NEPHROLOGY
KAPLAN
2001 Kaplan Medical (800) 533-8850 or (949) 476-6282

Nephrology
< .... o ....  ,ccO01 Kaplan Medical (800) 533-8850 or (949) 476-6282
I. Acute Renal FailuremClassifications
A. Pre-Renal
Any cause of decreased renal perfusion.
1. Volume deficits
a. Hemorrhage
b. Poor oral intake
c. Burns
d. Diuretics
e. Gastrointestinal (GI) loss (vomiting, diarrhea, etc.)
f. Third spacing of fluids (e.g., panereafitis or peritonitis)
g. Sweating
h. Osmotic diuresis (e.g., diabetes)
i. Low aldosterone conditions (e.g., Addison's disease)
2. Cardiovascular
a. Congesuve heart failure
b. Pericardial disease (constrictive pedcarditis, tamponade)
c. Coarctation of the aorta
3. Decreased oncotic pressure (decreased albumin)
a. Nephrotic syndrome
b Catabolic states
4. Decreased systemic vascular reststance (e.g., shock)
Sepsis (any cause) bacterial, anaphylactic, neurogeaic, cardmgenic
5. Hepatorenal syndrome
Essentially, kidney disease secondary to liver disease; the kidneys themselves are normal, with laboratory
features similar to pre-renal causes.
6. Renal artery stenosis (particularly with use ofACE inhibitors)
B. Post-Renal (about 5% of cases)
Any cause of obstruction to the outflow of urine, from kidney to exit of urethra (e.g., staghorn calculus in renal
pelvis: neoplasm causing obstruction at any level; clot in ureter;, prostatic hyperplasia; strictures; neurogenic
bladder (i.e., functional obstructive); urethral obstruction.)
C. Intra-Renal
The most complex, but the following is a complete classificataon
1. Tubulo-interstitial
a. Ischemic
1) Acute tubular necrosis (ATN) is a poorly defined term that has no characteristic histologic features.
It implies a combination of ischemia (poor perfusion) and sometimes a toxic component.
2) Hypotensmn
a) 60% related to surgeD'
b) 40% medical
c) Duration of hypotension is critical: i.e., the longer the duration of hypotension, the greater the
incidence of ATN.
225413.00197 1'

 Nephrology • Acute Renal Ia o  .... e py ....
3) Toxins
Contrasts, drugs, pigments (e.g. rhabdomyolysis).
Three phases
a) Prodromal
The time between the insult and the onset of renal failure
b) Oligunc (< 400 cc/day)/Anuric (< 100 cc/day)
c) Postoliguric
A diuretic phase when recovery occurs, i.e., diuresing all accumulated fluid
Table 1. ..... Diagnosis: Howto Confirm the Difference BetweenPre.reland!ATN ' .....
Based on Lab Values
rine sm ........... :;  500." ,< 350
Udne Na + ........  <20 > 40
e N + ' :. .?" > Zo -=::-;'- :-" "'- ::: =-:;: -:>::;-  ..........
........................................ . ............
Urine:sediment - ;:; .......... 'sCant:-: .....  ,Full (brownish pigmented graAu!arc;
In ATN, teur Cfiot netrate.  I prerel, you hold ontoall ree H20-ndЈ
;  ..... ., ........  .. _ ,... ..... :: - =... ....
b. Allergic interstitial nephritis
1) Etiology
a) Drugs: These are the same drugs which, in general, cause allergic reactions.
i) Penicillins (almost any of them)
ii) Sulfonamides (antibiotics as well as diuretics like thiazides, furosemide and acetazolamide)
iii) Tuberculosis medications (Rifampin is most common).
iv) Allopurinol (also associated with evidence of hepatic injury)
b) Infections: virtually a_ origin (e.g., viral, bacterial, fungal)
2) Diagnosis
a) Fever, rash, eosinophilia (blood) as well as eosinophiluria (urine), hematuria, proteinuria (< 2
4 h)
b) Biopsy
Normal glomeruli with interstittal edema and eosinophils
3) Treatment
a) Stop offending agent
b) Short courses of steroids may help Usually a self-limited disease
c. Pigments (hemo/myoglobin)
Etiology
Hemoglobinuria from hemolysis (such as ABO incompatible blood transfusmns). Myoglobinuria
(rhabdomyolysis) that is usually associated with decreased intravascular volume and crush injuries,
seizures or severe exercise. ATN occurs secondary to precipitation of pigment in tubules and direct toxic
injury.
d. Proteins e.g., myeloma (Bence-Jones proteins)
(see Nephrotic Syndrome)
225413.00197

....  .... pe /vglrblogy Acute Renal Failure
Crystals
1) Oxalate
a) Primary hyperoxaluria
b) Ethylene glycol ingestion with increased anion gap acidosis. Diagnosis made by finding
calcium oxalate crystals in the urine. Treatment is wth alcohol, (which competes with alcohol
dehydrogenase) and with dialysis
2) Urate
Secondary to tumor lysis syndrome, chemotherapy, hematologic malignancies, and gout. Urate
precipitates in an acid environment (as opposed to calcium oxalate, which precipitates in an alkaline
environment). Treatment is with allopurinol, hydration, and alkalinization of the urine
f. Hypercalcemia
Leads to tubular epithelial damage, distal RTA, and nephrogenic diabetes insipidus.
g. Toxins
1) Analgesics
a) 2-10% of end-stage renal disease in the United States and up to 20% of end-stage disease in
Australia is due to analgesics.
i) Female/male ratio, 5:1. Phenacetin (largely metabolized to acetaminophen) and aspirin
especially in combination
ii) Secondary to prostaglandin inhibition (prostaglandins dilate the afferent arteriole and
increase renal blood flow) as well as papillary necrosis
b) NSAID
Complex, a combination of
i) Interstitial nephritis
ii) Direct toxic effect
iii) Papillary necrosis
iv) Inhibition of vasodilators (prostaglandins)
c) Diagnosis of analgesic nephropathies: sterile pyuria, hematuna, flank pain, mild protemuna,
history (need lg/d of ingestion for I-3 years to develop it)
d) Differential diagnosis of papillary necrosis
i) Analgesics
ii) Diabetes
iii) Sickle cell disease
iv) Urinary obstruction
v) Chronic pyelonephritis
e) Treatment: non-specific
2) Aminoglycosides
a) Renal failure occurs in 10%-30% of patients receiving these drugs
b) Hypokalemia and hypomagnesemia, are associated findings
c) This is a nonoliguric disease that is usually delayed 7-10 days after exposure.
3) Cepha]osporins/tetracyclines
4) Amphotericin B
Associated with nephrogenic diabetes insipidus and renal tubular acidosis ('RTA). Increasing
blood urea nitrogen (BUN)/creatimne, potassium wasting.
5) Contrast agents
Very common, especially with the following underlying problems:
Increasing age, diabetes, dehydration, myeloma, baseline renal disease. Occurs secondary to: direct
tubular damage, hypertonicity, intense vasoconstriction, tubular precipitation
225413.00197 3

