Renal Congenital Anomalies: oligohydramnios → compression of developing fetus → limb deformities, facial anomalies (eg. low-set ears and retrognathia, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs → pulmonary hypoplasia (cause of death) causes include ARPKD, obstructive uropathy (eg. posterior urethral valves), bilateral renal agenesis, chronic placental insufficiency

Potter Sequence (Syndrome) POTTER sequence is associated with: Pulmonary hypoplasia Oligohydramnios (trigger) Twisted face Twisted skin Extremity defects Renal failure (in utero)

Cx = (UxV)/Px = volume of plasma from which the substance is completely cleared per unit time If Cx \ GFR: net tubular secretion of X If Cx = GFR: no net secretion or reabsorption ``` Cx = clearance of X (mL/min) Ux = urine concentration of X (eg, mg/mL) Px = plasma concentration of X (eg, mg/mL) V = urine flow rate (mL/min) ```

Renal - First Aid Flashcards by Grazielle Verzosa

Kidney Embryology:

week 4
then degenerates

Pronephros

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Kidney Embryology:

functions as interim kidney for 1st trimester
later contributes to male genital system

Mesonephros

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Kidney Embryology:

permanent
first appears in 5th week of gestation
nephrogenesis continues through weeks 32–36 of gestation
aberrant interaction between ureteric bud and metanephric mesenchyme tissues may result in several congenital malformations of the kidney (eg. renal agenesis, multicystic dysplastic kidney)

Metanephros

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Kidney Embryology:

derived from caudal end of mesonephric duct
gives rise to ureter, pelvises, calyces, and collecting ducts
fully canalized by 10th week

Ureteric Bud

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Kidney Embryology:

metanephric blastema
ureteric bud interacts with this tissue
interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)

Metanephric Mesenchyme

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Kidney Embryology:

last to canalize → most common site of obstruction (can be detected on prenatal ultrasound as hydronephrosis)

Ureteropelvic Junction

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Renal Congenital Anomalies:

oligohydramnios → compression of developing fetus → limb deformities, facial anomalies (eg. low-set ears and retrognathia, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs → pulmonary hypoplasia (cause of death)
causes include ARPKD, obstructive uropathy (eg. posterior urethral valves), bilateral renal agenesis, chronic placental insufficiency

Potter Sequence (Syndrome)

POTTER sequence is associated with:

Pulmonary hypoplasia
Oligohydramnios (trigger)
Twisted face
Twisted skin
Extremity defects
Renal failure (in utero)

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Renal Congenital Anomalies:

inferior poles of both kidneys fuse abnormally
as they ascend from pelvis during fetal development, the kidneys get trapped under inferior mesenteric artery and remain low in the abdomen
kidneys function normally
associated with hydronephrosis (eg. ureteropelvic junction obstruction), renal stones, infection, chromosomal aneuploidy syndromes (eg. Turner syndrome; trisomies 13, 18, 21), and rarely renal cancer

Horseshoe Kidney

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Renal Congenital Anomalies:

condition of being born with only one functioning kidney
majority asymptomatic with compensatory hypertrophy of contralateral kidney, but anomalies in contralateral kidney are common
often diagnosed prenatally via ultrasound

Congenital Solitary Functioning Kidney

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Congenital Solitary Functioning Kidney:

ureteric bud fails to develop and induce differentiation of metanephric mesenchyme → complete absence of kidney and ureter

Unilateral Renal Agenesis

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Congenital Solitary Functioning Kidney:

ureteric bud fails to induce differentiation of metanephric mesenchyme → nonfunctional kidney consisting of cysts and connective tissue
predominantly nonhereditary and usually unilateral
bilateral leads to Potter sequence

Multicystic Dysplastic Kidney

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Renal Congenital Anomalies:

bifurcation of ureteric bud before it enters the metanephric blastema creates a Y-shaped bifid ureter
duplex collecting system can alternatively occur through two ureteric buds reaching and interacting with metanephric blastema
strongly associated with vesicoureteral reflux and/or ureteral obstruction
↑ risk for UTIs

Duplex Collecting System

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Renal Congenital Anomalies:

membrane remnant in the posterior urethra in males
its persistence can lead to urethral obstruction
can be diagnosed prenatally by hydronephrosis and dilated or thick-walled bladder on ultrasound
most common cause of bladder outlet obstruction in male infants

Posterior Urethral Valves

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Kidney Anatomy and Glomerular Structure

Left kidney is taken during donor transplantation because it has a longer renal vein.
Afferent = Arriving
Efferent = Exiting
Renal Blood Blow: renal artery → segmental artery → interlobar artery → arcuate artery → interlobular artery → afferent arteriole → glomerulus → efferent arteriole → vasa recta/peritubular capillaries → venous outflow

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Course of Ureters

Course of Ureters: arises from renal pelvis, travels under gonadal arteries → over common iliac artery → under uterine artery/vas deferens (retroperitoneal)
Gynecologic procedures (eg. ligation of uterine or ovarian vessels) may damage ureter → ureteral obstruction or leak.
Muscle fibers within the intramural part of the ureter prevent urine reflux.
3 Constrictions of Ureters:
- Ureteropelvic Junction
- Pelvic Inlet
- Ureterovesical Junction
Water (ureters) flows over the iliacs and under the bridge (uterine artery or vas deferens).

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Fluid Compartments

HIKIN’: HIgh K⁺ INtracellularly
60–40–20 rule (% of body weight for average person):
- 60% total body water
- 40% ICF, mainly composed of K⁺, Mg²⁺, organic phosphates (eg. ATP)
- 20% ECF, mainly composed of Na⁺, Cl^–, HCO₃^–, albumin
Plasma volume can be measured by radiolabeling albumin.
Extracellular volume can be measured by inulin or mannitol.
Osmolality = 285–295 mOsm/kg H2O

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Glomerular Filtration Barrier

Responsible for filtration of plasma according to size and charge selectivity.
Composed of:
- fenestrated capillary endothelium
- basement membrane with type IV collagen chains and heparan sulfate
- epithelial layer consisting of podocyte foot processes
Charge Barrier
- all 3 layers contain ⊝ charged glycoproteins that prevent entry of ⊝ charged molecules (eg. albumin)
Size Barrier
- fenestrated capillary endothelium (prevent entry of > 100 nm molecules/blood cells)
- podocyte foot processes interpose with basement membrane
- slit diaphragm (prevent entry of molecules > 50–60 nm)

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Renal Clearance

Cx = (UxV)/Px = volume of plasma from which the substance is completely cleared per unit time

If Cx < GFR: net tubular reabsorption of X
If Cx > GFR: net tubular secretion of X
If Cx = GFR: no net secretion or reabsorption

Cx = clearance of X (mL/min)
Ux = urine concentration of X (eg, mg/mL)
Px = plasma concentration of X (eg, mg/mL)
V = urine flow rate (mL/min)

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Glomerular Filtration Rate

Inulin clearance can be used to calculate GFR because it is freely filtered and is neither reabsorbed nor secreted.
GFR = Uinulin × V/Pinulin = Cinulin = Kf [(PGC – PBS) – (πGC – πBS)]
- GC = glomerular capillary
- BS = Bowman space
- πBS normally equals zero
- Kf = filtration coefficient
Normal GFR ≈ 100 mL/min.
Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR because creatinine is moderately secreted by renal tubules.
Incremental reductions in GFR define the stages of chronic kidney disease.

