MEDL350L Urinalysis Exam #1

Basic functions of kidneys (1-2)

1. filtration: remove waste & toxic byproducts of metabolism;

   1. function of glomerular capsule & capillaries; requires endothelial, mesangial, & epithelial cells

2. chem modification & concentration of filtrate: Retention or excretion of most of the filtered salts (ex: Pi, HCO3-) & water

   1. function of renal tubules (epithelial cells)

Basic functions of kidneys (3-5)

3. Endocrine organ: Oxygen sensing & secretion of EPO to maintain RBC

   1. Renin to maintain water & Na+ balance

   2. Vitamin D activation (tubular epithelial cells convert precursor to active form)

4. Water conservation and blood pressure balance

5. Acid-base balance

Nephron: Compromised on, # of nephrons, avg adult output

• comprised of many epithelial & endothelial cells

• average adult kidney contains 1,000,000 nephrons

• normal adult urine output = ~800-1,200 mL/day

  • Compulsive water drinkers & individuals with polydipsia may increase

  • Lithium, ethanol, diuretic medications and caffeine can increase

Renal function & Cardiac function: Cardiac output, low BP, HTN & DM

• Kidneys receive 25% of cardiac output, filtration is driven by high arteriolar blood pressure (BP)

• Low BP perfuses the kidney inadequately & is a cause of acute kidney failure

• Hypertension and DM (diabetes) are leading causes of chronic kidney

  disease

Renal function: Filtration (glomerulus, PT, plasma proteins that can be filtered)

• contains a glomerulus enclosed in a capsule, tubules & associated peritubular capillaries

• Cell-free filtration of small molecules in plasma occurs in the glomerulus where 20% of the plasma water and content is filtered into the proximal tubule (PT)

• Plasma proteins < 60 kDa are filterable, but neg charge repulsion between 60 kDa albumin & 3 filtration barriers prevents most from entering the PT

Renal function: Filtration (pos charged plasma proteins, filtrate modification, small filtered proteins)

• Smaller and more pos charged plasma proteins are freely filtered

• Filtrate enters tubules → chemically modified: 99% of water & Na+ are reabsorbed, with other electrolytes and glucose

• Small filtered proteins & glucose are catabolized inside tubular cells

Renal function: Capillary anatomy, salts reabsorbed, DT

• Juxtaposition of peritubular capillaries is important anatomical feature: H2O & salt can easily pass & balance

• Most salts are reabsorbed constitutively from PT & LOH

• DT adjusts, or “fine tunes,” excretion or retention of salts depending on need

3 Filtration barriers in glomerulus

1. Fenestrated endothelial cells prevent passage of cells into filtrate & make for a more highly permeable barrier than ordinary capillaries

2. Basement membrane (GBM) beneath endothelium is enriched in non-linear type 4 collagen in a “pickup stick” array

3. Epithelial cell projections (foot processes) wrap around GBM → filtration slits in “curving waterslide” – enriched in a transmembrane protein (nephrin & podocin) mesh

Glomerulus: Podocytes

• primary arms & secondary projections (pedicels or foot processes) wrapping around glomerular capillaries

• projections interdigitate to form narrow filtration slits

Filtration barriers in glomerulus: Neg/Pos Charges

• High density of neg charge in all 3 layers: Repels neg charged RBC, WBC, PLTs and many plasma proteins

• in healthy kidney: proteins that are highly neg charged & large (> 60kDa) are unlikely to pass through filtration barriers

  • Example: albumin (>200 negative charges/molecule)

• Proteins that are small (<60 kDa), which carry neutral or pos charge are filtered & catabolized in tubular cells

Glycation

• as seen in Diabetes Mellitus

• diminishes neg charge in barriers & allows passage of albumin into filtrate: diabetic nephropathy/proteinuria (microalbuminuria/macroalbuminuria)

• Albuminuria is a predictor of kidney disease progression and vascular disease in individuals with DM

MESANGIAL CELLS

• close contact with the glomerulus, and are responsible for keeping them in the right conformation

• can cause contraction or movement of the glomerulus

Renal function testing: Creatine, PCr storage, PCr potential

• measurement of the filtration marker creatinine in plasma and urine, a spontaneous, non-catalyzed decomposition product of creatine (Cr) & creatine phosphate (PCr)

• Creatine phosphate (PCr) is synthesized & stored in skeletal muscle using energy from ATP hydrolysis