 Nephrology • Acute Renal Fal °  .... e p, ....
6) Anti-neoplastics
Cisplatin/methotrexate/cyclosporns/mitomycin
7) Radiation
With doses above 2.000 rads to the kidneys
8) Metals
Lead, mercury, gold, lithium (nephrogenic diabetes insipidus)
9) Cyclosporine
Vascular
Many of these are often classified with the glomerular disorders
a. Wegener's granulomatosis
This is a form of polyarteritis nodosa that has granulomas. It is a renal/pulmonary disease that often
presents with hemoptysis, sinusitis, oral lesions, and otitis. Characteristic presence of anti-neutrophil
cytoplasmic antibodies (ANCA). Treatment is with cytotoxics and steroids.
b. Henoch-Schonlein purpura
Purpura, arthralgias, GI involvement with colic and bleeding, renal failure and fever, presence of
hematuria and proteinuria without edema or hypertension. It is a form of IgA deposition disease like
Berger's but with extrarenal involvement, Usually no specific treatment is needed. Treated with steroids
in severe refractory cases only.
c. Polyarteritis nodosa
Vascular inflammation and destruction leads to glomerular ischemia. Treat with steroids and
cytotoxics like most vasculitides
d. Thrombotic thromboeytopenic purpura (TTP, adults), and Hemolytic uremic syndrome (HUS,
children).
1) Renal failure
2) Microangiopathie hemolytic anemia
3) Decreased platelets
Thrombotic thrombocytopcmc purpura has the same three findings with:
a) Fever
b) Neurological changes
4) Treatment:
a) HUS is most often self-limited, requinng no treatmenL Steroids arc sometimes used in severe
cases
b) TTP is treated with plasmapheresis and steroids.
e. Cryoglobulius IgM and IgG deposition. Treat with plasma exchange
f. Hypertension (see end-stage renal disease)
g. Diabetes (see nephrotic syndrome)
4 " 7.254 i 3.(X)197

.............. lhrology Acute Renal Failure
3. Glomerular
The difference between glomerulonephritis and rapidly progressive glomerulonephritis is time course, i.e.,
most everything that causes glomerulonephritis can also deteriorate quickly, hence, rapidly progressive
glomerulonephritis.
a. Acute glomerulonephritis
1) Post-infectious glomerulonephritis
a) AJ." Virtually any infectious agent can cause glomerulonephritis (e.g., bacteria, viruses,
Rickettsia, protozoans). Group A beta hemolytic streptococci is the most common cause.
b) Presentation:
• 10 days to several weeks after pharyngitis
• "Smoky" urine signifying hematuria and proteinuria with hypertension and edema
particularly of the periorbital areas
° The course is usually self-limited with all symptoms resolving spontaneously over several
wee'ks or months.
c) Diagnoss: The clinical presentauon combined with several serologic tests is sufficient. Biopsy is
seldom necessary. Elevated ASLO (anti-streptolysin O) and AHT (antlhyaluronidase) and
decreased complement (C3) are the most helpful.
d) Treatment: Largely symptomatic and aimed at control of hypertension and fluid retention.
2) Systemic Lupus Erythematosus (SL])
The etiology, diagnosis and treatment arc covered as part of SLE management in the Rhcumatology
section. The presentation is extremely variable and can range from chronic, asymptomatic proteinuria
all the way to rapidly progressive glomerulonephntis and the need for dialysis.
3) Goodpasture's Svndr0m
a) Etiology: Idiopathic disorder characterized by antibodies against basement membranes.
b) Presentation: Exclusively pulmonary and renal. Seldom with other systemic manifestations.
Hematuria/hemoptysis.
c) Diagnosis: Rising BUN/creat, worsening chest x-ray; proteinuria and confirmed by presence of
anti-basement membrane antibodies.
d) Treatment: Plasmapheresis to remove circulating antibody.
4) Ithopathic rapidly progressive glomerulonephritis
In addition, to those secondary to systemic diseases there is an idiopathic form characterized by
numerous crescent formation, acute renal failure, and positive ANCA without immune deposits.
This is a severe disease of unknown etiology that responds to steroids on a limited basis.
5) IgA nephropathy Olerger's disease)
a) Disease of those younger than 35 years
b) Often follows a viral illness
c) Charactet'ized by hematuria, increased serum IgA, and lgA deposition in skin. Similar to
Henoch-Schonlein purpura, but limited solely to renal manifestations.
6) Alport's syndrome
Hereditary: renal failure with hearing loss and ocular defects
22541.()197 5

 Nephrology • Acute Renal ar ° orae p, ....
b. Nephrotic syndrome
1) Etiology: Almost all the vasculitides and glomeruloriephritides can cause nephrotic syndrome. Most
causes of glomerulonephritis can go on to become nephrotic. Diabetes, amyloid, and multiple
myeloma are examples of systemic diseases producing renal abnormalities leading to nephrotic
syndrome. In addition, there are certain idiopathic causes listed below with disease limited solely
to the kidney and indistinguishable clinically. Only one tenth of childhood nephrotic syndrome is
secondary to systemic disease, while in adults, systemic diseases are much more common causes.
a) Nil lesion (minimal change disease)
Accounts for 90% of childhood and 15% of adult nephr0tic syndrome. It is characterized by
fusion of foot processes histologically without light microscopic abnormalities (i.e.. only
abnormal on electron microscope, hence the name "minimal change disease"). There is no
immune deposition and the treatment is with steroils, which are very effective
b) Membranous nephropathy
This is the most common idiopathic form in adults. There are immune deposits and steroids
are of little use
c) Membranoproliferative
Characterized by tmmune deposits and low complement
d) Mesangial
e) Focal segmental glomeruloselerosis
Typical of heroin nephropathy, and AIDS Nephropathy Presents wRh hematuria and
increasing BUN/creatinine. Only 20% of patients are steroid-responsive, hence, there ts a greater
use of cytotoxic agents
2) Presentation
a) Proteinuria (> 3.5 g/d)
b) Hypoalbuminemia (secondary to above)
c) Edema
d) Hypeflipidemia
e) Hyperlipiduria
f) Although hypereoaguability commonly occurs, it is not part of the definition of nephrotic
syndrome (it is secondary to increased urinary loss of antithrombin lII)
3) Diagnosis
• 24-hour urine sample to document the massive proteinuria
• .Rising BUN/crcatmine
• Biopsy is the 9.IILg way to ultimately tell the difference between the five idiopathic types listed
above
4) Treatment: Steroids are the best |nttlal treatment. Each of those listed above respond in varying
degrees.