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Effective Renal Plasma Flow

Effective renal plasma flow (eRPF) can be estimated using para-aminohippuric acid (PAH) clearance.
Between filtration and secretion, there is nearly 100% excretion of all PAH that enters the kidney.
eRPF = UPAH × V/PPAH = CPAH
Renal Blood Flow (RBF) = RPF/(1 − Hct)—usually 20–25% of cardiac output
Plasma Volume = TBV × (1 – Hct)
eRPF underestimates true renal plasma flow (RPF) slightly.

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Filtration

Filtration Fraction (FF) = GFR/RPF
- Normal FF = 20%
Filtered Load (mg/min) = GFR (mL/min) × plasma concentration (mg/mL)
GFR can be estimated with creatinine clearance.
RPF is best estimated with PAH clearance.
Prostaglandins Dilate Afferent arteriole (PDA)
Angiotensin II Constricts Efferent arteriole (ACE)

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Changes in Glomerular Dynamics

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Calculation of Reabsorption and Secretion Rate

Filtered Load = GFR × Px
Excretion Rate = V × Ux
Reabsorption Rate = filtered – excreted
Secretion Rate = excreted – filtered
Fe_Na = fractional excretion of sodium

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Glucose Clearance

Glucose at a normal plasma level (range 60–120 mg/dL) is completely reabsorbed in proximal convoluted tubule (PCT) by Na⁺/glucose cotransport.
In adults, at plasma glucose of ∼ 200 mg/dL, glucosuria begins (threshold).
At rate of ∼ 375 mg/min, all transporters are fully saturated (Tm).
Normal pregnancy is associated with ↑ GFR.
With ↑ filtration of all substances, including glucose, the glucose threshold occurs at lower plasma glucose concentrations → glucosuria at normal plasma glucose levels.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors (eg. -flozin drugs) result in glucosuria at plasma concentrations < 200 mg/dL.
Glucosuria is an important clinical clue to diabetes mellitus.
Splay Phenomenon
- Tm for glucose is reached gradually rather than sharply due to the heterogeneity of nephrons (ie. different Tm points)
- represented by the portion of the titration curve between threshold and Tm

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Nephron Physiology: Proximal Convoluted Tubule

* contains brush border * reabsorbs all glucose and amino acids and most HCO₃^–, Na⁺, Cl^–, PO₄^3–, K⁺, H₂O, and uric acid * isotonic absorption * generates and secretes NH₃, which enables the kidney to secrete more H⁺ * PTH—inhibits Na⁺/PO₄^3– cotransport → PO₄^3– excretion * AT II—stimulates Na⁺/H⁺ exchange → ↑ Na⁺, H₂O, and HCO₃⁻ reabsorption (permitting contraction alkalosis) * 65–80% Na⁺ reabsorbed

Nephron Physiology: Loop of Henle

Thin Descending Loop of Henle * passively reabsorbs H₂O * via medullary hypertonicity (impermeable to Na⁺) * concentrating segment * makes urine hypertonic Thick Ascending Loop of Henle * reabsorbs Na⁺, K⁺, and Cl⁻ * indirectly induces paracellular reabsorption of Mg²⁺ and Ca²⁺ through ⊕ lumen potential generated by K⁺ backleak * impermeable to H₂O * makes urine less concentrated as it ascends * 10–20% Na+ reabsorbed

Nephron Physiology: Distal Convoluted Tubule

* reabsorbs Na⁺ and Cl⁻ * impermeable to H₂O * makes urine fully dilute (hypotonic) * PTH— ↑ Ca²⁺/Na⁺ exchange → Ca²⁺ reabsorption * 5–10% Na⁺ reabsorbed

Nephron Physiology: Collecting Tubule

* reabsorbs Na⁺ in exchange for secreting K⁺ and H⁺ (regulated by aldosterone) * Aldosterone * acts on mineralocorticoid receptor → mRNA → protein synthesis * In principal cells: ↑ apical K⁺ conductance, ↑ Na⁺/K⁺ pump, ↑ epithelial Na⁺ channel (ENaC) activity → lumen negativity → K⁺ secretion * In α-intercalated cells: lumen negativity → ↑ H⁺ ATPase activity → ↑ H⁺ secretion → ↑ HCO₃⁻/Cl⁻ exchanger activity * ADH * acts at V₂ receptor → insertion of aquaporin H₂O channels on apical side * 3–5% Na⁺ reabsorbed

Renal Tubular Defects

The kidneys put out **FaB**ulous **G**littering **L**iquid**S** (from front to end of tube). * **Fa**nconi Syndrome * **B**artter Syndrome * **G**itelman Syndrome * **L**iddle Syndrome * **S**yndrome of Apparent Mineralocorticoid Excess

Renal Tubular Defects: * generalized reabsorption defect in PCT → ↑ excretion of amino acids, glucose, HCO₃^–, and PO₄^3–, and all substances reabsorbed by the PCT * may lead to metabolic acidosis (proximal RTA), hypophosphatemia, and osteopenia * caused by hereditary defects (eg, Wilson disease, tyrosinemia, glycogen storage disease), ischemia, multiple myeloma, nephrotoxins/drugs (eg. ifosfamide, cisplatin, expired tetracyclines), and lead poisoning

Fanconi Syndrome

Renal Tubular Defects: * resorptive defect in thick ascending loop of Henle (affects Na⁺/K⁺/2Cl^– cotransporter) * metabolic alkalosis, hypokalemia, and hypercalciuria * autosomal recessive * presents similarly to chronic loop diuretic use

Bartter Syndrome

Renal Tubular Defects: * reabsorption defect of NaCl in DCT * metabolic alkalosis, hypomagnesemia, hypokalemia, and hypocalciuria * autosomal recessive * presents similarly to lifelong thiazide diuretic use * less severe than Bartter syndrome

