Renal Flashcards
Approach to patient with kidney issue
Laboratory testing: • Serum Creatinine & Urea Nitrogen • Creatinine clearance (Estimated GFR) • Urinalysis with microscopic examination • Urine Electrolytes and Osmolality • Spot Urine Protein and Creatinine ratio • 24 hours Urine Collection • Assessing Urine Output -Oliguria (400cc/day)
History and Physical examination
Imaging:
• Kidney Imaging (U/S, Doppler, Nuclear scan, MRI, Angiogram)
Invasive testing:
• Kidney Biopsy
Indication for renal biopsy
- Acute kidney injury
- Nephrotic or nephritic syndrome
- Hematuria
- Systemic Disease
- Transplant Allograft
ONLY perform biopsy if:
- Cannot determine with less invasive procedure
- Suggestion of parenchymal disease
- Differential diagnosis includes diseases that have different treatments and courses
Serum creatinine as measurement of GFR
Non-protein waste product of skeletal muscle metabolism
15-25 mg/kg/day= proportional to muscle mass; Serum concentration dependent on:
- Excretion (glomerular filtration)
- Secretion into lumen
Changes in creatinine excretion have hyperbolic relationship with GFR:
- jump from 1 to 2 mg/dL–> 50% loss of nephrons
Conditions changing creatinine excretion:
Decreased creatinine: less muscle mass
- Hepatic cirrhosis
- Limb amputation
- Spinal cord injury
- Morbid obesity
Increased creatinine: more muscle mass or drugs:
• Influence of muscle mass
• Blocking proximal secretion
- cimetidine, trimethoprim, probenecid
• Interference with Jaffe rxn e.g. ketones, methanol, cephalosporins, isopropanol
(mass spectroscopy, HPLC et al)
Urinalysis
Blood: strip detects peroxidase
- blood, myoglobin, free hemoglobin
Leukocyte alkaline esterase detects polys.
Nitrate: detected by a reaction with an azo dye
- presence suggests bacteria
Protein: depends on urine concentration.
- 1+ as significant as 3+
Specific gravity closely approximates osmolality
- If specific gravity is high then concentrating ability likely intact
Urinary sediment types
Casts
RBCs
Crystals
Indications for Renal Ultrasound
To quantify kidney size
To evaluate for hydronephrosis
To evaluate the perirenal space for abscess or hematoma
To screen for ADPKD (polycystic kidney disease)
To localize the kidney for invasive procedures
To evaluate for kidney vein thrombosis (doppler US)
To assess kidney blood flow (doppler US)
Indications for IV pyelography
IV contrast dye given- monitor kidney excretion
To assess renal size and contour
To investigate recurrent urinary tract infection
To detect and locate calculi
To evaluate suspected urinary tract obstruction
To evaluate the cause of hematuria
Indication for radionuclide studies
To quantify total kidney function and the contribution of each kidney
To evaluate kidney parenchymal integrity
To evaluate kidney infection or scar
To evaluate renovascular hypertension
Little benefit when the single kidney GFR is below 15 ml/min
Glomerular filtration agent (renal scan)
- Freely filtered by the glomerulus and is not reabsorbed
- To estimate GFR
- Technetium diethylenetriamine pentaacetic acid (99mTc-DPTA)
Tubular secretion agents (renal scan)
- Evaluate renal blood flow and function
- Plasma clearance
- Technetinum mercaptoaceyltriglycine (99mTc-MAG3)
Tubular fixation agents (renal scan)
- Bound to the tubules and delineates the contuor of functional renal tissue
- To assess cortical scarring from pyelonephritis and/or vesicoureteral reflux
- Technetium dimercaptosuccinate [99mTc-DMSA]
Indication for renal CT
To further evaluate a renal mass
To display calcification pattern in a mass
To delineate the extent of renal trauma
To guide percutaneous needle aspiration or biopsy
To diagnose adrenal causes for hypertension (50% of HTN is genetic, other causes linked to renal function)
Indication for renal MRI/MRA
- Diagnosing renovascular lesions
- To assess renal vein thrombosis
- Evaluation of potential living kidney donors and transplanted kidneys
- To evaluate suspected pheochromocytoma
- Delineating complex mass where CT is not definitive
- Staging kidney neoplasms, particularly in evaluating for renal vein or inferior venal caval extension of tumor
Indication for renal angiography
- Suspected artery lesions: atherosclerotic or fibrodysplatic stenoic lesions of the renal arteries, aneursysms, arteriovenous fistulae.