II. End-Stage Renal Disease (renal failure to the point of needing dialysis)
A. Etiology
Black persons > white persons
1. Diabetes, 30%
2. Hypertension, 25%
3. Glomerulonephritis, 15
4. Unknown, 15%
5. Cystic disease, 4%
6. Other, 11%
B. Clinical and laboratory manifestations and their treatment
1. Hyperkalemia
2. Hypocalcemia/hyperphosphatemia
Secondary to decreased production of 1,25 dihydroxy vitamin D2 in the kidney, as wall as peripheral
resistance to parathyroid hormone. This results in increased fecal loss of calcium, decreased urinary loss of
phosphorus, and the deposition of calcium and phosphorus in soft tissue, more often in the acute form. The
secondary hyperparathyroidism eventually leads to calczum leaching from bones.
3. Hypermagnesemia
Secondary to decreased urinary loss, rarely symptomatic. The only treatment is to avoid magnesium-
containing medications.
4. Hypertension and accelerated atherosclerosis
In part secondary to increased sodium retention and to an altered renin-angiotensin-aldosterone axis.
The increased atherosclerosis is partly secondary to increased lipids.
5. Pericarditis
6. Anemia
One of the major problems with end-stage renal disease. Secondary to decreased erythropoietin production
Treated with erythropoietin and transfusions.
7. Infections/altered leukocyte function
A leading cause of morbidity and death
8. Increased bleeding
Unclear etiology, likely secondary to altered platelet function, with an increased bleeding time
9. Osteodystrophy
Because of secondary hyperparathyroidism and leaching of calcmm from bones with osteomalacia and osteitis
fibrosa resulting. Treat with vitamin D, phosphate binders (Amphojel). and calcium replacement.
10. Neuropathy and encephalopathy
Resulting in seizure, lethargy, myopathy.
11. Hyperuricemia
12. Pruritus
C. Indications for Dialysis: initiation of dialysis is never dependent on any specific BUN/creatinine level.
1. Hyperkalemia
2. Acidosis
3. Fluid overload
4. Pericarditis
5. Encephalopathy

III. Fluid And Electrolyte Disorders
A. Hyponatremia
1. Pseudohyponatremia
a. Hyperlipidemia
b. Hyperglycemia (Ha+ decreases by 1.6 mg% for every 100 rag% increase in glucose above normal.)
(Memorize this relationship)
2 Hypervolemic states: Secondary to decreased intravascular volume with increased baroreceptor stimulation
and increased ADH (antidiuretic hormone) production. Also secondary to decreased water delivery to
dilating segments of the nephron and decreased free-water clearance.
a. Congestive heart failure
b. Nephrotie syndrome
c. Cirrhosis
3 Hypovolemic states: All these forms rcqmre ingestion of hypotom" fluids to drive the sodium down. With GI
losses, diuretics and burns it is the replacement with hypotoni" fluid that gives the hyponatremia.
a. Any GI loss:
Vomiting, diarrhea, nasogastric suction, etc.
b. Skin losses:
Burns, cystic fibrosis, sweating, etc.
c. Diuretics
d. Sah-losing nephropathies
With GI losses, duiretics and bums it is the replacement with hypotonic fluid that gives the hyponatremia.
e. Addison's disease (Glucocorticoid insufficiency)
4. Euvolemic states
a. Psychogenic polydipsia (> 10-15 L/day intake is needed).
b. Hypothyroidism
c. Syndrome of inappropriate secretion of ADH (SIADH)
I) Etiologies
a) CNS: Practically any abnormality (infection, stroke, tumor, vascnlitis, psychosis)
b) Pulmonary: Practically any abnormality (pneumonia. pulmonary embolus, TB, asthma,
atelectasis, pneumothorax)
c) Drugs
1) Oral hypoglycemcs
2) Haldol
3) Cyclophosphamide
4) Vincristine
d) Neoplasm
Most commonly Iung (oat cell), but also pancreas, duodenum or thymus
2) Presentation. The symptoms of any cause of hyponatremia begin generally below a value of 125
meq/L. They are almost entirely neurologic in nature. Headache, lethargy, obtundation and
eventually coma and seizures are most common.
3) Diagnosis
Urine osmolality > (greater than) serum osmolality in the presence of hyponatremia is generally
diagnostic. Serum ADH levels are not used. Urine sodium > 40 is typical.
4) Treatment: Corrections should not be faster than 12 meq per day. Overly rapid correction results in
central pontine myelinolysis. This is destruction of the brainstem, giving paraparesis, dysarthria or
dysphagia.
a) Mild (approximately 120-130) fluid resmction to less than 1000 cc per day.
b) Moderat (approximately 110-120) loop diuretic and normal saline to give a net free-water loss.
3 22413.o019,

