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Renal development

The kidneys arise from the embryological intermediate mesoderm. The homeobox genes Lim-2 and Pax-2 are involved in early kidney development. The three sequential progenitors of the kidney, which are derived from the nephrogenic cord, are the: Pronephros, Mesonephros, Metanephros.



The pronephros develops in week 4, is non-functional, and degenerates.



The mesonephros develops and functions as an temporary kidney in week 4-8. The mesonephric duct, which connects the mesonephros to the cloaca, derives: Wolffian duct in the male genitourinary tract (e.g. vas deferens, epididymis, seminal vesicles); Ureteric bud (caudal end of the mesonephric duct); Trigone of the bladder (caudal end of the mesonephric duct)



The metanephros develops in week 5 and begins functioning around week 10 ultimately giving rise to the adult kidney. The fetal metanephros is located in the sacral region, and ascends in the adult kidney to T12 - L3. The metanephros is composed of the ureteric bud and the metanephric mesoderm. The aberrant interaction between these 2 tissues may result inn several congenital malformations of the kidney


Metanephric mesoderm

The metanephric mesoderm gives rise to metanephric vesicles, which become S-shaped renal tubules, ultimately forming: Renal glomerulus, Renal capsule (Bowman's capsule), Proximal convoluted tubule, Loop of Henle, Distal convoluted tubule, Connecting tubule (connects the distal convoluted tubule to the cortical collecting duct - don't confuse with collecting tubules)


Ureteric bud

The ureteric bud penetrates the metanephric mesoderm and branches to give rise to the: Collecting duct, Minor calyx, Major calyx, Renal pelvis, Ureter. The urinary system and genital system meet at the common urogenital sinus, eventually becoming the urinary bladder and external genitalia.


Ureteropelvic junction

he ureteropelvic junction (UPJ) is the last portion of the developing ureter to canalize. Thus, the UPJ is most common site of obstruction during fetogenesis leading to hydronephrosis.


Potter sequence

Potter phenotype is caused by the Potter sequence occurring sequentially: Bilateral renal agenesis leads to failure of fetal renal excretion, causing oligohydramnios, resulting in decreased amniotic fluid. This causes multiple anomalies (Potter phenotype) and early death. The POTTER sequence phenotype is associated with: Pulmonary hypoplasia, Oligohydramnios, Twisted face, Twisted skin, Extremity defects, Renal failure (in utero). Common deformations observed in the Potter sequence phenotype include: Facial deformities (e.g. Potter facies, flattened “parrot beak” nose, low-set ears, micrognathia); Limb deformities (e.g. rocker-bottom feet, talipes equinovarus).



Oligohydramnios fails to provide the fetus with adequate amniotic fluid necessary to mature the lungs, leading to pulmonary hypoplasia with severe respiratory failure and early neonatal death. Oligohydramnios allows contact of fetal skin with amnion creating amnion nodosum (nodules of fetal squamous epithelial cells on placental surface). Maternal abdominal ultrasonography may detect bilateral renal agenesis during the prenatal period. Potter's phenotype can also be caused by: Autosomal recessive polycystic kidney disease (ARPKD) and posterior urethral valves


Horseshoe kidney

Horseshoe kidney occur when the right and left kidneys fuse (90% are fused at the inferior pole; 10% are fused at the superior pole). Horseshoe kidneys become trapped under the inferior mesenteric artery (at vertebral level L3). Patients with horseshoe kidneys have normal renal function. Horseshoe kidneys may compress ureters, potentially causing: Ureteropelvic junction obstruction, Hydronephrosis, Renal stones, Infection. Horseshoe kidney is associated with the following chromosomal aneuploidy syndromes: Edwards syndrome, Down syndrome, Patau syndrome, Turner syndrome. Horseshoe kidney can rarely be associated with renal cancer, especially Wilms tumor.


Multicystic dysplastic kidney

Multicystic dysplastic kidney occurs due to an abnormal interaction between ureteric bud and the metanephric mesenchyme. Multicystic dysplastic kidney renders the affected kidney nonfunctional. Gross examination of a multicystic dysplastic kidney shows a kidney composed of macroscopic cysts compressing dysplastic renal parenchyma composed primarily of connective tissue. Most patients with multicystic dysplastic kidney have unilateral disease, which is asymptomatic. Patients have compensatory hypertrophy of contralateral kidney. Patients with bilateral multicystic dysplastic kidneys have no renal function, resulting in oligohydramnios and Potter’s syndrome. Bilateral multicystic dysplastic kidney disease is incompatible with life. Multicystic dysplastic kidney is often associated with an atretic proximal ureter. Multicystic dysplastic kidney is most often diagnosed via prenatal ultrasound.


Duplex collecting system

Duplex collecting system is a condition in which two ureters drain a single kidney. Duplex collecting system can arise via 2 etiologies: The ureteric bud, the embryological origin of the ureter, can bifurcate before it enters metanephric blastema. Alternatively, duplex collecting system can arise when two ureteric buds reach and interact with metanephric blastema. Duplex collecting system is associated with: Vesicoureteral reflux (VUR), Ureteral obstruction, often due to a ureterocele, Urinary tract infections. Duplex collecting system is most often diagnosed via prenatal ultrasound, which often shows hydronephrosis of the affected kidney due to VUR. If a duplex collecting system isn't diagnosed in utero, children can present with recurrent urinary tract infections.


Renal anatomy

The kidneys are located against the dorsal wall of abdomen, just beneath the diaphragm and are retroperitoneal (i.e., posterior to the peritoneum). The left kidney is usually taken during donor transplantation because it has a longer renal vein. Each kidney is divided into two regions: the outer renal cortex and the inner renal medulla.


The renal cortex

The renal cortex contains the: Glomeruli, Convoluted tubules, Cortical collecting ducts.


The renal medulla

The renal medulla contains the: Loops of Henle and Medullary collecting ducts. Projections of the renal medulla form pyramids, topped by papilla. Each papilla drains urine into a minor calyx, which convene to form a major calyx. The major calyx drains urine into the ureters, and subsequently, the bladder.



The functional unit of the kidney is the nephron. Each kidney contains approximately one million nephrons, each with a renal corpuscle and a renal tubule. There are two types of nephrons, cortical and juxtamedullary. In contrast to cortical nephrons, juxtamedullary nephrons have: longer Loops of Henle, lower renin content, different tubular permeability properties, different postglomerular blood supply (vasa recta).


The renal corpuscle

The renal corpuscle is composed of a tuft of capillaries called the glomerulus, surrounded by the Bowman’s capsule.


The renal tubule

The renal tubule is divided into several segments in the following order (from proximal to distal): Proximal convoluted tubule, Proximal straight tubule, Thin descending limb of the loop of Henle, Thin ascending limb of the loop of Henle, Thick ascending limb of the loop of Henle, Distal convoluted tubule, Cortical collecting duct, Medullary collecting duct.


RBF (renal blood flow)

RBF (renal blood flow) is normally ~20% of cardiac output. The renal cortex receives ~90-95% of total RBF. The renal medulla receives ~5-10% of total RBF. To reach the kidney, arterial blood leaves the descending (abdominal) aorta to enter the renal artery. Note: the renal artery emerges from the descending aorta at the level of L2 (second lumbar vertebra).


Renal capillary beds

The kidney is relatively unique as it has 2 capillary beds arranged in series: glomerular capillaries and peritubular capillaries. Glomerular capillaries are high pressure, allowing filtration of solute and water out of the systemic bloodstream and into the urine. Peritubular capillaries are low pressure, allowing reabsorption of solute and water from urine into the systemic bloodstream.