- Large vessel vasculitis
- Unexplained hematuria
- Kidney transplantation
- Diagnoses for renal vein thrombosis
- Complex or highly unusual renal masses or trauma etc
“Can be used for diagnostic or for therapeutic purposes”
Definition of Acute renal failure (ARF)
Acute loss of kidney function
- Typically connotes acute drop in GFR
Multiple definitions of this, typically based on changes in:
- Serum Creatinine
- Urine output
Other definitions of ARF:
- Oliguria: <50cc UOP/day
- Azotemia: elevated blood urea nitrogen (BUN ) without symptoms of uremia
- Uremia: buildup of toxins that are cleared by the kidney. Most of these toxins are unknown.
* * An elevated Urea level alone is NOT sufficient to diagnose uremia
Differential diagnosis of ARF
- Prerenal causes
- Intrinsic causes:
- Tubular necrosis
- Interstitial nephritis
- Acute glomerulonephritis - Postrenal causes
Pre-renal azotemia
Elevated nitrogen levels in blood NOT due to kidney damage
- Renal blood flow decreased–> decreased GFR–> decreased clearance of metabolites
- Kidney is intact and cells are not damaged
- Kidney avidly reabsorbs salt and water to try and preserve intravascular blood volume and renal blood flow.
Features:
- History of volume depletion
- Exam consistent with volume depletion
- Fractional Excretion of Na (FENa) < 1 %
- Urine Na < 20 mEq/L (low if kidney is Na avid, tubules intact)
- Urine Osm > 500 mOsm/L
- Increased BUN/Creatinine Ratio
- Bland urinalysis
- Ultimate Test: Give Fluid
- If immediate improvement, then it’s pre-renal
Hepato-renal syndrome
Advanced liver failure- toxins usually cleared by liver cause:
- Splanchnic vasodilatation
- Renal vasoconstriction
- Urine Looks Like Pre-Renal Azotemia
- Urine Na < 20mEq/L
- Bland UA
- Does not get better with saline
Post-renal obstruction
In patients with two functioning kidneys, both need to be effected to produce significant renal failure Causes: - Urethral obstruction – most common - Obstruction of a solitary kidney - Bilateral ureteral obstruction
Causes:
- Urethral obstruction
- Bladder neck obstruction (prostatic hypertrophy, bladder carcinoma, bladder infecion)
- Bilateral ureter obstruction:
1. Intraureteral: - Sulfonamide, uric acid crystals, blood clots/stones
2. Extraureteral: - tumor (cervix, prostate, endometriosis)
- Retroperitoneal fibrosis
- Ureteral ligation/edema due to pelvic operation
Diagnosis of post-renal obstruction
• Historic predisposition:
Benign Prostatic Hypertrophy
Abdominal malignancy
Nephrolithiasis
• Symptoms of obstruction:
Urinary frequency/urgency (suggesting urethral obstruction)
Patients with post-renal ARF do NOT need to be anuric. A partial obstruction may still lead to enough back-pressure to decreased kidney function
Urinalysis: bland sediment
Urine lytes: not helpful
Evidence of obstruction: renal U/S, abdominal CT
Acute tubular necrosis/ injury (ATN/ATI): types
Defined as sudden death of tubular cells (NOT glomerular cells)
There are two sub-categories of ATN:
- Ischemic ATN: results from severe renal hypoperfusion. Ischemia results in death of susceptible tubular cells
- Nephrotoxic ATN: injury secondary to substances that directly damage renal tubules, leading to cell death
Acute tubular necrosis: causes
Ischemic:
- Septic shock
- Extensive trauma
- Massive hemorrhage
- Post-operative
- Pancreatitis
- Pregnancy- post-partum hemorrhage
- Transfusion reactions
Toxic:
- Radiocontrast media
- Antibiotics (aminoglycosides, amphotericin)
- Myoglobin (rhabdomyolysis)
- Hemoglobin
- Heavy metals (mercury, arsenic, lead, bismuth, uranium, etc.)
