Medical Pathology: Kidney (Renal) Disease PDF

Medical Pathology: Kidney (Renal) Disease CHRIS BORGMAN, OD ASSOCIATE PROFESSOR [email protected] WIL MCGRIFF, OD, MPH ASSOCIATE PROFESSOR [email protected] Lecture Objectives — — — — — Be able to use renal function tests and urinalyses to diagnose kidney dysfunction. Know miscellaneous kidney dis...

Medical Pathology: Kidney (Renal) Disease CHRIS BORGMAN, OD ASSOCIATE PROFESSOR [email protected] WIL MCGRIFF, OD, MPH ASSOCIATE PROFESSOR [email protected] Lecture Objectives — — — — — Be able to use renal function tests and urinalyses to diagnose kidney dysfunction. Know miscellaneous kidney disease & nephrotic syndrome causes, pathophysiologies, and clinical findings. Know kidney failure causes, pathophysiologies, associations, & clinical findings (acute & chronic). Know renal and urinary cancer pathophysiologies and clinical findings. Know urinary tract disease causes, pathophysiologies, and clinical findings. NBEO Outline Renal and Urogenital System 1. Epidemiology 2. Symptoms and signs of urogenital and renal disorders a. Acute renal failure b. Chronic renal failure c. Glomerulonephritis d. Pyelonephritis e. Nephrotic syndrome f. Diabetic nephropathy g. Neoplasms of the urinary tract h. Sexually transmitted diseases i. Cystitis 3. Diagnostic testing and imaging 4. Pathophysiology and diagnosis Urinary System — Kidneys (paired) ¡ Filter blood ¡ Manufacture urine — Ureters (paired) ¡ Transport urine — Urinary bladder (single) ¡ Stores urine — Urethra (single) ¡ Transports urine Urine Production — Normal production: 750 – 2000 mL/day — Clear, amber-colored fluid ¡ 95% water ¡ 5% dissolved solids ÷Metabolic wastes — Not normally found in urine: ¡ Plasma proteins ¡ Blood cells ¡ Glucose ÷ >200 mg/dL Urine/Renal Lab Testing & Imaging Urinalysis — Visual analysis — Common contaminants: — Test strips/dipsticks ¡ — Microscopic analysis ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ Leukocytes Blood Specific Gravity Urobilinogen Ketone Glucose Protein Bilirubin Nitrite pH Renal Function Tests — Glomerular filtration rate (GFR) ¡ ¡ ¡ Volume of fluid filtered by glomeruli per unit time Normal range: 100-130 mL/min M≈F — Inulin ¡ Gold Standard ¡ Plant starch ; IV infusion required ¡ Completely filtered by glomerulus = accurate GFR — Creatinine clearance rate ¡ Byproduct of muscle metabolism (creatine à increased ATP) ¡ Compare blood levels vs. renal clearance (urine) ¡ Close estimate of GFR (slightly overestimates GFR) — Blood urea nitrogen (BUN) ¡ Byproduct of protein & DNA breakdown/metabolism in liver BUN/Creatinine/GFR in Kidney Disorders BUN Blood Creatinine Urine Creatinine GFR Normal Kidney Function 7-18 mg/dL 0.6-1.3 mg/dL 500-2000 mg/day 100-130 mL/min Kidney Dysfunction Elevated Elevated Reduced Reduced Medical Terms of Abnormal Blood Tests in Renal Dysfunction — Azotemia ¡ No clinical signs of renal failure are present ¡ *Only labs are abnormal Decreased GFR ÷ Increased blood urea nitrogen (BUN) ÷ Increased blood creatinine ÷ ¡ ¡ Almost always discovered incidentally on routine lab tests Can progress to uremia over time — Uremia ¡ Azotemia + Clinical signs and symptoms of renal failure Hypertension (NaCl and H2O retention à increased blood volume) ÷ Anemia (decreased erthyropoetin production) ÷ Edema (NaCl and H2O retention) ÷ Oliguria (low GFR à reduced ability to produce