Renal diseases and pregnancy

Dr. Shreyash Trived

Dr. (Prof.) V. Priyadarshi Unit

AGENDA Renal adaptation to pregnancy

UTI and acute pyelonephritis

Hypertensive disorders of pregnancy

Acute kidney injury in pregnancy

Chronic kidney disease and pregnancy

Renal adaptation to pregnancy Kidney length increases by 1-1.5 cm and volume by

30%.

Physiological dilatation of the urinary collecting system with hydronephrosis in 80% of women, more pronounced on the right side

Estrogen, progesterone and prostaglandins may also affect ureteral structure and peristalsis

Contd.. Renal plasma flow increases out of proportion to GFR.

GFR increases by 40-65% as a result of an even larger increase of renal blood flow.

The increase in GFR results in a physiological decrease in creatinine, urea and uric acid levels.

Creatinine clearance rises to 150-200ml/min and average serum creatinine decreases to 0.5-0.6 mg/dl.

Thus a serum creatinine level of 1mg/dl which is normal in nonpregnant state may reflect renal impairment in the pregnant patients.

Contd..

Blood urea nitrogen(BUN) decreases from an average 13 to 8-10 mg/dl

A reset in the osmostat occurs, resulting in increased thirst and decreased serum sodium levels (by approximately 5 mEq/L) compared with non-pregnant females and also decreased osmolality.

Contd.. Increased urinary excretion of protein, amino acids,

uric acid, glucose and calcium occurs as result of the elevated GFR. Hence, proteinuria in pregnancy is considered abnormal when it exceeds 300mg/day compared with an upper limit of normal of 150mg/day in the non-pregnant population.

UTI And Acute Pyelonephritis Most frequent renal problem encountered during

gestation.

Asymptomatic bacteriuria in pregnancy

Acute pyelonephritis in pregnancy

Asymptomatic bacteriuria in pregnancy Needs to be treated more aggressively in the setting of

pregnancy.

Untreated in pregnancy, can lead to overt cystitis and pyelonephritis in up to 40% of patients.

Increased risk of premature delivery and low birth weight.

Screening Quantitative urine culture is preferred for screening.

More than 1lakh bacteria/ml of a single species is considered significant

Screening is recommended during the first prenatal visit and is repeated only in high risk women

Treatment If asymptomatic bacteriuria is found prompt

treatment is warranted, usually with a cephalosporin for 3 to 7 days.

A single dose of fosfomycin has also been used successfully.

A follow up culture two weeks after the therapy is necessary to ensure eradication of bacteriuria.

Contd.. Suppressive therapy with nitrofurantoin or cephalexin

is recommended for those patients with bacteriuria that persists after two courses of therapy.

ACUTE PYELONEPHRITIS Pyelonephritis

70% have asymptomatic bacteriuria

Mostly in second trimester

Symptoms – Pain, fever, dysuria

Complication – Endotoxic Shock, DIC, ARF

Treatment

Hydration

IV Antibiotics

Change to oral antibiotics for 10-14 days

HYPERTENSIVE DISORDERS

IN PREGNANCY

GESTATIONAL HTN: WORKUP Determine the severity of HTN

24 hour urinary protein

Evaluate for the signs/symptoms of preeclampsia

R/O end organ damage

GESTATIONAL HTN: MANAGEMENT MILD Gestational hypertension:

Managed as outpatients

No anti hypertensive therapy

No antenatal steroids

Regular monitoring of fetal well being with the help of obstetrician.

Deliver patients no later than EDD.

Contd… SEVERE Gestational hypertension:

1. SBP>/= 160 and DBP>/= 110 – treat with antihypertensive agents.

2. >34 weeks – deliver.

3. <34 weeks– give steroids.

GESTATIONAL HTN 15-25% risk of progression to preeclampsia.

22-47% risk of recurrence in subsequent pregnancy.

Associated with development of hypertension later in life.

PRE ECLAMPSIA

It is a multisystem disorder of unknown etiology.