- Insecticides
- Chemotherapy
- Uric acid, calcium
- Need to hydrate patients when exposed to nephrotoxic substances to dilute toxicity
Acute tubular necrosis: Diagnosis
- History: prolonged hypotension, muscle crush, toxin exposure, drugs, coma, seizures
Urine sediment:
- granular casts on urinalysis
- Casts= mucoprotein secreted by renal tubule cells
- -> decreased GFR–> increased accumulation of casts
Urine lytes:
- Na > 20 mEq/L or FENa> 1%
Pathology finding (rare to biopsy):
- Normal glomeruli
- Tubular epithelial cells flattened with pyknotic nuclei, swelling and necrosis of cells with sloughing into tubules
- Interstitium – edema with minimal cellular infiltrate
Acute interstitial nephritis: casues
Allergic reaction in kidney
Typically due to medications:
- NSAIDs
- PPI
Acute interstitial nephritis: diagnosis
History:
- Drug hypersensitivity
- Eosinophil > 10% in periphery
Urine WBCs with negative culture (no infection)
- Casts with no pyelonephritis
- No urinary obstruction/inflammation of kidneys on imaging
Gold standard diagnosis: kidney biopsy
Acute glomerulonephritis
Inflammation of glomeruli, typically auto-immune
Urine sediment:
- Dysmorphic RBCs
- RBC casts, WBC casts
- Proteinuria
Causes: Acute post-infectious glomerulonephritis Autoimmune diseases: - SLE - Polyarteritis nodosa - Henoch-Schonlein purpura - Goodpastures syndrome ANCA vasculitis (most common cause in hospital)
Renal athero-emboli
Small atheromatous crystals flecking off arterial wall–> kidney
- After manipulation of arteries (post-embolization)
- Loss of kidney function after 1-2 weeks
- Urine bland, maybe eosinophilia
- PE may show emboli (fingertips)
- No specific treatment
Management of ARF
- Pre-renal:
- replace fluid
- CHF: treat arrhythmias, inotropes, reduce load - Post-renal:
- Remove cause/bypass obstruction (EMERGENCY when creatinine begins to elevate) - Acute tubular necrosis:
- No interventions will improve renal function after onset of acute tubular necrosis
Supportive care of Acute Renal Failure
- Intravascular volume (overloaded):
- low salt diet, water restriction
- diuretic use - Hyponatremia:
- restrict free water, avoid D5W in IVF???? - Hyperkalemia:
- Renal diet, eliminate K/K-sparing diuretics
- K-binding ion exchange resin in colon
- Glucose/insulin, 50-100 mEq NaHCO3, albuterol, Ca-gluconate - Metabolic acidosis:
- Sodium bicarb to maintain HCO3 > 15 - Hyperphosphatemia, hypermagnesemia, hypocalcemia
- Phosphate-binding agents
- Avoid milk
- Discontinue Mg-containing antacids (malox, mylanta)
- Ca-gluconate, Ca-carbonate
Long-term outcomes of ARF
- Pre-renal: recovery complete if perfusion restored
- Post-renal: almost complete recovery with fast resolution of obstruction (within 1 week)
- ATN:
- Mild injury: complete recovery
- Prolonged oliguria: decreased recovery
- > 50% mortality in ICU patients with ATN and HD support (Hemodialysis) - AIN: complete recovery after agent withdraw
- Renal arteroemboli: rare recovery
Cockroft-Gault estimation of Creatinine Clearance
(24 x age x ideal weight(kg))/ (72x (serum creatinine))
Stages of Chronic kidney disease
Based on creatinine clearance: Stage 1: normal GFR with signs of kidney disease Stage 2: GFR 60-99 (mild impairment) Stage 3: GFR 30-59 (moderate impairment) Stage 4: GFR 15-29 (severe impairment) Stage 5: GFR <15 Stage 6: renal replacement therapy
Symptoms of real failure
Mild: minimal fatigue, salt and H2O retention (edema, HTN)
Moderate dysfunction: more fatigue and edema, mildly impaired cognition, appetite preserved
Severe dysfunction: fatigue, loss of appetite (nausea, vomiting)
- Symptoms= UREMIC
Signs of severe uremia
Asterixis
Seizures
Pericardial friction rub: serosanguinous pericardial fluid
Lab abnormalities:
- prolonged bleeding time (platelet dysfunction)
- profound anemia
- low calcium and high phosphate- sometimes with subperiostial bone resorbtion on x-ray
- high alkaline phosphotase (secondary hyperparathyroidism)
- low bicarbonate (metabolic acidosis)
- high potassium
Complications and therapy of uremia:
Treated with medical management:
- Anemia (Hg 9-10: avoid transfusion)
- Pulmonary edema
- Vascular calcification (bone disease)
- Severe acidosis
- Bone disease
Treated with renal dialysis/replacement:
- Peripheral nervous system dysfunction
- Pericarditis
- Malnutrition
Preservation of GFR
Renal disease tends to be progressive, even if an insult is recognized and eliminated
Concept of progressive glomerular damage
Hyperfiltration injury
Efferent vs. afferent vasoconstriction
Physician uses anti-hypertensives to preserve renal function (ACE-I, ARB) by lowering GFR
- See slight elevations in creatinine (demonstrative benefit)
Diabetes: progression to nephropathy
Type 1 diabetics:
First 20 years: diabetes result in overt proteinuria in 15-20% of cases (if no proteinuria by 30 years, home free)
- All who develop proteinuria also have retinopathy and/or neuropathy
- Nephrotic range proteinuria (3+ g/day)
- Followed by end-stage renal disease in 5 years
Type 2 diabetics:
- Less predictable (onset unknown)
- May or may not include retinopathy/neuropathy
- Same pathology
Albuminuria in diabetes
- Microalbuminuria = >30 mg albumin daily
- Overt nephropathy > 300mg/day (nephrotic syndrome approximately 3,000 mg/day
- Routine urinalysis can’t detect microalbuminuria
- Microalbunuria portends nephropathy
Control/prevention of Diabetic nephropathy
- Controlling BP to less than 130/80
- Utilizing ACE inhibitors and ARB’s
- Diuretics
- Disrupt RAAS
- Very tight blood sugar control
- Type 2 outcome less predictable because of comorbidities like hypertensive renal disease, atherosclerosis, obesity
- Now overt proteinuria =5%, ESRD= 0.8%
Anemia due to nephropathy
Begins with GFR < 60 ml/min
- Progressive hemoglobin decline as GFR falls further
- Major cause = erythropoeitin deficiency
Treatment:
- Recombinant erythropoeitin injections
- Iron supplementation
- Target Hgb 9-10 grams- NOT TO NORMAL
Why correct anemia?