Gitelman Syndrome

Renal Tubular Defects: * gain of function mutation → ↑ activity of Na⁺ channel → ↑ Na⁺ reabsorption in collecting tubules * metabolic alkalosis, hypokalemia, hypertension, and ↓ aldosterone * autosomal dominant * presents similarly to hyperaldosteronism, but aldosterone is nearly undetectable * treated with Amiloride

Liddle Syndrome

Renal Tubular Defects: * in cells containing mineralocorticoid receptors, 11β-hydroxysteroiddehydrogenase converts cortisol (can activate these receptors) to cortisone (inactive on these receptors) * hereditary deficiency of 11β-hydroxysteroid dehydrogenase → excess cortisol → ↑ mineralocorticoid receptor activity * metabolic alkalosis, hypokalemia, hypertension * ↓ serum aldosterone level * autosomal recessive * can be acquired from glycyrrhetinic acid (present in licorice), which blocks activity of 11β-hydroxysteroid dehydrogenase * treated with K⁺-sparing diuretics (↓ mineralocorticoid effects) or corticosteroids (exogenous corticosteroid ↓ endogenous cortisol production → ↓ mineralocorticoid receptor activation)

**S**yndrome of **A**pparent **M**ineralocorticoid **E**xcess Cortisol tries to be the **SAME** as Aldosterone.

Relative Concentrations along Proximal Convoluted Tubules

* Tubular inulin ↑ in concentration (but not amount) along the PCT as a result of water reabsorption. * Cl⁻ reabsorption occurs at a slower rate than Na⁺ in early PCT and then matches the rate of Na⁺ reabsorption more distally. Thus, its relative concentration ↑ before it plateaus.

Renin-Angiotensin-Aldosterone System

Renin-Angiotensin-Aldosterone System: * secreted by JG cells in response to ↓ renal perfusion pressure (detected by renal baroreceptors in afferent arteriole) * ↑ renal sympathetic discharge (β1 effect) * ↓ NaCl delivery to macula densa cells

Renin

Renin-Angiotensin-Aldosterone System: * helps maintain blood volume and blood pressure * affects baroreceptor function * limits reflex bradycardia, which would normally accompany its pressor effects

Angiotensin II

Renin-Angiotensin-Aldosterone System: * released from atria and ventricles in response to ↑ volume * may act as a “check” on renin-angiotensin-aldosterone system * relaxes vascular smooth muscle via cGMP → ↑ GFR, ↓ renin * dilates afferent arteriole, constricts efferent arteriole, and promotes natriuresis

* ANP—atria * BNP—ventricles

Renin-Angiotensin-Aldosterone System: * primarily regulates serum osmolality * also responds to low blood volume states * stimulates reabsorption of water in collecting ducts * also stimulates reabsorption of urea in collecting ducts to maintain corticopapillary osmotic gradient

ADH

Renin-Angiotensin-Aldosterone System: * primarily regulates ECF volume and Na⁺ content * responds to low blood volume states * responds to hyperkalemia by ↑ K⁺ excretion

Aldosterone

Renal Physiology: * consists of mesangial cells, JG cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, located at distal end of loop of Henle) * JG cells secrete renin in response to ↓ renal blood pressure and ↑ sympathetic tone (β1) * macula densa cells sense ↓ NaCl delivery to DCT → ↑ renin release → efferent arteriole vasoconstriction → ↑ GFR * maintains GFR via renin-angiotensin-aldosterone system * in addition to vasodilatory properties, β-blockers can decrease BP by inhibiting β1‑receptors of the JGA → ↓ renin release

Juxtaglomerular Apparatus

Kidney Endocrine Functions: * released by interstitial cells in peritubular capillary bed in response to hypoxia * stimulates RBC proliferation in bone marrow * often supplemented in chronic kidney disease

Erythropoietin

Kidney Endocrine Functions: PCT cells convert 25-OH Vitamin D3 to 1,25-(OH)2 Vitamin D3 (Calcitriol, active form)

Calciferol (Vitamin D)

Kidney Endocrine Functions: * paracrine secretion vasodilates the afferent arterioles to ↑ RBF * NSAIDs block renal-protective _____ synthesis → constriction of afferent arteriole and ↓ GFR; this may result in acute renal failure in low renal blood flow states

Prostaglandins

Kidney Endocrine Functions: * secreted by PCT cells * promotes natriuresis * at low doses, dilates interlobular arteries, afferent arterioles, efferent arterioles → ↑ RBF, little or no change in GFR * at higher doses, acts as a vasoconstrictor

Dopamine

Hormones Acting on the Kidneys

Potassium Shifts: shifts K⁺ into cell → hypokalemia

* Hypo-osmolarity * Alkalosis * β-Adrenergic Agonist (↑ Na+/K+ ATPase) * Insulin (↑ Na+/K+ ATPase)—**in**sulin shifts K+ **in**to cells

Potassium Shifts: shifts K+ out of cell → hyperkalemia

Hyperkalemia? **DO LAβSS**: * **D**igitalis (blocks Na+/K+ ATPase) * Hyper**O**smolarity * **L**ysis of Cells (eg. crush injury, rhabdomyolysis, tumor lysis syndrome) * **A**cidosis * **β**-blocker * High Blood **S**ugar (insulin deficiency) * **S**uccinylcholine (↑ risk in burns/muscle trauma)

Electrolyte Disturbances: * nausea * malaise * stupor * coma * seizures

↓ Na⁺

Electrolyte Disturbances: * irritability * stupor * coma

↑ Na⁺

Electrolyte Disturbances: * U waves and flattened T waves on ECG * arrhythmias * muscle cramps * spasm * weakness

↓ K⁺

Electrolyte Disturbances: * wide QRS and peaked T waves on ECG * arrhythmias * muscle weakness

↑ K⁺

Electrolyte Disturbances: * tetany * seizures * QT prolongation * twitching (Chvostek sign) * spasm (Trousseau sign)

↓ Ca²⁺

Electrolyte Disturbances: * stones (renal) * bones (pain) * groans (abdominal pain) * thrones (↑ urinary frequency) * psychiatric overtones (anxiety, altered mental status)

↑ Ca²⁺

Electrolyte Disturbances: * tetany * torsades de pointes * hypokalemia * hypocalcemia (when \< 1.2 mg/dL)

↓ Mg²⁺

Electrolyte Disturbances: * ↓ DTRs * lethargy * bradycardia * hypotension * cardiac arrest * hypocalcemia

↑ Mg²⁺

Electrolyte Disturbances: * bone loss * osteomalacia (adults) * rickets (children)

