2. INTRODUCTION
• Following renal preservation surgery and live donor renal transplantation ,
deleterious effects seen on the remaining renal tissue which initially
functions to restore renal excretory capacity
• Hyperfiltration of remaining nephrons occurs – altered nephron
hemodynamics – progressive azotemia,hypertension, and proteinuria
3. CONTD….
• Inspite of Understanding of vascular, metabolic,immunologic disorders that
effect glomeruli and renal interstitium ,chronic renal insuffenciency once
established progresses to end stage renal failure
• Attempts in preventing ESRD is unsuccessful
5. MECHANISM OF INJURY
• Result of multiple common insults to kidney - end result of sclerosis
• Occurs through fibroblasts,collagen deposition ,mesangial matrix dearrangements -
disruptions of kidney functions ( filtration, secretion,absorption )
• Progressive renal disease - END STAGE KIDNEY ( small kidney, reduced
renalmass , glomeruli with loss of capillaries , localised areas of cell proliferation ,
progressive scarring ,collapsed capillary beds )
8. FURTHER CONSEQUENCES
• Increase in GFR, reduction in renal mass
• Increase in transglomerular capillary pressure ( PGc)
• Afferent and efferent arteriolar dilatation secondary to stimulation of renin and
angiotension system (RAS )
• Release of angiotensin II (AII) , prostaglandins E2 -regulation
• Other vasoactive compounds like atp, histamine,bradykinin ,endothelin
,epgf,acth,anp ,pth ,glucocoticoids ,vasopressin,adenosinrs
• Activation of coagulation cascade
9. CLINICAL FEATURES &PATHOLOGY
• Proteinuria ,hypertension ,renal insufficiency
• Earliest and most striking changes - glomerular microvasculature +
tubulointerstitial involving the subsequent phases of pathologic process
• Glomerular hypertrophy and glomerular sclerosis ( HALLMARK OF
HYPERFILTRATION NEPHROPATHY )
10. PATHOGENESIS
• 1) microthrombosis – altered hemodynamics and increased blood flow - shear stress on
vascular endothelium – cell swelling, cell surface protrusions, seperating from basement
membrane
• Promotes along with endothelial cell proliferation + platalet adhesion
• 2) microaneurysms – increases both hydrostatic pressure and capillary diameter causes
significant increase in the tension exerted on the capillary wall ( LAPLACE ‘S LAW )
• vessel wall - platelets, fibrin, inflammatory cells ( acute phase )
• organised cell debris, plasma proteins & vacoulated macrophages - segmental capillary
collapse
11. CONTD…
• 3) mesangial matrix – proliferation of mesangial cells + increased deposition
of extracellular material ( + diabetes ) -diffuse/focal mesangial expansion
• 4) subendothelial hyalin – along with eosinophilic material deposition,
responsible for pre existing arterial &arteriolar changes
• Infiltrating macrophages & lymphocytes - progresses glomerulosclerosis
12. MICROSCOPIC PATHOLOGIC CHANGES
• Large cystoplasmic vacoules
• Focal retraction of epithelial cell podocytes - distorsion of foot processes
,slit diaphragms ,seperation of epithelium from basement membrane
• Deposition of fluids,serum proteins, macromolecules in the lamina densa
and occuluding the lumen
13. CLINICAL SITUATIONS PROMOTING
THE DEVELOPMENT OF RENAL
HYPERFILTRATION
• Diabetes mellitus
• Hyperfiltration associated with solitary kidney ,kidney of normal pregnancy
• Long term parenteral nutrition
14. DIABETES MELLITUS
• In newly diagnosed IDDM ,GFR is elevated and may fall to normal values with
control of hyperglycemia
• In IDDM – presence of minimally elevated urinary albulmin excretion is predictive
risk of developing overt proteinuria
• Decline of renal function in diabetes is faster in hyperfiltrating diabetes than in
diabetes with out proteinuria
15. RENAL ABLATION IN SOLITARY
KIDNEY
• Long term renal function was found to remain stable in most patients with a
reduction in renal mass more than 50 %, increased risk for
proteinuria,glomerulopathy,and progressive renal failure
• Risk is higher in patients with reduction of renal mass >75 %
• GFR is decreased from 1/5 th of normal - CRF- ESRD
16. RENAL TRANSPLANTATION &
HYPERFILTRATION INJURY
• Slow progressive decline in GFR + proteinuria + arterial hypertension
+structural changes in the allograft – changes of hyperfiltration
nephropathy
• Graft loss is most commonly due to late /chronic rejection
18. NON IMMUNOLOGIC CAUSES
• Alloantigen – independent factors contribute to chronic graft dysfunction
• Factors include organ procurement , preservation, allograft implantation
,reperfusion
• Many cases of late allograft loss – immunologically mediated chronic
rejection
19. TRANSPLANT DONOR
CHARACTERISTICS
• Factors contributing to hyperfiltrtion mediated chronic graft loss include
• Solitary kidneys Very young donors (< 2 yr old )
• Elderly donors
• Female donors for male recipients
• Cases involving prolonged ischemia
20. OTHER CONTRIBUTING FACTORS
• Obese patients
• Patients on high protein diet
• Steroid therapy
• Hypercholestremia
• Increased glomerular filtration – progressive glomerulopathy - increasing
glomerular hypertension
21. MANAGEMENT AND PREVENTION OF
HYPERFILTRATION
• 1) Protein restriction diet -adminstration of enzyme converting inhibitors
- decreased proteinuria and rate of detoriation of renal function
• Dosage – 0.6 g of high quality protein/kg of body weight per day
• 0.3 g/kg of body weight of vegetable proteins + amino acids
• Regimen 0.3 g/kg/day + ketoacids
• 2) weight loss – reduction of proteinuria
22. CONTD…...
• 3) ACE inhibitors
• MOA – lowers bp by improving glomerular hemodynamics do not usually
ameliorate glomerular injury
• In IDDM ,captopril reduces the rate of proteinuria + microalbuminuria
with out hypertension ( by reducing efferent arteriolar resistance and
lowered intraglomerular pressures )
24. CONTD…
• 5) calcium channel blockers – nifedipine /diltiazem are commonly used
• MOA – cyclosporine reduce renal perfusion and decrease GFR - progressive
ischemic injury - glomerular ,interstitium ( counteracts the hemodynamic effects
and stabilize bp )
• 6) steroid withdrawal – which normally induces nonimmunological glomerular
hypertension
25. CONTD…
• 7) intravenous human recombinant superoxide dimutase ( rh –SOD )
• Intervention to preserve functional renal reserve following organ
preservation
• Given intraoperatively to cyclosporine treated recepients of cadaver
allografts showed beneficial effect in preventing acute and chronic rejections
26. Contd…
• 8) prevention of hyperfiltration in renal transplant
• Augmenting nephron supply and brenners proposal to improve the size
match of the donor kidney with that of the recipient with tranplanting
kidneys from donors less than 2 yrs ( cleveland clinic study )
Editor's Notes
These situations involve immunological conditions where nephron mass of donor kidney is believed and insuffecient to meet metabolic demands of the recepient – results in elevated blood flow –metabolic demands of kidney