- Increased feeling of well being
- Reversal of LVH
- Improved cognition
- Improved cognition
- Improved life expectancy
- Forestall dialysis ?
Correction of Platelet deficiency in nephropathy
- Desmopressin – increased multimeric form of factor VIII vonWillebrand factor (increases platelet “stickiness”)
- Tachyphylaxis after 2nd dose
- Cryoprecipitate
- Conjugated estrogen – delayed onset, longer effect
- PRCB to hct > 30%
Metabolic acidosis
Cause= fall in serum bicarbonate
Symptoms:
- Normal anion gap, then high anion gap
- Bicarb < 16 is symptomatic
Treatment:
- Oral bicarbonate or citrate: 30-40 meq daily usually does the trick
Renal bone diseases
Renal osteodystrophy–> elevated PTH–> Osteitis fibrosa (cystica)
Low bone turn over disease (osteoporosis)
Osteomalacia
Osteitis fibrosa
- High PTH due to: hypocalcemia, hyperphosphetemia, low calcitriol level,
- Low calcium due to low calcitriol level
- High phosphate due to decreased GFR
- Result of increased PTH: too rapid bone turnover, abnormal bone (woven vs. trabecular)
Management:
- Maintain PTH at 2-3 times normal value (uremic bone resistance to PTH)-target varies with GFR (keep endogenous PTH low- Cinacalcet)
- Begin measuring PTH in stage 3 kidney disease
- Raise calcium to normal (vitD analogs, calcium carbonate, calcium acetate, calcitriol)
- Keep phosphate below 5 (phosphate binder= calcium acetate, calcium carbonate, sevelamer,or lanthanum carbonate with meals)
- Keep C X P < 55
- Kidney transplantation
Low bone turnover (adynamic) bone disease
High calcium X phosphate product; Low PTH
- May result from overzealous management of PTH with phosphate binders containing calcium
Result: vascular calcification, valvular calcification
** Most ESRD patients develop coronary calcifications
Osteomalacia
Historically iatrogenic
Heavy metal (aluminum) deposits at calcification front in bone
Don’t use aluminum hydroxide as a phosphate binder
Dietary consideration in ESRD
Protein restriction: malnutrition vs. minimal renal preservation effect
Potassium: 2 gram restriction. Usually clearance less than 25 ml/min
Low phosphate with stage 3-4 CKD
Sodium restriction: from day one
Fluid – variable
Renal replacement therapy (hemodialysis)
Hemodialysis: thrice weekly for 4 hours per treatment in center
- Short daily hemodialysis-home?
- Nocturnal hemodialysis-home?
