Systemic disease in End-Stage Renal Disease

Systemic disease in patients with end stage renal disease 腎臟科 邱炳芳  Renal failure itself or renal replacement therapy influence Topics  SLE  Liver cirrhosis  COPD  DM SLE in End-Stage Renal Disease Lupus Activity 【Am J of medicine July 1996 】 Clinical activity： 1 year：55% 5 10% 10 0% 【AJKD Jan,1993】 mechanism of  activity of SLE following onset of ESRD  cellular and humoral immunity （result of uremia） removal of lupus factor by dialysis lack of renally producted mediator immune complex phagocyted in lung during dialysis natural end point of SLE 【Am J of medicine July 1996 】【AJKD Jan,1993】 mortality   mortality   old age rapid progression of renal failure with clinical lupus activity cause of mortality【AJKD Jan,1993】  < 3 months：infection ，florid SLE > 3 months：infection ，cardiovascular disease Non-lupus：5 years svrvival 60% 【Am J of medicine July 1996 】 Presentation of flare up of lupus in ESRD factors that influence the lupus flare up in ESRD   method of dialysis： PD >  HD young age at diagnosis & initiation of dialysis【J of Rheumatology Feb, 1998】 21 11  Hx of seizure（cerebral vasculitis）【J of Rheumatology Feb, 1998】  Pregnancy 【nephron 1997】  black race and low socioeconomic state 【AJKD 1999】 Serological parameter B C3：812+- 214 （pre-HD） 382+- 105（post-HD） C4：184+- 46 （pre-HD） 102+- 33（post-HD） Transplantation ：【KI 1996】 allograft loss in patient with SLE Conclusion:  Lupus activity may persisted for 5 years after ESRD  mortality：as others <3 Month： Lupus activity > 3 Month：as others  Presentation：polyarthritis , fever , ± serositis  Serological parameter：C3, C4, Ds-DNA  Tx: steroid , NSAID Dialysis in patients with liver and renal failure 1.Ccr GFR ??? •Scr,measured and calculated Ccr all significantly overestimate GFR cause： •decreased hepatic creatine synthesis •increased tubular creatinine secretion •decreased skeletal muscle mass. (Am J Kidney Dis 41:269-278) 2. Dz NH3  Ammonia production： •liver（main）, skeletal m, brain, and kidney dietary or cellular proteins transamination to yield Lglutamate oxidative deamination by L-glutamate dehydrogenase (Figure 1 ). •Colon: bacteria degradate peptides and urea by deaminases and ureases •nonoxidative deamination of amino acids and adenosine plus the oxidation of physiologic amines( epinephrine and dopamine )  Ammonia (NH3) ：diffuses freely across lipid membranes ammonium (NH4+) ： not readily penetrate membrane  physiologic pH ：98.5% ammonium (NH4+) Alkalemia ： diffusion into the brain (and other tissues)  hypokalemia：intra-tubular acidosis uptake glutamine from medullary capillary renal ammoniogenesis precipitate encephalopathy in patients with liver disease （figure2）（figure3） Coagulation in liver failure patient： • deficiency of coagulation factor ；thrombocytopenia； low grade fibrinolysis with/without DIC antiaoagulation free if predilution in CRRT • endotoxin activate the endothelial cell and macrophage to release the tissue factor  intrinsic pathway   thrombosis • antithrombin III and heparine cofactor II less effect of heparin • prostacyclin，serine protease inhibitors ( nafamostat maleate （anti-inflammation and thrombosis）and kallikrein （inflammation） ) ESRD patient with tense ascite secondary to decompensated liver cirrhosis Effective method to remove the intra-abdominal fluid in uremic patient： • therapeutic paracentesis with/without albumin infusion • PD • slow ultrafiltration with prolong duration • peritoneovenous shunt • portosystemic shunt • ascites ultrafiltration • ascites reinfusion-ultrafiltration dialysis (ARD)  Peritoneal Dialysis：【Adv Perit Dial 1994;10:73-6】【Perit Dial Int 1996;16 Suppl 1:】 a. disadvantage： 1.Risk of peritonitis     indwelling of Tenckhoff catheter GNB, streptococci and listeria predominant HIV + , immunosuppressed due to lupus or myeloma pathogenetic mechanisms：   translocation of bacteria from the gut to the mesenteric lymph nodes bacteremia from general abnormal host defense mechanisms.  