Spectrum of renal diseases

Question 1

What are the clinical manifestations of nephropathies?

Answer 1

Failure to thrive
abdominal mass
hematuria
asymptomatic proteinuria
hypertension
anemia
polyuria
oligoanura
polydipsia
oedema
acidosis
respiratory distress
enuresis
uti (CAKUT is a risk factor for UTI)
renal osteodystrophy
renal failure
electrolyte abnormalities
Vomiting, Diarrhea

Question 2

Causes of Glomerulonephritis

Answer 2

Causes of idiopathic nephrotic syndrome (MCD, MPGN, MGN, FSGS) and secondary nephrotic syndrome (Hep B, HIV, Hep C, Syphilis, Heavy metals - Gold, Mercury, Obesity)
Congenital (within 3months of life) and Infantile (3m to 1 year) Nephrotic syndrome
Causes of Nephritic syndrome - PIGN, igA nephropathy
Systemic vasculitides with secondary renal involvement - SLE, Henoch Schonlein purpura vasculitis, Anti-neutrophilic cytoplasmic autoantibody vasculitis
Congenital glomerulonephritis - Alport’s

Question 3

Causes of Cakut

Answer 3

Agenesis - Dysplasia - Hypoplasia
Cystic Kidney disease
Obstructive Uropathies - PUJ (commonest), VUJ, PUV
Other causes of non-obstructive urinary tract dilatation - Prune Belly
Reflux nephropathies - VUR, UTI’s
Neurogenic bladder

Question 4

Where are the kidneys located

Answer 4

They are retroperitoneal, between the costovertebral angle.

Question 5

Describe the functional structure of the kidney

Answer 5

Tubules in Interstitium
Glomerulus - Filtration of fluids, solutes and waste

Interstitial cells are mesangial cells - Tissue macrophages in Kidney.

There’s deposit of complement and immunoglobulin in interstitium - stain under immunoflourescence.

Efferent arteriole is narrower than afferent.

Question 6

Anatomy of the Nephron - Tubules and blood supply

Answer 6

Tubules are more susceptible to ischemia and hypoxia, so ATN more common than Cortical necrosis.

Tubules can regenerate.

Peritubular capillaries aid tubules to transform substances and secrete some.

Question 7

What are the functions of the kidney?

Answer 7

*Homepstasis
Water and electrolyte balance
Nitrogenous waste disposal (urea, cr, Uric acid)
Acid base balance

*Hormogenesis
Erythropoietin from the interstitium
Ca2+ & PO42- metabolism via Vit D3 activation (1 hydroxylation - in 1,25 hydroxycholeciferol) - Renal Rickets

Question 8

What are the consequences of a failed Kidney?

Answer 8

Failed homeostatic function
*Accumulation of metabolic waste - raised BUN, SCr: Uraemia (feeling unwell &lack of energy)

• Failed excretion of daily H+ load - acidosis
• K+ build up - HyperK+
• Retention of PO42- & Mg2+ and reciprocal fall of Ca2+ (solubility product - PO4 2.2+ Ca =5)
• Poor urine output - Fluid retention - Oedema
• Abnormal urine chemistry (protein and blood) and sediments (sloughed tubular epithelium, RBC cast)

Question 9

Consequences of a chronically injured Kidney (>3months)

Answer 9

Fibrosis - then loss of critical nephron mass - glomerulus and tubules is shed (broad waxy casts - nephron).

Small shrunken kidney.
Impaired synthetic function- decreased erythropoietin production (normochromic anemia)
Decreased production of 1a hydroxyl add - 1,25 vit D3 deficiency - renal osteodystrophy

Question 10

What are the traditional marker for Kidney Injury

Answer 10

Serum Creatinine - endogenous, metabolic product of the muscles, excreted by the Kidney.

Urine output determination
Urine dipstick for proteinuria and blood

Question 11

What is the issue with SCr as a marker of Kidney injury

Answer 11

Creatinine levels rise after ~50% of renal function is lost (time lag before it rises
Levels depends on muscle bulk

Question 12

What are the newer bio markers for Kidney injury? (Early rise)

Answer 12

Neutrophil Gelatinase Associated Lipocalin [Blood and Urine]
AKIM -1 (urine)
Cystatin C (blood)
IL-18

Question 13

Who is at risk of acute Kidney Injury?

