Nephritis, Nephrotic Syndrome and Acute Kidney Injury

What is acute kidney injury (AKI)?

Abrupt decrease in kidney function, resulting in the retention of urea and other nitrogenous waste products

What is prerenal AKI?

Damage before the kidney causes decreased blood flow to the kidneys

What are some causes of prerenal AKI?

hypotension, heart failure, MI, vascular occlusion, sepsis, medication

What medications can cause prerenal AKI?

ACE-I/ARB, anesthetics, NSAIDs, Epinephrine

What is intrarenal (intrinsic) AKI?

Damage to the kidney causing decreased functioning

What are some causes of intrarenal AKI?

acute tubular necrosis, glomerulonephritis, lupus, nephrotoxins, rhabdomyolysis, prolonged hypotension, infections, vascular disease

What medications can cause intrarenal AKI?

penicillin analogues, cephalosporins, sulfonamides, ciprofloxacin, acyclovir, rifampin, phenytoin, interferon, PPI

What is postrenal AKI?

Damage after the kidneys that casues obstruction

What are some causes of postrenal AKI?

renal calculi, tumors, BPH, neurological related retention, phimosis

What are the symptoms of AKI?

Anorexia, N/V, Pruritus, Fatigue, Weakness, and SOB

What are the clinical signs of AKI?

change in volume/mental status, edema, HTN, pericardial friction rub, arrhythmias, rales, decreased urine output

What levels of urine outputs indicate the difference between nonoliguria, oliguira, and anuria?

Nonoliguria: > 500mL

Oliguria: < 500mL

Anuria: < 100mL

What are the critical levels of BUN and Creatinine?

BUN: >100mg (>50 is worrisome)

Creatinine: >4mg/dl

What BUN/Creatinine ratios are consistent with prerenal, renal, and postrenal azotemia?

Prerenal: >20/1

Renal: ~10-20/1

Postrenal: variable ratio

What fractional excretion of Na may be consistent with a prerenal or intrinsic cause AKI?

prerenal: < 1%

Intrinsic: > 3%

When is fractional excretion of urea beneficial?

patients on diuretics; < 35% in prerenal disease

When is GFR calculation less accurate?

extreme muscle mass, unusual diets, elderly patients, DKA, liver disease, medications (flucytosine, ASA, cimetidine, probenecid)

What general lab findings are seen in AKI?

elevated BUN/Cr, urine casts, proteinuria, hematuria, hyperkalemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, and anemia

What are differentiating lab factors to diagnose prerenal AKI?

- BUN > 20:1

- Osmolarity >500

- normal UA

- decreased volume

- Urine Na+ < 20,

- Na+ excretion <1%

What are differentiating lab factors to diagnose intrinsic (renal) AKI?

- BUN < 20:1

- Osmolarity 250-300

- Dark Granular Casts

- Oliguric or Nonoliguric

- 2-4+ proteinuria

- Urine Na+ > 30

- Na+ excretion > 3%

What are differentiating lab factors to diagnose postrenal AKI?

- BUN < 20:1

- Osmolarity > 400

- Hyaline Casts

- Absent

- Urine Na+ < 20

What imaging may be needed for postrenal azotemia?

Ultrasound or possibly CT (non contrast)

How is Prerenal Azotemia managed?

volume restoration +/- inotropes reversal of vascular resistance, close monitoring of BUN/Cr

How is Intrinsic Azotemia managed?

Treat underlying cause

How is Postrenal Azotemia managed?

identify location of obstruction, foley catheter (urethral or bladder) or urology consult (ureter, renal pelvis)

What is contrast nephropathy?

renal tubular epithelial cell toxicity 24-48 hours after exposure to radiographic contrast agents

What are predisposing factors for contrast nephropathy?

diabetes, advanced age, pre existing renal disease, CHF, recent exposure to ACE-1 and NSAIDs

What is the prevention and treatment of contrast nephropathy?

hydration, lower volume contrast, hold metformin +/- acetylcysteine

What is acute tubular necrosis?

renal medullary ischemia

What exogenous toxins most often cause acute tubular necrosis (ATN)?

radiographic contrast agents,* aminoglycosides,* cisplatin, MTX, ethylene glycol, amphotericin B

What labs are seen with acute tubular necrosis?

- BUN/Cr <10-15

- Muddy brown casts

- FEN > 3%

What is the treatment for acute tubular necrosis?

- Treat or remove precipitating cause

- Manage fluids and electrolytes

What is interstitial nephritis?

edema and tubular damage from interstitial inflammation

What is the pathogenesis of Interstitial nephritis?

Cell-mediated immune reaction where T-Lymphocytes cause direct toxicity and release lymphokines

What are the most common causes of interstitial nephritis?

Penicillin, Sulfa or NSAIDs (MC) but can also be infection with CMV or Strept.

What are the symptoms of interstital nephritis?

fever, maculopapular rash, arthralgias

What are the lab findings with interstitial nephritis?

plasma eosinophilia, RBC/WBC casts, proteinuria (NSAID-induced)

What is the management of interstitial nephritis?

self-limiting, short-term dialysis, removal of inciting agent, +/- steroids

What causes focal intrinsic glomerulonephritis?

IgA nephropathy and SLE

What causes diffuse intrinsic glomerulonephritis?

SLE, membranoproliferative, rapidly progressive, postinfectious, vasculitis

What are the symptoms of glomerulonephritis?

hypertension, edema (periorbital and scrotal), oliguria

What laboratory findings are seen in glomerulonephritis?

elevated serum creatinine, hematuria, proteinuria

What is the treatment of glomerulonephritis?

immunosuppressants and supportive care

What are the indications for dialysis?

