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Acute Kidney Injury (AKI) – Terra Swanson

Background:

  • Definition based on 2012 KDIGO Guidelines: 
  • Rise in serum creatinine (sCr) > 0.3 mg/dL within 48 hours, or increase > 1.5 x baseline in 7 days  

  • Urine volume \<0.5 cc/Kg/H for at least 6 H

Framework for AKI 

  • Pre-renal/hemodynamic AKI:  
  • Volume depletion: GI losses, hemorrhage, burns, critical illness increased insensible losses 

  • Decreased effective circulating volume: cardiorenal, hepatorenal, hemodynamic effects of ACEi/ARB 

  • Afferent arteriole constriction [NSAIDs, Iodinated contrast] 

  • Renal vein thrombus 

  • Intra-renal: Glomerular, tubular, or interstitial diseases
  • ATN = Most common form of intrinsic AKI. Can be Ischemic or toxic

    • Toxins can be broken down further into endogenous (e.g. rhabdo) and exogenous (e.g. drugs)
  • Acute Interstitial Nephritis (AIN): Usually drug induced (NSAIDs, PPIs, beta lactam abx)  

  • Glomerulonephritis

  • Other causes:  

    • Crystalline nephropathy: IV acyclovir, tumor lysis, ethylene glycol 

    • Small vessel disease: MAHA, TTP, HUS

    • Large vessel disease: Aortic dissection, renal artery stenosis  

  • Post-renal: Can occur at any level of the GU system 
  • Ureteral: stones, external compression (malignancy, LAD, abscess) 

  • Bladder: neurogenic bladder, malignancy, obstructing blood clot 

  • Urethra: BPH, prostate cancer, prostatitis  

  • Pre-renal azotemia and acute tubular necrosis comprise the majority of inpatient acute kidney injuries

Evaluation 

  • History and volume exam

  • Labs: CMP, urinalysis, protein/Cr ratio

  • 500cc-1L IV fluid challenge: If sCr improves to baseline in \<48H then the insult was likely pre-renal. If not, then look for other etiologies

  • Evaluate for obstruction: I/O cath, Foley, Post Void Residual >250 cc

  • Who needs a renal ultrasound? 

  • No obvious cause of AKI

  • Abrupt oliguria or anuria (think renal vein thrombus or obstruction)

  • High suspicion for bladder outlet obstruction (PVRs might give you same data) 

  • Add doppler to evaluate for renal artery stenosis (or if working up resistant hypertension) 

  • Urine Electrolytes 
  • FENa \<1% or FEUrea \<33% (if on diuretics) suggest pre-renal physiology

    • Caveat, only validated in oliguric patients and more difficult to interpret after fluids, diuretics, etc

    • Not needed in the initial work-up of all patients with AKI. If high suspicion for pre-renal etiology, trial fluid challenge and assess response first

  • Urine sodium can be used to assess Na avidity: UNa > 40 suggests ATN and UNa \< 20 suggests pre-renal

Management

  • All causes
  • Minimize fluctuations in blood pressure

  • Consider holding anti-hypertensive medications, especially ACEi/ARB (remember to determine plan to resume at/after discharge)

  • Avoid unnecessary nephrotoxins

  • Dose-adjust medications for changing renal function

  • Pre-Renal
  • True volume depletion- Intravenous volume expansion

  • Cardiorenal syndrome- Decongestion/diuresis

  • Hepatorenal syndrome- See Hepatology section for more information

  • Post-renal
  • Relieve Obstruction: I/O cath, foley, Urostomy (Urology), percutaneous nephrostomy (IR)

  • Monitor for post-obstructive diuresis

  • Intra-renal
  • ATN- supportive care, monitor for post-ATN diuresis. If delayed recovery, may need outpatient dialysis

  • Glomerulonephritis- Consult AKI service for assistance with biopsy and selecting immunosuppressive agents if needed

  • AIN- Review meds, consult nephrology for possible biopsy and recommendations for steroids

  • Monitor for renal recovery 
  • Suspect concomitant ATN if sCr declines with volume expansion, diuresis, or relief of obstruction but remains a few points above baseline
  • When to consult Nephrology
  • Urgent indication for dialysis (see “Renal Replacement Therapy”)

  • Abrupt anuria

  • Cr worsening or urine output inadequate w/o clear cause

  • Need for kidney biopsy  

Additional Information 

  • Rhabdomyolysis: UA positive for blood but no RBCs on microscopy
  • Toxic damage due to myoglobin

  • Serologic markers of muscle injury: elevated CK, AST>AST with normal ALK Phos 

  • Fluids adjusted to urine output goal of 200-300 mL/hr until CK declines

    • Consider isotonic bicarb for initial 1-2L of IVF urine alkalinization to reduce precipitation
  • Avoid calcium repletion for hypocalcemia unless symptomatic 

  • Post-obstructive diuresis 
  • Necessary process to clear accumulated uremic toxins

  • Replace ~50% of urine output to prevent pre-renal azotemia

  • Monitor calcium, phosphorus, and magnesium in severe post-obstructive diuresis

Contrast Induced AKI (CI-AKI) – Trey Richardson

Background

  • When someone develops an AKI do your due diligence and evaluate for the usual causes of AKI, regardless of when they were given contrast

  • Mechanism of injury: direct toxic effect leading to tubular necrosis and arteriolar vasoconstriction leading to medullary ischemia

KDIGO Criteria for CI-AKI:

  • sCr increase by 0.5mg/dl or 25% increase in sCr from baseline 48 H after radiologic procedure where intravenous contrast was administered

Who is at risk for CI-AKI?

  • Normal kidney function: incidence of CI-AKI is 1-3%

  • Pre-existing CKD: Incidence of CI-AKI may be as high as 20% in patients with CKD 4-5

  • Other risk factors include: diabetes, heart failure, and advanced age

  • No real sCr or eGFR threshold below which iodinated contrast is contraindicated, especially in patients for whom imaging will alter management (e.g. acute stroke, PE, STEMI)

Risk reduction strategies

  • Volume expansion with isotonic crystalloid (PRESERVE Trial) in patients with AKI or eGFR \<30 ml/min/1.73m^2 who are clinically hypo or euvolemic
  • 1cc/kg/hr for 6-12 hours before/during and 6-12 hours after the procedure in patients at high risk for CI-AKI. This rate can be decreased based on the risk for hypervolemia
  • If the patient is volume overloaded, they probably should not receive volume expansion prior to a contrasted study

  • Never delay a necessary procedure out of concern for worsening renal function. If in doubt, talk to nephrology

Iodinated contrast in CKD-5/ESRD patients

  • Iodinated contrast does not need to be dialyzed immediately

  • Avoid giving if you are trying to preserve residual kidney function in ESRD on PD

Gadolinium contrast for MRI

  • Contraindicated in any AKI or if GFR \<30 in CKD given risk of nephrogenic systemic fibrosis.

Approach to Chronic Kidney Disease – Terra Swanson

Definition of CKD

  • Decreased kidney function or one or more markers of kidney damage for 3 or more months

  • History of kidney transplant

  • GFR \< 60; Staging helps risk-stratify pts likely to progress or develop complications of CKD

  • CKD IIIa: eGFR 45-60

  • CKD IIIb: eGFR 30-44

  • CKD IV: eGFR 15-30

  • CKD V: eGFR \< 15

  • Markers of kidney damage
  • Albumin/Cr ratio

    • Mild: 0-30 mg/g

    • Moderate: 30-300 mg/g

    • Severe: >300 mg/g

  • Urine sediment: RBC casts, WBC casts, oval fat bodies or fatty casts, granular casts

  • Electrolyte derangements

  • Abnormalities on histology

  • Structural abnormalities: (cysts, hydronephrosis, scarring, masses, renal artery stenosis)

When to refer to nephrology clinic

  • eGFR \< 45

  • Persistent urine albumin/creatinine ratio > 300 mg/g

  • Urine protein/creatinine ratio greater than 500 mg/g

  • Rapid loss of kidney function (> 30% decline over 4 months)

  • Hematuria not 2/2 urologic condition or if there are RBC casts on UA

  • Inability to identify presumed cause of renal dysfunction

  • Difficult to manage complications (hyperkalemia, anemia, bone-mineral disease, HTN)

  • Confirmed or presumed hereditary kidney disease (PCKD suspected)

Complications of CKD

Imbalance of water homeostasis

  • As renal mass declines the ability to both concentrate and dilute the urine is impaired

  • This manifests as hyponatremia (no end-organ to respond to ADH) and edema

  • Treat this with water restriction, diuretics or, eventually, ultrafiltration

Metabolic acidosis

  • Correcting serum bicarbonate to a goal of 23-30 meq/L slows decline in renal function and protects against bone-mineral complications of chronic metabolic acidosis

  • Can calculate bicarbonate deficit to estimate dose of bicarbonate

  • If bicarb \< 22, consider:

  • Sodium bicarb 650 mg TID (8mEq bicarb per 650mg tablet) up to 5850mg/day (70 mEq or 3 tabs TID)

  • Sodium citrate (Bicitra): 1mL = 1 mEq * Careful in cirrhosis since citrate cannot be metabolized

  • Baking soda (sodium bicarbonate): 1 teaspoon = 59 mEq HCO3 (careful of Na load)

HTN in CKD

  • Goal BP \< 120/80 (Class 2B recommendation) based on SPRINT trial, ACC/AHA 2017, and KDIGO 2021 guidelines

  • All comers: Diet (e.g. DASH) and lifestyle modifications

  • CKD without albuminuria or DM:

  • Start pharmacotherapy based on ASCVD risk as well as risk for other target organ damage
  • CKD with moderate to severe albuminuria w/ or w/out DM
  • ACEi or ARB titrated to maximally tolerated dose (Class 1B recommendation)

  • Thiazide-like diuretics (see CLICK trial for chlorthalidone in advanced CKD)

  • Loop diuretics can assist with volume driven HTN in patients with CKD 4-5

  • HTN in kidney transplant
  • CCBs or ARBs are first line (Class 1C recommendation)
  • Consider stopping ACE-i/ARB if:
  • GFR declines >30% over 4 months. Consider evaluation for renal artery stenosis

  • K > 5.5 despite low K diet, optimizing dose of diuretics, or adding K-binders

Anemia in CKD

  • Multifactorial: decreased EPO production, impaired iron absorption, uremic toxins suppressing bone marrow, loss of blood in dialysis circuit, and from GI AVMs

  • Indications for iron supplementation in non-dialysis patients:

  • ALL patients with TSAT \<20% and ferritin \<100 ng/mL

  • Patients with Hb \<13 and TSAT \<30% and ferritin \<500 ng/mL

    • Can start with PO supplementation (see Anemia section). Reassess iron levels in 1-3 mos; if not appropriately ↑, consider IV iron repletion
  • Dialysis patients:
  • IV Iron preferred method of repletion for HD patients with

    • TSAT \< 20% and ferritin \< 200

    • TSAT \<30% and ferritin \<500 AND with Hb \< 10 OR are on EPO

  • Dosing: usually administered at HD sessions

    • 125 mg ferric gluconate at consecutive HD sessions x 8 doses

    • 100 mg iron sucrose at consecutive HD sessions x 10 doses

    • Ferumoxytol 510mg at the end of two HD sessions 1-4 weeks apart

  • Indications for EPO

    • Pts w/ Hb \<10 who are not iron deficient (ferritin >500) or who’s anemia persists despite adequate iron repletion

Hyperkalemia (Goal K \< 5.5)

  • Patients with diabetic nephropathy (T4 RTA) and CKD 5-ESRD are at the highest risk

  • Strategies to mitigate hyperK

  • Low K diet (\< 40-70 mEq/day or 1500-2700 mg/day)

  • Loop diuretics

  • GI cation exchangers

    • Patiromer (Veltassa): binds K in colon in exchange for calcium

    • Sodium zirconium cyclosilicate (Lokelma): binds K throughout intestine in exchange for sodium and H+

    • Do not use Kayexelate as chronic therapy

  • Treat metabolic acidosis

Mineral bone disease in ESRD

  • Avoid calcium supplementation in mild or asymptomatic hypocalcemia

  • Replace vitamin D to >20 (weak evidence)

  • Phos goal \< 5.5

  • Sevelamer: use lowest dose effective to achieve Phos \< 5.5

    • Phos 5.5-7.5: initial dose 800 TID with meals

    • Phos 7.5-9.0: initial dose 1200-1600 TID with meals

    • Phos > 9: initial dose 1600 TID

    • Can titrate dosing by 400 to 800 mg per meal at 2-week intervals

  • Restrict dietary phos to 900 mg/day

  • PTH goal in CKD3: 2x ULN

  • PTH Goal in ESRD: 2-10x ULN

Diabetes in CKD

  • Individualize A1C goals. Both the ADA and VA-DOD have guidelines for selecting A1C targets

  • Treatment:

  • Metformin remains first-line but should be dose-reduced based on eGFR

    • eGFR > 45: Maximum daily dose of 2000mg/day (1000mg bid)

    • eGFR \< 45: Reduce max daily dose to 1000mg/day (500mg bid)

    • eGFR \< 30: Discontinue if high risk for volume mediated AKI/chronically ill

  • SGLT-2 inhibitors for patients with eGFR > 30 reduces progression to ESRD and death from renal or cardiovascular causes (Evidence: DAPA-CKD, CREEDENCE)

  • Finerenone (non-steroidal MRA)- would ask nephrology for help if considering this option since relatively new and increased risk for hyperkalemia. (Evidence: FIDELIO)

Dialysis initiation

  • Early (CKD3a or 3b) referral to nephrology has better outcomes

  • Uremic symptoms: fatigue, sleep disturbance, N/V, decreased appetite, dysgeusia, itching, hiccupping

  • Refractory hyper K

  • Refractory hypertension

  • Plot your patient’s eGFR using the graph function in EPIC or CPRS to determine trajectory (normal age-related decline after age 60 is ~ 1ml/min/m2)

Renal Replacement Therapy (RRT) Basics – Daniel Motta

Background/Terminology

  • Dialysis (diffusive clearance)- solutes diffuse down concentration gradients through a semipermeable membrane separating blood and dialysate

  • Dialysate (dialysis bath)- electrolyte solution used to create concentration gradient for dialysis. Customizable to treat specific electrolyte and acid-base derangements

  • Effluent- Fluid removed during dialysis or ultrafiltration

  • Ultrafiltration- Hydrostatic pressure “pushing” water through a membrane. There is no dialysate solution used during ultrafiltration. Solutes are removed through the process of solvent drag. The effluent in this case is isotonic to plasma

  • Total ultrafiltration (UF) - overall ultrafiltration volume produced during treatment

  • UF net - net ultrafiltrate volume removed from the patient by the machine. The overall volume can be completely replaced (net even), partially replaced, or not replaced at all. UF net is the difference between UF and the volume replaced in the circuit

  • Timing of dialysis- There are several studies in this space (IDEAL, IDEAL-ICU, AKIKI, STARRT, ELAINE). In both the outpatient and the inpatient setting, there is no compelling evidence that early start dialysis improves mortality compared to later starts

Outpatient Modalities

  • Intermittent hemodialysis (iHD)

  • In home hemodialysis

  • Peritoneal dialysis

If someone with ESRD is admitted:

  • Urgent ESRD consult if acute need, otherwise can consult them routinely

  • Routine orders include MWF phos checks and a renal diet

  • For peritoneal dialysis pts, their diet can be more liberal and include low phos only or even regular diet (Can just ask what diet he/she follows at home)

Acute Setting

  • Indications: AKI leading to life-threatening changes in fluid, electrolyte, and acid-base balance or toxic ingestion [AEIOU]
  • Acidosis: Severe metabolic acidosis (serum pH\<7.1) refractory to correcting volume status or other electrolyte derangements

  • Electrolytes: Severe hyperkalemia >6.5 despite medical management (e.g. loop diuretics, IV fluids, GI cation exchangers, correcting acidemia, etc.)

  • Intoxication: Dialyzable toxins and medications

    • Alcohols: ethylene glycol, methanol, isopropyl alcohol, diethylene glycol, and propylene glycol

    • Medications: lithium, salicylates, valproic acid, phenytoin, barbiturates, carbamazepine, vancomycin, aminoglycosides, etc.

  • Overload: Severe fluid overload (e.g., pulmonary edema) refractory to diuretics

  • Uremia: Uremic complications: encephalopathy, pericarditis, platelet dysfunction

  • Can perform furosemide stress test to help predict who is likely to recover their kidney function
  • If Lasix naïve, administer 1mg/kg as a bolus. If on a loop diuretic, administer 1.5 mg/kg as a bolus

  • If within the hour they have made 200 cc of urine, then they are likely to regain kidney function

  • Modalities
  • iHD: Ideal for removal of toxins (e.g. alcohols, dialyzable meds). Use with caution in hypotensive patients

  • CRRT: Set a rate of volume removal (typically 0-200 cc/hr) less rapid fluid/electrolytes shifts better tolerated in patients with hemodynamic instability

    • Anti-coagulation options- to prevent clotting of circuit

      • None

      • Heparin (preferred). Can be either within the circuit or systemic if indicated for another reason (e.g. DVT/PE).