Local factors：intrahepatic shunting and the impairment of bactericidal activity in ascitics 2. Protein loss： 3. serum lactate（metformine 、advanced liver disease、 thiamine deficiency） bicarbonate-based PD solution ( physioneal ) 4. undefined risk of reactivation lupus b. advantage： －improvement of dyspnea due to cardiac insufficiency and ascites －certain types of case (lupus with intractable vascular thrombosis, intolerance of ultrafiltration ) －Ring-larsen et al (1973)：17 Pt ，correction of electrolyte imbalance but there was no favored outcome －Wilkinson et al（1977）：84 Pt，effective in patient with ascites and possibily reversible liver disease 。but no benefit in patient with chronic progressive hepatic condition ( cirrhosis ) Transport of water and solutes in uremic patients with chronic hepatic disease in CAPD.【Advances in Peritoneal Dialysis. 6:23-5, 1990】【Adv Perit Dial 1996;12:39-42】  CLD patients showed 1). high or high average transport 2). increased UF： making the use of hypertonic bags unnecessary probably due to the influence of hepatic lymph production CLD patients can be managed either with CAPD or with short frequent exchanges（APD）  C. Hemodialysis  dialysate content：HCO3-，K （influence on encephalopathy）  dialysate Na： －high sodium profile－central pontine demyelination， ,inter-dialytic thirst and inter-dialytic BW gain  －low sodium profile－intradialytic hypotension  pre-dialytic hypotension （投影片 5）  intradialytic hypotension：inadequate dialysis  hypoxemia（hepatopulmonary syndrome，1/3 in CLD；atelectasia） C1. slow ultrafiltration with prolong duration   4 - 5 sessions per week high cost/compliance F.ascites ultrafiltration：【AJKD，Dec，1996】【AJ KD 1997 May;29(5):815】   use the same equiment as for ordinary hemodialysis， and incurring the same cost no hemodynamic instability  risk of DIC ? G.ascites reinfusion-ultrafiltration dialysis 【Nephrologie 2001;22(1):25-8】【AJ KD 1998 Jul;32(1):】      Reinject the ascites fluid into the arterial line, allowing its UF and control of its flow. less rapid and severe reappearance of ascites and correction of hypoalbuminemia less intradialytic hypotension no major complication satisfied adequency ( URR=67%) 透析患者與呼吸衰竭相關問題 a.Oxygenation b.Ventilation c.Lung edema and renal perfusion 衝突 a.oxygennation  生物相容性差透析膜低血氧 調高FiO2 b.Ventilation 同時存在呼吸酸及代謝酸中毒時 【Am J of Nephrology 2001 Sep-Oct】 透析液中 HCO3與身體酸中和 PCO2 intradialytic hypotension & 惡化respiration acidosis without invasive ventilation：risk of respiratory failure c.Lung edema and renal perfusion Lung edema：interstitial fluid Renal perfusion：intravascular effective volume •Crystal & colloid solution •Osmotic pressure & oncotic pressure •P osm = Total Osmo/ TBW=2 (Na + K)exchangeable / TBW PNa= (Na + K)exchangeable / TBW hypernatremia :TBW , exchangeable Na & K •Effective osmolality = tonicity Water distribution:  TBW= 0.6 x lean BW  ICF= 3/5 TBW ; ECF= 2/5 TBW (ECFNa)  interstitial fluid =3/4 ECF ; intra-vascular= ¼ ECF  effective vol (baroreceptor sensible) = 30 % intra-arterial (70% in vein )  aqueous phase = 93% intra-vascular Vol (7%:protein, lipid)  ＃ fluid challenge : free water < crystal < colloid  ＃ N/S : isotonic ? Question :hyper Na + Bun/Cr ↑ and edema ? ＃edema= interstial fluid expansion effective Vol : Bun/Cr Question : BW gain + hyper Na ? ＃third space (ICF & ECF):not equilibrium with ECF -intestine obstruction (GI tract) - pancreatitis (retroperitoneal space) - crush injury - peritonitis (peritoeum) , parapneumonic effusion - burn (subcutaneous) - venous system obstruction DM and ESRD A. RENAL HANDLING OF INSULIN