Course of ureters

Ureters pass under the uterine artery and under the ductus deferens (retroparitoneal). Water (ureters) under the bridge (uterine artery, vas deferens. Gynecologic procedures involving ligation of the uterine vessels traveling in the cardinal ligament may damage ureter causing ureteral obstruction or leak.


Body fluid compartments

The 60-40-20 rule of body fluid compartments: 60% of body weight is water, 40% of body weight is intracellular fluid (ICF), 20% of body weight is extracellular fluid (ECF).


Intracellular fluid (ICF)

The major cations within the ICF are potassium and magnesium.


Extracellular fluid (ECF)

The ECF is further divided into two compartments: the interstitial fluid and the plasma. The major cation within ECF is sodium; the major anions are chloride and bicarbonate. ECF volume is measured by inulin.


Intracellular fluid (ICF)

Interstitial fluid is normally 15% of total body weight.


Plasma volume

Plasma volume is measured by radiolabeled albumin. Plasma volume is normally 5% of total body weight. Normal blood osmolality is 285 - 295 mOsm/kg H2O.


Glomerular filtration barrier

The glomerular filtration barrier is made up of three layers: Capillary endothelial cells, Negatively-charged glomerular basement membrane (GBM), Podocytes. Capillary endothelial cells of glomerulus contain numerous large pores (fenestrae) that allow anything smaller than a red blood cell (RBC) size to pass through. A negatively-charged glomerular basement membrane (GBM) sits below the fenestrated glomerular endothelium. The negative charge of the GBM helps it repel small, negatively charged proteins (e.g., albumin). Heparan sulfate provides the negative charge to the GBM. The GBM is made of Type IV collagen. Podocytes line the other side of the GBM and form a tight network of foot processes (pedicles) that regulate ultrafiltration of proteins into Bowman’s space. Only ions (e.g. Na+, K+, Cl-, HCO3-) and small molecules (e.g., glucose, amino acids, peptides) pass freely through podocytes.


Renal clearance

Renal clearance indicates the volume of plasma cleared of a substance per unit time. Renal clearance is calculated by the formula: C(x) = U(x)V/P(x). Where: C(x) = clearance of substance x (mL/min), U(x) = urine concentration of substance x (mg/mL), V = urine flow rate (mL/min). P(x) = plasma concentration of substance x (mg/mL). If C(x) is less then GFR, then there is a net tubular reabsorption of X (example: Na+, glucose, amino acids, HCO3-, Cl-). If C(x) is greater then GFR, then there is net secretion of X [example: Para-aminohippurate (PAH)]. If C(x) = GFR, then there is no net secretion or reabsorption of X (example: inulin).


Glomerular filtration rate (GFR)

GFR is functionally measured by looking at inulin clearance because inulin is filtered, but neither reabsorbed nor secreted by renal tubules. GFR = C-inulin = (U-inulin x V) / P-inulin. Where: C-inulin = clearance of inulin (mL/min), U-inulin = urine concentration of inulin (mg/mL), V = urine flow rate (mL/min), P inulin = plasma concentration of inulin (mg/mL). GFR normally decreases with age. In healthy patients, this decrease in GFR is not accompanied by a rise in serum creatinine, since creatinine is derived from muscle mass, which also decreases with age. Creatinine clearance slightly overestimates GFR because creatinine is also secreted by the proximal tubules. Creatinine clearance (CCr) is used to estimate GFR: GFR ≈ CCr = UCr V / PCr.


Starling equation

Another way to express GFR is through use of Starling equation: GFR = Kf [ (Pgc – Pbs) – (Pigc – Pibs)]. Where: Kf – filtration coefficient of glomerular capillaries. Pgc – glomerular capillary hydrostatic pressure, which is constant along the length of the capillary. Pbs – Bowman’s space hydrostatic pressure. Pigc – glomerular capillary oncotic pressure. Pibs – Bowman’s space oncotic pressure. The driving force for glomerular filtration is the net ultrafiltration pressure across the glomerular capillaries. This results in an increased GFR. The value of oncotic pressure in Bowman's space is usually zero since only a small amount of protein is filtered.


Effective renal plasma flow (eRPF)

Renal plasma flow can be approximated by measuring the clearance of paraaminohippuric acid (PAH) because it is both filtered and secreted in the proximal collecting tubule (PCT) resulting in near 100% excretion of all PAH entering the kidney. eRPF=Urine PAH*V/Plasma PAH=Clearence PAH. RBF=RPF/(1-Hematocrit). V = urine flow rate (ml/min or ml/24hr)


Renal blood flow

RBF = [ RPF / (1-Hematocrit) ]. Where: RBF = renal blood flow. RPF = renal plasma flow


Filtration fraction

Filtration fraction is the fraction of renal plasma flow (RPF) filtered across the glomerular capillaries. Filtration fraction = GFR / RPF. Normally, 20% of RPF is filtered; 80% leaves through efferent arterioles to enter the peritubular capillaries. An increase in FF leads to an increase in the protein concentration of peritubular capillary blood, which leads to increased reabsorption in the proximal tubule. A decrease in FF leads to a decrease in the protein concentration of peritubular capillary blood and decreased reabsorption of water in the proximal tubule. Prostaglandins preferentially dilate afferent arteriole (increasing RPF, GFR, so FF remains constant). NSAIDs inhibit this. Angiotensin II preferentially constricts efferent arteriole (decreasing RPF, increasing GFR so FF increases). ACE inhibitors prevents this.


Effects of afferent arteriole constriction on GFR, RPF, and FF (GFR/RPF)

GFR decreases, RPF decreases, FF (GFR/RPF) does not change


Effects of efferent arteriole constriction on GFR, RPF, and FF (GFR/RPF)

GFR increases, RPF decreases, FF (GFR/RPF) increases


Effects of an increase in plasma protein concentration on GFR, RPF, and FF (GFR/RPF)

GFR decreases, RPF does not change, FF (GFR/RPF) decreases


Effects of a decrease in plasma protein concentration on GFR, RPF, and FF (GFR/RPF)

GFR increases, RPF does not change, FF (GFR/RPF) increases


Effects of constriction of ureter on GFR, RPF, and FF (GFR/RPF)

GFR decreases, RPF does not change, FF (GFR/RPF) decreases


Calculation of reabsorption and secretion rate

Filtered load=GFR x Plasma concentration. Excretion rate= V x Urine concentration. V = urine flow rate (ml/min or ml/24hr). Reabsorption= filtered- excreted. Secretion= excreted- filtered.


Glucose clearance

Glucose at a normal plasma level is completely reabsorbed in PCT by Na/glucose cotransport. At plasma glucose of around 200 mg/dL, glucosuria begins (threshold is reached). At about 375 mg/dL, all transporters are fully saturated (Tm). Glucosuria is an important clinical clue to diabetes mellitus. Normal pregnancy may decrease ability of PCT to reabsorb glucose and amino acids, leading to glucosuria and aminoaciduria.


Amino acid clearance

Amino acids are reabsorbed in the proximal convoluted tubule via cotransport with Na+.


Hartnup disease

Hartnup disease is a hereditary defect of the intestinal and renal reabsorption of neutral amino acids. Hartnup disease is inherited in an autosomal recessive manner. Patients with Hartnup disease present with the symptoms of pellagra, including the classic triad of: Diarrhea, Dementia (including ataxia and hallucinations), Dermatitis, aka “Casal necklace”. Insufficient reabsorption of tryptophan is responsible for the symptoms of Hartnup disease. Patients with Hartnup disease present with the symptoms of pellagra because there is insufficient tryptophan for conversion to niacin. Patients with Hartnup disease have neutral aminoaciduria. Patients with Hartnup disease are treated with a high-protein diet and supplemental nicotinic acid.


Na+/K+ ATPase

Na+/K+ ATPase in the basolateral membrane extrudes Na+ from renal tubular cells into the interstitium, thereby lowering intracellular Na+ and maintaining a gradient that favors passive Na+ reabsorption from the lumen into the renal tubular cells.


