• onset within minutes, lasts 30-60 min (may require repeat doses during treatment course of

hyperkalemia)

Acute Management nf Hyperkalemia

Curr Heart Failure Rep 2019;16:67-14

Rirpose: Outline and review ttecurrent evidence

behind the acute medical management ol

hyperkalemia, including the three principal

strategies o!stabilizing the myocardium,

intracellular shifting of serum K-. and enhancing

elimination via urinary or fecal excretion.

1. Stabilizing the Myocardium:The protective effects

of Ca tailson myocardial slabilization should

be seen within 5 min of administration.Doses can

be repeated in 5 min intervals if life-threatening

ECO changes persist. There are concerns regarding

calcium use in d goxin toxicity causing irreversible

non-contractile states. No lile-threotening

dysrhythmias occurred within1h ol calcium

administration.

2. Intracellular Shilling ol Potassium:Regular Insulin

hasshown effectivenessat decreasing serum K',

with IV insulin decreasing scrum Kby 0.8 mmolil

at1h. The main side effect of insulin-induced

hypoglycemia can be managed with IVdextrose.

Albuterol hasan onset within 1S-30 min ol

administration, causing maximal decreases

by 1mmotflat 1 h.There is little evidence to

suggest thatsodium bicarbonate has a role in the

management of hyperkalemia, except in the case

of concomitant metabolic acidosis.

3. Enhanced Excretion:Though limited evidence

for acute management,it is recommended to

administer loop diuretics and sodium polystyrene

sulfonate toelirainate K*.fcirebcs may precipitate

or worsen AVI in patientswith poor volume status,

while sodium polystyrene sulfonate should be used

with caution due tosevere 61sale effectssuch as

ulceration, bleeding,colonic ischemia/necrosis,

and intestinal perforation.

2.Shift K'

intoCells

• regular insulin (Insulin R) 10-20 units IV,with 50-100 mL D50W to prevent hypoglycemia

onset of action 15-30 min,lasts 4-6 h

monitor capillary blood glucose qlh because of risk of hypoglycemia

can repeat q4-6 h

caution giving D50VV before or without insulin if hyperkalemia is severe:hypertonic glucose

increases plasma osmolality, promoting extracellular water and Shift, and can cause a serious

arrhythmia

• p2-agonist (Ventolin*) in nebulized form (dose = 2 cc or 10 mg inhaled) or 0.5 mg IV

onset of action 30-90 min,stimulates Na * /K'

ATPase

• caution if patient has heart disease as may result in tachycardia

3. Enhance K< Removal from Body

• via urine (preferred approach)

• furosemide ( £40 mg IV ), may need IV NS to avoid hypovolemia

• fludrocortisone (synthetic mineralocorticoid) if suspecting aldosterone deficiency

• via (il (if renal function is severely impaired)

• cation exchangers: patiromer 8.4 g PO 01)(up to 25.2 g/d), zirconium cyclosilicate, or sodium

polystyrene sulfonate (Kayexalate*)

practically, patiromer and zirconium are not currently widely employed due to high cost

sodium polystyrene sulfonate (Kayexalate*) should be used with caution, as they may lead to

the development of colonic necrosis and intestinal perforation

osmotic laxatives e.g.lactulose can support G1 excretion of K +in the form of diarrhea

• dialysis (renal failure, life threatening hyperkalemia unresponsive to therapy)

Hyperphosphatemia

Definition

• serum phosphate >1.45 mmol/L

phosphate binds to serum calcium to create insoluble precipitates in soft tissues and blood vessels,

thereby resulting in hypocalcemia

hypocalcemia subsequently triggers the development ofsecondary hyperparathyroidism in

patients with advanced CKD on dialysis

Etiology

• typically results from decreased renal excretion of phosphate

Table 8. Etiology of Hyperphosphatemia

Increased Phosphate Load Reduced Renal Clearance Pseudohyperphosphatemia

61 intake (rectal enema. 61 bleeding)

IV phosphate load|K- Phos \ blood transfusion ) Hypoparathyroidism

Endogenous phosphate (tumour lysis

syndrome, ihabdomyolysis, hemolysis,lactic Tumour calcinosis (ability of kidney lo

and ketoacidosis)

AcuteXhionic renal failure Hyperglobulincmia

Hyperlipidemia

Acromegaly Hyperbilirubinemia

specifically deal phosphate is defective)

Clinical Features

• non-specific, include ectopic calcification in soft tissues and vessels, renal osteodystrophy

symptoms consistent with hypocalcemia

Treatment

• acute:IV saline, hemodialysis ifsymptomatic;

• chronic:low P04 3~diet, phosphate binders (e.g.CaCO.x,lanthanum carbonate,sevelamer with meals)

r

*

Symptoms i of Hypocalcemia

• Tetany

• Seizures

• Hypotension

• OT prolongation

• Papilledema

• Psychiatric manifestations

L J

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NPI6 Nephrology Toronto Notes 2023

Hypophosphatemia

Symptoms usually present when

phosphate <0.32 mmol/L (1.0 mg/dL)

Treat asymptomatic patients if

phosphate <0.32 mmol/L

Definition

• serum phosphate <0.80 mmol/L

Etiology

• acute hypophosphatemia often caused by intracellular shifts of phosphate superimposed on chronic

phosphate depletion

• chronic hypophosphatemia often caused by decreased renal phosphate reabsorption

• severe chronic hypophosphatemia often caused by chronic starvation or malabsorption (e.g. in

patients with alcoholism) or chronic use of phosphate binders(e.g. patients with CKD)

Severe bums can cause

hypophosphatemia due to POa5 losses

through the skin

Table 9. Etiology of Hypophosphatemia

Excessive Skeletal

Mineralization

Inadequate Intake Renal Losses Shift into Intracellular Fluid

Starvation

Malabsorption (diarrhea,

steatorrhea)

Antacid use

Alcoholism

Osteoblastic melastascs

Post paralhyroidcctomy (referred Respiratory alkalosis

to as'hungry bone syndrome'

) Starvation releeding (stimulated

by insulin)

Hyperparathyroidism

Diurclics

X-linkcd or autosomal dominant

Irypophosphalemic Rickets

Fanconi syndrome

Multiple myeloma

Early postrenal transplant

Recovery from metabolic acidosis

Clinical Features

• instability of cell membranesleading to hemolytic anemia or rhabdomyolysis

• MSK weakness, respiratory depression, low cardiac output/CHF from weakened cardiac muscles:

symptoms arise due to low ATP production

• neurological symptoms: irritability, encephalopathy,seizures, coma

• hematologic symptoms: hemolytic anemia, decreased release of oxygen from hemoglobin, impaired

leukocyte and platelet function (leading to worsening infections/defective clotting)

