CKD - Intro and pathophysiology Flashcards
CKD encompasses a spectrum of pathophysiologic process associated with:
Abnormal kidney function and a progressive decline in GFR
The risk of CKD progression is closely linked to:
Both the GFR and the amount of albuminuria
What does ESRD represent?
A stage (stage 5 CKD) where the accumulation of toxins, fluids, and electrolytes normally excreted by the kidneys lead to death unless the toxins are removed by RRT
The pathophysiology of CKD involves what mechanisms?
- Two broad sets of mechanisms of damage:
- initiating mechanisms specific to the underlying etiology (e.g., abnormalities in kidney development or integrity, immune complex deposition and inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium); and
- hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology and lead to further decline in kidney function
The responses to reduction in nephron number are mediated by:
- Vasoactive hormones
- Cytokines
- Growth factors
- Note:*
- Eventually, these short-term adaptations of hyperfiltration and hypertrophy to maintain GFR become maladaptive as the increased pressure and flow within the nephron predisposes to distortion of glomerular architecture, abnormal podocyte function, and disruption of the filtration barrier leading to sclerosis and dropout of the remaining nephrons
What are the secondary glomerular changes associated with a reduction in nephron number and when the short term adaptations of hyperfiltration and hypertrophy to maintain GFR become maladaptive?
- Distortion of glomerular architecture
- Abnormal podocyte function
- Disruption of the filtration barrier
- Enlargement of capillary lumens and focal adhesions
- Note:*
- These lead to sclerosis and dropout of the remaining nephrons
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include:
- Small for gestation birth weight
- Childhood obesity
- Hypertension
- Diabetes mellitus
- Autoimmune disease
- Advanced age
- African ancestry
- Family history of kidney disease
- Previous episode of acute kidney injury
- Presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract
T/F. It has been increasingly recognized that one or more episodes of acute kidney injury are associated with an increased risk of developing CKD
True
Many rare inherited forms of CKD follow a Mendelian inheritance pattern, often as part of a systemic syndrome, with the most common in this category being ____
Autosomal dominant polycystic kidney disease
Recent research in the genetics of predisposition to common complex diseases has revealed DNA sequence variants at a number of genetic loci that are associated with common forms of CKD. A striking example is the ____.
Finding of allelic versions of the APOL1 gene, of West African population ancestry, which contributes to the severalfold higher frequency of certain common etiologies of nondiabetic CKD (e.g., focal segmental glomerulosclerosis) observed among African and Hispanic Americans, in major regions of continental Africa and the global African diaspora
T/F. To stage CKD, it is necessary to rely on serum creatinine concentration
- False
- To stage CKD, it is necessary to estimate the GFR rather than relying on serum creatinine concentration
Equations that estimate GFR are valid only if ____.
The patient is in steady state, that is, the serum creatinine is neither rising nor falling over days
GFR peak and decline
- Peak GFR
- Normal annual decline
- Lower in which gender
- Peak GFR
- ~120 mL/min per 1.73 m2) attained during the third decade of life
- Normal annual decline
- Begins after peak at ~1 mL/min per year per 1.73 m2, reaching a mean value of 70 mL/min per 1.73 m2 at age 70
- Lower in which gender
- Female
Albuminuria measurement
- Preferred measure pointing to glomerular injury
- Significant level for above
- Presence of albuminuria in general serves as
- Preferred measure pointing to glomerular injury
- Urinary albumin to creatinine ratio (UACR)
- Significant level for above
- UACR above 17 mg albumin/g creatinine in men and 25 mg albumin/g creatinine in women serves as a marker not only for early detection of primary kidney disease, but for systemic microvas-cular disease as well
- Presence of albuminuria in general serves as
- A well-studied screening marker for the presence of systemic microvas-cular disease and endothelial dysfunction
- Note:*
- The cumbersome 24-h urine collection has been replaced by measurement of urinary albumin to creatinine ratio (UACR)
The five most frequent categories of causes of CKD
- Diabetic nephropathy
- Glomerulonephritis
- Hypertension-associated CKD (includes vascular and ischemic kidney disease and primary glomerular disease with associated hypertension)
- Autosomal dominant polycystic kidney disease
- Other cystic and tubulointerstitial nephropathy
