1

NEPHROPATHY IN PREGNANCY

Conf. Dr. Mircea PENESCU

2

RENAL PATHOLOGY IN PREGNANCY

• PRIMARY NEPHROPATHY IN PREGNANCY Is a de novo hypertensive syndrome occuring in primiparous

woman during the third trimester of pregnancy,associating proteinuria and oedema.

-Synonimous with : pregnancy vascular-renal syndrome, toxicosys (toxemya) in pregnancy, preeclampsia (endotheliosys as injury marker), pure dyspregnancy, late genuine of gestation(pregnancy) status

• SECONDARY NEPHROPATHY IN PREGNANCY Reveals preexisting renal injury before pregnancy, worsened

by or took of latency by pregnancy, even from the first trimester

-Synonimous with : superadjoinned preeclampsia, hypertension aggravated by pregnancy, secondary to gestation status

3

PRIMARY NEPHROTATHY IN PREGNANCY

• Occurs after the 20-th week of the first pregnancy and retrocedes after birth, not being to repeat oneself again during the next pregnancies

• Hypertension syndrome is defined by values of blood pressure over 14/8 cm Hg

• Proteinuria – characteristic element – may exceed 5 gr/24 hrs

• Oedema – as a consequence of proteinuria as well as of complex endocrine-humour mechanisms

• Constant physiopathological element – generalised vascular spasm

• Constant hystopathological element – endotheliosis

• Occasionally, anomalies of coagulation

4

• Occurence : in about 7 % of pregnant women

• Favourably circumstances :

- Parity : 6-10 times more frequent in first

pregnancies

- Genetic element : familial aggregation

- Age of pregnant women : younger women, 15-19

years are more endangered

- Circumstances connected with pregnancy status

- Increased occurence in hydramnious, hydatiform

mola and twins

- Chronic malnourishing increases occurance

PRIMARY NEPHROPATHY IN PREGNANCY

5

Theory of generalised vascular spasm : Presence of high levels of hypertensive substances :

• SRAA – rennin is doubling in week 8, amounting to 10 times the normal level in week 20

• ARP is increasing by 4 times in week 8

• Aldosterone exceeds by 10 times normal level in week 38

• Cathecolamin teco, vasopressin???? Ad prolactine are increased

• Vascular hyperactivity to pressor endogenous amines and peptides

• Progesterone – (decrease of its production deprives the organism of its vasodilating and natriuretic action)

• Prostaglandines – quantities in excess of PG E and F are physiologically antagonistic next to the effects of AT 2 ; shortage in secreting PG exposes organism to vasopressing influences

PRIMARY NEPHROPATHY IN PREGNANCY PATHOGENICAL THEORIES

6

• Coagulation anomalies theory

• In PNP, various degrees of chronical type CIVD appear, slowly, of low intensity, caused by lack of balance in clotting and fibrinolyse

• Placenta and decidua are rich sources of thromboplastine, whose release in ischemy may induce CIVD

• Immunological theory

• Appears together with conception and disappears after delivery

• Hystological lesions reproduce the ones in certain forms of GN

• Disseminated thrombosis are similar to generalised Schwartzman reaction

• Deposits of Ig and complement are present in glomerules

• Source of Ig involved seems to be ischemyac placenta

PRIMARY NEPHROPATHY IN PREGNANCY PATHOGENICAL THEORIES

7

• Macroscopy : • normal volume with subcapsular patches and pale-yellowish

cortex/cortical ?

• MO:• Growing up to double of the volume of glomerules

• Endotheliosis of glomerular cappilaries = marked tumefaction of endothelial cells with narrowed lumens and aspect of glomerules emptied of blood

• marked intersticial oedema with messangial hypercellularity

• extreme tummefaction of the glomerules may induce hernia of the glomerule in the initial TCP segment = onting

PRIMARY NEPHROPATHY IN PREGNANCY Pathological anathomy(1)

8

• ME : • endotheliosis

• MB thickenning (amorphous deposits of fibrinoide to this

level)

• Intensive secretory activity in the juxta-glomerular aparatus

(abundance of the paracrystaline granules)

• IF:• Subendothelial osmiofile deposits

• IgG, IgM and sometimes C deposits

PRIMARY NEPHROPATHY IN PREGNANCY

Pathological anathomy (2)

9

• Defining elements : • Appearance in primeparous women

• Setting up during the last trimester of pregnancy

• Retrocession after delivery

• Non-repetitive in further pregnancies

Subjective symptoms : headache (stronger during nighttime), irritability, irascibility, eyesight disorders, hearing disorders

