Acute and chronic kidney disease Notes

NOTES NOTES ACUTE & CHRONIC KIDNEY DISEASE GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES DIAGNOSIS ▪ Decline of kidney function DIAGNOSTIC IMAGING TYPES Ultrasound, CT scan ▪ Obstructive renal failure Acute kidney injury (AKI) ▪ Decline over < three months ▪ Divided by cause ▫ Prerenal azotemia: kidney hypoperfusion ▫ Intrarenal azotemia: injury within kidney ▫ Postrenal azotemia: obstructed urine outflow distally Chronic kidney disease (CKD) ▪ Decline over > three months ▪ Any etiology causing decreased kidney function SIGNS & SYMPTOMS ▪ Electrolyte imbalance (e.g. ↑ K+, ↓ Na+, ↓ Ca2+) ▪ Decreased waste elimination (azotemia/ uremia) ▪ Fluid retention 762 OSMOSIS.ORG LAB RESULTS ▪ Urine electrolytes, osmolality, cellular casts, proteinuria, hematuria ▪ Acid-base status, electrolytes, protein levels ▪ Blood urea nitrogen (BUN)-to-creatinine ratio (BUN:Cr) ▫ Prerenal azotemia: > 20:1 ▫ Renal azotemia: < 15:1 ▫ Postrenal azotemia: > 15:1; over time, < 15:1 TREATMENT MEDICATIONS ▪ Correct acid-base status, electrolytes, volemia OTHER INTERVENTIONS ▪ Hemodialysis (not used for prerenal azotemia)

Chapter 106 Acute & Chronic Kidney Disease CHRONIC KIDNEY DISEASE osms.it/chronic-kidney-disease PATHOLOGY & CAUSES ▪ Gradual decline of kidney function over ≥ three months ▪ Affects all physiologic roles of kidney ▪ ↓ Glomerular filtration rate (GFR) → ↓ waste products excretion → build-up of nitrogenous compounds → ↑ BUN, Cr, urea (azotemia/uremia) ▫ Inflammation (e.g uremic pericarditis) ▫ Interferes with neurotransmitter metabolism → encephalopathy ▫ Platelet dysfunction → bleeding (platelet adhesion, aggregation) ▫ Excess urea through eccrine glands → crystallizes on skin → uremic frost ▪ ↓ reabsorption, secretion → impaired electrolyte homeostasis ▫ ↑ K+, ↓ Na+, ↓ HCO3-, ↓ Ca2+ ▪ Impaired hormone secretion ▫ ↓ erythropoietin → anemia ▫ ↓ GFR → ↑ renin → hypertension ▫ ↓ vitamin D activation → ↓ intestinal absorption of Ca2+ → hypocalcemia CAUSES ▪ Hypertension (most common) ▫ ↑ blood pressure → hypertrophy/ sclerosis of renal arteries → hypoperfusion, ischemic injury → growth factor secretion by macrophages → mesangial cells regress to mesoangioblasts, secrete extracellular matrix → glomerulosclerosis, loss of function ▪ Diabetic nephropathy ▫ ↑ blood glucose → non-enzymatic glycosylation of efferent arterioles → initial hyperinflation → mesangial cells secrete structural matrix → nodular glomerulosclerosis, loss of function ▪ Less common ▫ Glomerulonephritis (e.g. lupus nephritis); rheumatoid arthritis; HIV nephropathy; long term medication use (e.g. NSAIDs); polycystic kidney disease RISK FACTORS ▪ Family history ▪ Reflux nephropathy ▪ Other congenital kidney disorders COMPLICATIONS ▪ Uremic fibrinous pericarditis, uremic gastroenteritis ▪ Renal osteodystrophy → increased risk of skeletal fractures; caused by secondary hyperparathyroidism (compensatory parathyroid hormone release due to lack of vitamin D) ▪ Renovascular hypertension ▫ Development/exacerbation of hypertension due to increased RAAS ▪ Congestive heart failure ▪ Coma, death by severe encephalopathy SIGNS & SYMPTOMS ▪ Less advanced stages usually asymptomatic ▪ Oliguria ▫ Urine output < 400mL in 24 hour ▪ ↑ fluid volume ▫ Peripheral edema ▪ Azotemia/uremia ▪ Skin ▫ Uremic pruritus, excoriations ▪ GI tract ▫ Ulcerations, bleeding, diarrhea, vomiting ▪ Encephalopathy ▫ Fatigue, somnolence, appetite loss, asterixis, confusion OSMOSIS.ORG 763