Proximal convoluted tubule (PCT)

The PCT has a distinctive brush border packed with microvilli. The fluid within the PCT is isosmotic, since solutes are reabsorbed isosmotically within this part of the nephron. A sodium-glucose linked transporter (SGLT) in the PCT reabsorbs glucose, while a variety of dedicated Na+ co-transporters reabsorb amino acids. Reabsorption of phosphate is directly linked to a sodium/phosphate cotransporter in the proximal tubule. PTH (parathyroid hormone) induces sodium/phosphate cotransporter endocytosis, leading to decreased reabsorption of phosphate. Reabsorption of filtered HCO3- is directly coupled to renal secretion of H+ via the action of carbonic anhydrase and the Na+/H+ antiporter. For each HCO3- filtered, one H+ is secreted into the renal tubular lumen. 67% of filtered Na+ and H2O reabsorption in the PCT.


The reabsorption of filtered HCO3

The reabsorption of filtered HCO3 in the PCT involves 5 steps: 1. Na+/K+ ATPase on the basolateral membrane extrudes Na+ from renal tubular cells into the interstitium, thereby lowering intracellular Na+. 2. Na+ enters the cell from the renal tubular lumen in exchange for H+ via the Na+/H+ antiporter. 3. This luminal H+ may combine with filtered HCO3- via the action of luminal carbonic anhydrase (located in the brush border of the proximal tubule) to produce water and CO2. 4. This luminal CO2 can then diffuse into the cell, where it is converted by intracellular carbonic anhydrase back into H+ and HCO3-. 5. This intracellular HCO3- is transported through the basolateral membrane into the interstitial fluid and ultimately the bloodstream. Since Angiotensin II stimulates the Na+-H+ antiporter in the proximal tubule, it also stimulates the reabsorption of HCO3- and H2O. Thus, increased reabsorption of HCO3- can cause a metabolic alkalosis in the setting of volume contraction, also known as a contraction alkalosis.


Thin descending limb of the Loop of Henle

The thin descending limb of the Loop of Henle allows passive reabsorption of water, but is impermeable to sodium, which concentrates the tubular fluid, increasing its osmolarity greater than the osmolarity in plasma (TFosm/Posm > 1.0). This makes urine hypertonic.


Thick ascending limb (TAL) of the Loop of Henle

The thick ascending limb (TAL) of the Loop of Henle is impermeable to water, but allows reabsorption of: Na+, K+ (or NH4+), Cl-, Ca2+, Mg2+. Reabsorption of ions in the thick ascending limb is facilitated by an active Na-K(NH4)-2Cl co-transporter (NKCC symporter) within the luminal membrane. NH4+ competes with K+ for reabsorption by this transporter. Reabsorption of ions, but not water, results in dilution of the tubular fluid, making the fluid osmolarity decrease to less than the osmolarity in plasma. K+ leak channels allow K+ to leak into the tubular lumen of the ascending limb, thereby generating an electrochemical potential gradient that drives further reabsorption of the following cations: K+, Mg2+, Ca2+. 10-20% of Na is reabsorbed here.


Distal convoluted tubule (DCT)

The distal convoluted tubule (DCT) reabsorbs of NaCl by an NaCl co-transporter, making the tubular fluid here becomes hypotonic. The distal convoluted tubule is lined by simple cuboidal cells with NO brush border. Increased sodium absorption in the late distal convoluted tubule and collecting ducts is mediated by aldosterone. The distal convoluted tubule (DCT) is the site of action for PTH-driven Ca2+ reabsorption in the kidney. In the nephron, PTH acts at the proximal convoluted tubule to decrease phosphate reabsorption and at the distal convoluted tubule to increase calcium reabsorption. 5-10% of Na is reabsorbed here.


Collecting tubules

The collecting tubules are the final branch of the nephron consisting of two cell types: principal cells and intercalated cells.


Principal cells

Principal cells, located in the collecting tubules, reabsorb Na+ and H2O and secrete K+. Principal cells are sites of aldosterone and antidiuretic hormone (ADH) action. Aldosterone increases Na+ reabsorption [via epithelial sodium channel (ENaC)] and K+ secretion [via renal outer medullary potassium channel [ROMK)] in principal cells. Antidiuretic hormone (ADH) acts at the V2 receptor on principal cells to activate the adenylyl cyclase-cAMP pathway, thereby stimulating the insertion of aquaporin-2 (AQP2) channels into the apical plasma membrane. The majority (90%) of cases of hereditary nephrogenic diabetes insipidus are caused by a mutation in the V2 receptor, rendering it unable to stimulate adenylyl cyclase.


Intercalated cell

There are two types of intercalated cell located in the collecting tubules: alpha-intercalated and beta-intercalated. Activity of these cells plays a major role in acid-base homeostasis.


Alpha-intercalated cells

Alpha-intercalated cells, located in the collecting tubules, secrete H+ (and reabsorb K+) via an apical H+/K+-exchanger as well as an H+-ATPase. Alpha-intercalated cells also reabsorb bicarbonate by a basolateral Cl-/HCO3- exchanger. Aldosterone acts at alpha-intercalated cells to increase H+ secretion by stimulating the H+-ATPase. Under conditions of K+ depletion, reabsorption of K+ by alpha-intercalated cells predominates over K+ secretion by principal cells, resulting in net K+ reabsorption. Under conditions of K+ surplus, K+ secretion by principal cells predominates over K+ reabsorption by alpha-intercalated cells, resulting in net K+ secretion.


Beta-intercalated cells

Beta-intercalated cells, located in the collecting tubules, secrete HCO3- (and reabsorb Cl-) via an apical Cl-/HCO3- exchanger. Beta-intercalated cells also reabsorb H+ by a basal H+-ATPase.


Renal tubular defect

The kidneys put out FABulous Glittering LiquidS. FAnconi syndrome is the 1st defect (PCT). Bartter syndrome is next (thick ascending loop of Henle). Gitelman sindrome is after Bartter (DCT). Liddle syndrome is the last (collecting tubule). Syndrome of apparent mineralocorticoid excess (collecting tubules).


Fanconi syndrome

This is a generalized reabsorption defect in the PCT. It is associated with increased excretion of nearly all amino acids, glucose, HCO3, and PO4. It may result in metabolic acidosis (proximal renal tubular acidosis). Causes include hereditary defects (eg Wilson disease, tyrosinemia, glycogen storage disease), ischemia, multiple myeloma, nephrotoxins/ drugs (eg expired tertracyclines, tenofovir), lead poisoning.


Bartter syndrome

Reabsorptive defect in the thick ascending loop of Henle. It is autosomal recessive. It affects Na/K/2Cl cotransporter, resulting in hypokalemia and metabolic alkalosis with hypercalciuria.


Gitelman syndrome

It is a reabsorptive defect of NaCl in the DCT. It is autosomal recessive. It is less severe than Bartter syndrome. It leads to hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria (Bartter leads to hypercalciuria).


Liddle syndrome

It is a gain of function mutation that increases Na reabsorption in the collecting tubules (by increasing the activity of epithelial Na channel). It is autosomal dominant. It results in hypertension, hypokalemia, metabolic alkalosis, and a decrease in aldosterone. Treatment is amiloride.


Syndrome of apparent mineralocorticoid excess

This is a hereditary deficiency of 11 beta-hydroxysteroid dehydrogenase, which normally converts cortisol into cortisone in mineralocorticoid receptor-containing cells before cortisol can act on the mineralocorticoid receptors. Excess cortisol in these cells from enzyme deficiency, causes an increase in mineralocorticoid receptor activity, leading to hypertension, hypokalemia, metabolic alkalosis. There are low serum aldosterone levels. This disorder can be acquired from glycyrrhetic acid (present in licorice), which blocks activity of 11 beta hydroxysteroid dehydrogenase.