< a o;l)yc(z > Fluid and Electrolyte Disorders
c) Severe (approximately < 110 with symptoms) hypenonic saline
d) Chronic
Lithium and demeclocycline cause a nephrogenic diabetes insipidus. This makes the kidney
insensitive to ADH.
B. I-lypernatremia
1. Etiology:
a. Insensible losses: Extra-renal loss without intake of hypotonic fluids. Increased skin loss (sweating,
burns, fever, exercise) or respiratory infections.
b. GI loss: osmotic diarrhea (e.g., lactulose, malabsorptlon), some infectious diarrhea.
c. Renal:
i) Nephrogenic Diabetes Iusipidus (qXrDI), secondary to renal disease, increased calcium, decreased
potassium, lithium, demeclocycline, sickle cell disease and others.
2) Central DI (CDI)
Idiopathic, trauma, infectious, tumor, granulomatous, hypoxic brain damage or from neurosurgery.
Idiopathic most common.
3) Osmotic diuresis: diabetic ketoaeidosis (DKA), non-ketotlc hyperosmolar coma, mannitol,
diuretics.
2. Presentation: primarily neurologic.
Lethargy, weakness, irritability, seizures, and coma are present with severe hypernatremia of any cause.
Diabetes insipidus gives a dilute diuresis of 3-20 liters/per day.
3. Diagnosis: CDI vs. NDI
Watching for a decrease in urine volume after administering ADI-I disungmshes CDI from NDI.
Figure 8-1: Water Restriction Test
Urine
Volume
Giving
A
...... Complete NDI
Central DI
 Normal
r
Serum Osmolarity
225413.C)019 g

oa e pcc >
4. Treatment: Acute hypernatremia is treated with isotonic fluids intravenously. Correction of sodium should not
be greater than 1 mEq every two hours or 12 mEq/L per day. Complications of overly rapid correction
include cerebral edema, permanent neurologic damage or seizures.
a. Central Diabetes Insipidus (CDI).
I) Correct the underlying cause, if possible.
2) Give vasopressin (ADH). It can be given subcutaneously, intravenously, intramuscularly or by nasal
spray. (All routes except oral).
b. Nephrogenic DI
1) Correct underlying cause, if possible.
2) Diuretic or NSAIDS. NSAIDS work by inlfibiting prostaglandins which impair concentrating ability.
NSAIDS will increase the acuon of ADH at the lddney.
C. Hypokalemia
1. -Etiology
a. Decreased oral intake, (rare)
Clay ingestion (binds K +. preventing absorption)
b. Increased entry into cells (transcellular shift)
1) Alkalosis--
Cellular buffering causes H + release from cells
2) Increased insulin
Promotes K* entry into cells with glucose
3) adrenergic activity
c. GI losses
Vomiting, diarrhea, tube drainage, etc.
d. Increased urinary loss
1) Primary hyperaldosteronism/Conn's syndrome
2) Diuretics
3) Cushing's disease
4) Licorice (contains glycyrrhizic acid, which has mineralocorticoid activity)
5) Bartter's syndrome
Primary inability to reabsorb NaC1 from Loop of Henle, resulting in increased reran, increased
aldosterone
2. Presentation
a. Symptoms usually start when potassium falls to < 2.5 to 3.0 meq/L.
b. Muscle weakness, paralysis, cardiac arrhythmias, U-wave on EKG, T-wave flattening,
rhabdomyolysis, nephrogenic DI.
3. Treatment
a. Correction of underlying cause when possible.
b. Repletion
1) IV maximum 10 mEq/h
2) Oral: should be less than 200 meq/day.
3) GI tract slows absorption
4) Potential complication of too rapid repletion is fatal arrhythmia.
1 0 225413.00197

..... I;0 cc> Fluid arld Electrolyte Disorders
D. Hyperkalemia
I. Etiology
a Increased intake (orally or by IV)
Usually in presence of impaired excretion
b. Movement from cells to _extra-cellular_fluid (ECF)
1) Pseudohyperkalemia
Secondary hemolysis, mechanical trauma during venipuncture, platelet count > 1,000,000 (106),
WBC count > 100,000 (10.
2) Acidosis
Secondary cellular buffering (H + moves into cells, K + out)
3) Insulin deficiency
4) Tissue breakdown
Rhabdomyolysis, tumor lysis, after seizures or severe exercise.
5) Periodic paralysis
Mild, brief episodes of muscle weakness with mild increase in K + (<5.5). Diagnosis with recurrent
attacks and farmly history.
c. Decreased urinary excretion
1) Renal failure
2) Hypoaldosteronism
Type IV RTA, adrenal enzyme deficiency
3) Primary adrenal insufficiency
(Addison's disease) or adrenalectomy
4) Potassium-sparing diuretics
Triamterene, amiloride, spironolactone
2. Presentation: muscular weakness can begin usually with K + levels > 6.5.
Abnormal cardiac conduction is the most common cause of death.
3. Diagnosis:
EKG fiadings: Peaked T waves, widened QRS, short QT.
4. Treatment
a. Calcium chloride
"Membrane stabilization," (most emergent treatment in presence of EKG abnormalities.). Effect is
immediate and short-lived.
b. Sodium bicarbonate
Alkalosis drives K + into cells. Do not give in same IV line as calcium.
Forms CaCO 3 precipitates
c. Glucose and insulin
Drives K + intracellular, takes 30-60 minutes to work
d. Cation exchanges re,sins (Kayexalate)
Resin absorbs 1 meal K ч per gram and releases 1 rnEq Na ч. G:ven with Sorbitol to prevent constipation
It must be given with the above treatments since they only cause cellular redistribution of K ч and do not
remove it from the body. It can also be given as a retention enema for some who cannot take it orally.
e. Dialysis

 Nephrology • Renal Tubulgrd:i .............
IV. Renal Tubular Acidosis (RTA)
A. Distal (Type I)
1. Etiology
a. Usually sporadic
b. Also secondary to autoimmune disease (e.g., Sjigren's)
c. Drugs
Amphotericin, lithium.
d. Nephrocalcinosis, sickle cell.
2. Presentation
a. Inability to develop a high H ч concentration in urine. Urine pH is >, 5.4.
b. Secondary hyperaldosteronism and hypokalemia.
c. Nephrocalcinosis and nephrolithiasis.
3. Diagnosis
Acid load test; give ammonium chloride which should lower urine pH secondary to increased H + formation,
With type I RTA. the urine pH remains elevated. Serum bicarbonate = 10
4. Treatment
Oral bicarbonate because bicarbonate reabsorption in the proximal tubule still works.
B. Proximal (Type II)
I. Etiology
Fanconi's syndrome, Wilson's disease, myeloma, vitamin D deficiency, chronic hypocalcemia, and certain
drugs
2. Presentation
a. Inability to absorb bicarbonate. The initial urine pH is basic (until the body loses enough bicarbonate
that it is within the'range of absorption of the distal tubule), then the urine will become acidic (pH <
5.4)
b. Also with hypokalemia and a serum bicarbonate of 18-20
c. Patients with type II get bone lesions (osteomalacia and rickets), while type I get kidney stones. Both
get hypokalenda.
3. Diagnosis
a. Patients are unable to absorb bicarbonate loading, and have a basic urine in the presence of acidemia
b. Normal individuals do not excrete bicarbonate in their urine until serum bicarbonate is > 24.
4. Treatment
Mild volume depletion will enhance proximal bicarbonate reabsorption (a type of contraction alkalosis).
C. Hyporeninemic/Hypoaldosteronism (Type IV)
1. Etiology
a. An aldosterone deficiency of any cause or adrenal insensitivity to angiotensin II, which normally
stimulates aldosterone release.
b. Diabetes (50%)
c Addison's disease
d. Sickle cell disease
d. Renal insufficiency
2. Presentation
a. Usually asymptomatc hyperkaierma
b. Mild to moderate renal insufficiency
c. Hyperchloremic metabolic acidosis (non-anion gap)
1  22513 (X197

