Download ABIM_Nephrology

Nephrology Board Review
Outline







Hypertension
Kidney in pregnancy
Clinical Evaluation of Kidney
AKI
CKD
Glomerulonephritis
Electrolytes
Outline






Hypernatremia,hyponatremia
Hypokalemia, hyperkalemia
Hypercalcemia, hypocalcemia
Nephrolithiasis
Genetic diseases of Kidney
Renal Replacement Modalities
JNC Stratification
BP
Normal
SBP (mm Hg)
< 120
DBP (mm Hg)
< 80
Pre- Hypertension
120-139
80-89
Stage One
140-159
90-99
Stage Two
>160
100
Office Bp measurements





Use auscultatory method with properly
calibrated and validated instrument
Patient should be seated for 5 minutes in a chair
with feet rested on the floor and arm supported
at chest level.
Appropriate size cuff should be used to ensure
accuracy.
Atleast 2 measurements should be made.
We should provide written and verbal
confirmation of bp numbers and goal
Ambulatory BP monitoring




ABPM is warranted for evaluation of “white coat
HTN” in the absence of target organ injury.
ABPM values are lower than clinic settings.
Awake, individuals with HTN have an average
value >135/85 mm Hg and during sleep
>120/75mm Hg.
Bp drops by 10-20% during the night, and if not
then it may signal CV disease. “Non Dippers”
Lifestyle Modification
Modification
Approximate SBP reduction
(range)
Weight reduction
5–20 mmHg/10 kg wt loss
Adopt DASH Diet
8–14 mmHg
Dietary NA
reduction
2–8 mmHg
Physical activity
4–9 mmHg
Moderation of
alcohol consumption
2–4 mmHg
Causes of Secondary HTN



Renal disorders: parenchymal disease:
GN, Nephrotic syndrome, PCKD, CKD;
Renovascular Disease
Endocrine Disorders: Pheo, Primary
hyperaldosteronism, Cushings syndrome,
Carcinoid, Hyperthyroid or
hypothyroidism, Hyperparathyroidism,
Acromegaly.
Secondary HTN





OSA
Polycythemia
Medications such as steroids, EPO, CSA,
Prograf..
Stimulants/drugs/etoh
Coarctation of Aorta, Liddle’s syndrome,
Gordon’s syndrome, 11 Beta
hydroxysteroid deficiency, Licorice, GRA
Laboratory Evaluation








Routine Tests
EKG
Urinalysis
Blood glucose and Hct
Serum Potassium, Creatnine and Calcium
Fasting Lipid profile
Optional Tests: urinary Albumin excretion
More extensive tests are not warranted unless
BP Control is not achieved.
Principal Cell
Algorithm for RX of Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Without Compelling
Indications
With Compelling
Indications
Stage 1 Hypertension
Stage 2 Hypertension
(SBP 140–159 or DBP 90–99 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
(SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually
thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
Heart Failure
POST MI
CAD risk
DM
CKD
Recurrent Stroke
Aldost Inhibitor
CCB
ARB
Ace Inhibitor
Beta Blocker
Diuretics
Compelling
Indications
Differential Diagnosis of Azotemia





Etiologies of elevated Cr:
Kidney disease
Large Muscle mass, AA
Medications that block creatnine secretion
cimetidine, trimethoprim, probenecid
Substances that interfere with creatnine
assay- cefoxitin, flucytosine, acetoacetate,
bilirubin
Acute Kidney Injury
Definition of Acute Kidney Injury


Loss of renal function measured as GFR
over hours to days
Expressed clinically as the retention of
nitrogenous waste products in the blood.
Definitions




Azotemia- accummulation of nitrogenous
wastes
Uremia- symptomatic renal failure
Oliguria- urine output <400-500ml/24hrs
Anuria- urine output<100ml/24hrs
Causes of Anuria

Obstruction (vast majority of patients with
anuria)
Bilateral renal cortical necrosis
Fulminant glomerulonephritis (usually
some type of rapidly progressive
glomerulonephritis)
Acute bilateral renal artery or vein
occlusion (rare)
Classification of the Etiologies of
AKI
Acute Kidney Injury
Prerenal
Acute Tubular
Necrosis
Intrinsic
Acute Interstitial
Nephritis
Acute
Glomerulonephritis
Postrenal
Acute Vascular
Syndrome
Intratubular Obstruction
Differential Diagnosis of Acute
Renal Failure



Prerenal acute renal failure
True intravascular depletion Sepsis,
hemorrhage, overdiuresis, poor fluid intake,
vomiting, diarrhea
Decreased effective circulating volume to the
kidneys Congestive heart failure, cirrhosis or
hepatorenal syndrome, nephrotic syndrome

Impaired renal blood flow because of exogenous
agents Angiotensin-converting enzyme
inhibitors, nonsteroidal anti-inflammatory drugs,
CSA. Hypercalcemia. Abdominal compartment
syndrome with increased renal vein pressures
Diagnostic Criteria for HRS




Major criteria: Low GFR (<40ml/min or
cr>1.5mg/dl)
Absence of shock, ongoing bacterial
infection, treatment with nephrotoxins or
volume loss
No improvement with diuretics or volume
expansion with 1.5L of isotonic saline
Proteinuria<500mg/dl and no US evidence
of obstruction or parenchymal dz.
Diagnostic Criteria for HRS







