Renal Disease and Pregnancy:-ByOmnia Abd Elazim:-Supervised by prof:-Ahmed Fathy Elkoraie
:Agenda The normal kidney in Pregnancy. pregnancy-induced hypertension. Acute kidney injury in pregnancy. Chronic kidney disease and pregnancy. End-stage renal disease and pregnancy. Transplantation and pregnancy.
Renal Function During PregnancyRenal plasma flow increases by 50-70% in pregnancy,and this change occur mainly in the first twotrimesters. This is the factor that lead to anincreased glomerular filtration rate (GFR). The GFRpeaks around the 13th week of pregnancy and canreach levels up to 150% of normal. So, both BUNand creatinine levels, the plasma markers of GFR,are decreased. This decrease has clinicalsignificance in that a normal BUN or creatinine levelin a pregnant female may actually indicate .underlying renal disease
Similarly, in the initial part of pregnancy, increasedlevels of progesterone enhance relaxation of thearterial smooth muscles and thus decreaseperipheral vascular resistance.So, a blood pressurefall of approximately 10 mm Hg occurs in the first 24weeks of pregnancy. The blood pressure graduallyreturns to a prepregnancy level by term; thus, aconsistent normal or prepregnancy blood pressuremay suggest the presence of a condition that .hypertension predisposes patients to
The drop in blood pressure in normalpregnancy occurs despite increased levels ofrenin, angiotensin, and aldosterone. There isresistance to the hypertensive effects of bothendogenously and exogenously administeredangiotensin. The resistance has beenattributed to production of prostacyclin byplacental endothelial cells as well as other.vasodilators
Renal vasodilatation in pregnancyEDRF; Endothelial Derived Relaxing Factor,)(NOVasodilatory PG’sRelaxinET;Endothelin.All lead to increase RPF& GFR
Electrolytes & Acid Base ChangesElevated progesterone levels stimulatehyperventilation and result in a state of mild respiratory alkalosis and a blood gas of PH: 7.44PCO2: 30HCO3: 22
A reset in the osmostat occurs, resulting inincreased thirst and decreased serumsodium levels (by approximately 5 mEq/L)compared with nonpregnant females and .also decreased osmolality
Hyponatremia during pregnancy parallels theincreased release of human chorionicgonadotropin (HCG), which appears tomediate these changes via the release ofrelaxin. Serum potassium levels are normaldespite increased serum aldosterone,perhaps due to the potassium-sparing effectsof elevated progesterone levels in.pregnancy
Total serum calcium levels fall in pregnancy but ionizedcalcium remains normal. Accelerated renal andplacental production of calcitriol leads to increasedgastrointestinal absorption of calcium and absorptivehypercalciuria with urine calcium as high as 300.mg/daySerum parathyroid hormone (PTH) concentrationsare lower than normal, partly in response to higher.serum levels of calcitriol
Increased urinary excretion of protein,aminoacids,uric acid,glucose and calcium occursas result of the elevated GFR.Hence,proteinuria in pregnancy is consideredabnormal when it exceeds 300mg/daycompared with an upper limit of normal of.150mg/day in the nonpregnant population
The anatomic changes inpregnancyThe anatomic changes are primarily in the collectingsystem. A dilatation of the ureters and pelvis occursand it is secondary to the smooth muscle–relaxingeffect of progesterone. This dilatation is often moreon the right side secondary to dextrorotation of theuterus and dilatation of the right ovarian venousplexus. This can lead to urinary stasis and, anincreased risk of developing urinary tract infections ).(UTIs
There is also an increase in overall kidney size. by about 1-1.5 cmthese changes may persist for up to 12 weekspostpartum and should not be over- .interpreted as obstructive uropathy
Renal Changes in Normal Pregnancy Anatomic 1 cm incerased in length. Dilatation of the collecting system. Physiologic 50% increased in GFR: normal BUN 9 mg/dL, creatinine 0.5mg/dL Respiratory alkalosis: normal PCO2 27 – 32 mm Hg, HCO- 3 18 – 22 mEq/L Decreased serum osmolality: normal 276 – 278 mOsm/L Doubling of uric acid clearance: normal 3 – 4 mg/dL Decreased Tubular reabsorption of glucose 40% increased in renal blood flow Decreased afferent and efferent arteriolar resistance Decreased BP: normal < 125/75 mm Hg 2nd trimester, < 125/85 mm Hg 3rd trimester Increased Prostacyclin and thromboxane Increased Renin (8x), angiotensin (4x), aldosterone (10 – 20x)