      • Citrate (need to monitor calcium frequently)

    • Complications of CRRT: Infections, hypophosphatemia

  • Access
  • Dialysis catheter (aka: Vascath)

    • Non-tunneled catheter (Trialysis) used for acute dialysis

    • Different lengths depending on site (see procedures section)

  • Tunneled dialysis catheter (ex: Permcath)

    • Typically used as a bridge to fistula/graft placement

    • Placed by IR

Peritoneal Dialysis Peritonitis

Background

  • Typically occurs due to contamination with pathogenic skin bacteria during exchanges or due to exit-site/tunnel infection

  • Usually presents with cloudy effluent fluid and abdominal pain. Can also be asymptomatic

  • Important history to obtain: recent contamination, accidental disconnection, endoscopic or gynecologic procedure, as well as the presence of constipation or diarrhea

  • Definitive diagnosis requires 2 of the following:

  • Clinical features consistent with peritonitis

  • Positive dialysis effluent culture

  • Dialysis effluent with WBC > 100 with PMN > 50%

    • Even if WBC count \< 100, presence of > 50% PMNs is still strong evidence of peritonitis in pts with rapid cycle PD

Evaluation

  • Examine catheter exit site

  • Culture peritoneal fluid (requires specific technique, done by nephrology)

  • Peritoneal cell count with diff, gram stain and culture

  • Obtain peripheral blood cultures if there is concern for sepsis

Management

  • All PD orders, intraperitoneal antibiotics, and prescription adjustments should be directed by ESRD consult service (page them overnight if concerns)

  • Treatment with intraperitoneal antibiotics should be started immediately after specimens have been obtained if there is high clinical suspicion

  • Empiric antibiotics regimen should cover both gram-positive and gram-negative organisms, typically with vancomycin and third generation Cephalosporin

  • Systemic antibiotics are generally not necessary unless pts have systemic signs of sepsis

  • Pts with relapsing, recurrent or repeat peritonitis will likely need catheter removal

Secondary prevention

  • Treatment with intraperitoneal OR IV antibiotics (for any infection requiring > 1 dose of antibiotics) requires prophylaxis for fungal peritonitis with either:
  • Nystatin 400,000 to 500,000 units orally TID

  • Fluconazole 200 mg every other day or 100 mg qdaily

  • Dialysate should be drained the day of endoscopies or gynecological procedures

Intravenous Fluids – Chandler Montgomery

Indications for intravenous fluid

  • Restoration or maintenance of tissue perfusion

  • Correction of electrolyte abnormalities

  • Nutritional supplementation in those without reliable enteric access

Categorized into crystalloids and colloids

  • Crystalloid = water + electrolytes

  • Colloid = water + proteins/large molecules

Terms

  • Osmolarity: osmoles of solute per L of solution

  • Tonicity: ability to induce movement of water across a membrane

  • Buffer: anions such as lactate, acetate, gluconate which are metabolized to bicarbonate in vivo with the goal of sustaining normal plasma pH

Crystalloids

  • Isotonic fluids used for volume resuscitation
  • After ~ 30 mins, redistribute such that only 25% remains w/in intravascular space
  • Balanced solutions (ex: Lactated Ringer’s, Plasma-Lyte)= have electrolytes concentrations similar to plasma
  • NS may lead to renal vasoconstriction, AKI, hemodynamic instability, increased mortality

    • SMART and SALT-ED: balanced solutions had lower rates of death, new renal replacement therapy, or persistent renal dysfunction compared to NS
  • Situations where NS may be preferred:

    • Cerebral edema/traumatic brain injury

    • Hypovolemic hyponatremia

    • Pre-existing hypochloremic metabolic alkalosis (e.g. after vomiting or over diuresis)

  • Notes on LR

    • The small amount of K in LR (~4 mEq/L) is unlikely to significantly exacerbate hyperkalemia

    • Lactate in LR is sodium lactate. No hydrogen ions are being added to plasma

Common crystalloid solutions:

Fluid Na Cl K Ca Mg Glucose Buffer Osmolarity Tonicity
Plasma ~140 ~100 ~4 ~2.4 1.0 ~0.85 Bicarb ~24 ~290 NA
Normal 0.9% saline 154 154 0 0 0 0 0 308 Isotonic
Lactated Ringer’s 130 109 4.0 2.7 0 0 Lactate 28 273 Isotonic

Plasma-Lyte/

Normosol

140 98 5.0 0 3.0 0

Gluconate 23

Acetate 27

295 Isotonic
D5W + 150 mEq HCO3- 150 0 0 0 0 50 Bicarb 150 300 Isotonic
3% Saline 513 513 0 0 0 0 0 1026 Hypertonic
D5W 0 0 0 0 0 50 0 252 Hypotonic

Colloids

  • Albumin: extracted from human plasma
  • 5% - Used after plasma exchange

  • 25% - raises oncotic pressure and restore intravascular volume

    • Uses: Post-LVP, diagnosis and treatment of hepatorenal syndrome, SBP (see Hepatology)

    • Evidence base for use outside of above indications is poor (SAFE trial)

  • Blood Products: Packed RBCs, FFP, cryoprecipitate, etc

Acid-Base – Ned Hardison and Trey Richardson

Background

  • Abnormal serum H+ concentrations lead to impaired cellular function (cardiac arrest, vasodilation, decreased response to catecholamines), electrolyte abnormalities (e.g. hypo- and hyperkalemia, hypo- and hypercalcemia), impaired glucose metabolism, impaired drug metabolism, and a whole host of other complications that translate to increased morbidity and mortality

  • ABG/VBG reference ranges:

  • pH = 7.36-7.44 (~7.32-7.40)

  • PCO2 = 36-44 mmHg

  • pO2: 60-100 mmHg

  • HCO3 = 22-26 mEq/L

  • Useful formulas
  • pH on ABG = VBG pH + 0.035

  • Anion Gap= Na-(Cl+Bicarb)

  • Normal Anion Gap= 12-14

  • Calculated Osmolarity= 2[Na]+ ([Glucose]/18) + ([BUN]/2.8)

  • Osmolar gap= Measured osmolarity – Calculated osmolarity

  • Winter’s formula for respiratory compensation for AGMA: expected pCO2 = 1.5 (serum bicarb) +8 ± 2

    • Shortcut: Expected p**C**O2 ≈ l**a**s**t t**w**o d**i**g**i**t**s o**f p**H

General Approach to Acid-Base Derangements

  • Step 1: Determine if the patient is acidemic or alkalemic (look at the pH)

  • Step 2: Determine the primary disorder (metabolic or respiratory)

  • Step 3: Calculate anion gap (see section below)

  • Step 4: Is there appropriate compensation?

  • Step 5: Evaluate for secondary disorders

Anion Gap Metabolic Acidosis

Background

  • Na+ is the predominant cation in normal plasma. Cl- and HCO3- are the predominant anions. There are anions that are not directly measured (e.g. most binding globulins, immunoglobulins, clotting factors, and other proteins). These unmeasured anions are responsible for the normal anion gap of ~12 meq/L. When there are extra unmeasured anions within the plasma, the anion gap increases

Differential

  • GOLDMARK: Glycols, oxyproline (acetaminophen metabolite), L-lactate, D-lactate, methanol, ASA, renal failure/uremia, ketoacids

    Evaluate for secondary disorders

  • Corrected bicarbonate

  • Corrected H**C**O3 = patient’s H**C**O3 + (patient’s anion gap - 12)

    • Corrected H**C**O3 > 26, coexisting metabolic alkalosis,

    • Corrected HCO3 \<22 coexisting non-AG metabolic acidosis

Osmolar Gap

  • If there is an anion gap, it is worthwhile to always calculate an osmolar gap. You will be surprised the number of toxic ingestions you catch this way

Non-anion gap metabolic acidosis (NAGMA)

  • There are two places from which people can waste bicarbonate- the kidneys and the gut
  • The urine anion-gap, which corresponds to unmeasured urinary NH4+ (primary means of renal acid excretion), can differentiate between the two

  • Urine anion gap = Unmeasured cations (NH4+) – unmeasured anions = U­Na + UK – UCl

    • Positive value-> low NH4+-> renal losses

      • RTA

      • Carbonic anhydrase inhibition: acetazolamide, topiramate

      • Adrenal insufficiency

      • Normal saline infusion

    • Ne-GUT-ive value->high NH4+->kidneys working appropriately-> GI losses

      • Diarrhea

      • Pancreatic fistula

      • Ureterosigmoidostomy

  • Caveat: Proximal RTA has a normal distal urine acidification and has a negative urine AG

Managing Metabolic Acidosis

  • Lactic acidosis is the most common cause of anion gap metabolic acidosis that we encounter

  • In general, avoid use of bicarbonate to treat lactic acidosis

  • Remember: H+ + HCO3- \<-> H2CO3 \<-> H2O + CO2. While administering bicarbonate will transiently improve pH, carbonic acid will eventually form and ultimately worsen acidemia
  • In acute NAGMA, reasonable to give bicarbonate when bicarb \<12 or pH \<7.1-7.2
  • Pay close attention to other electrolyte levels, especially potassium as it shifts back into cells

Metabolic Alkalosis

Background

  • Metabolic alkalosis occurs as a primary disorder or as compensation for respiratory acidosis. A thorough history and exam can usually clarify which of these two scenarios is occurring

