Genitourinal

Question 1

Acute Kidney Injury - AKI

Answer 1

• Inc in serum creatinine >50% [at/over 0.3mg’dL] in 48h OR inc in blood urea nitrogen/BUN (Azotemia).
• RIFLE Criteria: 3 progressive level of AKI
  -> Risk, Injury, Failure w/ 2 outcome determinants: Loss and End stage renal disease
• Phases of AKI: oliguric [maintenance phase: dec in urine output <400mL/d, azotemia, hyperkalemia, metabolic acidosis -> diuretic phase of inc urine output, hypotension, hypokalemia => recovery phase
• Sx of uremia: N/V, malaise, HA, altered sensorium, metabolic acidosis

3 MAJOR TYPES:
1- PRE renal
2- POST renal
[1+2 are reversible]
3- INTRA renal [intrinsic]

Pre-renal azotemia

• characterized by decreased renal perfusion w/ nephrons still structurally intact
• in not correct, prerenal azotemia may lead to intrinsic injury [Acute tubular necrosis (ATN)]
• **prerenal AKI most common type of AKI [40-80%] in outpatients but ATN is the most common type in hospitalized pt.

Etiologies
REDUCED RENAL PERFUSION HALLMARKS

• **Hypovolemia: renal vol loss [ex: diuretics therapy], GI loss [diarrhea or vomiting] or blood loss
• afferent arteriole vasoconstriction - nonsteroidal anti-inflammatory [NSAIDS] drugs due to inhibition of prostaglandins = minimize protective afferent arteriolar vasodilation [normally PG are recruited to inc renal blood flow via afferent arteriolar dilation].
  -> calcium inhibitors [cyclosporin, tacrolimus], IV radiocontrast media
• Efferent arteriole dilation - Ex: RAAS blocker like ACEi, ARBs may limit efferent renal arteriolar constriction out of proportion to afferent arteriole constriction, diminishing GFR.
• Hypotension. relative hypovolemia in edematous states [ex: CHF w/ dec pump function]

DIAGNOSIS
EVIDENCE OF WATER + ELECTROLYTE CONSERVATION since the renal parenchyma is till intact:

• inc BUN > inc creatinine [**BUN: creatinine ratio >20:2]
• Sodium conservation: fractional excretion of sodium [**FENa] <1% and urine sodium >20mEq/L
• *water conservation: concentrated urine specific gravity [>1.020] and **increased urine osmolarity [>500mIsm/kg].
  -> Serum cystatin C is nonspecific for AKI

MANAGEMENT
VOLUME DEPLETION

• Vol repletion [ex: normal saline] to restore vol and renal perfusion is the mainstay tx of prerenal AKI [unlike ATN, prerenal azotemia rapidly responds to tx]
• with sufficient IV fluid replacement, return of the serum creatinine to the previous baseline within 24-72h is considered to represent correction of prerenal disease, where as persistent AKI is considered to represent ATN
• The aim is to achieve a positive fluid balance of 500ml/day

Question 2

prerenal azotemia vs. Acute tubular Necrosis

Answer 2

Prerenal azotemia

• Creatinine: increases slower than 0.3mg/dL/day
• Urine Sodium [UNa], FENa [fractional excretion of sodium]: dec in urin Na+ <20mEQ/: FENa+ <1%
• urinalysis [UA]:
  ->normal UA or bland sediment.
  ->HIGH SPECIFIC GRAVITY [>1.020].
  -> inc Urine osmolarity >500
• response to vol replacement: creatinine rapidly improves with IVF
• blood urea nitrogen [BUN/Cr]: inc BUN:Cr >20:1

Acute tubular necrosis

• Creatinine: inc at/over 0.3-0.5mg/dL/day
• Urine Sodium [UNa], FENa [fractional excretion of sodium]: **urine Na+ >40 mEq/L; FENa+ >2% **
• urinalysis [UA]:
  ->CASTS: epithelial, granular, or muddy brown casts
  -> LOW SPECIFIC GRAVITY [<1.015]
  -> dec Uosm: <500, often 200-500
• response to vol replacement: creatinine won’t improve much
• blood urea nitrogen [BUN/Cr]: BUN:Cr at/under 10-15:1

Question 3

Acute Tubular Necrosis

Answer 3

• a type of intrinsic AKI characterized by acute destruction and necrosis of the renal tubules of the nephron
• Most common type of INTRISIC AKI [50%]. most common cause of AKI in hospitals

ISCHEMIC

• PROLONGED PRE-RENAL AZOTEMIA associated w. hypotension or hypovolemia. sepsis
• EXOGENOUS: radiocontrast dye [immediate] Aminoglycoside and/or vancomycin ~5-10 days after exposure [incidence reduced w/ IV]. Calcineurin inhibitors [ex: Cyclosporine, Tacrolimus], NSAIDs, Amphotericin B, Methotrexate, Cisplatin, Foscarnet, Cidofovir, Tenofovir.
• ENDOGENOUS: uric acid precipitation [tumor lysis syndrome], pigments [myoglobinuria (rhabdomyolysis), hemoglobin], lymphoma, leukemia, Bence-Jones proteins [Multiple myeloma]

DIAGNOSIS

**DISTINGUISHING PRE-RENAL VS. ATN: UA, response to IV fluids, and fractional excretion of sodium [FENa].

• URINALYSIS: renal tubular epithelial cells and granular [muddy brown] cast: sloughing off of tubular cells into the nephrons.
  -> labs may show HYPERkalemia and HYPERphophotemia
• Unlike prerenal, sodium and water reabsorptive abilities are lost in ATN, resulting in *low urine specific gravity [ isosthenuria** inability to concentrate urine], low urine osmolarity <500. INC fractional urine sodium >40 and BUN:Cr ration at/under 15:1.