In normal pregnancy the interaction between vasodilator and vasoconstrictor systems stabilizes the BP.

In preeclampsia this balance is lost due to endothelial dysfunction which is preceded by decreased uterine blood flow and placental ischemia.

Resulting vasospasm affects almost all the vessels, most importantly uterus, kidney and brain.

PRE -ECLAMPSIA

BASIC MECHANISM OF MULTIPLE ORGAN DAMAGE Increased vasoconstriction.

Decreased organ perfusion.

Increased endothelial dysfunction– capillary leak-edema, pulmonary edema, proteinuria.

Activation of coagulation: DIC, reduced platelets.

Hemoconcentration.

RENAL SYSTEM INVOLVEMENT Decreased renal perfusion d/t decreased blood volume

and increased afferent arteriolar pressure .

Decreased GFR d/t:

1. Glomerular capillary endotheliosis.

2. Endothelial damage.

3. Mesangial swelling and disruption of basement membrane.

SCREENING Adequate antenatal care.

Risk assessment– nulliparous women or women with other risk factors should be assessed more frequently during the third trimester.

Uterine artery Doppler ultrasound may detect abnormal uterine artery waveform– this is presently the most promising screening procedure.

Biomarkers for pre eclampsia– Placental protein 13(PP13),Sflt1, PIGF.

PREVENTION Many strategies have been studied, unfortunately none

have proven unequivovally effective.

1. Aspirin (75mg OD)– is only recommended in high risk pregnancies.

2. Calcium supplementation– should be considered in women with low baseline calcium intake and high risk.

MANAGEMENT AND TREATMENT OBJECTIVES:--

1. Prevention of complications.

2. Prevention of eclampsia.

3. To ensure minimal fetal and maternal morbidity.

HOSPITALISATION Ideally every patient should be hospitalised for

detailed evaluation.

Mild uncomplicated preeclampsia – rest, high protein diet and sedatives are prescribed– patient is investigated and checked after one week or earlier– if treatment fails pt is to be admitted.

She should be warned against ominous symptoms–headache, visual disturbance, vomiting , epigastric pain, scanty urine.

INVESTIGATIONS BP check– 4 times per day.

Platelet count

Coagulation profile

Uric acid

Creatinine

LFT.

24 hour urinary protein

Ophthalmoscopy

Treament modalities Restricted physical activity.

Diet– adequate amt of protein(100gm), calorie Sedatives– Diazepam 5mg at bed time.

Antihypertensives:--

Methyl dopa- 250-500 mg tid to qid

Labetalol- 200 mg tid

Nifedipine- 10-20 mg bid

Hydralazine- 10-25 mg bid

Diuretics are avoided

ACEI and ARBs are contraindicated

TIMING OF DELIVERY The definitive treatment of preeclampsia is delivery.

Timing of delivery depends upon:

1. Severity

2. Duration of pregnancy

3. Response to treatment

Contd.. Depending upon the response to treatment, pts are

grouped into:

A. Preeclamptic features completely subside.

B. Partial control– BP at steady high level.

C. Severely increased BP with ominous signs.

Contd.. Group A– 1. Remote from term pt is discharged with

advice to follow up after one week. 2.Near term sheshould be kept till completion of 37th week.

Group B-- >37 weeks– termination without delay.<37 weeks– expectant treatment upto 34 weeks with continuous monitoring.

Group C– termination is considered irrespective of the duration of pregnancy.

Contd.. Magnesium and seizure prophylaxis—

used in severe preeclampsia—

loading dose– 4-6 gm i.v over 15-20 minutes

maintenance dose– 1-2 gm/hr i.v infusion

With continuous monitoring for toxicity.

MANAGEMENT OF ECLAMPSIA Resuscitation – maintain airways.

Oxygen inhalation.

Anti convulsants– MgSO4 is the agent of choice.

Hemodynamic stabilisation– fluids

Deliver by 6-8 hrs.

Postpartum care.