Treatment

• treat underlying cause

• initiate when serum [PO4

J-] <0.64 mmol/L. Use PO therapy if asymptomatic, orsymptomatic and

[PQi3-] >0.32 mmol/L. Use IV therapy if symptomatic and [PO43-] <0.32 mmol/L

• PO PO43-: 2-4 g/d divided B1D-Q1D (start at 1 g/d to minimize diarrhea), encourage PO43-rich

diet

IV PO4

3-: only forseverely symptomatic patients or inability to tolerate oral therapy

Hypermagnesemia

Definition

•serum magnesium >1.05 mmol/L

Etiology

•AKI/CKD

•Mg 3

'-containing antacids or enemas

•IV administration of large doses of MgSO 1 (e.g.see Obstetrics. Prccclampsla, OB26)

Clinical Features

•rarely symptomatic

•drowsiness, hyporeflexia,respiratory depression, heart block, cardiac arrest, hypotension

Treatment

•discontinue Mg:

'

-containing prod

•10% calcium gluconate 10-20 mL 1V (Mg 2

'

-antagonist) for acute reversal of magnesium toxicity

•hemodialysis if renal failure, consider peritoneal dialysis in setting of hemodynamic compromise

ucts

Hypomagnesemia

Ybu will be unable to correct

hypokalemia or hypocalcemia without

first supplementing magnesium If patient

is hypomagnesemic

Definition

• serum magnesium <0.70 mmol/L

n

Etiology LJ

61 losses

Starvation/malabsorption

Vomiling/dlarrhca

Alcoholism

Acule pancreatitis

Excess renal loss

2° hyperaldosler onism due to cirrhosis and CHF

Hyperglycemia

Hypokalemia

Hypercalcemia

Loop and thiazide-type diuretics

Nephrotoxic medications

Proton-pump inhibitors

Early postrenal transplant

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NP17 Nephrology Toronto Notes 2023

Clinical Features

• tremors, nausea and vomiting, lethargy/weakness,seizures, paresis,Chvostek and Trousseau signs,

ECG changes (widened QKS, prolonged PR, 1-wave abnormalities), and arrhythmiasincluding

Torsades de Pointes

Treatment

• treat underlying cause

• encourage increased dietary intake e.g.fruits

• oral Mg 2

'salts unless patient hasseizures or other severe symptoms

• Mg -+1M /1V; cellular uptake of Mg 2

'

isslow, therefore repletion requiressustained correction

• discontinue diuretics

» in patients requiring diuretics, use a K * -sparing diuretic to minimize magnesuria

Acid-Base Disorders

• acid-base homeostasis influences protein function and can critically affect tissue and organ function

with consequences to cardiovascular,respiratory,metabolic,renal,and CNS function

• normal concentration of [HC03 ~

]= 24 mEq/L (range:21-27 mEq/L for arterial blood gassample)

• normal pC02

= 40 mmHg (range:36-44 mmHg)

• each acid-base disorder has an associated compensation

inadequate compensation or overcompensation can indicate the presence of a second add-base

disorder (e.g.in metabolic acidosis, inadequate compensation meansthere is also respiratory

acidosis; overcompensation means there is also respiratory alkalosis)

• most commonly assessed using an arterial blood gassample

• see Respirologv, R6 for more information on respiratory acidosis/alkalosis

§ PH Causes of Increased Osmolar Gap

Methanol

Ethylene glycol

Ethanol

Polyethyleneglycol

Mannitol

Sorbitol

I T

( Low (pH <7.35) ] ( High (pH >7.45) Nonna I )

,

Acidemia ( No Disturbance ] Alkalemia

,

£ 1 Mixed Disturbance £ 1

Low High low

Useful Equations

AG -[Na*]-[CT]-[HCOsj(normal range

-W-MmEql)

HCO, uca HCOr pCO:

Metabolic acidosis

41 HCO:

= 41 pCO;

Respiratory acidosis

Acute: T 10 pCQ=11 HCO 3

Chronic:T 10 pCQ= T 3 HCO 3

Respiratory alkalosis

Acute: 4 10 pCO

- 42 HCO ,

Chronic: 4 10 pCOr.~ 4 5 HCO ,

Metabolic alkalosis

110 HCOb = T 5-7 pCO ,

Osmolar Gap ~ measured serum

osmolality - calculated osmolality

(normal <10 mEqt)

-

"

Two Salts and a Sticky BUN'

Figure 10.Approach to add-base disorders. Equalities represent the appropriate compensatory changesin

pCOz or HC03-in response to the primary disturbance

Calculated Osmolality - 2JNa*]+[Urea]+

[Glucose](+t2S[Ethanor)

Approach

1.Identify the Primary Disturbance

respiratory acidosis, metabolic acidosis,respiratory alkalosis, metabolic alkalosis

2.Evaluate Compensation.If compensation is not appropriate,second add-base disorder islikely

present

compensation occurs in the same direction asthe primary disturbance

3.Calculate Plasma AG

. AG = [Na *] -([HCOr] + [CT J )

baseline = 12, normal range 10-14 mEq/L

AG can be altered by plasma albumin level:for each 10 g/L fall in albumin,lower baseline AG by 3

mEq/L (e.g. if plasma [albumin]

= 20 g/L,expect AG = 6 mEq/L)

albumin is an unmeasured polyanion largely responsible for the normal anion gap

4.Calculate Osmolar Gap

osmolar gap = measured osmolality - calculated osmolality

calculated osmolality = (2 x [Na '

|) + [ureaj + [glucose|(all units are in mmol/L)

normal osmolar gap <10

If OG >10, consider methanol poisoning, ethylene glycol poisoning, or another cause of

acidosis plus ethanol ingestion +

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NP18 Nephrology Toronto Notes 2023

5.If AG elevated, compare increase in AG with decrease in HC03-

• if increase in AG < decrease in HC03 there is a coexisting non-AG metabolic acidosis

if increase in AG > decrease in HC03 there is a coexisting metabolic alkalosis

Metabolic Acidosis

•characterized by decreased blood pH (<7.35) and a decreased bicarbonate concentration

Clinical Features

•hyperventilation (Kussmaul Breathing)

•decreased cardiac output and tissue perfusion (reduced responsiveness to catecholamines)

Causes of Increased A6 Metabolic

Acidosis

MUDPILESCAT

Methanol

Uremia

Diabetic ketoacidosis

Paraldehyde

Isopropyl akohollron/lbuprofen/

Indomethacm

Lactic acidosis

Ethylene glycol

Salicylates

Cyanide and Carbon monoxide

Alcoholic ketoacidosis

Toluene

Etiology and Pathophysiology

1. increased AG metabolic acidosis (4 types)

lactic acidosis (2 types)

L-lacticacid

- type A:due to tissue hypoperfusion (any cause ofshock), ischemic bowel, profound

hypoxemia

- type B:non-hypoxic -multiple causes;the most common isfailure to metabolize

normally produced lactic acid in the liver due to severe liver disease;other causes

include:excessive alcohol intake,thiamine deficiency,metformin accumulation

(metformin interferes with electron transport chain), certain antiretrovirals,large

tumours,mitochondrial myopathies

D-lactic acid:rare syndrome characterized by episodes of encephalopathy and metabolic

acidosis

(§!