urine) ÷ Renal Imaging — Ultrasounds — X-rays PKD Normal — CT/MRI Kidney Stones Kidney Stones PKD Leading causes of death in US in 2021 1. Heart disease 2. Cancer 3. COVID-19 4. Accidents/unintentional injuries 5. Stroke 6. Chronic lower respiratory diseases 7. Alzheimer’s disease 8. Diabetes 9. Liver disease 10. Kidney disease https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm Renal Disease Overview • Nephritic Syndromes (aka glomerulonephritis): -Acute Glomerulonephritis -SLE Nephropathy -Other vasculitides -Post-infectious • *Nephrotic Syndromes: -Diabetic Nephropathy* -Minimal Change Disease • Miscellaneous Diseases: -Acute Tubular Necrosis -Hypertensive Nephrosclerosis Duration: <3 months = acute >3 months = chronic Severity: Nephrotic > Nephritic Nephritic vs. Nephrotic Syndromes? Renal Disease Nephritic Nephrotic (-) Proteinuria or (+)Mild Proteinuria (+)Massive Proteinuria (+)Hematuria (-)Hematuria Renal Diseases Overview • Nephritic Syndromes (aka glomerulonephritis): -Acute Glomerulonephritis -SLE Nephropathy -Other vasculitides -Post-infectious • Nephrotic Syndromes: -Diabetic Nephropathy -Minimal Change Disease } } (+) mild proteinuria (+) hematuria (+) massive proteinuria (-) hematuria • Miscellaneous Diseases: -Acute Tubular Necrosis -Hypertensive Nephrosclerosis Severity: Nephrotic > Nephritic Nephrotic Syndrome — Nephrotic Diseases: 1. 2. *Diabetic Nephropathy (50%) Minimal Change Disease — Risk factors ¡ ¡ ¡ ¡ — Acute vs. chronic (>3 mo) — Signs and symptoms: ¡ ¡ ¡ ¡ ¡ **Proteinuria (massive)** ÷ “Foamy” urine ÷ Aka: albuminuria Hypoalbuminemia Hyperlipidemia Edema Hypertension ¡ Infections Diabetes Autoimmune diseases Toxins Medications — May resolve completely or progress to ESRD — Treatment ¡ ¡ ¡ ¡ ¡ Steroids HTN treatment Statins Plasmapheresis Immunosuppression 1. Diabetic Nephropathy — *Most common cause of renal disease ¡ ¡ *30-44% of ESRD caused by DM àLeading cause of ESRD in US *Leading cause of death in T1DM • See Lecture 5 – DM 2 (Borgman) — MOA: Endothelial glycation à BM damage — Characterized by: ¡ ¡ Nephrotic syndrome Diffuse glomerulosclerosis — Risk factors: ¡ ¡ ¡ ¡ Type 1 DM > Type 2 DM Concomitant HTN Smoking Race (AA>Hispanics>Asian>White) — Treatment ¡ ¡ BG, BP, lipid control, smoking cessation Dialysis and/or transplant 2. Minimal Change Disease — *Most common cause of nephrotic syndrome in children ¡ *Idiopathic cause (70-90% cases) ¡ Secondary causes: NSAIDs, vaccines, viral infections — 80%-90% of cases in children; 10-20% adults ¡ M>F; usually between 1-7 yo — Edema of the face is often noted first — Pathology only visible w/ electron microscopy ¡ Loss of foot processes on podocytes ¡ Appearance of microvilli ¡ Vacuolation — Treat w/ steroids ¡ 95% achieve total recovery Renal Disease Overview • Nephritic Syndromes (aka glomerulonephritis): -Acute Glomerulonephritis -SLE Nephropathy -Other vasculitides -Post-infectious • Nephrotic Syndromes: -Diabetic Nephropathy -Minimal Change Disease } } (+) mild proteinuria (+) hematuria (+) massive proteinuria (-) hematuria • Miscellaneous Diseases: -Acute Tubular Necrosis -Hypertensive Nephrosclerosis Severity: Nephrotic > Nephritic 1. Acute Tubular Necrosis — Defn: Extensive necrosis of tubular epithelial cells ¡ *Most common cause of acute renal failure (45-47% cases) ¡ Glomeruli are spared ¡ Recovery is possible with timely