..... 6°ra'CO° > ° Acid-Base Disturbances
3. Diagnosis
Continue high unne sodium with oral salt restriction
4. Treatment
Administration of Fludrocortisone. Fludrocortisone has a high degree of mineralocorticoid effect and is
similar to administering aldosterone
V. Acid-Base Disturbances
A. Alkalosis (high pH)
1. Metabolic
a. H + ion loss
Exogenous steroids
1) GI loss (vomiting, et cetera)
2) Renal loss (Conn's syndrome, Cushing's)
3) Decreased chloride intake
4) Diuretics
b. HCO3 retention
1) Bicarbonate administration
2) Contraction alkalosis
3) Milk-alkali syndrome
c. H + movement into cells
Hypokalemia
2. Respiratory
a. Hyperventilation of any cause
1) Anemia
2) Pulmonary embolus
3) Sarcoid
4) Anxiety
5) Pain
b. Anion gap = (Na + + K +) - (I-ICO' + CI')
Normal 8-14
B. Acidosis 0ow pH)
1. Metabolic
a. Non-anion gap
1) Diarrhea
2) Renal tubular acidosis
b. Anion gap LA MUD PIE (mnemonic)
Lactate (sepsis, ischemia, et cetera)
Aspirin
Methanol
Uremia
Diabetic ketoacidosis (DKA)
Paraldehyde, Propylene glycol
Isopropyl alcohol. INH
Ethylene glycol
zs4.oos 13

 Nephrology • Acid-Base [ic ...........
2. Respirator
Hypoventilation of any cause
a. Chronic obstructive pulmonar disease (COPD)
b. Pickwickian
c. Obesity
d. Suffocation
e. Opiates
L Sleep apnea
C. Important Principles
1 Principle I
For ever change of 10 in pCO 2 (up or down) there is an opposite change of 0.08 in pH (i.e., as CO 2
increases, pH decreases and as CO 2 decreases, pH increases)
2. Principle II (Table 2).
Table/2. Primary DisturbancedTlieirCtmpensabryResponses -
Disorder pH (H +) Primary.  !:Coition :.,,:.Me/:hanisms of Compensation
..etabolic acidosis $ 1" ...............  HCOIII" !ipC2/! ?:.   ........ Increases' respirato te
:. ;:: ..   .. .. ...  .. ...... . ...... ,.. ,, .:...
,Resito.cidosis   :- ...... '.  i ....  ... . .2436 hours for maximu m effe."
Resato W alkalosis  "  .. p':. '" .: ........ ; "Rnarl .... f birbonate.
. :.. . ...... . ..   . ..
3. Principle IH
The body does not overcompensate.
For example, patients do not "'over breath into respiratory alkoloss" as respiratory compensation for metabolic
acidosis. Correction is made to just short of normal.
14 22541].00197

.....  ....  wlephfology Nephrolithiasis 
VI. Nephrolithiasis
A. Etiology
1. Occurs in 1-5% of the population
2. Composition of stones
• Calcium oxalate 70 %.
• Calcium phosphate 10 %.
• Mg/aluminurn/phosphate (Struvte) 5-10%
• Uric acid 5%
• Cysteine 1%
3. Hypercalciuria
a. Increased absorption
1) Vitamin D intoxication
2) Increased vitamin D with sarcoid and other granulomatous disease
3) Familial
b. Idiopathic renal hypercalciuria
c. Resorptive
1) Hyperparathyroidism (10-30% of pauents present with stones)
2) Multiple myeloma, metastatic disease to bone, hypercalcemia of malignancy
4. Hyperoxaluria
a. Primary familial
b. Enteric
With fat malabsorption, the fat binds to calcium, leaving oxalate to be reabsorbed in increased amounts.
5. Hypocitraturia
Citrate usually binds with calcium and prevents calcium absorption. Low citrate leads an increase m calcium
absorption. Causes of hypocitraturia include any acidotic condition.
6. Uric acid stones
They form in an acid environment and are associated with diseases like gout, hematologic malignancies, and
Crohn's disease.
7. Cystinuria
Only associated with the genetic disorder
8. Infection
Urinary infection with urease-producing organisms like Proteus, Staphylococcus, Psendomonas, and
Klebsiella give a highly alkaline urine that produces struvite stones.
B. Presentation
1. Constant flank pain (not colicky), hematuriao and pain radiating to groin.
2. Stones < 5 mm should pass spontaneously
C. Diagnosis
1. Plain x-ray (80% yield)
2. Ultrasound
3. Strain the urine
4. Check serum and unne calcmm
5. Intravenous pyelogram
D. Treatment
1. Analgesia, hydration, and bed rest are the mainstays of treatment.
2. Shockwave lithotripsy for stones < 2 era. Unfortunately, the fragments may cause obstruction themselves
3. Percutaneous removal. This requires more anesthesia and hospital stay