  • In order for metabolic alkalosis to occur, there has to be both an inciting phase (e.g. volume depletion) and a maintenance phase (e.g. hypochloremia or hypokalemia)

Presentation

  • Most symptoms of metabolic alkalosis (confusion, nausea, vomiting, tremors) occur as a result of other electrolyte abnormalities (hypocalcemia, hypokalemia)

  • Serum pH of >7.55 is likely the threshold where symptoms will develop

Causes

  • Saline responsive (e.g. hypochloremia)
  • True volume depletion

  • NG suction/Nausea/vomiting

  • Diuretic use

  • Saline refractory
  • Hypokalemia

  • Milk-Alkali syndrome

  • Mineralocorticoid excess states

  • Bartters Syndrome

  • Gitelman’s Syndrome

Treatment

  • Saline Responsive/Hypochloremia
  • If volume deplete, then normal saline is treatment of choice

  • If alkalosis develops in setting of diuresis, then make sure replacing KCl and consider acetazolamide

  • Saline refractory
  • Hypokalemia- replenish potassium stores

  • Hyperaldosteronism- covered in more detail in the endocrinology section

  • Bartter syndrome and Gitelman syndrome - replace electrolytes and refer to nephrology

Electrolytes

Hypercalcemia – Rebecca Choudhry and Trevor Stevens

Background

  • Total serum Calcium >10.5

  • Most (99%) Ca+2 is anhydrous and stored in bone. The remaining 1% is 60% bound (mostly to albumin), and 40% ionized and able to exert a physiologic effect

  • Remember, there is an inverse relationship between pH and Ca2+. As pH declines, serum Ca increases due to H+ binding to albumin and releasing Ca2+

  • Don’t forget to correct calcium level if hypoalbuminemia (or check ionized calcium level),

  • Corrected Ca2+ = ((Normal albumin – Patient’s albumin) x 0.8)) + Patient’s Ca2+

    • This equation Is less reliable at very low albumin

Presentation

  • Ca+2 > 12 can cause shortened QT interval, 2nd and 3rd degree heart block, ventricular arrhythmias, and ST elevations mimicking MI

  • Severe manifestations uncommon at Ca+2 \<14

  • “Stones, bones, thrones, belly groans, and psychiatric overtones”

  • Bone pain

  • Polydipsia/polyuria- due to nephrogenic DI

  • Nausea/constipation

  • Depressed mood/cognitive impairment

  • Decreased level of consciousness

Evaluation

  • Measure PTH
  • Normal or ↑ PTH

    • Primary hyperparathyroidism: ↑ Ca+2 and ↓ PO4-3

    • Tertiary hyperparathyroidism (autologous secretion of PTH in CKD/ESRD)

    • Familial hypercalciuric hypercalcemia (often asymptomatic, no treatment required).

    • Li toxicity

  • ↓ PTH

    • Humoral hypercalcemia of malignancy (PTHrP)

    • Malignancy (boney metastases)

    • Excess vitamin D intake

    • Granulomatous disease: 1,25 dihydroxy vitamin D, 25 hydroxyvitamin D, or ACE level

    • Milk-alkali syndrome

    • Medications (classically HCTZ)

    • Thyrotoxicosis

    • Adrenal insufficiency

Management

  • If Ca+2 \< 12 and asymptomatic
  • Encourage PO hydration

  • Normal saline if hypovolemic

  • Evaluate for underlying cause

  • If Ca+2 > 12 with symptoms or Ca > 14
  • Trend Ca q8 hrs, EKG, monitor on telemetry; strict I/Os ± foley catheter

  • Volume expansion w/ NS bolus followed by continuous infusion at ~ 200cc/hr

    • Goal UOP 100-150cc/hr
  • Add loop diuretic (Lasix) once patient is volume expanded

  • Bisphosphonates

    • Zoledronic acid 4mg IV (EGFR >60), Pamidronate 90mg IV (EGFR 15-60)
  • If Ca+2 >14 or neurologic symptoms, consider subq (not intranasal) calcitonin

    • VUMC: requires approval from an oncology or endocrine attending

    • Tachyphylaxis after ~48H

  • Additional Information

  • In CHF pt, consider early addition of a loop diuretic, especially if volume overloaded

  • In ESRD pt with hypercalcemia (rare), patient with oliguric AKI not responsive to IVF, or pt with severely elevated Ca 16-18, consult endocrine and nephrology early

  • In pts with sarcoidosis or lymphoma, consider glucocorticoids

Hypocalcemia – Trey Richardson

Background

  • Can be divided into low parathyroid hormone and high parathyroid hormone states
  • Low PTH

    • Magnesium deficiency

    • Post-operative for parathyroidectomy

    • DiGeorge syndrome

    • Medications: Bisphosphonates, denosumab, aminoglycosides, gadolinium

    • Acidemia (Serum Ca is inversely proportional to pH)

    • Infiltrative disease: sarcoid, hemochromatosis, malignancies

    • Autoimmune hypoparathyroidism

    • CRRT (if using regional citrate anticoagulation)

  • High PTH

    • Late-stage CKD

    • Hyperphosphatemia

    • Vitamin D deficiency

    • Pseudohypoparathyroidism/Parathyroid resistance

    • Consumption/deposition: Pancreatitis, rhabdomyolysis, some osteoblastic metastases

    • Sepsis or critical illness

Presentation

  • Chvostek and Trousseau’s signs , laryngospasm, seizures, widened QRS and arrhythmias

  • Hemodynamic instability

Evaluation

  • Check PTH, albumin, iCal, VBG, Vitamin D

  • Review medications for possible offenders

Management

  • Under most circumstances there is no need to replace calcium. Instead, focus on correcting the underlying perturbation (e.g. acidemia, hypomagnesemia, treating pancreatitis, etc. )

  • If hemodynamic instability, cardiac electrical instability, seizures then aggressive intravenous replacement is warranted.

  • Also consider preemptive repletion for patients requiring high-volume of blood transfusions (citrate in blood products can cause hypocalcemia)

  • 1 g of CaCl is equivalent to 3 grams of Ca Gluconate

  • Avoid treatment in hyperphosphatemia, advanced CKD/ESRD, and rhabdomyolysis

Hypernatremia – Lauren Chan

Overview of dysnatremias

  • Fluctuations in serum Na reflect fluctuations in plasma free water

  • Sodium is the major driver of tonicity. The clinical signs and symptoms of serum Na fluctuations are related to changes in tonicity with most profound effects on cerebral tissue

  • Two major mechanisms maintain plasma osmolarity between 275 and 290: Thirst and secretion of ADH. When these mechanisms malfunction, dysnatremias occur

Background

  • Definition: Na+ >145

  • Hypernatremia = decreased free water

  • Almost always due to inadequate free water intake (ICU patients, dementia, limited mobility, tube feeding/TPN, impaired thirst/adipsia from hypothalamic stroke). Hospital acquired hypernatremia is iatrogenic and correlates with poor outcomes

  • Can also occur from: Na+ overload (salt poisoning, iatrogenic from NS infusion, over correction), osmotic diuresis (hyperglycemia, SGLT-2 inhibitors, urea, mannitol), diabetes insipidus

Presentation

  • Lethargy, irritability, confusion

  • Seizures, coma, hemorrhagic stroke, or subarachnoid hemorrhage (from the effects of hypertonic serum on cerebral vasculature)

Evaluation

  • Step 1: Treat underlying cause (vomiting, hyperglycemia, medications)

  • Step 2: Determine volume status: If severely hypovolemic, the patient will need IV crystalloid to restore volume in addition to free water

  • Step 3: Estimate and replace free water deficit (FWD):

  • FWD = TBW x [(serum Na/140) - 1]
  • Step 4: Account for ongoing insensible losses and electrolyte free water clearance
  • Rule of thumb for accounting for electrolyte free water clearance. This is in addition to replacing free water deficit

    • 0-1 Liter of urine output: Ignore, no need to replace

    • 1-3 Liters of urine output: Replace half of the losses

    • >3 liters of urine output: Replace all urine losses

  • No evidence that overcorrecting hypernatremia is harmful. In fact, there is increased mortality with overly cautious correction or under correction

  • If able, replace free water enterally. Otherwise, administer D5W intravenously

Additional Information

  • Pts w/ suspected DI: Consult Nephrology (may require desmopressin or may receive desmopressin once stabilized to differentiate between central and nephrogenic DI)

  • Pts with hypokalemia: giving K decreases total amount of free water you are giving the pt

Hyponatremia – Lauren Chan

Background

  • Definition:
  • Mild: Na+ 130-134

  • Moderate: Na+ 125-129

  • Severe: Na+ \<125

  • Hyponatremia occurs when free water reabsorption (i.e. ADH is on) or intake exceeds free water excretion

