Challenges of glucose control in ckd
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The document discusses diabetes and kidney disease, emphasizing that diabetic patients can develop renal issues, including diabetic kidney disease and proteinuria. It highlights the effects of medications like linagliptin on albuminuria, showing significant reductions in levels over 24 weeks while maintaining GFR. Lastly, it addresses the management of extreme hyperglycemia in kidney disease patients, particularly focusing on insulin deficiencies and the risks associated with the use of icodextrin in diabetes management.
Challenges of glucose control in ckd
- 1. DDiiaabbeetteess aanndd KKiiddnneeyy Dr.Sampathkumar MD,DNB,DM,FRCP MMHRC 1
- 2. 22 ssiiddeess ooff tthhee ccooiinn 2
- 3. AALLLL ppaattiieennttss wwiitthh DDiiaabbeetteess aanndd PPrrootteeiinnuurriiaa//RReennaall ffaaiilluurree hhaavvee ddiiaabbeettiicc rreennaall ddiisseeaassee .. You may be wrong 50% of the times ! 3 Common Pitfall
- 4. IInnddiiccaattiioonnss ffoorr RReennaall BBiiooppssyy 4
- 5. DDiiaabbeettiicc NN aalloonngg wwiitthh IInnffeeccttiioonn rreellaatteedd GGNN
- 6. P Endocap. Prroolliiff ttoo 110000% ccrreesscceennttss
- 7. PPrrooggrreessssiivvee ggrraaddeess ooff CCKKDD 7
- 8. FFiillttrraattiioonn PPrreessssuurree ++1155 mmmm HHgg 8
- 9. DDiiaabbeettiicc gglloommeerruullaarr ddiisseeaassee FFlliittrraattiioonn PPrreessssuurree ++3355 9 80 mm
- 10. RReennaall aanndd ccvv rriisskk iinnccrreeaasseess oonnccee mmiiccrrooaallbbuummiinnuurriiaa ccrroosssseess 66 mmgg//gg Albuminuria Renal risk CV event 0-10 1 1 10-20 2.34 1.9 20-30 12.4 9.8 10
- 11. NNeeww ccllaassssiiffiiccaattiioonn ooff aallbbuummiinn eexxccrreettiioonn 11
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- 16. 16 CKD
- 17. 17 This patient develops KWD within 5 years though his Hb A1 c was 6.5 %
- 18. IInnssuulliinn ddyynnaammiiccss iinn CCKKDD 18
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- 21. IInnssuulliinn hhaallff lliiffee iinn CCKKDD 21
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- 25. UUssee ooff OOHHAAss iinn CCKKDD 25
- 26. MMeettffoorrmmiinn CCoonnttrroovveerrssyy iinn CCKKDD…….. 26
- 28. MMAALLAA-- MMeettffoorrmmiinn AAssssoocciiaatteedd LLaaccttiicc AAcciiddoossiiss • Decreased Utilisation vs hepatic dysfn ANAEROBIC GLYCOLYSIS SHOCK STATES LIVER DYSFN TYPE B METFORMIN Balance •2-10 per 100,000 patients receiving metformin /year •MALA accounts for 0.1-1% total patients admitted to ICU •Mortality is high – 30-50%
- 29. 22 ssiitteess wwhheerree MMeettffoorrmmiinn aaccttss 29
- 30. HHyyppootteennssiioonn rraatthheerr tthhaann mmeettffoorrmmiinn lleevveell wwhhiicchh ddeetteerrmmiinneedd LLaaccttaattee aaccccuummuullaattiioonn 30 Conclusion from this study
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- 32. SSFFUU iinn CCKKDD • Depends on Renal or Hepatic metabolism • Depends also on whether metabolites have hypoglycemic effects 32
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- 38. Drug exposure(AUC) in renal impairment ccoommppaarreedd ttoo ppaattiieennttss wwiitthh nnoorrmmaall rreennaall ffuunnccttiioonn Drug Mild RI Moderate RI Severe RI Hemodialysis Metformin NA NA NA NA Glibenclamide NA NA -45% NA M1+M2 Glimepiride M2 NA -55% +100% -55% +400% NA Repaglinide NA +19% +32% +32% Pioglitazone NA -17% to -43% 17% to -43% NA Sitagliptin +61% +126% +277% +350% Vildagliptin +40% +71% +100% NA Saxagliptin +16% +41% +108% NA (Active +67% +192% +347% NA metabolite) Alogliptin +70% +110% +220% +280% Linagliptin +29% +56% +41% +54% Exenatide -19% -3% NA +227% A.J Scheen. Expert Opinion on Drug Metabolism and Toxicology: 2013
- 39. Linagliptin in a recent study lowered aallbbuummiinnuurriiaa oonn ttoopp ooff ssttaannddaarrdd AACCEEii//AARRBB tthheerraappyy iinn ppaattiieennttss wwiitthh TT22DDMM Albuminuria Lowering by Linagliptin is independent of the Improvement in Glucose Linagliptin significantly lowers albuminuria on top of recommended standard treatment for diabetic nephropathy 24 weeks’ treatment Effect of linagliptin on albuminuria in humans* Adjusted mean change in albuminuria (24 weeks)1 Placebo Linagliptin 24 weeks’ treatment Effect of linagliptin on albuminuria in humans* Adjusted mean change in albuminuria (24 weeks)1 Placebo Linagliptin -29% in albuminuria vs placebo after 24 weeks’ treatment** potential for additional kidney benefit Proven renal safety with potential for additional kidney benefit 1. Inclusion criteria: Stable ACE/ARB background; albuminuria 30-3000 mg/g creatinine; GFR > 30. *Albuminuria-lowering evidence for linagliptinwill