 Nephrology • Her ed ita ry <C: 5 ie .........
VII. Hereditary Cystic Disease
Adult Polycystic Kidney Disease
1. Etiology
a. Genetic
Prevalence of 1:200 to 1:1000
b. Pathogenesis is uncertain
2. Presentation
a. Flank pain, hematuria (mlcro and gross), infections, and calculi.
b. May also present as asymptomatic on screening of family members.
c. Extra-renal manifestations
1) Hepatic cysts (40-60%)
2) Colonic diverticula
3) Hypertension
4) Intracranial aneurysm (10-40%)
5) Mitral valve prolapse (25%)
3. Diagnosis
Ultrasound and CT scan
4. Treatment
Nonspecific, management of complications (UTI, calculi, and hypertension)
B. Simple Cysts
They are very common and if they are smooth-walled with no debris in the cyst, they can be managed without
any further treatment or need for diagnostic tests. Cysts with irregular walls or debris inside should be
aspirated to exclude malignancy.
VIII. Hypertension
A. Essential Hypertension
1. Definition: A systofic blood pressure of 140 mmHg or a diastolic > 90 on multiple readings in the absence
of a specific, identifiable underlying cause. It is divided into classifications as follows:
.... ............. .:.,: ,, .,. ..... , : ,. ,..:
2. Etiologypidemiolo
An esdma[ 50 llion edcs have gh blood presse. spi muluple eoes on e mechsm.
•ere is NO r under.dog of what es sen heion. en herion accoun
for > 95 % of  c of hypeeion. It h more common  cg age and is found in hf e
population over age 60. It is more on in men an women until er menopause. It  more coon 
the black popaon at I ag, and e incidee of end o dage h mo common in blac as
well. Onset is usuly between ages 25-55.
1 6 225413.00197

..... 0 .... e ,olephrology • Hypertension
3. Presentation:
The most common presentation of essential hypertension is an asymptomatic patient on whom the
elevation of blood pressure is found during a routine examination or during evaluation for other medical
problems.
When symptoms are associated with hypertension, t s more correct to think of them as either (a) the acute
symptoms associated with a hypertensive emergency; (b) long-term complications from end-organ damage, or;
(c) concomitant symptoms of the diseases underlying secondary causes of hypertension.
a. Hypertensive emergency: Signs and symptoms of cardiac, neurologic, renal and retinal involvement
are the most common. These include evidence of stroke, subarachnoid hemorrhage, encephalopathy,
myocardial ischemia and abnormalities on fundoscopic examination. These can acutely and most
commonly result in headache, dizziness, chest pain, dyspnea, blurred vision and palpitations.
(Hypertensive emergency is covered in full later in these notes.)
b. Long-term complications
1) Cardiac - Myocardial ischemia or infarction, congestive heart failure, left ventricnlar
hypertrophy, aortic aneurysm and dissection. On physical exam, an $4 gallop, accentuated A2
heart sound and prominent left ventricular impulse can be present.
2) Cerebrovascular - Transient ischemic attack (TIA) or stroke.
3) Renal Proteinuria - microscopic hematuria, and elevation of BUN/creatinine which may lead to
the necessity of dialysis.
4) Retinopathy - Hemorrhages, exudates, arteriolar nat-rowing and papilledema. They result in
blurred vision, scotomata and sometimes blindness.
c. Secondary Hypertension - The presentauon depends upon the individual cause. For example:
Renovascular disease gives an abdominal bruit; Cushing's disease gives weight gain, moon-like
facies, striae and ecchymoses: Pheochromocytoma gives episodic hypertension associated with
headache, palpitations and sweating; Primary aldosteronism (Conn's syndrome) gives muscular
weakness and polyuria/polydipsia from hypokalemia. There are discussed more fully later in the
notes.
4. Diagnosis
a. Confhanation of Hypertension
As much as 20%-25% of mild office hypertension is artifactual in nature. These initial elevated readings
merely represent a manifestation of anxiety on the part of the patient to the doctor and medical
environment. This is known as "wldte-coat hypertension." In this case, we are talking about patients who
have no evidence of end-organ damage. When these patients are given time to adjust to the environment
by being allowed to sit quietly before the reading is taken, their pressure will lower. When these patients
are given an ambulatory pressure-monitoring device to measure their own pressure at home or work,
many of them will normalize their pressure. In addition, with each subsequent visit to the physician's
office, the patient's p(essure will often lower toward its true value.
Hence, prior to labehng a patient with a mild elevation as truly hypertensive and initiating therapy, the
following steps are necessary.
1) Allow the patient to sit quietly for five minutes before the pressure is measured.
2) Never label a patient as hypertensive after only a single reading.
3) Repeat the reading from 3-6 times over several months before confirming the diagnosis and
initiating therapy.

 Nephrology ° Hypertension < ....  ....  p, >
b. Laboratory investigation
Most routine lab testing will generally be normal. Testing is usually kept within the bounds of those done
during a routine medical evaluation. The purpose is to evaluate the extent of end-organ damage as well as
to exclude some forms of secondary hypertension. The reasons listed are the most common ones, not the
only ones
Basic studies include.
• Urinalysis for protein, glucose and red blood cells.
• Hematocrit.
• Serum potassium to exclude hyperaldosteronism.
• Serum creatinine and BUN.
- Electrocardiogram to evaluate for left ventricular hypertrophy.
• Glucose and plasma lipid analysis as an indicator of atherosclerotic risk.
5. Treatment
a. Lifestyle modification
Patients with confirmed mild and moderate hypertension should initially be treated with
nonpharmacologic modifications in lifestyle. These include weight reduction in the obese, dietary
sodium restriction, aerobic exercise and avoiding excessive alcohol intake.
Patients with severe hypertension (diastolic >110) should generally be started immediately on drug
therapy. There is a linear correlation of increasing weight with increasing blood pressure. Obesity further
increases cardiovascular risk by increasing LDL-cholesterol, decreasing HDL and decreasing glucose
tolerance. There is generally a 0.5-1.0 mm Hg drop m diastolic blood pressure for every kilogram of
weigh that is lost.
b. Drug treatment
1) Who to treat?
Patients who continue to have a diastolic blood pressure > 90 mm Hg despite a 3-6 month trial
of non-pharmacologic therapy should generally be started on antihypertensive drugs.
The decrease in end-organ damage such as myocardial infarction and stroke with drug treatment is
generally eater in those who have a higher baseline blood pressure. In other words, someone who
has a diastolic pressure greater than 110 will show a much greater reduction in risk of stroke with
drug therapy compared with someone whose diastolic pressure is only 90-95 mm Hg
2) What to use?
There are almost 50 different medications approved for the initial treatment of hypertension, not
including combination medications. The major medications with their individual characteristics are
listed at the end of this section.
General principles are:
a) In the absence of a specific indication or contraindication, diuretics and beta-blockers are still
recommended as initial treatment.
b) Every attempt should be made to individualize therapy based on the characteristics of each
patient. To do this, you must be familiar with the characteristics of each class of drugs listed later
in these notes.
3) What are the indications for specific hypertensive groups?
a) Diabetics: Should be treated with ACE inhibitors, because they prevent the development of
nephropathy.
b) Post-myocardial infarction (ischemic heart disease). Should be treated with beta-blockers.
c) Diminished left-ventricular systolic function (such as with congestive heart failure or post-
myocardial infarction). Should receive ACE inhibitors.
d) Black patients: Most effectively treated with diuretics or calcium channel blockers. Black
patients are least effectively treated with ACE inhibitors.
e) Pregnant patients are best treated with labetalol or hydralazine.

