,
HUS, vasculitis), Glomerulus(primary IGA nephrompathy, FSGS; secondary DM nephrophaty, lupus
nephritis), Tubulointerstitial (PCKD, drug/toxin induced chronic tubulointerstitial nephritis,reflux),
Obstructive (stones, BPH)
o Usually no specific symptoms but: BP elevation = congestive cardiac failure; accumulation of urea =
azotemia/uremia = lethargy, pericarditis, encephalopathy
o Hyperkalemia, decreased EPO production, fluid overload, hyperphosphatemia and hypocalcaemia
(vitamin D3 deficiency)
o Tertiary hyperparathyroidism, metabolic acidosis (due to decreased HCO3- production = bone
health/breathing disruption), accelerated atherosclerosis
Urolithiasis: anywhere in UT, peak age 20-30 and males affected more commonly
o Most important pathogenic factor = increased urinary concentration supersaturation --<
precipitation; low urine volume can also cause this
o Calcium stones 5% have hypercalcemia and hypercalciuria (hyperparathryoidisim, diffuse bone
disease, sarcoidosis) ; 55% have hypercalciuria without hypercalcemia (absorptive hypercalciuria,
intrinsic impairement in renal reabsoprtion of calcium, renal hypercalciuria, idiopathic fasting
hypercalciuria with normal parathyroid function)
o 20% = associated with increasd uric secretion (calcium oxalate stones); associated with hyperoxaluria
in 5%
UQ LECTURES RENAL:
Week 1:
The Clinical Problem of Chronic Renal Failure
CRF is usually asymptomatic but measuring eGFR and protein can help detect it; protein: usually <150
mg/24 hours; transient increases with exercise/fever, orthostatic proteinuria when standing up
HT, DM, Smoking = modifiable risks for developing CKD; Presentation of CKD (generally asymptomatic,
nonspecific if any: malaise, fatigue, LOA, pruritis, dyspnea,restless legs)
o DM2 is causing rise in incidence of CKD; CKD is potent independent risk factor for CVS disease
o

Protein: usually <150 mg/24 hours; transient increases with exercise/fever, orthostatic proteinuria when
standing up
HT, DM, Smoking = modifiable risks for developing CKD; Presentation of CKD (generally asymptomatic,
nonspecific if any: malaise, fatigue, LOA, pruritis, dyspnea,restless legs)
Principles of Dialysis
-