anna, and Dr. Alireza Zahirieh,staff editors

Acronyms

Basic Anatomy Review.

Embryology of theKidney

Renal Structure and Function

Renal Hemodynamics

Assessment of RenalFunction

Measurement of Renal Function

Urinalysis

Urine Microscopy

Urine Biochemistry

Electrolyte Disorders

Sodium Homeostasis

Hyponatremia

Hypernatremia

Diabetes Insipidus

Potassium Homeostasis

Hypokalemia

Hyperkalemia

Hyperphosphatemia

Hypophosphatemia

Hypermagnesemia

Hypomagnesemia

Acid-Base Disorders..

Metabolic Acidosis

Metabolic Alkalosis

Polyuria

Acute KidneyInjury.

Parenchymal Kidney Diseases

Glomerular Diseases

Glomerular Syndromes

Tubulointerstitial Disease

Vascular Diseases of the Kidney

Analgesic Nephropathies

Systemic Disease with Renal Manifestation.

Diabetes

Scleroderma

Multiple Myeloma

Malignancy

Chronic Kidney Disease:

Management of Complications of CKD

Hypertension

Hypertensive Nephrosclerosis

Renovascular Hypertension

Renal Parenchymal Hypertension

Cystic Diseases of theKidney

Adult Polycystic Kidney Disease

Autosomal Recessive Polycystic Kidney Disease

Medullary Sponge Kidney

EndStage Renal Disease.

Presentation of End StageRenal Disease

Renal Replacement Therapy

Dialysis

Renal Transplantation

Common Medications

Landmark Nephrology Trials

References

NP2

....NP2

NP5

NP8

NP17

NP20

NP22

NP33

NP36

NP37

NP38

NP39

NP41

.NP42

n . NP43 L J

.... NP44

NP48

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XP1 Nephrology Toronto Notes 2023

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NP2 Nephrology Toronto Notes 2023

Acronyms Pronephros

.§

ACEI angiotensin converting enzyme DIC

inhibitor

ACR albumin to creatinine ratio

ADH antidiuretic hormone

AC anion gap

AIN acute interstitial nephritis

AKI acute kidney injury

ANA antinuclear antibody

ARB angiotensin receptor blocker

ASA acetylsalicylic acid

ASOT anti-streptolysin-0titer

ATN acute tubular necrosis

AV atrioventricular

AVM arteriovenous malformation

c-ANCA cytoplasmic antineutrophil

cytoplasmic antibody

C4S culture and sensitivity

CHF congestive heart failure

CKD chronic kidney disease

creatinine

CrCI creatinine clearance

CV cardiovascular

CVVHD continuous veno- venous

hemodialysis

OSW 5% dextrose in water

OCT distal convoluted tubule

DDAVP 1-desamino-8-d-arginine

vasopressin

Dl diabetes insipidus

disseminated intravascular

coagulation

diabetic ketoacidosis

diabetes mellitus

extracellular fluid

estimated glomerular filtration

e> NS normalsaline a

p- ANCA perinuclear anti-neutrophil

cytoplasmic antibody

PCT proximal convoluted tubule

PJP Pneumocystis jiroveci

pneumonia

PKO polycystic kidney disease

parathyroid hormone

R&M routine and microscopy

RAAS renin-angiotensin-aldosterone

system

RBF renal blood flow

RCC renal cell carcinoma

renal plasma flow

RPGN rapidly progressive

glomerulonephritis

RRT renal replacement therapy

RTA renal tubular acidosis

SIADH syndrome of inappropriate

antidiuretic hormone

SLE systemic lupus erythematosus

SLED sustained low efficiency dialysis

TBW total body water

tubulointerstitial nephritis

TIP thrombotic thrombocytopenic

purpura

UAG urine anion gap

urinary tract infection

-

=

DKA

DM ©

ECF

eGFR

rate

ESR erythrocyte sedimentation rate PTH

ESRD end-stage renal disease

FENa fractional excretion of sodium

filtration fraction

FSGS focalsegmental

glomerulosclerosis

GBM glomerular basement

membrane

GFR glomerular filtration rate

glomerulonephritis

KAART highly active antiretroviral

therapy

HBV hepatitis B virus

HCTZ hydrochlorothiazide

HCV hepatitis C virus

HPF high power field

HSP Henoch-Schonlein purpura

HTN hypertension

HUS hemolytic uremic syndrome

IVP intravenous pyelogram

IOC level of consciousness

MDRD modification of diet in renal

disease

FF

RPF

GN

U

Cr Mesonephros

Degenerating

pronephros

TIN

UTI

Basic Anatomy Review

Embryology of the Kidney

• originatesfrom urogenital ridge of the intermediate mesoderm

• pronephros develops at the end of tvk 3, then degenerates along with adjacent pronephric duct,

disappearing completely by end of wk 4

• mesonephros develops caudal to the pronephros in wk 4,degenerates, and the remnants form the

mesonephric (Wolffian) duct of the male reproductive system

• metanephros develops caudal to the mesonephros in wk 5 from the metanephric blastema and the

ureteric bud of the mesonephric duct,forming the definitive kidney

excretory system:metanephric blastema -» nephrons (Le.glomeruli, Bowmans capsule, PCT, loop

of Henle,OCT)

collecting system:ureteric bud > collecting ducts, calyces, renal pelvis, ureters

• kidneys ascend from the pelvis into the retroperitoneum,gaining a blood supply from the

abdominal aorta to form the renal arteries

=CF

V

Metanephros

Degenerating Renal Structure and Function mesonephros

The Nephron

• basic structural and functional unit of the kidney, approximately 1 million per kidney

• 2 main components:glomerulus and attached renal tubule

• direction of blood flow:afferent arteriole -» glomerular capillaries -> efferent arteriole -> vasa recta (the

capillaries surrounding the tubules) -> renal venules

Metanephric

^

, {Ureteric bud

\j\ephric duct

r n

L

Figure 1. Kidney embryology

The pronephros and mesonephros

develop then degenerate in

succession.Ultimately,the

definitive kidney develops from the

metanephric blastema and ureteric

bud of the mesonephric duct

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NP3 Nephrology Toronto Notes 2023

Table 1. Major Kidney Functions

Function Mechanism Affected Elements

1.Waste Excretion Glomerular filtration Excretion of nitrogenous products of protein

metabolism (urea.Cr)

Excretion of organic acids( urate) and organic

bases(Cr)

Breakdown and excretion ol drugs (antibiotics,

diuretics) and peptide hormones (most

pituitary hormones, insulin, glucagon )

Controls volume status and osmolar balance

Controls potassium concentration

Acid-base balance

Acid -base balance

Alters Ca 1

\Mg!