Relative concentrations along proximal convoluted tubules

TF/P= Tubular fluid/ Plasma. When TF/P is greater than 1, solute reabsorption is slower than water, causing net secretion (PAH and cretinine fall in this category). When creatinine. When TF/P=1, solute and water reabsorption is at the same rate (insulin falls in this category). When TF/P is less than 1, solute is reabsorbed more quickly than water, leading to net reabsorption (amino acids, electrolytes and urea fall in this category). Tubular insulin increases in concentration (but not in 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. This, its relative concentration increase before it plateaus.


Macula densa

Macula densa provide signal for the juxtaglomerular apparatus (JGA) smooth muscle cells to secrete renin.



Renin (also known as angiotensinogenase) circulates in blood to cleave a plasma alpha globulin, angiotensinogen (made in the liver) to angiotensin I.


Angiotensin I

Angiotensin I is cleaved by angiotensin-converting enzyme (ACE) to Angiotensin II. ACE is primarily secreted by lung and kidney vascular endothelium.


Angiotensin II (AT II)

Actions of angiotensin II (AT II): 1. Potent vasoconstriction (via angiotensin II receptor, type 1 (AT1) on vascular smooth muscle) causing an increase blood pressure. 2. IncreasedNa+/H+ exchange and HCO3- reabsorption in proximal tubule. This is the mechanism of contraction alkalosis. 3. Increased release of aldosterone causing increased intravascular volume. 4. Increased release of ADH causes increased intravascular volume. 5. Stimulates hypothalamus to increased thirst sensation. 6. Increases the filtration fraction (FF) by constricting the efferent arteriole of the glomerulus, thereby increasing the GFR and decreasing RPF. This protects the kidney in states of volume depletion. 7. Modulates baroreceptor function to limit reflex bradycardia, which is a normal response to AT II-induced vasoconstriction.


Juxtaglomerular apparatus (JGA)

The stimulus for renin release is the juxtaglomerular apparatus (JGA) perception of: Decreased renal blood pressure, Decreased NaCl delivery to distal tubule sensed by the macula densa, Increased sympathetic tone. Technically, only the delivery of Cl- is sensed by the macula densa. However, Na+ and Cl- usually travel together, so Cl- delivery can be considered a proxy of Na+ delivery to the distal convoluted tubule. Renin is produced by juxtaglomerular cells of the juxtaglomerular apparatus. Juxtaglomerular cells are modified smooth muscle cells found in walls of the afferent arterioles.



ANP is a potent vasodilator, which relaxes vascular smooth muscle by increasing intracellular cGMP. ANP dilates the afferent glomerular arteriole while constricting the efferent glomerular arteriole, thereby increasing GFR. ANP inhibits the reabsorption of NaCl via cGMP-dependent inhibition of Na+ reabsorption in the inner medullary collecting duct and Cl- in the cortical collecting duct. ANP reduces renin and aldosterone secretion.



It is also a potent vasodilator with the same mechanism as ANP but it is released by the ventricle. Nesiritide is a recombinant form of BNP used for the treatment of heart failure.



Primarily regulates osmolarity. It also responds to low blood volume states. It is secreted in response to increased plasma osmolarity and decreased blood. volume. It binds to receptors on principle cells, causing an increased in number of aquaporins and increased H2O reabsorption.



Primarily regulates ECF volume and Na content. It responds to low blood volume states (via AT II) and increase plasma concentration. It causes an increase in Na reabsorption, increases K secretion, and increases H secretion.



It is released by interstitial cells in the peritubular capillary bed of the kidney in response to hypoxia


1 alpha-hydroxylase

Located in the PCT cells and converts 25-OH vitamin D to 1, 25-(OH)2 vitamin D (active form). It is activated by PTH.



It is secreted by JG cells in response to decreases renal arterial pressure and increased renal sympathetic discharge (beta 1 effect).



Paracrine secretion from vasodilates the afferent arterioles to increase RBF. NSAIDs block renal-protective prostaglandin synthesis causes constriction of afferent arteriole and a decrease in GFR. This may result in acute renal failure.


Parathyroid hormone (PTH)

It is secreted in response to decreased plasma Ca concentration, increased plasma PO2 concentration, or decreased plasma 1, 25 (OH)2 D3 production (increasing Ca and PO4 absorption from gut via vitamin D).



Causes nausea and malaise, stupor, coma, seizures



Causes irritability, stupor, coma.



Causes U waves on ECG, flattened T waves, arrhythmias, and muscle spasm.



Wide QRS and peaked T waves on ECG, arrhythmias, and muscle weakness.



Causes tetany, seizures, GT prolongation



Causes stones (renal), bones (pain), groans (abdominal pain), thrones (increases urinary frequency), psychiatric overtones (anxiety, altered mental status), but not necessarily calcuria.



Causes tetany, torsades de pointes, hypokalemia.



Causes decreased deep tendon reflex, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia



Causes bone loss, osteomalacia (adults), rickets (children)



Causes renal stones, metastatic calcifications, hypocalcemia.


Causes of potassium shifts out of the cell (causing hyperkalemia)

Digitalis (blocks Na/K ATPase), hyperOsmolarity, Lysis of cells (eg crush injury, rhabdomyolysis, cancer), Acidosis, Beta blocker, high blood Sugar (insulin deficiency). Patients with hyperkalemia? DO LABS.


Causes of potassium shifts into the cell (causing hyperkalemia)

Hypo-osmolarity, alkalosis, beta-adrenergic agonist (increased Na/K ATPase), insulin (increased Na/K ATPase). INsulin shifts K INto cells.


Metabolic acidosis

Metabolic acidosis is defined as an acidotic pH (over 7.37) with a decrease in HCO3- levels. Causes of metabolic acidosis are separated into two categories: increased anion gap and normal anion gap. In metabolic acidosis, pH is decreased, PO2 is decreased, HCO3 is decreased. Compensatory response is hyperventilation (immediate), causing PCO2 to be less than 40 mmHg. Metabolic acidosis can be broken down into anion gap (AG) and non-anion gap acidosis.


Increased anion gap metabolic acidosis

Anion gap calculation: AG (mEq/L) = [Na] – ([Cl] + [HCO3]). Normal = 10-15 mEq/L. Causes of anion gap metabolic acidosis include: Ketoacidosis (starvation, DKA, alcohol use), Exogenous toxins (methanol, ethylene glycol, salicylates), Lactic acidosis (ischemia, shock), Renal failure (decreased NH4+ excretion), Significant uremia, Drugs: paraldehyde, INH. Useful Mnemonic: MUDPILES (Methanol, Uremia, DKA, Paraldehyde, INH, Lactic acidosis, Ethylene glycol, Salicylates)


Normal anion gap metabolic acidosis

Normal anion gap is 8-12 mEq/L causes include (HARD-ASS): Hyperalimentation, Addison disease, Renal tubular acidosis, Diarrhea, Acetazolamide, Spironolactone, Saline infusion.


Winters formula

Winters formula is used to evaluate respiratory compensation in the presence of a metabolic acidosis. If the patients Pco2 differs significantly from the Pco2 predicted by the formula, a mixed acid-base disorder is present: Pco2 = 1.5 [HCO3-] + 8 ± 2


Metabolic alkalosis

Metabolic alkalosis is defined as a serum pH over 7.43 with an increase in serum HCO3- levels. PCO2 is increased, HCO3 is increased. The compensatory response is hypoventilation, leading to a PCO2 over 40 mmHg. Causes include loop/thiazide diuretics, vomiting, antacid use, and hyperaldosteronism.


