ภาวะแทรกซ้อนทางเมตะบอลิกในผู้ป่วยล้างไตทางช่องท้อง

1. Metabolic Complications in Patients
Ongoing Peritoneal dialysis
Piti Niyomsirivanich, MD.

2. Outlines
• Metabolic syndrome
• Hyperglycemia
• Dyslipidemia
• Protein loss
• Na
• K
• Mg and vascular calcification
• PO4
• Ca

3. Metabolic Syndrome
• Central obesity
• High blood pressure
• High triglyceride
• Low HDL-cholesterol
• Insulin resistance

4. Metabolic Syndrome

5. WHR = Waist hip ratio

6. ระบาดวิทยาของโรคอ้วนและภาวะ
ไตเสื่อม
• Ejerblad et al.
– BMI > 25 kg/m2  CKD 2-3 X
– BMI > 35 kgm2 c diabetes  17.7 X
• Hsu et al.
– BMI 25-29.9 kg/m2  1.87 X
– BMI 30-34.9 kg/m2  3.57 X
– BMI 35-39.9 kg/m2  6.12 X
– BMI > 40 kg/m2  7 X
• Central adiposity Versus Peripheral adiposity

7. Metabolic syndrome & kidney disease
• Chen et al.
– Metabolic syndrome
increase risks of kidney
disease 2.6 X
– 3 risk factors 3.38 X
– 4 risk factors 4.23 X
– 5 risk factor 5.85 X
• Palaniappan et al.
– Metabolic syndrome
increased risk
albuminurea

8. Mechanism of CKD in obesity with
metabolic syndrome
• Inflammation
• Renin angiotensin system
• Lipotoxicity
• Hemodynamic factors

9. Cytokine

10. Cytokine from adipose tissue

11. Cytokines
• 1. Leptin
– 167 amino acid
– Adipocyte-derived hormone
– More fat more leptin
– Pass Blood brain barrier
– Inhibit neuropeptide Y  decrease appetide

12. Leptin and Energy balance

13. Mechanism of leptin
Leptin
secrete via kidney

14. IL-6 and CRP
• Produced from visceral , peripheral tissue
• decrease cytokine signal and leptin
• Adiponectin
• Increase TGF-b1  kidney fibrosis
• Increased CRP from hepatocyte  metabolic
syndrome visceral adiposity and
atherosclerosis

15. TNF-a
• 26-kDa
• Macrophage
• Increased in metabolic syndrome
• Adipogenesis & lipogenesis

16. MCP-1
• Pro-inflammatory cytokines  macrophage
– Increased glucose uptake  insulin induced
insulin receptor tyrosine phosphorylation
insulin resistance

18. Adiponectin
• 30 kDa
• Produced from subcutaneous fat > visceral fat
• Insulin sensitizing , anti inflammatory , anti-
artherogenic
• Increased in thinner person
• Decreased in obesed person

19. RAS
• Obesity  increase renin , angiotensinogen ,
ACE , Angiotensin II , aldosterone
• Angiotensinogen , angiotensin II increase
adipocyte growth
–  lipogenesis , hepatic gluconeogenesis
,glycogenolysis
– Inh. Lipolysis , insulin dependent glucose uptake
•  metabolic syndrome

20. Conclusion

21. Metabolic syndrome in PD patient
• Cardiovascular death
• LANDMARK STUDY (Longtitudinal Assessment of Numerous Discrete Modification
of Atherosclerosis Risk in Kidney Disease)

22. FBM & CD-163 (pro-inflammatory marker)
Axelsson et al.

23. Treatment of metabolic syndrome
• Low glucose in dialysate  icodextrin
• Control blood sugar
• Reduced peritonitis  inflammation
• RAS blockage
• PPAR agonists (thiazolidinedione)  insulin
sensitizer
• HMG-CoA reductase
• Cardiovascular risks

24. Hyperglycemia

25. Insulin resistance in CAPD
• 1/3 of insulin renal excretion
• CKD  insulin resistance
– increased insulin
– Hyperparathyroidism
– Animia
– Malnutrition
• Osmitic agent (glucose) absorption
• Insulin resistance  decrease function of
lipoprotein lipase

