Ischemic and toxic renal injury and renal disease in pregnancy

Ischemic and toxic renal injury and Renal disease in pregnancy

Presentor : Dr. Pallavi PrasadModerator : Dr. Manoj Jain

Acute Renal Failure/Acute Tubular Injury

Pathology of Acute Renal Failure/Acute Tubular Injury

• Enlarged and swollen kidneys• On cut section, the tissue bulges above the cut surface and

has a flabby consistency. • The cortex is widened and pale. • The outer medulla may appear as a deep red band

Histopathology of Acute Tubular Injury

• Glomeruli – spared• Glomeruli- ischemic collapse• Bowman's space - dilated

“Tubularization” of parietal epithelial cells

Histopathology of Acute Tubular Injury

postischemic ATI nephrotoxic ATI

The sites of tubular damage along the nephron differ between the two forms

Ischemic Acute Tubular Injury

Early : minimal alterations to severe cell swelling to individual cell necrosis with denudation of the basement membrane

Shedding of both viable and necrotic epithelial cells into the tubular lumen.

Brush border of proximal tubules is thinned or absent. Blebs of apical membrane and intact cells Individual cell necrosis Hyaline, granular, cellular, and/or pigmented casts are seen in

the distal portions of the nephron and in the collecting ducts

Tubular cells showing severe cell swelling

single tubular cell loss

Detached necrotic tubular cells Granular casts with necrotic cell debris

Apical blebbing

Intact tubular cells in the urine

Intact exfoliated tubular cells in tubular lumen

Tubular cell casts in collecting ducts in papilla

Nephrotoxic Acute Tubular Injury

• Extensive epithelial necrosis• Involves nephrons more uniformly than in the ischemic form

Nephrotoxic Acute Tubular Injury : LM features

• Alterations in the surface of the cells (loss of brush border (detectable on PAS), loss of basolateral infoldings, and blebbing of apical cytoplasm)

• Cytoplasmic swelling and vacuolation• Intracellular inclusions• Extensive tubular cell necrosis• Loss of individual tubular cells• Intraluminal proteinaceous cellular debris, casts, or crystals• Tubular dilatation with flattening of tubular epithelium• Tubular rupture with urinary extravasation• Regenerative changes

Severe cell swelling with IvIg

Isometric vacuolization

• Tubular simplification • The denuded basement membrane gaps are covered by

spreading of adjacent viable epithelial cells

regenerative changes

Ki-67

Erythrocyte congestion and nucleated cells in dilated vasa recta in outer medulla

Coagulative necrosis, with cell debris in tubular lumina

Oxalate crystals in allograft kidney

Pathology of Specific NephrotoxinsNephrotoxin Findings

Amphotericin Calcification of tubules

Anaesthetic agents, antiretroviral, sulphonamides, radiocontrast agents

crystals

Cocaine Pigmented casts

Antiretroviral agents Crystalsgranulomas

Aminoglycosides ATI, TIN

Cyclosporine Intratubular calcificationNodular hyalinosis of blood vessels

Calcification of tubular cells [amphotericin]Striking vacuolization of smooth muscle cells

Crystalline precipitates [intravenous acyclovir]

Indinavir crystal

Pigmented casts [cocaine]

Thrombotic microangiopathy [tacrolimus]

Renal disease in pregnancy

Urinary tract infections

Hypertensive Disorders of Pregnancy

HELLP Syndrome

Acute Renal Failure in Pregnancy

Pregnancy and Pre-Existing Renal Disease

I) Renal Infection in Pregnancy• In infected emboli• In pregnancy, retrograde spread from an infected focus lower

down the urinary tract• Impaired contractility of the ureter• Mechanical obstruction by a gravid uterus in women when

standing

multiplication and spread of bacteria

Renal Infection in Pregnancy

• Pyelitis or pyelonephritis• Asymptomatic bacteriuria

• Symptomatic infections during pregnancy• Bacteriuria has no established histopathological basis

II) Hypertensive disorders of pregnancy

Chronic hypertension

Chronic hypertension with superimposed preeclampsia

Late/transient hypertension

Preeclampsia and eclampsia

Hypertensive disorders of pregnancy

1) Chronic hypertension : Renal insufficiency developed in 4% of

non-proteinuric pts (24% of proteinuric pts) Fibromuscular

dysplasia- young females

2) Chronic hypertension with superimposed preeclampsia

3) Late/transient hypertension

4) Preeclampsia and eclampsia :

GFR reduced..