MANAGEMENT

• REMOVE OFFENDING AGENT + IV FLUIDS are first line. IV fluids given before and after IV contrast
• no other therapy proven to benefit ATN. N-acetylcysteine may be added to in contrast-induced cases
• furosemide used only when clinically indicated [critical AKI w/ vol overload]
• *prognosis: most pt return to baseline within 7-21 days after injury**

URINALYSIS: most important noninvasive test regarding the possible etiologies

• RBC cast, with hematuria, dysmorphic red cells = Acute glomerulonephritis [AGN] or vasculitis
• MUDDY BROWN [GRANULAR] OR EPITHELIAL CELL CASTS = ATN
• WBC casts, pyuria [free WBC cells] = Acute intestinal nephritis or pyelonephritis
• WAXY CASTS: acellular with sharp edges = narrow waxy casts: CHRONIC ATN/ Glomerulonephritis, Broad waxy casts: End stage renal disease [tubal dilation]
• FATTY CASTS: Maltese crosses”, oval fat bodies = nephrotic syndrome [due to hyperlipidemia]
• HYALINE CASTS = Nonspecific [may be seen in normal urine]. Tamm-Horsfall protein are secreted by tubular epithelial cells
• Normal or near normal UA: few cells with little to no casts = AKI: prerenal or postrenal, hypercalcemia, multiple myeloma.
• Hematuria + pyuria [ excluding red cell casts] = UTI, AIN, glomerular disease, vasculitis
• Pyuria alone = most common due to infx. sterile pyuria in tubulointestinal disease

FENA % = [urinary cinc Na/plasma Na] x [Plasma cr/urine cr] X 100

Question 4

Acute interstitial Nephritis

Answer 4

**Tubulointerstitial nephritis: A type of intrinsic AKI characterized an inflammation or allergic tubulointerstitial injury

Question 5

Postrenal Azotemia [obstructive uropathy]

Question 6

Hydronephrosis

Question 7

Horseshoe kidney

Question 8

Chronic Kidney Disease [CKD] + end-stage renal disease [ESRD]

Answer 8

Normal GFR = 120-130ml/min/1.73m2
Chronic kidney disease: progressive functional decline at/over 3 months to years are evidenced by:

• proteinuria, abnormal urine: sediments, serum/urine chemistries
• abnormal imaging studies
• inability to buffer or make urine or excrete nitrogenous waster
• dec in synthesis of vit D/erythropoietin

Chronic kidney disease staging

• Stage 0 = at risk pt: DM, HTN, chronic NSAID use, AA/Hispanic/Asian, age >60, SLE, s/p kidney transplant, FH of kidney disease. Normal GFR, normal urine
• Stage 1 = kidney damage w/ normal GFR [or >90] = proteinuria, abnormal UA, serum, imaging
• Stage 2 = GFR 89-60
• Stage 3 = GFR 59-30 [3a = 59-45 and 3b = 44-30]
• Stage 4 = GFR 29-15
• Stage 5 = GFR <15. End stage renal disease [ESRD] = uremia req dialysis and/or transplant

ETIOLOGY

• DM most common cause of ESRD
• HTN second most common cause
• Glomerulonephritis, polycystic kidney disease, rapidly progressive glomerulonephritis, etc

CLINICAL MANIFESTATIONS

• Most pt w/ stage I-IV CKD have no sx
• uremia: n/v, fatigue, malaise, metallic taste, hiccups, altered mentation, irritability, muscle cramps, restless leg, easy bruising, fluid overload, encephalopathy, pericarditis
• HTN is most common finding. may develop vol overload [edema]

DIAGNOSIS
PROTEINURIA: single best predictor of disease progression

• spot urine albumin/Ucreatinine ratio [ACR] preferred over 24h urine collection
  -> spot test est grams of protein loss/day
• labs in advanced CKD:
  -> Inc BUN and creatinine
  -> Hyperphosphatemia, hyperkalemia
  -> hypocalcemia
  -> Metabolic acidosis
• UA: abnormal sediment - may have RBC casts, WBC casts etc. Broad waxy casts seen in ESRD [the cast take the shape of dilated and damaged tubules]. Urine dipstick
• Estimated GFR: CKD-Epi most accurate; MDRD. Cockroft-Gualt used for Creatinine clearance [ex: renally dosing med excreted by kidneys]
• Renal US: bilateral small, echogenic kidneys [<9-10cm] classic in advanced CKD.
  -> Large kidneys may be seen in diabetic retinopathy and polycystic kidney disease.

MANAGEMENT

• HTN: BP control reduces cardiovascular disease risk
• Proteinuria: ACE inhibitors or Angiotensin receptor blockers [ARBs] in early disease. SGLT2i
• Diabetes control: hemoglobin A1C goal <7.0% if pre-dialysis and not at risk for hypoglycemia
• Hyperlipidemia: LDL <100mg/dL, TG <150mg/dL, HDL>50mg/dL
• Renal osteodystrophy: low serum calcium + high phosphate. Managed by active vitamin D [calcitriol] + phosphate binders [ex: Calcium Acetate, Calcium carbonate]; Lanthanum or Sevelamer used if both calcium & phosphate levels are elevated
• Hypocalcemia and osteomalacia: replace vit D and calcium
• Dialysis: end stage disease [stage 5], acidosis, electrolyte imbalances, ingestion, overload [volume] and uremia. Renal transplant for some end-stage renal disease.
  -> Dialysis indicated if GFR at/under 10mL/min and or serum creatinine at/over 8mg/dL [in diabetics, if GFR at/under 15ml/min and or serum creatinine at/over 6mg/dL]

Question 9

Cardiovascular complications of Chronic Kidney Disease

Question 10

Acute Glomerulonephritis [AGN] (Acute Nephritic Syndrome)