Henderson-Hasselbalch equation

The Henderson-Hasselbalch equation is used to calculate pH: pH = pK + log {[A-] / [HA]}. Where: [A-] = base form of buffer (mM)/H+ acceptor; [HA] = acid form of buffer (mM)/H+ donor. pH = pK when the concentrations of A- and HA are equal. Using the Henderson-Hasselbalch equation, plasma pH can be determined: pH = 6.1 + log [HCO3-]/[0.03xPCO2]. Where: 6.1 is the pKa for carbonic acid 0.03 is the factor that relates PCO2 to the amount of CO2 dissolved in plasma


Respiratory acidosis

Respiratory acidosis is defined as a serum pH under 7.37 with an increase in pCO2 (over 45). pH is decreased, PCO2 is increased, HCO3 is increased. The compensatory response is increased [HCO3] reabsorption (delayed). Causes include ariway obstruction acute lung disease, chronic lung disease, opioids, sedatives, weakening of respiratory muscles. Hypoventilation


Respiratory alkalosis

Respiratory alkalosis is defined as a pH over 7.43 with a decrease in pCO2 (under 35). pH increases, PCO2 decreases, HCO3 decreases. The compensatory response is a decrease renal HCO3 reabsorption (delayed). Causes include hysteria, hypoxemia (eg high altitude), salicylates (early), tumor, pulmonary embolism. Hyperventilation.


Renal tubular acidosis

Renal tubular acidosis (RTA) is a defect in tubular function that causes a non-anion gap hyperchloremic metabolic acidosis due to a failure of the kidneys to excrete acid or reabsorb bicarbonate. There are three types of RTA: Type 1 (distal), Type 2 (proximal), Type 4 (mineralocorticoid resistant)


Distal (type 1) renal tubular acidosis

Urine pH is above 5.5. It is due to a defect in ability of alpha intercalated cells to secret H, which prevents new HCO3 generation causing metabolic acidosis. It is associated with hypokalemia. There is an increase risk for calcium phosphate kidney stones (due to an increase in urine pH and increased bone turnover). Causes include amphotericin B toxicity, analgesic nephropathy, congenital anomalies (obstruction) of the urinary tract.


Proximal (type 2) renal tubular acidosis

Urine pH is under 5.5. It is due to a defect in PCT HCO3 reabsorption causing increased excretion of HCO3 in urine and subsequent metabolic acidosis. Urine is acidified by alpha intercalated cells in collecting tubule. It is associated with hypokalemia and increased risk for hypophosphatemic rickets. Causes include Fanconi syndrome and carbonic anhydrase inhibitors.


Hyperkalemic (type 3) renal tubular acidosis

Urine pH is under 5.5. It is due to hypoaldosteronism leading to hyperkalemia, which decreases NH3 synthesis in PCT, thus decreasing NH4 excretion. Causes include decreased 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).


Casts in urine

The presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin. Bladder cancer and kidney stones causes hematuria with no casts. Acute cystitis causes pyuria with no casts.


RBC casts

Sign of glomerulonephritis and malignant hypertension.


WBC casts

Sign of tubulointerstitial inflammation, acute pyelonephritis, and transplant rejection.


Fatty casts (oval fat bodies)

Sign of nephrotic syndrome


Granular (muddy brown) casts

Sign of acute tubular necrosis


Waxy casts

Sign of end stage renal disease/chronic renal failure.


Hyaline casts

It is nonspecific. It can be a normal finding, often seen in concentrated urine samples.



Less than 50% of the glomeruli are involved. An example is focal segmental glomerulosclerosis.



More than 50% of the glomeruli are involved. An example is diffuse proliferative glomerulonephritis.



Hypercellular glomeruli. An example is membranoproliferative glomerulonephritis.



Thickening of glomerular basement membrane (GBM). An example is membranous nephropathy.


Primary glomerular disease

A primary disease of the kidney specifically impacting the glomeruli. For example minimal change disease.


Secondary glomerular disease

A systemic disease or disease of another organ system that also impacts the glomeruli. For example SLE or diabetic nephropathy.


Nephritic syndrome

It occurs due to GBM disruption. Signs and symptoms include hypertension, increased BUN and creatine, oliguria, hematuria, RBC casts in urine. Proteinuria often in the subnephrotic range (less than 3.5 g/day) but in severe cases it may be in the nephrotic range. Examples include acute poststreptococcal glomerulonephritis, rapidly progressive glomerulonephritis, IgA nephropathy (Berger disease), Alport syndrome, membranoproliferative glomerulonephritis. NephrItic=Inflammatory process. When it involves glomeruli, it leads to hematuria and RBC casts in urine. It is associated with azotemia, oliguria, hypertension (due to salt retention), and proteinuria.


Nephrotic syndrome

It occurs due to podocyte disruption, causing impairment of the charge barrier. There is massive proteinuria (over 3.5 g/day) with hypoalbuminemia, hyperlipidemia, edema. It may be primary (direct podocyte damage) or secondary (podocyte damage from systemic process [eg diabetes]). Examples include focal segmental glomerulosclerosis (primary or secondary), minimal change disease (primary or secondary), membranous nephropathy (primary or secondary), amyloidosis (secondary), diabetic glomerulonephropathy (secondary). NephrOtic=prOteinuria, with hypoalbuminemia, resulting in edema and hyperlipidemia. There is frothy urine with fatty casts. Severe nephritic syndrome may be present with nephritic syndrome features (nephritic-nephrotic syndrome) if damage to GBM is severe enough to damage charge barrier. It is associated with hypercoagulable state (due to loss of immunoglobulines in urine and soft tissue compromise by edema).


Nephritic-nephrotic syndrome

Severe nephritic syndrome with profound GBM damage that damages the glomerular filtration charge barrier causing nephrotic range proteinuria (over 3.5 g/day) and concomitant features of nephrotic syndrome. It can occur with any form of nephritic syndrome, but is most commonly seen with diffuse proliferative glomerulonephritis and membranoproliferative glomerulonephritis.


Acute poststreptococcal glomerulonephritis

A nephritic syndrome. It is most frequently seen in children. It occurs about two weeks after a group A streptococcal infection of the pharynx or skin. It resolves spontaneously. It is a type III hypersensitivity reactions. It presents with peripheral and periorbital edema, cola-colored urine, and hypertension. There are increased anti-DNase B titers and decreased complement levels.


Light microscopy (LM) findings of acute poststreptococcal glomerulonephritis

Light microscopy (LM) findings include glomeruli enlarged and hypercellular.


Immunofluorescence findings of acute poststreptococcal glomerulonephritis

Starry sky granular appearance, lumpy bumpy due to IgG, IgM, and C3 deposition along GBM and mesangium.


Electron microscopy findings of acute poststreptococcal glomerulonephritis

Subepithelial immune complex (IC) humps.


Rapidly progressive (cresentic) glomerulonephritis (RPGN)

A nephritic syndrome. Crescents consist of fibrin and plasma proteins (eg C3b) with glomerular parietal cells, monocytes, and macrophages. There are several disease processes may result in this pattern, in particular: goodpasture syndrome (hematuria/hemoptysis, treatment is emergent plasmapheresis), granulomatosis with polyangiitis (PR3-ANCA/c-ANCA), microscopic polyangiitis (MPO-ANCA/p-ANCA). There is a poor prognosis with rapidly deteriorating renal function (days to weeks).


Light microscopy findings with rapidly progressive glomerulonephritis (RPGN)

Crescent moon shaped


Goodpasture syndrome

Type II hypersensitivity; antibodies to GBM and alceolar basement membrane creating linear immunofluorescent staining.


Diffuse proliferative glomerulonephritis

A nephritic syndrome. It is due to SLE or membranoproliferative glomerulonephritis. It is the most common cause of death in SLE. DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.