Answer 13

Critically ill patient requiring ICU care
Hypovolemic patient - Diarrhoea and Vomiting +/- dehydration, Shock, Burns, Septicemia, Nephrotic Syndrome.
Glomerulonephritis
Severe sepsis/Severe malaria
Receiving nephrotoxics including radiographic contrast
Hypoxia - Asphyxia, Pneumonia, Cyanosed, Severe asthma, Status epilepticus/prolonged convulsion

Hemoglobinuria/Myoglobinuria (crushed injury)
Abnormal urinalysis - proteinuria/hematuria, WBC’s/nitrite

Question 14

Other causes of Kidney injury in Children

Answer 14

Chronic malformation of the kidney structure/adjoining urinary tract - CAKUT

Question 15

Spectrum of Kidney Diseases (1)

Answer 15

Inflammatory conditions of the Kidney (Nephritis)

Glomerulo-Nephritis- Nephrotic or nephrotic
Tubulointerstitial Nephritis including pyelonephritis
CAKUT including cystic kidney diseases
Other hereditary nephropathies - cong nephrotic, cong nephritis (Alport), cong TIN (nephronophthisis)

Question 16

Spectrum of Kidney Diseases - may lead to failure

Answer 16

Tubulopathies (eg. cystinosis- Fanconi syndrome, Barters
Metabolic (eg. oxalosis)
Ischemic or toxic injury
Malignancies ( Wilma tumor, leukemia, leukemia

Question 17

Causes of TIN

Answer 17

Drug-induced - antibiotics, analgesics, anti-oxide drugs
Hereditary TIN - nephronophthisis

Diagnosis is made when eosinophils infiltrating the kidney, peripheral eosinophilia(red staining white cells) on biopsy.

Eosinophils in urine.

Question 18

The three classical features of Prune Belly Syndrome

Answer 18

Wrinkled abdomen (absent abdominal wall)
Cryptorchidism
Hydroureters (with or without Hydronephrosis)

Question 19

What are the Pre-renal causes of AKI

Answer 19

Volume loss - Real (loss through vomiting, diarrhea, hemorrhage )or apparent ( septicemia - blood vessels dilate)

Question 20

What are the intrinsic and post renal causes of AKI?

Answer 20

Unresolved pre-renal ARF - uncorrected diarrhea, shock (acute tubular necrosis)
Hypoxia conditions 
Toxins and poisons
Drugs
Glomerulonephritis
Tubulointerstitial nephritis

Post-renal events - any cause of obstructive uropathy

Question 21

What are the causes of Chronic Kidney Disease / End Stage Renal Failure?

Answer 21

Unresolved AKI (For 3 months - RF to ESRF)
CAKUT
Progressive renal insult from persistent proteinuria (induced fibrosis in Kidney), nephrotoxic drug use (NSAIDs) infections (HIV), tubular disorders etc.

Question 22

What are the three systems for classifying AKI?

Answer 22

RIFLE, AKIN, KDIGO
All are based on changes in SCr from baseline (as proxy for GFR) or urine output

Rationale: To allow for standardized definition and comparison of results.

Also identify the patient who is at risk of kidney injury to allow for more stringent monitoring.

Question 23

What are the general differences between the three classification systems?

Answer 23

RIFLE classifies AKI into 5 stages
AKIN and KDIGO classify AKI into 3 stages.
Additional 2 for RIFLE are just outcome measures.

Third criteria for KDIGO combines both RIFLE and AKIN

Question 24

What does RIFLE define AKI (stage 1- Risk of Kidney dysfunction)as?

Answer 24

Increase in SCr of 1.5x (not 2)baseline (150% rise) or GFR decreases by 25% within 7 days
Or
Decrease in urine output of <0.5ml/kg/hr over >6 hrs (8hrs for children) -

Measure ace at least 2 times.

Question 25

How many stages does RIFLE classify AKI into?