- Peritoneal dialysis: at home, often at night
- Dialytic mortality: 24% annually
Renal transplantation
Deceased donor: - 95% one year patient survival - 90% one year graft survival - half-life 8-10 years - 4-6 year wait Live donor: - 98% one year pt - 94% one year graft survival - half-life 17 years
Donor issues: cadaver and live organ “quality”
Recipient issues: age and comorbidity
Renal transplant risks
- Surgical-bleed/hematoma/lymphocoele/MI
- Immunosuppression risk = meds
- Induction meds: IL2 receptor bockers, antithymocyte globulin
- Calcineurin inhibitors-cyclosporine, tacrolymus
- Antimetabolite = sirolimus, mycophenolic acid
- Corticosteroids
Osmolality calculation
2 x {Na+} + Glu/18 + Urea/2.8
- Can be directly measured by lab
Tonicity
“Effective osmoles”= Tonically active osmoles are confined to one side of cell membrane or the other
- Water moves across ICF and ECF to maintain equal tonicity between compartments (since Na and K cannot move)
Effective= Na, K, Cl, Mannitol
Ineffective= urea, ethanol
* Glucose can be effective or ineffective (depending on insulin)
- Can NOT be directly measured by lab
Physiology of response to changes in effective vascular volume, tonicity
RAAS responds to effective vascular volume (total body Na)
Hypothalamus responds to tonicity (amount of water in spaces= concentration of Na)
- Secretes ADH and stimulates sensation of thirst
- 10% reduction in effective vascular volume overrides tonicity and stimulates hypothalamic secretion of ADH + thirst
ECF volume
Na is major osmole of ECF
- Total body Na determines ECF volume
- Stable hemodynamics is dependent on stable ECF volume (maintained by Na balance)
Na Intake (dietary) = Na Output (renal and extrarenal)
- Renal excretion of Na is the major way of regulate Na content in body
- Extrarenal Na loss can outpace Na intake under certain conditions (diarrhea, burns, blood loss) leading to total body Na loss and abnormally low ECF volume (hypovolemia)
ECF volume disorder
Abnormalities in total body sodium content
- Normal total body sodium=euvolemia
- Too little sodium=volume depletion/ hypotension
- Too much sodium=volume overload/ edema
Osmolar disorders
Abnormalities in sodium concentration= abnormalities of water balance
- Too much water (relative to sodium) =hyponatremia
- Too little water (relative to sodium) =hypernatremia
IV fluid administration to correct water balance
IVF used to give NaCl–> Isotonic Saline
- Often called “normal saline”
- Tonicity is comparable to the aqueous portion of blood
IVF used to give water–> 5mg/dl dextrose
- Often called “D5W”
- Giving pure water IV would lyse red cells
5mg/dl dextrose is close to iso-osmolar initially, but the dextrose gets metabolized
- This leaves behind water
Renal handling of Na
Glomerulus: Na is freely filtered
- Daily Na filtered=
GFRxPna=180Lx140meq/L=25,200meq
- Kidneys have an enormous capacity for Na excretion
Tubules: >99% of filtered Na is reabsorbed
- Daily Na intake 80 to 250 meq
- Changes in daily Na intake only require very small adjustments in the rate of Na reabsorption
- Increased renin/AngII/aldo activity leads to increased Na reabsorption
Action of diuretics on various parts of kidney
CAI (acetazolamide)= proximal tubule
Furosemide= loop of henle
Thiazide= Distal tubule
Amiloride= Collecting duct
Effect of sodium depletion/hypovolemia on kidneys
Decreased venous return to heart--> decreased CO--> decreased BP--> increased baroreceptor stimulation--> increased sympathetic tone--> increased renin secretion--> 1. Angiotensin II formation--> vascular constriction and Na reabsorption 2. Angiotensin II--> aldosterone--> Na reabsorption
ADH: MOA
insert water channels into collecting duct luminal surface to increase water reabsorption
Medullary collecting tubule= water impermeable (without ADH)
- Need high osmotic gradient between medullary lumen and interstitium
- Allows for water to exit out of lumen down concentration gradient–> reabsorption
Maximal urinary concentration= determined by osmotic gradient in medulla and ADH secretion (max 1200 osmol)
Osmole intake and urine volume
Osmole intake = 600-1000 mOsmol per day
- Na, K, and protein (majority of osmol intake in western diet–> converted to urea)
Osm intake must = osmol output
- If ADH level fixed, Osm intake determines Urine volume
(ex: Urine osm= 300 msosm/L, Osm intake= 600 mosm; urine volume= 2 liters (600/300))
Stimuli for thirst
- Hypertonicity
- Habit (For normal people, drinking “8 glasses of water daily” has no proven health benefit!)
- Dry mouth
- Social conventions
- True volume depletion
- Effective volume depletion
Disorders of thirst
Psychogenic polydipsia or compulsive water drinking
- Normal individuals can excrete 12-15 liters/day of free water
- Psychiatric illness or drugs for its treatment can interfere with water excretion
Decreased water intake
- Physical disability limiting access to fluids
- Primary hypodipsia from lesions of the thirst center (rare)
- Geriatric hypodipsia (common)
Polyuria
> 3 L of urine daily
- Water diuresis: inability to concentrate urine: Uosm300
- “Mixed” diuresis: Uosm 150-300
Hyponatremia measurement
High serum osmol: hyperglycemia Normal serum osmol: hyperlipid, protein Low serum osmol: everything else - Hypo-osmolar hyponatremia: to develop patient must have: 1. Fluid intake (IV/PO) 2. [Osm] of fluid in< [Osm] fluid out
Hypo-osmolar hyponatremia
- Is kidney doing right thing?
