CKD and Management

8/3/2019 CKD and Management

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Renal circulation

Arteries (down) Veins (up)

Abdominal aorta Vena cava

Renal artery Renal vein

Segmental arteries -

Lobar arteries -

Interlobar artery Interlobar vein

Arcuate arteries Arcuate vein

Interlobular artery Interlobular vein

Afferent arterioles Efferent arterioles

Glomerulus Glomerulus


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100 times greater blood flow than otherorgans of the body

25 % of the total blood flow

>90% of blood passes through theglomerulus

Cortical glomeruli:

High pressure capillary network inglomerulus.

Blood flowing through the peritubuler

capillary is deprived of water content


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Two successive capillary network More RBC in cortical glomeruli

Uneven blood flow

Juxta medullary Glomerulus: Not affected by systemic BP

Less oxygen is required for medulla

Blood flow to kidney is regulated by RASand by Na concentration in DCT (Macula

densa)


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What is kidney damage ?

Structural abnormalities:

Pathological, Radiological

Functional abnormalities:

Composition of blood and/or urine


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Urine Protein Urinary protein >150mg/day abnormal

Urinary Albumin >30 mg/day abnormal

Micro-albumin30-300mg/day(Measured using

ELISA or radio-immunoassay)

Albumin >300mg/day can be measured bydipstick or albustix.

Dipsticks are semiquantitative. As a rough

guide .Trace ~ 0.15-0.3 g/L....+ ~0.3 g/L

.++ ~ 1 g/L

....+++ ~ 2.5-5 g/L

.++++ >10 g/L


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Albumin:Creatinine Ratio

First morning sample is usually preferable

Urinay excretion of creatinine is

constant(~10 mmol/day)

If urine albumin is 30 mg/day to 300mg/day ACR will be 3 to 30

mg/mmolMicro-albuminuria

If>300 mg to < 3500 mg then ACR is >30 to < 350 mg/mmol Overt Proteinuria

If ACR >350 mg/mmol Nephrotic


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Urine RBC

Haematuria 2 rbc/hpf in spun urine

Dipsticks are as sensitive as microscopy

Microscopy is the gold standard

Dysmorphic RBC indicates glomerular

bleeding.


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Cell/Casts

Leucocytes - May be a feature ofTIN Lymphocytes feature ofChronic TIN

Eosinophils(hansels or wrights stain)-

associated with TIN, also possible inRPGN.

Renal tubular cells- ATN, TIN

Casts are Tamm-Horsfall mucoproteinwithin the renal tubules conferring a

characteristic cylindrical shape.


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Hyaline casts: nonspecific

Granular casts: most of the time non-

specific

Red cell cast: Diagnostic of GN

WBC casts: Acute PN and TIN


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Blood tests

S. Creatinine convenient indirect

measure of GFR- derived from metabolism

of creatine in skeletal muscle. Little short

term variation.

S. Urea disproportionate increase in pre-

renal renal dysfunction


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What is GFR ?

Volume of plasma filtered by all nephrons

of both kidneys per minute.

1.2 millions of nephrons in each kidney.

MW- 65,000 daltons


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Creatinine clearance = Y ml/min

Plasma concentration of creatinine = 1

mg/dl=0.01 mg/ml Urine volume in 24 hrs = 1440 ml

Urine concen. of creatinine = 1 mg/ml

Amount of creat in urine= 1440 ml x 1 mg/ml=1440 mg

Y ml/min x [24x 60] min x 0.01 mg/ml =

1440 mg Y ml/min x 1440 min x 0.01 mg/ml = 1440 mg

1440 Y ml x 0.01 mg/ml = 1440 mg

14.40 Y mg = 1440 mg > Y =1440/14.40=100


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Decreased GFR without kidney damage:

Individuals with GFR 60 to 89 mL/min/1.73 m2

without kidney damage are classified as

decreased GF

R. Older patient (global glomerular sclerosis and

cortical atrophy).