▪ ↑ K+ (> 5.5mEq/L) ▫ Cardiac arrhythmias ▪ Anemia ▫ Low erythropoietin production by kidneys DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound ▪ Etiological investigation; polycystic kidney disease (PCKD), renal artery stenosis, hydronephrosis, etc.; decreased kidney volume LAB RESULTS ▪ Iron deficiency anemia ▪ Metabolic acidosis, ↑ PO3-, ↑ K+, ↓ Na+, ↓ HCO3-, ↓ Ca2+ ▪ Biopsy ▫ Glomerulosclerosis/interstitial fibrosis OTHER DIAGNOSTICS ▪ Rise of serum Cr over months/years ▪ Increased blood urea nitrogen:creatinine (BUN:Cr) ▪ Cr clearance to assess glomerular filtration rate (GFR) ▫ Stage I: kidney damage with normal/ increased GFR (> 90mL/min/1.73m2) ▫ Stage II: mild reduction in GFR (60– 89mL/min/1.73m2) ▫ Stage IIIa: moderate reduction in GFR (45–59mL/min/1.73m2) ▫ Stage IIIb: moderate reduction in GFR (30–44mL/min/1.73m2) ▫ Stage IV: severe reduction in GFR (15–29mL/min/1.73m2) ▫ Stage V: end stage kidney failure (GFR < 15mL/min/1.73m2 or dialysis) TREATMENT MEDICATIONS ▪ ACE inhibitors, angiotensin II receptor antagonists (ARBs) SURGERY ▪ Kidney transplantation ▫ Severe (e.g. Stage V CKI) OTHER INTERVENTIONS ▪ Dialysis ▫ Severe (e.g. Stage V CKI) ▪ Hemodialysis ▫ Remove excess waste products, fluids via artificial kidney (dialyzer) ▪ Peritoneal dialysis ▫ Remove excess waste products, fluids via peritoneal membrane POSTRENAL AZOTEMIA osms.it/postrenal-azotemia PATHOLOGY & CAUSES ▪ Acute kidney injury due to obstructed urine outflow distally → ↑ nitrogenous compounds in blood ▪ Obstruction of urine outflow → reversal of Starling forces → pressure backs up to kidneys, tubules → reduced pressure gradient between arterioles, tubules → 764 OSMOSIS.ORG ↓ GFR CAUSES ▪ Compression ▫ Ureters (e.g. intra abdominal tumors); urethra, benign prostatic hyperplasia (BPH) ▪ Obstruction ▫ Ureters; urethra, kidney stones

Chapter 106 Acute & Chronic Kidney Disease ▪ Congenital abnormalities ▫ Vesicoureteral reflux COMPLICATIONS ▪ Hydronephrosis; urinary tract infection (UTI), obstruction, urosepsis SIGNS & SYMPTOMS ▪ Normotensive/hypertensive ▪ Renal colic ▫ Acute complete obstruction, dysuria, urgency, overflow incontinence, frequent urination ▪ Abdominal distention ▫ Urinary retention ▪ Costovertebral angle tenderness ▪ Pain ▫ Bladder distention, secondary infection, stones, masses ▪ Decreased urine output, hematuria ▫ Stones DIAGNOSIS DIAGNOSTIC IMAGING Renal ultrasound ▪ Detect obstruction; hydronephrosis, stones > 3mm ▫ Echogenic foci, acoustic shadowing CT scan ▪ Confirmation ▪ Hyperdense foci; dilation of ureter LAB RESULTS ▪ Urinalysis ▫ UNa+ < 20 mEq/L; over time > 40mEq/L ▫ FENa > 1%; severe: FENa > 2% ▫ Uoms > 500mOsm/kg; over time 350mOsm/kg OTHER DIAGNOSTICS ▪ Physical exam ▫ Palpable bladder ▪ Digital rectal examination ▫ Enlarged prostate TREATMENT SURGERY ▪ Percutaneous nephrostomy, lithotripsy ▫ Obstruction by stones OTHER INTERVENTIONS ▪ Short term hemodialysis (severe) ▪ Placement of Foley catheter, ureteral stent/ nephrostomy OSMOSIS.ORG 765

PRERENAL AZOTEMIA osms.it/prerenal-azotemia PATHOLOGY & CAUSES ▪ Acute renal injury ▫ Kidney hypoperfusion → increased nitrogenous compounds in blood (BUN, Cr) ▪ Decreased blood flow to kidney → ↓ glomerular filtration rate (GFR), accumulation of waste products (BUN, Cr) in blood → azotemia ▪ ↓ GFR → renin–angiotensin–aldosterone system (RAAS) activation → aldosterone secretion → Na+, water retention → urea follows Na+ → ↑ BUN:Cr (> 20:1) CAUSES ▪ Absolute fluid loss ▫ Burns, dehydration, long term vomiting, diarrhea, hemorrhage ▪ Relative fluid loss ▫ Congestive heart failure, distributive shock ▪ Renal artery stenosis/embolus ▪ Liver failure ▫ Portal hypertension → systemic, splanchnic vasodilation → ↓ effective blood volume, ↑ sequestration in peritoneal cavity (ascites) → relative hypovolemia → ↓ renal perfusion RISK FACTORS ▪ Gastrointestinal (GI) tract disorders (e.g. diarrhea, vomiting) ▪ Liver disease ▪ Congestive heart failure SIGNS & SYMPTOMS ▪ Oliguria: urine output < 400mL in 24 hours ▪ Azotemia: confusion, lethargy, asterixis, appetite loss, nausea, bleeding (platelet dysfunction), uremic frost 766 OSMOSIS.ORG ▪ Dehydration: dry mucous membranes, skin turgor loss, thirst, xerostomia (dry mouth), tachycardia, orthostatic hypotension ▪ Congestive heart failure: jugular vein distention, edema ▪ Underlying liver failure: ascites DIAGNOSIS DIAGNOSTIC IMAGING Doppler renal ultrasound ▪ Renal artery stenosis/embolus LAB RESULTS ▪ Absolute fluid loss ▫ ↑ Na+, ↑ Ca2+, ↑ hematocrit, ↑ HCO3, ↑ protein/albumin ▪ Relative fluid loss ▫ ↓ Na+, ↓ protein/albumin ▪ Urine sodium (UNa+) < 20mEq/L ▪ Fraction of sodium excreted to sodium filtered (FENa) < 1% ▪ Urine osmolality (Uoms) > 500mOsm/kg OTHER DIAGNOSTICS ▪ BUN:Cr > 20:1 TREATMENT MEDICATIONS ▪ Diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta blockers, nitrates, positive inotropic agents ▫ Congestive heart failure OTHER INTERVENTIONS ▪ Correct fluid, electrolyte imbalances with IV fluids ▫ Crystalloid solutions: isotonic solutions containing electrolytes, small organic molecules (e.g. isotonic saline, Ringer’s

