Your SlideShare is downloading. ×
8-1. Progression of CKD to CRF. Vladimir Dlin (eng)
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Saving this for later?

Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime - even offline.

Text the download link to your phone

Standard text messaging rates apply

8-1. Progression of CKD to CRF. Vladimir Dlin (eng)

638
views

Published on

Published in: Health & Medicine

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
638
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
18
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Progression of chronic kidney diseases: mechanisms, risk factors, treatment strategies Dlin V.V., Konkova N.E. Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia
  • 2. History and conception of problem • The conception was developed at the beginning of XXI century by U.S. National Kidney Foundation (National Kidney Foundation) and published in 2002. It’s development was continued by experts from the European Dialysis and Transplant Association (ERA-EDTA) and KDIGO (Kidney Desease: Improving Global Outcomes) • The purpose of the conception: - early detection of kidney disease - slowing down the progression of kidney disease - reduction the risk of cardiovascular complications - prevention of kidney lesions - the use of common criteria and universal classification - the use of common terminology
  • 3. Importance of the problem The high prevalence of CKD in the world: 1-5 stage of CKD - 12-15% of the population 3-5 stage of CKD - 6-8 % of the population
  • 4. THE PREVALENCE OF CKD IN THE WORLD
  • 5. Importance of the problem Renal mortality in patients with kidney disease is low. Cardiovascular pathology as a major factor of patient’s death is ignored.
  • 6. Importance of the problem Renal factors of cardiovascular risk: albuminuria / proteinuria systemic inflammation oxidative stress anemia hyperhomocysteinemia Smirnov A. et al., 2005
  • 7. FREQUENCY OF CARDIOVASCULAR DISEASE IN CHRONIC KIDNEY DISEASE (per 100 patients / year) kidney diseases infarction disturbance of cerebral blood flow peripheral vasculopathy atheroscler osis cardiovascul ar death CKD - 1,6 7,6 6,9 14,1 5,5 CKD+ 3,9 16,6 19,9 35,7 17,7 CKD – chronic kidney disease C.R.. Harper, 2008
  • 8. FREQUENCY OF CARDIOVASCULAR DISEASE IN PATIENTS IN RELATION TO GLOMERULAR FILTRATION RATE the estimated frequency GFR – glomerular filtration rate Matthew R., 2005
  • 9. The structure of mortality (%) in patients with ESRD by age (Russian Register of renal replacement therapy, 1998-2007) CVD – cardiovascular disease
  • 10. The main markers of kidney damage, suggestive of the presence of CKD marker Albuminuria / proteinuria notes persistent increasing in urinary albumin excretion greater than 10 mg/day (10 mg albumin/g creatinine) – see recommendation hematuria, cylindruria, leykotsituriya (piura) Persistent changes of the urinary sediment Changes of renal imaging studies anomalies of the kidney cysts, hydronephrosis, resizing kidneys, etc. Changes of of blood and urine composition Persistent decrease of GFR less than 60 mL/min/1,73m2 Morphological changes of the lifetime nephrobiopsy changes in serum and urinary electrolyte concentration, impaired HGA and others, including the characteristic of the "tubular dysfunction syndrome" (Fanconi's syndrome, renal tubular acidosis, Bartter's syndrome and Gitelman, nephrogenic diabetes insipidus, etc.) in the absence of other markers of kidney damage should be taken into account the signs of “chronization” (sclerotic changes of kidneys, changes of membranes, etc.)
  • 11. Terminology • CKD - the common notion reflecting the presence of common risk factors of development and progression of different nephropathy. • The diagnosis of CKD is based on the presence of markers of kidney damage and/or GFR < 60 ml/ min for at least 3 months.
  • 12. Normal GFR in children and adolescents Age / Sex The average GFR ± σ (ml/min/1,73m2) 1 week 41 ± 15 2-8 weeks 66 ± 25 > 8 weeks 96 ± 22 2-12 years 133 ± 27 13-21 years(m) 140 ± 30 13-21 years(f) 126 ± 22
  • 13. Estimation of GFR • estimation of GFR in general clinical practice (outpatient) will be based of calculation formulas (eGFR), including gender, age, the patient and the concentration of creatinine in serum • clearance methods of GFR’s determination will be used at the hospital