Minor criteria
Urine volume <500ml/day
UNa<10mmol/L
Urine osm>plasma osm
Urine rbc<50 per high power field
Serum sodium <130 mmol/L
Arroyo et al Hepatology 1996
AKI in Liver disease





Pre renal azotemia
HRS
ATN
Interstitial Nephritis
Glomerular syndromes: IGA,
cryoglobulinemia, MPGN, Membranous
Nephropathy
Precipitating factors for HRS






SBP
Severe Bacterial Infection
GI Bleed
Major surgery
Aggressive diuresis
Paracentesis
Abdominal Compartment Syndrome
Clinical setting
Trauma patient following massive volume
resuscitation, post liver tx, mechanical
limitations to abd wall such as burn
injuries, post surgery etc.
Bowel obstruction or pancreatitis.
Clinical manifestations include: respiratory
compromise, decreased CO, intestinal
ischemia, oliguric AKI

Abdominal Compartment Syndrome



Pathophysiology of AKI- Increased renal
venous pressure, increased parenchymal
pressure, decreased perfusion
Diagnosis- suspect in distended abdomen.
Excluded if bladder pressure<10 and dx
when bladder pressure >25mm Hg.
Treatment Abdominal decompression
Differential Diagnosis of Acute
Renal Failure



Postrenal acute renal failure
Benign prostatic hypertrophy or prostate
cancer, cervical cancer, retroperitoneal
disorders, pelvic mass or invasive pelvic
malignancy, intraluminal bladder mass
(clot, tumor or fungus ball), neurogenic
bladder, urethral strictures
intratubular obstruction (crystals or
myeloma light chains),
Intrinsic AKI





ATN
AIN
AGN
Acute vascular syndromes
Intratubular obstruction
Acute Interstitial Nephritis


Acute Kidney injury due to lymphocytic
infiltration of the interstitium
Classic triad fever rash and eosinophilia
(described in the methicillin patients and
occurrs <30% of cases)
Acute Interstitial Nephritis












Drug induced
PCN
Cephalosporins
Sulfa
Rifampin
Phenytoin
Furosemide
NSAIDS
PPI
Ciprofloxacin
Malignancy
Idiopathic









Infection related
Bacterial
Viral
Rickettsial
TB
Systemic diseases
SLE
Sjogrens syndrome
TINU
Common Drugs That Can Cause
Allergic Interstitial Nephritis











Allopurinol (Zyloprim)
Cephalosporins
Cimetidine (Tagamet)
Ciprofloxacin (Cipro)
Furosemide (Lasix)
Nonsteroidal anti-inflammatory drugs
Penicillins
Phenytoin (Dilantin)
Rifampin (Rifadin)
Sulfonamides
Thiazide diuretics
Acute Interstitial Nephritis






History
Preceeding illness or
drug exposure
Physical exam
Fever, rash
Lab finding
eosinophilia






Urine findings
Non nephrotic
proteinuria
Hematuria
Pyuria
Wbc casts
eosinophiluria
Acute Interstitial Nephritis




Pearls
NSAID AIN is often without urine eos.
3 sets of urine without eos has a NPV of
>95% for AIN (other than from NSAIDs)
Urine eos can be positive in
pyelonephritis, GN, Radiation nephritis and
AIN
Acute Interstitial Nephritis



Treatment
Discontinue offending drug
Steroid therapy may hasten recovery but
no RCT only case cohorts.
Acute Glomerulonephritis
RPGN- 3 types
1. Ab mediated against basement
membrane. Anti GBM dz
2. Ag-Ab complex deposit in the GBM: SLE,
HepC, post strep, post infectious,
endocarditis associated, IGA
3. Pauci immune: Wegner’s, Microscopic
polyangiitis, Churg strauss
Acute Glomerulonephritis





Proteinuria and hematuria. Quantify the
proteinuria.
Acitve urinary sediment with dysmorphic
red blood cells or rbc casts.
Low complements in SLE, MPGN, post
strep or endocarditis or infections.
ANCA and Anti GBM titers.
ANA
Vascular Syndromes








Macrovascular:
Renal artery thromboembolism
Renal artery dissection
Renal vein thrombosis
Microvascular
Atheroembolic disease
TTP
HUS
Atheroembolic disease


Risk Factors: Atherosclerosis, HTN, HLP,
DM
Precipitating risk factors: Arterial
catheterization, arteriography,
anticoagulation, vascular surgery,
thrombolytic surgery
Atheroembolic disease




General: fever, myalgias,
weight loss
Cutaneous: livedo
reticularis, digital
ischemia
Neurologic- TIA, CVA,
AMS, Spinal cord infarct
GI- anorexia, bowel
ischemia, pancreatitis,


Muskuloskeletal- myositis
Eyes- amaurosis fugax,
retinal cholesterol emboli
Atheroembolic disease


Serum chemisterieselevated bun, cr,
amylase, cpk, lfts
Hematologyleukocytosis,
eosinophilia, anemia,
thrombocytopenia


Serologies- increased
esr and low
complements.
Urine- eosinophiluria,
proteinuria,
hematuria, pyuria
Atheroembolic disease