• PCr has a higher phosphate transfer potential than ATP and is used to quickly recharge ADP (conversion to ATP) in exercising & exhausted muscle

Renal function testing: Cr produce rate, Cr circulating levels, Cr indicator, Increases in circulating Cr

• Creatinine is produced at a steady state rate

• Circulating levels depend on an individual’s muscle mass & the renal filtration rate

• A reliable index of filtration, creatinine is an indicator of the number of functioning nephrons in the kidney

• Increases in circulating creatinine are seen when ≤ 50% of functional nephrons or nephron activity is lost

Creatine kinase (CK/CPK)

• catalyzes the reversible conversion of creatine and creatine phosphate

• CK has the highest activity in brain, skeletal and cardiac muscle and moderate activity in smooth muscle and other organs

Laboratory Estimation of the GFR (Glomerular Filtration Rate): Collection, define renal clearance, ideal marker of filtration

• requires 24-hour urine collection

• Renal clearance is defined as the volume of plasma that must flow through the kidneys/minute to completely remove a substance from circulation

• Ideal marker of filtration or clearance should:

  • be freely filterable (e.g., not protein-bound like calcium)

  • not be further metabolized (metabolic end-product)

  • be produced at a steady state level

  • not be secreted by tubules

Laboratory Estimation of the GFR (Glomerular Filtration Rate): Cr plasma, urine, and clearance RR

• Plasma creatinine level meets ¾ criteria for an ideal clearance marker

• Plasma creatinine reference range: 0.5-1.5 mg/dL (lower in children)

• Urine creatinine RR: 20-275 mg/dL ♀ / 20-320 mg/dL ♂

• Creatinine clearance RR: Male: 97 to 137 mLs/min, Female: 88 to 128 mLs/min

Calculated formulas of GFR (eGFR): Sample used, normal Cr clearance value, filtration marker

• use plasma creatinine and/or cystatin C & doesn’t require 24-hour urine collection

• Calculated creatinine clearance is normal if > 60 mL/min

• novel filtration marker:

  • Cystatin C is a cysteine protease inhibitor produced primarily by all nucleated cells

  • Due to low molecular weight and positive pI, (+ charge) it is easily filtered

  • serum concentration is independent of gender, age, or muscle mass

Glomerular Filtration Rate (GFR) & Creatinine Clearance formulas

• UV/P (U = urinary Cr in mg/dL; V

Renal clearance: Renal plasma flow (RPF): Define, 20% RPF, RR

• volume of plasma that passes through the glomeruli in both kidneys in one minute, normally 625 mL/min

• 20% of RPF is normally filtered per minute (125 mL/min) using the ideal filtration marker inulin

• Renal clearance of creatinine is approximately 100 mL/min

  • This value = 100 mL of plasma is completed cleared of creatinine every minute in an individual with healthy kidneys

Renal clearance: Cr secretion, marker for filtration, rate of Cr/PCr decomposing

• Cr can be secreted directly into the filtrate by the tubules → secretion quickly reaches a saturation point → not considered to have a significant effect on filtration

• Perfect marker of filtration = inulin; It has to reach steady state by IV infusion → clinical use impractical

• Rate at which Cr & PCr spontaneously decompose into creatinine is a physical constant, making for a steady state production without the need to infuse a xenobiotic

Water & Sodium balance: MD function & decreased [NaCl]

• Macula Densa (MD) is a component of the distal tubule (DT) that senses NaCl concentration delivery

• Decreased [NaCl] delivery drives MD to release prostaglandins:

  • Dilate afferent arteriole decreasing resistance, increasing capillary hydrostatic pressure & GFR

  • Increase renin release from the JGA, eliciting aldosterone secretion from adrenal cortex in the “RAAS.”

  • Aldosterone, a mineralocorticoid increases the rate of K+ excretion and Na+ retention by the DT

  • Net effect is to increase sodium and water retention, increasing BP

  • JG cells sense stretch via baroreceptors, decreased BP, increases renin secretion independently of MD

Water & Sodium balance: Increased [NaCl], net effect, autoregulatory mechanisms

• Increased [NaCl] delivery to the MD results in vasoconstriction of afferent arteriole, decreasing GFR and renin secretion

• Net effect is to decrease sodium and water retention, decreasing BP

• Autoregulatory mechanism helps regulates balance of water, Na+ & BP, keeping GFR constant in the context of variable arterial pressure

Renin-Angiotensin-Aldosterone Axis (pathway & results)