Causes of Non-AG Metabolic Addosis

HARDUP

Hyperalimentation

Acetazolamide

- occurs in the setting of carbohydrate malabsorption (e.g.short bowelsyndrome),

colonic bacteria metabolize carbohydrate load into D-lactic add, diminished colonic

motility, and impaired D-lactate metabolism RTA’

ketoaddosis Diarrhea’

Ureteroenteric fistula

Pancreaticoduodenal fistula

diabetic

starvation

alcoholic (decreased carbohydrate intake and vomiting)

toxins

methanol (toxic to brain and retina, can cause blindness and brain death):metabolized to

formic acid

ethylene glycol (toxic to brain and kidneys):metabolized to oxalic add (envelope shaped

crystalsin urine) and multiple other acids

salicylate (e.g. ASA) overdose: causes acidosis due to salicylic acid, and also accumulation of

lactic acid (salicylate at toxic levels impairs electron transport chain) and ketoacid (salicylate

activatesfat breakdown)

advanced renal failure

e.g.serum Cr increased at least 5x above baseline - a very low GBR causes retention of H+

and

decreased NHi

'

excretion;the retained acid is buffered by bicarbonate resulting in reduced

serum concentrations of bicarbonate

*

Most common

3Clinical Scenariosthat Produce a

Mixed Disorder with Near Normal pH

(e.g.increased AG metabolic acidosis +

respiratory alkalosis)

• Cirrhosis

- ASA overdose

• Sepsis

2. non-AG metabolic acidosis (hyperchloremic acidosis; involvesincreased bicarbonate excretion that is

replaced with Ch)

diarrhea (HCOs-lossfrom G1 tract)

RTA

type 1RTA (distal):inability to secrete Htin collecting duct,leading to impaired excretion of

ammonium into urine

type II RTA (proximal):impaired HC03- reabsorption

type 111 RTA:combination of Types 1 and 11 and is extremely rare

type IV RTA:defective ammoniagenesis characterized by hyperkalemia,due to decreased or

hyporesponsiveness to aldosterone

to help distinguish renal causesfrom non-renal causes, use Urine AG = (Na+ + K'

) -Clcalculation establishes the presence or absence of unmeasured positive ions (e.g.NH4

T

) in urine

if UAG <0,suggests adequate NHi 1

excretion in urine (likely nonrenal cause:diarrhea)

if UAG >0,suggests problem islack of NHr

'

in urine (likely renal cause:distal RTA)

Treatment of Metabolic Acidosis

1. treat underlying cause, e.g.:

• in DKA: fluid resuscitation, K'supplementation, and insulin

in Type A lactic acidosis: restore tissue perfusion

in methanol or ethylene glycol poisoning:ethanol/fomepizole ± dialysis

in ASA overdose:alkaline diuresis ± dialysis

2. correct coexisting disorders of K'

(see Hyperkalemia,NPI4 )

n

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NP19 Nephrology Toronto Notes 2023

3. consider treatment with exogenous alkali (e.g. NaH(X)J) if:

severe reduction in |HCl)3 ) e.g. <8 mmol/L, especially with very low pH (<7)

no metabolizable anion (e.g.salicylate, formate, oxalate, or sulphate); note that lactate and

ketoacid anions can be metabolized to HC03-

• note: risks ofsodium bicarbonate therapy

hypokalemia: causes K 'to shift into cells (correct K 'deficit first)

ECE volume overload: Na 1

load given with NaHCOs, can exacerbate pulmonary edema

overshoot alkalosis: abrupt, poorly tolerated transition from overly aggressive alkali loading,

partial conversion of accumulated organic anions to HC03-, and persisting hyperventilation

Metabolic Alkalosis

•characterized by increased blood pH (>7.45) and an increased bicarbonate concentration

Pathophysiology

•requires precipitating event and maintenance factors

•precipitating factors

G1 (vomiting, NG tube) or renal loss of H+

exogenous alkali (oral or parenteral administration), milk alkali syndrome (hypercalcemia)

loop/thiazide diuretics: increased distal H 'secretion and proximal HC()3 Teabsorption; ECI-

'

volume depletion also contributes to a contraction alkalosis

post-hypercapnia: renal compensation for respiratory acidosis is HCO3

"

retention, rapid

correction of respiratory disorder results in transient excess of HCO3-

•maintenance factors

• volume depletion: reduced G1

:

R, increased proximal reabsorption of Na 'and HC03-, and

increased aldosterone

hyperaldosteronism (1° or 2°): distal Na 'reabsorption in exchange for K 'and H'excretion leads

to metabolic alkalosis and hypokalemia

hypokalemia: transcellular K * /H'exchange, stimulus for ammoniagenesis and HCO3

-

generation

Evaluate Compensation (identify co-existing respiratory acid-base disorders)

•hypoventilation (an upper limit to compensation exists - breathing cannot be stopped)

Treatment

•correct underlying disease, replenish K 'and Mg -' deficits, and possibly K ’-sparing diuretic

•saline sensitive metabolic alkalosis (most common)

urine chloride <20 mEq/L, characterized by ECE contraction and hypokalemia

volume repletion ± carbonic anhydrase inhibitor (e.g. acetazolamide) to facilitate loss of HCO3

-

in

urine

•saline resistant metabolic alkalosis

urine chloride >20 mEq/L, characterized by ECi:

expansion and hypertension (increased

mineralocorticoids)

remove source of aldosterone or glucocorticoid ± spironolactone

[ Metabolic alkalosis (T pH, T HCO, ) )

£ 1

( Uc<20 mEq/L ) [ Up>20 mEq/L )