MANAGEMENT OF CHRONIC HYPERTENSION IN PREGNANCY There is little evidence that treatment of mild to

moderate hypertension has a clear benefit for either mother or fetus.

Aggressive treatment of mild to moderate hypertension may adversely affect fetal growth.

Current guidelines suggest that treatment should be initiated only if there is evidence of end organ damage or BP exceeds 150-160/100-110.

In those receiving therapy prior to pregnancy, tapering or discontinuing therapy should be considered unless BP exceeds these levels.

ACUTE KIDNEY INJURY IN

PREGNANCY

AKI in Pregnancy Incidence of ARF in pregnancy is 1:20000

Causes of renal failure in pregnancy can be divided into :

Early pregnancy:- 1. Hyperemesis gravidarum, 2. Septic abortion.

Late pregnancy:-PIH and its complications, HELLP, Post- partum HUS, Acute fatty liver of pregnancy, Volloss-APH, PPH, sepsis

Causes of AKI

The most common cause of AKI during pregnancy is prerenal azotemia due to hyperemesis gravidarum or vomiting from acute pyelonephritis

Pregnancy-specific conditions- preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy are complicated by acute renal failure.

Obstetric complications- septic abortion and placental abruption are associated with severe acute tubular necrosis and bilateral cortical necrosis

Obstructive uropathy

TYPES OF ACUTE RENAL FAILUREACUTE TUBULAR

NECROSIS

RENAL CORTICAL

NECROSIS

Less serious serious

Reversible Irreversible

a/w sepsis & htn a/w obstetric causes&

pre-eclampsia

Kidney lesion- focal,

dilatation & flattening of

epethelium of

DCT,pigmented cast in

lower part of nephrons

Kidney lesion-

focal,patchy

confluent/gross resulting

from thrombosis of renal

vascular system

TYPES OF ACUTE RENAL FAILUREACUTE TUBULAR

NECROSIS

RENAL CORTICAL

NECROSIS

Patint have high grade

temperature, vomiting,

diarhoea

Oliguria which can lead to

anuria, azotoemia

&consumptive

coagulopathy

Shock occurs rapidly &

may have mild jaundice,

pallor& cyanosis

Extra-renal manifestations

like cardic dilatation, CHF,

lethargy, convulsions

Most patient respond to

volume resuscitation

&vigorous antibiotics in

ICU

_

Treatment of AKI in pregnancy Supportive—prompt restoration of volume deficits,

antibiotics and in later pregnancy expedient delivery.

Acute cortical necrosis– no specific therapy; dialysis when needed.

TTP/HUS Pregnancy appears to be a/w increased risk of TTP (

usually before 24 weeks of gestation) and HUS ( near term or post partum).

HUS/TTP is characterized by thrombocytopenia, hemolysis, and variable organ dysfunction including acute renal failure.

Patients are thought to have TTP when neurological symptoms dominate, and HUS when renal failure is the dominant presenting feature

ACUTE FATTY LIVER OF PREGNANCY

c/f- abdominal pain and jaundice, typically occurring after week 34 of gestation.

Bilirubin is elevated, with mild elevations of aspartateaminotransferase and alanine aminotransferase levels also. Severe cases can present with fulminant hepatic failure.

The disorder is commonly associated with acute renal failure. Noninvasive imaging can also provide evidence of fatty liver. Pathogenesis- microvesicular fatty infiltration of

hepatocytes, which may related to defective mitochondrial beta-oxidation of fatty acid

Rx- Immediate delivery and supportive care. Most patients fully recover

CLINICAL FEATURES

HUS/TTP HELLP AFLP

Hemolytic anemia +++ ++ +/-

Thrombocytopenia

+++ ++ +/-

Coagulopathy - +/- +

CNS symptoms ++ +/- +/-

Renal failure +++ + ++

Hypertension +/- +++ +/-

Proteinuria +/- ++ +/-

Elevated AST +/- ++ +++

Elevated bilirubin ++ + +++

Anemia ++ + +/-

Ammonia Normal Normal High

Effect of delivery on disease

None Recovery Recovery

Management Plasma Exchange Supportive care,Delivery

Supportive care, Delivery

Chronic kidney disease and pregnancy

CKD AND PREGNANCY Women who enter pregnancy with chronic renal

disease are at increased risk for adverse maternal and fetal outcomes, including rapid decline of renal function and perinatal mortality.

