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Changes in urine volume

Nephrotic syndrome
Etiology: Primary: Minimal change disease, membranous nephropathy, focal
segmental glomerulosclerosis
Secondary: Diabetic nephropathy, SLE, amyloidosis, infections (eg:
HBV, HCV, HIV), malignancy (lymphoma, leukemia)
Pathophysiology: Increase permeability of the filtration barrier, loss of negative
charge of the membrane
Symptoms: Hypoalbuminaemia, Proteinuria (>3.5g/day), Oedema,
Hyperlipidemia, Hypercoagulability, Immunosuppression

Nephritic syndrome
Etiology: Primary: Post streptococcal glomerulonephritis, IgA nephropathy,
Membranoproliferative glomerulonephritis, Rapidly progressive
Secondary: Goodpasture syndrome, SLE, Henoch-Schonlein purpura
Pathophysiology: Cellular proliferation in glomerulus (mesangial and
endothelial), presence of inflammatory cells (neutrophils, macrophages)
Symptoms: Hematuria, Proteinuria, Hypertension, Oliguria, Uremia

Management of glomerular disease

Investigation: Urine FEME- detect RBC, WBC, cast, bacteria
24 hour urine collection- determine total urine protein
Serology- determine underlying cause
Renal biopsy- determine pattern of glomerular damage

If secondary, treat underlying cause

If primary, use immunosuppressive therapy
ACEI for antiproteinuric effect (caution in renal impairment)

Case Scenario
Mrs BE , 35 years old , presents with fever ,
arthralgia and rash for 4 days.
She has been unwell for around 2 months. Her
problems began with symptoms of dyspepsia ,
which started after taking some ibuprofen for
her knee pain which she developed after a car
accident in year 2010.

Initially she had self-medicated with Gaviscon

and ranitidine (obtained from her local
pharmacy), but her indigestion became so
severe that around 1 month ago she attended
her GP.

She was prescribed omeprazole which relieved

her symptoms within a few days. About a week
later she noticed a faint red rash on her arms.
Since then, she has felt increasingly unwell with
daily fevers, arthralgia of the small joints of the
hand and intermittent loin pain.

There is no history of upper or lower respiratory

tract symptoms. Her only other regular
medication is the OCP, which she has been
taking for 7 years.
She has no past medical history or family
history of renal or autoimmune disease.
She does not smoke nor does she drink
alcohol. Works as an accountant.

Temperature : 37.4 degree Celsius
Blood pressure : 145 / 90 mm Hg
Erythematous , macular rash predominantly over the
dorsum of the forearms as well as the legs
Mild tenderness in both flanks
Examination is otherwise unremarkable

Full blood count Hb 12.1 g/dL WBC 11.1 10^9/L
(eosinophils 1.2, normal range : 0.040.44), Platelets
534 10^ 9 /L
Urine dipstick : Protein +++ , blood ++ , leucocytes +
ESR - 48 mm/h, CRP - 36 mg/L,
LFT -normal, Albumin 34 g/L

Acute Kidney Injury

- Previously known as Acute renal failure
- Abrupt and often but not necessarily
reversible loss of renal function, which
develops over hours to days and is
characterised by rise in serum creatinine and
urea often together with oliguria or anuria

3 Categories of Acute Kidney Injury

1. Pre-renal AKI
2. Renal AKI
3. Post-renal AKI

1. Pre-renal AKI
Any cause of hypoperfusion:
- hypoperfusion
- hypovolemia
- low oncotic pressure
- congestive heart failure
- constrictive pericarditis
- renal artery stenosis

Diagnostic Testing for Pre-renal AKI

1. BUN to creatinine ratio of >15:1 and often >20:
2. Urinary sodium is low (<20)
3. Fractional excretion of sodium <1 percent (a
low urine sodium)
4. Urine osmolality >500
5. Hyaline casts

2. Renal AKI
- Tubular injury: acute tubular necrosis, ATN
- Ischemia, contrast dye, myeloma, heme pigment
- Interstitium: acute interstitial nephritis, AIN
- Allergic and drug reactions
- Infections (HIV and toxoplasmosis)
- Glomerular: glomerulonephritis