Presentation

  • Mild to moderate symptoms: lethargy, N/V, dizziness, confusion, fatigue, cramping

  • Severe symptoms: obtundation, coma, respiratory arrest, seizure

Evaluation and Management

  • Step 1: Serum osm 
  • >295: Hyper-osmolar, presence of other molecules that contribute to serum osmolarity 

    • Glucose, mannitol, iodinated contrast

    • If hyperglycemic, corrected serum Na+ = measured Na+ + 1.6*[(glucose – 100)/100]  

      • If corrected Na+ is normal, treat hyperglycemia; not a water balance problem 

      • If corrected Na+ is low, there is hypotonic hyponatremia + coexisting hyperglycemia 

    • Renal failure (urea) and ethanol: Ineffective osmoles that can freely diffuse across cells and do NOT lead to hyponatremia

  • 275-295: Iso-osmolar 

    • Pseudohyponatremia 2/2 hypertriglyceridemia, paraproteinemia, or lipoprotein X: Serum Na not actually low, due to how the lab is calculated 
  • \<275: Hypo-osmolar à Step 2 

  • Step 2: Urine Osm
  • Surrogate for ADH activity

  • Uosm \<100 or Uosm \< Sosm correlates with low ADH

    • Primary polydipsia: Free water intake>output  

    • Tea and toast: Lack solute to effectively concentrate urine 

    • Beer drinkers’ potomania: Mixture of the two above

  • Uosm >100 or Uosm > Sosm correlates with high ADH Step 3 

  • Step 3: Urine Na
  • Is ADH on in the setting of decreased effective arterial bloodvolume (EABV) or decreased mean arterial pressure (i.e. appropriate ADH)?

  • UNa \<20: Low EABV à RAAS upregulation w/ Na avidity-> appropriate ADH release

    • If true volume depletion, then trial 500cc-1L NS bolus and monitor serum Na. IVF bolus->Increase EABV à ↓ ADH release à ↑ free water excretion

    • If edematous state (e.g. heart failure or cirrhosis), then decongestion with diuretics may improve serum Na

  • UNa >40: Euvolemic with no stimulus for ADH-> SIADH

    • SIADH from: n/v, malignancy, meds, surgery, pulmonary disease, hormones, pain, bladder distension: ↑ ADH out of proportion to stimulus  

      • Treat with water restriction. Can add NaCl or urea tabs if fluid restriction is severe 

      • Water restriction (L/day) = 600 / uosm (600 mEq Na in American diet/day)

      • Salt wasting: diuretics, cerebral salt wasting (aka hypovolemic SIADH), SSRIs

      • Other: Hypothyroidism, adrenal insufficiency 

  • If still stumped, can check a FeNa and measure a serum uric acid
  • FeNa \<0.5 % suggests appropriate ADH activity.

  • High uric acid suggests some degree of volume depletion and appropriate ADH activity.

Rate of correction

  • Acute (\<48 hrs)
  • If symptomatic, give 150 cc bolus 3% NaCl up to two times.

  • Monitor Na+ q1-2 hr

  • Goal is an initial rapid 4-6 mEq/L correction and then hold

    • May require Hypertonic Saline infusion with DDAVP clamp if at risk of over-correcting
  • Chronic (>48 hrs or unknown, higher risk for osmotic demyelination if corrected too quickly):
  • Goal Na+ correction rate 4-6 mEq/L over 24 hrs (Max 8mEq/L)

When to call Nephrology

  • If you are worried about rapid over-correction:
  • High risk patients are those with rapidly reversible causes

    • Low solute states (Beer drinker’s potomania, psychogenic polydipsia, tea-toast)- as soon as they decrease their excess free water intake, they will rapidly clear free water

    • Volume depletion- as volume is replaced and the stimulus for ADH release is switched off, then they will rapidly clear the excess free water if they have normal underlying kidney function

  • High risk for ODS includes: chronic liver disease, Na \<105 meq/dL, alcoholism, and malnutrition.

  • Consideration of DDAVP clamp

Hyperkalemia – Mengyao Tang and Amanda Morrison

Background

  • Causes:
  • Cellular shifts: Acidemia, Rhabdomyolysis, TLS, beta blockade

  • Aldosterone deficient states: T4 RTA, Primary adrenal insufficiency

  • Decreased distal tubular delivery: Volume depletion

  • Decreased clearance: AKI, CKD, ESRD

  • Excessive intake

  • Medication-related: ACEi, ARB, MRA, NSAIDs, TMP/SMX, digoxin, heparin

  • Pseudo-Hyperkalemia: hemolysis, severe leukocytosis

  • Symptoms are rare, but usually manifest as cardiac dysrhythmias

Evaluation

  • Confirm hyperkalemia with repeat BMP

  • Check EKG for hyperkalemic changes (sensitivity for EKG findings in hyper K is poor)

  • K+ 5.5-6.5: peaked T waves, prolonged PR interval

  • K+ 6.5-8: prolonged QRS, loss of P wave, ST elevation, ectopic beats

  • K+ >8: sine wave pattern, asystole, PEA, VF

Management

  • If EKG changes or signs of instability
  • Calcium gluconate 1g IV (effective within 3-5 min)

    • Stabilizes cardiac membrane for ~60mins

    • SHOULD BE REPEATED HOURLY while hyperkalemic

  • Shift K+ (temporizing measures)
  • D50 w/ regular insulin 10 units (can order using Adult Hyperkalemia order set in epic)

    • Use 5 units if there is renal impairment

    • Lasts for 4-6hrs (can be longer in renal impairment)

  • Correct acidosis- Consider using isotonic bicarb

  • Beta Agonists (e.g. high-dose albuterol nebulizer); lasts 2-4 hrs

    • Note that typical albuterol nebulizer is 2.5mg, need 10-20mg to have an effect
  • Increase K+ Excretion
  • Loop diuretic- if the kidneys work, use them

    • If there is AKI or a volume deficit can administer with IVF
  • Volume expansion with IVF: Increases distal Na delivery and K excretion. NS and LR are likely equally effective.

  • GI cation exchangers

    • Kayexalate (Polystyrene sulfonate)- only effective if having BMs. 60g PO q2h until bowel movement (If using oral, ensure patient is having bowel movements and is not obstructed, could cause bowel injury/ necrosis). PO can take up to 6hrs to work. Consider per rectal administration for faster action but DO NOT GIVE WITH SORBITOL per rectum

    • Lokelma (Sodium-zirconium-cyclosilicate) 10 g PO TID for 48 H. Actively exchanges K for other cations within the small bowel and works within 2 hours. Remember to stop once the K is normal since can cause hypokalemia. Also keep in mind the high Na content of Lokelma (400mg/5g dose of lokelma)

      • Needs approval from nephrology
  • Hemodialysis: Consult nephrology early if severe hyper K+

Hypokalemia – Peter Thorne and Patrick Steadman

Background

  • Potassium (K+) \< 3.5 mEq/L

  • 98% of total body K+ is intracellular (majority in muscle cells)

  • Goal: prevent life threatening complication (e.g. arrhythmia), replace deficit, elucidate cause

  • Insulin and catecholamines (Beta adrenoreceptors) are key drivers of transcellular shifts

  • H+ and K+ will trade places to maintain electroneutrality

Presentation

  • Malaise, weakness, myalgias, decreased gastrointestinal motility

  • EKG changes:

  • Mild: ST segment depression, decreased T wave amplitude

  • Severe: U-waves (most commonly seen in precordial leads V2 and V3)

  • Severe hypokalemia can lead to rhabdomyolysis

Evaluation

  • History: decreased K+ intake, increased entry into cells (ex: elevated beta-adrenergic activity, hypothermia), GI losses, urinary losses (diuretics, hypomagnesemia, RTA, tubular defects, hyperaldosteronism)

  • If concomitant metabolic alkalosis: Normal/low BP suggests diuretic use, vomiting or Gitelman/Bartter syndromes

  • Hypertension suggests renovascular disease or primary mineralocorticoid excess

  • Labs: BMP, CBC, VBG, urine electrolytes, magnesium, POC glucose, CK. Possibly aldosterone, renin, cortisol pending clinical context

  • Imaging: Renal US, CT AP

Management

  • Check Mg+2, replete to 2; Give empirically while waiting for serum Mg+2

  • K+ preparation (route); replete to 4

  • Choice of agent:

  • KCl is used for repletion in the hospital

    • PO tablets for mild asymptomatic hypokalemia

    • IV can be given through peripheral (rate is 10mEq/hr, may have burning sensation) or central access

  • K+ bicarbonate can be dissolved and put through G tube

    • Useful in pts with hypokalemia and metabolic acidosis
  • Dose:
  • Normal renal function: 10 mEq K+ is expected to raise serum [K+] by 0.1 mEq/L

  • Significant CKD or AKI: at risk of overcorrection

    • Shortcut: multiply the mEq by the Cr = how much K+ expected to rise

    • Once K+ higher than 5.5, K+ increases much faster and rules above do not apply

Hyperphosphatemia – Peter Thorne and Amanda Morrison

Background

  • Phosphate (PO4-3) >4.5mg/dL

  • Etiologies:

  • Cellular shifts: Cellular lysis (TLS, Rhabdomyolysis), Acidemia

  • Increased intake/absorption or iatrogenic hyperphosphatemia (Over repletion, Vitamin D toxicity, use of Fleet’s enemas, etc.)