- tonicity too low
- ADH should be absent (test for ADH with urine osmolality–> urine should be < 100 mosmol)
- A low urine osmol that is NOT < 100 (ie there is still ADH or urine is not maximally diluted) when the plasma osmol is low means there is:
- inappropriate ADH secretion OR
- > 10% effective intra-vascular volume depletion (blood loss)
- kidney damage (v. common)
Urine Osm < 100 mosmol:
- RARE conditions: psychogenic polydipsia, beer potomania (tea and toast diet), osmostat reset, or “you fixed it” hyponatremia
Determine causes of inappropriate ADH secretion
- Evaluate volume states (hypo-, hyper-, eu-volemic)
- History
- Orthostatic vitals (HR)- change of > 10% when sitting–> standing
- Urine [Na] < 20 mEq/L (volume depleted)
- Rule out diuretcs, kidney disease, etc.
Hypervolemia states
Determined by Extra-cellular fluid volume
CHF
Cirhosis Nephrosis
Hypovolemia states
GI losses Sweating Thiazides Cerebral Na wasting Aldosterone deficiency
Euvolemic states
SIADH
Glucocorticoid deficiency (glucocorticoids prevent fluid overload)
Hypothyroidism
Reset Osmostat (hypothalamus damaged–> fluid balance reset at new level causing fluid overload)
Causes of SIADH
Idiopathic Drugs (ADH release enhanced): - TCA, amitrptyline, haldol, morphine, vincristine, cyclophosphamide Drugs promoting ADH action: - ASA, NSAIDs Cancers: SCLC (paraneoplastic syndrome Brain damage Meningitis Infections Hypothyroidism
Treatment of Hypovolemic hyponatremia
Normal saline
Indications:
1. Dangerous hypovolemia (organ dysfunction, unstable vitals) –> bolus regardless of effect on hyponatremia
2. Mild-moderate hyponatremia and:
- Clearly due to volume depletion
- SIADH with urine electrolyte content < Saline (Electrolyte content = 2 x (U[Na] + U[K]), Can lower urine electrolyte content by giving Lasix)
- Benefit: Less risk of over-correction, Easier to fix volume status (since you can give more)
- Risks:
1. Can worsen hyponatremia in SIADH
2. If urine electrolyte content > saline electrolyte content, then water from saline will be retained in body
3. Over-correction still possible especially in hypovemic hyponatremia:
- Volume status restored before resolution of hyponatremia –> ADH drops to zero. Brisk water diuresis ensues–> rapid over-correction.
- Important example of “You fixed it” hyponatremia
Hypertonic saline
- only used in severe cases (CNS symptoms; Na < 120 mEq/L; unsure if SIADH vs volume depletion, but don’t want drop in [Na])
- Benefit: Increases Na regardless of cause of hyponatremia
- Risk: Can over-correct, and delays restoration of volume status in patient with undetected volume depletion
Treatment of Euvolemic hyponatremia
Fluid restriction:
+/- Hypertonic Saline (+/- Lasix)
+/- Vaptan (largely experimental- blocks ADH effect)
+/- NaCl or Urea tablets (chronic management)
+/- Demeclocycline (chronic management)
Treatment of Hypervolemic hyponatremia
Fluid restriction
Lasix
+/- Vaptan (largely experimental)
Risks of hyponatremia
If [Na] > 120, probably not an emergency
If [Na] < 120, then need to guess how well-compensated patient is:
- How quickly did this happen? (prior serum [Na]?)
- The faster the change, the more dangerous
- Is patient symptomatic?
Mild: Nausea, Headache
Moderate: Mental Status Change (can be subtle)
Severe: Seizure, Coma, Death
- Reversing disorder needs to be done gradually (over a couple of days) to avoid other complications of disrupting homeostasis
- Order FREQUENT LABS for serum [Na] and admit to ICU for close monitoring
Overcorrection of hyponatremia
Osmotic demyelination: Signs/Symptoms: - Dysarthria/Dysphagia - Weakness/paresis - Seizures - Lethargy/confusion/obtundation/coma - Often irreversible Occurs 2-6 days after over-correction
- Incidence: Unknown (Probably not that frequent)
High risk groups:
- Overcorrection: >12 mEq [Na] over 24 hours
- Females who have not had menopause
- Alcoholism
- Malnutrition, liver disease, hypokalemia
Treatment of hypernatremia
Water!