1 i

[ Saline responsive ] [Assess volume status )

r * T

Gl losses [Post-hypercapnia ] [ Volume depleted ] [ Normal ECF volume ]

•Vomiting

•NG tube

Prior diuretics

•Volume depleted I i

Diuretic use Saline resistant

I

[Check blood pressure)

£ 1

Hypertensive n

•1° hyperaldosteronism

•T hyperaldosteronism

•Cushing's syndrome

Normotensive

•Exogenous alkali

•Severe hypokalemia

•Banter'

s, Gitelman's

L J

Note:cannot use U«Jo assess volume status inpresence of olkalemia:

t HCftexcretion,drags Na -*

t No excretion

liraUrine chloride

Figure 11. Approach to metabolic alkalosis +

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NP20 Nephrology Toronto Notes 2023

Polyuria

Definition

• output >3 L/d. Distinguish from urinary frequency, where urination occurs multiple times per day but

the total volume over 24 h is <3 L

Etiology

• drugs (most commonly diuretics)

• excessive caffeine, alcohol intake

• increased water intake (psychogenic polydipsia,IV fluids)

• uncontrolled diabetes mellitus(osmotic diuresis)

• neurological:diabetes insipidus (central and peripheral), cerebral salt-wasting syndrome

• genitourinary: post-obstructive diuresis, cystitis/UTI

Clinical Features

• must distinguish between true polyuria and urinary'frequency

• look for sources of external fluid intake (IV fluids, tube feedings)

• assess for neurological changes (stroke, trauma, postoperative) (for central diabetes insipidus)

• assess for drugs that may cause nephrogenic diabetes insipidus(c.g. lithium)

• abrupt onset suggests central diabetes insipidus (deficient ADH)

Investigation Findings

• 24 h urine collection >3L

• laboratory findings that may point to specific etiologies:

hyperglycemia and/or glucosuria suggests osmotic diuresissecondary to uncontrolled diabetes

mellitus

hyponatremia may suggest free water intake secondary to polydipsia

hypernatremia may suggest free water loss secondary to diabetes insipidus

• check urine osmolality:

Uimn <100 mOsm/kg, consider causes of water diuresis(Dl, psychogenic polydipsia)

Uoim 100-300 mOsm/kg, consider causes of mixed polyuria (partial Dl,CKD)

Uosm >300 mOsm/kg, consider causes of osmotic diuresis(hyperglycemia, azotemia, excesssolute

intake)

• water deprivation test ifsuspected Dl,see Diabetes Insipidus,\, P12 for complete workup for diabetes

insipidus

Treatment

• specific to etiology

Acute Kidney Injury

Definition

• abrupt decline in renal function leading to increased nitrogenous waste products normally excreted

by the kidney

• formerly known as acute renal failure

The 2 most common causes of acute

kidney injury in hospitalized patients are

prercnal azotemia (decreased perfusion)

and ATN;remember that prerenal failure

can lead to ATN Clinical Features

• decreased G1

;

R

• weight gain and edema

• azotemia (increased BUN,Cr)

• abnormal urine volume:formally <0.5 ml/kg/h for >6 h but can manifest as anuria, oliguria, or

polyuria Differentiating Prerenal from ATN

Prerenal ATH Table 10. Classification of Acute Kidney Injury

Urine Normal RBC.

CRITERIA RIFLE AKIN KDIGO Microscopy pigmented

granular casts

> 40 m£g/l

<350 mOsmf

Serum Creatinine Increased 2-3 times baseline Increase of >26.4 pmol /L or

increase by >50% within 48 h

Increase of s26.4 pmol/l within 48

h or Increase by >50% within 7 d Unne|Na *| < 20

GfR Decreased >50%

<0.5 ml/kg/h for >12 h

N/A H /A Urine >500

Urine Output <0.5 ml/kg/h for >6 h «0.5 mL/kg/h for >6 h osmolality kgH20

FENa <1% >2%

Plasma|Ureaj/ >20 >1015 n

LJ

|C«I

lesponse Return to Persistent

of Cr to fluid baseline 1-3 d elevation

repletion

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NP21 Nephrology Toronto Notes 2023

r AKI )

Cluesto Prerenal Etiology

• Clinical; Decreased BP. increased HR.

and orthostatic HR and BP changes,

oliguria

• Increased[urea]»Increased [Cr]

• Urine[Ha *

]<10-20 mmoU

• Urine osmolality >500 mOsrriVg

• Fractional excretion of Na *<T%

Cluesto Renal Etiology

• Appropriate clinical context

• Urinalysis positive for casts;

• Pigmented granular - ATN

• WBC - AIN

. RBC -GN

• Systemic features,anemia,

thrombocytopenia.HTN. mildmoderate ECF volume overload

Duesto Postrenal Etiology

- Known solitary kidney

• Older man

• Recent retroperitoneal surgery

• Anuria

. Palpable bladder

• Ultrasound shows hydronephrosis

• Fractional excretion of Na *>2-3%

• Urine osmolality 250-300 mOsmVg

[ Renal ]

'

Postrenal ( Prerenal ) (especially if solitary kidney)

]

T T T T

[ Hypovolemia ] 1^

Neurogenic Disordered j

Autoregulation

•NSAIDs

•ACEI/ARBs

•Calcineurin inhibitors

(cyclosporine,tacrolimus)

•Hypercalcemia

Anatomic

•Ureter

•Bladder

•Urethra

T T

Effective

• Low cardiac

output

•Cirrhosis

• Sepsis

•3rd spacing

Absolute

•Hemorrhage

•Glloss

•Skin loss

•Renal loss

i T *

Glomerular

•GN

Vascular

•Vasculitis

•Malignant HTN

•Thrombotic microangiopathy

•Cholesterol emboli

•Large vessel disease

Interstitial

•AIN

Tubular

•ATN

Figure 12. Approach to AKI

Investigations

• blood work:CBC, electrolytes,Cr, urea (think prerenal if increase in urea is relatively greater than

increase in Cr), Ca 2+, PO-P

*

• urinalysis: albumin, hemoglobin, VVBCs, glucose, pH, urobilinogen,specific gravity

• urine volume,C&S, R&M:sediment, casts, crystals

• urinary indices:electrolytes, osmolality

• urine chemistry: urine Na +

and FENa

• Foley catheterization (rule out bladder outlet obstruction)

• fluid challenge (e.g.fluid bolus to rule out most prerenal causes)

• imaging: abdomen U/S (assess kidney size, hydronephrosis, postrenal obstruction)

• indicationsfor renal biopsy

• diagnosis is not certain

• prerenal azotemia or ATN is unlikely

• oliguria persists >2-4 d

RPGN,signs ofsignificant glomerular disease (proteinuria, RBC casts) despite normal kidney

size/echogenicity

Taiag of lihfetioi cf Ren=ltepfeccaeit Therapy

ii Acute Kidafj lajxry

EJM 2020353:240-51

Firpose Sscdati:

*

escstefetiefcn|far

citistica of rega.