IN NORMAL SUBJECT (KI ,1997 suppl 62)  normal：50% portal insulin elimination in liver ( first phase effect)  MW 6000 ：freely filtered  total renal insulin clearance＝60﹪by glomerular filtration and 40 ﹪secretion proximal tubular cell : endocytosis , into lysosomes , metabolized to amino acids  < 1 % of filtered insulin appears in the final urine. impaired during the renal failure  enhanced in subjects receiving exogenous insulin B. HANDLING OF INSULIN IN PATIENT WITH ESRD 1.increased peripheral insulin resistance  GFR <25 ml/min (11-43 ml/min)  skeletal m (leg ) is the primary site  possible mechanisms： －uremic toxin and excess PTH of intracellular GLUT-4 －insulin-stimulated translocation － insulin antagonist：glucagon ,Growth hormone pseudouridine, TNF- the insulin resistance －endothelin-1, －anemia：EPO  －metabolic acidosis 2.decreased insulin degradation  little change in the metabolic clearance rate of insulin in renal disease until substantial reduction in GFR  Increased peritubular insulin uptake to compensate for reduced filtration until the GFR has fallen to less than 15 to 20 mL/min  concomitant decline in hepatic insulin metabolism； reversed with adequate dialysis 3. blunted insulin secretion  suppress insulin release in chronic renal failure： －metabolic －excess acidosis of calcitriol (1,25-dihydroxyvitamin D) PTH ： or EPO：EPO increase insulin secretion －deficiency －Anemia 4.augmented hepatic glucose output  increased the hepatic gluconeogenesis in ESRD MONITORING GLYCEMIC CONTROL  hemoglobin A1c methods  affected by renal failure：column- and ion-exchange chromatography and agar gel electrophoresis. ∵ carbamylated Hb and interference in the presence of elevated concentrations of urea,  false elevations in the HbA1c level  not affected by renal failure：Boronate-agarose affinity chromatography ； thiobarbituric acid method adequate Glycemic control －fasting blood glucose is below 140 mg/dL (dialysis handbook 2th edit ) －one-hour postprandial value of less than 200 mg/dL －glycated hemoglobin：6 to 7 in type 1 diabetics； 7 to 8 in type 2 diabetics.  glucose tolerance test cannot be use to diagnose diabetes in dialysis patient  ↓resistance：exercise, EPO, correction of malnutrition & meta acidosis , low protein diet , supplyment with amino acid-keto acid supplements；start of dialysis (PD>HD) SPECIAL PROBLEM 1. Hyperglycemia  microvascular disease can cause erratic absorption of insulin from the subcutaneous tissue, particularly if the patient does not rotate injection sites 2. Severe hyperglycemia and ketoacidosis  hypovolemia and marked hyperosmolality do not occur since glucosuria & profound renal loss of potassium is absent in anuric individuals.  minimal symptoms, thirst，weight gain，pulmonary edema  TX： －fluid －low replacement：not important doses of intravenous insulin (commonly beginning concentrations must be monitored at a dose of 2 units/hour) －potassium 3. Hypoglycemia  exclusion insulin, oral hypoglycemic agent therapy, Propranolol, salicylates, and disopyramide  alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency.  Spontaneous uremic hypoglycemia －deficiency of precursors :alanine, of gluconeogenesis  deficient gluconeogenesis；concurrent hepatic disease  impaired glycogenolysis  diminished renal gluconeogenesis ( reduction in functioning renal mass )  impaired renal insulin degradation and clearance  deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon.  Postdialysis ；secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate  decreased caloric intake：underdialysis or occult infection or malignancy 4. Alternating hypoglycemia and hyperglycemia  patients often have gastroparesis & complicates the timing of insulin injections.  Delayed injection of insulin as meal ??? Thanks for your attention !