Chronic Kidney Disease.pdf

The Urinary Tract Kidney: Chronic Kidney Disease Dr. Mohammed I. Malki Assistant Professor of Pathology College of Medicine, Qatar University Annex Building, Office 8 [email protected] Content  Chronic kidney disease • Definition • Pathophysiology • Stages • Morphology • Clinical presentation...

The Urinary Tract Kidney: Chronic Kidney Disease Dr. Mohammed I. Malki Assistant Professor of Pathology College of Medicine, Qatar University Annex Building, Office 8 [email protected] Content  Chronic kidney disease • Definition • Pathophysiology • Stages • Morphology • Clinical presentation Chronic Kidney Disease (CKD)  Either kidney damage or a decreased glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 for at least 3 months  End stage kidney failure result of progressive scarring from any type of kidney disease • Glomeruli, tubules, interstitium and vessels are sclerosed  Most common causes: • Diabetes (up to 50%) • Hypertension (up to 30%) • Glomerular diseases • Urinary tract obstruction  Treatment: • Dialysis or Transplantation Chronic Kidney Disease (CKD) Criteria for CKD (either one of the following criteria must be present for > 3 months)  Marker of Kidney Damage (One or more) • Albuminuria: ( urine ACR > 3 mg/mmol or 24 hours urine albumin >30 mg/24 hours) • Hematuria: urine sediment abnormalities (RBC cast, etc.) • Electrolyte abnormalities due to renal tubular disorders (RTA, Fanconi syndrome, etc.) • Abnormalities detected on histopathology (GN, TIN etc.) • Structural abnormalities detected on imaging (Cysts, Scar, etc.) • History of kidney transplant Or  Decrease GFR: GFR < 60 ml/min/1.73 m2 with or without kidney damage CKD ‐ Pathogenesis Hypertension  Glomerular and vascular changes:  Elevated systemic blood pressures cause a hypertrophic response leading to intimal thickening of the large and the small vasculature  The mechanisms are compensatory at first, but later lead to glomerular damage  Global sclerosis – ischemic injury to the nephrons causes death  Focal segmental sclerosis – glomerular enlargement for compensation of the loss of nephrons in other areas of the kidney  Interstitial nephritis:  The vascular and glomerular disease lead to tubular atrophy and an intense chronic interstitial nephritis  Chronically these changes lead to tubular and glomerular loss causing nephrons loss  With the death of some nephrons, less are available to maintain the GFR  Gradual decline in the GFR is noticed as the nephrons continue to die Malignant Hypertension (blood vessels)  Blood pressure usually greater than 200/120 mm Hg  Occurs in about 5% of hypertensive individuals in USA  Higher in developing countries  It may arise de novo (i.e., without preexisting hypertension), or it may appear suddenly in an individual who had mild hypertension  Pathogenesis: Malignant Hypertension Morphology  Fibrinoid necrosis:  Formation of pink fibrin of small renal arteries  Hyperplastic arteriolosclerosis  Homogeneous, granular eosinophilic appearance  Proliferation of intimal cells after acute injury produces an onion‐skin appearance  Marked narrowing of interlobular arteries and larger arterioles (obliteration)  Necrosis also may involve glomeruli as well as arterioles Fibrinoid necrosis of small renal arteries Hyperplastic arteriolosclerosis (onion-skin lesion) Malignant Hypertension  Clinical Features:  Papilledema, encephalopathy, cardiovascular abnormalities, and renal failure  Early symptoms (increased intracranial pressure )  Headache, nausea, vomiting, and visual impairment, particularly the development of scotomas, or “spots” before the eyes  Renal Manifestations  Marked proteinuria and hematuria but no significant alteration in renal function  Present with severe acute kidney injury and renal failure CKD ‐ Pathogenesis  Diabetes CKD ‐ Pathogenesis Light photomicrographs illustrating various stages of developing glomerular lesions and tubulointerstitial disease in diabetic nephropathy. (a) A normal glomerulus (b) Thickened basement membranes (arrowheads) and expanded mesangial regions (asterisks) (c) The nodular appearance of the mesangial regions characteristic of Kimmelstiel-Wilson lesions (asterisks) (d) The tubulointerstitial lesions include thickened tubular basement membrane (TBM), hyalinization of afferent arteriole (ART), and fibrosis of the interstitium (INT). Abbreviations: c, capillary lumen; En, endothelial cell; Ep, visceral epithelial cell (podocyte); Me, mesangium; US, urinary space. CKD ‐ Pathogenesis CKD – Stages CKD – Morphology Gross ‐ Features:  Kidneys are symmetrically contracted  Damage in blood vessels or glomeruli  Kidney