Preeclampsia and Eclampsia

• Nephrosclerosis = 74% of patients had hypertension on follow-up.

• 9.4% of preeclamptic patients without vascular lesions developed hypertension.

Hyperuricemia, Na retention,

FDPs, fibronectin- raised

Platelet counts – reduced

Urine : RBCs, WBCs, casts

Pathogenesis for preeclampsia

Gross appearance

• No distinctive changes visible to the naked eye • Normal size /slightly enlarged• Cortex is pale and widened in the larger kidneys• Glomeruli - unduly prominent

Microscopic findings in preeclampsia and eclampsia

• Glomeruli : enlarged and swollen, bloodless • Lobular pattern from capillary expansion producing cigar-

shaped lobules. • Glomerular capillary lumina are narrowed /obstructed b/o

mesangial and endothelial cell swelling and hypertrophy= glomerular capillary endotheliosis

Microscopic findings in preeclampsia and eclampsia

• Endotheliosis-like lesions :• Pathognomonic for preeclampsia• Normotensive patients with abruptio placentae • Normal pregnancy

glomerular capillary loops are ballooned at the tubular pole

herniation of the glomerular tuft into the proximal tubule pouting

bubbly appearance in the consolidated areas

segmental hyaline droplets in the podocytes

glomerular basement membrane splitting

endotheliosis lesion and segmental early TMA

endotheliosis lesion and extensive severe TMA

fibrinoid necrosis Intraluminal fibrin

double contours of the GBM segmental sclerosis and hyalinosis

intraluminal fibrin and early intimal proliferation

Frequency and course of glomerular lesions associated with preeclampsia

Lesion Frequency Course

Endotheliosis Invariable Reversible over weeks to months

Foam cells Rare peripartum, more frequent postpartum

Resolve

Subendothelial deposits Frequent peripartum Electron microscopic deposits resolve over first week, Ig staining resolves over 2-3 months

Glomerular basement membrane reduplication

severe disease Usually resolves rapidly, may persist for months

Fibrin or related products Rare by light microscopy; frequent by EM and IF

Resolution over weeks

Focal segmental glomerulosclerosis

Variable Not clinically progressive

Microscopic findings in preeclampsia and eclampsia

• Tubulointerstitium : IFTA, resorption droplets, casts• Blood vessels :a) Medial hypertrophy of arteriesb) Hyalinosisc) Arterio and arteriolosclerosis

Electron microscopy

• Swelling of endothelial and mesangial cells• lysosomes• Mesangial cell interposition• Vacuolisation, droplets, dense bodies, cytoplasmic strands• Glomerular epithelial cells vacuolisation & swelling• Increased lucency of lamina rara interna

Double contour of GBM

Electron micrograph from a 19-year-old woman with eclampsia

prominent mesangium

intracapillary cell with numerous empty spaces

Marked increased lamina rara interna

Lucent expanded subendothelial zone with scattered granular material

III) HELLP syndrome

Develops rapidly Benign to catastrophic

Marked coagulation abnormalities

HemolysisLFT abnormalities

ATN (31)Cortical necrosis (1)

IV) Acute Renal Failure in Pregnancy

Acute pyelonephritis Preeclampsia, eclampsia, and HELLP syndrome Uterine hemorrhage Septic abortion Cortical necrosis Acute fatty liver of pregnancy Postpartum hemolytic uremic syndrome