• Objective symptoms : • HTA over 145/90 mm Hg

• Oedematous syndrome

• Cardiomegalya, tachycardia with galloping rhythm

• Painfull hepatomegalya (due to stasis)

• Pallidness due to haemodilution

PRIMARY NEPHROPATHY IN PREGNANCY Symptomathology

10

• Urine ex. : – Discreet oligurya up to oligoannurya

– Non-selective proteinurya between 1 to 10 g/24 hrs

– Urinary sediment : rare haematias, cylinders, relatively frequent L and epithelium

• Renal function investigations :– Uricemya over 4,5 mg/dl = predictive test

– Nitrogenous retention products generally normals

– Relative lowering of FSR, FPR, FG and FF

• Coagulation disorders : (moderate hypercoagulability = Chronic CIVD)

– Factors IO,II,V,VII,VIII,IX and X are raised

– Plattelet adhesiveness is raising

– Fibrinolyse inhibition

– PDF raising

PRIMARY NEPHROPATHY IN PREGNANCY

Laboratory investigations :

11

• Common or thypical form : preeclampsia (eclampsia)

• Hypertensive syndrome

• Oedematous syndrome

• Proteinuria

• Coagulation abnormalities

• Neurologycal symptoms : (headache, anxiety, insomnia, etc.)

• Cardio-vascular : palpitations, dyspnoea, pre-cordial discomfort)

• Digestive ( nausea, vomiting)

• Less manifest forms : two of the three main symptoms present : either HTA + oedemas, or oedemas + proteinuria, etc.

• Monomanifest forms : oedematous, hypertensive, proteinuric

Pending on the intensity of the symptoms, there are minor, major and subclinical forms

PRIMARY NEPHROPATHY IN PREGNANCY Clinical forms :

12

• In the medium forms, (preeclampsia) NGP became a therapeutic controllable syndrome

• Maternal mortality decreased the 10 last years from 5-12 % under 1 %

• Foetus mortality maintains to 25 %

• 30 % of new born babies from mothers with PGP are prematures

• Incidence of perinatal mortality is of 6-10 % in cases of preeclampsia and of 50 % in cases of eclanpsia

• After delivery of after surgical empting of the uterus, preeclamptic crisis dissapear, consciousness reappears, diuresis restores, oedemas and proteinuria dissapear

PRIMARY NEPHROPATHY IN PREGNANCY

Evolution :

13

• Neurologic complications : Eclampsia -severe accident with major vital risks for mother and

foetus, complicating preeclampsia

Paroxystmal raise of HTA = severe hypertensive encephalopathy, dominated by convultions, and leading towards coma

• Incidence : 5-10 % in primeparous women with PNP

• Foetal mortality in eclampsia is of 40-50 %

• Obstetrical complications :• abort

• Foetus death in uterus

• Retroplacental haematoma

• Hypotrophy or foetal prematurity

• Renal complications : CRF during the last trimester of pregnancy

PRIMARY NEPHROPATHY IN PREGNANCY Complications :

14

Symptomatology of eclampsia : • HTA over 17/11 cm Hg

• Visceral oedema till anasarca ????

• Oliguria

• Cardiac failure EPA

• Retinian oedema

• Renal function injury

• Raised haemoglobulinemia and haemoglobunuria

• Hyperbilirubinemia

Early clinical simptoms : severe headache, irradiative „in stick?”epigastric ache, vomiting

PRIMARY NEPHROPATHY IN PREGNANCY Eclampsia

15

• Convultions, initially localised,of Jacksonian type, then generalised, of epileptyc attack type

• Loss of consciousness

• Fixed eyes, dilatated pupils

• Apneea, for 15-60 seconds, followed by severe generalised contraction

• Respiration becomes profound, noisy, stertorous and generalised convultions are present

• Medium lasting is of 1-2 minutes, followed by variable intensity coma

• After the end of the eclamptic attack, hemiplegia or hemiparesis, either provisional or definitive, may occur

PRIMARY NEPHROPATHY IN PREGNANCY Eclamptic crisis

16

• Biologically, are obvious :• Acidosis• Hyperuricemia• Hyponatriemia• sometimes CIVD• Renal function injury – CFR

• Ostetrical risks parameters in eclanpsia :• Important and sudden raises of AT• Massive proteinuria (raise the risks by 10 times)• HTA of malignant aspect and massive protenuria raise the

risks by 20 times • Sudden raise of uricemia• Sudden lowering of placental lactogene hormone• Thrombocytopenia• Sudden lowering of estrioluria