Treatment:
Avoid anticoagulation
Avoid vascular intervention
Nutrition support
Dialysis
Intratubular Obstruction
Intratubular crystal deposition

Tumor lysis syndrome- acute urate
nephropathy

Ethylene glycol toxicity- calcium oxalate
deposition

Medication associated- indinavir, acyclovir
Intratubular protein deposition- multiple myelom
with bence jones protein deposition
ATN


Ischemic- prolonged
prerenal azotemia,
hypotension,
hypovolemic shock,
cardiopulmonary
arrest,
cardiopulmonary
bypass
Sepsis



Nephrotoxins
Drug inducedradiocontrast,
aminoglycosides,
ampho B, Cisplatinum
Pigment nephropathy
hemoglobinuria,
myoglobinuria
Nephrotoxins
















Acyclovir (Zovirax)
Tenofovir
Aminoglycosides*
Amphotericin B (Fungizone)
Angiotensin-converting enzyme inhibitors*
Cancer drugs: cisplatin (Platinol AQ), ifosfamide (Ifex)
Cocaine
Cyclosporine (Sandimmune)
Foscarnet (Foscavir)
Heavy metals
Myeloma light chains
Nonsteroidal anti-inflammatory drugs*
Oxalic acid
Pentamidine (NebuPent, Pentam 300, Pneumopent)
Pigment: hemoglobin, myoglobin
Radiocontrast media*
ATN




Prevention of ATN
Identification of high risk patients
Timing of insult
Repeated insults.
Blood and Urine Studies to Distinguish
Prerenal from Intrinsic Acute Renal Failure

Type of renal failure BUN-to-creatinine Urine osmolality
Prerenal acute renal
failure
Intrinsic acute renal
failure
>20:1
>500 mOsm
<20:1
250 to 300
mOsm
Fractional excretion
of sodium*
<1%
>3%
Findings on Urinalysis in the Broad
Categories of Acute Renal Failure










Prerenal acute renal failure
Scant; few hyaline casts
Postrenal acute renal failure
Scant; few hyaline casts, possible red cells
Acute tubular necrosis
Epithelial cells, muddy-brown, coarsely granular casts, white blood
cells, low-grade proteinuria
Allergic interstitial nephritis
White blood cells, red blood cells, epithelial cells, eosinophils,
possible white blood cell cast, low to moderate proteinuria
Glomerulonephritis
Red blood cell casts, dysmorphic red cells, moderate to severe
proteinuria, oval fat bodies
Management of CKD








Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Metabolism
Cardiovascular Risk
Diet/Nutrition
Etiology/Progression



In the MDRD study Rate of Progression of
CKD varies based on :
Underlying disease, proteinuria,
Stage of CKD, comorbidities and
treatments.
Retrospective analysis of MRFIT data
showed that :1+proteinuria-3.1%, 2+
15.7%, GFR 60-30 2.4%, GFR <30 41%
over a 10 year period.
Access






GFR <25ml/min or rapid progression consider
placement of hemodialysis access.
Transplant referral at GFR<30 and placement on
transplant list at <20.
AVF
AVG
Tunneled Catheter
Periotenal dialysis
Adequacy



Is the GFR adequate to avoid: volume overload,
uremic sxs- nausea, malnutrition, pericarditis,
lethargy, hyperk, acidosis. Most common
reasons to start- malnutrition and volume
overload.
GFR<15ml/min per NKF are indications to
consider the risks and benefits to initiating
dialysis.
European Best Practice guidelines state
GFR<6ml/min and consider at 8-10
40
1.0
0.9
A
B
0.8
0.7
0.6
0.5
0
P-values:
Overall <.001
A vs B =.013
A vs C <.001
B vs C <.001
C
Incidence (%)
Reduction in Survival due
to CV Mortality
Proteinuria and Risk of
CV Mortality,Stroke, and CHD
Events in Type 2 Diabetes
30
P<.001 for
trends
20
10
0
0 10 20 30 40 50 60 70 80 90
Months
A: UPC <150 mg/L
B: UPC 150-300 mg/L
CHD, coronary heart disease; UPC, urinary protein concentration.
* Defined as CHD death or nonfatal MI.
Adapted from Miettinen H et al. Stroke. 1996;27:2033-2039.
Stroke
CHD Events*
C: UPC >300 mg/L
IRMA 2 - Results
% Reduction in Urinary Albumin
Excretion
% Reduction in UAER
0%
-5%
-2%
-10%
-15%
-24%
-20%
-25%
-30%
-38%

-35%
-40%
Placebo
Irbesartan 150 mg
Irbesartan 300 mg
 p < 0.001 for Irb 300 mg vs Irb 150 mg
Adapted from Parving HH. et al. N Engl J Med 2001;345(12):870-878.
20
IRMA 2 Primary End Point:
Time to Overt Proteinuria
Control (n=201)*
Irbesartan 150 mg/d (n=195)*
Irbesartan 300 mg/d (n=194)*
Patients (%)
15
RRR=39%
P=.08
10
RRR=70%
P<.001
5
0
0
3
6
12
Follow-up (mo)
18
22
24
RRR, relative risk reduction.
Control defined as placebo.
* Adjunctive antihypertensive therapies (excluding ACE inhibitors, ARBs, and dihydropyridine CCBs)
could be added to all groups to help achieve target BP levels.
Adapted from Parving H-H et al. N Engl J Med. 2001;345:870-878.
81
BP