Renal Cortical Necrosis• Classic coagulative necrosis• Marked congestion• Tubular and glomerular architecture is preserved but gradual

loss of viable cytologic structure occurs. • The cytoplasm becomes homogeneous and eosinophilic, and

the nuclei demonstrate condensation and karyorrhexis

Renal Cortical Necrosis

• Polymorphonuclear leukocytic infiltration• As the lesion progresses, the central necrotic area becomes

smaller, and organization around the periphery• Eventual collapse of the central necrotic area and

replacement by collagenous scarring

Sheehan and Moore in 1952 :

Focal

Minor

Patchy

Scattered ~ 5mm

2-3 mm lesions mainly in the outer cortex

2/3rds of cortical tissue

IV) Acute Renal Failure in Pregnancy

Acute Fatty Liver of Pregnancy Fatty vacuolization in renal tubulesTubular regeneration or focal necrosisIntraglomerular thrombi- reported rarely

Septic shock transient decrease in the GFR

Uterine Hemorrhage abruptio placentae, DIC

Postpartum HUS

Postpartum Hemolytic Uremic Syndrome

schistocytes

Postpartum HUS

Fibrin thrombiSegmental hyalinosis

Tubular regeneration

Cortical necrosis

intimal fibrosismedial

hypertrophy TMA-like lesions

EclampsiaPreeclampsia

Specific Renal Diseases and Pregnancy

Antiphospholipid antibodies

• Increase in prevalence in patients with SLE during pregnancy ; poor outcome.

Vascular thrombosis

Decreased renal function

Hemolytic anemiaThrombocytopeni

a

Decidual vasculopathy

Antiphospholipid antibodies

• Acute fibrinoid lesions with fibrin thrombi in glomeruli, arterioles, and arteries

• Double contours of capillary walls• Recanalizing thrombi and cellular intimal proliferation• Vasculitis involving medium- sized and smaller arteries

• IgA Nephropathy• Mesangial (non-IgA) glomerulonephritis was associated with

the best prognosis• DPGN with advanced tubular atrophy, interstitial fibrosis, and

arteriosclerosis• Superimposed focal and segmental hyalinosis and sclerosis or

diffuse mesangial proliferation poor prognosis• Membranous Glomerulonephritis• Favorable renal prognosis • Nephrotic-range proteinuria poor fetal outcome

Systemic and Genetic Diseases

Diabetes Mellitus Increased proteinuria and serum creatinine

Anti-Glomerular Basement Membrane Antibody Disease

Pregnancy ameliorates the activity of antibodies

Kidney Transplant no adverse long-term effect on renal allograft function or survival was detected

Renal Cancer incidental detection during pregnancy because of the routine use of ultrasound

Case-1

• 24y/F• Non diabetic / non hypertensive• Post partum acute kidney injury• Decreased urine output, high grade fever, breathlessness,

nausea• Advanced renal failure , received 4 sessions of hemodialysis

outside• ? TMA/ renal biopsy proven acute cortical necrosis

Acute cortical necrosis

Case-2

• 29y/F• Non diabetic / non hypertensive• Abdominal pain / vomiting ( 1-2 episodes ), diarrhoea ( 8 -10

episodes), decreased urine output, edema• Found to have moderate renal failure / given 3 sessions of HD

outside • Referred to SGPGIMS for further management

• Lab investigations:• S creatinine : 3.3 mg/dl• TLC = 7.5• Platelet count = 298• Reti count = 2%• PBS : anisocytosis, schistocytes+• Antids-DNA, ANA = negative

• ?HUS/TTP

TMA with ATN

Case-3

• 31y/F• Non- diabetic, non- hypertensive• Underwent LSCS • C/o reduced urine output and passing pinkinsh urine 3- 4 days

after delivery, loose stools for 1 day, progressive edema of limbs

• On evaluation outside, AKI, anemia and reduced platelet count

• HD done outside but due to non- recovering renal functions patient was referred to SGPGIMS

• Lab investigations:• S creatinine : 4.2 mg/dl• TLC = 4.4• Platelet count = 177• Reti count = 2.6 %• PBS : Normocytic normochromic• ANCA negative• ANA = 2+ at 1:80• Urine = 25-30 RBCs/hpf

• ?TMA/ Acute cortical necrosis due to PPH

Patchy cortical necrosis with TMA and ATN