10-6-08 Chronic Kidney Disease
CKD
 Chronic Kidney Disease – either a GFR < 60 or a structure/function abnormality, for over 3 months
 Prevalence – 100,000 new ESRD patients/year; huge healthcare cost (8-10% budget!)
 Staging – from 1 (mild) to 5 (severe)
o Stage 5 – GFR < 15 (think 15% fxn.), double Stage 4 (<30), double Stage 3 (<60), Stage 1 >90
o QUIZ: Stages 4 & 5 – huge drop-off in # of patients, since most die from CV disease before this
o Stage “6” – ESRD, associated with renal failure (also stage 5?)
 CV Disease – predicted by renal failure, associated with albuminuria (high urine albumin  CV death)
 ESRD – only the tip of the iceberg (10-15% of pop has CKD)
CKD Epidemiology
 Susceptibility Factors – put individual at higher risk of kidney damage:
o Elderly, Fam Hx, low kidney mass (glomeruli overworked), low birth weight, race, income

Initiation Factors – will initiate kidney damage:
o Diabetes/HTN/CAD – linked to obesity, and again can initiate kidney damage
o Autoimmune disease, Infection, Obstruction, Drugs (NSAIDS, gentamycin), hereditary
 Progression Factors – will hasten progression of CKD  ESRD:
o HTN, proteinurea – two key factors, both imply glomerulus overworked
o Poor glycemic control – among diabetics, this will greatly speed progression
o Smoking, dyslipidemia, race (African American), family Hx
CKD Progression
 HTN & Kidney Disease – downward spiral:
o Kidney Disease – increased Na+, RAAS, SNS activation, endothelin excess, NO deficiency…
o HTN – arteriosclerosis, atherosclerosis, glomerular HTN, microvascular injury, CHF
 Glomerulus – remaining viable glomeruli become overworked  glomerular hypertrophy
o Angiotensin II – dilates the afferent arteriole to the glomerulus  glomerular HTN
o Endothelin-1 – constricts the efferent arteriole from the glomerulus  glomerular HTN
 Proteinuria – triggered by glom. damage & tubular cell overload  vasoactive, inflammatory response
 Cytokines – signaled by glomerular damage  inflammation, fibrogenic factors also signalled
o Fibrogenic Factors: TGFβ, PDGF
 Tubulointerstitial Scarring – from concert of damaged glomerulus, proteinurea, & inflammatory cytokine
 ESRD – predicted by tubulointerstitial scarring; even in GFR okay, be wary of rapid ESRD progression
CKD Progression Steps
1) Initial pathogenic insult – HTN, DM, infection, obstruction, drugs, hereditary disease…
2) Reduced nephrons – decreased filtration capability put extra burden on remaining ones…
3) Glomerular hypertrophy – as a result of extra work, leading to glomerular damage
4) Proteinuria, Cytokines – allow for glomerular hypertrophy, but invoke inflammatory/fibrotic cascade
5) Tubulointerstitial Scarring  ESRD final common pathway
CKD Podocyte Depletion Hypothesis
 Glomerular Injury – can lead to a number of processes effectively depleting podocytes:
o Podocyte loss – direct loss of podocytes, from necrosis/apoptosis/detachment
o Glomerular enlargement – fewer podocytes per unit of surface area, if podocyte # constant
o Phenotype switch – podocytes can switch to less active phenotypes if in a diseased state
 ESRD – will only result from glomerular injury if podocytes effectively depleted
 Avoid ESRD – if glomerular injury does not cause glomerulosclerosis & effective loss of podocytes
CKD Complications
 Cardiovascular – can cause HTN  leads to atherosclerosis, cardiomyopathy, valve disorder, CHF
o Common Risk Factors – elderly males, HTN, Cholesterolemia, DM, Smoking, inactive, Fam H x
o Other Risk Factors – albuminuria, homocysteine, lipidemia, Ca/P probs, oxidative stress
 Other Common Complications – inflammation, bone prob. (Ca/P), anemia, fluid/electrolyte imbalances
 More complications – include infections, neuromuscular, depression, hyperlipidemia, insulin resistance
 Malnutrition – CKD patients have hyperalbuminuria  hypoalbuminemia, Fe deficiency, weight loss… starting in stage 3;