Answer 25

``` R- Risk of Kidney dysfunction I- injury to the Kidney F- Failure of Kidney function L- Loss of kidney function E- End stage renal failure (5 stages) ```

Question 26

Stage 2 RIFLE classification for AKI (Kidney Injury)

Answer 26

SCr has risen by 2%, but not up to 3% (200% rise) or GFR decreases by 50% Or Urine Output <0.5ml/kg/hr over >12 hrs

Question 27

Stage F, L, ERIFLE definition of AKI

Answer 27

Scr has risen >/= 3x baseline (300% rise) OR GFR decreases by 75% OR Scr level > 350úmol/l or acute rise >44úmol/l Or Urine output of <0.3ml/kg/hr for 24 hours OR anuria for 12 hours If it persists for 1 month, you’ve lost function (L) - need for RRT If it persists for 3 months, you’ve gotten to ESRF (E) - need for RRT

Question 28

How does AKIN define AKI?

Answer 28

An abrupt (within 48hours) absolute increase in Scr of >/= 26.4ûmol/l (0.3mg/dL) OR %age increase in Scr of >/= 50% (I.e. baseline x1.5) OR Oliguria of <0.5ml/kg/hr for >6hrs AKI should only be diagnosed after achieving adequate hydration and after excluding any urinary tract obstruction.

Question 29

Staging of AKI by AKIN Criteria

Answer 29

Stage 1 1.5 - 2 fold rise in Scr from baseline (150-200% increase) OR Any absolute rise of >/= 26.4 ümol/l in 48 hours Stage 2 >2-3 fold increase in SCr from baseline (200-300% increase) Stage 3 >3 fold increase in SCr from baseline (>300% rise) OR Any SCr >/= 354ümol/l with acute rise of at lease 44ümol/l (Urine output criteria same as RIFLE)

Question 30

How does the KDIGO criteria define AKI?

Answer 30

* Absolute rise in SCr of >/= 26.4 ûmol/l (0.3mg/dL) within 48 hours OR * Increase in SCr of 1.5x baseline (%age rise in SCr of >/= 50%) within 7 days OR * Oliguria of <0.5ml/kg/hr for > 24hours

Question 31

KDIGO staging of AKI

Answer 31

Stage I: 1.5 to <2 fold increase in SCr from baseline Stage II: >/=2 to <3 fold increase in SCr from baseline Stage III: >/= 3 fold increase in SCr from baseline

Question 32

Complications of AKI in Failure (RIFLE-F, AKIN III, KDIGO III)

Answer 32

``` Pulmonary edema (water imbalance) CCF Hypertension Hyperkalemia Acidosis Hyper PO42- & hypoCa2+ - convulsion Uraemia if azotemia is severe or prolonged Can lead to death ```

Question 33

Treatment of AKI

Answer 33

Consider if the injury is pre-renal, intrinsic or post-renal Pre-renal - There’s hypovolemia *Fluid resuscitation (20ml/kg of NS). Repeat hourly if necessary for 1-2 doses ``` Intrinsic AKI (from tubular necrosis) Fluid restriction (if Oliguria). Insensible loss [400ml/m2/day] + previous day’s output. If markedly hypervolemjc and anuric, total fluid restriction + diuretic challenge. ``` ``` Urethral catheterization (low obstruction at urethra)/other urinary diversion procedures for post-renal AKI. For high obstruction- nephrostomy for massive hydronephrosis Lower obstruction (PUV) - Vesicostomy ``` (Also direct treatment at primary cause)

Question 34

How is Hyperkalemia from AKI treated?

Answer 34

*Myocardial stabilization (prevent cardiac arrest) Ca gluconate 10% (0.5ml/kg IV over 5- 10 min). Protects heart from effect of K *Intracellular K shift B2 agonist e.g. Salbutamol (nebulize), epinephrine NaHCO3 Insulin with Dextrose *K elimination from the body Kayaxelate (sodium polystyrene - switches Sodium for K) Dialysis ``` *Supporting measures Avoid K-rich diet (banana, coconut, tomato) Avoid drugs (amoxiclav, AceI) that cause hyperK ```

Question 35

Indication for Dialysis in AKI in Failure -1

Answer 35

*Failure of conservative mgt Pulmonary edema unresponsive to diuretics Hyperkalemia not controlled by conservative treatment Severe metabolic acidosis (can cause heart to stop beating) * Increase of >20% of initial body weight * Prolonged Oliguria-Anuria (2-3days) * Uraemic pericarditis

Question 36

Indications for Dialysis - AKI in Failure 2

Answer 36

* Multisystem failure (liver, brain, kidney, septicemia) * Uraemic encephalopathy * Severe hyponatremia (<110mmol/l) or hypernatremia (>140mmol/l) * Severe uraemia >30mmol/l of blood urea * To make room for volume therapy (eg. Transfusion, TPN) in the oligo-anuric patient