Light microscopy findings of diffuse proliferative glomerulonephritis

Wire looping (think WIRE LUPus) of capillaries.


Electron microscopy findings of diffuse proliferative glomerulonephritis

Subendothelial and sometimes intramembranous IgG-based immune complexes often with C3 deposition.


Immunofluorescence findings of diffuse proliferative glomerulonephritis

Granular appearance.


IgA nephropathy (Berger disease)

A nephritic syndrome. It is the renal pathology of Henoch-Scholein purpura. It often presents with renal insufficiency or acute gastroenteritis. There are episodic hematuria with RBC casts. It is not to be confused with Buerger disease (thromboangiitis obliterans)


Light microscopy findings of IgA nephropathy

Mesangial proliferation


Electron microscopy findings of IgA nephropathy

Mesangial immune complex deposits


Immunofluorescence findings of IgA nephropathy

IgA based immune complex deposits in mesangium.


Alport syndrome

A nephritic syndrome. It is due to a mutation in type IV collagen causing a thinning and splitting of glomerular basement membrane. It is most commonly x-linked recessive. It causes eye problems (eg retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness; can't see, can't pee, can't hear a buzzing bee. Basket weave appearance on EM.


Membranoproliferative glomerulonephritis (MPGN)

A nephritic syndrome. There are two types. MPGN is a nephritic syndrome that often copresents with nephrotic syndrome.


Type I membranoproliferative glomerulonephritis (MPGN)

Subendothelial immune complex deposits with granular immunofluorescence; tram-track appearance on PAS stain and H and E stain due to GBM splitting caused by mesangial ingrowth. Type I may be secondary to hepatitis B or C infection. It may also be idiopathic.


Type II membranoproliferative glomerulonephritis (MPGN)

There are intramembranous immune complex deposits, "dense deposits". Tye II is associated with C3 nephritic factor (stabilizes C3 convertase causing there to be a decrease in serum C3 levels).


Focal segmental glomerulosclerosis

It is the most common cause of nephrotic syndrome in african americans and hispanics. It can be primary (idiopathic) or secondary to other conditions (eg HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, chronic kidney disease due to congenital malformations). Primary disease has inconsistent response to steroids. It may progress to chronic renal disease.


Light microscopy findings of focal segmental glomerulosclerosis

Segmental sclerosis and hyalinosis.


Immunofluorescence findings of focal segmental glomerulosclerosis

nonspecific for focal deposits of IgM, C3, C1.


Electron microscopy findings of focal segmental glomerulosclerosis

Effacement of foot process similar to minimal change disease.


Minimal change disease

It is the most common cause of nephrotic syndrome in children. It is often primary (idiopathic) and may be triggered by a recent infection, immunization, or immune stimulus. rarely, it may be secondary to lymphoma (eg cytokine mediated damage). Primary disease has excellent response to corticosteroids.


Light microscopy findings of minimal change disease

normal glomeruli (lipid may be seen in PCT cells).


Immunofluorescence findings of minimal change disease

It is negative


Electron microscopy findings of minimal change disease

Effacement (fusion) of foot processes.


Membranous nephropathy

It is the most common cause of primary nephrotic syndrome in caucasian adults. It can be primary (idiopathic) or secondary (eg antibodies to phospholipase A2 receptor, drugs [eg NSAIDs, penicillamine], infections [eg HBV, HCV], SLE, solid tumors). Primary disease has a poor response to steroids. It may progress to chronic renal disease.


Light microscopy findings of membranous nephropathy

diffuse capillary and GBM thickening


Immunofluorescence findings of membranous nephropathy

Granular as a result of immune complex deposition. Nephrotic presentation of SLE.


Electron microscopy findings of membranous nephropathy

spike and dome appearance with subepithelial deposits.



It can cause a nephrotic syndrome. Kidney is the most commonly involved organ in systemic amyloidosis. It is associated with chronic conditions (eg multiple myeloma, TB, rheumatoid arthritis). Congo red stain shows apple green birefringence under polarized light.


Diabetic glomerulonephropathy

Nonenzymatic glycosylation of GBM, which increases the permeability and thickening of the GBM. Nonenzymatic glycosylation of efferent arterioles increases GFR, causing mesengial expansion.


Light microscopy findings of diabetic glomerulonephropathy

Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis.


Kidney stones

Nephrolithaisis is the precipitation of solute, normally present in the urine, as a stone. Kidney stones form due to a high concentration of solutes in the urine and a low urine volume. There are four main types of kidney stones which are discussed below: Calcium oxalate and/or calcium phosphatate, Ammonium magnesium phosphate ("Struvite" or "Staghorn"), Uric acid, Cystine. Kidney stones present with colicky pain and hematuria, often with unilateral flank tenderness.


Calcium kidney stones

80% of stones. It precipitates at increased pH (calcium phosphate) and at decreased pH (calcium oxalate). They are radiopaque on x-ray. There are envelope or dumbbell-shaped calcium oxalate. Oxalate crystals can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia, malabsorption (eg Crohn disease). Calcium oxalate stones are the most common kidney stone presentation in patients with hypercalciuria and normocalcemia. Treatment is hydration, thiazides, and citrate.


Ammonium magnesium phosphate kidney stones

15% of stones. It precipitates at an increased pH. It is radiopaque on x-ray. There are coffin lid urine crystal in urine. It is also known as struvite. It is caused by infection with urease positive bugs (eg proteus mirabilis, staphylococcus saprophyticus, klebsiella) that hydrolyze urea to ammonia causing urine alkalinization. They commonly form staghorn calculi. Treatment includes eradication of underlying infection, surgical removal of stone.


Uric acid kidney stone

5% of kidney stones. It precipitates at a decreased pH. It is radiolUcent (Uric). There are rhomboid or rosettes urine crystals in urine. Risk factors include decreased urine volume, arid climates, and acidic pH. Visible on CT and ultrasound, but not x-ray. There is a strong association with hyperuricemia (eg gout). It is often seen in diseases with increased cell turnover, such as leukemia. Treatment includes alkalinization of urine and allopurinol.


Cystine kidney stone

1% of kidney stones. It precipitates at decreased pH. It is radiolucent on x-ray. There are hexagonal crystal in urine. There are hereditary (autosomal recessive) condition in which cystine-reabsorbing PCT transporter loses function, causing cystinuria. Cystine is poorly soluble, thus stones form in urine. It is mostly seen in children. It can form staghorn calculi. It is sodium cyanide nitroprusside test positive. SIXtine stones have SIX sides. Treatment is alkalinization of urine.



Distention/ dilation of renal pelvis and calyces. It is usually caused by urinary tract obstruction (eg renal stones, BPH, cervical cancer, injury to ureter). Other causes include retroperitoneal fibrosis, vesicoureteral reflux. Dilation occurs proximal to site of pathology. Serum creatinine becomes elevated only if obstruction is bilateral or if patient has only one kidney. It leads to compression and possible atrophy of renal cortex and medulla.


von Hippel Lindau syndrome

von Hippel Lindau syndrome is an autosomal dominant disease associated with deletions in VHL gene on chromosome 3. Patients often develop RCC, especially multifocal and/or bilateral RCCs.


Renal cell carcinoma

It originates from PCT cells with polygonal clear cells filled with accumulated lipids and carbohydrates. It is most common in men between the ages of 50-70 years old. There is increased incidence with smoking and obesity. It invades renal vein then IVC and spreads hematogenously and metastasizes to the lung and bone. It is the most common primary renal malignancy. It is associated with gene deletion on chromosome 3 (sporadic or inherited as von Hippel-Lindau syndrome). RCC=3 letters= on chromosome 3. It is a silent cancer because it commonly presents as a metastatic neoplasm.