\ POrHomeostasis

Increase osmolality ol medullary cytoplasm to

match medullary concentration gradient

Red blood cell production

Calcium homeostasis

lubular secretion

Tubular catabolism

2.Electrolyte Balance and Osmoregulation lubular NaCI and water reabsorplion

Tubular K’secretion

Tubular H Secretion

HCOrsynthesis and reabsorplion

TubularCaT*

. Mij'

, POP transport

Osmolytc synthesis

3. HormonalSynthesis Erythropoietin production (cortex)

Vitamin 0 activation: 25|OH|Vitamin 0

converted to1.2S(0H):Vitamin D (proximal

tubule)

Renin production ( juxtaglomerular apparatus) Alters vascular resistance and aldosterone

secretion

Alters ECF volume

Alters vascular resistance

4. Blood Pressure Regulation Na* excretion

Renin production

Gluconeogenesis (Irom lactate, pyruvate, and Glucose supply maintained in prolonged

amino acids) starvation

Clearance and degradation ol circulating Maintains glucose homeostasis

insulin

5. Glucose Homeostasis

The Glomerulus

• site where blood constituents are filtered through to the kidney tubules for excretion or reabsorption

• filtration occurs across the glomerular filtration barrier (endothelium, GBM, podoevtes) into

Bowman’sspace

• there is a filtration barrier to albumin due to its size and negative charge, which is repelled by the

negatively-charged GBM

• consists of following cell types:

I . mesangial cells

structural function:support glomerular capillaries; can alter GI R through contractile

activity

• secretory function: matrix components, pro- and anti-inflammatory cytokines, and

chemokines

secretions are responsible for minimizing the accumulation of macromolecules in the

mesangial space and GBM

2. capillary endothelial cells

part of the glomerular filtration barrier; help form the plasma filtration apparatus due to their

fenestrated nature and glycocalyx; contribute to the production of the GBM

interface with blood - target for antibodies and contact site for neutrophils and lymphocytes

3. visceral cells (podocytes)

part of the glomerular filtration barrier; helps form the plasma filtration apparatus due to

their interdigitated foot process forming slit diaphragms; contribute to the production of

extracellular matrix proteins (collagen and laminin) making up the GBM

4. parietal cells

lines the interior of Bowmans capsule and contains a podocyte progenitor population

5. juxtaglomerular cells

smooth muscle cells in lining of afferent arteriole; produce,store, and secrete renin

r T

i j

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NPl Nephrology Toronto Notes 2023

Afferent arteriole

Renal Hemodynamic Parameters

RBF - 20% olCO,

-U/mln

RPF - RBF'II-Hct)

GFR --120 tnL/min in healtliy adult

199% ol this volume is reabsorbed)

FF - GFR/RPF (normally 20%)

Prostaglandins -dilation NSAIOs - constriction

Efferent arteriole

ACEI- dilation AngiotensinII- constriction

Afferent arteriole

M

Bowman's space

.

1

'

J 1

Proximal

t. tubule

Juxtaglomerular^- »

cells A •1».

-

,

j

Efferent arteriole

Endothelium -

Mesangial cell 2

8

%

Podocyte

(visceral epithelium) Bowman's capsule S

(parietal epithelium)

Figure 2. The glomerulus

The Renal Tubules

• reabsorption and secretion occur between the renal tubules and vasa recta forming urine for excretion

• each segment of the tubule selectively transports varioussolutes and water and is targeted by specific

diuretics

rg ACTIVE

|requ

*

es ATRI

(B) PARACEILUIAR

QL REGULATED,hormone

^^

(e.g. angiotensin II,aid.ANF)

C) H?0 PERMEABLE segment

^

HjO IMPERMEABLE segment

0 «

^

ang.II

NaVH'

exchange

Na /PO.* co-transport

(PTH a vitamin Dl NaCI S%

Na’

/K- i.r

- n -

-

r

INa* 80%)

K' Na'

i HiO

£

A

Glucose 90V:

Ammo acids 90%

HCO, 90%

— HCOi K'

2 H’ Na' Ca'

- HWU t

O

£ H.O 80%

o

rv ^

aldosterone 2

L

I

PROXIMAL Na*

TUBULE

Osmotic diuretics

DISTAL TUBULE

O Thetide diuretics K- \

ENaC channels <

No' 10% K- - 2CI

(ADH) co-transport

THICK ASCINOINC UMS

(loop olHeal#}

Loop diuretics

e

3 u

^

AOPIbyADH

ADH receptor

'

ADH

=: s &

( Ca1,

- MQ1

,

® \/

a I

$ COLLECTING DUCT %tpifHigdniitbci a.

§

AQP chnnnol i

I

H,0

2 A 2J :* •

DESCENDING THIN LIMB

(loop ol Nonlo)

ASCENDING THIN LIMB

(loop ol Honlol

Loop d/wetict,

syntonises osmolytes.

impermeable to Hi 0

§

6

3

£ B

L.

Figure 3. Tubular segments of the nephron

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XP5 Nephrology Toronto Notes 2023

Renal Hemodynamics

• GIR

GFR is the rate of fluid transfer between glomerular capillaries and Bowman'

s space, expressed as

9

the sum of the filtration across all nephrons

average GFR of 180 L/d or 125 mL/min/1.73 m of which 99% of the filtrate is reabsorbed

normal urine output is 0.5-2.0 mL/kg/h in adults

• Cil'

R is highest in early adulthood, and decreases thereafter starting around age 40

• renal autoregulation maintains constant Cil'

R over mean arterial pressures of 70- 180 mrnHg

• 2 mechanisms of autoregulation to maintain Cil'

R homeostasis:

myogenic mechanism: release of vasoactive factors in response to changes in perfusion pressure

(e.g. low Cil'

R > decreased perfusion pressure > release of prostaglandin > afferent arteriolar

dilation > increased Gl-

'

R)

tubuloglomerular feedback: changes in Na ' delivery to macula densa lead to changes in afferent

arteriolar tone (e.g. high Cil'

R > increased Na 'delivery > afferent constriction > decreased GFR )

• filtration fraction

• percentage of RPF filtered across the glomeruli

expressed as a ratio: IT'

= GFR/RPF; normal = 0.2 or 20%

• angiotensin If constricts renal efferent arterioles which increases IT, thereby maintaining Cil'

R

• renin is released from juxtaglomerular apparatus in response to low Na 'delivery to the macula densa,

which is an indicator of decreased RPF

renin is an important enzyme in the RAAS pathway, that converts angiotensinogen to

angiotensin 1

Glometular Filtration Rate

GFR Kf|iP- 6(1)

ultrafillration coefficient

hydrostatic pressure difference

between glomerular capillaries

andBowman'sspacc

60 osmotic pressure difference

between glomerular caplllatlcs

and Bowman'

sspace

6P - 411 net outward pressure

XI

6P

Considerable variation in GFR is

observed based on age. biological sex,

ethnicity and BMI

Stimuli for Renin Release

from Kidney:

1.Renal artery

hypotension:1in stretch

of afferent arteriole

2.Sympathetic activation

(via juxtaglomerular cell

Adrenergic receptors)

3. INa delivery to macula

densa in OCT

Angiotensin II Effects:

1.Vasoconstriction

2. T vascular smooth

muscle growth

3.t Na * reabsorption

4. T aldosterone

5. T bicarbonate products

Angiotensinogen

Renin

Angiotensin Angiotensin II I

Adrenal cortex

Stimulation of Na -

retention in the

kidney

Aldosterone Clincically relevant

outcomes:

1. Net T total body water,

sodium

2. t vascular tone

Vasoconstriction

Via angiotensin II receptors 0-»o

1

Thirst

'

t systemic blood Hypothalamus

volume and pressure

t Fluid intake

Postorior pituitary g

—————————I

'Aloxondro Ho 2022 aftor Francos Young 2005. Nicola Clough 2014

ADH release

Figure 4. Renin-angiotensin-aldosterone system

Assessment of Renal Function

Measurement of Renal Function

• most renal functions decline in parallel with a decrease in GFR

• inulin clearance and iothalamate radiotracer are the gold standard for measuring GFR, but very rarely

used clinically

• clinically, GFR is estimated using serum creatinine concentration, [Cr], known as eGFR

Cr filtered = Cr excreted (atsteady state)

Cr reasonably estimates GFR asit isfreely filtered at the glomerulus with little tubular

reabsorption

Crfiltered -Crexcreted

[Cr]plasma x GFR -[Cr]urine x urine flow

rate (mL/min)

GFR ~

Cr'

urme x urine flow rate

[Cr]plasma

r i

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XP6 Nephrology Toronto Notes 2023

however,Cr is a metabolite of creatine phosphate, and therefore increased muscle mass increases

Cr production. Ihus,one needs to consider body mass, ethnicity, age, and biological sex when

determining eGT'

R

there is also 10% to >50% tubular secretion of Cr, depending on renal function

• newly discovered biomarkers such as Cystatin C, which are not affected by muscle mass, may provide

more accurate eGFR values

At steady state[Cr]serum a1/CrCI

Ways to Estimate GFR Using Serum Creatinine Concentration

1.estimate GFR using CKD-EP1 equation

• the best current and most accurate equation

calculated using serum Cr, age, biological sex, and race

overestimates Gl-R, resulting in lower prevalence of CKD diagnoses when used instead of MDRD

formula or Cockcroft-Gault equation

2. measure CrCl- 24 h urine collection

calculation provides reasonable estimate of GFR

Gl-R/d = (urine|Cr] x 24 h urine volume)/(plasma (Cr])

must use same unitsfor urine [Cr] and plasma [Cr]

3.estimate GFR with new Cr and cystatin C-based equations

serum Cr and cystatin C values used with age and sex to estimate GFR (excludes the race variable)

• more accurate than CKD-EPI with race omitted

CKD-EPI Equation

eGFR (ml/min/1.73 m*) -141*minfSCr/n.

1)a x max(SCr/K.1)

“

<» x 0.993age

x (1.018 if female) x (1.159 for Black

individuals)

(SCr] measured in mg/dl;1mg/dL (Cr]-

88.4 pmol/L

K *0.7 tor females and 0.9 for males

a - 0.329 for females and -0.411 for

males

mln/max indicates the minimum/

maximum of SCr/x or 1

Cystatin C

Cystatin C is a renal biomarker shown

to be potentially superior to scrum Cr

In determining eGFR and delecting

impaired filtration rate . However, its

clinical use remains limited pending

Increased adoption and testing

availability

Limitations of Using Serum Cr Measurements

1. must be in steady state

constant GFR and rate of production of Cr from muscles

sudden injury (e.g. AKI) may reduce GFR substantially, however,serum Cr will not immediately

reflect sudden reduction in Gl'

R until new Cr steady state is reached

2.GFR must fall substantially before plasma [Cr] rises above normal laboratory range

with progressive renal failure, remaining nephrons compensate with hyperfiltration

• GFR is relatively preserved despite significant structural damage

3. plasma [Cr] is influenced by the rate of Cr production

• lower production with smaller muscle mass (e.g. female, elderly, low weight)

• e.g. consider plasma|Cr] of 100 pmol/L in both of these patients

- 20 yr lean man who weighs 100 kg, GFR = 144 mL/rnin

- 80 yr woman who weighs 50 kg, GFR = 30.6 mL/min

clinical correlation:GFR decreases with age but would not be reflected as a rise in serum Cr due to

the age-associated decline in muscle mass

4.tubular secretion of Cr increases as GFR decreases

• serum Cr and CrCl overestimate low GFR

• certain drugs (cimetidine,trimethoprim) interfere with Cr secretion

5.errorsin Cr measurement

• very high bilirubin level causes [Cr] to be falsely low

• acetoacetate (a ketone body) and certain drugs(cefoxitin) create falsely high [Cr]

Clinical Settings in which Urea Level

is Affected Independent of Renal

Function

Disproportionately High Urea

. Volume depletion (prerenal azotemia)

• Gl hemorrhage

• High protein diet

• Sepsis

• Catabolic state with tissue

breakdown

• Corticosteroid or cytotoxic agents

Disproportionately Low Urea

• Low protein diet

Measurement of Urea Concentration • Liver disease

• urea isthe major end-product of protein metabolism

• plasma urea concentration reflects renal function but should not be used alone as it is modified by a

variety of other factors

• urea production reflects dietary intake of protein and catabolic rate;increased protein intake or

catabolism (sepsis, trauma, Gl bleed) causes increase in urea level

• ECF volume depletion causes a rise in urea independent of GFR or plasma [Cr]

• in addition to filtration, a significant amount of urea is reabsorbed along the tubule

• reabsorption isincreased in hypernatremic states

• typical ratio of urea to [Cr] in serum is 1:12 in SI units(using mmol/L for urea and pmol/L for Cr)

Estimating Urine Osmolality

Last 2digits of the specific gravity x 30 -

urine osmolality appro ximately

(e.g.specific gravity of 1.020=600

mOsm)

Urinalysis

•use dipstick in freshly voided urine specimen to assess the following:

1. Specific Gravity

•ratio of the mass of equal volumes of urine/H20

•range is 1.001-1.030

•values <1.010 reflect dilute urine, values >1.020 reflect concentrated urine

•value usually 1.010 (isosthenuria:same specific gravity as plasma) in ESRD

n

u

2. pH

•urine pH is normally between 4.5-7.0; if persistently alkaline, consider

• RTA (types 1-1V)

UT1with urease-producing bacteria (e.g. Proteus)

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NP7 Nephrology Toronto Notes 2023

3.Glucose

• freely filtered at glomerulus and reabsorbed in proximal tubule

• causes of glycosuria include:

1.hyperglycemia >9-11.1 mmol/L leadsto filtration that exceeds tubular resorption capacity

2.increased GT'

R (e.g. pregnancy: the proximal convoluted tubule is unable to reabsorb the glucose

and amino acids)

3.proximal tubule dysfunction (e.g. laneoni

’ssyndrome)

4.sodium-glucose cotransporter 2 (SGLT2) inhibitors (i.e.-flozin drugs) which are prescribed for