emerge from MARLINA 1218.89. **ADA 2012, 953-P 39 n 95% CI 59 -20%, +23% 168 -42%, -22% -4% -33% -29% p < 0.05 Albuminuria: Early marker for renal damage Marker for endothelial dysfunction Cardiovascular risk factor Lowering of albuminuria is associated with kidney & CV protection Definitions Microalbuminuria UACR ≥ 30 mg/g creatinine < 300 mg/g creatinine Macroalbuminuria UACR ≥ 300 mg/g creatinine -29% in albuminuria vs placebo after 24 weeks’ treatment** – Mean GFR remains unchanged after treatment initiation with linagliptin up to 24 weeks -29% in albuminuria vs placebo after 24 weeks’ treatment** lowers albuminuria on top of recommended diabetic nephropathy ACE/ARB background; albuminuria 30-3000 mg/g creatinine; GFR > 30. lowering evidence for linagliptinwill emerge from MARLINA 1218.89. **ADA 2012, 953-P n 95% CI 59 -20%, +23% 168 -42%, -22% -4% -33% -29% p < 0.05 -29% in albuminuria vs placebo after 24 weeks’ treatment** unchanged after treatment initiation with linagliptin up Possible mechanism: The reno-protective effect of linagliptin as studies in preclinical model Inhibition of podocyte damage and Inhibition of myofibroblast transformation Increased GLP-1 receptor expression
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- 42. EExxttrreemmee HHyyppeerrggllyycceemmiiaa iinn CCKKDD 42
- 43. CCaassee HHiissttoorryy • 67 yrs old male in altered sensorium • Type 2 Diabetes, CAD • On OHA for the past 5 y • Fever,Dysuria – 7 d • Pain abdoment -1 d • Altered sensorium – 12 h • On Glimepride, Metformin ,Metoprolol, Losartan, eplerenone,Asprin,atorvastatin
- 44. PPhhyy EExxaammiinnaattiioonn • Significant volume depletion • FEBRILE -101,RR 19 /PM • BP -100/70 • JVP-Collapsed • S1,S2 FAINT, Lung Bases - clear • Abdomen- Left Lumbar area tender • Catheter draining turbid urine • Drowsy, Neck supple,No FND,Plantar – Flexor Bil
- 45. LLaabb • Urine – Pus cells +++, Bacteria ++ • Hb – 9.8, TC – 18,300. P 84,L14,E2 • B.Sugar- 604, B Urea – 87,S.Creat-2.3 • Na -147,K – 6.2,Cl – 112, HCO3 – 18.PCO2- 35,pO2 -90 • Ketone body – neg • ABG - P H – 7.32 Pyuria Hyperglycemia Azotemia HyperNa,HyperK,Met.Acidosis
- 46. 3 major ggrraaddeess ooff iinnssuulliinn ddeeffiicciittss
- 47. WWHHYY IISS HHEE NNOOTT KKEETTOONNEEMMIICC
- 48. Calculated osm
- 49. ECF hyperosmolality pprroodduucceess IICCFF ddeehhyyddrraattiioonn RF PREVENTS GLYCOSURIA
- 50. ICF ECF K, P Na , G Urea Water Ethanol Insulin lack and hyperosmolality drives K outside
- 51. 6600 kkgg // 1100%% DDeeffiicciitt//NNaa 114477 6 / 3L 1 L/I hr 0.45 %Sal. H2O /po
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- 55. HHeemmooddiiaallyyssiiss ffoorr sseevveerree hhyyppeerrggllyycceemmiiaa iinn CCKKDD 55 Extreme hyperglycemia with ketoacidosis and hyperkalemia in a patient on chronic hemodialysis.Hemodial Int. 2008 Oct ; 12 Suppl 2:S43-7.
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- 57. CCAAPPDD ppaattiieenntt • Dialysate contains • Glucose in high • Concentration • Hyperglycemia severe and common 57
- 58. IIccooddeexxttrriinn uussee iinn ddiiaabbeettiicc ppaattiieenntt • Icodextrin is Polymer of Glucose • False high reading of Blood Glucose if • GDH/PQQ strips are used • Risk of iatrogenic hypoglycemia due to misdiagnosis and over reaction 58
- 60. PPoosstt ttrraannssppllaanntt DDiiaabbeetteess • Tacrolimus • Cyclosporine • Steroids • CMV • HCV • Metabolic syndrome 60
- 61. 4455 yyrrss ffeemmaallee ,, RReennaall TTXX iinn MMMMHHRRCC aatt 11999999..PPrreesseennttss wwiitthh pprrootteeiinnuurriiaa ,, eeddeemmaa 61
- 63. HHyyppooggllyycceemmiiaa VVss HHyyppeerrggllyycceemmiiaa iinn 63 CCKKDD-- TTiigghhtt rrooppee wwaallkk!! If he falls your reputation also falls !!
Editor's Notes
- #39: Slide 44, 45: Drug exposure (AUC) in renal impairment compared to patients with normal renal function The table summarizes the risk of supratheurapeutic levels of different oAD in different levels CKD. And thus requiring dose modification based on creatinine clearence.
- #40: In retrospective pooled analysis of type 2 DM patients with evidence of albuminuria, 80% being microalbuminuria. Linagliptin showed 29% RRR in albuminuria compared to placebo on top of the recommended ACE I/ARB therapy at the end of 24 weeks, this indicate potential for additional kidney benefit with renal safety. Slide 41: Linagliptin in a recent study lowered albuminuria on top of standard ACEi/ARB therapy in patients with T2DM This reduction in MA was rapid compared to the structural changes that can be appreciated. The reduction was independent of Blood pressure and blood glucose control.