- Give isotonic solution as bolus to avoid tonicity disorder
Do NOT bring serum [Na] down by more than 12 mEq/day
Central vs Nephrogenic Diabetes insipidus
- Cannot reach urine osmol of 600 or more
Central: no ADH secretion
- Should be corrected by dDAVP
- Treatment: dDAVP (or excess water intake)
Nephrogenic: kidneys don’t respond to ADH
- Will not correct with dDAVP
- Treatment: discontinue offending meds, administer thiazide diuretics (paradoxical), NSAIDs, Na-restriction
Renal Dysplasia
Congenital anomalies of the kidney and urinary tract (CAKUT) due to:
- Malformation of renal parenchyma resulting in failure of normal nephron development–> renal dysplasia, renal agenesis, renal tubular dysgenesis, and polycystic renal diseases.
- Abnormalities of embryonic migration of the kidneys as seen in renal ectopy (eg, pelvic kidney) and fusion anomalies, such as horseshoe kidney.
- Abnormalities of the developing urinary collecting system as seen in duplicate collecting systems, posterior urethral valves, and UPJ obstruction
Kidneys are variable in size but most are smaller
- Discovered during routine antenatal screening.(increased echogenicity as a result of abnormal renal parenchymal tissue, poor corticomedullary differentiation, and parenchymal cysts.)
- By 20 weeks gestation, fetal urine accounts for 90 percent of the amniotic volume. Oligohydramnios is a clue .
- Associated urological findings- abnormalities of the renal pelvis and calyces (congenital hydronephrosis) and ureters (duplicating collecting system), megaureter, ureteral stenosis, and vesicoureteral reflux (VUR).
- Symptomatic presentation due to urinary tract infection, hematuria, fever, and abdominal pain
Clinical:
Important Contributor to ESRD in children (Especially in bilateral disease)
- In past, thought was that progressive loss of renal function was due to associated collecting system abnormality leading repeated bouts of pyleonephritis
- Modern belief is that parenchymal abnormalities are the cause of progressive decline in renal function
Management:
- Medical prophylaxis of UTI versus surgical correction of collecting system abnormalities
- No convincing evidence that surgery is superior
- Severe reflux with very frequent and/or severe UTI’s is
nevertheless often managed surgically.
- The rate of spontaneous resolution is dependent upon age, grade of reflux, and whether the reflux is unilateral or bilateral.
Cystic kidney disease
Types:
- Autosomal dominant polycystic kidney disease
- Autosomal recessive polycystic kidney disease
- Medullary sponge
- Mdullary cystic disease/nephronophthisis
- Simple renal cysts- few, no disease
- Acquired cystic disease of renal failure
Autosomal dominant polycystic kidney disease (ADPKD)
AKA—Adult Polycystic Kidney Disease - Common congenital disease—1/1000 births
- Accounts for 5% of all adult renal failure
- Initial symptoms occur between 30 & 50 yrs
- Back pain is most common complaint
- Half of all ADPKD pts will require transplantation or dialysis
Symptoms:
- Typically asymptomatic until the fourth decade of life
- loin “fullness”
- Palpable flank masses in adults
- Hematuria (gross clots)
- Azotemia
- Uremia
Pathogenesis:
- 85% of cases show mutation in PKD 1 gene on chromosome 16 (40s-50s, worse outcome)
» Protein = polycystin-1
– 15% of cases show mutation in PKD 2 gene on chromosome 4 (70s-80s, better prognosis)
» Protein = polycystin-2 – Both proteins reside in tubular cell cilia
» Defects affect calcium signaling
» Mutations result in abnormal renal tubular growth
Gross pathology:
- Bilateral Enlargement
- Up to 4500 g
- Distorted shape
- Multiple cysts of varying sizes filled with clear, straw-colored fluid
Histo:
- Simple cysts lined by flattened cuboidal and columnar epithelium
- Arise from proximal and distal tubules as well as from the collecting ducts
- Normal renal parenchyma can be present between the cysts
Associated path:
- Hepatic Cysts—33% of cases
- Splenic Cysts—10% of cases
- Pancreatic Cysts—5% of cases
- Cerebral Aneurysms—No Family history- 6 % prevalence, family history -21% prevalence.
- Diverticular Disease of the colon often seen
Clinical Management of PKD
Supportive Care – Monitor Creatinine – Aggressive blood pressure control » ACEI, especially if there is evidence of proteinuria. » Avoid caffeine, DASH diet
Future therapies:
– Vaptans (ADH antagonists) have been effective
in animal studies in preventing progression – Human Studies are ongoing
Antibiotics:
- Some drugs do not penetrate cysts well. - Fluoroquinolones, TMP- sulfa,
chloramphenicol best for cyst penetration.