Acid-Base Disturbance

Electrolytes (hyperkalemia)

Ingested Toxins

Overload (diuretics)

Uremia (AMS, seizure, pericarditis)

What is Nephritic syndrome?

Glomerular disorders characterized by inflammation leading to capillary wall damage of endothelial cell layer and GBM

What are the characteristic findings of nephritic syndrome?

mixed proteinuria < 3.5g/24hrs, hematuria (RBC casts), reduced filtration (oliguria, anuria, azotemia)

What is a classic example of Nephritic syndrome?

post-infectious

What is Nephrotic syndrome?

non-inflammatory damage to the podocytes (flatten) and lose the ability to hold back large molecules like protein

What are the characteristic findings of Nephrotic syndrome?

Albumineria > 3.5g/24hrs), hypoalbuminemia, anasarca, lipiduria (oval fat bodies), hypercoagulation

What is a classic example of Nephrotic syndrome?

Minimal Change Disease

What is IgA Nephropathy (Berger's disease)?

Most common cause of primary glomerulonephritis due to IgA antibody deposition mesangium

What are the risk factors for IgA Nephropathy?

Celiac disease, HIV, MGRS, chronic liver disease (alcoholic cirrhosis)

What is the prominent symptom of IgA Nephropathy?

Gross hematuria +/- protein

What is the management of IgA Nephropathy?

ACE-I/ARB +/- SGLT2 if proteinuria, treat dyslipidemia, sodium restriction <2g/d, protein restriction, smoking cessation, weight control, excercise

What is post-streptococcal glomerulonephritis?

Nephritic syndrome MC in children 5-12 y/o 2-3 weeks after streptococcal infection (pharyngitis or cellulitis)

What are the symptoms of post-streptococcal GN?

edema, hematuria, HTN, and renal insufficiency (áCr)

What labs are seen in post-streptococcal GN?

Elevated anti-streptolysin O Ab, Positive anti-DNAase B Ab, and Low complement levels (C3, CH50)

What is the treatment of post-streptococcal GN?

penicillin/amoxicillin if infection still present, supportive care, resolution after 3-4 weeks

What is Anti-Glomerular Basement Membrane Antibody (Goodpasture's)?

Condition isolated to the kidneys peaking in 3rd decade for males and 6th-7th decade for females

What are the symptoms of Anti-Glomerular Basement Membrane Antibody (Goodpasture's)?

hematuria, proteinuria (<3.5g/d), hemoptysis, malaise, weight loss, fever, arthralgias

What labs are obtained in Anti-Glomerular Basement Membrane Antibody (Goodpasture's)?

UA, BUN, Cr, Serum anti-GBM, CXR, CT, renal biopsy

What is the treament for Anti-Glomerular Basement Membrane Antibody (Goodpasture's)?

Plasmapheresis with Corticosteroids and cyclophosphamide

What are the risk factors for Lupus Nephritis?

50% of SLE patients, higher in AA and Hispanic patients

What is the diagnostic criteria for Lupus Nephritis?

Anti-dsDNA complex deposition, Elevated Cr, proteinurea/hematura, confirmed on kidney biopsy

What is the treatment for Lupus Nephritis?

Immunosuppressive therapy

What is ANCA Glomerulonephritis?

Characterized by necrotizing glomerulonephritis with little or no deposition of Immune-complexes or complement

What labs are seen in ANCA Glomerulonephritis?

Proteinuria, ESR/CRP, ANCA markers, kidney biopsy +/- pulmonary findings

What is the treatment for ANCA Glomerulonephritis?

Cyclophosphamide and glucocorticoids, rituximab, plasmapheresis

What is Membranoproliferative GN?

a histologic lesion (not a specific disease) causing thickened GBM AND Increased mesangial and endocapillary cellularity

What are the causes of Membranoproliferative GN?

monoclonal gammopathies, autoimmune/rheum conditions, infections, complement

What are the symptoms of Membranoproliferative GN?

Hematuria, variable proteinuria, elevated Cr

What is the management of Membranoproliferative GN?

treat underlying cause, sodium/potassium restriction, BP control, RAS inhibition, dyslipidemia treatment +/- SGLT2

What is Focal Segmental Glomerulosclerosis?

histologic lesion associated with heroin, anabolic steroids, obesity, HIV, COVID, and prior inflammatory glomerular disease

What are the symptoms of Focal Segmental Glomerulosclerosis?

HTN, AKI, hematuria

What is the treatment of Focal Segmental Glomerulosclerosis?

Immunosuppressive therapy - glucocorticoids +/- tacrolimus with general kidney protective measures

What is the minimal change disease?

Nephrotic syndrome that can be idiopathic or secondary from NSAIDs, malignancies, infections, or allergies

What are the symptoms of minimal change disease?

sudden/severe proteinurea, hypoalbuminemia, microscopic hematuria, hyperlipidemia

What is seen on biopsy with minimal change disease?

Light microscopy shows no changes (EM shows fusion of foot processes)

What is the treatment of minimal change disease?

Corticosteroids

What is membranous nephrotic syndrome?

#1 cause of nephrotic syndrome in adults without DM associated with SLE, malignancies, infections, and BMT

What diagnostic testing is positive in Membranous Nephropathy?

C3, C4 and autoantibodies against a podocyte antigen may be detected (PLA2R)

What is the treatment for Membranous Nephropathy?

Low risk: monitor for 5 years'

Mod-High risk: immunosuppression

What is Diabetic Nephropathy?

Leading cause of ERSD that rarely requires a kidney biopsy

WHat labs are seen with Diabetic Nephropathy?

Micro (30 to 300mg/d) or macro (>300mg/d) albuminuria, decreased eGFR, creatinine ratio < 30

What is the management of Diabetic Nephropathy?

BP control, glycemic control, lifestyle modification, lipid loweirng +/-