  • 14. Methods of GFR’s estimation • Simple ways to calculate GFR based on measurements of serum parameters without hour urine collection: 1. Schwart’s formulas 2. Formulas of Cockroft DW., Gault MH. 3. MDRD (Modification of Diet in Renal Disease) 4. CKD-EPI method eGFR (the most suitable in the clinical practice) Levey AS. et al., 2000
  • 15. eGFR in children on the basis of serum creatinine and growth (according to Schwartz) • GFR (ml/min/1,73m2)= [0,0484*х Height (сm)]/Scr (mmol/l) *k= 0,0616 for boys >13 years
  • 16. CKD-EPI formula (modification of 2011 year) race gender Serum creatinine mg/100 ml formula White and other female ≤ 0.7 144*(0.993) Age*Cr/0.7)-0.328 White and other female > 0.7 144*(0.993)Age*Cr/0.7)-1.21 White and other male ≤ 0.9 141*(0.993) Age*Cr/0.9)-0.412
  • 17. Stages of CKD in based on GFR (National Kidney Foundation KD, 2002 in modification of Smirnov et al., 2008) stages Kidney function GFR ml/min/1,73 m2 С1 high and optimal >90 С2 slightly decreased 60-89 С3а moderately reduced 45-59 С3б significantly reduced 30-44 С4 drastically reduced 15-29 С5 ESRD <15
  • 18. Albuminuria • Albuminuria (normal < 10 mg/day) – integral sign of CKD [A. Smirnov et al., 2010] and represents: - increased permeability of cell membranes (size-selectivity, the chargeselectivity); - transport changes in the proximal tubule; - increased hemodynamic burden on the glomerules; - presence of systemic and renal endothelial dysfunction; - the degree of glomerular/interstitial sclerosis due to glomerular and tubular transport protein disturbances and subsequent activation of profibrotic cytokines • Albuminuria – risk factor of total and cardiovascular mortality, ESRD, acute kidney injury and progression of CKD
  • 19. Stage of albuminuria/proteinuria (Levey A.S. et al., 2010 ) urea albumine (mg/creatinine, g) Stage Kidney function А0 optimum А1 increased А2 high А3 very high <10 10-29 30-299 300-1999 А4 nephrotic ≥2000
  • 20. The stage of CKD should be indicated in the diagnosis after the nosologic form of renal disease Examples of diagnosis: • Kidney’s anomaly: a partial doubling of right renal pelvis. CKD C1A0 • Hypertensive nephrosclerosis. CKD C3aA1 • Focal segmental glomerulosclerosis. Nephrotic syndrome. CKD С3аА3 • IgA-nephropathy. Isolated urinary syndrome. CKD С1А3.
  • 21. Classification and characteristic of main risk factors of CKD type definition description increase susceptibility of factors increasing susceptibility to CKD kidney to damage older age, family history of CKD, low renal weight, low birth weight, racial and ethnic differences factors of initiation of CKD cause direct damage of kidneys diabetes, blood hypertension, autoimmune diseases, systemic infections, urinary tract infections, urinary stones, urinary tract obstruction, drug toxicity, genetic diseases factors of progression of CKD promote the progression of renal damage and accelerate the rate of decline in renal function high level of proteinuria, high blood pressure, poor control of blood glucose level in diabetic patients, dyslipidemia, smoking factors of ESRD increase morbidity and mortality in patients with ESRD inadequate dialysis (Kt/V); temporary vascular access, low albumin level, high levels of phosphorus and delayed treatment
  • 22. Risk factors of CKD nonmodifiable modifiable older age diabetes male sex blood hypertension low number of nephrons (low birth weight) autoimmune diseases racial and ethnic peculiarities chronic inflammation, systemic infections hereditary factors (including family history of CKD) urinary stones, urinary tract infection urinary tract obstruction drug toxicity high protein diet dyslipidemia smoking obesity/metabolic syndrome hyperhomocysteinemia pregnancy
  • 23. Factors of progression of CKD nonmodifiable modifiable older age persistent activity of the basic renal pathology male sex high levels: - systemic blood pressure - proteinuria low number of nephrons (low birth weight) uncontroled diabetes racial and ethnic peculiarities obesity/metabolic syndrome dyslipidemia smoking anemia metabolic acidosis pregnancy disturbed calcium-phosphorus metabolism (hyperparathyroidism) high protein and sodium diet
  • 24. CKD as independent risk factor for the development and progression of cardiovascular disease Groups of risk for cardiovascular disease: • group of intermediate risk - CKD stages C1-C2 and albuminuria A1; • group of high risk - CKD stages C1-C2 and albuminuria A2-A3 or CKD stage C3a, regardless of the level of albuminuria/proteinuria; • group of very high risk - CKD stages C3B - C5 regardless of the level of albuminuria/proteinuria