Frequency of live births now exceeds 90% in these women, the risk for preterm delivery, IUGR, perinatalmortality, and preeclampsia are significantly elevated.

Contd.. Overall maternal and fetal prognosis correlates with

the degree of hypertension, proteinuria, and renal insufficiency prior to conception.

Current consensus suggests the degree of renal insufficiency, rather than the underlying renal diagnosis, is the primary determinant of outcome

Relationship between pregnancy and kidney disease. Effects of pregnancy on

kidney disease

Worsening proteinuria

Loss of kidney function

Hypertension and preeclampsia

Effects of kidney

disease on pregnancy

Infertility

Preterm delivery

IUGR

Decreased fetal survival

Preeclampsia

Contd..1. Preserved/mildly reduced renal function, Cr < 1.4

– good outcome for pregnancy and renal disease

2. Initiating pregnancy with S. creatinine >2mg/dl

– >30% risk for accelerated decline in renal function

3. Severe renal insufficiency, Cr > 2.5

– >70% preterm labour and >40% experience preeclampsia.

Diabetic nephropathy Pregnant women with diabetic nephropathy may also

develop worsening proteinuria and hypertension.

Complications- preeclampsia

still birth

Good control of blood glucose & blood pressure before and during pregnancy improves perinatal & maternal out come.

LUPUS NEPHRITIS AND PREGNANCY SLE increases the risk of adverse pregnancy outcomes.

Superimposed renal disease increases the risk even further.

Specific subsets of women with SLE are at especially high risk—

-- women with SLE and antiphospholipidantibody.

-- proliferative lupus nehritis

Contd.. Women with lupus should postpone pregnancy until

lupus activity is quiescent and immunosuppressives are minimized.

Prophylactic therapy with steroids does not appear to prevent a lupus flare during pregnancy

Immunosuppressive (e.g., steroids, azathioprine) have been used to manage lupus flares during pregnancy.

LUPUS FLARE AND PREECLAMPSIA Unfortunately, both syndromes share the common

presenting symptoms of hypertension and proteinuria, hence distinguishing the two can be a clinical challenge.

LUPUS FLARE-UP VERSUS PREECLAMPSIA

PESLE

++Proteinuria

++Hypertension

-+RBCs cast

++Azotemia

-+Low C3, C4

-+/-Abnormal liver

function test results

-+/+Low platelet count

-+Low leukocyte count

Pregnancy in Renal Transplant Patients Successful renal transplantation results in return to

normal hormonal level and fertility within 6 months of in approx. 90% women of child bearing age.

There is substantial risk of low birth weight, pre term delivery and ectopic pregnancy.

American Society of Transplantation currently suggests that for women on stable, low doses of immunosuppressive agents, with normal renal function, and with no prior rejection episodes, conception could be safely considered as early as 1 year post transplant.

Contd.. Pregnancy itself does not appear to adversely affect

graft function in transplant recipients, provided baseline graft function is normal and significant hypertension is not present.

The most common complication of pregnancy in transplant recipients is hypertension, which affects between 30% and 75% of pregnancies among transplant recipients.

Preeclampsia complicates 25% to 30% of pregnancies in renal transplant patients,

Antihypertensive agents of choice include methyldopa, nonselective β-adrenergic antagonists (i.e., labetalol), and calcium channel blockers.

Cyclosporine (or tacrolimus) and steroids, with or without azathioprine, form the basis of immunosuppression during pregnancy

Although high-dose steroids have been associated with fetal malformations and maternal infections, this remains a mainstay of treatment of acute rejection during pregnancy

Thankyou

for kind attention