'-repiaeierttierapy n petets

dt111 win are cCxa#y B.

Methods, 1bt-

=::-a tCTcrov -jtntica ,

patiati wti ill.Fcle-fswere raatalf assgoed a

receive cecreteratid reg rea of reKhe?2cesKa;

Serepy (n.tiead witoa 12:eftirigttij

aterz »ere

=et) orcsi=sd3rd stiitigjfn ltd

recakeaacerert tterajwes1searaged s

-

less

rlcafcns deve aced orill»22 k(.be prazrj

octimewas al-casse cortalty at901

Results: 2427 ofe» 3019 radonsed paterts

were related j

tiei»el.piectioo-a-tiHtasalysa.

Tte 90-day “ortzlty was433 cctbeacratratiil

grajp aod 43JL n aresteaded sratagy gi.p|I8

LOO:95«!033to 2.09.HI32L4.-sag SO-dey

sarrrors.coaraaed referee oa recekealeceareat

teray was10.4L r tie acceleread jar aod S OL

*

:tesaeadard yrmp (24 U-t 95L 012432-43'

).

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’

23.OL istieaccelerated

goto and163L w tiestandard g-rcp(M.001).

Conclusion Aaxn)crocaly natertswith

ac.te odrey iijiiy.ao ecceereted raial-repacereti

ssargy was not assocated wta lowerEortatty risk

ran standard staetegj atSOd.

Treatment

1. preliminary measures

• prerenal

correct prerenal factors:optimize volume status and cardiac performance using fluids that

will stay in the plasma subcompartment (NS, albumin, blood/plasma), hold ACEI/ARB

(gently rehydrate when needed, e.g.CHF),and NSAIDs

• renal

address reversible renal causes:discontinue nephrotoxic drugs, treat infection, and optimize

electrolytes

correct ECF volume,supportive care, consider corticosteroid or immunosuppressive therapy

postrenal

consider obstruction:structural (stones,strictures) vs.functional (neuropathy)

for obstruction to cause AKI, must have functionalsolitary kidney or obstruction affecting

both kidneys

treat with Foley catheter insertion, indwelling bladder catheter, nephrostomy,stenting

2. treat complications

• fluid overload

NaCl restriction

high dose loop diuretics

• electrolyte imbalances (hyperkalemia, hyperphosphatemia, hypocalcemia, hypo/

hypermagnesemia, hyperuricemia)

• acid-base disturbances

• adjust dosages of medications cleared by kidney (e.g. amiodarone,digoxin, cyclosporine,

tacrolimus,some antibiotics,and chemotherapeutic agents)

• dialysis

3. definitive therapy depends on etiology

Avoid NSAIDs in patients with diarrhea,

heartfailure, or renal failure

Renal transplant is not a therapy for AKI

LJ

Drugs Implicated in Prerenal Azotemia

• Diuretics

. NSAIDs

. ACEL ARBs +

Prognosis

• high morbidity and mortality in patients with sustained AKI and multi-organ failure

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NP22 Nephrology Toronto Notes 2023

Parenchymal Kidney Diseases

Glomerular Diseases

HISTOLOGICAL TERMS OF GLOMERULAR CHANGES

Extent of Changes

• histological terms describing the number of glomeruli affected in a given condition:

diffuse:majority of glomeruli abnormal

focal:some glomeruli abnormal

• histological terms describing the extent to which individual glomeruli are affected in a given

condition

global: entire glomerulus abnormal

• segmental: only part of the glomerulus abnormal

Types of Changes

• proliferation: hyperplasia of one of the glomerular cell types (mesangial, endothelial, parietal

epithelial), with or without inflammatory cell infiltration

• crescent formation: parietal epithelial cell proliferation and mononuclear cell infiltration form

crescent-shape in Bowman’sspace (hallmark of inflammatory glomerulonephritis)

• membranous changes: capillary wall thickening due to immune deposits or alterations in basement

membrane

CLINICAL FEATURES OF GLOMERULAR DISEASE

Important Points to Remember

• glomerular diseases have diverse clinical features including hematuria, proteinuria, HTN, edema, and

decreased GFR

• each glomerulopathy presents as one of four major glomerular syndromes(these are NOT

diagnoses)

1. asymptomatic urinary abnormalities

- proteinuria

- hematuria

2. nephritic syndrome

- acute GN

- rapidly progressive GN

3. nephrotic syndrome

4. ESRD

• glomerulopathies can be caused by a primary disease or can occursecondary to a systemic disease

• some glomerulopathies can present as more than one syndrome at different times

The Nephritic-Nephrotic Spectrum

• glomerular pathology can present with a clinical picture anywhere on a spectrum with pure nephritic

(inflammation of glomeruli) and pure nephrotic syndromes(abnormal glomerular permeability) at

the extremes

Nephrotic Intermediate Nephritic

Homaturia.iGFR Proteinuria

FSGS

Membranous glomerulopathy

Minimal change

Membranoproliterative GN

Focal proliferative GN

•IgA nephropathy

•Idiopathic membranoproliferative GN

•Hepatitis B,hepatitis C

•SLE

•Cryoglobulinemia

Diffuse proliferative GN

Crescentic GN

Figure 13.Spectrum of glomerular pathology

Proteinuria

•hallmark of nephrotic syndromes

•composition of normal urine protein: albumin, lower molecular proteins (such as immunoglobulin

light chain), or proteins secreted by the tubular epithelial cells (e.g. Tamm- Horsfall mucoprotein)

•24 h urine protein: gold standard to assess degree of proteinuria

• upper limit of normal daily excretion of total protein is 150 mg/d

• upper limit of normal daily excretion of albumin is 30 mg/d, albuminuria that persistsfor >3 mo

is considered CK1)

•spot/random urine ACR: used to screen for diabetic nephropathy and proteinuric renal disease

+

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NP23Nephrology Toronlo Notes 2023

• microalbuminuria:ACR >2.0 mg/mmol

• marker of vascular endothelial function

• an important prognostic marker for CKD (see Diabetes Insipidus, NPI2)