↓ PO₄³⁻

Electrolyte Disturbances: * renal stones * metastatic calcifications * hypocalcemia

↑ PO₄³⁻

Features of Renal Disorders

Acid-Base Physiology

Acidosis and Alkalosis

Renal Pathology: disorder of the renal tubules that causes normal anion gap (hyperchloremic) metabolic acidosis

Renal Tubular Acidosis

Renal Tubular Acidosis: * inability of α-intercalated cells to secrete H⁺ → no new HCO₃^– is generated → metabolic acidosis * urine pH \> 5.5 * ↓ serum K⁺ * caused by Amphotericin B toxicity, analgesic nephropathy, congenital anomalies (obstruction) of urinary tract, and autoimmune diseases (eg. SLE) * associated with ↑ risk for calcium phosphate kidney stones (due to ↑ urine pH and ↑ bone turnover)

Distal Renal Tubular Acidosis (Type 1)

Renal Tubular Acidosis: * defect in PCT HCO₃^– reabsorption → ↑ excretion of HCO₃^– in urine → metabolic acidosis * urine can be acidified by α-intercalated cells in collecting duct, but not enough to overcome the increased excretion of HCO₃^– → metabolic acidosis * urine pH \< 5.5 * ↓ serum K⁺ * caused by Fanconi syndrome, multiple myeloma, and carbonic anhydrase inhibitors * associated with ↑ risk for hypophosphatemic rickets (in Fanconi syndrome)

Proximal Renal Tubular Acidosis (Type 2)

Renal Tubular Acidosis: * hypoaldosteronism or aldosterone resistance * hyperkalemia → ↓ NH₃ synthesis in PCT → ↓ NH₄⁺ excretion * urine pH \< 5.5 (or variable) * ↑ serum K⁺ * caused by ↓ aldosterone production (eg. diabetic hyporeninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency) or aldosterone resistance (eg. K⁺-sparing diuretics, nephropathy due to obstruction, TMP-SMX)

Hyperkalemic Tubular Acidosis (Type 4)

Casts in Urine

* presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin * bladder cancer, kidney stones → hematuria, no casts * acute cystitis → pyuria, no casts

Casts in Urine: * glomerulonephritis * hypertensive emergency

RBC casts

Casts in Urine: * tubulointerstitial inflammation * acute pyelonephritis * transplant rejection

WBC casts

Casts in Urine: * “oval fat bodies” * nephrotic syndrome * associated with “Maltese cross” sign

Fatty casts

Casts in Urine: * “muddy brown” * acute tubular necrosis (ATN)

Granular casts

Casts in Urine: end-stage renal disease/chronic renal failure

Waxy casts

Casts in Urine: * nonspecific * can be a normal finding * often seen in concentrated urine samples

Hyaline casts

Nomenclature of Glomerular Disorders: \< 50% of glomeruli are involved

Focal

Nomenclature of Glomerular Disorders: \> 50% of glomeruli are involved

Diffuse

Nomenclature of Glomerular Disorders: hypercellular glomeruli

Proliferative

Nomenclature of Glomerular Disorders: thickening of glomerular basement membrane (GBM)

Membranous

Nomenclature of Glomerular Disorders: * 1° disease of the kidney specifically impacting the glomeruli * Minimal Change Disease

Primary Glomerular Disease

Nomenclature of Glomerular Disorders: * systemic disease or disease of another organ system that also impacts the glomeruli * SLE Nephritis * Diabetic Nephropathy

Secondary Glomerular Disease

Glomerular Diseases

Renal Pathology: * massive proteinuria (\> 3.5 g/day) with hypoalbuminemia, resulting edema, hyperlipidemia * frothy urine with fatty casts * disruption of glomerular filtration charge barrier may be 1° (eg. direct sclerosis of podocytes) or 2° (systemic process [eg. diabetes] secondarily damages podocytes) * severe nephritic syndrome may present with _____ features if damage to GBM is severe enough to damage the charge barrier * associated with hypercoagulable state due to antithrombin (AT) III loss in urine and ↑ risk of infection (loss of immunoglobulins in urine and soft tissue compromise by edema)

Nephrotic Syndrome Nephr**O**tic = pr**O**teinuria

Causes of Nephrotic Syndrome

* Minimal Change Disease (Lipoid Nephrosis) * Focal Segmental Glomerulosclerosis * Membranou Nephropathy * Amyloidosis * Diabetic Glomerulonephropathy

Nephrotic Syndrome: * most common cause of nephrotic syndrome in children * often 1° (idiopathic) and may be triggered by recent infection, immunization, immune stimulus * rarely, may be 2° to lymphoma (eg. cytokine-mediated damage) * 1° disease has excellent response to corticosteroids * Imaging: * LM—normal glomeruli (lipid may be seen in PCT cells) * IF—⊝ * EM—effacement of podocyte foot processes

Minimal Change Disease (Lipoid Nephrosis)

Nephrotic Syndrome: * most common cause of nephrotic syndrome in African-Americans and Hispanics * can be 1° (idiopathic) or 2° to other conditions (eg. HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, or congenital malformations) * 1° disease has inconsistent response to steroids * may progress to CKD * Imaging: * LM—segmental sclerosis and hyalinosis * IF—often ⊝ but may be ⊕ for nonspecific focal deposits of IgM, C3, and C1 * EM—effacement of foot processes similar to minimal change disease

Focal Segmental Glomerulosclerosis

Nephrotic Syndrome: * also known as Membranous Glomerulonephritis * can be 1° (eg. antibodies to phospholipase A2 receptor) or 2° to drugs (eg. NSAIDs, penicillamine, gold), infections (eg. HBV, HCV, syphilis), SLE, or solid tumors * 1° disease has poor response to steroids * may progress to CKD * Imaging: * LM—diffuse capillary and GBM thickening * IF—granular due to IC deposition * EM—“spike and dome” appearance of subepithelial deposits

Membranous Nephropathy

Nephrotic Syndrome: * kidney is the most commonly involved organ * associated with chronic conditions that predispose to amyloid deposition (eg. AL amyloid, AA amyloid) * Imaging: * LM—Congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium

Amyloidosis

Nephrotic Syndrome: * most common cause of ESRD in the United States * hyperglycemia → nonenzymatic glycation of tissue proteins → mesangial expansion * GBM thickening and ↑ permeability * hyperfiltration (glomerular HTN and ↑ GFR) → glomerular hypertrophy and glomerular scarring (glomerulosclerosis) leading to further progression of nephropathy * LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)