Diagnostic Testing for Renal AKI

1. BUN to creatinine ratio closer to 10:1
2. Urinary sodium >40
3. Urine osmolality <350

3. Post-renal AKI (obstructive uropathy)

Any cause of obstruction:
- stone in the bladder or ureters
- strictures
- cancer of the bladder, prostate or cervix
- neurogenic bladder (atonic or noncontractile,
such as from multiple sclerosis or diabetes)

Diagnostic Testing for Post-renal AKI

1. Urinalysis: frequently normal
2. Elevated BUN-to-creatinine ratio of >15:1
3. Haematuria if stones, hemorrhage,
malignancy, or prostatic hypertrophy

Urine FEME
Blood BUN , creatinine , ABG , Calcium , phosphate
X-rays (KUB)
Ultrasound (KUB)
Intravenous urography
CT abdomen
Renal biopsy

Administer glucose and insulin to correct hyperkalaemia if
K+> 6.5 mmol/L
Consider administering sodium bicarbonate (100 mmol) to
correct acidosis if pH < 7.0 (> 100 nmol/L)
Discontinue potentially nephrotoxic drugs and reduce doses
of therapeutic drugs according to level of renal function
Match fluid intake to urine output plus an additional 500 mL
to cover insensible losses once patient is euvolaemic
Measure body weight on a regular basis as a guide to fluid

Non-renal causes of imbalanced serum urea

to creatinine ratio
Gastrointestinal bleeding
High protein diet (E.g TPN - Total parenteral
High muscle mass
Steroid use
State of metabolic distress (Sepsis)

Chronic Kidney Disease

Patients details






R/N no:

HTAN 5008

Chief Complaint
Bilateral leg swelling for 2 months

History of Presenting Illness

B/L leg swelling (2 months)

progressively worsen
no pain, erythema, weakness, numbness

B/L scrotal swelling (1 month)


no pain, changes in sensation

Exertional dyspnea (1 month)


duration: less than 5 minutes

relieved upon rest
no cough, URTI symptoms, chest pain, palpitation, sweating, headache, nausea

Increased urinary frequency (5 days)


reduced urine volume

no changes in color or characteristic

Reduced bowel movement (5 days)

No abdominal enlargement or pain, no UTI symptoms, no fever

Past Medical History


gouty arthritis (since 2007)

affects both big toes
aggravated by peanuts
medications: allopurinol, colchicine

2) h/o urolithiasis (2007)

3) renal failure (2007)
4) h/o haemodialysis (2007-2012)

Rt IJC for 8 weeks

Lt AV fistula 2007-2012

5) hypertension (since March 2015)


medication: amlodipine
noncompliant to medication and diet

Family History

mother had CKD

married, has 8 children
son (35 years old) has kidney disease

Social History

works as a rubber tapper

chronic smoker (40 pack years)
stopped 2 years ago

does not consume alcohol or take any drugs

water restriction 800cc/day

noncompliant to hypertensive diet

Physical Examination

alert, conscious, responsive

not in any pain or respiratory distress
I/V cannula attached on left hand

BP: 188/88mmHg
PR: 82 bpm, regular rhythm, strong volume
RR: 17 bpm
SpO2: 96%


no scars, visible pulsation

apex beat not deviated
S1 S2 heard
no additional heart sounds or
murmurs, no thrills, no heaves
trachea not deviated
symmetrical chest expansion
bibasal dullness on percussion
increased vocal resonance
vesicular breath sound
bibasal crepitation


no scars, visible pulsation or

abdomen distended, umbilicus
soft, non-tender
no hepatomegaly, no splenomegaly
negative fluid thrills and shifting


B/L pedal edema




92.6 fL


31.2 pg


4.3 x 10^9/L


132 x 10^9/L

Renal Profile:

139 mmol/L


5.5 mmol/L


19.8 mmol/L


662 mol/L


15.4 mmol/L


T. CaCO3 1.5g TDs

IV lasix 40mg OD
T. allopurinol 150mg OD
T. iberet folate 1/1 OD
T. amlodipine 10mg OD

Pathophysiology and progression of

Chronic Kidney Disease

Risk factor related to chronic kidney disease

Risk factor



Susceptibility factors

Increase susceptibility to kidney damage

Older age, family history of CKD, reduction in kidney

mass, low birthweight, US racial or ethnic minority status,
low income or education

