Fundamentals of Nephrology - PDF

1. Fundamentals of Nephrology Renal/ Urinary System Suzanne Riskin, M.D. Assistant Professor of Foundational Science Dr. Kiran C. Patel College of Osteopathic Medicine Nova Southeastern University 1 ...

1. Fundamentals of Nephrology Renal/ Urinary System Suzanne Riskin, M.D. Assistant Professor of Foundational Science Dr. Kiran C. Patel College of Osteopathic Medicine Nova Southeastern University 1 Lecture Objectives 1. Describe the overall organization of the renal system and identify the associated disorders 2. Identify the components of the glomeruli, tubules, and blood vessels 3. Describe the use of serum chemistries for assessment of renal function, particularly blood urea nitrogen (BUN) and creatinine 4. Discuss the measurement of creatinine clearance and glomerular filtration rate 5. Identify the normal and abnormal findings on urinalysis including urine sediments 6. Define parenchymal, prerenal and obstructive renal disease 7. Define the distinction between acute and chronic renal disease 2  Fundamentals of Nephrology Upper urinary tract: kidneys, renal vasculature, parenchyma and collecting system The lower urinary tract includes the peristaltic ureters, bladder, and urethra (Urology) Excretory system: Renal cortical glomeruli → renal tubules of nephron (modifies ultrafiltrate) → plasma ultrafiltrate →excretion of H20 and solutes Functions: 1. Filtration 2. Reabsorption 3. Secretion. 4. Excretion Excretion of the waste products of metabolism, regulation of body salt and water, maintenance of acid balance (pH), secretion of hormones, prostaglandins The image shows six diagrams depicting transport activities of the major nephron segments. Kidney and Its Collecting System - ClinicalKey (nova.edu) Approach to the Patient with Renal Disease or Urinary Tract Disease | Harrison's 3 Principles of Internal Medicine 21e | AccessMedicine | McGraw Hill Medical (nova.edu) Disease of the Renal/ Urinary System Disease can occur at any level Asymptomatic: incidental renal mass, stone on US, invisible microhematuria from UA. Detected by labs or imaging. Nonspecific: fatigue Organ specific but not diagnostic: proteinuria Diagnosis specific: PCKD (polycystic kidney disease) Screening with comorbidities: DM screen for Renal Colic and polycystic kidney disease. Multiple hypoechoic cystic structures at yellow arrows. albuminuria Hornburg, Kalvis; Truong, Jimmy; Chenevert, Laura. Published October 1, 2022. Volume 29. Article 101473- 101473. © 2022 Medications: polyuria/ polydipsia/ nocturia with lithium, renal failure with Pb exposure, bladder cancer with aniline dye. All nephrotoxicity Social history: renal failure with Pb exposure, bladder cancer with aniline dye. All nephrotoxicity 4 Approach to the Patient with Renal Disease or Urinary Tract Disease | Harrison's Principles of Internal Medicine 21e | AccessMedicine | McGraw Hill Medical (nova.edu)  Gold Standard for initial w/u Renal Disease UA Examination Kidney Disease - Clinical Dipsticks Sediment Morphology How do patients with kidney disease typically present? Several ways: Abnormal labs: ↑ BUN (blood urea nitrogen) and SCr (serum creatinine), ↓eGFR (estimated glomerular filtration rate), or abnormal serum electrolyte values Asymptomatic: microscopic hematuria, proteinuria, microalbuminuria on urinalysis Changes in urinary frequency, problems with urination: polyuria, hematuria, nocturia, urgency New-onset hypertension Worsening edema in dependent areas Nausea, vomiting, malaise – all non-specific Ipsilateral flank pain: diagnosis of obstructing nephrolithiasis Incidental findings on routine imaging: horseshoe kidney, congenitally absent or ptotic kidney, asymmetric kidneys, angiomyolipoma, kidney mass, polycystic kidneys Symptoms related to underlying systemic disease: skin changes and/or rash with scleroderma, vasculitis, systemic lupus erythematosus [SLE], arthritis due to gout or SLE 5 History and physical diagnosis - ClinicalKey (nova.edu) Glomerular Filtration Rate Glomerular filtration: hydrostatic pressure across the glomerular capillary wall Oncotic pressure inside the capillary partially offsets filtration. Oncotic pressure is determined by unfiltered plasma proteins. As this concentration ↑, oncotic pressure rises and driving force for filtration drops to zero approaching efferent arteriole. Glomerular filtration rate (GFR): most exact indicator of glomerular function. Rate (mL/min) at which a substance in plasma is filtered through the glomeruli Measured by administered inulin: polysaccharide GBM = Glomerular Basement Membrane that cannot be broken down and is completely FP = Podocyte foot processes filtered. It is a marker by measuring the rate at which it appears in the urine. All of it is filtered. 