Ckd refrat

7/28/2019 Ckd refrat

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CKD


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KIDNEY DIDEASE

Prevalent in identifiable groups

Aging , > 50

DM

Hypertension

Cardiovascular disease, CVD

Family members

Herbal medicine (jamu), Analgetics


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Progression of CKD

Mechanisms of ongoing renal injury Deposition IC, Ag, Ab, matrix, collagen, fibroblasts

Intracapillary coagulation

Vascular necrosis

Hypertension & increased Pglom

Metabolic disturbances, e.g. DM, hyperlipidemia Continuous inflammation

Nephrocalcinosis ; dystrophic & metastatic

Loss of renal mass / nephrons

Ischemia; imbalance between renal energy demands and supply

Results in Glomerulosclerosis

Tubular atrophy

Interstitial fibrosis


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Figure 69.5A Antihypertensive regimens in

chronic kidney disease (CKD).

a,Algorithm 1: Initial antihypertensive therapy.

*Assumes nonpharmacologic therapy to control

blood pressure (BP) is in place (see text) and that the

patient does not have renovascular hypertension,

congestive heart failure, ischemic heart disease, orhypertensive urgency. This approach focuses on BP

control in proteinuric nephropathies, but is also

appropriate for hypertensive nephrosclerosis,

polycystic kidney disease, and interstitial

nephropathies. The suggestion to add a diuretic

before an angiotensin receptor blocker (ARB) is

arbitrary but can be justified by the evidence that adiuretic increases the antihypertensive effect of an

angiotensin-converting enzyme (ACE) inhibitor, is

often needed in chronic kidney disease to control

fluid retention, is inexpensive, and may increase the

renoprotective effects of the ACE inhibitor, ARB, or

the combination. Emphasize salt restriction in

autosomal dominant polycystic kidney disease rather

than diuretic therapy, which may promote cystgrowth. Details of diuretic therapy were discussed

previously.


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Figure 69.5B Antihypertensive regimens

in chronic kidney disease (CKD).. b,

Algorithm 2:

Recommended therapy if algorithm 1 fails to

control BP. *Diltiazem and verapamilsustained-release preparations are

recommended. Clonidine recommended for

individuals receiving insulin because it does

not greatly affect glucoregulation and for

those who have difficulty with a -blocker

(e.g., bronchospasm, cardiac

conduction). The -blocker/clonidinecombination is usually well tolerated, but

may cause bradycardia.


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Therapy CKD

Specific Therapy. depends on etiology &histopathology

Decrease proteinuria / albuminuria

Tightly control Blood Pressure < 125 / 75 ACE-I, ARB, non-dihydropyridine-CCB,.

Tightly control Blood Sugar

Manage hyperlipidemia Stop smoking

Low protein diet 0.6 0.8 g /kg BW/day


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Manage Anemia and other co morbidities,

Manage Cardiovascular ds,

Complications of decreased kidneyfunction

Preparation for kidney failure and RRT

Initiation of RRT


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Compensatory renal changes in

CKD

Hypertrophy of residual nephrons

Increased RBF per nephron, but

decreased total RBF

Increased Single Nephron GFR / SNGFR

Increased osmotic / solute load

Hyperfiltration

Increased intraglomerular pressure / Pglom


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## NEPHRONS

Pcap +flow

Glomerular Protein Glomerular

injury flux hyperfiltration

Glomerulosclerosis

## NEPHRONS


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Pattern of excretory adaptation

Increased filtered load; Cr, BUN Decreased tubular reabsorption; Na, H2O

Increased tubular secretion; K+, H+, Cr

Limitation of nephron adaptation Magnitude

Time, ~response to intake / load, production Abrupt changes in intake / production may not be

tolerated Trade off, expense to other systems E.g. to preserve P balance PTH increases


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Volume

Urine,

Uosm,

U(Na,K,H)


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Multiple mechanisms of chronichypoxia in the kidney.

Mechanisms of hypoxia in the kidney of chronic kidneydisease include loss of peritubular capillaries (A),

Decreased oxygen diffusion from peritubular capillariesto tubular and interstitial cells as a result of fibrosis of thekidney (B),

Stagnation of peritubular capillary blood flow induced bysclerosis of "parent" glomeruli (C),

Decreased peritubular capillary blood flow as a result ofimbalance of vasoactive substances (D),

Inappropriate energy usage as a result of uncoupling ofmitochondrial respiration induced by oxidative stress (E),

Increased metabolic demands of tubular cells (F), and

Decreased oxygen delivery as a result of anemia (G).


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Treatment modalities that target chronichypoxia in the kidney

Improvement of anemia by EPO

Preservation of peritubular capillary blood flow byblockade of the renin-angiotensin system

Protection of the vascular endothelium

VEGF Dextran sulfate

Antioxidants to improve the efficiency of cellularrespiration

HIF-based therapy (hypoxia inducible factor) Prolyl hydroxylase inhibitors Gene transfer of constitutively active HIF


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Intact nephron hypothesis Using experimental animals; urine from each kidney was collected seperately

Before After End

K1 K2 K1 K2 K2

GFR 50 50 55 14 24

NH3 excr 49 51 66 25 40

NH3 excr/100mlGFR 100 100 120 121 167

K2 was partially K1 removed

removed

Conclusion

-Normal renal tissue undergoes hypertrophy to compensate for loss offunctioning nephrons

-Normal tubules adapt, increase in function as other tubules are lost

-Diseased nephrons / tubules adapt in the same way ~

increase NH3 excr / 100mlGFR

-Even diseased nephrons can increase their GFR


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The Uremic Syndrome Nervous system

Impaired concentration, perceptual thinking, Peripheral neuropathy; primarily sensory, paresthesias, restless leg syndrome Autonomic neuropathy; impaired baroreceptor function, orthostatic hypotension, impaired

sweating Uremic encephalopathy

Hematology system Anemia is invariably present when renal function fall


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Cardiovascular system Cardiovascular disease is the leading cause of death in patients

with CKD stage 4-5 Accelerated Atherosclerosis / CAD

Hypertension, ~ 80% of all uremic patients

Pericarditis

Metabolic abnormalities Lipids; increase in tot. triglycerides, Lp(a), LDL, decrease HDL

Carbohydrate metabolism; insulin resistance, decreased needfor OAD / insulin in DM

High prolactin; galactorrhea

Men : testosteron is low, FSH / LH normal or high

Women: pg E2 & progesterone are low, FSH /LH normal orslightly elevated

Abnormalities of thyroid gland function test, normal TSH


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Figure 72.2 Relationship between hemoglobin(Hb) and estimated glomerular filtration rate

(GFR).

Data are from a cross-sectional survey of

individuals randomly selected from the general U.S.

population (NHANES III). Results and 95%

confidence interval are shown for males (a) and

females (b) at each estimated GFR interval.


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Clinical manifestation:

musculoskeletal symptoms

pruritus

metastatic calcification, vascular calcification & calcifilaxis


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Peripheral neuropathy e.g..: sensory loss, paresthesias, motor function loss

Autonomic neuropathy e.g. : orthostatic hypotension, arrhytmia, gastroparesis

Sleep disorders. Restless legs Syndrome


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