DM2;lower the threshold for glucosuria by preventing glucose reabsorption from the filtrate

4. Protein

• dipstick only detects albumin; other proteins (e.g. Bence-|ones, Ig,Tamm-Horsfall) maybe missed

• microalbuminuria (morning ACR of 2.0 - 20 mg/mmol) is not detected by standard dipstick; greater

than these ranges would be macroalbuminuria

• gold standard: 24 h timed urine collection for total protein

24 h Urine Collection

• Discard first morning specimen

• Collect allsu bsequent urine for the

next 24 h

• Refrigerate between voids

• Collect second morning specimen

5. Leukocyte Esterase

• enzyme found in VVBC and detected by dipstick

• presence of W BGs indicates infection (e.g. U IT) or inflammation along the urinary tract including

prostate, bladder, ureter, pelvis, and interstitium (e.g. AIN)

Positive dipstick for leukocyte esterase

and nitritesis highly specific for

diagnosing a UTI

6. Nitrites

• endogenous nitrates in urine are converted to nitrites by some bacteria (most commonly £. coli)

• high specificity but low sensitivity for UTI

7. Ketones

• positive in alcoholic/diabetic ketoacidosis, prolonged starvation, fasting

8. Hemoglobin

• positive in hemoglobinuria (hemolysis), myoglobinuria (rhabdomyolysis), and true hematuria ( KBCs

seen on microscopy)

Nitrite Negative Bacteria

Enterococci

Staphylococci

Nitrite Positive Bacteria

Enterobacterioceoe (e.g.f. coli)

Urine Microscopy

Table 2. Comparison of Urinary Sediment Findings

Active Sediment - Suggestive of

Parenchymal Kidney Disease

Bland Sediment * Less Likely

Parenchymal Kidney Disease

Any one or more of the

following seenon microscopy

Red cell casts

White cell casts

Only hyaline casts

Small quantities ol crystals

Muddy-brown granular or epithelial ceil casts Small amount olbacteria

<2 red cells per HPF

<4 white cells per HPF

>2red cells per HPF

»4 while cells per HPF

1. CELLS

Erythrocytes

. hematuria >2 RBCs per HPT

• dysmorphic RBCs and/or RBC castssuggest glomerular bleeding (e.g. proliferative GN)

• isomorphic RBCs or no castssuggest extraglomerular bleeding (e.g. bladder cancer)

Leukocytes

• pyuria = greater than upper limit of normal:>4 WBCs per HPT

• indicatesinflammation or infection

• if persistentsterile pyuria present (i.e.negative culture), consider: chronic urethritis, prostatitis,

interstitial nephritis, calculi, allergic cystitis,interstitial cystitis, papillary necrosis, renal

tuberculosis, viral infections, N. gonorrhoeae,C. trachomatis infection

Eosinophils

• detected using Wright’s or Hansel’s stain (not affected by urine pH)

• consider AIN, atheroembolic disease

n

L J

Oval Fat Bodies

• renal tubular cells filled with lipid droplets

• seen in heavy proteinuria (e.g. nephrotic syndrome)

2. CASTS +

• cylindrical structuresformed by intratubular precipitation of Tamm-Horsfall mucoprotein; cells may

be trapped within the matrix of protein

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NP8 Nephrology Toronto Notes 2023

Table 3. Interpretation of Casts

Casts Interpretation

Hyaline Costs

RBC Costs

WBC Casts

Physiologic (concontialotl urine,lever,exercise)

Glomerular bleeding (prolilerative GH,vasculitis)

Inlection (pyelonephritis)

Inflammation (interstitial nephritis)

Pigmented GranularCasts (heme granular casts,muddy brown) AIN

Acute proliferative GN

Fatty Casts Nephrotic syndrome (proteinuria >3.5 g/d)

3. CRYSTALS

• uric acid:consider acidic urine, hyperuricosuria,tumour lysissyndrome

• calcium phosphate:alkaline urine

• calcium oxalate:consider hyperoxaluria,ethylene glycol poisoning, nephrolithiasis

• sulfur:sulfa-containing antibiotics

Urine Biochemistry

• commonly measure: Na 1 , K\C1-, osmolality, and pH

• spot urine more useful to assess renal physiology, 24 h urine collection more reflective of mineral

balance

• no “normal ” values; electrolyte excretion depends on intake and current physiological state

• results must he interpreted in the context of a patient'

s current state, for example:

1.ECF volume depletion: expect low urine ( Na* ) (kidneys should be retaining Na *)

urine [Na 1

) >20 mmol/L suggests a renal problem or the action of a diuretic

urine [ Na 1 j <20 mmol/L suggests a prerenal problem

2.daily urinary potassium excretion rate should be decreased (<20 mmol/d) in hypokalemia

if higher than 20 mmol/d,suggests renal contribution to hypokalemia

• osmolality is useful to estimate the kidney’

s concentrating ability

• FENa refers to the fractional excretion of Na+ (Na excreted in urine/Na filtered through kidney)

l-

'

ENa <1% suggests the pathology is prerenal

• urine pH is useful to grossly assess renal acidification

low pH (<5.5) in the presence of low serum pH is an appropriate renal response

• a high pH in thissetting might indicate a renal acidification defect (e.g. RTA Type I)

Fractional Excretion of Sodium

FENa *

[Na

*

] urine X [Ct]plasmn

[Na plasma X [Cr]urine X 100 *

]

Electrolyte Disorders

Sodium Homeostasis

• hyponatremia and hypernatremia are disorders of water balance

hyponatremia usually suggests too much

hypernatremia usually suggests too little water in the ECF relative to Na < content

• solutes (such as N a ' , K , glucose) that cannot freely traverse the plasma membrane contribute to

effective osmolality and induce transcellularshifts of water

water moves out of cells in response to increased ECF osmolality

water moves into cells in response to decreased ECF osmolality

• ECF volume is determined by Na+content rather than concentration

Na deficiency leadsto ECF volume contraction

Na +excessleads to ECF volume expansion

• clinical signs and symptoms of hyponatremia and hypernatremia are secondary to cells (especially

brain cells) shrinking (hypernatremia) orswelling (hyponatremia)

water in the ECF relative to Na 'content

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XP9 Nephrology Toronto Notes 2023

Table 4. Clinical Assessment of ECF Volume- (Total Body Na-)

Fluid Compartment Hypovolemic Hypervolemic

Intravascular

Increased

Normal lo increased

JVP Decreased

Orlhostalic drop

Tachycardia

Normal

8lood pressure

Auscultation ol heart

Auscultation ol lungs

Interstitial

Shin turgor

Edema (dependent)

Other

Urine output

8ody weight

Hematocrit,serum protein

Urine sodium

IVC sire

IVC collapse oninspiration

S3

Inspiratory crackles

Decreased

Absent

Normal/increased

Present

Decreased"

Decreased

Increased

IncreasedlDecreased'"

<2.1cm

>50%

Variable

Increased

Decreased

Decreased

>2.1cm

<50%

'Refers to effective circulating volume (ECV). which is the ECF volumeadequately perfusing tissues

"It there is arenal abnormality (e.g.osmotic diuresis),the urineoutput may beincreased despite the presenceot hypovolemia

'"Inhypovolemia,urine sodium can beIncreased due torenallosses,or decreased due to extra-renal losses

'"’IVC ultrasound during respiration assesses central venous pressure/right atrial pressure;lung ultrasound lor B-liries can alsobe used lor

assessment ot pulmonary congestion

Hyponatremia

Definition

• serum [Na +

J <135 mmol/L

• can be associated with hypo-osmolality (most common), iso-osmolality, or hyperosmolality

• consider if it is associated with “appropriate” (hypovolemia) vs. “inappropriate” (euvolemia) ADH

secretion

• if appropriate ADH secretion, is it real vs. effective volume loss?