6 Glomerular Filtration Rate Cinulin=GFR =Uinulin × V/Pinulin =Kf[(PGC–PBS)–(πGC–πBS)] (GC = glomerular capillary; BS = Bowman space; πBS normally equals zero; Kf =filtration coefficient). Normal GFR ≈ 100mL/min. Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR because creatinine is moderately secreted by renal tubules. 7 First Aid Creatinine (Cr) and estimated glomerular filtration rate (eGFR) Excreted creatinine (Cr): most commonly used marker to assess kidney function Creatinine (Cr): by-product of creatine phosphate metabolism in muscle. Produced at a constant rate. Dependent upon muscle bulk and meat consumption Creatinine is cleared from the blood entirely by the kidney. Because of this, it is a commonly used endogenous marker for assessment of glomerular function Calculated clearance of creatinine → eGFR Mean serum values of Cr are dependent on sex and ethnicity. Men: 1.13 mg/dL due to higher muscle mass and Cr excretion Women: 0.93 mg/dL Mean values have been shown to be higher in Americans from African heritage without Spanish speaking cultural influence (non-Hispanic Black Americans) → considered when calculating the eGFR Cr Cl (creatinine clearance) should be corrected for BSA (body surface area) Cr Cl overestimates GFR by around 10%–20% because of tubular secretion 8 Blood urea nitrogen (BUN) Normal metabolism (urea cycle) results in the Ratio of BUN:Cr production of nitrogen-rich ammonia in the liver More useful information than either BUN or Cr Ammonia is refined to urea. Ammonia excreted alone: primarily (85%) by the kidneys Distinguish prerenal from renal causes of Urea excretion is less accurate (but increases kidney failure earlier – early detection) than creatinine to Prerenal disease is 20:1 measure kidney function Intrinsic renal disease is Pathological states lead to elevated urea 10:1 excretion: upper GI bleed, dehydration, catabolic states, high protein diets 9 Cystatin C Low-molecular-weight protein, functions as a protease inhibitor Cystatin C is measured in serum and urine: normally not found in urine Serum levels of cystatin C are inversely correlated with the glomerular filtration rate (GFR) Formed at a constant rate→filtered by the kidneys→ reabsorbed and metabolized by proximal renal tubules Less dependent on age, gender, ethnicity, diet, and muscle mass compared to creatinine May be more specific than creatinine for estimation of GFR 10 Effective Renal Plasma Flow Effective renal plasma flow (eRPF): estimated using para-amino hippuricacid (PAH) clearance. Nearly 100% of all PAH that enters the kidney is filtered and secreted. eRPF = UPAH × V/PPAH = CPAH Renal blood flow (RBF) = RPF/(1−Hct). Usually 20–25% of cardiac output eRPF underestimates true renal plasma flow (RPF) slightly Myogenic reflex is first line of defense against Glomerulus with its juxtaglomerular apparatus fluctuations in RBF. Acute changes in pressure constrict including the macula densa and adjacent afferent or dilate afferent arteriole. Mediated by macula densa arteriole (senses conc. solute and tubular flow rate) Approximately 20% of renal plasma flow is filtered into Bowman space Ratio of GFR/ RPF determines filtration fraction 11 GFR = glomerular filtration rate RPF = renal plasma flow FF = filtration fraction 12 Renal Clearance Cx = (UxV)/Px = volume of plasma from which the substance is completely cleared in the urine per unit time. If Cx < GFR: net tubular reabsorption and/or not freely filtered. If Cx > GFR: net tubular secretion of X. If Cx = GFR: no net secretion or reabsorption Cx = clearance of X (mL/min) Ux = urine concentration of X (mg/mL). Px = plasma concentration of X (mg/mL) 13 First Aid V= urine flow rate (mL/min) Determinants of sodium and water balance TGF Sense and trigger autonomic vasogenic reflex Angiotensin II-mediated vasoconstriction of efferent arteriole 14 View Large | AccessMedicine | McGraw Hill Medical (nova.edu)  Urinalysis Component Results Interpretation Color Dark yellow Concentrated. Dehydration. Exercise. Bilirubin. Glucose. Vitamins Red or pink Beets, blackberries, menses, Hb, myoglobin, drugs. Turns red - porphyria. Green/Blue Asparagus, pseudomonal UTI, biliverdin, propofol Amber Bile Brown/Black/Tea Chloroquine, fava beans, alkaptonuria Smoky Nephritic glomerulonephritis. Acidic pH in urine converts Hb to hematin Black with light Alkaptonuria (increase in homogentistic acid) Clarity Cloudy Normal. If alkaline, due to phosphates. If acidic, due