CKD Flashcards
chronic kidney disease (CKD) - defined
*defined by 3 or more months of:
-kidney damage
OR
-decreased kidney function
chronic kidney disease (CKD) - etiologies
- glomerular diseases:
-DIABETES, autoimmune diseases, systemic infections, drugs, neoplasias - vascular diseases:
-atherosclerosis, HTN, ischemia, vasculitis, thrombotic microangiopathy - tubulointerstitial diseases:
-chronic UTIs, stones, obstruction, drug toxicity - cystic diseases:
-polycystic kidney disease
decreased kidney function
*GFR is best overall index of kidney function for healthy individuals & those with CKD
*GFR = sum of the filtration rates in all of the functioning nephrons
*healthy glomeruli collectively filter 180 liters per day
*normal GFR in healthy young adults ~125 mL/min
*GFR < 15 mL/min is defined as kidney failure
measured GFR
*measurement of ideal urinary clearance filtration markers
*gold standard is inulin or lothalmate
estimated GFR
*serum biomarkers input to complex equations to approximate the true GFR
*this is routinely done in clinical practice
*note that all of the equations for eGFR have limitations
chronic kidney disease (CKD) due to kidney damage - defined
*preserved GFR
*histopathological abnormalities
*abnormalities in serum/urine tests or abnormalities on imaging that may lead to a drop in GFR (e.g. albuminuria, polycystic kidney disease)
chronic kidney disease (CKD) due to decreased kidney function - defined
*drop in GFR (GFR < 60 mL/min per 1.73 m^2)
*with or without kidney damage
stage I chronic kidney disease (CKD)
*kidney damage with normal or increased GFR
*GFR > 90
stage II chronic kidney disease (CKD)
*kidney damage with mild decreased GFR
*GFR 60-89
stage III chronic kidney disease (CKD)
*moderately decreased GFR
*GFR 30-59
stage IV chronic kidney disease (CKD)
*severely decreased GFR
*GFR 15-29
stage V chronic kidney disease (CKD)
*kidney failure
*GFR < 15 (or dialysis)
who should be screened for CKD?
*all patients who have increased susceptibility or have potential inciting factors should be screened for CKD
*most screening is done with serum creatinine based estimating equations
CKD progression
*chronic kidney disease is often PROGRESSIVE and leads to IRREVERSIBLE loss of renal function
*once GFR falls below about 50% of normal, kidney function tends to continually decline, even if the initial insult has been eliminated
adaptive hyperfiltration
*a compensatory process in which the kidneys adapt to the initial damage by increasing the filtration rate in the normal (undamaged) nephrons
*results in long-term damage to the remaining nephrons
*manifested by more proteinuria and progressive CKD
effects of proteinuria in chronic kidney disease (CKD)
*proteinuria itself contributes to progressive nephron damage
*excessive tubular reabsorption → protein overload; the reabsorbed tubular proteins signal pro-inflammatory mediators and macrophage recruitment
*complement activation → alterations of cytoskeleton, production of ROS, & synthesis of more pro-inflammatory mediators
*inflammation → accumulation of ECM collagen, fibronectin, and other components → interstitial fibrosis
SGLT2 inhibitors in CKD
*SGLT2 inhibitors block reabsorption of glucose in the proximal tubule
*lowers the renal glucose threshold → substantial glycosuria (increased release of glucose in the urine)
*also have effects independent of glycemic control
risk factors for progression of CKD
*PROTEINURIA!!!
*hypertension
*type of underlying disease (diabetes, PKD)
*African American ancestry
*male gender
*obesity
*smoking
*high protein diet
*phosphate retention
*metabolic acidosis
mainstays of CKD management to slow progression
- treat the underlying cause, if possible
- address modifiable risk factors (correct HTN, initiate statin therapy, encourage smoking cessation, use ACEi or ARB + SGLT2 inhibitor)
- prepare for renal replacement therapy (RRT = dialysis) or transplant
medical complications of CKD
*HTN
*cardiovascular disease
*anemia
*secondary hyperparathyroidism
*metabolic acidosis
*dyslipidemia
*uremia
pathogenesis of CKD → HTN
- sodium retention: Na+/H2O balance disrupted as GFR declines
- increased activation of RAAS: prob due to regional ischemia & scarring
- enhanced activity of sympathetic nervous system
- secondary hyperparathyroidism: rise in intracellular calcium → vasoconstriction
- impaired nitric oxide synthesis & endothelium-mediated vasodilation
why is HTN an important complication of CKD?
*HTN is an independent risk factor for cardiovascular disease (CVD)
*each increment of 20/10 mmHg above 115/75 doubles your risk of a cardiovascular event
*CVD is the leading cause of death in patients with CKD
treatment of HTN when diabetes or CKD present
*goal is < 140/90
*initiate ACEi or ARB +/- SGLT2 inhibitors
*purpose: slow progression of CKD and reduce rate of cardiovascular complications
pathogenesis of CKD → anemia
*CKD results in decreased EPO (erythropoietin) from peritubular cells
*as GFR decreases, anemia is more severe
*other causes include:
-absolute of functional iron delivery
-shortened RBC survival (esp dialysis pts)
-blood loss due to uremic platelet dysfunction
-nutritional deficiencies
-inflammation
-ACEi use
treatment of anemia in pts with CKD
*exclude non-renal causes of anemia (GI blood loss, B12 deficiency, etc)
*correct iron deficiency (oral or IV iron supplementation)
*initiate erythrocyte stimulating agents (ESA) - recombinant human EPO
note - generally do not treat to a Hb > 12-13
pathogenesis of CKD → secondary hyperparathyroidism
- decreased GFR → substantial increases in phosphate retention
- FGF-23 increases to improve renal phosphate clearance (increase excretion of phosphate)
- high FGF-23 levels suppress 1,25 Vitamin D activity
- low vitamin D activity → HYPOCALCEMIA
- PTH secretion increases to maintain normocalcemia
- clinically apparent rise in phosphorous is a very late finding
complications of secondary hyperparathyroidism due to CKD
- mineral bone disease → renal osteodystrophy → increased risk of fractures, esp hip fractures → increase in mortality
- soft tissue and extra-skeletal calcifications (in coronary or peripheral arteries, skin or soft tissue [calciphylaxis])
treatment of secondary hyperparathyroidism in CKD pts
*control serum phosphate levels
*control metabolic acidosis
*suppress PTH levels (active oral vitamin D supplementation - calcitriol)
*consider subtotal parathyroidectomy
pathogenesis of CKD → metabolic acidosis
*increasing tendency to retain hydrogen ions in patients with CKD
*leads to progressive metabolic acidosis
*consequences: increased bone resorption, enhances protein catabolism, contributing to malnutrition
treatment of metabolic acidosis in CKD pts
*oral bicarbonate supplementation
pathogenesis of CKD → dyslipidemia
*abnormal lipid metabolism is common in patients with renal disease/CKD
*initiate statin therapy to treat
pathogenesis of CKD → uremia
*uremia: clinical syndrome attributed to accumulation of uremic toxins (we often use UREA as a marker)
*associated with ADVANCED CKD (stage V)
*symptoms: fatigue, pruritus, dysgeusia, anorexia, nausea, vomiting, restless legs
*signs: serositis, pericarditis, asterixis, skin changes, weight loss/malnutrition, platelet dysfunction, peripheral neuropathy
treatment for uremia in advanced CKD pts
*renal replacement therapies (dialysis or transplant)