Diabetic Glomerulonephropathy

Renal Pathology: * inflammatory process * when glomeruli are involved, leads to hematuria and RBC casts in urine * associated with azotemia, oliguria, hypertension (due to salt retention), proteinuria, and hypercellular/inflamed glomeruli on biopsy

Nephritic Syndrome Nephr**I**tic = **I**nflammatory

Causes of Nephritic Syndrome

* Acute Poststreptococcal Glomerulonephritis * Rapidly Progressive (Crescentic) Glomerulonephritis * Diffuse Proliferative Glomerulonephritis * IgA Nephropathy (Berger Disease) * Alport Syndrome * Membranoproliferative Glomerulonephritis

Nephritic Syndrome: * most frequently seen in children * ~ 2–4 weeks after group A streptococcal infection of pharynx or skin * resolves spontaneously in most children * may progress to renal insufficiency in adults * type III hypersensitivity reaction * presents with peripheral and periorbital edema, cola-colored urine, and HTN * ⊕ strep titers/serologies and ↓ complement levels (C3) due to consumption * Imaging: * LM—glomeruli enlarged and hypercellular * IF—(“starry sky”) granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition along GBM and mesangium * EM—subepithelial immune complex (IC) humps

Acute Poststreptococcal Glomerulonephritis

Nephritic Syndrome: * poor prognosis, rapidly deteriorating renal function (days to weeks) * Imaging: * LM * crescent moon shape * crescents consist of fibrin and plasma proteins (eg. C3b) with glomerular parietal cells, monocytes, macrophages * several disease processes may result in this pattern which may be delineated via IF pattern * Linear IF due to antibodies to GBM and alveolar basement membrane: * Goodpasture Syndrome—hematuria/hemoptysis, type II hypersensitivity reaction, treated with plasmapheresis * Negative IF/Pauci-immune (no Ig/C3 deposition): * Granulomatosis with Polyangiitis (Wegener)—PR3-ANCA/c-ANCA * Microscopic Polyangiitis—MPO-ANCA/p-ANCA * Granular IF * PSGN * DPGN

Rapidly Progressive (Crescentic) Glomerulonephritis

Nephritic Syndrome: * often due to SLE (“**wire lup**us”) * often present as nephrotic syndrome and nephritic syndrome concurrently * Imaging: * LM—“**wire loop**ing” of capillaries * IF—granular * EM—subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition

Diffuse Proliferative Glomerulonephritis

Nephritic Syndrome: * episodic hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings) * renal pathology of IgA vasculitis (HSP) * Imaging: * LM—mesangial proliferation * IF—IgA-based IC deposits in mesangium * EM—mesangial IC deposition

IgA Nephropathy (Berger Disease)

Nephritic Syndrome: * mutation in type IV collagen → thinning and splitting of glomerular basement membrane * most commonly X-linked dominant * eye problems (eg. retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness * Imaging: * EM—“basket-weave”

Alport Syndrome “**Can’t see**, **can’t pee**, **can’t hear a bee**.”

Nephritic Syndrome: * often co-presents with nephrotic syndrome * Ttype I * may be 2° to hepatitis B or C infection * may also be idiopathic * subendothelial IC deposits with granular IF * Type II * associated with C3 nephritic factor (IgG antibody that stabilizes C3 convertase → persistent complement activation → ↓ C3 levels) * intramembranous deposits, also called dense deposit disease * in both types, mesangial ingrowth → GBM splitting → “tram-track” appearance on H&E and PAS stains

Membranoproliferative Glomerulonephritis

Renaal Pathology: * can lead to severe complications such as hydronephrosis and pyelonephritis * obstructed _____ presents with unilateral flank tenderness, colicky pain radiating to groin, and hematuria * treat and prevent by encouraging fluid intake * most common presentation: * calcium oxalate _____ in patient with hypercalciuria and normocalcemia

Kidney Stones

Kidney Stones: * Precipitates with: hypocitraturia * X-Ray: radiopaque * CT Scan: radiopaque * Urine Crystal: envelope or dumbbell shape * most common (80%) * more common than calcium phosphate stones * hypocitraturia often associated with ↓ urine pH * can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia, malabsorption (eg. Crohn disease) * Treatment: * thiazides * citrate * low-sodium diet

Calcium Oxalate

Kidney Stones: * Precipitates with: ↑ pH * X-Ray: radiopaque * CT-Scan: radiopaque * Urine Crystal: wedge-shaped prism * Treatment: * low-sodium diet * thiazides

Calcium Phosphate

Kidney Stones: * Precipitates with: ↑ pH * X-Ray: Radiopaque * CT-Scan: Radiopaque * Urine Crystal: coffin lid * also known as struvite * account for 15% of stones * caused by infection with urease ⊕ bugs (eg. *Proteus mirabilis*, *Staphylococcus saprophyticus*, *Klebsiella*) that hydrolyze * urea to ammonia → urine alkalinization * commonly form staghorn calculi * Treatment: * eradication of underlying infection * surgical removal of stone

Ammonium Magnesium Phosphate

Kidney Stones: * Precipitates with: ↓ pH * X-Ray: radiolucent * CT-Scan: minimally visible * Urine Crystal: rhomboid or rosettes * about 5% of all stones * Risk Factors: * ↓ urine volume * arid climates * acidic pH * strong association with hyperuricemia (eg. gout) * often seen in diseases with ↑ cell turnover (eg. leukemia) * Treatment: * alkalinization of urine * allopurinol

Uric Acid radiol**U**cent

Kidney Stones: * Precipitates with: ↓ pH * X-Ray: faintly radiopaque * CT-Scan: moderately radiopaque * Urine Crystal: hexagonal * hereditary (autosomal recessive) condition in which Cystine-reabsorbing PCT transporter loses function, causing cystinuria * transporter defect also results in poor reabsorption of Ornithine, Lysine, and Arginine * Cystine is poorly soluble, thus stones form in urine * usually begins in childhood * can form staghorn calculi * sodium cyanide nitroprusside test ⊕ * Treatment: * low sodium diet * alkalinization of urine * chelating agents if refractory

Cystine “**SIX**tine” stones have **SIX** sides. **COLA**: * **C**ystine * **O**rnithine * **L**ysine * **A**rginine

Renal Pathology: * distention/dilation of renal pelvis and calyces * usually caused by urinary tract obstruction (eg. renal stones, severe BPH, congenital obstructions, cervical cancer, injury to ureter) * other causes include retroperitoneal fibrosis and vesicoureteral reflux * dilation occurs proximal to site of pathology * serum creatinine becomes elevated if obstruction is bilateral or if patient has an obstructed solitary kidney * leads to compression and possible atrophy of renal cortex and medulla