  • 25. RISK FACTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH CKD nonmodifiable: • gender, • age, • race, • genetic predisposition common modifiable: • blood hypertension • metabolic factors • endothelial dysfunction nephrogenic modifiable: • chronic inflammation • anemia • metabolic acidosis • hyperparathyroidism • hyperhomocysteinemia atherosclerosis heart disease
  • 26. The incidence of arterial hypertension in patients with chronic kidney disease (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) % 100 90 80 70 60 BH by Korotkov method BH by ABPM 50 40 30 20 10 0 SRNS AS Aspr ADPKD TMAP (HUS) RN SRNS – steroid resistant nephrotic syndrome AS – Alport syndrome ТМАP (HUS) – thrombotic microangiopathy (hemolytic uremic syndrome) AD PKD – autosomal-dominant polycystic kidney disease RN – reflux nephropathy
  • 27. PECULIARITIES OF RENAL ARTERIAL HYPERTENSION (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) RN RN TM AP AD (H PK U S) D TMAP (HUS) ADPKD AS AS SR N S SRNS 0% 50% nightly / daily BH 100% daily BP 0% 50% 100% diastolic / systolo-diastolic HP systolic HP SRNS – steroid resistant nephrotic syndrome AS – Alport syndrome ТМАP (HUS) – thrombotic microangiopathy (hemolytic uremic syndrome) AD PKD – autosomal-dominant polycystic kidney disease RN – reflux nephropathy
  • 28. FREQUENCY OF COMPLICATIONS OF ARTERIAL HYPERTENSION IN PATIENTS WITH PROGRESSIVE KIDNEY DISEASE (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) 100 80 60 62,5 40 44,4 20 0 40,0 30,4 17,4 SRNS angiopathy 33,3 28,6 23,1 4,5 11,8 AS Aspr ADPKD TMAP (HUS) RN left ventricular hypertrophy SRNS – steroid resistant nephrotic syndrome AS – Alport syndrome AD PKD – autosomal-dominant polycystic kidney disease ТМАP (HUS) – thrombotic microangiopathy (hemolytic uremic syndrome) RN – reflux nephropathy
  • 29. The risk of cardiovascular complications in children with steroidresistant nephrotic syndrome (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) data Left ventricular hypertrophy retinal angiopathy SRNS ≥ 4 years 2,8 2,7 the severity of blood hypertension (explicit) 9,7 0,56 systolo-diastolic blood hypertension 2,1 7,2 the lack of antihypertensive therapy 2,3 9,2 RR>2,0 – high risk of cardiovascular disease
  • 30. Primary prevention of CKD is the elimination or minimization of the risk factors for its development: • clinical supervision of patient from high-risk group; • the control of modifiable risk factors of development and progression of CKD; • control of GFR and albuminuria.
  • 31. Secondary prevention of CKD • slowing the progression of CKD (renoprotection) • preventing the development of cardiovascular disease (cardioprotection)
  • 32. Correction of common risk factors for the development and progression of renal and cardiovascular disease • • • • • • metabolic and hemodynamic changes glycemia dyslipidemia uricemia blood hypertension anemia
  • 33. Common approaches of primary and secondary prevention of CKD stage recommendations The presence of risk factors for CKD Regular screening for CKD, measures for reduction of the risk of development CKD С1 (normal renal function) Diagnosis and treatment of the kidney disease, correction of common risk factors of progression of CKD. Identification of CVD, correction of therapy, monitoring of risk factors of progression of CVD. С2 (initial reduction of GFR) previous measures + estimation of the rate of progression CKD, correction therapy С3 А и В (moderate reduction of GFR) previous measures + detection, prevention and treatment of systemic complications of renal dysfunction (anemia, dizelektrolitemiya, acidosis, hyperparathyroidism, hyperhomocysteinemia, etc) С4 (marked reduction of GFR) previous measures + preparations for renal replacement therapy С5 (ESRD) renal replacement therapy + identification, prevention and treatment of systemic complications of renal dysfunction
  • 34. Nephroprotective and cardioprotective therapy • • • • ACE inhibitors AT1-receptor blockers calcium channel blockers statins, etc.
  • 35. Treatment of blood hypertension in patients with chronic kidney disease medicines with nephroprotective effect • inhibitors of angiotensinconverting enzyme • blockers of ATII receptor type 1 • calcium channel blockers (nondihydropyridine)? medicines without nephroprotective effect • beta-blockers • diuretics • calcium channel blockers (dihydropyridine)