Per JNC VII ACEI/ARB preferred agents in
CKD (even if not hypertensive but prot).
Most prominent in patients on low sodium
diet, on diuretics and volume depletion.
Reduction in proteinuria and
intraglomerular pressure.
Antifibrotic effects
Other agents
BP



Aggressive BP lowering effective in
proteinuric (<1gm/day) patients.
Response to reduction in proteinuria in
multiple studies predicts a better outcome.
BP control is important for CVD protection
and renoprotection.
Approach to the hyponatremic
patient
Hyponatremia
High Osmolality
Normal Osmolality
Low Osmolality
Hyponatremia with high or Nml
Osmolality





TRANSLOCATION
GLUCOSE
MANNITOL
GLYCINE
MALTOSE



PSEUDOHYPONATRE
PROTEIN
LIPIDS
Pseudohyponatremia




Normally serum is 93%water and 7%
lipids.
If non aqueous portion of serum rose to
20%
Serum measured Na would be:
150x0.8=120 as opposed to 150x0.93
Pseudohyponatremia
Approach to the hyponatremic
patient with Low plasma osm
Hyponatremia with low Osm
Normally Dilute urine
<100mosm
Psychogenic Polydipsia
Uosm>100mosm
Low Solute intake
Low Solute intake
Urine flow= urinary solute excretion
urinary osmolality
Sources of urinary solutes
Psychogenic Polydipsia




Usually acute
Common in institutionalized schizophrenics
Abnormal weight gains (as much as 10%)
Episodic symptoms that resolve with water
restriction
Beer Potomania



Large intake of fluid with beer as sole
source of nutrition
Beer sodium content <2meq/L
Beer Potassium content 10-12meq/L
Beer Potomania

Assume Beer consumption of 5L
Na intake
10mM
K intake
50mM
Obligatory urea excre 80mM

V=Soluteexcretion




Uosm
5=200
40
Approach to the hyponatremic
patient with low plasma osm
Low plasma osm
Normally dilute urine
Uosm<100
Uosm>100mosm
Almost always vasopressin
mediated
Hyponatremia in Edematous
disorders




Reflects advanced disease and poor
prognosis
Decreased delivery to diluting sites
Increased vasopressin levels
Increased AQP2 expression
Cerebral Salt wasting





Most common in subarachnoid
hemorrhage
Increased ANP and BNP
Loss of sodium, volume depletion which
then leads to increased ADH.
Different from SIADH as volume depleted.
Treat with saline
Features of SIADH




Clinically euvolemic
Uosm>100mosm
Una=Na intake usually >20meq/L
Low bun and Uric acid
Malignancies and SIADH




Most common with small cell lung ca (1015%)
mRNA for AVP in tumor
Head and neck tumors
Other isolated cases
Treatment of Hyponatremia




Three key Questions
How long has the hyponatremia been
present?
Does the patient have symptoms?
Does the patient have risk factors for the
development of neurologic complications?
Duration of Hyponatremia acute




<48hrs
Severe brain edema
Rapid correction is well tolerated
BUT WHEN IN DOUBT…Treat as chronic
Patients at increased risk for
neurologic complications





Post op menstruant females
Elderly women on HCTZ
Children
Hypoxemic patients
Psychogenic polydipsia
Duration of Hyponatremia Chronic



48hrs or unknown duration
Mild cerebral edema <10%
Sensitive to correction
Symptomatic vs Asymptomatic






Symptomatic hyponatremia warrents aggressive
correction. (sz, severe neuro abnormalities).
Most likely to occur in acute setting such as:
Post op menstruating females
Exercise induced hyponatremia
Hyponatremia associated with ecstasy
Hyponatremia in patients with intracerebral
pathology,
Self induced water intoxication
Symptomatic hyponatremia



Aggressive correction at a rate of 1.52meq/L per hour for 3-4 hrs or until sxs
resolve.
Usually with hypertonic saline at
0.5ml/kg/hr
However no more than 10-12meq/24hrs
and 18meq/48hrs.
Asymptomatic but <115 or 110


Such patient if they have sxs such as
confusion, lethargy, gait disturbances will
benefit from rise of 1meq/L/hr for 3-4 hrs
but no faster than 8meq/24hrs.
IF asymptomatic and >120meq/L then
would benefit from free water restriction
or treatment of volume depletion but no
faster than 6-8meq/24hrs.
Risk factors for Development of
Osmotic demyelination





Alcoholism
Malnutrition
Burns
Severe Potassium depletion
Elderly women on thiazide diuretics
Urine flow= urinary solute excretion
urinary osmolality
Hypernatremia
Causes of hypernatremia




1.
2.
3.
4.
Inappropriately high water losses
Insufficient water intake
High Na intake without adequate water
Thirst center/osmoreceptor lesion
4. Impaired thirst or osmoreceptors


Causes usually tumor, granulomatous dz,
ischemia, primary aldosteronism, age.
Na>146 but not thirsty. Dilute urine after
any H20 with impaired osmoreceptors
3. High NaCl intake without water