  • Decreased phosphate clearance (Acute or chronic renal disease, hypoparathyroidism, pseudohypoparathyroidism)

Presentation

  • Symptoms are usually secondary to coexistent hypocalcemia (psychosis, seizure, perioral paresthesia’s, muscle weakness)

  • Can cause acute phosphate nephropathy with phosphate containing laxatives

  • Calciphylaxis if concurrent hypercalcemia (high Ca+2 x PO4-3product)

Evaluation

  • Labs: BMP (calcium, creatinine), VBG, Vit D, PTH, PTHrP, lactate

Management

  • Acute
  • If renal function normal, can often treat with IVF (promote PO4-3 excretion)

  • Consider need for calcium supplementation (see hypocalcemia section)

  • If renal function impaired and severe hypocalcemia present = consider hemodialysis

  • Chronic
  • Usually secondary to chronic renal failure, goal PO4-3 3.5-5.5 in CKD patients

  • Renal diet (low PO4-3)

  • PO4-3 binders: Ca+2 containing (calcium carbonate and calcium acetate) and non Ca+2 containing (sevelamer, lanthanum, and iron based such as ferric citrate)

    • Sevelamer is significantly more expensive than calcium containing binders

      • Given 3 times daily with meals, started at 800mg (Can be ↑ to 1,600mg TID)

      • Should not be given if pt is not eating

    • Calcium acetate: started at 1334mg TID with meals

  • Limit dose changes to chronic binders upon discharge

  • Need to avoid calcium containing binders in patients with calciphylaxis

Hypophosphatemia – Peter Thorne

Background

  • Required for metabolic pathways (ATP production!)

  • Most renal reabsorption occurs in proximal tubule via sodium-phosphate cotransporter

  • Common causes

  • Internal redistribution, reduced intestinal absorption

  • Refeeding syndrome

  • Alkalemia

  • Phos binders on purpose or inadvertently (calcium, aluminum, magnesium antacids)

  • Excessive loss (diarrhea, CRRT, increased urinary excretion)

  • Proximal tubular dysfunction such as in Fanconi Syndrome

  • Hyperparathyroidism causes renal phos wasting

  • Post-parathyroidectomy leading to hungry bone syndrome

  • Vitamin D deficiency or resistance

Presentation

  • Mild Hypophosphatemia (serum >2.0) rarely symptomatic

  • PO4-3\< 2.0: Muscle weakness

  • PO4-3\< 1.0: Heart failure, respiratory failure, rhabdomyolysis, seizures

  • Failure to wean from ventilator

Evaluation

  • Urine PO4-3 level if cause not readily apparent

  • Calculate Fe PO4-3 ([U PO4-3 x PCr x 100]/[P PO4-3x UCr])

  • Fe PO4-3 \< 5% = normal renal response to hypophos: redistribution or ↓ absorption

  • Fe PO4-3 > 5% = renal phos wasting

Management

  • Caution replacing in pts with impaired renal function: start with half suggested dose

  • If K+ > 4 and patient requires IV repletion, may need to use sodium PO4-3 in place of K+ PO4-3 IV; po preferred unless severe or symptomatic, or patient cannot take po

  • K-Phos neutral: oral, each 250mg tablet has 8 mmol of PO4-3 and 1.1mEq of K+

  • K+ PO4-3: IV, each mL has 3mmol PO4-3, 4.4 meq K+

  • Na+ PO4-3: IV, each mL has 3mmol PO4-3

  • PO4-3>1.5: PO: 40 – 80 mmol K+Phos neutral (aim for 1 mmol/kg) divided into 3-4 doses/day

  • PO4-3 1.25 - 1.5: oral 100 mmol K+ PO4-3neutral in 3-4 divided doses if asymptomatic

  • IV: 30 mmol K+ PO4-3over 6 hours (aim for 0.4mmol/kg) if symptomatic
  • PO4-3\<1.25: IV: 80mmol K+Phos over approximately 12 hours (aim for 0.5mmol/kg)
  • Check serum PO4-3 2-12 hrs after last dose of PO4-3 to determine if additional needs

Hypomagnesemia – Mike Tozier

Background

  • Definition: Mg2+ \< 1.8 mg/dL, most pts asymptomatic until \<1.2 mg/dL. Severe [Mg+2] \< 1 mg/dL

  • Causes:

  • GI losses: Diarrhea, malabsorption, acute pancreatitis, EtOH use, TPN, vomiting, NG suction, GI fistulas, anorexia, short gut syndrome, small bowel bypass

  • Drugs: PPIs, loop diuretics, thiazides, digoxin, amphotericin, aminoglycosides, foscarnet, cisplatin, calcineurin inhibitors, laxatives, pentamidine

  • Kidney losses: post-ATN diuresis, Bartter syndrome and Gitelman syndrome

  • Cellular shifts: DKA treatment/recovery, refeeding, hungry bone syndrome, correction of metabolic acidosis, pancreatitis, EtOH withdrawal

  • Other: DM, hyper Ca, hyperthyroid, hyperaldosteronism, burns, lactation, Vit D deficiency, heat, prolonged exercise, mitral valve prolapse, pseudohypomagnesemia 2/2 EDTA tube, lactation

Presentation

  • Refractory hypocalcemia or hypokalemia, arrhythmias, muscle weakness

  • Severe symptoms: seizures, drowsiness, confusion, coma, arrhythmias

  • Vertical nystagmus, tetany (Chvostek sign, Trousseau), tremors, fasciculations

Evaluation

  • EKG: Initially wide QRS, peaked Ts. Progresses to wide PR, diminished T, arrhythmias

  • Labs: Ca+2, K+, can use FEMg (order urine Mg+2 and Cr, serum Cr and Mg) or 24-hour urine for Mg to distinguish renal vs GI etiology (FEMg>2% renal, \<2% GI)

Management

  • Correct underlying cause, replete based on severity (Dosing below for normal GFR)

  • Oral: asymptomatic pts, can cause GI symptoms, not well absorbed

  • Sustained release (Mg Chloride or Mg L-lactate) better tolerated and absorbed, though standard preparations (Mg oxide) are faster acting

  • Mg chloride: 3-4 tabs BID (total 30 to 56 meq [15 to 28 mmol]) for severe hypo Mg

  • 2-4 tabs daily (total 10 to 28 meq [5 to 14 mmol]) for mild hypo Mg

  • Mg oxide: 400-800 mg BID (20 to 40 mmol [40 to 80 meq]) for mod-severe hypo Mg

  • Intravenous: for symptomatic patients or if GI intolerance to oral
  • Mg \<1 mg/dL: 4 to 8g of MgSO4 (32 to 64 meq [16 to 32 mmol]) over 12 to 24 hrs

  • Mg 1 to 1.5 mg/dL: 4 g MgSO4 (16 to 32 meq [8 to 16 mmol]) over 4 to 12 hrs

  • Mg 1.6 to 1.9 give 1 to 2 grams MgSO4 (8 to 16 meq [4 to 8 mmol]) 1-2 hrs

    • VUMC only has 4g bags of IV mag so would need to ask nurses to only infuse ½ bag
  • Infusion rate should not exceed 2 g/hr to minimize urinary excretion

Additional Information

  • Renal impairment: replete with caution, reduce dose by 50-75% and monitor closely

  • If persistent hypo Mg in pts requiring diuresis, try K-sparing diuretic (e.g. Amiloride)

  • Treat concomitant hypokalemia, hypocalcemia or hypophosphatemia

  • In pts with concomitant hypophos and hypocalcemia, IV Mg alone -> worse hypophos

Approach to Urinalysis – Laura Binari, Patrick Steadman

Background

  • 3 components: Gross Evaluation, Dipstick Analysis, Microscopic Exam

  • Indications: dysuria, gross hematuria, fever + GU symptoms, AKI, volume overload

  • If Foley, obtain sample from catheter, not the urine bag

  • Spinning Urine

  • At VUMC, take sample to lab on 4th floor to centrifuge the sample at 1500 rpm for 5 minutes, remove supernatant and then resuspend sediment, place drops of urine on the slide, examine with microscope

  • At the VA, there is a microscopy room where you can spin urine as well

  • Ideally, the specimen should be a fresh catch (\<2-4 hours old); Beware: casts like to migrate to the edges of the coverslip!

