Know more about chronic kidney disease

Chronic kidney disease- introduction:

CKD: decrease number of functioning nephrons

GFR: single nephrons GFR * number of functional nephrons

Interstitial fibrosis tubular atrophy glomerular sclerosis

TGF- beta: key molecule in pathogenesis of CKD

Chronic kidney disease- causes:

Causes of CKD	Rate of fall of GFR
Diabetic nephropathy	8-10 ml/min/year
Chronic glomerular nephropathy	6-8 ml/min/year
Ischemic nephropathy	4-6 ml/min/year
Chronic tubule-interstitial disease	2-4 ml/min/year

Grading of CKD:

Grades	GFR
Grade 5	< 15 ml/min (End stage renal disease)
Grade 4	15 – 29 ml/min
Grade 3	30 – 59 ml/min
Grade 2	60 – 89 ml/min
Grade 1	>90 ml/min

Determinants of GFR:

Decrease nephron number causes increase intra glomerular pressure. Which result in increase in pore size of nephron. It gradually causes leakage of proteins.

Proteinuria – accumulation of proteins in podocyte ( angiotensin 2 mediated )

Decrease gene actctivation

TGF – beta

Chronic kidney disease – approach :

A – Anemia , access , acidosis
B – bone mineral disease , blood pressure
C – cardiac
D – dry weight , diuretic use
E – electrolytes: Na , K , Ca , P

Uremia:

Creatinine and urea : largely depend on GFR for excretion. An inverse relation with GFR.
Phosphorus, uric acid, K ,H : tubules increase excretion as GFR declines. Either by excretion or decrease absorption.
Na ( normal throughout CKD ): rate of excretion of Na per surviving nephron increase.

Access:

AV fistula : least chance of infection. Take 6 weeks for maturation.
AV graft
Catheter : right IJV
Temporary or cuffed tunnelled permanent catheter. Risk of infection.

Anemia in CKD:

< 12g/dl in male or < 11g/dl in female is anemia in CKD patient.

Target Hb to be achieved – 11g/dl

Anemia start appearing in CKD grade 3 onwards.

Anemia leads to progression of LVH, which result in to diastolic heart failure. Which finally results in to increase cardiovascular mortality. Anemia independently decrease GFR.

Causes for anemia in CKD:

Absolute or relative deficiency of erythropoietin.
Erythropoietin: produce from cortical and outer medullary peritubular interstitial fibroblasts.
Anemia of chronic disease.
Nutritional deficiency: iron deficiency anemia, folic acid , etc.
Decrease red cell survival time in CKD.
Increase PTH : bone marrow fibrosis.
Uremia: bleeding

Investigations of anemia in CKD:

Pleuripotent hematopoetic stem cells – blood forming unit erythroid – colony forming unit erythroid – normoblast – reticulocyte – RBC

CKD patient with Hg 7.5 g/dl

Total leucocyte count − Normal

Platelets – Normal

Hypo-proliferative
Reticulocytes production index < 2
Hyper-proliferative
Reticulocyte production index > 2
RPI= Hg of patient/ target Hg *reticulocytes/2
MCV < 100 Fl
Serum ferritin – iron store – decreased
Serum ferritin – iron in circulation bound to transferrin – decrease
TIBC – decrease
% saturation of transferrin = decreased < 33%

Management of anemia in CKD:

Parenteral iron formulations:

Iron sucrose 200mg
Ferric carboxymaltose
Ferric isomaltose

Erythropoietin therapy:

Recombinant human EPO- EPO alpha: 1^st generation
50 unit/kg/week
Darbepoetin alpha : 2^nd generation
Methoxy polyethylene glycol beta

CKD – acidosis and blood pressure:

H + NH3 – NH4 : major form of acid excretion.

Up to grade 5 CKD : normal anion gap acidosis (NAGMA)

Grade 5 CKD : HAGMA + NAGMA

Issues with acidosis :

Depression mayocardium
Promotes calcification
Diastolic disfunction

Blood pressure:

Blood pressure target in CKD : < 130/80

Preferred combination for treatment: ACE inhibitor or ARB + Ca channel blocker

24 hr ambulatory BP monitoring : preferred in CKD patients.

Bone mineral disease:

90% -high bone turnover – osteitis fibrosa cystica.

10% – low bone turnover – adynamic bone disease.

Phosphorus – normal endothelial cells – osteoblast – trap calcium.

Normal level of phosphorus : 2.5 -4.5 mg/dl.

>5.5 mg/dl

Osteocytes – FGF – 23 – inhibit reabsorption of phosphorus through klotho receptors. It causes resistance to phosphorus. It result in to hyperphosphatemia. Which ultimately present with calcification.

High bone turnover state :

Decrease calcium
Increase phosphorus
Increase PTH – secondary hyperparathyroidism
Increase bone formation
Increase bone resorption
No time for mineralisation

Ca(OH)2 Appatite – CaPO4

↓

Early fracture

Bone pain

Resorbed bone replaced by : bone + cyst + fibrous tissue

Osteitis fibrosa cystica

Low bone turnover state / adynamic bone disease : (PTH< 200pg/ml)

Increase calcium supplements
Drugs decrease PTH , increase calcium
High Ca dialysate

Increase risk of calcification.

Management of high and low bone turnover state in CKD:

Treatment of high bone turnover:

Correction of hyperphosphatemia:

Pure phosphat binders: sevelamer , lanthanum, sucroferric oxyhydroxide

Calcium containing phosphate binders : in decreased calcium states : calcium acetate and CaCO3

Increase Ca , increase PTH : cincalcet – calcium sensing receptors agonist

Increase PTH

↲ ↳

Secondary hyperparathyroidism tertiary hyperparathyroidism

Decrease calcium PTH (>1500pg/ml)

Increase PTH increase calcium

Increase phosphorus increase phosphorus

Treatment of low bone turnover state : cutoff all calcium supplements

Cardiac manifestation in CKD:

ACS – most common death in CKD

Rate of rise of trop 1 : most preferred marker.

LVH : diastolic dysfunction
Calcification : irreversible
Uremic toxins : asymmetric dimethyl arginine
Malnutrition inflammation atherosclerosis
Increased Oxidized LDL , increased small dense LDL

Sudden cardiac death : hyperkalemia

Cardiac evolution in CKD :

Trop 1
Standard ECHO
Dobutamine stress test ECHO
Angiogram

CKD – diuretic and electrolytes:

Diuretics:

Furosemide or torsemide

Diuretics resistance : tubular epithelial cells are clogged with uremic toxins

↓

Drug doesn’t enter lumen

Electrolytes:

K : causes sudden cardiac death

P : can convert vascular endothelial cells into osteoblast

↓

Calcification

Uremia:

uremic encephalopathy : 100% response to dialysis.

Uremic pruritus.

Uremic pericarditis – heparin free intensive dialysis .

Uremic gastritis.