• BP decreases → kidney produces Renin → Renin activates Angiotensinogen to Angiotensin I → Angiotensin-converting enzyme (ACE) converts to Angiotensin I to II → Angiotensin II activate pituitary to produce Aldosterone → Aldosterone acts on kidney for Na+ retention → BP rises (vasoconstriction)

• results: increased sympathetic drive, Na+ & H2O retention, vasoconstriction/increased BP, Anti-diuretic hormone secretion (H2O retention)

ACE Inhibitors & Angiotensin II receptor blockers

• inhibitors (Lisinopri) & blockers (ARBs; Losartan) are typical first choices in treating hypertension (HTN)

• Calcium channel blockers, beta-adrenergic blocking agents and older agents (various diuretics which can either be Ca or K) wasting or sparing are also used in treating volume overload and HTN

Aldosterone-to-Renin ratio (ARR): Function, potent, type of activity, secretion stimulated by

• Aldosterone increases the rate at which the kidney tubules dump K+ into the urine & rate at which Na+ is moved from the filtrate back into circulation

• Aldosterone is the major, most potent mineralocorticoid

• Cortisol also has mineralocorticoid activity

• Aldosterone secretion can be stimulated by ATII, & independently by hyperkalemia

Aldosterone-to-Renin ratio (ARR)

• ARR is calculated as the aldosterone to renin activity (A/R) ratio

• Informative in differentiating primary from secondary hyperaldosteronism (HA)

• Clinical signs of HA are an inappropriately high circulating level of aldosterone → low plasma K+ & (ECG) cardiac conduction abnormalities

• Plasma Na+ is usually not affected in HA since there are Atrial Natriuretic Factors (ANFs) in the heart

• ANFs = hormones that respond to increased stretching of the atria, powering the dumping of sodium into the urine when it’s elevated

• The ANFs offset the hypernatremic effect of aldosterone

Aldosterone-to-Renin ratio (ARR): Primary hyper- caused by & Secondary is caused by

• Primary hyperaldosteronism is caused by an adrenal adenoma secreting inappropriately high levels of mineralocorticoid → hypokalemia

• Hyperaldosteronism may be secondary to decreased arterial perfusion/pressure to the kidney in heart failure, or to congenital/acquired conditions that narrow the renal arteries (stenosis), as renin secretion is provoked in response → HA

Aldosterone-to-Renin ratio (ARR): Primary vs Secondary Aldosterone & Renin

• Primary HA: Elevated aldosterone → increased movement of Na+ from the filtrate back into circulation → raising blood pressure.

  • Increase in BP is sensed by the heart and kidney → renin release is suppressed (classical negative feedback loop)

• Secondary HA: Renin is likely continuously secreted due to vascular/cardiovascular problems → decreased blood flow to the kidney

  • Negative feedback effect is chronically dampened in the setting of low perfusion

Aldosterone-to-Renin ratio (ARR): Primary vs Secondary HA ARR

• ARR is higher in primary HA

• ARR ratio is lower in secondary HA

Licorice intoxication

Renal Water Balance

• Angiotensin II induces secretion of antidiuretic hormone (ADH or arginine vasopressin) from posterior pituitary

• ADH recruits water channels (aquaporin-2) to the apical membrane of connecting tubules and collecting ducts in the late (distal) nephron

• Aquaporins allow for free passage of water from the filtrate back into circulation

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): Etiology, ADH secretion, result effects

• etiology: Paraneoplastic syndromes (ex: ectopic ADH secretion from small cell lung cancer cells, medication, etc.)

• Characterized by excessive ADH secretion → Too much water moves into vascular space

• Dilutional hyponatremia & increased urine osmolality (can use serum not plasma)

Central Diabetes Insipidus (DI): Etiology, ADH secretion, result effects, test

• etiology: head injury, brain trauma, radiation therapy, severe illness

• not enough of ADH is secreted → H2O lost via inability of kidney conservation

• Extreme thirst, copious & dilute urine (up to 20 L/day), hypernatremia decreased urine osmolality, increased serum osmolality

• Overnight water deprivation test (must be done in hospital) shows inappropriately dilute urine next morning

• pituitary issues

Nephrogenic Diabetes Insipidus (DI)

• ADH resistance: inherited or acquired defects in vasopressin type-2 receptor or aquaporin-2 genes → ADH insensitivity

• inherited/acquired

Reagent test strips/”Dipsticks”