treatment 37% fatality rate ÷ 3.5% progress to ESRD ÷ *Ischemic acute tubular necrosis (50%) 1. ¡ ¡ *Vascular collapse (shock/hypotension) (39%) Pre-renal vessel occlusion (HTN, DM, clamping, renal thrombosis) Toxic acute tubular necrosis (25%) 2. ¡ ¡ *Intravenous use of diagnostic x-ray contrast media (36%) Antibiotics, NSAID’s, other drugs/substances Mehta RL et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66:1613-21 2. Hypertensive Nephropathy — MOA: sclerosis of renal arteries and glomeruli 2° chronic HTN — 2nd most common cause of ESRD (25-27% cases in US) — Risk Factors: ¡ M>F (4:1); AA>Hispanics>Caucasians; concomitant DM diagnosis — Duration and severity of HTN both play roles — Two Types: 1. Benign Nephrosclerosis (55%) ÷ 2. 1-5% progress to renal failure Malignant Nephrosclerosis (diastolic >130 mmHg) (45%) ÷ 33% progress to renal failure — Treatment: ¡ ¡ ¡ BP control (<140/90 ideally) Other systemic risk factor control (BG, lipids, smoking, etc.) Dialysis and/or transplantation Renal Failure Stages of Kidney Dysfunction Question in past from students: Kidney failure & ESRD = same thing End Stage Renal Disease (ESRD) — Aka à kidney failure Normal — Defn: GFR <15 mL/min ¡ ~786k cases in 200 ¡ *Also stated: <10% normal renal function ¢ Math à [14 mL/min ÷ 130 mL/min = 10.8%] — **Primary causes in the U.S. ¡ Diabetes #1 ¡ Hypertension #2 — AA>Hispanics>Caucasians — Treatment options ¡ Dialysis ¡ Transplantation ¡ Acceptance of death from uremia ESRD ESRD in USA ~80% of cases involve: • *DM -- #1 • *HTN -- #2 • GN -- #3 https://www.freseniuskidneycare.com/kidney-disease/ckd/causes Acute Renal Failure — aka: “Acute Kidney Injury” — GFR: <15 mL/min by definition — Onset: days to weeks — Causes ¡ *Vascular collapse (shock) à ATN ÷ ¡ ¡ ¡ ¡ ¡ (45-47% cases) Toxic damage to tubules Severe hemolysis Muscle disorders Acute vascular disease Urinary tract obstruction Acute Renal Failure — Signs and symptoms ¡ Acute oliguria ¡ Azotemia/Uremia ¡ Fatigue ¡ Loss of appetite ¡ Headache ¡ Nausea ¡ Vomiting — Reversible! — Treatment ¡ Address underlying cause ¡ Diuretics ¡ Dialysis ¡ Transplant Chronic Renal Failure — >3 mo duration — Signs and symptoms — Irreversible damage ¡ ¡ ¡ — Risk factors ¡ ¡ ¡ ¡ ¡ **Diabetes **Hypertension *Chronic glomerulonephritis PKD Idiopathic (~18%) ¡ ~80% ¡ ¡ ¡ *Oliguria *Azotemia/Uremia *Fatigue Loss of appetite Headache Nausea Vomiting — Treatment ¡ ¡ Hemodialysis Transplantation In 2018, 7% of Medicare budget ($36.6B) went to chronic kidney disease Tx! Renal Failure Treatment Options: --Dialysis --Transplantation Dialysis — Dialysis = “split apart” — MOA: Mechanical removal of wastes from the blood Imitates functions of the nephrons — Life expectancy is 10-15 years shorter for dialysis than transplant patients ¡ — Two Types of Dialysis: 1. Hemodialysis (HD) 2. Peritoneal dialysis (PD) — HD & PD are considered equivalent in efficacy ¡ Pros/cons to each that should be considered for each patient National Kidney Foundation (www.kidney.org) 1. Hemodialysis • In 2020, 71% of ESRD patients underwent hemodialysis (~560k) • Typical schedule: M/W/F or T/Th/Sat • Usually about 3-4 hours duration 2. Peritoneal Dialysis — ~29% cases in US in 2020 — Peritoneum is used as dialysis filter ¡ Much less common in the U.S. — Provides more flexibility in treatment for patients ¡ Can be done at home ¡ 4-6 “swells” or “exchanges” per day ¡ Must be done daily ¡ Continuous filtration overnight possible too ¡ Increased potential for infection National Kidney Foundation (www.kidney.org) What Gets Filtered Out In Dialysis? Kidney Transplantation — Indicated for ESRD — 22,800 kidney transplants in the U.S. in 2020 ¡ 95% 1-year survival rate ¡ ~90k on the waiting list in the U.S. in 2021 — Transplant rejection is primary concern (~8% cases) ¡ ¡ ¡ ¡ ¡ ¡ • • Generalized edema Tenderness over the graft site Oliguria Hematuria Weight gain Fatigue https://www.niddk.nih.gov/health-information/health-statistics/kidneydisease#:~:text=More%20than%20661%2C000%20Americans%20have,with%20a%20functioning%20kidney%20transplan Hart A, et al. OPTN/SRTR 2015 Annual Data Report: Kidney. Am J Transplant. 2017 Jan;17 Suppl 1:21-116.t Kidney Transplantation Needs — The need for kidney donors is high! https://www.organdonor.gov/learn/organ-donation-statistics Ophthalmic Manifestations of Renal Disease — Band keratopathy — Posterior subcapsular cataract — Renal Retinopathy (HTN) Renal & Urinary Cancers Urinary Tract Cancers Renal Cell Carcinoma — 80-90% of kidney cancers ¡ Usually 50-70 years of age ¡ Men>Women — Risk factors ¡ Smoking (30%) ¡ Familial history ÷ ¡ Von Hippel-Lindau Syndrome Preexisting renal disorders — Symptoms ¡ Hematuria* ¡ Weight loss ¡ Dull flank pain ¡ Palpable mass — Tx: nephrectomy, radiation, transplantation Nephroblastoma — aka: “Wilms’ Tumor” ¡ ¡ *Most common kidney cancer in children (~500 cases/yr) Usually Dx between 3-4 yo — Idiopathic (~90%) ¡ Rarer genetic forms found (2-10%) — 95% cases are unilateral ¡ ¡ 36% unilateral cases develop ESRD 90% bilateral cases develop ESRD — Risk factors ¡ ¡ ¡ Race: AA>Caucasian>Asian Sex: F>M Family Hx — Signs and symptoms ¡ ¡ ¡ ¡ ¡ *Palpable abdominal mass Pain Hypertension Hematuria *Eyes à Aniridia (25-30% cases) — Tx: excision, radiation, chemo, transplant ¡ 90% 5-year survival rate Transitional Cell Carcinoma — 98% of bladder cancers ¡ Usually over 65 years of age ¡ Men>Women (3:1) ¡ 4th most common cancer in men ¡ 8th most common cancer in women — Risk factors ¡ Smoking (50%) ¡ Occupational exposures (30%) ¡ Chronic bladder irritation — Signs and symptoms ¡ Hematuria* ¡ Dysuria ¡ Polyuria — Tx: surgery and/or chemo ¡ 70% 5-year survival rate Other Diseases of the Urinary Tract • • UTI Nephrolithiasis Diseases of the Urinary Tract: Background — Causes: ¡ Bacterial — Common Sx infections ¡ *Hematuria ¡ Diabetes ¡ *Dysuria ¡ Autoimmune ¡ *Polyuria diseases ¡ High blood pressure ¡ Toxic damage ¡ Neoplasms ¡ Hypoxia ¡ Oliguria ¡ Proteinuria ¡ Peripheral ¡ Back edema pain ¡ High blood pressure 1. Urinary Tract Infection — Location ¡ ¡ ¡ ¡ Urethritis Cystitis Ureteritis Pyelonephritis — F>M — Causes ¡ ¡ *Escherichia coli (70-90%) Stasis of urine flow — Common signs and symptoms ¡ ¡ ¡ ¡ Fever Dysuria Bacteriuria Pyuria — Dx à culture — Treatment à oral antibiotics 2. Nephrolithiasis — Defn: “kidney stones” ¡ ¡ ¡ ¡ ~9% population Men > Women White > African-American Obese > healthy weight — Causes ¡ ¡ ¡ ¡ Solute supersaturation Low urine volume Abnormal urine pH Infection — Types of stones ¡ *Calcium, Uric acid, Struvite — Signs and symptoms ¡ ¡ Hematuria Renal colic — Treatment options: ¡ ¡ ¡ Hydration/pain meds à urinate Shock wave/ultrasound Surgical removal Questions? — [email protected] — Tower 932