• microalbuminuria is the earliest sign of diabetic nephropathy

Pathologic Proteinuria

[ Protoinuria )

Tubulointerstitial

• Normally low molecular weight

proteins (<60 kOa) pass through

glomerular filtration barrier and are

reabsorbed inproximal tubule

• Proximal tubule dysfunction causes

impaired reabsorption and increased

excretion ol low molecular weight

proteins

• Albumin (>60 kDa) is not affected:

thus,edema is partly secondary to

salt and water retention

Glomerular

• Normally,the filtration barrier is

selectively permeable to size (<60

kDa) and charge (repels negative

particles):thus,albumin is filtered

to a very limited extent through a

normal glomerulus

• Damage to any component of

the glomerular filtration barrier

results in loss of albumin and other

high molecular weight proteins;

thus,edema is secondary to

hypoalbuminemia (low oncotic

pressure),but also due to enhanced

renal tubular reabsorption of filtered

sodium and water (possibly due

to filtered proteins stimulating the

action of cortical collecting duct

epithelial sodium channel)

Overflow

• Increased production of low

molecular weight proteins vrhich

exceeds the reabsorptive capacity of

the proximal tubule

• Plasma cell dyscrasias produce

light chainIg (multiple myeloma,

Waldenstrom's macroglobulinemia,

monoclonal gammopathy of

undetermined significance)

£

f Pathologic J

Physiologic

•Orthostatic

•Absence of proteinuria overnight

•Usually resolves spontaneously

•Transient (exercise, fever, CHF)

*

I I

Glomerular

(loss of large proteins (albumin])

Overflow

(overproduction of low molecular

weight proteins)

•e.g.multiple myeloma, amyloidosis,

Waldenstrom’s macroglobulinemia

Tubulointerstitial

(impaired resorption)

•<2 g/d

•e.g.Fanconi'

s syndrome

*

T

Secondary

•Systemic disease

•SLE.DM,vasculitis

•Infectious disease

•HIV.hepatitis B and C,bacterial endocarditis

•Hereditary/metabolic

•Alport's,Fabry's,sickle cell,PCKD

•Medications

•NSAIDs,gold,heavy metals

•Cancer

•Lymphoma, solid tumour

•Others

•Cryoglobulinemia, hypertensive nephrosclerosis

Primary

•Minimal change GN

•Membranous GN

•FSGS

•Membranoproliferative GN

•Post-streptococcal GN

•IgA nephropathy

Figure 14. Classification of proteinuria

Table 11. Daily Excretion of Protein

Daily Excretion Stage of Nephropathy ACR PCR

'

ISO rng total protein (and'

30

mg albumin)

30-300 mg albumin

>3500 mg total protein/1.73m2

body surface area

Variable amountof proteinuria

Normal <2.0mg/mmol <15 mg/mmol

Microalbuminuria

Nephrotic range proteinuria

>20 mg/mmol

»220 mg/mmol »300 mg/mmol

Can be seen withglomerular

disease

Possible tubular disease because

of failure to reabsoib filtered

proteins

Up to 2000 mg petd

Investigations

• urea,creatinine,ACR,PCR

• urine R&M, C&S, urine dipstick

• further workup (if degree ofproteinuria >0.5 g/d, casts,and/or hematuria)

• CBC,glucose,electrolytes, 24 h urine protein and albumin,and Cr

• urine and scrum Immunoelectrophoresis,abdominal/pelvic U/S

• serology:ANA,RF,p-ANCA (MPO), c-ANCA (PR3),C3,C4,HBV,HCV,HIV, ASOT

• consider urology consult and possible cystoscopy if not clearly a nephrologic source for hematuria or

if >50 yr of age

L J

+

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NP2INephrology Toronto Notes 2023

Glomerular Syndromes

1. ASYMPTOMATIC URINARY ABNORMALITIES

Clinical/Lab Features

• often have rapid decline in Gl-R, anemia, elevated inflammatory markers, ECF volume replete, or

mildly overloaded

• proteinuria (usually <2 g/d) and/or microscopic or macroscopic hematuria

isolated proteinuria

can be postural

occasionally can signal beginning of more serious GN (e.g. I-

'

SGS, IgA nephropathy, amyloid,

diabetic nephropathy)

hematuria with or without proteinuria

IgA nephropathy (Berger’s disease):most common type of primary glomerular disease

worldwide,frequently presents after viral upper respiratory tract infection (presents most

frequently with gross hematuria)

- more common in White and Asian papulations, and in the 2nd and 3rd decades of life

- may be associated with cirrhosis, HIV infection, celiac disease

- mesangial deposition of IgA (more dominant) and C3seen on immunofluorescence

microscopy

- potential treatment includes:RAAS blockers if proteinuria,steroids, and steroid sparing

agents (azathioprine, cyclophosphamide, mycophenolate mofetil, and biologiessuch as

rituximab)

hereditary nephritis (Alport Syndrome;Type IV collagen mutation): X-linked nephritis often

associated with sensorineural hearing loss; proteinuria <2 g/d

» thin basement membrane disease: usually autosomal dominant, without proteinuria; benign

benign recurrent hematuria: hematuria associated with febrile illness, exercise, or

immunization; a diagnosis of exclusion after other possibilities are ruled out

2. NEPHRITIC SYNDROME

[ Glomerulonephritis with Nephritic Features j

£ £ 1 1

Anti-GBM Mediated

(RPGN Type I) (15%)

Linear IF pattern due to IgG and C3

deposition along capillary loops

Immune Complex Mediated

(RPGN Type II)|24%)

Granular pattern due to subendothelial

or subepithelial deposits of IgG and C3

Non-lmmune Mediated

(RPGN Type III) 160%)

Pauci-immune: no immune staining

Double Antibody Positive Disease

(RPGN Type IV)

• Has features of TypeIand Type III

• Double antibody positive

*

j

[ anti-GBM ) c »ve ] [ ANCA tve J

C3 normal Decreased C3

T . i T I

With lung ( c-ANCA tve ] ( p-ANCAtve ]

hemorrhage

Without lung

hemorrhage

• IgA nephropathy

• Henoch-Schonlein

purpura

• Membranoproliferative

L- :.