Initiation factors

Directly initiate kidney damage

Diabetes, high blood pressure, autoimmune disease,

systemic infections, urinary tract infections, urinary
stones, lower urinary tract obstruction, drug toxicity

Progression factors

Cause worsening kidney damage or

faster decline in GFR

Higher level of proteinuria, higher blood pressure, poor

glycemic control in diabetes, smoking

End-stage factors

Increase morbidity and mortality in

kidney failure

Lower dialysis dose, temporary vascular access, anemia,

lower serum albumin level, late referral to nephrologists

Possible causes of glomerular scarring and proteinuria:

A rise in intraglomerular capillary pressure
Increase in glomerular permeability
Adaptive glomerular hypertrophy due to reduced
arteriolar and increased glomerular blood flow when
there is reduced nephron mass.
Glomerular hyperfiltration, in response to nephron
loss, was postulated as a common pathway for the
progression of CKD.

Angiotensin II modulates intraglomerular capillary pressure and GFR,

causing vasoconstriction of postglomerular arterioles, thereby increasing
the glomerular hydraulic pressure and filtration fraction.
Increased intraglomerular capillary pressure causes haemodynamic
injury to the capillary wall, resulting in glomerular sclerosis.
Angiotensin II also modulates cell growth by upregulating TGF-, a potent
fibrogenic cytokine, increasing collagen synthesis and causes epithelial cell
transdifferentiation to myofibroblast which contributes to matrix formation.
Proteinuria promotes secretion of pro-inflammatory mediators, which
promote interstitial inflammatory cell infiltrate and augment fibrosis and
progression of CKD.

Complications of ckd
1. Anaemia
-Erythropoietin deficiency
-Bone marrow toxins retained
-Bone marrow fibrosis 2o hyperparathyroidism
-Haematinic deficiency
-Increased RBC destruction during dialysis
-Abnormal RBC membranes
-Increased blood loss

2. Renal osteodystrophy
-Reduced excretion of phosphates
-Release of FGF 23 and other phosphaturic agents by osteoblast
-FGF 23 downregulates 1-alpha-hydroxylase and causes phosphaturia
-Decreased 1-alpha-hydroxylase reduces activation of vitamin D
-Reduced activation and hypocalcemia causes secretion of PTH
-Vitamin D required for calcium gut absorption
-PTH promotes bone resorption and increased proximal renal tubular
reabsorption of calcium
-Secondary hyperparathyroidism causes increased osteoclastic activity
and bone marrow fibrosis.

3. Pruritus
-due to retention of nitrogenous waste products
of protein catabolism

Systolic dysfunction due to :
-Myocardial fibrosis
-Abnormal myocyte function due to uraemia
-Calcium overload and hyperparathyroidism
-Carnitine and selenium deficiency
-Coronary artery calcification

Treatment of CKD
The medical care of patients with CKD should focus on the following:

Delaying or halting the progression of CKD

Diagnosing and treating the pathologic manifestations of CKD
Timely planning for long-term renal replacement therapy

Delaying or halting the progression of CKD

Treatment of the underlying conditions

Blood pressure control : ACE Inhibitors or Angiotensin Receptor Blockers
Management of protein : Vitamin D supplementation
Avoiding nephrotoxic drugs including intravenous (IV) radiocontrast media,
nonsteroidal anti-inflammatory agents (NSAIDs), and aminoglycosides

Treating the pathologic manifestations of


Anemia: erythropoietin treatment (Hb level to 10-12 g/dL)

Mineral and bone disorder: phosphate binders (eg, calcium acetate,
sevelamer carbonate, lanthanum carbonate)
Metabolic acidosis: Bicarbonate supplementation
Cardiovascular risk:
statin or statin plus ezetimibe (not for adults with dialysis-dependent CKD)
low-dose of aspirin
Oedema: high doses of loop diuretics(furesomide) with restriction of fluid
and sodium intake.
Restless legs: clonazepam or gabapentin

Renal replacement therapy

Peritoneal Dialysis
Renal Transplant


blood flows on one side of a semipermeable membrane while dialysis fluid

flows in the opposite direction on the other side.
Solute transfer occurs by diffusion.


fluid overload with oliguria

metabolic acidosis
uremic symptoms
GFR <15
acute poisoning

Patient's blood is passed through a set of tubing (a filtration circuit) via a
machine to a semipermeable membrane(the filter) where waste products and
water (collectively called ultrafiltrate) are removed by convection.