Vegetarian diets, unilateral nephrectomy,

extracellular fluid volume depletion, and systemicillnesses associated with reduced kidney

perfusion, such as heart failure and cirrhosis


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In 2002, K/DOQI: Stage 1: Kidney damage with normal or increased GFR (>90

mL/min/1.73 m2) Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2)

Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2)

Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2)

Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m2 ordialysis)

In stage 1 and stage 2 chronic kidney disease, GFR alone

does not clinch the diagnosis. Other markers of kidney

damage, including abnormalities in the composition of bloodor urine or abnormalities on imaging studies, should also be

present in establishing a diagnosis of stage 1 and stage 2

chronic kidney disease.


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Pathophysiology

In the face of renal injury (regardless of the

etiology), the kidney has an innate ability to

maintain GFR, despite progressive

destruction of nephrons, by hyperfiltration

and compensatory hypertrophy of the

remaining healthy nephrons.


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The hyperfiltration and hypertrophy of

residual nephrons, a major cause of

progressive renal dysfunction.

This is believed to occur because ofincreased glomerular capillary pressure,

which damages the capillaries and leads

initially to secondary focal and segmentalglomerulosclerosis and eventually to global

glomerulosclerosis.


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Factors other than the underlying disease process and

Glomerular hypertension that may cause progressive renal

injury include the following:

Systemic hypertension

Acute insults from nephrotoxins or decreased perfusion

Proteinuria

Increased renal ammoniagenesis with interstitial injury

Hyperlipidemia

Hyperphosphatemia with calcium phosphate deposition

Decreased levels of nitrous oxide

Smoking

Uncontrolled diabetes


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Hyperkalemia

No hyperkelaemia if both aldosterone secretion anddistal flow are maintained. Another defense against

potassium retention in patients with chronic kidney

disease is increased potassium excretion in the GI tract,

which also is under control of aldosterone.

Therefore, hyperkalemia usually develops when the GFR

falls to less than 15-20 mL/min .

potassium-rich diet or if serum aldosterone levels are

low,

use of angiotensin-converting enzyme (ACE) inhibitorsor

nonsteroidal anti-inflammatory drugs (NSAIDs).

acidemia or from lack of insulin


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Metabolic acidosis unable to produce enough ammonia in the proximal tubules

to excrete the endogenous acid into the urine in the form ofammonium.

In chronic kidney disease stage 5, accumulation of

phosphates, sulfates, and other organic anions are the

cause of the increase in anion gap.

Metabolic acidosis has been shown to have

deleterious effects on protein balance-

Negative nitrogen balance

Increased protein degradation Increased essential amino acid oxidation

Reduced albumin synthesis

Lack of adaptation to a low protein diet


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Hence, metabolic acidosis is associated with protein-

energy malnutrition, loss of lean body mass, and

muscle weakness.

However, this leads to an increase in fibrosis andrapid progression of kidney disease.

Metabolic acidosis is a factor in the development of

renal osteodystrophy.

Acidosis may interfere with vitamin D metabolism,

and patients who are persistently more acidotic are

more likely to have osteomalacia or low-turnover

bone disease.


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Salt and water handling abnormalities

Extracellular volume expansion and total-body

volume overload results from failure of sodium and

free water excretion.

This generally becomes clinically manifest when

the GFR falls to less than 10-15 mL/min, whencompensatory mechanisms have become

exhausted.


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Anemia Normochromic normocytic anemia

principally develops from decreased renal synthesis of

erythropoietin

No reticulocyte response occurs.

EPO is produced by peritubular interstitial fibroblasts in

the outer renal medulla and deep cortex of the kidney.

Several mechanisms are implicated, including:

relative deficiency of erythropoietin

diminished erythropoiesis due to toxic effects of uraemia on

marrow precursor cells reduced red cell survival

increased blood loss due to capillary fragility and poor platelet

function

reduced dietary intake and absorption and utilisation of iron.