• SLE 1

•Infective endocarditis

• Post-infectious GN

• Cryoglobulinemia

I V • Granulomatosis • Churg-Strauss

• Microscopic

polyangiitis

• Goodpasture's

disease

• Anti

-GBM

disease

with

polyangiitis

Figure15.Approach to nephritic syndrome

ACUTE NEPHRITIC SYNDROME

• a subset of nephritic syndrome in which the clinical course occurs over days

• etiology can he divided into low and normal complement levels

• frequently immune-mediated, with lg and G3 deposits found in GBM; but may be pauci-immune and

caused by an ANCA vasculitis

Clinical/Lab Features

« proteinuria (less than range for nephrotic syndrome, <3.5 g/1.73 m 2/d)

• hematuria (microscopic or macroscopic)

• azotemia (increased Cr and urea)

• RBC casts and/or dysmorphic RBCs in urine

• HTN (due to salt and water retention)

• peripheral edema/puffv eyes

ri

L J

Treatment

• depends on etiology

• pulse steroid therapy and other immunosuppression (steroid sparing agents such as azathioprine and

cyclophosphamide, mycophenolate mofetil, and biologiessuch as rituximab), BP control (with RAAS

agents), plasma exchange, monitoring for progression to ESRD

+

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NP25 Nephrology Toronto Notes 2023

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

• a subset of nephritic syndrome in which the clinical course occurs over weeks to months

• clinical diagnosis, not histopathological

• any type of GN can present as RPGN (except minimal change disease)

• additional etiologies seen only as RPGN: anti

-GBM disease and granulomatosis with polyangiitis

(previously called Wegener'

s granulomatosis)

• crescentic GN (identified by pathology) is frequently seen in RPGN resulting from proliferation of

parietal epithelial cells and is the most aggressive form of glomerular disease

Interventions(of Renal Vasculitis in Adults

Catiline D8Sfit it*

201S:CDD03232

ftrpote: toassess benefitsind harms of any

ett notation used 1«the letaimenl of renal vasculitis

n adults.

Methods Misin Cothunt Kidney and Transplant

Specralned Register investigating any intervention lot

the treatment of renal vascalitrsin adults.

Conclusions:Plasma tuhange was effective in

patients with severe AKIsecondary to vastulilis.

Pulse cyclophosphamide resulted in an increased risk

of relapse (compared to conbnuoos oral) but required

reduced dose.Ritunmib and mytophenollle moldJ

were comparable m efficacy to cyclophosphamide,

iiatbiooifflt. methotieule and leflunomide were

effective asmaintenance theiapy.

Clinical Features

• oliguria

• hypertension

• fatigue

• edema

Investigations

• fibrous crescents typically present on renal histopathology

• RBC casts and/or dysmorphic RBCs in urine

• classified by immunotluorescence staining

• Type I: anti-GBM mediated (15% of cases)

• Type II: immune complex mediated (24% of cases)

• Type III: Pauci-immune (ANCA associated vasculitis) (60% of cases)

• Type IV:double antibody positive (anti-GBM and ANCA) See landmaik Nephrology trialstable for more

information on SlISS-tN which details the efficacy

and safety of IV bdimmabas an add on therapy in

the management of lupus nephritis.

Treatment and Prognosis

• treatment: underlying cause if post-infectious;corticosteroids and cyclophosphamide or other

cytotoxic agent and plasmapheresis to manage cases such as anti-GBM antibody

• prognosis:50% recovery with early treatment, depends on underlying cause

3. NEPHROTIC SYNDROME

Definition

• distinct constellation of clinical and laboratory features of renal disease defined by the presence of

heavy proteinuria (protein excretion greater than 3.5 g/24 h),hypoalbuminemia (less than 3g/dL),

and peripheral edema

Clinical/Lab Features

• heavy proteinuria (>3.5g/1.73 m -/d)

• hypoalbuminemia

• edema

• hyperlipidemia (elevated LDL cholesterol due to increased liver albumin production), lipiduria (fatty

casts and oval fat bodies on microscopy)

• hypercoagulable state (due to antithrombin HI, Protein C, and Protein S urinary losses)

• patient may report frothy urine

• glomerular pathology on renal biopsy (nephrotic syndrome is always caused by glomerular pathology)

• minimal change disease (or minimal lesion disease or nil disease): e.g. glomeruli appear normal

on light microscopy

membranous glomerulopathy

• TSGS

• membranoproliferative GN

nodular glomerulosclerosis

• each can be idiopathic orsecondary to a systemic disease or drug (sirolimus can cause proteinuria

without obvious glomerular pathology;sirolimus rarely causes nephrotic syndrome)

Table 12. Nephrotic Syndrome

Minimal Change Membranous Focal Segmental Membranoproliferative Nodular

Glomerulopathy Glomerulosclerosis Glomerulonephritis Glomerulosclerosis

Hodgkin's

lymphoma

(primarily) and

Non-Hodgkin

lymphoma

NSAIOs

Steroids

HBV.SU,solid

tumours (lung,

breast.Gl)

Reflux nephropathy,

HIV, HBV, obesity,

sickle cell disease

HCV. nialaria. SU.

leukemia, lymphoma,shunt

nephritis

Secondary DM, amyloidosis

Causes

Drug Causes

Therapy

Gold, penicillamine Heroin

Reduce BP.ACEI.

steroids

rT

AspirinACEI.

dipyridamole (Persantine1

’)

- controversial

Steroids,

cytotoxic agents

(cyclophosphamide),

immunosuppressive

agents(calcineurin

inhibitors,

cyclosporine),

ACEIIARB for

proteinuria

Treatunderlying cause 1

_ J

+

Note:the most common secondary causesare diabetes mellitus and amyloidosis

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NP26 Nephrology Toronto Notes 2023

4. END STAGE RENAL DISEASE

• see But Stage Renal Disease, NP39

Investigations for Glomerular Disease

• blood work

• first presentation: electrolytes,Cr, urea, albumin,fasting lipids,ACR '

• determining etiology:CBC, ESR,serum immunoelectrophoresis (for amyloidosis or multiple i r- D-s 20CS;S71SV205

myeloma),C3,C4, ANA, p-ANCA, c-ANCA, cryoglobulins, HBV and HCY serology, ASOT, VDRL, U:.S »M~5SIKC- e-iate-s

MDir.««9 l«at >0X1.s e saderes:

aalps.proitCTni.jrj fitetioa sajtin

rdej«ditlsredttia abitjfor dselMttrre3

"arajjof fcpos septrCs bet stti& Of rteireSed

o Ctasgnu .->:qcal Ss3

(att-

*

OU.SfrraC3) tiif taae iSiitySofict

reswssa totratsart 3rdaajOe aadoofjas

Stooteifoal cforaatiw.