Hydronephrosis

Renal Pathology: * polygonal clear cells filled with accumulated lipids and carbohydrate * often golden-yellow due to ↑ lipid content * originates from PCT → invades renal vein (may develop varicocele if left sided) → IVC → hematogenous spread → metastasis to lung and bone * manifests with hematuria, palpable masses, 2° polycythemia, flank pain, fever, and weight loss * most common 1° renal malignancy * most common in men 50–70 years old * ↑ incidence with smoking and obesity * associated with paraneoplastic syndromes * associated with gene deletion on chromosome 3 (sporadic, or inherited as von Hippel-Lindau syndrome) * Treatment: * surgery/ablation for localized disease * immunotherapy (eg. Aldesleukin) or targeted therapy for metastatic disease, rarely curative * resistant to chemotherapy and radiation therapy

Renal Cell Carcinoma “**PEAR**”-aneoplastic Syndromes * **P**THrP * **E**ctopic **E**PO * **A**CTH * **R**enin **RCC** = **3** letters = chromosome **3**

Renal Pathology: * benign epithelial cell tumor arising from collecting ducts * large eosinophilic cells with abundant * mitochondria without perinuclear clearing (vs. chromophobe renal cell carcinoma) * presents with painless hematuria, flank pain, and abdominal mass * often resected to exclude malignancy (eg. renal cell carcinoma)

Renal Oncocytoma

Renal Pathology: * most common renal malignancy of early childhood (ages 2–4) * contains embryonic glomerular structures * presents with large, palpable, unilateral flank mass and/or hematuria * “loss of function” mutations of tumor suppressor genes WT1 or WT2 on chromosome 11 * May be a part of several syndromes: * WAGR complex * Denys-Drash syndrome * Beckwith-Wiedemann syndrome

Nephroblastoma (Wilms Tumor)

Nephroblastoma (Wilms Tumor): * Wilms tumor * aniridia (absence of iris) * genitourinary malformations * mental retardation/intellectual disability (WT1 deletion)

WAGR Complex * **W**ilms tumor * **A**niridia (absence of iris) * **G**enitourinary malformations * mental **R**etardation/intellectual disability (WT1 deletion)

Nephroblastoma (Wilms Tumor): * Wilms tumor * diffuse mesangial sclerosis (early-onset nephrotic syndrome) * dysgenesis of gonads (male pseudohermaphroditism) * WT1 mutation

**D**enys-**D**rash Syndrome * **D**iffuse mesangial sclerosis * **D**ysgenesis of gonads

Nephroblastoma (Wilms Tumor): * Wilms tumor * macroglossia * organomegaly * hemihyperplasia (WT2 mutation)

Beckwith-Wiedemann Syndrome

Renal Pathology: * also known as Urothelial Carcinoma * most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters, and bladder) * can be suggested by painless hematuria (no casts) * Associated with: * Phenacetin * smoking * aniline dyes * Cyclophosphamide

Transitional Cell Carcinoma **P**ee **SAC**: * **P**henacetin * **S**moking * **A**niline dyes * **C**yclophosphamide

Renal Pathology: * chronic irritation of urinary bladder → squamous metaplasia → dysplasia and squamous cell carcinoma * Risk Factors: * *Schistosoma haematobium* infection (Middle East) * chronic cystitis * smoking * chronic nephrolithiasis * presents with painless hematuria

Squamous Cell Carcinoma of the Bladder

Urinary Incontinence: * outlet incompetence (urethral hypermobility or intrinsic sphincteric deficiency) → leak with ↑ intra-abdominal pressure (eg. sneezing, lifting) * ↑ risk with obesity, vaginal delivery, and prostate surgery * ⊕ bladder stress test (directly observed leakage from urethra upon coughing or Valsalva maneuver) * Treatment: * pelvic floor muscle strengthening (Kegel) exercises * weight loss * pessaries

Stress Incontinence

Urinary Incontinence: * overactive bladder (detrusor instability) → leak with urge to void immediately * associated with UTI * Treatment: * Kegel exercises * bladder training (timed voiding distraction or relaxation techniques) * Antimuscarinics (eg. Oxybutynin)

Urgency Incontinence

Urinary Incontinence: features of both stress and urgency incontinence

Mixed Incontinence

Urinary Incontinence: * incomplete emptying (detrusor underactivity or outlet obstruction) → leak with overfilling * associated with polyuria (eg. diabetes), bladder outlet obstruction (eg. BPH), neurogenic bladder (eg. MS) * ↑ post-void residual (urinary retention) on catheterization or ultrasound * Treatment: * catheterization * relieve obstruction (eg. α-blockers for BPH)

Overflow Incontinence

Renal Pathology: * inflammation of urinary bladder * presents as suprapubic pain, dysuria, urinary frequency, and urgency * systemic signs (eg. high fever, chills) are usually absent * Risk Factors * female gender (short urethra) * sexual intercourse (“honeymoon cystitis”) * indwelling catheter * diabetes mellitus * impaired bladder emptying * Causes: * *E. coli* (most common) * *Staphylococcus saprophyticus*—seen in sexually active young women (*E. coli* is still more common in this group) * *Klebsiella* * *Proteus mirabilis*—urine has ammonia scent * Lab Findings: * ⊕ leukocyte esterase * ⊕ nitrites (indicate gram ⊝ organisms) * sterile pyuria and ⊝ urine cultures suggest urethritis by *Neisseria gonorrhoeae* or *Chlamydia trachomatis*

Urinary Tract Infection | (Acute Bacterial Cystitis)

Renal Pathology: * neutrophils infiltrate renal interstitium * affects cortex with relative sparing of glomeruli/vessels * presents with fever, flank pain (costovertebral angle tenderness), nausea/vomiting, and chills * causes include ascending UTI (*E. coli* is most common) * hematogenous spread to kidney * presents with WBCs in urine +/− WBC casts * CT would show striated parenchymal enhancement * Risk Factors: * indwelling urinary catheter urinary tract obstruction * vesicoureteral reflux * diabetes mellitus * pregnancy * Complications: * chronic pyelonephritis * renal papillary necrosis * perinephric abscess * urosepsis * Treatment: antibiotics

Acute Pyelonephritis

Renal Pathology: * the result of recurrent episodes of acute pyelonephritis * typically requires predisposition to infection such as vesicoureteral reflux or chronically obstructing kidney stones * coarse, asymmetric corticomedullary scarring, blunted calyx * tubules can contain eosinophilic casts resembling thyroid tissue (thyroidization of kidney)