Hypertension, the most common medicalcomplication of pregnancy, occurs in up to10% of pregnancies; it is associated with asignificant increase in maternal and fetalmorbidity and mortality and is the leading .cause of premature birth
hypertension in pregnancy is defined as asystolic blood pressure of over 140 mm Hgand a diastolic blood pressure greater than.90 mm Hg
Types of pregnancy-inducedhypertensionGestational hypertension) 1de-novo hypertension occurring alone after20/40 whichresolves post-partum. Risk factor for essential.hypertension in later life
Chronic hypertension) 2Pre-eclampsia) 3Chronic hypertension with superimposed) 4pre-eclampsia
Hypertension and adverse outcomes inpregnancyProgressive increase in perinatal mortality with each•.5mmHg increased in MAPMAP > 90mmHg during 2nd trimester correlates with•.increased incidence of IUGR, pre-eclampsiapregnant women with MAP> 90mmHg in 2nd 1/3•. trimester progress to pre-eclampsia
Gestational hypertension( 1Gestational hypertension is defined ashypertension that appears after midterm, isnot associated with proteinuria, and resolvesafter delivery. Women at risk for thiscondition are those with a positive familyhistory of hypertension and patients withobesity and multiparity. Women withgestational hypertension are at risk for.chronic hypertension
Chronic hypertension( 2Chronic hypertension is defined as a prepregnancyblood pressure of greater than 140/90 or ashypertension occurring before 20 weeks gestation.The definition may also include some hypertensivewomen with minimal proteinuria diagnosed duringpregnancy that does not resolve with delivery. Fisheret al showed by renal biopsy that these women may.have nephrosclerosis rather than preeclampsia
Chronic hypertension increases the risk of pre-eclampsia, perinatal mortality, small forgestational age (SGA) babies, prematuredelivery,, gestational diabetes, intrauterinegrowth retardation, and second-trimester .fetal death
treatment:-During pregnancyAntihypertensive drugs*methyldopa / labetalol = 1.CCB / hydralazine = 2 No ACE inhibitor/ARB after conception/1st trimester..Early delivery for severe hypertension*.Bed rest*
:-treament of hypertensive urgencyHydralazine: IV 5mg, then 5-10mg q30min.or infusion 0.5-10mg/h/Labetalol: IV 20mg then 20-80mg q20-30min.max 300mg or infusion 1-2mg/minNifedipine: PO/SL 5-10mg PO, then 10-20mg every 2-. 6 hrs.Nitroprusside: IV 0.5-10mcg/kg/min
Common medications in hypertensionACE inhibitors, ARBs. 1 Not safe to use Fetal oligohydramnios pulmonary hypoplasia,skeletal deformitiesDiuretics. 2 Not safe to use Maternal volume depletion; fetal thrombocytopenia, hemolytic anemia, jaundiceb-Blockers. 3 Not safe to use Fetal bradycardia, hypoglycemia, respiratory distressLabetalol. 4 Widely used Limited dataMethyldopa. -5 Safe to use Limited long-term follow-up shows no developmental problem in childrenClonidine. 6 Not safe to use Limited dataCalcium channel. 7 Safe to use Potentiates the hypotensive effect ofblockers magnesium; limit use to refractory hypertensionHydralazine. 8 Safe to use Given intravenously for acute, severe hypertension
Pre-eclampsia( 3Pre-eclampsia is characterized by the triadof edema, hypertension, and proteinuria, inpreviously normotensive women that typicallyoccurs after 20 weeks gestation and.resolves with deliveryEclampsia :is defined as the occurrence of .seizures in women with pre-eclampsia
:-Cause.unknown–.Abnormal placentation–.Maternal endothelial dysfunction–.Genetic factors–.Increased maternal inflammatory response–.Immunologic factors–.Infectious diseases–.Predicting pre-eclampsia – no good markers•
Risk Factors for Preeclampsia – Primigravida. – Different father in pregnancy for multigravida. – Diabetes. – Preexisting hypertension. – Renal disease. – Twin gestation. – Hydatidiform mole. – Fetal hydrops. – Family history.