decreased protein intake, nausea, vomiting, gastroparesis, abnormal protein metabolism, low-protein diets
CKD & Solute Handling
 Na+ - doesn’t change throughout any stage of CKD
 K+, PO4, urate – can increase in very late stages (<25% GFR) of CKD
 Urea, creatinine – increase throughout most of progression (<50% GFR) of CKD
Metaboic Acidosis
 Primary mechanisms – retention of organic acids, renal tubular acidosis (due to decreased ammonium production)
 H+ buffering by bone – decreased bone mineral, catabolic, inhibits normal growth in children
 Bone effects – increased osteoclastic and decreased osteoblastic activity
 Mineralization and extraskeletal calcification
Screening
 Recommended – diabetics, HTN, CVD
 Considered - >55yo, fam hx, exposure to drugs, certain cancers, infections (histo, TB), CT diseases, obesity, dyslipidemia,
anemia, gout/hyperuricemia
 Universal screening – not recommended
NKF CKD STAGES
Clinical Action Plan
Stage
Description
GFR
Action
ml/min/1.73 m2
At increased risk
>60
with CKD risk factors
Screening
CKD risk reduction
1
Kidney damage with
mildly decreased GFR
>90
Diagnosis & treatment
Treatment of comorbidities
Slowing progression
CVD risk reduction
2
Kidney damage with
mildly decreased GFR
60–89
Estimating progression
3
Moderately decreased
GFR
30–59
Evaluating and treating
complications
4
Severely decreased
GFR
15–29
Preparation for kidney
replacement therapy
5
Kidney failure
<15
(or dialysis)
Kidney replacement
therapy if uremic
National Kidney Foundation
CKD Management
 Acute vs. Chronic CKD – treatment decisions based on if CKD is acute/chronic:
o Acute CKD – assume this until disproven… can be reversed
o Chronic CKD – patient will have sallow complexion, skin/nail change, GFR trend, tubular casts, reduced kidney
size, presence of chronic anemia, 2o hyper-PTH
 Reversible Causes of CKD – can be pre-renal, renal, or post-renal:
o Pre-renal – systemic; hypotension/hypovolemia, CHF, liver failure, vasoconstriction
o Renal – worsening underlying renal disease, nephrotoxicity (to contrast dye)
o Post-renal – distal to kidneys, including urinary tract obstruction
 Slow Progression – GFR decline may be inevitable, but can slow this progression in several ways
o Strict BP Control – ACEIs, ARBs, salt restriction, diuretics (HCTZ GFR >40, Loop <40)  below 130/80, but
avoid hypotension too; absolute must to use ACEI/ARB in diabetics, still good for non-diabetics
o Glycemic Control – in diabetics
o Other Interventions – aldosterone blockade, lipid therapy (statins)
 Nutrition
o Calories – 30-35 kcal/kg
o Sodium restricition - ~2gm/day
o Potassium (2 g/day), phosphorus (800-1000 mg/day), exercise
o Protein restriction – unless under strict monitoring, don’t limit b/c of malnutrition risk
CKD & Anemia
 Onset – anemia usually becomes prevalent at GFR < 60; very high prevalence with CKD
 Indicator – anemia predictive of CKD progression, CV Disease, hospitalization, death
 Erythropoetin (EPO) Deficiency – main caused of CKD anemia, from low synthesis (idiopathic)
 Other Causes – lack diet Fe, vitamin deficient (B12, Folate, C), inflammation, blood loss, shorter RBC life
 Consequences – decreases performance leading to increased compensatory measures:
o Decreased performance – cardiac function, cognitive function, exercise, quality of life
o Increased compensation – cardiac output, LVH, transfusions needed
 Treatment – give erythropoesis stimulating agent (ESA) when Hb < 10-11
 ESA Controversy – if Hb target is set too high with ESA, higher mortality!  currently studied
ESRD
 ESRD Preparation – accomplished through patient education, dialysis/x-plant preparation
o Patient education – explain ESRD process, counseling… optimal referral time GFR < 30
o Hemodialysis preparation – figure out fistula (vascular access) placement
o Peritoneal dialysis preparation – place peritoneal catheter, prepare PD training
o Renal Transplant preparation – find living donor ideally…