If the urine osmolality is unknown,

assume the urine is hypo-osmolar/dilute

[ Hyponatremia )

Iso-Osmolar

1280-295 mOsm/kg)

• Retenbon inECF ol large volumes

ol isotonic fluids that do not

contain sodium (e g. mannitol)

• Pseudohyponatremia -lab artifact

seen wtUi severe hyperlipidemia

or paraproteinemia (e g. multiple

myeloma)

Hypo-Osmolar (dilutional)

(<280 mOsnVkg)

• Most common cause of

hyponatremia

• Excess water in relation lo

sodium stores which can be

decreased,normal, or increased

• Categorized by volume status

as determined by clinical

assessment

Hyper-Osmolar (Iranslocalional)

(>295 mOsm/kg)

•Extra osmoles in ECF draw

water out ot cells diluting die

Na 'in ECF

•Usually glucose (rarely

hypertonic mannitol)

•Every 10 mmol/Lincrease in

blood glucose results in

3 mmol/L decrease inNa '

i T

Euvolemic

U„,„>100

• SIADH (normal UNa)

• Adrenal insufficiency

• Hypothyroidism

Hypovolemic

Uu >20

• Diuretics (especially thiazides)

• Salt-wasting nephropathy

Hypervolemic

U„<20 and Feu<1% (renal losses)

• CHF

• Cirrhosis and ascites

• Nephrotic syndrome

• Pregnancy Hi,

<10 and Feu <1% (extra-renal losses)

• Diarrhea

• Excessive sweating

• Third spacing (e.g. peritonitis,

pancreatitis,burnsl

Uo,

*

<100

•Psychogenic polydipsia

•Low solute -

"

tea & toast"

l

)„>20 and Fe

-

,,>1% (renal losses)

• AKI.CKD

Figure 5. Approach to hyponatremia

Signs and Symptoms

• depend on degree of hyponatremia and. more importantly, velocity of progression from onset

• hyponatremia = swollen cells

• acute hyponatremia (<24-48 h) more likely to be symptomatic

• chronic hyponatremia (>24- 48 h ) less likely to be symptomatic due to adaptation

• adaptation: normalization of brain volume through loss of cellular electrolytes (within hours) and

organic osmolytes (within days)

• neurologic symptoms predominate (secondary to cerebral edema ): headache, nausea,malaise,

lethargy, weakness, muscle cramps, anorexia,somnolence, disorientation, personality changes,

depressed reflexes, decreased LOC

Symptoms of Central Pontine

Myelinolysis

• Cranial nerve palsies

• Ouadriplegia

. Decreased LOC

ri

+

Complications

• cerebral edema and increased intracranial pressure resulting in nausea, headaches, decreased LOC,

seizures,coma, brain herniation, and death

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•risk of brain cell shrinkage with rapid correction of hyponatremia

• can develop osmotic demyelination of pontine and extrapontine neurons; may be irreversible (e.g.

central pontine inyelinolysis)

symptom onset may be delayed 2-6 d; begins as dysarthria, dysphagia, paresis, movement

disorders -> later on seizures,lethargy, confusion, disorientation, obtundation, coma

Risk Factorsfor Osmotic Demyelination

« low serum [Na '

] of <115 mmol/L at presentation and/or duration of hyponatremia >2 d

•associated hypokalemia,malnutrition, liver disease, alcoholism

•overly rapid correction of|Na '

), i.e. rise in|Na *|>8 mmol/L/24 h if chronic hyponatremia,e.g.:

inappropriate sodium replacement

suppression of ADH by restoring euvolemia with isotonic fluid, or by stopping a reversible

stimulus of SIADH (organic disorders; medications e.g. SSKIs; limbic system activation e.g.

nausea, pain,surgical stress;see 'Table 5, N P I I )

discontinuation of thiazides; depriving water in patient with psychogenic polydipsia

Investigations for Hyponatremia

• EC1-

'

volume status assessment (see Table 4, NP9)

• serum electrolytes,glucose, Cr

• serum osmolality, urine osmolality

• urine Na +(urine Na +<10-20 mmol/L suggests volume depletion asthe cause of hyponatremia)

• assess for causes of S1ADH (see Table 5)

• TSH, free T4, and cortisol levels

• consider CXR and possibly CT chest ifsuspect pulmonary cause of SIADH (e.g. paraneoplastic

syndrome by small cell lung cancer)

• consider CT head ifsuspect CNS cause of SIADH (i.e.subarachnoid hemorrhage)

Treatment of Hyponatremia

• general measures for all patients

1.treat underlying cause (e.g. restore ECE volume if volume depleted, remove offending drug, treat

pain, nausea,etc.)

2.restrict free water intake in S1ADH (<1000 mL/d)

3.promote free water loss

4.carefully monitorserum Na+, urine volume,and urine tonicity

5.monitor frequently that correction is not too rapid

• monitor urine output frequently:high output of dilute urine is the first sign of dangerously rapid

correction of hyponatremia as the stimulus for ADH is diminished with the correction of hypovolemia

A. Known Acute (known to have developed over <24-48 h)

• commonly occurs in hospital (dilute IV fluid, postoperative increased ADH)

• less risk from rapid correction since adaptation has not fully occurred

• if symptomatic

correct rapidly with 3% NaCl at 1-2 cc/kg/h up to serum|Na t

| 125-130 mmol/L

may need furosemide to address volume overload

• if asymptomatic, treatment depends on presence of risk factorsfor ODS

goal is to promote a negative balance of free water

restrict free water intake

promote free water loss by administration of furosemide with salt tablets, oral urea, or

vasopressin receptor 2 antagonists (e.g. tolvaptan)

if ODS risk factors present, aim to correctserum sodium more slowly

do not give 3% NaCl if hyponatremia is autocorrecting due to water diuresis

B.Chronic or Unknown

1.ifsevere symptoms(seizures or decreased LOC)

must partially correct acutely

aim for increase of Na 1by 0.5-1 mmol/L/h for 4-6 h

limit total rise to 8 mmol/L in 24 h

• IV 3% NaCl at 1 -2 cc/kg/h

may need furosemide

2.ifasymptomatic

water restrict to <1 L/d fluid intake

• consider IV 0.9% NS + furosemide (reduces urine osmolality, augments excretion of H’