;-Clinicallypreeclampsia usually begins after 20 weeks of :-pregnancy.it manifested by . De novo hypertension .New onset proteinuria
Severe Pre-eclampsia:-Preeclampsia with one or more of the followingSystolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg on two occasions*.at least 6 hr apart while on bedrestProteinuria >5 g in a 24-hr urine specimen or dipstick proteinuria ≥3+*.on two random urine samples at least 4 hr apart).Oliguria (<500 mL urine output over 24 hr*disturbances *Severe headache, mental status changes, visual .
Hepatocellular injury (transaminase elevation *). to at least twofold over normal level). Thrombocytopenia (<100,000* *growth restriction. Fetal.Cerebrovascular accident*.pulmonary edema or cyanosis*
PathologyThe characteristic pathologic changes in the kidney of women withpreeclampsia include swelling of the endothelial cells(glomerular endotheliosis), ballooning of capillary loopsinto the tubule, fibrinogen and lipid in endothelial cells, and.occasional foam cellsRarely, changes similar to focal sclerosis occur, with reversalpostpartum. Ischemic changes are less marked than in other.organs.The renal pathologic changes resolve 2 – 4 weeks postpartum
Prevention of PreeclampsiaTwo interventions have been extensivelyinvestigated to determine whether theyprevent preeclampsia: low-dose aspirin andcalcium supplementation. Despite initialpromise, the effects of these two treatments.have been disappointing in large trials
:-ManagementDelivery if viable / termination if remote from.termTemporizing measures if stablematernal/fetal unit and benefit of increased.fetal maturity outweight riskAntihypertensive therapy: PO or IV (not).diuretics.Seizure control – magnesium sulfate
Indications for delivery ≥ 36 weeks gestation. BP ≥ 160/110 after 24 hours of hospitalization. HELLP syndrome. ≥ 3 g of protein in 24 hours. Rising serum creatinine. Headache, blurred vision, scotomata, right upper quadrant pain, clonus.
Chronic hypertension with( 4superimposed pre-eclampsiaIf the systolic blood pressure exceeds 200 mmHg, pre-eclampsia superimposed on chronichypertension is suggested. In this setting,pulmonary capillary permeability may beincreased, resulting in pulmonary edema,central nervous system excitability mayoccur, causing hyper-reflexia and cerebral.hemorrhage
Diagnosis of pre-eclampsiasuperimposed on chronichypertension:If proteinuria prior to 20 wk is absentNew-onset proteinuria in a woman with * . chronic hypertension
If proteinuria prior to 20 wk is present, any ofthe following raise concern for superimposed:preeclampsia. A sudden increase in proteinuria.A sudden increase in hypertension. Thrombocytopenia. Increased in liver enzymes
HELLP SyndromeHELLP, a syndrome characterized by hemolysis, elevated liver enzyme levels and a low platelet count, is an obstetric complication that is frequently misdiagnosed at initial presentation. Many investigators consider the syndrome to be a variant of pre-eclampsia.
Clinical Presentation 90%of patients present with generalized malaise, 65 % with epigastric pain, 30 % with nausea and vomiting, 31 percent with headache.
The physical examination may be normal in patients with HELLP syndrome. %.right upper quadrant tenderness 90- 1. Edema is not a useful marker- 2Hypertension and proteinuria may be- 3. absent or mild
DiagnosisHaemolysis Abnormal peripheral smear : spherocytes, schistocytes, triangular cells and burr cells Total Bilirubin level > 1.2 mg/dL Lactate dehydrogenase level > 600U/LElevated liver function test result Serum aspartate amino transferase level > 70U/L Lactate dehydrogenase level >600 U/LLow platelet count Platelet count < 150 000/mm3
Complications The mortality rate for women with HELLP syndrome is approximately 1.1 % From 1 to 25 % of affected women develop serious complications such as DIC, placental abruption, adult respiratory distress syndrome, hepatorenal failure, pulmonary edema, subcapsular hematoma and hepatic rupture. A significant percentage of patients receive blood products.
Infant morbidity and mortality rates range from 10 to 60 %, depending on the severity of maternal disease. Infants affected by HELLP syndrome are more likely to experience intrauterine growth retardation and respiratory distress syndrome.