- Do not adjust dose for UTI in renal insufficiency.
Autosomal recessive polycystic kidney disease
AKA—Infantile Polycystic Kidney Disease
- Rare—1/10,000 to 1/50,000 births
- 75% of affected infants die perinatally
- Rare cases can manifest in older children
Clinical correlates:
- Results in Oligohydramnios (decreased amniotic fluid as fetal kidneys can’t properly filter blood, produce urine)
- Causes Pulmonary Hypoplasia due to mass effects
- See Associated Hepatic and Pancreatic Cysts
- Infants often have biliary dysgenesis and hepatic fibrosis
Pathogenesis:
Mutations in the PKHD1 gene
- Protein = fibrocystin
- Fibrocystin is involved in cell proliferation and adhesion
- Fibrocystin is found in the kidneys, liver, and pancreas
Pathology:
- Disease is Bilateral
- Enlarged Kidneys (often impede delivery)
- Fusiform Cysts of Collecting Ducts – Affects cortical and medullary ducts
- Cysts Arranged Radially, Perpendicular to renal capusule
- Accompanying interstitial fibrosis and tubular atrophy (due to compression)
Nephrocalcinosis: differential
Nephrocalcinosis with hypercalemia and hypercalciuria: associated with systemic problems: - Primary hyperparathyroidism – Sarcoidosis - Vitamin D therapy - Milk alkali syndrome
Nephrocalcinosis without hypercalcemia but presence of hypercalciuria- not systemic problem
– Distal RTA
- Medullary sponge kidney
- Premature infant with lasix usage
Medullary sponge kidney
Unknown pathogenesis:
Epidemiology:
- Sex predilection-slight male predominance
- Symptomatic cases usually emerge at 30-60 yrs
- Nonhereditary
Symptoms:
- flank pain, dysuria, hematuria, gravel sized stones.
- Hypercalciuria in 50% of symptomatic pts
Clinical course:
- Increased risk of kidney stones and urinary tract infection
- Excellent long-term prognosis – progressive disease very rare
Pathology:
- May be associated with hemihypertrophy
- bilateral in 75% of patients
- Cysts involve the branches of collecting ducts and papillae
- Glomeruli are normal if secondarily affected by distal obstruction
- Kidneys are not enlarged and are symetrical
- Discovered in work-ups of nephrolithiasis
Microscopic
– Flattened cuboidal or transitional epithelium
– Intracystic calcifications
– Associated intersitial inflammation
Acute renal failure: differential
- Acute tubular injury due to hypotension/ sepsis
- Staphylococcal pyelonephritis with abcess formation.
- Obstructive uropathy
- Prerenal from volume depletion (febrile)
Acute tubular injury
Etiology:
- Ischemic
- Toxic
- Inflammatory
- Immunologic
- Atrophy
- Viral
Management:
- Keep Mean arterial pressure>65
- No nephrotoxins
- Adjust Antibiotics dosage
- Once euvolemic, cautiously give IVF based on insensible losses and urine output
- Assess need for renal replacement therapy based on daily labs and clinical picture.
Sterile pyuria: differential infectious or non-infectious causes
Infectious causes
- A recently (within last 2 weeks) treated UTI
- Chlamydial urethritis
- Prostatitis
- Appendicitis – if appendix lies close to ureter or bladder
- Renal tract tuberculosis
- Adenovirus, BK,rejection – in immunocompromised patients
Non infection related
- Recent cystoscopy and urinary tract surgery
- Urinary tract stones
- Urinary tract neoplasm
- Interstitial nephritis
- Polycystic kidneys
- Interstitial cystitis-( cystoscopy shows inflammation with ulceration)
- SLE and other systemic inflammatory diseases, Kawasaki disease
Interstitial nephritis
Causes:
- DRUGS: NSAIDS, PCN, cephalosporins, rafampin, cimetidine, ciprofloxacin, allopurinol
- Infections: legionella, mycobacteria, streptococcus, CMV, BK polyoma etc
- Idiopathic- 8% Autoimmune disorders-SLE, sarcoidosis, Sjögren’s
syndrome.
- TINU (tubulo-interstital nephritis and uveitis) syndrome- flank pain, sterile pyuria, hematuria, proteinuria (usually subnephrotic range) and uveitis.
Histo:
- Key is eosinophilic infiltrate in interstitium - Variable amount of interstitial edema
- Can see “spill-over” effects on glomerulus
- Interstitial fibrosis is dependent on duration of disease.