Chapter 106 Acute & Chronic Kidney Disease lactate); most common ▫ Colloid solutions: hypertonic solutions containing larger molecules; albumin, hyperoncotic starch (e.g. glucose, dextrose) ▫ Blood transfusion: in case of hemorrhage Figure 106.1 The clinical appearance of uremic frost in an individual with azotemia. RENAL AZOTEMIA osms.it/renal-azotemia PATHOLOGY & CAUSES ▪ Acute renal injury caused by problem within kidney → increased nitrogenous compounds in blood ▪ Kidney injury → ↓ GFR → accumulation of waste products in blood → azotemia CAUSES Glomerular injury ▪ Glomerulonephritis ▫ Inflammation of glomeruli (e.g. poststreptococcal glomerulonephritis, Goodpasture’s syndrome, Wegener’s granulomatosis, IgA nephropathy) ▫ Deposition of immune complexes on glomerular basement membrane → activation of complement system → chemoattraction of macrophages, neutrophils → mediator release → inflammation, podocyte damage → protein, blood cell leakage → reduces pressure gradient between arterioles, tubules → ↓ GFR, oliguria Tubular injury ▪ Acute tubular necrosis: damage to tubular epithelial cells; shedding of tubular cells, granular casts in urine ▫ Ischemic tubular necrosis: caused by prerenal issues (hypoperfusion due to absolute, relative fluid loss) ▫ Nephrotoxic tubular necrosis: caused by nephrotoxins, like organic solvents (carbon tetrachloride), heavy metal poisoning (lead, mercury), ethylene glycol, radiocontrast agents, certain medications (aminoglycosides) ▪ Shedded tubular cells, granular casts obstruct tubule → ↑ tubular pressure → reduces pressure gradient between arterioles, tubules → ↓ GFR → oliguria Interstitial injury ▪ Acute interstitial nephritis ▫ Caused by Type I, IV hypersensitivity due to nonsteroidal anti-inflammatory drugs (NSAIDs)/penicillin/diuretics ▫ Inflammation of interstitium → renal papillary necrosis → hematuria ▪ Bilateral pyelonephritis Glomerular endotheliopathy ▪ Thrombotic microangiopathy, hyaline arteriolosclerosis, scleroderma OSMOSIS.ORG 767

RISK FACTORS OTHER DIAGNOSTICS ▪ Family history of congenital/systemic diseases (e.g. diabetes, hypertension, systemic lupus erythematosus, hepatitis B, C) ▪ BUN:Cr < 15:1 ▪ Interstitial nephritis ▫ Hypersensitivity, acute interstitial nephritis ▫ ↑ IgE: Type I ▫ Skin test: T-cell mediated Type IV ▫ Eosinophilia SIGNS & SYMPTOMS ▪ Oliguria, hematuria, flank pain, livedo reticularis (lace-like purplish skin discoloration) ▪ Fluid build-up ▫ Hypertension, hypertensive retinopathy, edema ▪ Azotemia ▫ Confusion, lethargy, asterixis, loss of appetite, nausea, bleeding (platelet dysfunction) ▪ Hypersensitivity ▫ Rash, fever, joint swelling/tenderness DIAGNOSIS LAB RESULTS UNa+ > 40mEq/L FENa < 2% Uoms > 350mOsm/kg Erythrocyte, leukocyte, epithelial casts: glomerulonephritis ▪ Pigmented muddy brown granular/tubular epithelial cells cylinders: acute tubular necrosis ▪ ▪ ▪ ▪ 768 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Glomerulonephritis; treat according to etiology (e.g. corticosteroids) ▪ Pyelonephritis ▫ Antibiotics OTHER INTERVENTIONS ▪ Avoid nephrotoxins/allergens ▪ Glomerulonephritis; treat according to etiology (e.g. plasmapheresis) ▪ Hemodialysis