Renal Disease - Part 1 PDF

Glomerular Disease Principles Jason Ryan, MD, MPH Glomerulus Functions Allow “ultrafiltrate” into Bowman’s space Water, electrolytes, glucose, amino acids Prevent filtration of most proteins Prevent filtration of red blood cells Glomerular pathology Proteinuria Hematuria Glomer...

Glomerular Disease Principles Jason Ryan, MD, MPH Glomerulus Functions Allow “ultrafiltrate” into Bowman’s space Water, electrolytes, glucose, amino acids Prevent filtration of most proteins Prevent filtration of red blood cells Glomerular pathology Proteinuria Hematuria Glomerular Filtration Barrier Capillary Endothelium Capillary Basement Membrane Podocytes (epithelium) Bowman’s Space Capillary Endothelium Fenestrated (i.e. has openings) Only small (~40nm) molecules pass through Repels red cells, white cells, platelets First barrier to filtration Capillary damage  RBC in urine  hematuria Capillary damage  inflammation  nephritis Basement Membrane Negatively charged molecules Type IV collagen Heparan sulfate Repels (-) molecules like albumin Also size barrier Only small (~4nm) molecules pass through Podocytes Also called epithelial cells Long “processes” called “foot processes” Wrap capillaries Slits between foot processes filter blood Further size barrier small (~4nm) molecules Damage  loss of protein barrier Albumin Small (~3.6nm) Can fit through all size barriers Negatively charged Repelled by GBM charge barrier Podocyte/GBM disease  albumin in urine Glomerular Diseases Breakdown of components of filtration barrier Things in urine that shouldn’t be there: Red blood cells Protein (especially albumin) Hematuria Urinalysis Dipstick: tests for the presence of heme Heme has peroxidase activity  reacts with strip Heme positive: hemoglobin or myoglobin Microscopy: red cells visualized Image courtsy of Bobjgalindo Image courtsy of J3D3 Hematuria Many, many causes Gross: abnormal color to urine from blood Microscopic: Incidental finding on urinalysis Can occur after exercise Common causes: UTI Kidney stones Feared cause: bladder cancer Glomerular disease is rare cause Glomerular Bleeding Red cell casts Dysmorphic red blood cells Acanthocytes Proteinuria Red, smoky brown or ““coca cola”” Clots generally not seen Image courtesy of Anwar Siddiqui Proteinuria Urine dipstick Color change indicates amount of protein Primarily detects albumin (good for glomerular disease!) 1+, 2+, 3+, 4+ Affected by urine concentration Proteinuria Urine protein-to-creatinine ratio “Spot urine” 1st or 2nd morning urine sample after avoiding exercise Normal ratio less than 0.2 mg/mg Proteinuria 24-hour urine collection Gold standard for protein evaluation Gives you grams/day or protein excretion Normal is less than 150 mg/day Cumbersome for patients Errors in collection common Glomerular Diseases Spectrum Nephritic Syndrome Nephrotic Syndrome RBC casts Massive proteinuria Mild proteinuria Hyperlipidemia Renal Failure Nephrotic Syndrome Filtration barrier to protein is lost RBC filtration barrier remains intact Massive proteinuria 4+ on dipstick >3.5g/day Triggers cascade of pathology  Nephrotic Syndrome ↓ immunoglobulins ↓protein Proteinuria Frothy urine ↓albumin ↓ ATIII Infection ↓ ECV ↓ plasma ↓GFR oncotic pressure Thrombosis ↑liver activity RAAS Na/H2O Fatty casts Hyperlipidemia Retention Edema Oval fat bodies Urine in Nephrotic Syndrome Urinary lipid may be present Trapped in casts (fatty casts) Enclosed by plasma membrane of degenerative epithelial cells (oval fat bodies) Under polarized light fat droplets have appearance of Maltese cross Nephrotic Syndrome Classic presentation Frothy urine Swelling of