Kidney Injury, Acute Kidney Disease, Drug Induced KD, Acids/Bases

Intact Nephron Hypothesis says our kidneys have a lot of reserve nephrons that can … until …

compensate for diseased nephrons to give the appearance of normal renal function until critical threshold of nephron loss occurs, then remaining nephrons can no longer compensate and clinical manifestations of CKD start appearing

Glomerulonephritis is caused acutely by … and chronically by …

autoimmune disease (lupus), infection, drugs — systemic disease (inflammation, HTN)

the initial filter of the glomerulus membrane is the

endothelial fenestrations

the basement membrane of the glomerulus membrane is a

dense layer preventing passage of large molecules

endothelial podocytes of the glomerulus membrane are 

negatively charged to repel other negatively charged molecules (proteins)

Two main mechanisms of glomerular injury are

immune infiltration of PMN leukocytes and immune complex deposition in basement membrane

Those two processes result in …. ultimately leading to a ….

foot process malformation and mesangial cell hyperplasia, leaky filter

…. is a hallmark of Glomerulonephritis

proteinuria

Nephrotic syndrome of GN:

proteinuria >3.5g/day, edema, non inflammatory, podocyte injury, hypercoag. + hyperlipid., hypoproteinemia

Nephritic syndrome of GN:

hematuria + pyuria, dec GFR, inflammation in glomerular capillaries, endothelial cell injury, granular casts in urine

Acute tubular necrosis (ATN) is the most common…

form of AKI in hospitals

Acute tubular necrosis is characterized by …. leading to …

sloughing of renal tubule cells leading to obstruction

Acute tubular necrosis is caused by

prolonged ischemia

which parts of the kidney are at highest risk of ATN? Why?

proximal tubule and ascending loop of Henle, high metabolic demand but low oxygen supply = ischemia that depletes ATP stores

ATN presents as … (7)

inc SCr and BUN, dec GFR and urination, “muddy brown casts”, acidosis, hyperkalemia, hypomag, FeNa >1%

Autophagy’s role in kidney injury is 

minimize irreversible damage but permanent damage is still possible if significant necrosis occurs

Heme Pigment Nephropathy is caused by

rhabdomyolysis dumping myoglobin in blood which gets filtered by the kidneys and precipitates, leading to obstruction and AKI

Heme Pigment Nephropathy is treated with

high doses of NS or sodium bicarb to dissolve myoglobin 

Tubulointerstitial nephritis or AIN is characterized by

inflammation of the interstitium

AIN is a

Type 4 hypersensitivity reaction usually caused by drugs

AIN has a triad of common symptoms, but its uncommon to present with all 3, they are: 

fever, rash, eosinophilia (WBC cast in urine)

the Gold Standard for Acute Interstitial Nephritis diagnosis is

renal biopsy

vasculitis is

immune mediated inflammation of blood vessels in kidneys

vasculitis is associated with

AIN and systemic vasculitis conditions (Wegner’s)

complications of AKI: (5)

edema, hyperkalemia, acidosis, uremia, CKD and CV disease risk

the role of RAAS is to

increase perfusion to kidneys

when the juxtaglomerular apparatus in the kidneys sense decreased perfusion, they release… which activates … from the liver

renin, angiotensinogen 

Angiotensinogen gets activated into Angiotensin I which is then activated by … from lungs/kidney endothelium into ….

ACE, Angiotensin II

Angiotensin II has a role in… (7)

sympathetic activity, tubular Na+Cl reabsorption, K excretion, water retention, aldosterone secretion, vasoconstriction, ADH release

Overactivation of RAAS leads to

hypervolemia, HTN which turns to AKI

pre-renal AKI is affected by

dec kidney perfusion or circulating volume

pre-renal AKI causative disease states

dehydration, hypovolemia, HF

pre-renal AKI affects the

afferent and efferent arterioles

post-renal AKI is affected by

ureter and urethra blockages

post-renal AKI disease states

BPH, nephrolithiasis, malignancy

prolonged kidney stone obstruction can lead to

hydronephrosis, fluid backup into kidneys

intrinsic AKI is affected by

glomerular injury, tubular obstruction, vessels around tubules

intrinsic AKI disease states

GN, AIN, ATN, vasculitis

ischemic ATN develops when

severe hypoxia overwhelms tubuloglomerular feedback

tubuloglomerular feedback prevents kidney damage by

constricting the afferent arterioles to reduce Na loss and decrease oxygen demand

ischemic ATN is improved by (6)

dec tubular transport, dec GFR, prostaglandin E2, adenosine, bradykinin, nitric oxide

ischemic ATN is worsened by (5)

nephrotoxic meds, NSAIDs, Angiotensin II, calcium, myoglobin

risk factors of drug-induced KD

elderly, nephrotoxins, HF, cirrhosis, diabetes mellitus, HTN

maintain adequate kidney perfusion in pts at risk of AKI by using

IV isotonic crystalloids

drugs that cause hemodynamic mediated injury 

afferent constriction: NSAIDs + Calcineurin Inhibs

efferent dilation: ACEi/ARBs

drugs that cause pre renal injury

dec perfusion to kidney: diuretics

Pre-Renal/ Hemodynamic mediated injury can be prevented by

good fluid intake  and avoiding nephrotoxins

in high risk patients, you should

give lowest dose of drugs that affect hemodynamics, hold diuretics

in pts with CKD, HF, cirrhosis, you should

avoid NSAIDs + ACEi/ARB combo

Pre-Renal/ Hemodynamic mediated injury Treatment

d/c offending, give IV fluids

drugs that cause Intrinsic Renal Injury - GN, AIN, vasculitis, ATN

GN - allopurinol

AIN - penicillins, NSAIDs, sulfas, beta lactams

vasculitis - propylthiouracil, allopurinol, phenytoin, levamisole

ATN - aminoglycosides, amphotericin B, IV contrast media

Aminoglycosides utilizes …. which improves efficacy by giving one high dose a day and …