  • 36. Indications for ACE inhibitors and BRA in patients with CKD • in patients with blood hypertension (for achievation of target blood pressure levels) • in patients with albuminuria / proteinuria A2-A3 (even in the absence of hypertension)
  • 37. Antihypertensive therapy • If the target level of blood pressure was not achieved by ACE inhibitors and BRA it’s necessary to add the hypotensive medicine of other pharmacological groups and/or diuretics
  • 38. The hypotensive effectiveness of RAAS inhibitors in children with progressive kidney disease (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) 100 80 75,0 60 71,4 66,7 63,6 58,3 40 20 0 37,5 SRNS SA SRNS – steroid resistant nephrotic syndrome AS – Alport syndrome AD PKD – autosomal-dominant polycystic kidney disease Sapr ADPKD TMAP(HUS) RN ТМАP (HUS) – thrombotic microangiopathy (hemolytic uremic syndrome) RN – reflux nephropathy
  • 39. Antihypertensive therapy • Clinical predictor of renoprotective efficacy of the drugs is partial (daily proteinuria <2.5 g / day) or total (daily proteinuria <0.5 g / day) remission of proteinuria in a few weeks or months after starting of treatment
  • 40. Dynamics of proteinuria in children with Alport's syndrome (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) on the therapy with ACE-inhibitors (n = 14) without ACE-inhibitors (n = 8) 12,5% 28,6% 7,1% 50% 50% 37,5% 14,3% - decreased proteinuria - proteinuria didn’t increase - deceleration of the rate of increasing of proteinuria - stable proteinuria - increased proteinuria Конькова Н..Е., 2011
  • 41. Dynamics of GFR in children with progressive course of Alport's syndrome (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) on the therapy with ACE-inhibitors (n = 9) 33,3% 22,2% 33,3% without ACE-inhibitors (n = 3) 100% 11,1% - increasing of GFR - stable GFR - deceleration of the rate of reduction of GFR - reduction of GFR Конькова Н.Е, 2011
  • 42. Frequency of blood hypertension in children with SRNS receiving different immunosuppressive therapy (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) Prograf+Pred Prograf Cyph+Pred MMF+Pred MMF CsA+Pred CsA Pred maxD Pred 0 20 40 60 80 100
  • 43. The effectiveness of antihypertensive therapy in children with SRNS in dependence of the number of antihypertensive drugs (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) 100 90 80 70 60 50 40 30 20 10 0 1 medicine 2 medicines hypotensive effect 3 medicines
  • 44. Principles of antihypertensive therapy in kidney diseases in children BH MONOTHERAPY (ACE-inibitors, calcium channel blockers, BRA II) CHRONOTHERAPY COMBINATION THERAPY ACE-inibitors + diuretics, ACE-inibitors + calcium channel blockers, ACEinibitors + beta-adrenoblockers, calcium channel blockers + diuretics, etc.
  • 45. CHRONOTHERAPY ABPM allows: to identify the peaks of blood pressure rises to calculate: Т/Р - duration of antihypertensive action of the drug N/D - uniformity of drug’s action in the daytime and night hours IND - uniformity of drug’s action during a day to optimize therapy  to reduce the risk of target organ’s damage
  • 46. CHRONOTHERAPY (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) • Hypotensive therapy of capoten without individual choice of time giving was effective in 57% of children with glomerulonephritis (n = 13). • The uniformity of the drug’s action during the daytime and nighttime periods was achieved in 45% of children. The uniformity of drug’s action during the day was seen in <25% and a sufficient duration of antihypertensive action of the drug - in 33% of children. Burgall А., 2002
  • 47. Effectivenes of hypotensive therapy individualized on the base of ABPM in children with glomerulonephritis (Nephrology department of Research Institute of Pediatrics & Children surgery, Moscow, Russia) 100 90 80 70 60 50 40 30 20 10 0 deterioration no changes improvement 2 weeks 4 weeks 6 weeks 8 weeks Burgall А., 2002
  • 48. Burgall А., 2002
  • 49. Conclusion Preventing initiation and progression of CKD: • correction of common modifiable risk factors for the development and progression of renal and cardiovascular disease; • primary and secondary prevention of CKD (factors increasing susceptibility to CKD, factors of initiation of CKD and factors of progression of CKD); • nephroprotective and cardioprotective early therapy; • SMBP control
  • 50. Thank you for your attention!