26. Glucose absorption
• Osmotic agent
– Glucose : cheap , stable , non toxic
• Absorp across membrane
• 60-80% of dialysate absorbed
• Glucose absorption APD < CAPD (shorter duration)
• Glucose 100-150 g per day absorbed
– 500-800 kcal/day significant weight gain 5-10%
– Increase insulin secretion  insulin resistance atherosclerosis
– Required increase hypoglycemic drug
– Amino acids
– Polyglucose solution

27. Minimized glucose absorbtion
• Appropriate salt and water management
– Decrease need for hypertonic solutions
• Non-glucose based solutions

28. Target of glucose control
• FBS < 140 mg/dl
• 1 hr post prandial glucose < 200 mg/dl
• HbA1C 7-8 mg/dl
• Uremia  increased measure HbA1C
(Carbymylated hemoglobin)
– Differentiate
• borate-agarose affinity chromatography
• Thiobarbituric acid

29. Hypoglycemia agent
• Not recommend oral hypoglycemic drugs
• May use Thiazolidinediones
– Except CHF
• Subcutaneous insulin

30. Subcutaneous insulin
• No guidelines
• Icodextrin
– CPG  glucose dehydrogenase-
pyrroloquinolinequinone , glucose dye
oxidoreductase enzyme  over estimate due to
maltose in blood
• Accu-check , FreeStyle
– Recommend  glucose dehydrogenase-nicotinamide
adenine dinucleotide , glucose dehydrogenase flavin
adenine dinucleotide ,glucose oxidase instead

31. IP insulin
• adventage
– Absorbed via lymphatic system  constant delivery 1 ml/min
– Less variation among administration
– Lower dosage than other route
– Lesser Atheroscleosis risk
• Disadventage
– More expensive
– Decrease HDL in some small studies
– Infection
– Subcapsular liver steatonecrosis  insulin induced triglyceride
accumulation in liver
– Malignant omentum syndrome  require more insulin

32. Insulin dosage
• Mutiple subcutaneous injection
• Total insulin per day
• Divided
– 10% at night time
– 85-90% at day time /3
• Added 1 ,2 ,3 unit/l for 1.5%D 2.5%D 4.25%D
• FBS < 140 mg/dl , CBG tid pc 1 hr < 200 mg/dl
• CCPD , NIPD for high transporter (rapid glucose
absorption)
•

35. • IP insulin
– Stability
– Peak concentration 90-120 min
– 60% dose absorbed
• Direct Via tenckhoff catheter
– Peak concentration 15 min

36. TZDs
• Insulin sensitizer
– Troglitazone  withdrawed
– Rosiglitazone
– Pioglitazone
– Ciglitazone  animal study
– Englitazone  animal study
• Excretedliver

39. Dyslipidemia

40. Lipoprotein

41. Lipoprotein
• Chylomicrons
– largest
– GI lymphatic
– A-I , A-II , A-IV , B-48 , C-I , C-II , C-III , E
• Very low density lipoprotein
– Liver  circulation
– B-100 , C-I , C-II , C-III , E
• IDL
– VLDL Lipoprotein lipase  triglyceride >> IDL
– B-100 , C-III , E
• LDL
– IDL Hepatic triglyceride lipase LDL
– B-100 , C
• HDL
– A-I , A-II , C-I , C-II , C-III , D , E
– return

43. Lipid metabolism : endogenous PW

44. Atherogenicity of lipoprotein
• Esp. LDL , LP(a)
• Small LDL > large LDL
• Lipoprotein (a) increased in patients with
proteinuria
• HDL
– Uremia  acute phase response (IL-6, CRP) 
decreased HDL

45. Glomerular response to lipid
• Nephron loss  renal adaptation (ขยายขนาด)
•  increase single nephron GFR
–  glomerulosclerosis and interstitial fibrosis in long term
• Leakage of lipoprotein
– Increase mesangial cell cytokine , increased macrophage
– Macrophage  ROS
– ECM  increased matrix glomerulosclerosis
– Endothelial  NO + endothelin , thromboxane A2
– PTC  endocytosis , endothelin-1  cell death
• Endothelin -1  peritubular capillary vasoconstriction , fibroblast ,monocyte
– JG apparatus  renin  increase BP

46. Lipid metabolism abnormality due to
kidney disease
• Increase carbohydrate intake due to protein
restriction
• Lipoprotein lipase abnormality
– Insulin resistance ,
– High PTH , uremic toxin
– Low Erythopoietin (unknown mechanism)