• CLIA waived test

• QC materials mandatory: Normal/ abnormal lyophilized human urine

• document: QC/QA & Date reagent opening & expiration

• test strip readers (better standardization)

Diagnostic sensitivity formula

TP / (TP + FN)

Test strips: Leukocytes (chromogen, normal, sensitivity/specificity, rule out, methodology)

• Chromogen is converted to a colored product by a neutrophil protease (esterase)

• normal = neg

• Sensitivity for UTI is poor (< 50%) & Specificity is better

• Better used to rule out UTI

• Methodology: Enzyme catalyzed colorimetry

Test strips: Nitrite (detects, normal, sensitivity, methodology)

• Detects nitrate reduction by gram negative bacteria such as E. Coli, Klebsiella, Proteus, & Enterobacter

• normal = neg

• Sensitivity (alone) for UTI < 30%

• Methodology: Greiss reaction: nitrite diazonium formation, colorimetry

(Test strips) Urobilinogen: Define, parallels, decreases associated with, normal, methodology

• Metabolite of bilirubin produced by gut flora that is partially reabsorbed from GI tract and excreted in urine

• Parallels increase in plasma bilirubin

• Decreases associated with biliary obstruction

• Normal: 0.2-1.0 mg/dL

• Methodology: Ehrlich’s reagent: p-dimethylaminobenzaldehyde, colorimetry

(Test strips) Bilirubin: Parallels, increased in, normal, methodology

• Parallels increase in plasma bilirubin

• Increased in biliary obstruction & other causes of hyperbilirubinemia (liver disease)

• Normal: none

• Methodology: diazonium salt, colorimetry

Test strips: Protein (most/less sensitive to, quant/qual, typically positive, microalbumin patches

• Most sensitive for the presence of abnormal levels of albumin in urine, less sensitive to immunoglobulins or Ig light-chains

• Semi-quantitative

• Typically positive in UTI

• Microalbumin patches or measurements for detection of early diabetic nephropathy

Test strips: Protein (quant/qual, normal, methodology)

• Quantitative tests from lab available for protein/creatinine ratio or 24-hour protein excretion

• Normal: negative

• Methodology: dye binding (DIDNTB)

Test strips: Blood (sensitive to, reactive to, confirmed by, normal, methodology)

• Patch is sensitive to the presence of heme-Fe found in Hb & myoglobin

• Reactive to intact and hemolyzed RBC & free Hb

• Should be confirmed by PPM

• Normal: none

• Methodology: heme Fe oxidizes Tetramethylbenzidine; colorimetry

Test strips: pH (urine pH, acid-base balance, normal, methodology)

• Normal urine is acidic but can become alkaline after meals (> 6)

• Should correlate with overall picture of acid-base balance in normal, & in metabolic/respiratory acidosis & alkalosis.

• Normal: 4.5 – 8.0

• Methodology: 2 pH indicators: methyl red and bromthymol blue

Test strips: Specific gravity (define, measures, elevated when, deionized water, urine specific gravity, chem formula)

• Sum of total solute concentration: salts, urea, other small molecules

• Measures overall concentrating ability of kidney

• Is elevated after water deprivation

• Specific gravity of ultra-pure deionized water = 1.000

• Urine is normally 1.005-1.030

• RCOOH + Na+ → COONa+ + H⁺

Test strips: Specific gravity (<1.003, >1.010, place in context, refractometer is sensitive to, reagent methodology)

• < 1.003 is probably not urine

• > 1.010 reflects concentrated urine

• Place in context of dehydration and water imbalances such as diabetes insipidus, SIADH, etc.

• Refractometer is sensitive to glucose, contrast materials, dipstick is not

• Reagent methodology relies on change in pKa of a polyelectrolyte, dissociation of H+ in presence of pH indicator

Test strips: Ketones (quant/qual, increased in, normal, methodology)

• Semi-quantitative

• increased in carbohydrate starvation; keto-acidosis

• normal = neg

• methodology: Na nitroprusside colorimetry

Test strips: Glucose (quant/qual, specific for, normal, methodology)

• Semi-quantitative; specific for glucose above renal threshold of glucose excretion; diabetes mellitus (DM)

• normal = neg

• methodology: glucose oxidase reaction produces peroxide which reacts with chromogen

Proteinuria

• Most plasma proteins are neg charged at pH (7.40) & are electrostatically repelled from the filtration barriers which carry a high density of neg charge

• The smaller (< 60 kDa) & more pos charged a plasma protein is → more likely it is to be filtered by the glomerulus & catabolized by renal tubular cells (RTCs)

• Albumin is small enough to be filtered but carries > 200 negative charges ay physiologic pH

• A very small amount of albumin & other proteins (Tamm-Horsfall protein) can be detected in normal urine.