IirUunI lipatiMfaaiaantftrairre:33

teotntis.g.CKO'C:- Is cosO^

atwatt

“

asoswas-nagerts are eifecnaga«st

orogtsso:& erd-stega rere:disease.losgSraefScacjlasOeea 4ero-s‘

raS4 ooy for

cjdopiosjtaride-Sased reg-eis.«tkt are

associateda?cossderaMe adia-se effects,ia

HIV, anti-GBM antibodies

• urinalysis: RBCs, WBCs, casts, protein

• 24 h urine for protein and CrCl

• radiology

• CXR (infiltrates, CHI'

, pleural effusion)

• renal U/S

• renal biopsy (percutaneous or open) if heavy proteinuria or renal insufficiency and cause is not

obviously diabetic nephropathy

• urine immunoelectrophoresis

for Bence|

- ones protein if proteinuria present

• renal pathology (light microscopy, immunofluorescence, electron microscope)

• serum protein electrophoresis

start- a-d redara-terotrials,ojtsateoaiate

notes Las derodstateda:leas:sisSareScacj

CK:oaredtnis pulse cyclegtsgtaarfeaal‘as a

nore teraraSle toucijproile.If fafaato respond

4y 6EO cossderiHesf)lag“erapjLFlares

foUonsgreassert are sot t-co~o- a-dreg;re

d gertteico-do.

End-Stage leaal Disease:>ajvsand

trass?la-tatocaSl£ taia teeg-tera xtrert a:d

graft-sama -ares corpara:le mtiaose odseried

-:o:-d aietc roa-SlE patrerts.T-arsoartet o-s

SeDeSodofcSoice.

SECONDARY CAUSES OF GLOMERULAR DISEASE

Amyloidosis

• nodular deposits of amyloid in mesangium, usually related to amyloid light chain (AL)

• presents as nephrotic range proteinuria with progressive renal insufficiency

• can be primary orsecondary to multiple myeloma, TB,rheumatoid arthritis,or malignancy

Systemic Lupus Erythematosus

• see Rheumatology.RH11

• lupus nephritis can present as any of the glomerular syndromes

• nephrotic syndrome with an active sediment is most common presentation

• GN caused by immune complex deposition in capillary loops and mesangium with resulting renal

injury

• serum complement, ANA, anti-DNA levels are usually low during periods of active renal disease

• children and males with SLE are more likely to develop nephritis

SLE Classification

1

Class I Class II Lie :I

, I Class IV Dm : ns vi

i i i i i

Minimal M

mesangial pre

lupus nephritis lupus nephritis

gial Focal

lupus nephritis

Diffuse

lupus nephritis

Membranous

lupus nephritis

Advanced sclerotic

ive lupus nephritis

. .

L

:

Treatment Treatment Treatment Treatment Treatment

I I i 1 i

Class I and II do not Steroids

need treatment directed

at renal lesions

Steroids

(controversial)

ESRD

planning

Lowest possible

e of steroids

and observation

dos +

cytotoxic drugs

(consider dialysis or renal

transplant with severe disease)

Prognosis

Renal survival 85% at 10 years with early initiation of therapy

Dialysis often ameliorates other symptoms of SLE

Figure 16. International Society of Nephrology/Renal Pathology Society classification of lupus nephritis 2003

IgA Vasculitis (Henoch-Schonlein Purpura)

• Systemic IgA vasculitis, tissue deposition of IgAl-dominant immune complexes affecting mostly

small vessels

• seen more commonly in children

• purpura on buttocks and legs, abdominal pain, arthralgia, and fever

• IgA and G3 staining of mesangium

• usually benign,self-limiting course, 10% progress to CKD

ANCA-Associated Vasculitis +

• c-ANCA most commonly associated with the clinical picture of granulomatosis with polvangiitis

• p-ANGA most commonly associated with the clinical picture of microscopic polvangiitis

• focal segmental necrotizing RPGN with no immune staining

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XP27 Nephrology Toronto Notes 2023

• may be indolent or fulminant in progression

• vasculitis and granulomas rarely seen on renal biopsy

• treatment typically involves cyclophosphamide and prednisone

Cryoglobulinemic Vasculitis

• cryoglobulins:monoclonal IgM and polyclonal lgG which precipitate at reduced temperatures, deposit

in walls ofsmall vessels

• presents as purpura, fever,Raynaud’

s phenomenon, and arthralgias

• at least 50% of patients have HCV

• renal disease seen in 40% of patients (isolated proteinuria/hematuria progressing to nephritic

syndrome)

• most patients have decreased serum complement (C4 initially)

• treat HVC, plasmapheresis

• overall prognosis: 75% renal recovery

Shunt Nephritis

• immune-complex mediated nephritis associated with chronically infected ventriculoatrial shunts

inserted for treatment of hydrocephalus

• commonly caused by .S'

, cpidermidis

• presents as acute nephritic syndrome with decreased serum complement

• nephrotic range proteinuria in 25% of patients

• treat by removing shunt and administering appropriate antibiotics;can consider a

ventriculoperitoneal shunt

HIV-Associated Renal Disease

1.direct nephrotoxic effect of HIV infection, anti-retroviral drugs (e.g. tenofovir,indinavir),and other

drugs used to treat HIV-associated infections

2.HIV-associated nephropathy

histology:focal and segmental glomerular collapse with mesangial sclerosis; “collapsing FSGS”

tubular cystic dilation and tubulo-reticular inclusions

• clinical features: predominant in African American men, heavy proteinuria, progressive renal

insufficiency (Apo-L-1 risk genotypes)

• prognosis: kidney failure within 1 yr without treatment

• therapy:short

-term, high dose steroids, ACEI, H A ART

Infective Endocarditis

• manifests as mild form of acute nephritic syndrome with decreased serum complement

• S.aureus is most common infecting agent

• treatment with appropriate antibiotics usually resolves GN

Hepatitis B

• can result in membranous nephropathy, membranoproliferative GN, and polyarteritis nodosa

Hepatitis C

• can result in membranous nephropathy, membranoproliferative GN, and cryoglobulinemia

Syphilis

• can result in membranous GN

Tubulointerstitial Disease IgA nephropathy is the most common

type of primary glomerular disease

worldwide

TUBULOINTERSTITIAL NEPHRITIS

Definition

• cellular infiltrates affecting primarily the renal interstitium and tubular cells

• functional tubule defects are disproportionately greater than the decrease in GFR

• classified as acute or chronic

Features of Nephritic Syndrome

PHAROH

Proteinuria

Hematuria

Azotemia

RBC casts

Oliguria

HTN

Signs and Symptoms