Rare
Seawater ingestion
NaCl poisoning
Hypertonic Na or bicarb boluses.
2. Insufficient water Intake



Usually when ill or in the hospital setting
Inadequate Free water
Common after surgery, high nutrient
intake, diuretics.
1. Inappropriately high water losses
Sites of water loss
1. insensible (sweat, breath)
2. GI (vomitting, NG, Diarrhea)
3. Kidney
DI



Vasopressinase production
Central (neurogenci) DI
Nephrogenic DI
Vasopressin (ADH) Receptors





V2
Makes collecting duct permeable to water
V1
Increases systemic BP
Expressed in vasculature, liver and brain
DI – lack of vasopressin


Gestational DI
Central DI
Gestational DI



1 in 300,000 pregnancies
Increased action of vasopressinase
normally from the placenta
Vasopressinase does not attack DDAVP as
rapidly
Central (neurogenic) DI


Acquired- tumor, trauma, autoimmune,
granulomatous, vascular
Congenital- autosomal dominant
Nephrogenic







Congenital
Acquired
Drugs- LI, demeclocycline
Hypercalcemia
Hypokalemia
Uretral obstruction
Renal insufficiency
Treatment





Acute<24hrs
Osmotic loss of brain water
Accumulation of electrolytes: Na, K
Chronic >24hrs
Accumulation of organic solutes such as
myo-inositol, sorbitol, others.
Distribution of Total Body K+





Intracellular fluid:
3500meq (140meq/L)
Muscle 2700meq
Liver 250meq
Erythrocytes 250meq
Bone 300meq


Extracellular Fluid
70meq (3.5-5meq/L)
Normal Potassium Balance
100 mEq K+
RBC
~250
Muscle
~2500
Extracellular fluid
65 mEq
Liver
~250
Bone
~300
90-95
mEq
5-10 mEq
Regulation of K+ homeostasis



2 systems
Intake/excretion
Shifts between intracellular and
extracellular
Intake/output




Avg american diet 100meq Potassium
90% Renal excretion. 10% GI
Aldosterone stimulates GI excretion of K
and in patients with renal failure this can
be increased 4 fold.
6-12 hrs to excrete an acute load.
Regulation of Renal Potassium
Excretion






5 factors
Aldosterone
High distal sodium delivery
High urine flow rate
High K+ concentration in tubular cells
Metabolic alkalosis
Principal Cell
Aldosterone



Directly increases Na/K ATPase in the collecting
duct cells leading to potassium secretion.
Medical conditions that impair aldo pdxndiabetic nephropathy, CIN, ACEI, NSAIDS,
heparin, spironolactone..
Conditions that increase aldo pdxn: primary
hyperaldo, secondary due to diuretics, volume
contraction…
Distal Sodium delivery


Diuretics such as thiazides, loop diuretics
increase distal sodium delivery which then
leads to increased distal sodium
absorbtion and excretion of potassium
Osmotic diuresis
Luminal Flow rate


Diuretics
Osmotic diuresis
Shifts




Insulin
Catecholamines
Acid base
Anabolism
Shifts


Epinephrine leads to stimulation of B2
adrenergic receptors which in turn
stimulate the Na/K ATPase in skeletal
muscle and lead to shift of K+ into the
cells.
Non selective B blockers block this effect.
Lab evaluation of Potassium
disorders



Uk>20 suggests renal etiology.
FEk normal 10%. Thus in hypokalemia it
should be lower and higher in
hyperkalemia.
TTKG: (Uk/Pk)/Uosm/Posm
Hypokalemia vs Potassium
Deficiency



Potassium deficiency can exist without
hypokalemia and hypokalemia can exist
without potassium deficiency
DKA presenting with hyperK but is
potassium deficient
Patient with hyperthyroid periodic
paralysis has hypok without deficiency
HYPOKALEMIA



<1% of individuals not taking meds
develop hypokalemia
Should always pursue workup
Frequently occurs in the setting of
diuretics, diarrhea, primary and secondary
hyperaldosterone states.
HYPOKALEMIA






Ventricular arrhythmias esp<2.5
Muscle weakness, predispose to rhabdo by
decreasing blood flow thru nitric oxide.
Tetany, parasthesia
Respiratory muscle weakness
Polyuria- nephrogenic DI
Increases renal ammonia production and
worsens hepatic encephalopathy. ileus
HYPOKALEMIA





Pseudohypokalemia
Cell shifts
Inadquate intake
GI loss
Renal loss
HYPOKALEMIA


Uptake in metabolically active cells such
as AML with marked leukocytosis
Can prevent this lab finding by rapidly
separating plasma cells or storing blood at
4deg celcius
Cell Shifts






Alkalosis- trivial effect
Insulin
B adrenergic activity- stress induced such as MI
or drugs such as theophylline intox, ritodrine,
terbutaline, albuterol
Anabolism- TPN, treatment of prenicious
anemia, rapidly growing leukemias
Hypothermia
Hypokalemic periodic paralysis
Shifts