Chronic Pyelonephritis

Renal Pathology: * rare * grossly orange nodules that can mimic tumor nodules * characterized by widespread kidney damage due to granulomatous tissue containing foamy macrophages * associated with *Proteus* infection

Xanthogranulomatous Pyelonephritis

Renal Pathology: * formerly known as acute renal failure * defined as an abrupt decline in renal function as measured by ↑ creatinine and ↑ BUN or by oliguria/anuria

Acute Kidney Injury

Acute Kidney Injury: * due to ↓ RBF (eg. hypotension) → ↓ GFR * Na⁺/H2O and urea retained by kidney in an attempt to conserve volume → ↑ BUN/creatinine ratio (urea is reabsorbed, creatinine is not) and ↓ FE_Na

Prerenal Azotemia

Acute Kidney Injury: * most commonly due to acute tubular necrosis (from ischemia or toxins) * less commonly due to acute glomerulonephritis (eg. RPGN, hemolytic uremic syndrome) or acute interstitial nephritis * in ATN, patchy necrosis → debris obstructing tubule and fluid backflow across necrotic tubule → ↓ GFR * urine has epithelial/granular casts * urea reabsorption is impaired → ↓ BUN/creatinine ratio and ↑ FE_Na

Intrinsic Renal Failure

Acute Kidney Injury: * due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies) * develops only with bilateral obstruction or in a solitary kidney

Postrenal Azotemia

Consequences of Renal Failure

* Decline in renal filtration can lead to excess retained nitrogenous waste products and electrolyte disturbances. * **MAD HUNGER**: * **M**etabolic **A**cidosis * **D**yslipidemia (especially ↑ triglycerides) * **H**yperkalemia * **U**remia—clinical syndrome marked by: * nausea and anorexia * pericarditis * asterixis * encephalopathy * platelet dysfunction * **N**a⁺/H2O retention (HF, pulmonary edema, hypertension) * **G**rowth retardation and developmental delay * **E**rythropoietin failure (anemia) * **R**enal osteodystrophy * 2 Forms of Renal Failure: * Acute (eg. ATN) * Chronic (eg. hypertension, diabetes mellitus, congenital anomalies)

Renal Pathology: * hypocalcemia, hyperphosphatemia, and failure of vitamin D hydroxylation associated with chronic renal disease → 2° hyperparathyroidism * high serum phosphate can bind with Ca²⁺ → tissue deposits → ↓ serum Ca²⁺ * ↓ 1,25-(OH)2D3 → ↓ intestinal Ca²⁺ absorption * causes subperiosteal thinning of bones

Renal Osteodystrophy

Renal Pathology: * acute interstitial renal inflammation * pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity (eg. diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin, NSAIDs) * less commonly may be 2° to other processes such as systemic infections (eg. *Mycoplasma*) or autoimmune diseases (eg. Sjögren syndrome, SLE, sarcoidosis) * associated with fever, rash, hematuria, pyuria, and costovertebral angle tenderness, but can be asymptomatic

Acute Interstitial Nephritis (Tubulointerstitial Nephritis) Remember these **P**’s: * **P**ee (diuretics) * **P**ain-free (NSAIDs) * **P**enicillins and cephalosporins * **P**roton pump inhibitors * Rifam**P**in

Renal Pathology: * most common cause of acute kidney injury in hospitalized patients * spontaneously resolves in many cases * can be fatal, especially during initial oliguric phase * ↑ FE_Na

Acute Tubular Necrosis

Stages of Acute Tubular Necrosis

1. Inciting Event 2. Maintenance Phase—oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, and uremia 3. Recovery Phase—polyuric; BUN and serum creatinine fall; risk of hypokalemia and renal wasting of other electrolytes and minerals

Acute Tubular Necrosis: * 2° to ↓ renal blood flow (eg. hypotension, shock, sepsis, hemorrhage, HF) * results in death of tubular cells that may slough into tubular lumen (PCT and thick ascending limb are highly susceptible to injury)

Ischemic

Acute Tubular Necrosis: * 2° to injury resulting from toxic substances (eg. aminoglycosides, radiocontrast agents, lead, cisplatin, ethylene glycol), crush injury (myoglobinuria), and hemoglobinuria * proximal tubules are particularly susceptible to injury

Nephrotoxic

Renal Pathology: * acute generalized cortical infarction of both kidneys * likely due to a combination of vasospasm and DIC * associated with obstetric catastrophes (eg. abruptio placentae) and septic shock

Diffuse Cortical Necrosis

Renal Pathology: * sloughing of necrotic renal papillae → gross hematuria and proteinuria * may be triggered by recent infection or immune stimulus * associated with sickle cell disease or trait, acute pyelonephritis, NSAIDs, diabetes mellitus

Renal Papillary Necrosis **SAAD** **pap**a with **pap**illary necrosis: * **S**ickle cell disease or trait * **A**cute pyelonephritis * **A**nalgesics (NSAIDs) * **D**iabetes mellitus

Renal Cyst Disorders: * numerous cysts in cortex and medulla causing bilateral enlarged kidneys ultimately destroy kidney parenchyma * presents with flank pain, hematuria, hypertension, urinary infection, and progressive renal failure in ~ 50% of individuals * mutation in PKD1 (85% of cases, chromosome 16) or PKD2 (15% of cases, chromosome 4) * death from complications of chronic kidney disease or hypertension (caused by ↑ renin production) * associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts, and diverticulosis * Treatment: * if hypertension or proteinuria develops, treat with ACE inhibitors or ARBs

Autosomal Dominant Polycystic Kidney Disease

Renal Cyst Disorders: * cystic dilation of collecting ducts * often presents in infancy * associated with congenital hepatic fibrosis * significant oliguric renal failure in utero can lead to Potter sequence * concerns beyond neonatal period include systemic hypertension, progressive renal insufficiency, and portal hypertension from congenital hepatic fibrosis

Autosomal Recessive Polycystic Kidney Disease

Renal Cyst Disorders: * also known as Medullary Cystic Kidney Disease * inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine * medullary cysts usually not visualized * smaller kidneys on ultrasound * poor prognosis

Autosomal Dominant Tubulointerstitial Kidney Disease

Renal Cyst Disorders: * filled with ultrafiltrate (anechoic on ultrasound) * very common and account for majority of all renal masses * found incidentally and typically asymptomatic

Simple Cysts

Renal Cyst Disorders: those that are septated, enhanced, or have solid components on imaging require follow-up or removal due to risk of renal cell carcinoma

Complex Cysts

Diuretics Site of Action

Diuretics: * osmotic diuretic * ↑ tubular fluid osmolarity → ↑ urine flow, ↓ intracranial/intraocular pressure * used for drug overdose and elevated intracranial/intraocular pressure * causes pulmonary edema, dehydration, and hypo- or hypernatremia * contraindicated in anuria and HF

Mannitol

Diuretics: * carbonic anhydrase inhibitor * causes self-limited NaHCO₃ diuresis and ↓ total body HCO₃⁻ stores * used for glaucoma, metabolic alkalosis, altitude sickness, and pseudotumor cerebri * alkalinizes urine * causes proximal renal tubular acidosis, paresthesias, NH₃ toxicity, sulfa allergy, and hypokalemia * promotes calcium phosphate stone formation (insoluble at high pH)

Acetazolamide “**ACID**”azolamide causes **ACID**osis.