PRIMARY NEPHROPATHY IN PREGNANCY

Eclamptic attack

17

Clinical

Paraclinical• Proteinuria up to 2 gr/24 hrs or over 3,5 gr/24 hrs in severe cases• Urinary sediment = differential diagnosis• Bacteriological ex. = overadded infections• Renal function ex. : raised ur, cr, uric acid; lowered Clcr,Clpah• Haemogram : anemia and leucocytosis• Electrophoresis : hypoproteinemia, hypoalbuminemia, hypo• gammaglobulinemia, hyperalpha 1 and 2 globulinemia (raised cerulo-

plasmyn + risk of eclampsia)• Seric enzymes (LDH, TGO, TGP, FA) raised in eclampsia• Coagulation tests indicate CIVD

– Foetoplacental evaluation through hormonal measurements : - lowering of plasmatic and urinary oestrogens values beginning with week 30 = major risks - values of placental lactogene hormone under 4 mg/dL beginning with week 30 = severe foetal suffering

PRIMARY NEPHROPATHY IN PREGNANCY Diagnosis :

18

• Prophylactic : • Hospitalization and investigations for the patients suspected of

eclampsia• Avoidance of diuretics (traditionally prescribed to every

pregnant woman with oedema)• Periodical check up of TA and G• Periodical urine ex.

• Curative Objectives : - mother’s protection against risks of HTA - maintenance of pregnancy as close as possible to the term

day - assurance of a normal foetal development

PRIMARY NEPHROPATHY IN PREGNANCY

Treatment

19

• Hygienic-dietetical treatment

- Medicinal treatment

1 Anti-HTA treatment will be applied in cases of tension above 17/11 cmHg

-Dopegyt, Aldomet 250-1000 mg/24 hrs

-Hydrazinophtaleines 25-100 mg/24 hrs

-Beta-blockers : Propranolol 40-120 mg/24 hrs, Atenolol 100-200 mg/24

hrs, Metoprolol 50-100 mg/24 hrs, Oxprenolol,Labetolol, etc

-Clonidine 0,1-0,3 mg

-Calcium antagonistics, but not before week 20

-Prozosin (Minipress)

-Diazoxid 300 mg i.v., in case of great emergencie

2. Diuretic medication – only in special situations (IC, EPA, eclampsia)

3. Antiadhezive – aggregational medication and anticoagulant (controversial) Aspirin, Dipiridamole, Prostacycline, Heparyne, etc.

4. Sedative medication : barbiturates, benzodiazepines)

PRIMARY NEPHROPATHY IN PREGNANCY Medical treatment

20

– Innitiating delivery labours stops eclampsia to start, but taking

such a decision induces a very heavy responsibility

– For patients aged under 34 years, innitiation of delivery labours is

temporized and pregnant woman is strictly monitorised. Could be

administered antihyper-tensives, diuretics, Dextran, Manitol, etc

Treatment for convultions :

• Magnesium sulphate 4 gr. i.v. in bolus + 5gr. i.m.profound, dose to repeate after 4-5 hours, depending on evolution

– Monitorise = to check up ROT, diurezis, respiration

– Fenobarbital 0,10 gr. - i.m. at a 2-4 hrs rate

– Sodium amital 0,25 gr.- i.v., slowly

– Diazepam 20 mg - i.v., slowly

– Mialgin 100 mg.- i.m.

– Obstetrical treatment = to evacuate the uterus

PRIMARY NEPHROPATHY IN PREGNANCY Treatment for eclampsia

21

SECONDARY NEPHROPATHY IN

PREGNANCY 1. Acute or chronic glomerulonephritis

– AGN = apparition of the tetrade oedema-HTA-proteinuria-haematuria in a pregnant woman who has had an acute amygdalitis 2-3 weeks before

– CGN (GNM, IgA GN, GNMP, MCD, GNF)

» 63 % of pregnant women carry pregnancies up to the term days

» 20 % have miscarriages or ask for procured abortions

» 17 % have premature deliveries

» 25 % lose their foetus (including perinative mortality)

» medium weight at birth = 3050 gr.

» in renal failure, foetal mortality raises significantly

» in HTA, foetal mortality raises from 21 % to 34 %

» NS raises the risk of foetal mortality

22

2 Nephrotic syndrome • Appears in MCD, GNExM, GNMP, colagenousis, diabetic

glomerulo- sclerosis, thrombosis of the renal veins, amyloidosis, syphilis, etc.

• Constitutes a group of high risk, necessitating a very

special monitorise

• Risks : miscarrige, abortion, premature delivery, foetal hypotrophy, injury of maternal renal function

• Foetal supervision techniques : echography, tocography, hormonal mea-surements and checking up of amniotic liquid (relatioship lecytine with

• sphyngomyeline in the amniotic liquid)

3 PNC and NIC

SECONDARY NEPHROPATHY IN

PREGNANCY

23

4 HTA– Chronic hypertension, irrespectively of the causes, i.e.

reno-vascular HTA, co-arctation of aorta, Cushing disease, primary hyperaldosteronism, feo-chromocytome, etc.