Gross Evaluation

  • Turbid: Infection, precipitated crystals, or chyluria

  • Color: Red Urine (broad DDx, see Hematuria section, includes certain meds such as rifampin/phenytoin), White (polyuria, phosphate crystals), Green (methylene blue), Pink (uric acid crystals, post-propofol infusion), Black (hemoglobinuria/myoglobinuria)

Dipstick Analysis

  • Quality of sample: should have zero squamous epithelial cells
  • Specific gravity: normal = 1.010

  • Surrogate for urine osmolality & hydration: can have falsely high specific gravity if large particles (contrast, glucose) present

  • Trick: Last 2 digits of S.G. x 30 = Uosm. For example: S.G. is 1.013; 13 x 30 = 390 mOsm/L

  • Urinary pH: normal pH is 5.5-6.5
  • Alkaline pH: bicarb suppl, vegan diet, urease producing organisms (staghorn calculi)

  • Acidic pH: uric acid stones, appropriate response to acidemia

  • Proteinuria: dipstick detects albumin ONLY (not paraproteins)
  • Mild albuminuria (30-300 mg/day) not detected by standard dipsticks

  • F/u with spot protein to Cr ratio or 24 hr urine collection (nephrotic range >3.5 g/day)

  • Transient: due to volume depletion, CHF, fever, postural, exercise-induced

  • Ddx: primary glomerular dx, secondary glomerular dx (DM, amyloid, infxn, sickle cell, etc.) vs tubular vs overflow (multiple myeloma)

  • Heme (see hematuria section): False(+) if semen, false(-) w/ ascorbic acid

  • WBC:

  • False(+) 2/2 contamination with squamous cells. If bacteria -> consider UTI/pyelo w/hematuria -> inflammation; May have sterile pyuria

  • Ddx includes chlamydia, ureaplasma, TB, malignancy, viral infxn, kidney stones, GN, urethritis, steroid, cyclophosphamide use

  • Ketones:
  • Never normal in urine; only detects acetic acid

  • Ddx: DKA, starvation ketoacidosis, pregnancy, keto diet

  • Glucose: max threshold at proximal tubule exceeded (~serum glucose 180 mg/dL)
  • DM, Cushing’s, liver/pancreatic dx, SGLT2i use; or a primary defect of proximal reabsorption (w/phosphaturia, uricosuria, amino aciduria think Fanconi syndrome)
  • Leukocyte esterase: enzyme released by lysed neutrophils, macrophages
  • Associated with pyuria and infections; false(-) from hematuria or glucosuria
  • Nitrites: reduction of urinary nitrates by nitrate reductase
  • Certain bacteria (e.g. Enterobacteriaceae) express, others (e.g. Enterococci) do not
  • Bilirubin: conjugated = water soluble (passes through glomerulus), unlike unconjugated
  • Liver dysfunction and biliary obstruction
  • Urobilinogen: end product of conjugated bilirubin, normally ~1.0mg/dL is normal
  • Can be elevated due to hepatocellular dx or hemolysis

Microscopic Examination of the Urine Sediment

  • Cells:
  • Dysmorphic RBCs (sign of GN), squamous epithelial cells (contamination), tubular cells (abnormal, indicates renal dx), neutrophils (UTI, AIN, TB, sterile pyuria), eosinophils (think AIN, not sensitive thus cannot exclude diagnosis)
  • Casts:
  • Hyaline (pyelo; CKD, normal subjects), RBC (GN), WBC (GN, pyelo, interstitial dx, inflammation), epithelial - renal tubular cells (ATN, interstitial nephritis, nephritic sx, heavy metal ingestion), granular or waxy (presence of kidney disease, but nonspecific), muddy brown casts (ATN); fatty (nephrotic syndrome)
  • Crystals:
  • Ca++ oxalate (envelope/dumbbell shape), uric acid (rhombic/rosette shaped, classically formed in acidic urine), cystine (hexagonal, found in cystinuria), Mg ++ ammonium phosphate (aka struvite stones, from increased ammonia production, in setting of urease producing bacteria such as Proteus or Klebsiella UTIs)

  • Calcium oxalate crystals + AKI, consider ethylene glycol intoxication

  • Uric Acid crystals + AKI, consider tumor lysis syndrome

Hematuria – Laura Binari/Patrick Steadman

Background

  • Definition: 3 urinalyses with three or more RBC/hpf; 1 urinalysis with 100 RBC/hpf or gross hematuria (1 cc blood/L urine can induce color change)

  • Causes:

  • Can be transient (exercise-induced, menses, trauma)

  • Concurrent pyuria/dysuria: consider urinary tract infection or bladder malignancy

    • Malignancy risk factors: male sex, age > 50, smoking Hx, exposures to benzene/aromatic amine, cyclophosphamide, indwelling foreign body, pelvis irradiation, chronic UTIs, heavy NSAID use, urologic disorders (nephrolithiasis, BPH)
  • Recent URI: think infection related glomerulonephritis, IgA, vasculitis, anti-GBM

  • Positive Family Hx of Hematuria: consider PKD, Sickle Cell Disease

  • Bleeding from other sites: think inherited/acquired bleeding disorder, anticoagulation

  • Unilateral Flank Pain: Ureteral calculus, renal malignancy, IgA Nephropathy

Glomerular Extraglomerular (Non-Glomerular Source)
Kidney

Ureter/

Bladder

Prostate/

Urethra

Other

IgA Nephropathy

IgA Vasculitis

Pyelo Cystitis BPH Exercise-Induced
Lupus Nephritis Renal Cell Carcinoma Urothelial Malignancy Prostate Cancer Bleeding Diathesis
Infection-related glomerulonephritis PKD Nephrolithiasis TURP Meds (AC)
Anti-GBM Disease (Goodpasture’s)

Sickle Cell

Papillary Necrosis

Ureteral Stricture Urethritis (STI) Menses
ANCA-associated Malignant HTN Hemorrhagic Cystitis (chemo/rads)

TB

Schistoso-miasis

Genetic (Thin Basement Membrane Nephropathy/Alport Syndrome)

Arterial embolism

Vein thrombus

Traumatic Foley/procedure

Evaluation

  • Step 1: Confirm the presence of hematuria
  • Dipstick positive heme: urinary RBCs (hematuria), free myoglobin or free hemoglobin

  • Centrifuge the urine

    • Red sediment -> true hematuria (urinary RBCs)

    • Red supernatant +

      • Positive dipstick: myoglobulin or hemoglobin

      • Negative dipstick porphyria, Pyridium, beets, rhubarb, or ingestion of food dyes

Glomerular Extraglomerular
Color (if gross hematuria) Red, Cola, Smoky Red/Pink
Clots Absent Present/Absent
Proteinuria May be >500 mg/day \<500 mg/day
RBC morphology Dysmorphic RBCs present Normal (isomorphic)
RBC casts May be present Absent
  • Step 2: Determine if there is a GLOMERULAR or NON-GLOMERULAR source of bleeding
  • Glomerular Bleeding:

    • Isolated Hematuria: Differential includes IgA Nephropathy, thin BM dx, Alport’s

    • Nephritic syndrome (new proteinuria, pyuria, HTN, edema, rise in Cr): post-infectious GN, MPGN, ANCA vasculitis, Goodpasture’s, lupus nephritis

    • Workup: anti-GMB, anti-DNase/ASO, ANA, ANCA, C3, C4, cryo, Hep B & C, HIV

    • Indications for Renal Biopsy: glomerular bleeding + risk factors for progressive disease, including albuminuria > 30 mg/day, new hypertension > 140/90 or significant elevation over baseline BP, rise in serum creatinine

  • Extraglomerular Bleeding (Imaging Section)

    • If historical clues suggest nephrolithiasis, start with non-con CT A/P

    • Gross Hematuria otherwise should be evaluated with CT A/P w/ and w/o contrast (CT urography); consult urology for cystoscopy (often done as outpatient referral)

    • If clots are passed, more likely to be secondary to lower urinary source, and if a high burden of clots poses a risk of obstruction (urologic emergency)

    • If extraglomerular bleeding with clots: hematuria catheter needs to be placed ASAP (2 valve catheter, 20-24 Fr (!); page urology if nursing unable to obtain)

  • CT Urography is more sensitive than IV pyelogram for renal masses and stones.