Hypokalemic Periodic paralysis
Intermittent acute attacks of muscle
weakness with hypok triggered by large
CHO meals, rest post exercise
2 forms- AD mutation in ca channel vs
thyrotoxicosis in asian and mexican males
60meq K for acute attack and then d/c
B blockers, correct hyperthyroid state
HYPOKALEMIA



Inadequate intake
Unusual
Kidney can lower K 5-15meq/day
HYPOKALEMIA




GI Loss
Urinary K<20meq/L
Diarrhea 30-50meq/L
Vomitting- Kloss is due to renal loss as
gastric juice has 5-10 meq/L but
secondary hyperaldo and metabolic
alkalosis
HYPOKALEMIA



Renal loss Urinary K> 20meq/L
No history of diarrhea
Divide into hypertensive vs. non
Primary Mineralacorticoid Increase





Incr R/A
DDXMalignant HTN
RAS
Renin secreting tumor
Primary Mineralacorticoid Increase




Decr R/Incr A
DDX- Conn’s syndrome
Bilateral adrenal hyperplasia
Gluc suppressible hyperaldo
Glucocorticoid Suppressible
Hyperaldo



AD
Chimeric gene formed by cross over of
genetic material joining ACTH response
element with coding region of aldo
synthase
Aldo secr from zona fasiculata
Primary Mineralacorticoid Increase






Decrease R and A
DDX
Cushings
Liddle’s
Syndrome of AME- 11 B OH steroid
dehydrogenase def vs acquired def
Activating mutation of mineralacorticoid
receptor
Liddle’s syndrome



HTN, Metabolic alkalosis and
hypokalemia.
Nml-aldo negates a protein
NED4 which would normally
remove the sodium channel
from the membrane. In
Liddle’s there is a mutation in
NED4 which leaves the sodium
channel constitutively open.
NO response to spironolactone
but does respond to
Triamterene
Syndrome of Apparent
Mineralacorticoid Excess



Def of
11BOHSDehydrogena
se
Genetic
acquired
Genetic Causes of Hypok Alkalosis
and HTN



Activating mutation of
mineralacorticoid
receptor
AD where the
receptor is
constitutively active.
It is also activated by
progesterone and
pregnancy may make
it worse.
Increase in Sodium delivery






Diuretics that act proximal to the cortical
collecting duct
Mg Def
Bicarbonaturia-Acidosis- Prox and distal
RTA
Nonreabsorbed anions
Bartters Syndrome
Gitleman’s syndrome
Increase Na Delivery




Bartter’s – NMl bp, hypokalemia, metabolic
alkalosis, high urine ca, low serum Mg
sometimes. Impaired urine concentration
Multiple Genetic defects can lead to this
GItleman’s- Nml Bp, hypokalemia, metabolic
alkalosis, low urine ca, normal urine
concentration, low serum mg.
One known genetic defect
Primary Increase in Distal Na
Delivery

Failure to reabsorb Hco3, Ketoanions,
PCN, Hippurate, salicylate obligates
increase distal Na Delivery
HYPERKALEMIA




Pseudohyperkalemia
Excess K intake
Cell Shifts
Impaired renal excretion- only cause of
sustained hyperkalemia
Hyperkalemia



Mechanical trauma during venopuncture
Familial pseudohyperkalemia- enhanced
temprature dependent leakage of K out of
rbc during venopuncture.
Increase wbc and plt count
Hyperkalemia




Cell injury- rhabdomyolysis, tumor lysis,
massive hemolysis, ischemia
Toxins/drugs: digoxin, Chan su,
tetrodotoxin, succinylcholine
DKA, Nonketotic hyperosmolar state
Hyperkalemic periodic paralysis
Hyperkalemic Periodic Paralysis



AD
Mutation in skeletal muscle Na channel
Episodic weakness precipitated by cold,
ingestion of small amounts of potassium
Hyperkalemia- shifts



Mineral acidosis
B blockade
Increase tonicity
Hyperkalemia- Impaired renal
excretion



Decrease in mineralacorticoid activity
Decrease in distal Na delivery
Abnormal cortical collecting duct
Hyperkalemia



Decrease in mineralacorticoid activity
Adrenal insufficiency
Drugs
Hyperkalemia- Abnormal CCD



Drugs- K sparing diuretics
Tubulointerstitial nephritis
Urinary obstruction
Treatment of Acute
Hyperkalemia
1)
2)
3)
Assess urgency
Stabilize myocardium: CaGluconate
Redistribute K+ from ECF to ICF
Ins/D50, Albuterol (high dose), NaHCO3, ?diur
4)
Remove K+ from body
Kayexalate, K loosing diuretics, dialysis
Questions


27 yo dancer with serum K 3, HCO3 20.
UNA 5, UK 7, UCL5
44 yo male with long h/o HTN, serum K 3,
HCO3 30, UNA 30, UK 40, UCL40 with low
renin and aldo ratio. Poor response to all
bp meds except bp controlled with
triamterene
Questions



25 yo college student with serum K 3,
HCO3 30, UNA 45, UK 45, Ucl 55.
21 yo asian male with h/o palpitations,
tremors who upon waking up in the am
could not move. Serum K 2.
45 yo male with metastaic cancer who
presents with hypotension, hyperkalemia,
hyponatremia. UK 5. FEK 5%, TTKG2
Questions