Maternal mortality amounts to 50 % in feochromocytom

– Chronic HTA with overadded pre-eclampsia (during the last trimestertakes the form of severe preeclampsia)

– Late or transitory HTA – appears in multiparous women, who after carring succesive pregnancies, develop during the last part of pregnancy moderate

– HTA, recovering 10 days after delivery

SECONDARY NEPHROPATHY IN

PREGNANCY

24

5 Pregnancy nephropathy in colagenousis

Lupus disease

• Pregnancy developes with apparently improvement of the nephropathy, but it exists a high frequency of foetal loses, predictible by dosing the Ac anti-cardio-lypine

• Occurance of pregnancy in LED must be strictly monitorised

• Maintenance of addapted doses of cortisone and imuran is recommanded, despite of the foetal risks

• Short treatment with corticoides high dosis immediatly after delivery

• Transplacental transfer of seric factor LE is possible

– PAN and SD – cautious prognostication

SECONDARY NEPHROPATHY IN

PREGNANCY

25

6 SNG in DM (diabetic nephropathy) • Worsening of renal function in 32 % of cases• Raised TA in 38 % of cases• Frequent appearance of overadded preeclampsia• Further evolution of nephropathy after delivery in 13 % of cases• Progressive worsening of renal function even after therapeutic abortion

7 PKR and pregnancy• normal bearing of pregnancy, PKR being clinically manifested only

after 30 years• appearance of colics, urinary infections, HTA, renal failure (already

ins talled disease)• genetic transmission of the disease contra-indicates pregnancy

8 Renal lithiasis • Raised frequency in pregnancy• Usually there are phosphate calculies, secondary to infections• In case of complications with risks of losing kidney, surgery is allowed even during pregnancy

SECONDARY NEPHROPATHY IN

PREGNANCY

26

RENAL DISEASES OCCURING DURING

PREGNANCY • Acute renal failure during the first trimester of pregnancy – septic abortion

• Acute renal failure during the last trimester of pregnancy – eclampsia, amniotic embolism, retroplacental haematom, foetal death in uterus, abruptio placentae, haemorrhagic shock through massive uterine haemorrhage, etc

• Acute renal failure speific to pregnancy

1. Severe acute degeneration of liver – obstetrical yellow pseudoatrophy)

• Appears either late, towards the end of pregnancy or

even after delivery

• Looks like a hepato-renal failure with intense jaundice

• Unknown ethyopathogeny

Clinically : high fever, uncontrolled vomiting, oligurrhia, jaundice

Mortality : 70-75 %

27

2 Post-partum idiopathic acute renal failure

– Diagnosis equation = triad : severe HTA, uremia, microangiopathic hae-

motithic anemia during the puerperal period in a woman that had an ap- parently normal pregnancy and delivery

– Uncertain ethiopathogeny implies responsibility of releasing thromboplas-

tinic substances of uterine origin through a syndrome similar to the pheno

menon Sanarelii-Schwartzman

– Dominant evolution of malignant aspect of HTA, with ICG, EPA, retinian

haemorrhages, hypertensive encephalopathy phenomena, etc.

» Mortality : 10-15

RENAL DISEASES OCCURING DURING PREGNANCY

28

3 Bilaterale cortical necrosis Intervene in severe forms of acute renal failure,

associating septicaemia and CIVD

Possible mechanisms :

» coagulation necrosis in multiparous women with lesions of arteriolar diffuse sclerosis already present

» prolonged vaso-spasm with CIVD

» major clinic sign – lake of reinstall of diuresis Certainty diagnosis = hystopathological (turgescent

kidneys with glomerules entirely destroyed and capillaries obstructed by fybrinoid thrombis

Irreversible evolution to uremia

RENAL DISEASES OCCURING DURING

PREGNANCY

29

• Urinary infections in pregnancy – 20 % of pregnant women aredelivering prematurely

• Unique kidney and pregnancy – pregnancy is possible on an unique kidney under conditions of strict monitorise

• Pregnancy to women with renal transplant is possible, there are about 2000 cases up to now, out of which :

• 22 % had therapeutically interrupted pregnancy• 16 % miscarried• 25 % premature deliveries• 45 % undergo caesarean operation• 30 % prevalence of eclampsia• 9 % reject of transplanted kidney• 15 % pregressive deterioration of renal function Cyclosporine has foetal toxicity !

RENAL DISEASES OCCURING DURING

PREGNANCY