Peritoneal Dialysis
Sterile solution containing glucose (called dialysate) is run through a tube into
the peritoneal cavity, the abdominal cavity around the intestine, where the
peritoneal membrane acts as a partially permeable membrane.

Continuous ambulatory peritoneal dialysis ( CAPD)

Automated peritoneal dialysis

Continuous cyclic peritoneal dialysis (CCPD)
Intermittent peritoneal dialysis (IPD)
Night intermittent peritoneal dialysis (NIPD)
Tidal intermittent peritoneal dialysis (TIPD)

Renal Transplant
best long-term outcome for patients with end-stage renal disease.
Types of graft:

Cadaveric donor
Non-heart beating donor
Living related donor
Live unrelated donation

Immunosuppressants: cyclosporin, azathioprine, prednisolone , pre-op anti-interleukin 2 receptor

antibodies (basiliximab)
Contraindications: cancer, active infections, uncontrolled ischaemic heart disease, acquired
immunodeficiency disease with opportunistic infections, active viral hepatitis ,extensive peripheral
vascular disease, mental incapacity.

RRT Comparison


Peritoneal Dialysis


Frequent traveling to dialysis

Needs to be on anticoagulants
(risk of thrombosis)
AV fistula for vascular access may collapse/risk of infection
Dietary restrictions

Renal Transplant

More freedom, can be done at

Greater liberty from dietary
Easily tolerable by patients with
poor cardiac reserve
No vascular access
Conserves residual kidney

Restores kidney function

completely (for 10-15 years)

Risk of peritonitis
Needs to be disciplined and
knowledgeable in handling

Long waiting list

Extremely costly
Risk of organ rejection
Need to be on
Need to undergo second
transplant after transplanted
kidney fails

Urinary Tract Infections (UTI)

Urinary Tract Infections (UTI)

Most commonly : Escherichia coli species (80-90% of cases)
Other causes : Klebsiella, Enterococcus, Proteus mirabilis and Staphylococcus
Most of the causative organisms are naturally present in the GI tract, which acts
as a natural reservoir for potential UTIs
Major defense against UTI : complete emptying of the bladder during urination.
Other mechanisms : urine acidity, vesicoureteral valve, and various
immunologic and mucosal barriers.
Spread via:
95% Ascension
5% Haematogenous

Symptoms and signs of UTI

Frequency of micturition
Suprapubic pain & tenderness
Smelly urine
Loin pain & tenderness
Fever & systemic upset



chills, rigors, flank pain, colicky abdominal pain, nausea, vomiting

Investigations & Treatment

Urinalysis (clean-catch, midstream specimen)

Microscopic examination of urine : > 10 WBCs/L

Dipstick tests

Urine culture
Culture criteria for symptomatic patients : Uncomplicated cystitis in women: > 10 3 /mL
Complicated UTI: > 10 5 /mL
Antibiotics: Amoxicillin/trimethoprim/cephalosporin (if resistance, co-amoxiclav(Augmentin)/

Acute Kidney Injury VS

Chronic Kidney Disease

Acute Kidney Injury

Chronic Kidney Failure


Rapid progressive loss of renal


Gradual loss of renal function

Onset & Duration of symptoms*

Acute, Hours to Days

Gradual, >3 months


Oliguria, Edema (Fluid overload),

Arrhythmia ( K+) , metabolic
acidosis (Unable to form HCO3-).

Oliguria/Anuria + Renal
osteodystrophy*, Anemia*, Edema
(fluid overload), mild metabolic
acidosis, pruritus (cutaneous urea


Possible due to pathological cause

Normochromic, normocytic Present

of AKI e.g Haemorrhage

due to erythropoetin production




Serum Calcium & Phosphate


Increased phosphate, decreased

(Increased calcium in secondary


Enlarged kidneys

Shrunken Kidneys/ Normal (PKD)