21 yo female medical student with serum
K 3, HCO3 30, UNA 5, UK 40, UCL <10
44 yo male with CLL with wbc 70,000,
K=7 without EKG changes
Same patient undergoes chemotherapy
and has K= 7 with EKG changes
Answers
1.
2.
3.
4.
5.
6.
7.
8.
Hypokalemic Periodic paralysis
Tumor Lysis
Hemolysis
Diuretic abuse
Laxative abuse
Liddle’s syndrome
Adrenal insuff
Vomiting
Clinical Presentation



Patients may present with classic
symptoms of renal colic and hematuria.
Others may present with atypical sxs such
as abdominal pain, nausea, difficulty
urinating, penile pain or testicular pain.
Asymptomatic nephrolithiasis may also be
detected on imaging.
Radiology




Ultrasound
Spiral CT – non contrast
IVP
KUB– calcium and cystine but not uric acid
and MAP
Calcium stones


Calcium oxalate most common. Risk
factors: low urine volume, male, obesity,
high sodium intake, high animal intake
with acidic urine (ethylene glycol)
Calcium phos stones form in patients with
RTA as low urinary citrate,
hyperparathyroid patients as high urinary
calcium and phos.
Treatment




Urine dilution
First urine with sp grav <1.012
Volume >2.1 L /day
Fluids at bed time
Uric Acid Urolithiasis




5% of uric acid stones are due to
secondary causes
Radiolucent
>800mg/dy in men and >750mg/dy in
women
Uric acid is less soluble than urate and at
ph<5.5 only 100mg/l is soluble.
Idiopathic Uric Acid Urolithiasis






Men more often than women
Usually over the age of 60
Often with gout
Nml blood and urine concentration of uric acid
Low Ph
Tx with 4-6gm/dy of bicarbonate in divided
doses. Moderate purine food intake. If still with
hyperuricosuria then allopurinol.
Infection Stones





MAP, Struvite.
Decreased incidence
3x higher in women than men
Urea splitting by urease producing
microorg Ph>8precipitation of MAP
Proteus, corynebacterium, ureaplasma
urealyticum, Serratia, Kleb pneum
Infection Stone




Radiopaque
Rapidly enlarge, difficult to treat.
May have an underlying calcium oxalate
stone.
Antibiotics, stone removal with
percutaneous nephrolithotomy.
Cystine Stone







Autosomal recessive defect of transepithelial
transport of dibasic aminoacids in the kidney
and intestine.
1-2% of stones in adults but 10% in children
2nd-3rd decade of life but upto 7th decade
3L/dy of urine
Alkalinize the urine to 7.5-8
Decrease methionine containing foods such as
lobster, crayfish..
D penicillamine or tiopronin which cleave
cystine.
CYSTINE:
Drug Induced stones




1% of stones
Sulfadiazine in high doses can cause
crystalluria.
Protease inhibitors.
Triamterene
Genetic Diseases of the Kidney




ADPKD
Hypertension, Fh, multiple bilateral renal
cysts.
Liver, pancreatic cysts, diverticula,
cerebral aneurysm, abd and thoracic
aneurysms, MVP
Renal failure by age 50.
Genetic dz of Kidney




Medullary Sponge
Benign
Hematuria, hypercalcuria,
nephrocalcinosis, UTI
IVP characteristic
Genetic Diseases of the Kidney






Alport’s
X linked in 80% of patients. 10% AR
Mutations in type IV collagen
Hematuria, proteinuria. Hearing loss.
Benign Familial Hematuria/Thin basement
Hematuria but no esrd
Genetic Dz of Kidney






Fabry’s dz
X linked
Def in alpha galactosidase
Proteinuria, neuropathy, angiokeratomas
Progress to esrd.
Check enzyme level. Renal bx
Pregnancy




Increase in GFR to 150ml/min
Decrease in bicarb to 22
Decreased Na due to increase free water
Increased baseline creatnine leads to
complications during pregnancy,
progression of renal dz and decreased
fertility
Pregnancy




Preeclampsia BP>140/90, proteinuria
usually after 20 weeks gestation, edema,
neurologic sxs,
Nullliparous women, renal dz, htn, obesity,
dm, extremes of age, multiple gestations.
Increased uric acid.
Tx bp, mg, deliver
Pregnancy





HELLP
TTP
HUS
Chronic HTN
Gestational HTN mid pregnancy but no
proteinuria
GN



Nephrotic syndrome- Edema, proteinuria
>3.5gm/day, hyperlipidemia, hypercoag
Bland urine sediment
Nephritic syndrome: HTN, RI, active urine
sediment.
GN- Nephrotic






Minimal change Dz:
Sudden onset
Heavy proteinuria
Young (<30)
Secondary causes: Hodgkins, Li, NSAIDs
Tx Steroids upto 16 weeks. 1mg/kg
GN- Nephrotic




FSGS
AA, bland sediment . Progresses to ESRD.
Secondary causes: HIV, Obesity, Solitary
kidney, heroin use, reflux nephropathy
Usually slow progressive. Ace and arbs
GN- Nephrotic





Membranous
Usually age >50
Secondary casues: solid tumors- lung,
breast, colon. SLE class 5, Hep B
1/3 progress, 1/3 resolve and 1/3 stable.
Cytoxan and prednisone
GN- Nephrotic