Proteinuria: Normal value in 24hr urine, glycation of proteins in DM, 30-300 mg/day, >300 mg/day, nephrosis

• norm value in 24 hour urine = < 150 mg/day total protein, < 20mg/day albumin

• Glycation of the proteins in the filtration barriers in DM diminishes the electrostatic repulsion of albumin & other proteins → progressively increasing their excretion

• 30-300 mg/day = moderately increased albuminuria (microalbuminuria) = increased risk for CV disease

• > 300 mg/day = severely increased albuminuria, overt proteinuria (macroalbuminuria)

• Nephrosis: > 3.0 g of protein excreted per day

Proteinuria: Protein/creatinine ratio, nephrosis, normal protein/creatinine ratio, ratios >3.5 mg/mg

• Urine protein/creatinine ratio (Spot 1st or 2nd void):

• Nephrosis: > 3.0 g of protein excreted per day

• Normal urine protein-to-creatinine ratio is less than 0.2 mg/mg

• Ratios greater than 3.5 mg/mg are in the nephrotic range for proteinuria

Renal glucose threshold (RTg)

• Glucose is filtered and reabsorbed by renal tubular cells within its normal circulating concentration (<100 mg/dL)

• Threshold for urinary excretion of glucose is plasma glucose > 180 mg/dL as this concentration exceeds the rate of reabsorption

• RTg may be higher in those with DM

Renal glucose threshold (RTg): Gliflozins (define, effective in, Empagliflozin, adverse effects)

• Medications that inhibit sodium-glucose cotransporter 2 (SGLT2) in the proximal tubule (PT), which reabsorbs 90% of filtered glucose

• Effective in lowering glucose levels in individuals with T2DM and treating heart failure & CKD.

• Empagliflozin = Jardiance

• Adverse effects: Ketosis, UTI, Yeast infections, Fournier’s Gangrene

Normal Urine sediment: Squamous epithelial cells (arise from, normal value, increases in, clue cells, subjective call)

• SECs arise from lower urinary tract (skin, urethra)

• Normally ≤15-20/hpf (400X)

• Increases in UTI, infection, inflammation of lower urinary tract

• Clue cells: speckled SECs found in some forms of bacterial vaginosis: Gardnerella vaginalis

  • Subjective call: fishy smell of sample may be better “clue”

Normal Urine sediment: Hyaline casts (morphology, formed in, normal value, increased in)

• Transparent, translucent & cigar-shaped

• Formed in distal tubules (DT) in matrix of Tamm-Horsfall protein

• Normally ≤5/lpf (100X)

• Increased numbers seen in dehydration, urinary stasis & illness

Normal Urine sediment: Harmless crystals (hyaline casts, Ca oxalate, uric acid)

• Hyaline casts: more than a few = considered to be abnormal

• Calcium oxalate: Maltese cross, envelope (vegetable source) – “stone former”

  • dihydrate = octahedral

  • monohydrate = dumbbell-shaped

• Uric acid: amorphous or football-shaped (purine end-product)

Urine pathological findings: RBCs (morph in older urine, increased in, chronic & painless hematuria)

• Puckered (crenated) appearance in older urine

• Increased in UTI and by strenuous exercise (marathon running, e.g.)

• Chronic and painless hematuria requires cystoscopy

Urine pathological findings: WBCs (morphology, urinary eosinophil)

• Grainy, granular surface with visible nuclei

• clumping and/or attached bacteria

• Urinary eosinophil count for interstitial nephritis (disseminated/inflammatory reaction to medications in kideys)

Urine pathological findings: Bacteria (usual morphology, most common gram neg & pos bacterium cultured)

• Usually motile rods

• Most common gram-neg organisms cultured:

  • Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae

• Most common gram-pos organisms cultured:

  • Enterococcus faecalis, Enterococcus faecium, Staphylococcus saprophyticus

Urine pathological findings: Yeast & Trichomonas (yeast: usually & trich: what, must be, tests available)

• yeast: Usually Candida; Urine contaminant

• trich: STD & Urine contaminant

  • Must be swimming to properly ID n sediment

  • DNA level tests available

Urine pathological findings: Renal transitional epithelial cells (morphology, arise from, indicative of)