O)

consider NaCl tablets as a source of Na +

3.refractory

furosemide and oral salt tablets

oral urea (osmotic aquaresis)

vasopressin receptor 2 antagonists (e.g. tolvaptan)

4.always pay attention to patient’s ECE volume status-if already volume-expanded, usually don't give

NaCl (tablet or IV); if already volume-depleted, almost never appropriate to give furosemide

C.Options for Treatment of Ovcrly-Rapid Correction

• give water (IV D5W)

• give ADH to stop water diuresis(DDAVP 1-2 pg IV )

<8>

Beware of Rapid Correction of

Hyponatremia

• Rapid correction of hyponatremia

can occur inadvertently, commonly

after stopping a reversible secondary

cause of SIADH.e.g.:

• Patient with SIADH secondary to

nausea is given an anti

-emetic

• Resolution of nausea causes a rapid

cessation of SIADH. leading to renal

excretion of excess water and rapid

increase in serum [Na+]

• Patient at risk of osmotic

demyelination

• High output dilute urine (>100 cc/h.

<100 mOsm/L) in the setting of

hyponatremia is usually the first sign

of dangerously rapid correction of

serum sodium

Correction of Na in hyponatremia

should not exceed 8mmol/L/24 h

unless definitely known to be <24-48 h

duration:frequent monitoring of serum

Na+ and urine output is essential

0

Concentration of|Na •) in Common

Infusates

. (Na ) in 0.45% NaCl- 77 mmol/L

. [Na 1

] in 0.9% NaCl

-154 mmol/L

. [Na '

] in 3% NaCl- 513 mmol/L

. [Na ] in 5% NaCl-855 mmol/L

. [Na *

] in Ringer'

slactate

-130 mmol/L

. [Na *]inD5W- 0

Impact of IV'Solution on Serum|Na '] +

• formula to estimate the change in serum [Na+] caused by retention of 1 L of any infusate

• [TBW = (for men) 0.6 x weight(kg);(for women) 0.5 x weight(kg)]

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SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

1. urine that is inappropriately concentrated for the serum osmolality

2. urine sodium >20-40 mmol/L -likely reflecting euvolemia

3. I

'

ENI >1%

Table 5. Disorders Associated with SIADH

Cancer Pulmonary CNS Drugs Miscellaneous

Small cell cancer

Bronchogenic carcinoma

Pancreatic

adenocarcinoma

Hodgkin'

s lymphoma

thymoma

leukemia

Pneumonia

Lung abscess

tuberculosis

Acute respiratory failure

Asthma

COPD

Positive pressure

ventilation

Hass lesion Postoperative state

Encephalitis

Subarachnoid hemorrhage SSBIs

Stroke

Head trauma

Acute psychosis

Acute intermittent

porphyria

Antidepressants

ICAs Pam

Severe nausea

Antineoplastics

Vincristine

HIV

Cyclophosphamide

Anti-epileptics

Carbamacepme

Barbiturates

Chlorpropamide

ACll

Other

DDAV7

Oxytocin

Nicotine H2O Deficit and TBW Equations

TBW - 0.6 x wt (kg) men

TBW - 0.5 *

wt (kg) women

Hypernatremia HiO deficit- TBW x ffNar]plasma140) / 140

Definition

• serum [Na +

] >145 mmol/L

• too little water relative to total body Na always a hyperosmolar state

• usually due to NL I water loss or insufficient intake, rarely due to hypertonic Na '

gain

• less common than hyponatremia because patients are protected against hypernatremia by thirst and

release of ADH

Correction of serum [Nr] in

hypernatremia should not exceed 12

mmol/L/24 h

Hypernatremia

I

1 L D5W approximately equals 1L of

free water

1 L 0.45% NS approximately equals 500

mL of free water Reduced Intake

1

• Elderly (dementia, swallowing

difficulty, stroke,bed-bound)

• Infant

• Coma

Surgical

Increased Losses

(without adequate intake)

Outcomes in Severe Hyponatremia Treated With

and Without Desmopressin

Am J Med 2018;131:1-317

Purpose:Rapid overcorrection of plasma Na

- in severe hyponatremia can lead to osmotic

demyelinabiM syndrome.IhisStudyseekstocom pare

outcomesin hyponatremia based on OOAVP usage

in treatment.

Methods: Retrospective study including all

admissions to internal medicine with hyponatremia

(plasma Na

-

<123 m£q/|L from 2004 to 2014 at 2

Toronto hospitals. Ihe primary outcome wassafe

Na

-

correction («12 mfq/lin any 24 h period and

<18 mlqJl in any 48 h periodl,lime lo reach Na-

>130 mEgflor hospital discharge. 0D4VP uses

were excluded lor 01 and for bleeding prevention in

thrpmbocytopenra.

Results: Among 1450 admissiors of 1274 patients(or

hyponatremia over the10 yr period, desmopressin

was administered in 284 admissions(17.5%).

fewer patientsreceiving OOAVP achieved safe Na -

correction within Ihe 24 h lime frame (70.0% vs.

85%:P<0.001). Ihe proportion of cases with sale

Na

-

correction was highest in Ihe proactive -DDAVP

treatment group,followed by reactive then rescue

treatment(78.6% for proactive vs. 29.3% for

reactive|.According loclinical or radiographic

findings.4 of 1450 admissions had suspected osmotic

demyelrnaban syndrome,two of which occurred

during DDAVP administration (0.79% incidence.95%

Cl 0.22-2.82],

Conclusions:Ihe rescue strategy of DDAVP

administration is not an idealstrategy, while the

proactive strategy was effective a!slowing Na*

rate of change.In patientsat nsk for osmotic

demyelinabon syndrome,a pcoactive DDAVP strategy

more often achieved a more stringent correction limit.

Extra-renal Losses

* Gl loss (diarrhea,fistulas)

• Insensible loss (exercise,

seizures)

Renal Losses

• Central Dl

• Nephrogenic Dl

• Osmetic diuresis (hyperglycemia,

mannitol,urea. NS. polyethylene glycol)

Figure 6. Approach to hypernatremia

Signs and Symptoms

• hypernatremia = shrunken cells

• acute hypernatremia (<24-48 h)

• chronic hypernatremia (>24-48 h), cells will have achieved adaptive mechanism: can import and

generate new osmotically active particles to normalize cell size

• nearly all cases of hypernatremia will be due to chronic hypernatremia

• acute hypernatremia primarily presents in patients with diabetes insipidus

• symptoms due to brain cell shrinkage: altered mental status,weakness, neuromuscular

irritability, focal neurologic deficits,seizures, coma, death

• ± polyuria, thirst, signs of hypovolemia

Complications

• increased risk of vascular rupture resulting in intracranial hemorrhage

• rapid correction may lead to cerebral edema

Treatment of Hypernatremia

• general measures for all patients

• give free water (oral or IV)

treat underlying cause

monitor serum Na frequently (q4h) to ensure correction is not occurring too rapidly