Diabetes- hyperfiltration, microalb,
nephrotic.
Bp, glucose control and ace/arb
Amyloidosis- primary (malignancy) vs
secondary from chronic inflammatory
state. Albuminuria, orthostatic
hypotension, liver abnml, cardiomyopathy.
GN- Nephrotic





Multiple myeloma
AKI- hypercalcemia
Light chains obstructing kidney
LCDD
Albuminuria vs proteinuria.
Nephritic dz- Anti GBM





0.5/1,000,000 per yr in caucasians
10-20% of cases RPGN
Mediated by antibodies to type IV collagen
found in GBM
Type IV collagen is also found in the lungs
Lung involvement more common in young
men  Goodpasture’s dz
Nephritic dz- Anti GBM




Can rapidly progress to widespread crescent
formation
Most common cause of death is pulmonary
hemorrhage in early disease
Pathology shows focal segmental
glomerulonephritis  diffuse proliferative GN
with extensive crescent formation
Immunofluorescence shows linear ribbon-like
deposition of IgG along the GBM
http://jeffline.tju.edu/Education/dl/NU570/cases/images/CASE8B-1.JPG
http://pathmicro.med.sc.edu/ghaffar/goodpasture.jpg
Nephritic dz- Pauci immune GN




Incidence of 2/100,000 per year
Peak in 60s with ♂=♀
Constitutional sx: lethargy, malaise,
anorexia, weight loss, fever, arthralgias,
and myalgias
ANCA+, normal C3C4, ↑ESR, leukocytosis,
NCNC anemia,
Nephritic dz- Pauci immune GN

Wegener’s granulomatosis





Small vessel vasculitis
Smoldering GN to RPGN in 77% of pts
Dominated by respiratory manifestations
such as sinusitis, nasal cartilage collapse,
cavitating lung lesions
Serology + for c-ANCA
Bx: focal progreesing to diffuse proliferative
GN, granulomas are rarely seen on kidney bx
Nephritic dz- Pauci immune GN

Microscopic polyangiitis





Mean age of onset 57 yrs men>women
Also a small vessel vasculitis
Systemic dz involving lungs, GI and skin
vasculitis
GN in 79% of pts
Immunofluroescence in both wegener’sand
microscopic polyangiitis shows paucity of
immune deposits
Immune complex GN

GN associated with a variety of infections




Poststreptoccoccal GN
Endocarditis
HCV
HBV
Poststreptoccoccal GN




Most commonly in children 2-6 years old
Caused by infxn with nephritogenic strains
of group A strep
Occurs about 2 weeks days after
pharyngitis or impetigo
Pts present with oliguric ARF
Poststreptoccoccal GN





Low C3, normal C4
>90% of pts have Abs to streptococcal
antigens such antistreptolysin O (ASO)
Renal lesion is typically a diffuse
proliferative GN
Immunofluorescence typically show a
granular pattern
Crescents are uncommon
http://www.med.niigata-u.ac.jp/npa/Lectures/Images/Slides/PSGN/2PSAGN_L.gif
http://cnserver0.nkf.med.ualberta.ca/cn/Schrier/Vol2/f3442-2.jpg
Lupus nephritis




40 to 85% of pts with SLE have renal
involvement
Mild urinary findings to CRF with nephritic
or nephrotic syndrome
ANA found in 95-99% of SLE pt though
nonspecific
Anti ds DNA is highly specific for SLE,
titers correlate with level of lupus nephritis
Lupus nephritis

5 classes of renal lesions in SLE






Class
Class
Class
Class
Class
I normal kidney
Do not present with
II mesangial proliferation acute nephritis
III focal prolifertive GN
IV diffuse proliferative GN
V membranous nephropathy
Correlation between clinical features and
dz activity is poor, bx is important in
guiding tx
GN- Nephritic









IGA nephropathy
Hematuria. Most common
1/3 synpharyngitic
1/3 proteinuria
1/3 progress to ESRD
HSP
Cresentic IGA
Ace plus arb, steroid
Secondary: HSP, chronic liver dz, HIV
GN- Nephritic
RPGN- 3 types
1. Ab mediated against basement
membrane. Anti GBM dz
2. Ag-Ab complex deposit in the GBM: SLE,
HepC, post strep, post infectious,
endocarditis associated, IGA
3. Pauci immune: Wegner’s, Microscopic
polyangiitis, Churg strauss
Acute Glomerulonephritis





Proteinuria and hematuria. Quantify the
proteinuria.
Acitve urinary sediment with dysmorphic
red blood cells or rbc casts.
Low complements in SLE, MPGN, post
strep or endocarditis or infections.
ANCA and Anti GBM titers.
ANA
SLE




Active serologies: low complements, pos
ana, anti double stranded DNA
Proteinuria and Hematuria
Must bx
Treat class 3,4 (maybe5) with cytoxan/
pred vs mycophenolate.
Pulmonary Renal syndrome






CHurg strauss
Wegner’s- anti proteinase 3
Goodpatures- anti gbm ab.
MPA- anti myeloperoxidase
SLE
cryoglobulinemia
Renal Replacement Modalities




IHD
PD
CRRT
Transplant