47. Hypertriglyceridemia in patient w CKD w/wo dialysis

49. Treatment
• Diet
– Fat < 30% of total calories
– Poly:mono:sat = <0.7 : 1 : 1-1.5 (Nephrotic Syndrome , post KT)
– decreased calories , simple sugar (CKD)
– High fiber
– 35 kcal/kg/day in < 60 yo
– 30-35 kcal/kg/day in > 60 yo
• Exercise
• Medication

51. HMG-CoA reductase inhibitor
• Inhibit HMG-CoA reductase
• Decreased cholesterol by 20-30%
• CYP3A4 and CYP 2C9
• Atorvastatin & pravastatin  decrease dose
• Rosuvastatin90% excreted from kidney 
avoid
• Rhabdomyositis , hepatitis

53. Ezethimibe
• Inhibit dietary & biliary cholesterol absorption
• Decrease LDL 20%
– Total cholesterol 15%

54. Bile acid binding resins
• Not recommend in patients with uremia
(increased VLDL)
• Others
– Fish oilhigh dose , expensive
– ACTH  short term study long term??
– Sevalemer decrease P ,LDL, increase HDL
– L-carnitine cofactor FA into mitochondria
• Not recommend due to adverse effect to muscle ,blood
– Heparin HD decreased TG , cholesterol
– Dialysis membrane

55. Treatment for dyslipidemia in PD
• LDL/apoB protein
– The lower the better
– Statins
– No equivalent studies have been done in PD
– NKF (National kidney foundation) ,KDOQI
,International Society for Peritoneal dialysis
• Elevated LDL-c w/wo CAD
• PD with dyslipidemia Rx as nonuremic pt. c CAD

56. Elevated triglycerides
• Always found in association with other lipid and lipoprotein
abnormalities
• Carbohydrate loading from the dialysis solution 
hypertriglyceridemia
• Na and water Mx  minimize the use of hypertonic
solutions
• Alcohol increase triglycerides
• Triglyceride > 350 mg/ml Rx
• Fibrate
– (benzofibrate ,fenofibrate ,gemfibrozil)dose reduced by 25%
– Muscle enzyme

58. Low HDL-c
• Fibrate class  raises HDL
• Reducing cardiac morbidity and mortality has
not been established

59. Antioxidants
Vit E not proven to reduce CV events
No trials both PD and HD

60. Protein loss
• Protein 0.5 g/L of dialysate drainage
– May 10-20 g/day
• Amino acid loss 2-3 g/day
• Albumin
• IgG 15%
• Protein loss greatest in high and high-average transporters
• Peritonitis
• Nephrotic syndrome

61. Hyponatremia/hypernatremia
• Hyponatremias
–  excessive water drinker
– Hyperglycemia  translocational hyponatremia
– 1.3 mmol/L : 100 mg/dl of Na
• Hypernatremia
– Rapid UF more water than salt convects across
membrane
– Short dwell PD more likely hypernatremia
– Esp. low transporters

62. Hypokalemia / Hyperkalemia
• Hypokalemia  10%-30% of CAPD patients
– Associate poor potassium intake
– Diet
– K < 3 mmol/L  K supplement
• Hyperkalemia  non compliance , excessive K
intake

63. Hypercalcemia / hypocalcemia
• Ca 2.5 ,3.5 mEq/L
• 3.5 mEq/L  positive calcium balance
• 2.5 mEq/L  slightly negative balance of calcium
• Concerns about vascular calcification  lower 2.5 mEqL
• Hypercalcemia
– Large doses of calcium based phosphate binders
– Rx
• Non-cacium based phosphate binder
• Stop Vit-D
• Ca 2.5mEq/L solution of dialysate
• Hypocalcemia
– Not common due to use of calcium base phosphate binder & Vit D
– Rx
• Cacium & vitamin D
• Ca 3.5 mEq/L dialysate solution

64. Magnesium and vascular calcification
• Mg depletion  increased risk of
atherosclerosis and cardioevents
• Excess > deficiency
• Higher dialysate solution Mg  suppress PTH
 adynamic bone disease
• Optimum Mg in dialysate remain unknown

65. Hypophosphatemia/hyperphosphatemia
• Calcium based Phosphate binder , Sevalemer
–  fall in serum bicarbonate
• Amino acid based dialysis solution has been
reported to lower the serum bicarbonate level
in some patients