• if evidence of hemodynamic instability,then must first correct volume depletion with NS bolus

• loss of water is often accompanied by loss of Na * ,but a proportionately larger water loss

ri

u J

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XPI2 Xcphiology Toronto Xotcs 2023

• encourage patient to drink pure water, as PO is preferred for fluid administration

• if unable to replace PO or NG,correct H:0deficit with hypotonic IV solution (IV D5W, 0.45% NS [half

normal salinej,or 3.3% dextrose with 0.3% NaCl [“2/3 and 1/3”])

• chronic hypernatremia:aim to lower serum sodium by 8-10 mEq/L in 24 h (often achieved by giving

free water at 1.35 mL/kg/h)

• acute hypernatremia: use formula to calculate water deficit. Replace entire water deficit within 24 h

(hourly infusion rate = water deficit in mL/24 h)

• infusion rate may need to be increased in order to account for ongoing losses in addition to initial

deficit

Diabetes Insipidus

Definition

•collecting tubule is impermeable to water due to absence of ADH or impaired response to ADH

•defect in central release of ADH (central Dl) or renal response to ADH (nephrogenic Dl)

Etiology

•central Dl: neurosurgery, granulomatous diseases, trauma, vascular events, and malignancy

•nephrogenic Dl

usually acquired - drugs(e.g. lithium),secondary to amyloidosis,sickle cell disease,Sjogren

syndrome, polycystic kidney disease, electrolyte imbalances (i.e. hypercalcemia)

congenital/hereditary

Diagnosis

•urine osmolality inappropriately low in patient with hypernatremia (U <>»m <300 mOsm/kg)

•serum vasopressin concentration may be absent/low (central), or elevated (nephrogenic)

•dehydration test: H:0 deprivation until loss of 3% of body weight or until urine osmolality rises above

plasma osmolality; if urine osmolality remains <300 (fails to concentrate urine), most likely Dl

A Copeptin-Based Approach to the Diagnosis ol

DiabetesInsipidus

NiJU 2018:379:428 3S

Purpose: Compansoo of the indirect water

deprivation test,a techaicaly cumbersome test with

direct detection of plasma copeptu.a precursorderived surrogate of arginine vasopressin.

Methods: from 2013 to 200, ISO patients with

hypotonic polyuria underwent both indirect

water-deprivation testing and hypertonic saline

infusion tests.In the biter lest, plasma copeptin

levels were measured when plasma Ka > increased

to >130 mmoifl after saine mfesion.foe primary

outcome was overal diagnostic accuracy of each

test compared with hnal reference diagnosis,as

determined by clinical history,test results and

treatment response, with copeptin levels masked.

lesulU: Among the141 patients included in final

analysis, the Indirect water-deprivation test showed

diagnostic accuracy in 108 patnnts(7C.fiV83%

Cl (8.9 lo 83.2)and the hypertonic saknc infusion

(copeptin cutoff >4.9 mmotil)showed diagnostic

accuracy in 136 patients(94.3%:93% Cl 92.1to

98.6. P‘

0.001). Ihe water-deprivation test correctly

distinguished primary polydipsia from partial central

Dl in 77 of 105 patients(23.3%:95% Cl 63.9 to 81.2)

while the hyperton itsaline test distinguished in 99 of

104 patieMs|95.2%;95% Cl 89.4 to 98.1.M.001).

Conclusion la pit a tswtl bypoMl cpOfiyaH l

direct measurement of hypertomc-salme stimulated

plasma copeptin levelsshowed greater diagnostic

accuracy than the water-deprivation test.

Management

•central Dl: administer exogenous ADH (e.g. DDAVP) 10 pg intranasally or 2 pig SC or IV

•nephrogenic Dl: patients may have partial or complete ADH resistance, and DDAVP is generally

ineffective

• maintain fluid intake to match losses, e.g. PO water, IV D5W, IV 0.45% NS

• treat underlying cause of nephrogenic Dl

thiazides can help by paradoxically reducing urine output: thiazides induce hypovolemia ->

stimulate proximal tubular reabsorption of sodium and water -> less delivery of glomerular

filtrate to the collecting duct -> lower urine volume

Potassium Homeostasis

•-98% of total body K 'stores are intracellular

•normal serum K '

ranges from 3.5-5.0 mEq/L

•in response to K '

rise,rapid removal from ECP is necessary to prevent life-threatening hyperkalemia

(K+ >6.5 mEq/L)

•insulin, catecholamines, and acid-base status influence K '

movement into cells

aldosterone has a minor effect

•potassium excretion is regulated at the DCT and collecting ducts

K’

excretion = urine flow rate x urine [K '

)

Factors which Increase Renal K+Loss

•hyperkalemia

•increased distal tubular urine flow rate and Na ^ delivery (thiazides and loop diuretics)

•increased aldosterone activates epithelial sodium channels in cortical collecting duct, causing Na +

reabsorption and K+excretion

•metabolic alkalosis (increases K + secretion)

•hypomagnesemia

•increased non-resorbable anions in tubule lumen: HCO 3

"

, penicillin,salicylate (increased tubular flow

rate increases K+secretion)

Hypokalemia s n

i j

Definition

. serum [K+ ] <3.5 mEq/L

Signs and Symptoms

• usually asymptomatic,particularly when mild (3.0-3.5 mmol/L)

• nausea/vomiting,fatigue,generalized weakness,myalgia,muscle cramps, and constipation

• ifsevere:arrhythmias,rhabdomyolysis, myoglobinuria, and rarely paralysis with eventual respiratory

impairment

+

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XP13 Nephrology Toronto Notes 2023

• arrhythmias occur at variable levels of K * ; more likely if digoxin use, hypomagnesemia, or CAD

• ECG changes are more predictive of clinical picture than serum|K '

|

• U waves most important (low amplitude wave following a T wave)

• flattened or inverted T waves

• depressed ST segment

• prolongation of Q-T interval

• sinus bradycardia

• with severe hypokalemia:P-K prolongation, wide QRS, arrhythmias; increases risk of digitalis

toxicity

• common arrhythmiasseen with hypokalemia: ventricular fibrillation, ventricular tachycardia

1 2 34 s

r

s

—

Normal Uwave U wave Progression <

Figure 7. ECG changes in hypokalemia

Hypokalemia is often accompanied by

metabolic alkalosis:

• K ^shifts from cells to ECF;H- shifts

into cells in response

• Plasma [HCOJ-]increases,while

intracellular pH decreases

• In response to low pH.renal tubular

cells secrete H'into lumen,and

increase renal ammoniagenesis and

excretion

• Resultant addition of more [HC03-]

into plasma •metabolic alkalosis

Approach to Hypokalemia

1. emergency measures if K+ <2.5 mEq/L:obtain ECG;if potentially life threatening, begin treatment

immediately

2. rule out transcellular shifts of K+ as cause of hypokalemia

3. assess contribution of dietary K+ intake

4.spot urine K:Cr

if <1.5 mEq/mmol consider G1 loss

if >1.5 mEq/mmol consider a renal loss

5. consider 24 h K'excretion

6. if renal Moss, check BP and acid-base status

7. may also assess plasma renin and aldosterone levels,serum|Mg- 11

[ Hypokalemia ]

t T

Redistribution into Cells (transcellular shills)