Diuretics: * sulfonamide loop diuretics * inhibit cotransport system (Na⁺/K⁺/2Cl⁻) of thick ascending limb of loop of Henle * abolish hypertonicity of medulla, preventing concentration of urine * stimulate PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs * ↑ Ca²⁺ excretion * used for edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, and hypercalcemia * causes ototoxicity, hypokalemia, hypomagnesemia, dehydration, allergy (sulfa), metabolic alkalosis, nephritis (interstitial), and gout

* Furosemide * Bumetanide * Torsemide **L**oops **L**ose Ca²⁺. **OHH DAANG**! * **O**totoxicity * **H**ypokalemia * **H**ypomagnesemia * **D**ehydration * **A**llergy (sulfa) * Metabolic **A**lkalosis * **N**ephritis (Interstitial) * **G**out

Diuretics: * loop diuretic * nonsulfonamide inhibitor of cotransport system (Na⁺/K⁺/2Cl⁻) of thick ascending limb of loop of Henle * used for diuresis in patients allergic to sulfa drugs * causes similar to Furosemide, but more ototoxic

Ethacrynic Acid **Loop** earrings hurt your **ears**.

Diuretics: * inhibit NaCl reabsorption in early DCT → ↓ diluting capacity of nephron * ↓ Ca²⁺ excretion * used for hypertension, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, and osteoporosis * causes hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia and sulfa allergy

Thiazide Diuretics * Hydrochlorothiazide * Chlorthalidone * Metolazone HyperGLUC: * hyper**G**lycemia * hyper**L**ipidemia * hyper**U**ricemia * hyper**C**alcemia

Diuretics: * Spironolactone and Eplerenone are competitive aldosterone receptor antagonists in cortical collecting tubule * Triamterene and Amiloride act at the same part of the tubule by blocking Na⁺ channels in the cortical collecting tubule * used for hyperaldosteronism, K⁺ depletion, HF, hepatic ascites (Spironolactone), nephrogenic DI (Amiloride), and antiandrogen * causes hyperkalemia (can lead to arrhythmias) * causes endocrine effects with Spironolactone (eg. gynecomastia, antiandrogen effects)

Potassium-Sparing Diuretics Ta**K**e a **SEAT**. * **S**pironolactone * **E**plerenone * **A**miloride * **T**riamterene

Diuretics: Electrolyte Changes Urine NaCl

* ↑ with all diuretics (strength varies based on potency of diuretic effect) * serum NaCl may decrease as a result

Diuretics: Electrolyte Changes Urine K⁺

* ↑ especially with loop and thiazide diuretics * serum K+ may decrease as a result

Diuretics: Electrolyte Changes ↓ Blood pH (Acidemia)

* Carbonic Anhydrase Inhibitors: ↓ HCO₃⁻reabsorption * K⁺ Sparing: aldosterone blockade prevents K⁺ secretion and H⁺ secretion, hyperkalemia leads to K⁺ entering all cells (via H⁺/K⁺ exchanger) in exchange for H⁺ exiting cells

Diuretics: Electrolyte Changes ↑ Blood pH (Alkalemia)

* Loop Diuretics and Thiazides * volume contraction → ↑ AT II → ↑ Na⁺/H⁺ exchange in PCT → ↑ HCO₃⁻ reabsorption (“contraction alkalosis”) * K⁺ loss leads to K⁺ exiting all cells (via H⁺/K⁺ exchanger) in exchange for H⁺ entering cells * in low K⁺ state, H⁺ (rather than K⁺) is exchanged for Na⁺ in cortical collecting tubule → alkalosis and “paradoxical aciduria”

Diuretics: Electrolyte Changes Urine Ca²⁺

* ↑ with loop diuretics: ↓ paracellular Ca²⁺ reabsorption → hypocalcemia * ↓ with thiazides: enhanced Ca²⁺ reabsorption

Angiotensin-Converting Enzyme Inhibitors

* Captopril * Enalapril * Lisinopril * Ramipril

Renal Drugs: * inhibit ACE → ↓ AT II → ↓ GFR by preventing constriction of efferent arterioles * ↑ renin due to loss of negative feedback. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator * used for hypertension, HF (↓ mortality), proteinuria, and diabetic nephropathy * prevent unfavorable heart remodeling as a result of chronic hypertension * in chronic kidney disease (eg. diabetic nephropathy), ↓ intraglomerular pressure, slowing GBM thickening * causes cough and angioedema (both due to ↑ bradykinin * contraindicated in C1 esterase inhibitor deficiency) * teratogen (fetal renal malformations) * ↑ Creatinine (↓ GFR) * causes hyperkalemia and hypotension * used with caution in bilateral renal artery stenosis because ACE inhibitors will further ↓ GFR → renal failure *

Angiotensin-Converting Enzyme Inhibitors Captopril’s **CATCHH**: * **C**ough * **A**ngioedema * **T**eratogen * ↑ **C**reatinine * **H**yperkalemia * **H**ypotension

Angiotensin II Receptor Blockers

* Losartan * Candesartan * Valsartan

Renal Drugs: * selectively block binding of angiotensin II to AT1 receptor * effects similar to ACE inhibitors, but do not increase bradykinin * used for hypertension, HF, proteinuria, or chronic kidney disease (eg. diabetic nephropathy) with intolerance to ACE inhibitors (eg. cough, angioedema) * causes hyperkalemia, ↓ GFR, and hypotension * teratogen

Angiotensin II Receptor Blockers

Renal Drugs: * direct renin inhibitor * blocks conversion of angiotensinogen to angiotensin I * used for hypertension * causes hyperkalemia, ↓ GFR, hypotension, and angioedema * relatively contraindicated in patients already taking ACE inhibitors or ARBs and contraindicated in pregnancy

Aliskiren