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Renal osteodystrophy

Combination of

Osteomalacia(Low ca and vit D) osteitis fibrosa ( high PTH)

Osteoporosis ( co-exist with low or high

turnover disease)

osteosclerosis


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Silent crippler

Calcium containing binders/Vitamin D/ Calcimimetics

Low turn overLow turn over High turnoverHigh turnoverPTH

Adynamic

bone

Adynamic

bone

OsteomalaciaOsteomalacia

450 pg/ml

Osteitis

fibrosa

Osteitis

fibrosa

Mild

SHPT

Mild

SHPT

Normal bone

turn over

Normal bone

turn over

Spectrum of renal bone disease


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C/F of renal osteodystrophy

Initially asymptomatic

Later Bone pain, arthralgia, muscle

weakness, pruritis(cutaneous calciumphosphate deposition), bony deformity.

Fracture

Adynamic bone dis-order-asymptomatic, high calcium

CV risk soft tissue and cardiac

calcification


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Treatment

Dietary phosphate restriction

Phos Binders(Aluminium

hydrochloride,CCPB,sevelamerHcl andLanthanum carbonate)

Removal through adequate dialysis

Vitamin D analogs Ca salt

Calcimimetic agents


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Tertiary Hyperparathyroidism is essentially

secondary hyperparathyroidism that is no

longer responsive to medications.

Also occurs after renal transplant, where

hypertrophied glands continue to

oversecrete PTH (set point alteration)

May require surger


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Diagnosis ofCKD

eGFR if less ARF untill otherwise

proved.

USG

S. Ca and S. phosphate

S. creatinine persistently high


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Halting progression ofCKD

Progression ofCKD is more often due to

secondary haemodynamic and metabolic

factors, than underlying disease actvity

Factors

Non-modifiable- underlying cause, race

Modifiable level of proteinuria, drugs,

disease activity, hypovolaemia, dyslipidaemia,

hyperphosphatemia,DM, Smoking


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Management

CKD stage 1-3 Small portion to ESRD

CV risk reduction should be emphasized

Stage 1,2 at least annual f/u Stage 3 at least 6 monthly f/u- ifHb < 11

gm/dl and S. ferritin level < 100 mg/dl then

start PO iron. Also do B12 and folate. Check S. ca and s. po4 and PTH annualy

IfPTH> 70 pg/ml - treat


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When to refer to a nephrologist ?

eGFR < 30 ml/min/ 1.73 m square

eGFR < 60 ml/min/1.73 m square and any of

Progressive fall ( >10 ml/min/m square in 2 successive years)

Microscopic haematuria

Proteinuria(ACR > 70mg/mmol)

>15% decline in eGFR with commencement of an ACEI andARB (? Renovascular disease)

Possiblesystemic illness(SLE, Myeloma)

PTH>70 pg/ml

eGFR > 60 ml/min/ 1.73 m square and

ACR >70gm/mmol

Abnormal renal imaging

Familly history of renal disease

Suspected ARF


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Complications ofCKD

Fluid overload

Salt losing state

Weight reduction < 0.5 to 1 kg/day

Hyperkakaemia Acidosis

Bone

Metabolism

Effects on Resp. system

Hyperkalaemia

Ionized Ca

Nutrition


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Uraemia

Many remains un-identified

Inflammation and oxidative stress,atherogenesis,

immune system disruption and anaemia.

Divided into small and middle molecules

< 500 d and >500 d

Middle molecules include-

B-2 microglobulin 12000d

Light chains

Complement factor D

cytokines


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When to start dialysis ?

GFR < 15 with uraemic symptoms

GFR < 10 with or without symptoms

Refractoryhyperkalaemia,acidosis,pulmonary

edema,pericarditis,encephalopathyand

neuropathy

Pre-emptive transplantation is the

treatment of choice. Consider when GFR

is

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CKD and Management

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