  • Prefer Renal and Bladder Ultrasound in pregnant patients

  • All pts w/gross hematuria that is non-glomerular in source, in whom infection has been ruled out, warrant cystoscopy. Additionally, all patients with clots need cystoscopy

Kidney Transplant Medicine – Trey Richardson

Introduction

  • The goal of this section is to serve as a guide for tackling the most common transplant complications as well as offer a few tips for managing immunosuppression while kidney transplant patients are admitted to the hospital

Alphabet soup

  • PRA: panel reactive antibodies

  • DSA: donor specific antibodies

  • CMV (-/+): indicates the CMV status of both the recipient and the donor

  • FK506 or FK: another name for tacrolimus

  • KDPI: Kidney donor profile index used to “grade” the quality of the donated organ

  • X/6 MM: indicates the number of HLA subtypes that are mismatched between donor and recipient

Infections in Kidney Transplant Recipients

Background

  • Infections in a kidney transplant recipient can be divided into 3 phases:
  • \<1-month post-transplant

    • Surgical site infections, nosocomial infections (e.g. C. Diff, CAUTIs, and CLABSIs), and donor-derived infections/reactivation of latent recipient infections predominate
  • 1-6 months post-transplant

    • Depleted immune-system regenerates increased risk for disseminated fungal (e.g. PJP, histo/blasto) and viral infections (HSV, adenovirus)
  • >6 months post-transplant

    • Risk for atypical infections persists, but common community acquired syndromes should still be on the differential
  • This section will focus on the most common infection in kidney transplant recipients- infections of the urinary tract

Evaluation

  • UA with culture 

  • Examine the native kidneys (CVA tenderness) AND the allograft (almost always in RLQ, denervated so the graft itself will not be tender, but the surrounding soft-tissue may)

  • Renal U/S (of both allograft and native kidneys) or CT AP if:

  • Early post-op (1 month)

  • Recurrent (2+ episodes in year)

  • History of nephrolithiasis or if sepsis/bacteremia

  • Blood cultures if systemic signs/symptoms

  • Consider testing for C. urealyticum, and sending fungal and AFB urine cultures if UA is recurrently positive but culture negative

Management

  • Remove or replace indwelling catheters

  • Review prior culture susceptibilities (if available)

  • Empiric antibiotic regimens:

  • Asymptomatic bacteriuria: treat with FQ or beta lactam for 5-7 days if \<3 mos post-transplant

  • Simple cystitis: Fluoroquinolones (ciprofloxacin 250 BID or Levaquin 500 mg daily), Augmentin (500 mg BID), 3rd gen cephalosporin (cefpodoxime 100 mg BID or cefixime 400 mg daily) or nitrofurantoin 100 mg BID (if GFR>30, only treats cystitis since drug only concentrates in the urine)

    • \< 6 mos post-transplant: treat for 10-14 days

    • >6 mos post-transplant: treat for 5-7 days

  • Complicated UTI/Pyelonephritis (cover Pseudomonas, gram negatives and Enterococcus): Ceftriaxone 2g daily (preferred), Cefepime 2g q8hrs (add Vancomycin when using cephalosporin if suspicious for enterococcus) or Pip-tazo 3.75g q6hrs, can also use meropenem 1g q8h (need ID approval)

    • Treat for 14-21 days

    • For stable pts with mild complicated UTI, can consider giving more narrow empiric antibiotics: Augmentin 875 mg BID or ciprofloxacin 500 mg q12h

  • MDR UTI: Consult transplant ID

    • Options: meropenem-vaborbactam, ceftolozone-tazobactam, ceftazidime-avibactam
  • In pts w/PCKD, include lipophilic antibiotic (such as ciprofloxacin) to penetrate cysts

Prevention

  • Bactrim used for PJP prophylaxis during first 6 mos post-transplant also prevents UTIs

  • Basic infection prevention measures for all comers (e.g. hydration, frequent voiding, wiping front to back, voiding after sexual intercourse)

Acute Kidney Injury of Kidney Transplant

Background

  • Most patients admitted to medicine services with kidney transplants are >3 months post-op. Therefore, we are typically not managing perioperative complications such as delayed graft function, or hyper-acute rejection. Below are the most common causes of acute kidney injury in kidney transplant recipients.

Evaluation

  • Signs and symptoms of UTI?

  • Assess volume status

  • Review meds for recent medication changes

  • Common offenders: NSAIDs, ACE, diuretics, azole antifungals

  • Medication non-adherence

  • Tacrolimus (FK) or cyclosporine (CsA) level
  • FK levels increase with n/v, diarrhea due to alterations in p-glycoprotein expression within inflamed GI tract

  • FK toxicity also causes diarrhea and volume depletion

  • Proteinuria:
  • Transplant patients with 1 g/day proteinuria usually get biopsies
  • Review donor characteristics (CMV status, PRA, % HLA antibodies present, DSAs)

  • BK PCR: consider only if unclear source of AKI and no recent titers

  • Serum PCR is test of choice
  • Renal transplant U/S (costly and not always warranted)
  • \< 1 week post-transplant: If acute graft dysfunction, look for thrombosis, urine/ureter leak

  • > 1 week post-transplant:

    • Cr does not respond to 48 hours of current management

    • Lack of clear, reversible causes

    • Hydronephrosis (can occur after stent removal 4-6 wks after transplant or due to perinephric fluid collection)

    • Arterial stenosis (↑ velocities in renal artery -- very concerning when velocity >300), tardus parvus waveforms)

    • Perinephric abscess with recurrent UTI/pyelonephritis

    • Urinoma (usually first 2-3 weeks), hematoma (after a biopsy)

  • Unique findings:

    • Resistive indices: reflect central renal vascular compliance. High indices in transplant patients signify parenchymal problem (rejection, infection, ATN)
  • Biopsy
  • To differentiate ATN vs rejection vs BK nephropathy vs recurrent disease (FSGS, lupus, etc.)

  • Post Biopsy Care:

    • Watch for bleeding and HTN

    • Blood can get into collecting system, then the capsule, and into the perinephric space causing Page Kidney (aka Pressure Tamponade)

      • Compressed renal vessels-> RAAS surge --> rapid, severe HTN (STAT page the renal fellow)

Kidney Transplant Rejection

Background

  • Rejection is divided into acute vs chronic and T-cell mediated or antibody mediated
  • Pathologists can determine the type of rejection and the chronicity by observing the structures that are acutely involved (e.g. tubulitis, glomerulitis, arteritis, and capillaritis) as well as the time course of involvement (e.g. presence of fibrosis)

  • Structures exhibiting fibrosis represent chronic rejection that is unlikely to respond to treatment, whereas acute inflammation may be amenable to acute therapies

  • This section will focus on acute rejection since this is the clinical entity we will most likely manage while on the wards

Acute Rejection

  • Acute T cell mediated rejection
  • Infiltration of the graft by lymphocytes and inflammatory cells characterized by tubulitis, interstitial inflammation, and arteritis (on occasion)

  • Treatment:

    • High dose glucocorticoids (methyl prednisolone) is first line (~ 5 days)

    • Thymoglobulin (polyclonal Ig anti-T cell)

      • Use depends on severity of rejection

      • Indicated if Cr fails to improve after steroids

      • T cell subsets are measured during treatment until depleted

    • Tacro target levels are reset to ~8-10 if treated for acute T cell mediated rejection

  • Acute antibody mediated rejection (ABMR)
  • Donor specific antibody mediated rejection characterized by glomerulitis, peri-tubular capillaritis (microcirculation inflammation), complement deposition (C4d staining), and presence of DSA

  • Treatment = B-cell depletion therapy

    • IV methyl prednisone 500 mg IV x 3-5 days

    • Plasmapheresis (If with high titers of DSA)

    • IVIG 2 g/kg (max 140 g)

    • Rituximab 375 mg/m2

Kidney Transplant Immunosuppression

Background

  • Most patients with kidney transplants are on triple therapy with an anti-metabolite (azathioprine or mycophenolate compound) or mTOR inhibitor + calcineurin inhibitor + prednisone

  • You may also come across patients who are on monthly infusions with belatacept, a selective T-cell co-stimulation blocker

Calcineurin inhibitors

  • Tacrolimus (FK), cyclosporine (CsA)
  • Envarsus XR is a once a day long acting formulation of tacrolimus

  • Common side-effects

    • Worsening kidney function: mediated by vasoconstriction to the afferent arterioles

    • Hypertension- treat with CCBs

    • Diabetes

    • Hand tremors, headache, nausea

    • Thrombotic microangiopathy

    • T4 RTA- hyperkalemia

    • Gingival hyperplasia

mTOR Inhibitors

  • Sirolimus, everolimus
  • Major side effects: Poor wound healing, rarely pneumonitis

Anti-metabolites

  • Azathioprine

  • Mycophenolate preparations: Mycophenolate mofetil (Cellcept, MMF), Mycophenolic acid (Myfortic)

  • Side effects: Bone marrow suppression- hold for lymphopenia; GI upset- hold for diarrhea

Additional Information for Overnight Admits:

  • Do not change immunosuppression
  • Exception: If pt has severe diarrhea, can hold night tacro dose and inform the day team
  • Daily tacrolimus or cyclosporine level (order qam at 5:00). Always order tacrolimus or cyclosporine dose at 6:00 am and 6:00 pm (regardless of what time patient takes at home, lab can only run am tacro levels at a certain time in batches)
  • EXCEPTION: If late afternoon admission, consider paging the fellow (since its early) and ask if they want the evening dose held until the am level comes back
  • Transplant patients with normal kidney function can have regular diet

Last update: 2022-06-09 16:32:41