• Metabolic alkalosis (K'/H' exchange across cell membranel

• Insulin(stimulates Na/K'ATPase)

• Catecholamines,pt-agonists Isalbutamol),theophylline

(stimulates Na' /KATPasel

• Tocolytic agents

• Uptake into newly forming cells

-Vitamin B injections in pernicious anemia

-Colony stimulating factors T WBC production

Decreased Intake

•Limited dietary intake

•Clay ingestion

Increased Loss

i

Spot urine ICCr^

I i

Spot urine K:Cr

<1.5mEq/mmol

Spot urine ICCr

>1.5mEq/mmol

; r

•

GlLosses

Diarrhea 1 C

•Laxatives

•Villous adenoma

Renal losses

T

Check BP

T 1

[Hypo- or normotensive ] Hypertensive

•1°hyperaldosteronism (e g. Conn's syndrome)

•2°hyperaldosteronism (renovascular disease,renin tumour)

[ Check acid base status) •Non-aldosterone mrneralocorbcoid (Cushing's,exogenous)

T V

Acideinic

•DKA

•RTA

Variable

•HypoMg

•Vomibng/NG

Alkalemic

•Diurebcs (furosemide,HCT2Imanifest as renal losses due to

hyperaldosteronism,metabolic alkalosis, and increased flow to collecting duct

•Inherited renal tubular lesions

-Banter's (loop of Henle dysfunction:furosemide-like effect)

-Gitelman'

s (DCT dysfunction: thiazide-like)

Figure 8.Approach tohypokalemia r n

c.

Treatment

•treat underlying cause

•if true K 1 deficit, potassium repletion

oral sources:food, tablets (K-Dur‘

), KC1liquid solutions (preferable route if the patient tolerates

PO medications)

IV: usually KC1 in saline solutions, avoid dextrose solutions(may exacerbate hypokalemia via

insulin release)

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• max 40 mmol/L via peripheral vein, 60 mmol/L via central vein, max infusion 20 mmol/h

• K’-sparing diuretics(triamterene, amiloride, spironolactone) can prevent renal Kioss

• restore Mg-’

before correcting K *

• if urine output and renal function are impaired, correct with extreme caution

• risk of hyperkalemia with potassium replacement especially high in elderly, diabetics, and patients

with decreased renal function

• use ACE inhibitor or ARB for CHI (reduces angiotensin 11 action and therefore reduces aldosterone

production)

• beware of excessive potassium repletion, especially if hypokalemia secondary to transcellular shift

Hyperkalemia

Definition

• serum [K*

|>5.0 mEq/E

Signs and Symptoms

• usually asymptomatic but may develop nausea, palpitations, muscle weakness, muscle stiffness,

paresthesias, aretlexia, ascending paralysis, and hypoventilation

• impaired renal ammoniagenesis and excretion and metabolic acidosis

• ECG changes and cardiotoxicitv (do not correlate well with serum [k

’

])

• peaked and narrow T waves

• decreased amplitude and eventual loss of P waves

• prolonged PR interval

• widening of QRS and eventual merging with T wave (sine-wave pattern)

• AV block

• ventricular fibrillation, asystole

1 2 3 4 5 .1

2-

—1

Peaking

Twave

Normal Peaked

Twave V

Figure 9.ECG changes in hyperkalemia

Table 6. Causes of Hyperkalemia

Pseudohyperkalemia Increased Intake Transcellular Shift Decreased Excretion

Sample hemolysis*

Sample taken from vein

whereIV KCI is running

Prolonged use ol tourniguet

leukocytosis (eilremel

thrombocytosis"(eitreme)

O.et Intravascular hemolysis

Rhabdomyolysis

tumour lysis syndrome

Insulin deficiency

Metabolic Acidosis

Drugs

(1-blockers

Digitalis overdose (blocks

Na /K-AlPase)

Succinylcholine

Decreased GFR

Renal failure

Low effective circulating volume

NSAlDs inrenal insufficiency

Normal GFR but

hypoaldosteronism (table 7)

KCItabs

IV KCI

Salt substitute

’Most common

"Usually when blood specimen has been sitting out long beloie being analyzed

Table 7. Causes of Hyperkalemia with Normal GFR Secondary to

Hypoaldosteronism

Decreased Aldosterone Stimulus (low Decreased Aldosterone Production

renin,low aldosterone)

Aldosterone Resistance (decreased

(normalrenin, low aldosterone) tubular response)

Associated with diabeticnephropathy.NSAlDs. Adrenal Insufficiency (e.g.Addison’s disease.

AIDS,metastatic cancer)

K- sparing diuretics:

Spironolactone

Amiloride

Triamterene

Renal tubulointerstitial disease

chronic interstitial nephritis.HIV

ACEI

Angiotensin IIreceptor blockers

Heparin

Congenital adrenal hyperplasia with

21-hydroxylase deficiency

Approach to Hyperkalemia

1.emergency measures:obtain ECG; if life threatening, begin treatment immediately

2.rule out pseudohyperkalemia; repeat blood test

3. hold exogenous K’ ( HO and IV ) and any medications that are K ’retaining

e.g.RAAS inhibitors(ACEI, ARBs), aldosterone antagonists, non-selective|

}-blockers ( propranolol/

labetalol) or affect K‘

excretion (i.e. NSAlDs)

4. assess potential causes of transcellular shift

5. determine eGlR

In patients with DM and increased [K*]

and hyperglycemia, often just ghnng

insulin to restote euglycemia is sufficient

to correct the hyperkalemia

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NP15 Nephrology Toronto Notes 2023

Treatment

• acute therapy is warranted if E(Xi changes are present or if patient is symptomatic regardless of|K '

|

• tailor therapy to severity of increase in|K '

|and EC(i changes

|K 11 <6.5 and normal E(Xi

treat underlying cause,stop K '

intake, increase the loss of K '

via urine and/or (il tract

• |K 11 between 6,5 and 7.0, no IXXi changes: add insulin to above regimen

• |K 1 j >7.0 and/or IXXi changes: first priority is to protect the heart, add calcium gluconate to above

<§;

Treatment of Hyperkalemia

C BIG K DROP

C Calcium gluconate

BIG pagonlst.Insulin. Glucose

K Kayexalatc'

DROP Diuretics. Dialysis

1. Stabilize Myocardium

• calcium gluconate 1-2 amps (10 rnL of 10% solution) IV

• antagonizes hyperkalemia induced membrane depolarization, protects cardiac conduction system, no

effect on serum [K +

J