to uric acid Decreased Bacteria. WBCs, Hb, Myoglobin SG (specific gravity) > 1.023 Concentrated. Prerenal disease. Excludes intrinsic renal disease. Normal = 1.016-1.022 40, UNa < 10, U/P Osm > 1 Labs: ↑ BUN/Cr, Hypercatabolic with ↑uric acid. ↑Na or ↓Na Hicks, Caitlin W.; Clark, Timothy W.I.; Cooper, Christopher J.; de Bhailís, Áine M.; De Carlo, Marco; Green, 20 Darren; Małyszko, Jolanta; Miglinas, Marius; Textor, Stephen C.; Herzog, Charles A.; Johansen, Kirsten L.; Reinecke, Holger; Kalra, Philip A.. Published February 1, 2022. Volume 79, Issue 2. Pages 289-301. © 2021. Intrinsic renal disease PMH: rhabdomyolysis, hemolysis, thrombotic US of a patient with ATN post cardiac arrest. Enlarged and microangiopathy, AIN, atheroemboli echogenic right kidney. Small amount of perinephric fluid ("kidney sweat") , a sign often seen in patients with renal failure Tublin, Mitchell, MD; Nelson, Joel B., MD; Borhani, Amir A., MD; Furlan, Alessandro, MD; Heller, Matthew T., MD, FSAR; Squires, Judy, MD. Published January 1, 2018. © 2018. Urinalysis: “muddy brown” granular casts, Tublin, Mitchell, MD; Nelson, Joel B., MD; Borhani, Amir A., MD; Furlan, Alessandro, MD; Heller, Matthew T., MD, FSAR; Squires, Judy, MD. Published January 1, 2018. © 2018. hematuria, dysmorphic RBCs, RBC casts in GN, WBC casts in AIN, eosinophilia, in atheroemboli Urine output: Oliguria. Normal. Polyuria Urine Chemistries: FENa 1-3%, U/P Cr < 40, Urine sediment demonstrating muddy brown, granular casts. Uduman, Junior, MD. Published January 1, 2022. © 2022. UOsm - isomotic Labs: Eosinophilia in allergic AIN, ↑phosphate, ↓Ca, ↑ PTH, metabolic acidosis Scanning microscopy showing dysmorphic red cells in 21 a patient with glomerular bleeding. Acanthocytes can be recognized as ring forms with vesicle-shaped protrusions (arrows). Postrenal disease PMH: Extrinsic ureteral obstruction, retroperitoneal disease, bladder outlet or urethral obstruction by prostate or cervical cancer Urinalysis: intrarenal obstruction by uric acid or calcium phosphate in tumor lysis syndrome, blood clots in lower urinary tract bleeding, CaOx after ethylene glycol ingestion Urine output: Anuria. Polyuria. Both anuria + polyuria Bhosale, Priya; Devine, Catherine; Gardner, Carly S.; Qayyum, Aliya. Published January 1, 2017. © 2017. Urine Chemistries: Early looks like FIG 36-27 Stage IV cervical cancer. Sagittal T2-weighted image ( A) and gadolinium-enhanced fat- saturated T1-weighted image ( B) show a large cervical mass extending into the lower uterine prerenal. Late looks like renal segment ( arrows) and vagina ( arrowhead). The mass also involves the bladder neck ( asterisk). Note the distended urinary bladder related to bladder outlet obstruction. Labs: Hydronephrosis on US, extrinsic or intrinsic disease on CT scan, tumors on MRI 22 Approach to the Patient with Renal Disease or Urinary Tract Disease | Harrison's Principles of Internal Medicine 21e | AccessMedicine | McGraw Hill Medical (nova.edu) Acute injury versus chronic renal disease Acute: ↑SCr in hours or days, or ↓UO for > 6hours ↑SCr > 26.5 mmol/L or 0.3mg/dL ↑SCr > 50% baseline UO < 0.5 mL/kg body wt Chronic: structural kidney damage. ↓GFR < 60 mL/ min per 1.73 square meter BSA for >3months 23 HCPs: CKD Associated With T2D - Treatment Option For Adults - Physician Sitehttps://www.treatckdandt2d.com Patient Case 54-year-old male with a past medical history significant for diabetes mellitus type II poorly controlled presents with an oozing wound on his foot after stepping on a nail. On ROS he denies polyuria, polydipsia or weight loss. His most recent HbA1C is 8.9 µg/dL. He has been on metformin and semaglutide for six months. Which of the following is useful to examine in the urine of this patient to evaluate for renal disease? A. albumin, protein B. epithelial cell casts C. BUN/Cr ratio 30:1 D. Tamm Horsfall protein E. WBC casts 24 Patient Case 34-year-old female survived a hospitalized bout with sepsis. Her blood pressure remained dangerously low throughout the hospital admission. She recovered and was recently discharged on long term antibiotic therapy. She presents to the clinic for follow up. Her past medical history is significant for esophageal atresia as a child that was treated with resolution of symptoms. She reports an increase in frequency of urination since discharge. A work-up reveals - FENa 1-3% U/P Cr < 40 UOsm - isomotic Which of the following is indicative of her new diagnosis, detected in the urine at this visit? What is the diagnosis? A. RBC casts B. muddy brown granular casts C. waxy casts D. white blood cells E. hyaline casts 25