B. Hypertensive Emergencies
1.
.....  .... ,  :Stephrology • Hypertension 
Definition: The acute onset of severe hypertension in association with severe and rapidly worsening
symptoms of end-organ damage. This usually happens with diastolic pressure > 120-130 mmHg. The terms
'malignant' and 'accelerated" hypertension are difficult to disfingmsh climcally, with 'malignant' usually
referring to the more severe syndrome.
2. Etiology/Epidemiology
The cause is unknown. Hypertenswe emergencies occur in about 1% of hypertensive patients.
3. Presentation
a. Neurologic: encephalopathy, headache, confusion, seizures, subarachnoid or intracerebral
hemorrhage.
b Cardiac: chest pain, myocardial infarction, palpitations, dyspnea, pulmonary edema, jugular
venous distension and gallops.
c. Nephropathy: acutely progressive hematuria, proteinuria, and renal dysfunctiofi.
d. Retinopathy: papilledema, hemorrhages, blurred vision.
4. Diagnosis
The laboratory evaluation is the same as with essential hypertension except that there is no concern of
artifactual 'white coat hypertension' given the clear symptoms. CT scan of the head may be necessary to
exclude hemorrhage. EKG is more important as an initial test in order to exclude infarction.
5. Treatment
Intravenous therapy is ndicated. Nitroprusside and labetalol are the two best agents. Nitroglycerin is
preferable in those who have evidence of myocardial ischemia. Enalaprilat is an intravenous ACE
inhibitor that is now being used as well. Other less commonly used agents include: esmolol, diazoxide and
trimethaphan.
The most important point in management is not to lower the pressure too far e.g., not < 95-100 mm
Hg diastolic) so as not to compromise myocardial or cerebral pcrfusion.
C. Secondary Hypertension
I. Definition: Hypertension in the presence of an identifiable underlying cause.
2. Etiology/Epidemiology
Less than 5% of cases of hypertension are secondary to an identifiable underlying cause. Renal artery
stenosis is the most common of these causes.
3. Who should be screened for secondary hypertension?
• Those who become hypertensive either very young or very old (< 25 or > 55).
• Those with a key feature of history, physical examination or laboratory abnormality consistent with a
particular form as described below.
• Patients who remain hypertensive despite increasing dosages and numbers of antihypertensive
medications, i.e., those refractory to what should normally be effective therapy.
a. Renal artery stenosis
This is due to arthrosclerotic disease in the elderly and fibromnscular dysplasm in young women.
Presenta,q'on: The key feature is an upper abdominal bruit radiating laterally which is present
in S0-70% of patients.
Diagnosis: The best inRial screening tests are the abdominal ultrasound and the captopril
renogram. The captopril renogram is a test that measures the uptake of a radioisotope before and
after the administration of captopril. A positive test is when there is decreased uptake of the isotope
(i.e., decreased GFR) after giving the captopril. The captopril renogram has now become the best
NONINVASIVE method of confirming the diagnosis of renal artery stenosis. The arteriogram is
still the best method of conf'h"ming the diagnosis, lnlavenous pyelography, duplex Doppler
ultrasonography and selective renal vein renin determinations can be useful as well.
Treatment: The best initial treatment is percutaneous transluminal angioplasty. If stenosis recurs,
then the procedure should be repeated. If angioplasty fails, surgical resection is attempted. Medical
therapy with ACE inhibRors should be reserved only for those in whom angioplasty or surgery
either fails or is not possible.
22s413.001s7 19

 Nephrology • Hypertension .....  ....  , ....
b. Primary Hyperaldosteronism (Conn's syndrome)
This is most commonly due to a unilateral adenoma. Adenomas can also be bdateral. The rest of the
cases are from bilateral hyperplasia. Cancer is rare as a cause of hyperaldosteronism.
Presentation: They key features are either:
i. Hypertension in association with hypokalemia found on routine screening tests.
ii. Symptoms of hypokalemia such as muscular weakness and plyuria and/or polydipsia from a
nephrogenic diabetes insipidus.
Diagnosis: Elevated aldosterone levels in urine and blood.
Treatment: Surgical resection in those with an adenoma. Potassium sparing diuretics such as
spronolactone in those with hyperplasia.
c Pheochromocytoma is most often due to a benign tumor of the adrenal gland. 10% are bilateral, 10% are
malignant, and 10% are extra-adrenal.
Presentation: The key feature is episodic hypertension in association with headaches, sweating,
palpitations and tachycardia. Pallor or flushing may also occur.
Diagnosis: The best initial test is urinary vanillylmandelic acid (VMA), metanephines and free
urinary catecholamines. Plasma catecholamine evaluation is helpful as well. CT and MRI scanning
is used to localize the site of the tumor.
Treatment: Alpha-adrenergic blockade followed by surgical removal.
d. Cushing's disease is most often due to ACTH hypersecretion by a pituztary adenoma.
Presentation: The key feature is hypertension in association with characteristic cushingoid
manifestations such as truncal obesity, buffalo hump, menstrual abnormalRies, striae and impaired
healing, etc.
Diagnosis: Dexamethasone suppression testing and 24-hour urine cortisol are the best initial tests.
Treatment: Surgical resection is best when possible.
e. Coarctation of the Aorta
The key feature is hypertension markedly greater in the upper extremities compared with the lower
extremities.
f. Miscellaneous
Other causes of secondary hypertension are the use of oral contraceptives, acromegaly, congenital
adrenal enzyme deficiencies and virtually any cause of chronic renal disease such as glomerulonephritis,
polycystic disease, diabetic nephropathy or chronic pyelonephritis.
D. Antihypertensive Medications
:!:Tli!|e:, .. :. i: I. :ii .ii.i:::-i.ii; . IIII:I<-.., :[([o0 p Diuretics
,.dah:  ..... ..................... .... ........ .:
o, -