surface: red‐brown and diffusely granular  Damage by chronic pyelonephritis  Uneven kidney with deep scare CKD – Morphology Microscopically ‐ Features:  Glomerular Sclerosis  Interstitial fibrosis with Lymphocytic infiltrates  Tubules atrophy  Loss of portions of the peritubular capillary network  Arteries (small/medium size)  Thick walled  Narrowed lumina CKD – Morphology The cortex is fibrotic, the glomeruli are sclerotic, there are scattered chronic inflammatory cell infiltrates, and the arteries are thickened. Tubules are often dilated and filled with pink casts and give an appearance of "thyroidization." CKD – Morphology Chronic glomerulonephritis: A Masson trichrome preparation shows complete replacement of virtually all glomeruli by blue-staining collagen. CKD – Clinical Presentations  Asymptomatic in stage 1‐3 with GFR > 30ml/min  Symptomatic in stage 4‐5 with GFR < 30ml/min  Early signs:  Polyuria/oliguria, Hematuria, Edema  Late signs:  Hypertension  Signs of anemia (pallor)  Signs of Uremia: • Brain (uremic encephalopathy): low concentration, confusion, lethargy, asterixis, coma • Heart: pericarditis CKD – Clinical Presentations • GIT: nausea & vomiting, anorexia, diarrhea • Reproductive system: erectile dysfunction, decreased libido, amenorrhea • Blood system: platelet dysfunction with tendency to bleed, infections due to WBCs dysfunction • Peripheral neuropathy: numbness, paraesthesia, restless leg syndrome • Skin: dry skin, pruritus, ecchymosis • Others: fatigue, hiccups, muscle cramps CKD – Pathophysiological Changes Sign/lab finding Symptoms Mechanism Generalized edema Swelling Water retention due to a loss of GFR leading to sodium and fluid retention. Fluid moves into the extravascular space, due to increased hydrostatic pressure, causing pitting edema in the lower extremity (fluid movement could also be due to hypoalbuminemia, in some diseases, leading to a low oncotic pressure) Pulmonary crackles Shortness of breath Fluid accumulation causes pulmonary edema and loss of air space causing ventilation-perfusion mismatch. This leaves less area for oxygen diffusion form the blood vessels Anemia Fatigue, reduced exercise capacity, and pallor Erythropoietin (EPO), the major erythropoiesis stimulator, is released from the kidneys; with renal failure, there is loss of EPO release Weight loss Loss of lean body mass Protein-energy malnutrition due to metabolic acidosis. Loss of kidney function results in impaired H+ secretion from the body Hyperkalemia Malaise, palpitations Inability of the kidneys to secrete potassium in the urine leads to life threatening arrhythmias CKD – Pathophysiological Changes Sign/lab finding Mechanism Mechanisms of renal osteodystrophy Hyperphosphatemia Damaged kidneys fail to excrete phosphate Also secondary to high parathyroid hormone levels Hypocalcemia Thought to be secondary to low Vitamin D3 levels. In early stages of CKD, low levels of calcitriol are due to hyperphosphatemia (negative feedback). In the later stages of CKD, low levels are hypothesized to be due to decreased synthesis of 1α-hydroxylase (enzyme that converts calcifediol to calcitriol in the kidneys) Secondary and tertiary hyperparathyroidism To compensate for the low calcium due to low Vitamin D levels, the parathyroid glands increase the parathyroid hormone secretion. This leads to a high bone turnover, always attempting to normalize the low calcium levels in the blood. Over time, this becomes maladaptive leading to extraosseous calcification, and parathyroid hyperplasia develops (tertiary hyperparathyroidism) CKD – Pathophysiological Changes Sign/lab finding Symptoms Mechanism Complications of uremia Urea and other toxins accumulate in the blood and cause life threatening issues. Ecchymosis, GI bleeding Increased tendency to bleed and ecchymosis Pericardial friction rub Chest pain, malaise Headaches, confusion, coma Uremia-induced platelet dysfunction Uremic pericarditis Uremic encephalopathy; adverse effects of urea on the CNS (Mechanisms unclear) Recommended Resource Robbin Basic Pathology (10th edition)  Chapter 14, page 573. Essential of Rubins Pathology (8th edition)  Diabetic Glomerulosclerosis, page 933.  Malignant Hypertension, page 617. Thank You Board Review Question In a patient suspected to have diabetic kidney disease, what is the earliest structural change in a kidney biopsy recognized by electron microscopy? A. Deposits of randomly oriented nonbranching fibrils in the mesangium B. Diffuse thickening of the glomerular basement membrane C. Diffuse effacement of podocytes' foot processes D. Electron dense subepithelial deposits E. Expansion of the mesangial regions