Presentation of renal cell carcinoma

It manifests clinically with hematuria, palpable mass, secondary polycythemia, flank pain, fever, weight loss.


Associated paraneoplastic syndromes with renal cell carcinoma

Ectopic EPO, ACTH, PTHrP.


Renal oncocytoma

Benign epithelial cell tumor. There are large eosinophilic cells with abundant mitochondira without perinuclear clearing (vs chromophobe renal cell carcinoma). It often presents with painless hematuria, flank pain, abdominal mass. It is often resented to exclude malignancy (RCC).


Wilms tumor (nephroblastoma)

It is the most common renal malignancy of early childhood (ages 2-4). It contains embryonic glomerular structures. It presents with large, palpable, unilateral flank mass and/ or hematuria. It occurs due to loss of function mutations of tumor suppressor genes WT1 or WT2 on chromosome 11. It may be a part of Beckwith-Wiedemann syndrome (Wilms tumor, macroglossia, organomegaly, hemihypertrophy) or WAGR complex: Wilms tumor, Aniridia, Genitourinary malformation, mental Retardation.


Transitional cell carcinoma

It is the most common tumor of urinary tract system (it can occur in renal calyces, renal pelvis, ureters, and bladder). It causes painless hematuria (no casts) suggests bladder cancer. It is associated with problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, and Cyclophosphamide. Histology will show papillary growth lined by transitional epithelium with mild nuclear atypia and pleomorphism.


Squamous cell carcinoma of the bladder

Chronic irritation of the urinary bladder causes squamous metaplasia, which can progress to dysplasia and squamous cell carcinoma. Risk factors include Schistosoma haematobium infection (Middle East), chronic cystitis, smoking, chronic nephrolithiasis. It presents with painless hematuria.


Acute bacterial cystitis (UTI)

Inflammation of the urinary bladder. It presents as suprapubic pain, dysuria, urinary frequency, urgency. Systemic signs include higher fever, chills, are usually absent. Risk factors include female gender (short urethra), sexual intercourse (honeymoon cystitis), indwelling catheter, diabetes mellitus, impaired bladder emptying.


Bacterial causes of acute cystitis

E. coli (most common), Staphylococcus saprophyticus (seen in sexually active young women, but E coli is still most common in this group), Klebsiella, Proteus mirabilis (urine has an ammonia scent).


Lab findings with acute bacterial cystitis

Positive leukocyte esterase, positive nitrites for gram negative organisms (especially E coli). Sterile pyuria and negative urine cultures suggest urethritis by Neisseria gonorhoeae or Chlamydia trachomatis.


Acute pyelonephritis

Neutrophils infiltrate renal intertitisum. It affects the cortex with relative sparing of glomeruli/vessels. It presents with fevers, flank pain (costovertebral angle tenderness). Causes include ascending UTI (E coli is the most common), hematogenous spread to kidney. It presents with WBCs in urine with or without WBC casts. CT shows striated parenchymal enhancement. Risk factors include indwelling urinary catheter, urinary tract obstruction, vesicourecteral reflex, diabetes mellitus, and pregnancy. Complications include chronic pyelonephritis, renal papillary necrosis, perinephric abscess, urosepsis. Treatment antibiotics.


Chronic pyelonephritis

It is the result of recurrent episodes of acute pyelonephritis. It typically requires predisposition to infection such as vesirecteral reflux or chronically obstucting kidney stones. There are coasrse, asymmetric corticomedullary scarring and blunted calyx. tubules can contain eosinophilic casts resembling thyroid tissue (thyroidization of the kidney).


Tubulointerstitial nephritis (Drug-induced interstitial nephritis)

It causes acute interstitial renal inflammation. Pyuria (classically eosinophils) and azotemia occurs after administration of drugs that act as haptens (small molecules that elicit an immune response only when attached to a large carrier such as a protein), inducing hypersensitivity. Nephritis typically occurs 1-2 weeks after certain drugs (eg diuretics, ppenicillin derivatives, proton pump inhibitors, sulfonamides, rifampin), but can occur months after starting NSAIDs. It is associated with fever, rash hematuria, and costobertebral angle tenderness, but it can be asymptomatic.


Diffuse cortical necrosis

Acute generalized cortical infarction of both kidneys. It is likely due to a combination of vasospasm and DIC. It is associated with obstetric catastrophes (eg abruptio placentae), septic shock.


Acute tubular necrosis

It is the most common cause of acute kidney injury in hospitalized patients. It spontaneously resolves in many cases. It can be fatal, especially during initial oliguric phase. There is an increase in FENa. Key findings includes granular (muddy brown) casts.


Stages of acute tubular necrosis

1. Inciting event. 2. Maintenance phase- oliguric; lasts 1-3 weeks. There is a risk of hypokalemia, metabolic acidosis uremia. 3. Recovery phase- polyuric; BUN and serum creatinine fall. There is a risk of hypokalemia.


Causes of acute tubular necrosis

It can be caused by ischemic or nephrotoxic injury. Ischemia is secondary to decreased renal blood flow (eg hypotension, shock, sepsis, hemorrhage, HF). It results in death of tubular cells that may slough into the tubular lumen (PCT and tick ascending limb are highly susceptible to injury). Nephrotoxic is secondary to injury resulting from toxic substances (eg aminoglycosides, radiocontrast agents, lead, and cisplatin), crush injury (myoglobinuria), hemoglobinuria. PCT is particularly susceptible to injury.


Renal papillary necrosis

Sloughing of necrotic renal papillae causes gross hematuria and proteinuria. It may be triggered by recent infection or immune stimulus. It is associated with sickles cell disease or trait, acute pyelonephritis, NSAIDs, diabetes mellitus. SAAD PAPa with papillary necrosis: sickle cell disease or trait, Acute pyelonephritis, Analgesics (NSAIDs), Diabetes mellitus.


Acute kidney injury

AKI is defined as an abrupt decline in renal function as measure by an increase in creatinine and increase in BUN. Includes prerenal azotemia, intrinsic renal failure, postrenal azotemia.


Prerenal azotemia

It is due to a decrease in RBF (eg hypotension) causes a decrease in GFR. Na/H2O and BUN retained by kidney in an attempt to conserve volume, which increases BUN/creatinine ratio (BUN is reabsorbed, creatinine is not) and FENa is decreased.


Intrinsic renal failure

It is generally due to acute tubular necrosis or ischemia/toxins. It is less commonly due to acute glomerulonephritis (eg RPGN, hemolytic uremic syndrome). In ATN, patchy necrosis causes debris to obstruct tubule and fluid back flow across necrotic tubule, which decreases GFR. Urine will have epithelial/granular casts. BUN reabsorption in impaired, which decreases BUN/creatinine ratio.


Postrenal azotemia

It occurs due to outflow obstruction (stone, BPH, neoplasia, congenital anomalies). It develops only with bilateral obstruction.


Lab findings with prerenal AKI

Urine osmolality (mOsm/kg) is over 500. Urine Na (mEq/L) is under 20. FENa is under 1%. Serum BUN/Cr is over 20.


Lab findings with intrinsic renal AKI

Urine osmolality (mOsm/kg) is under 350. Urine Na (mEq/L) is over 40. FENa is over 2%. Serum BUN/Cr is under 15.


Lab findings with postrenal AKI

Urine osmolality (mOsm/kg) is under 350. Urine Na (mEq/L) is over 40. FENa is over 1% (mild) or over 2% (severe). Serum BUN/Cr varies.