• Smaller than SEC, larger than WBCs; Larger N/C ratio than SEC

• Arise from renal pelvis and ureters

• Indicative of more serious inflammation, infection, transplant rejection, renal cell carcinoma

Urine pathological findings: Renal tubular epithelial cells

• Slightly larger than WBC; Large N/C ratio

• Indicative of serious pathology: acute renal tubular toxic injury, necrosis, transplant rejection, Renal Cell Carcinoma

Urine pathological findings: Renal casts (hyaline, granular, RBC, WBC, cells, waxy/broad)

• Hyaline, normal unless > 5/lpf

• Granular: non-specific finding seen in many conditions including stress, infections including UTI, severe illness

• RBC: contains RBC, Hb; seen in acute glomerulonephritis (AGN), pyelonephritis

• WBC: common finding in pyelonephritis, AGN

• epithelial & renal cells

• Waxy or broad cast: found in end-stage renal disease, indicative of tubular necrosis

Normal crystals: Can cause, concept of pre-test, lots of crystals, lots of casts

• Can cause kidney stones (especially calcium-oxalate) in those who are prone genetically, or by not drinking enough water

• Concept of pre-test probability helps to guide a clinician through nephrolithiasis

• If have lower flank/back pain & painful urination, & got lots of these crystals → pre-test probability is high that you have formed a stone

• Like normal crystals, squamous epithelial cells & hyaline casts can be seen in a healthy person’s urine

  • If see more than normal → suspicion of infectious or inflammatory causes should be raised

Urine pathological findings: Pathological crystals

• Aminoacidurias: disorders characterized by errors of amino acid metabolism

• Calcium oxalate / calcium phosphate

• Uric acid

• Struvite/Triple phosphate (associated with UTI involving urease + organisms)

Urine pathological findings: Triple phosphate/struvite

• Coffin lid shape

• Highly associated with gram neg UTI (Urease positive organisms; Proteus but not E. coli)

• More common in women than men

• Common veterinary finding

Urine pathological findings: Triple phosphate/struvite

• MgNH4PO4.6H20-Ca10.[PO4]6.CO3

• Form in highly alkaline urine

• Common finding in patients with anatomic abnormalities that lead to urinary stasis, such as congenital urinary malformations and obstruction of the ureteropelvic junction, a persistently hydronephrotic renal pelvis is also known to form struvite stones

Urine pathological findings: Triple phosphate/struvite

• Also found in gross hematuria, advanced age, hypertension, fever, urinary diversion surgery, neurogenic bladder, indwelling catheters, medullary sponge kidney, distal tubular acidosis, diabetes, and low serum phosphorous levels

• Staghorn calculi: Upper urinary tract stones that involve the renal pelvis and extend into at least 2 calyces

Acute renal failure (acute kidney injury)

• develops over period of a few days

• Tubular damage

• Acute blood loss: lack of perfusion to kidneys

• “Pressure pants”

• Reversible

Chronic kidney disease

progressive loss of nephrons (< 50% viable) usually caused by Diabetes Mellitus & high blood pressure (hypertension)

Nephrosis vs Nephritis

• Nephrosis: selective loss of protein, typically acellular urine

• Nephritis: inflammatory, infectious, cellular urine featuring casts & proteinuria

Glomerulonephritides

• IgA nephropathy: aka Berger’s disease, caused by deposition of IgA immune complexes in glomerulus

• Goodpasture syndrome: anti-GBM autoantibody disease (anti-collagen Ig) affecting lungs & kidneys

• Membranous nephropathy (glomerulonephritis)

• Rapidly progressive (crescentic) glomerulonephritis

Membranous nephropathy (glomerulonephritis)

autoantibody attacks podocyte antigens: the secretory phospholipase A2 receptor, thrombospondin & others causing endothelial damage and swelling

Rapidly progressive (crescentic) glomerulonephritis

• Rapid loss of renal function over a short period (days to weeks)

• Nephritis: proteinuria, micro or macroscopic hematuria, dysmorphic red blood cells (RBC), RBC casts, anti-GBM antibodies

• Cellular crescent formation in the glomeruli; proliferative cellular response seen outside the glomerular tuft within Bowman's capsule (crescents)

• Fatal if not treated

Nephrogenic diabetes insipidus

mutations in vasopressin type-2 receptor or aquaporin-2 genes causing ADH insensitivity