ankles Swelling around eyes (periorbital) Often mistaken for allergic reaction Serum total cholesterol >300mg/dl Proteinuria (>3.5g/day) Nephritic Syndrome Inflammatory process damages entire glomeruli Filtration barrier to RBCs and protein lost Glomerular damage: ↓GFR RBC in urine Dysmorphic RBC Casts Protein in urine Less than nephrotic syndrome due to lower GFR Cr rises Result ↑ ↑ BUN ↑Cr ↑BUN/Cr ratio Pre-Renal Failure Urinary Findings Lots of H2O resorbed Concentrated urine ↑Uosm Lots of Na resorbed ↓Una ↓Fena Pre Renal Failure Normal Pre-Renal Failure BUN (mg/dl) 20 60 Cr (mg/dl) 1.0 2.0 BUN:Cr 20:1 > 20:1 UNa (mEq/L) variable 90 Stage 2  GFR 60-89 Stage 3  GFR 30-59 Stage 4  GFR 15-29 (approaching dialysis) Stage 5  GFR 10WBC/hpf Culture >100,000 CFUs Image courtesy of J3D3 Risk Factors Women 10x more likely than men to get UTIs Shorter urethra, closer to fecal flora Sexual activity Urinary catheterization Diabetes Pregnancy Risk Factors Infants with vesicoureteral reflux Ureters insert abnormally into bladder Chronic reflux of urine back into ureters Urinary obstruction Anatomic abnormalities in children Bladder tumors in adults Enlarged prostate in older males Treatment Fluoroquinolones Ciprofloxacin, levofloxacin, ofloxacin Usually 3 day course Nitrofurantoin (Macrobid) Used in pregnancy Trimethoprim-sulfamethoxazole (TMP-SMX) Sterile Pyuria Some women with chlamydia/gonorrhea complain of urinary tract symptoms Urinalysis shows pyuria but no bacterial growth Majority women are asymptomatic with chlamydia or gonorrhea Chronic Pyelonephritis Consequence of recurrent pyelonephritis Vesicoureteral reflux in children Recurrent stones in adults Scarring of kidneys Corticomedullary scarring Blunted calyx “Thyroidization of kidney” Tubules contain eosinophilic material Looks like thyroid tissue on microscopy Cystic Kidney Disease Jason Ryan, MD, MPH Cystic Kidney Diseases 1. Multicystic Dysplastic Kidney 2. Autosomal Recessive Polycystic Kidney Disease 3. Autosomal Dominant Polycystic Kidney Disease 4. Medullary Cystic Kidney Disease Multicystic Dysplastic Kidney Abnormal ureteric bud-mesenchyme interaction Kidney replaced with cysts No/little functioning renal tissue Absent ureter Often detected in utero by ultrasound Multicystic Dysplastic Kidney If unilateral  remaining kidney hypertrophies If bilateral  Potter’s syndrome Oligohydramnios Failure of lung maturation Compressed face/limbs Not compatible with life Multicystic Dysplastic Kidney Spontaneous Non-inherited Different from other cystic disorders Subsequent pregnancies often okay Polycystic Kidney Disease Autosomal recessive (infants) Autosomal dominant (young adults) ARPKD Old name: “juvenile” PKD Occurs in infants Can occur with Potter’s syndrome Renal failure High blood pressure Key associations: Liver disease (fibrosis/cysts) Can cause portal hypertension (ascites) ADPKD Occurs in adults Microscopic cysts present at birth Too small to visualize with ultrasound Kidneys appear normal at birth Cysts develop over many years Inherited mutation of APKD1 or APKD2 genes ADPKD Image courtesy of Hg6996 ADPKD Key associations Berry aneurysm (subarachnoid hemorrhage) Liver cysts Mitral valve prolapse ADPKD Classic presentation Young adult High blood pressure (↑RAAS system) Hematuria Renal failure Family history of sudden death (aneurysm) Medullary Cystic Kidney Disease Autosomal dominant Cysts in collecting ducts of medulla Name is misnomer Most patients DO NOT have cysts Kidney fibrosis occurs  small, shrunken kidneys Contrast with ADPKD (enlarged kidneys) Often have early onset (adolescent) gout Renal failure Cystic Kidney Diseases