.....  ....  wlephrolgy • Hypertension
I. Diuretics:
a. Specific Indcatlons
Congestive heart failure, edematous states, black pauents
Least expensive
b. Major side effects
Decreases in potassium and magnes|um
Increases in calcium, uric acid, glucose, LDL-cholesterol
Gynecomastia
c. Relative contraindicatlons
Diabetes, gout, hyperlipidemia
2. Beta Blockers
Acebutolol Atenoloi
Penbutolol Labetalol
Betaxolol Pindolol
Bisoprolol Propranolol
Carteolol Timoloi
Metoprolol
Nadolol
(Combined alpha/beta)
a. Specific indications
Myocardial infarction or ischemic heart disease
Supraventricular arrhythmias.
Migraine headaches, glaucoma, anxiety (resting tachycardia).
Congestive failure from diastolic dysfunction
b. Major side effects
Bronchospasm, heart block, bradycardia, Raynaud's
phenomenon, depression, impotence, fatigue
Decreased HDL, increased triglycerides, hyperglycemia
c. Relative contraindications
Asthma or COPD, atriovcntricular conduction defects.
Congestive heart failure from systolic dysfunction.
Diabetes because of masking signs of hypoglycemia.
3. Angiotensin Converting Enzyme (ACE) Inhibitors
Benazepril Lisinopril
Captopril Moexipril
Enalapril Quinapril
Fosinopril Ramipril
Enalaprflat (only IV form)
a. Specific indications
Diabetics with hypertension to prevent nephropathy.
Congestive heart failure as afterload reduction.
Post-myocardial infarction with left ventricular impairment.
b. Major side effects
Cough. angioneurotic edema, neutropenia, hyperkalemia, taste disturbances, anaphylactoid reactions.
c. Relative contraindications
Less effective in black, patients
d Absolute contraindications
Bilateral renal artery stenosis, pregnancy.
22543.00197 2|

 Nephrology ° Hypertension
4. Calcium Channel Blockers
Amlodipine
Diltiazem
Felodipine
Isradipine
Nicardipine
Nifedipine
Verapamll
a. Specific indications
Angina pectoris, supraventricular arrhythmia
Migraine, Raynaud's phenomenon, esophageal spasm.
b. Major side effects
Peripheral edema, constipation, heart block, reflex tachycardia.
c. Relative contraindications
Atriovcntricular conduction defects.
Congestive hear failure from systolic dysfunction.
5, Alpha-adrenergic Blockers
Doxazosin
Prazosin
Terazosin
a. Specific indications
Patients with lipid disorders (they reduce LDL and increase HDL)
Prostatic hypertrophy, to reduce obstructive symptoms.
b. Major side effects
Syncope after the first dose, dizziness, headache.
c. Relative contraindications
None
6. Angiotensin receptor antagonists
Losartan
a. Specific indications
Those intolerant to ACE inhibitors (especially because of cough).
b. Major side effects: few. This is the newest class of antihypertensives.
c. Absolute contraindications
Pregnancy

.....  .... . ,e.ohrology Hypertension
The remainder of these medications should be considered second or third hne agents
7 Central acting sympatholytics
Clonidine
Guanabenz
Guanfacine
Methyldopa
a Specific indications
aonidine can be useful in opiate detoxffication.
b. Major side effects
Depression, fatigue, dry mouth, impotence, bradycardia, heart block, memory loss.
Methyldopa gives hepatitis and Coombs positive hemolytic anemia.
c. Relative contraindications
Use in the elderly or the depressed.
8. Direct vasodilators
Hydralazine
Minoxidil
a. Specific indications
Hydralazine is used in eclampsia.
Minoxidil is used locally to treat baldness.
b. Major side effects
Minoxidil gives marked fluid retention, pericardial effusion and hirsutism.
Hydralazine gives a lupus-like syndrome.
c Relative contraindications
Angina pcctoris

Nephrology Problems
1 What acid-base disorders arc represented by the following sets of artcnal blood test?
Answer:
A. Metabolic acidosis (low pH, low HCO 3- concentration, compensatory reduction in Pco2).
B. Respiratory alkalosis (high pH, low PCO 2 compensatory reduction in HCO 3- concentration). Note that a
low HCO 3- concentration does not necessarily imply a metabolic acidosis.
C. Combined respiratory and metabolic acidosis (low pH, high PCO2, low HCO 3- concentrauon).
D Metabolic alkalosis (high pH, high HCOff concentration, compensatory increase in PCO2).
2. Match the clinical histories with the appropriate arterial blood values
1. A 60-year-old man with chronic bronchitis develops persistent diarrhea
2. A markedly obesc-24-ycar-old man
3. A 14-year-old girl with a scvcrc acute asthmatic attack
4. A 56-year-old woman with chronic bronchitis is started on diuretic therapy for peripheral edema resulting
in a 3 kg weight loss.
Answer:
It is easiest to answer this problem by first determining the acid-base disorders represented by the three sets of
blood values
A. The low pH and high Pco2 indicate respiratory acidosis. In chronic respiratory acidosis, a Pco2 of 65 mm
Hg (25 mm Hg greater than normal) should be associated with a plasma HCO3- concentration of
approximately 33 mEq/L (3.S-mEq/L increase in the plasma HCO3- concentration for each 10-ram Hg
devation in the Pco2)- Thus, the HCO 3- concentration of 73 mEq/L represents a superimposed metabolic
alkalosis.

.....  ....  ,oўephrology • Hypertension
B. At a Pco2 of 60 mm Hg, the plasma HCO 3- concentration should be roughly 26 mEq/L in acute
respiratory acidosis (l-mEq/L increase per 10-mm Hg elevation in the Pco2) and 31 mEq/L in chronic
respiratory acidosis. Therefore, these values may represent acute respiratory acidosis or metabolic acidosis
(Iowering the HCO3- concentration from 31 to 26 mEq/L) superimposed on chronic respiratory acidosis
C. Chronic respiratory acidosis or metabolic alkaiosis (raising the HCO 3- concentration from 26-32 mEq/L)
superimposed on acute respiratory acidosis
From the history
1. Chronic bronchitis plus diarrhea suggests combined chronic respiratory acidosis and metabolic acidosis or
B.
2. Marked obesity suggests chromc hypercapnia or C.
3. Severe acute asthma suggests acute respiratory acidosis or B.
4. Chronic bronchitis plus diuretics suggests chronic hypercapnia with superimposed metabolic alkalosis or
A. The metabolic alkalosis in this case is on the basis of volume contraction from the use of the diuretic.
22541.00197 25