extended interval dosing, minimizes troughs and nephrotoxicity

Intrinsic Renal Injury - AIN treatment

stop offending, supportive care, aggressive steroids

IV contrast media will cause Contrast Induced Neuropathy, its risk factors are

large dose, high osmolal or ionic contrast media and short interval between doses

CIN prevention 

saline hydration, N-acetylcysteine, using low or iso-osmolal non-ionic contrast media - Iohexol and Iodixamol

Iohexol is non-ionic, 

low osmolal and low kidney injury risk

Iodixamol is non-ionic,

iso-osmolal, for patients with REALLY high risk of AKI

post-renal AKI (nephrolithiasis) can be prevented by

HYDRATING, manage risk factors (calcium + uric acid)

post-renal AKI (nephrolithiasis) is treated with

hydration to induce diuresis, pain management, Lithotripsy (disintegrates the stone)

Intra-Tubular obstruction (Rhabdomyolysis) is induced by which drugs? and can be prevented by?

statins, avoiding statin DDIs

Intra-Tubular obstruction (Rhabdomyolysis) is managed by

d/c offending, aggressive fluid administration, urinary alkalinization

how is urinary alkalinization done?

if urine pH <6.5, alternate NaCl and sodium bicarb IV

Lithium Induced CKD risk is increased by

diabetes insipidus, distal tube acidosis, chronic interstitial nephritis

Lithium Induced CKD is caused by

CUMULATIVE lithium exposure

Lithium Induced CKD can be prevented by

monitoring lithium, avoiding DDIs w/ HCTZ

Lithium Induced CKD is treated by

discontinuing lithium, Amiloride for symptoms only, hydration

Vancomycin associated AKI can be prevented by 

avoiding trough >15-20 mg/L and AUC >600

acids are

proton donors

bases are

proton acceptors

PaCO2 is the

amount of CO2 in blood

PaO2 is the

amount of O2 in blood

HCO3 is

bicarb

SaO2 is

oxygen saturation

Arterial Blood Gas values

pH        7.4

PCO2  40 mmHg

PO2     90 mmHg

HCO3   24 mEq/L

SaO2    95%

Anion Gap (mEq/L) =

Na - [Cl + HCO3]

normal anion gap value is

8-12 mEq/L

if high anion gap, it usually means theres a lot of

acids

acids in body are regulated via the lungs through …. and kidneys through ….

respiration in minutes, bicarb-carbonic acid system in days

the bicarb-carbonic acid system is regulated by

carbonic anhydrase, glomerular filtration of organic acids, secretion of titratable acids

in an ACIDIC env, the oxyhemoglobin curve shifts

to the right, hemoglobin has lower binding affinity to oxygen

in a BASIC env, the oxyhemoglobin curve shifts

to the left, binding affinity is too high

both shifts will result in

tissue hypoxia

 metabolic acidosis is caused by (3)

loss of bicarb (diarrhea), acidosis, accumulation of endogenous acids (renal failure)

metabolic acidosis is corrected by the lungs by

increasing ventilation, full correction in 12-24 hours

metabolic acidosis is corrected by the kidneys by

excreting titratable acids and generating more bicarb, takes days

metabolic acidosis presents as

tachypnea, arrhythmia, tachycardia, hyperkalemia

chronic metabolic acidosis causes

osteroporosis

metabolic acidosis emergent treatment needed if …. and is treated using,,,,

HCO3 <10 mEq/L or pH <7.2, IV sodium bicarb with potassium supp

chronic treatment of metabolic acidosis uses

oral sodium bicarb, correct underlying

Bicarb Deficit (mEq) =

0.5 L/kg x (bicarb desired - measured)

administering full bicarb deficit can cause

hypervolemia

IV bicarb is available in 1 mEq/mL in 50 mL ampoules and 150 mEq/1000mL D5W, which are used for …

ampoules - rapid correction, lots of fluid shifts

D5W - slower correction, large volume

oral bicarb AEs: 

GI, belching, flatulence

IV bicarb AEs:

edema, high sodium, low potassium, calciuresis, kidney stones, paradoxical intracellular/tissue acidemia, dec cardiac contractility

Sodium bicarb can also be used in patients with

salicylate poisoning

alternative alkali therapies: (2)

sodium acetate IV, only if functioning liver

citrate (PO)

chloride responsive metabolic alkalosis is caused by

vomiting, NG suction, excessive diuretic use

urine chloride <10 mEq/L

chloride responsive metabolic alkalosis is treated with

NS IV, consider Acetazolamide for patients who cannot tolerate fluid

chloride resistant metabolic alkalosis is caused by

excess MR activity: hyperaldosteronism, Cushing’s

urine chloride >20 mEq/L

Lungs will compensate for metabolic alkalosis by

decreasing ventilation within hours