Consequences of renal failure

It causes inability to make urine and exrete nitrogenous wastes. Consequences include (MAD HUNGER): Metabolic Acidosis, Diyslipidemia (especially increased tryglycerides), Hyperkalemia, Uremia, which is a clinical syndrome makred by increased BUN (this causes nausea and anorexia, pericarditis, asterixis, encephalopathy, platelet dysfunction), Na/H2O retention (HF, pulmonary edema, hypertension), Growth retardation and developmental delay, Erythropoietin failure (anemia), Renal osteodystrophy. There are two forms of renal failure: acute (eg ATN) and chronic (eg hypertension, diabetes mellitus, and congenital anomalies).


Renal osteodystrophy

Failure of vitamin D hydroxylation, hypocalcemia, and hyperphosphatemia causes secondary hyperparathyroidism. Hyperphosphatemia is also independently decreases serum Ca by causing tissue calcifications, whereas a decrease in 1, 25- (OH)2 D3 , which causes a decrease in intestinal Ca absorption. It causes subperiosteal thinning of bones.


Autosomal dominant polycystic kidney disease (ADPKD)

It was formerly known as adult polycystic kidney disease. . Numerous cysts causes bilateral enlarged kidneys and ultimately destroys the kidney parenchyma. It presents with flank pain, hematuria, hypertension, urinary infections and progressive renal failure. It is autosomal dominant due to a mutation in PKD1 (85% of cases, on chromosome 16) or PKD2 (15% of cases, on chromosome 4). Death is from complications of chronic kidney disease or hypertension (caused by increased renin production). It is associated with berry aneurysms, mitral valve prolapse, and benign hepatic cysts.


Autosomal recessive polycystic kidney disease (ARPKD)

It was formerly known as infantile polycystic kidney disease. It presents in infancy and is autosomal recessive. It is associated with congenital hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter sequence. Concerns beyond the neonatal period include systemic hypertension, progressive renal insufficiency, and portal hypertension from congenital hepatic fibrosis.


Medullary cystic disease

It is an inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine. Medullary cysts are not usually visualized with shrunken kidneys on ultrasound. There is a poor prognosis.


Simple vs. complex renal cysts

Simple cysts are filled with ultrafiltrate (anechoic on ultrasound). It is very common and accounts for the majority of all renal masses. It is found incidentally and typically asymptomatic. Complex cysts, including those that are septated, are enhanced or have solid components on imaging require follow up or removal due to risk of renal cell carcinoma.


Mechanism of mannitol

Acts on the proximal convoluted tubule. It is an osmotic diuretic. Increased tubular fluid osmolarity causing an increase in urine flow and a decrease in intracranial/intraocular pressure.


Clinical uses of mannitol

Drug overdose, elevated intracranial/ intraocular pressure.


Toxicity of mannitol

Pulmonary edema, dehydration. It is contraindicated in anuria and HR.


Mechanism of acetazolamide

It acts on the proximal convoluted tubules and is a carbonic anhydrase inhibitor. It causes self-limited NaHCO3 diuresis and decreased total body HCO3 stores.


Clinical uses of acetazolamide

Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri.


Toxicity of acetazolamide

Hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy. ACID azolamide causes ACIDosis.



Sulfonamide loop diuretic



Sulfonamide loop diuretic



Sulfonamide loop diuretic


Sulfonamide loop diuretics

Furosemide, bumetanide, torsemide


Mechanism of loop diuretics

They are sulfonamide loop diuretics and inhibit cotransport system (Na/K/2Cl) of thick ascending limb of loop of Henle. It abolishes hypertonicity of the medulla, preventing concentration of urine. It stimulates PGE release (vasodilatory effect on afferent arteriole), which is inhibited by NSAIDs. It increases Ca excretion. Loops Lose Ca.


Clinical use of loop diuretics

it is used to treat edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia.


Toxicity of loop diuretics

Ototoxicty, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout. OH DANG!



Non-sulfonamide loop diuretic. It is a phenoxyacetic acid derivative (not a sulfonamide). It has essentially the same action as furosemide. It is used in diuresis in patients allergic to sulfa drugs. The toxicity is similar to furosemide. It can cause hyperuricemia. It is never used to treat gout.


Thiazide diuretics

Chlorthalidone and hydrochlorothiazide



Thiazide diuretics



Thiazide diuretics


Mechanism of thiazide diuretics

They inhibit NaCl reabsorption in early DCT, which decreases diluting capacity of nephron. It decreases Ca excretion.


Clinical use of thiazide diuretics

It is used to treat hypertension, HR, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis.


Toxicity of thiazide diuretics

Includes hypokalemic metabolic alkolosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. Sulfa allergy (HyperGLUC)


K sparing diuretics

Spironolactone and epleronone, Triamterene, and Amiloride. The K STAys.


Mechanism of K sparring diuretics

Spironolactone and eplerenone are competitive aldosterone receptor antagonists in the cortical collecting tubule. Triamterene and amiloride act at the ame part of the tubule by blocking Na channels in the cortical collecting tubule.


Clinical uses of K sparing diuretics

It is used to treat hyperaldosteronism, K depletion, and HF.


Toxicity of K sparing diuretics

Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (eg gynecomastia, antiadnrogen effects0.


Diuretics that change urine NaCl

It is increased with all diuretics except acetazolamide. Serum NaCl may decrease as well.


Diuretics that change urine K

It is increased with loop and thiazide diuretics. Serum K may decrease as a result.


Diuretics that cause acidemia

Carbonic anhydrase inhibitors decrease HCO3 reabsorption. K sparing aldosterone blockade prevents K secretion and H secretion. Aditionally hyperkalemia leads to K entering all cells (via H/K exchanger) in exchange for H exiting cells.


Diuretics that change alkalemia

Loop diuretics and thiazides cause alkalemia through several mechanisms: Volume contraction increases AT II, which increases Na/H exchange in the PCT, causing an increase in HCO3 reabsorption (contraction alkalosis). K loss leads to K exiting all cells (via the 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 causing alkalosis and paradoxical aciduria.


Diuretics that change urine Ca

It is increased with loop diuretics because there is a decrease paracellular Ca reabsorption, which leads to hypocalcemia. It is decreased with thiazides because they enhance Ca reabsorption in the DCT.


ACE inhibitors

Captopril, enalapril, lisinopril, ramepril.



ACE inhibitor



ACE inhibitor



ACE inhibitor



ACE inhibitor


Mechanism of ACE inhibitors

They inhibit ACE, which decreases ACT II, causing a decrease in GFR by preventing constriction of efferent arterioles. Levels of renin increase as a result of loss of feedback inhibition. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator.


Clinical use of ACE inhibitors

They are used to treat hypertension, HF, proteinuria, diabetic nephropathy. They prevent unfavorable heart remodeling as a result of chronic hypertension. In diabetic nephropathy, there is a decrease in intraglomerular pressure, slowing GBM thickening.


Toxicity of ACE inhibitors

Cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformations), increased Creatinine (decreased GFR), Hyperkalemia, and Hypotension. It should be avoided in bilateral renal artery stenosis, because ACE inhibitors will further decrease GFR, leading to renal failure. Captopril's CATCHH.


Angiotensin II receptor blockers

Losartan, candesartan, valsartan.



Angiotensin II receptor blocker



Angiotensin II receptor blocker



Angiotensin II receptor blocker


Mechanism of angiotensin II receptor blocker

They selectively block binding of angiotensin II to AT1 receptor. It effects similar to ACE inhibitors, but ARBs do not increase bradykinin.


Clinical use of angiotensin II receptor blocker

It is used to treat hypertension, HF, proteinuria or diabetic nephropathy with intolerance to ACE inhibitors (eg cough angioedema).


Toxicity of angiotensin II receptor blocker

Hyperkalemia, decreased renal function, hypotension, teratogen.



It is a direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I. it is used to treat hypertension. Toxicity includes hyperkalemia, decreased renal function, hypotension. It is contraindicated in diabetics taking ACE inhibitors or ARBs.