:-Corticosteroids-1 The antenatal administration of dexamethasone in a high dosage of 10 mg intravenously every 12 hours has been shown to markedly improve the laboratory abnormalities associated with HELLP syndrome. Steroids given antenatally do not prevent the typical worsening of laboratory abnormalities after delivery. However, laboratory abnormalities resolve more quickly in patients who continue to receive steroids postpartum.
:-Magnesium sulphate-2Patients with HELLP syndrome should be treated prophylactically with magnesium sulfate to prevent seizures, whether hypertension is present or not.
Antihypertensive therapy-3should be initiated if blood pressure is consistently greater than 160/110 mm hg despite the use of magnesium sulfate. The goal is to maintain diastolic blood pressure between 90 and 100 mm hg.
:-Blood products-4 Patients who undergo cesarean section should be transfused if their platelet count is less than 50,000 per mm3. Prophylactic transfusion of platelets at delivery does not reduce the incidence of postpartum hemorrhage or hasten normalization of the platelet count. Patients with DIC should be given fresh frozen plasma and packed red blood cells.
Renal failure in early pregnancy:-prerenal azotemia-1 Causesassociated with Hyperemesis gravidarum--metabolic alkalosis; diagnosis is made byhistory. Treatment requires the .administration of intravenous fluidsHemorrhage associated with spontaneous-.abortion
Renal failure in early pregnancy:-Acute tubular necrosis-2 CausesSevere volume depletion associated withhyperemesis gravidarum, hemorrhage from spontaneous abortion, or shock secondary to .septic abortionSeptic abortion, most commonly due toEscherichia coli; in some cases, however,Clostridium, which can cause myonecrosis of the.uterus and myoglobinuria, is responsible
The diagnosis of acute tubular necrosis can beestablished via the clinical setting, urinalysis,.and urinary indicesTreatment includes fluids, antibiotics and, if.necessary, dialysis
Renal failure in early pregnancy:-Renal cortical necrosis-3 ;CauseThe disorder is most likely initiated byprimary disseminated intravascularcoagulation in the setting of severe renal.ischemiaThis is a rare cause of severe acute renalfailure; it is more commonly associated .with pregnancy
Renal cortical necrosis presents with grosshematuria, flank pain, and severeoliguria/anuria following an obstetric :catastropheseptic abortion, retained fetus, amniotic fluid ( ).embolism
Laboratory Studiescheck for hyperkalemia, hypocalcemia, metabolic* .acidosis, and elevated creatinine levelsA CBC count may reveal hemolytic anemia and* .thrombocytopeniaCoagulation studies detect low fibrinogen levels * .and increased fibrin-degradation productsUrinalysis detects hematuria, proteinuria, RBC* .casts, and granular casts
Imaging Studies Ultrasonography*The sonogram initially shows enlarged .kidneys with reduced blood flowCortical tissue becomes shrunken later in.disease progression
Imaging Studies *Contrast-enhanced CT scanningCT scanning with contrast are the most sensitive .imaging modalityDiagnostic features include absent opacification ofthe renal cortex and enhancement ofsubcapsular and juxtamedullary areas and of the .medulla without excretion of contrast mediumInitiating hemodialysis immediately after theprocedure may be necessary to minimize further.contrast-mediated renal damage
Histologic FindingsRenal cortical necrosis is classified into 5 pathologic forms, depending onseverity, as shown below. Renal cortical necrosis classifications are as :followsFocal pathologic form: Kidneys show focally necrotic glomeruli .without thrombosis and patchy necrosis of tubulesMinor pathologic form: Larger foci of necrosis are evident with .vascular and glomerular thrombiPatchy pathologic form: Patches of necrosis may occupy two thirds .of the cortexGross pathologic form: Almost all cortex is involved. Thrombosis of.the arteries is more widespreadConfluent pathologic form: Kidneys show widespread glomerular.and tubular necrosis with no arterial involvement
Recovery typically requires months, and renal.functional recovery is usually incomplete
Renal failure in early pregnancy:-pyelonephritis-4Acute pyelonephritis is associated with a GFR -reduction that can be reversed with treatment .of the underlying infection
Renal failure in early pregnancyTTP&HUS-5-:represent a spectrum that includesmicroangiopathic hemolytic anemia,thrombocytopenia, and renal failure, TTP is morelikely to occur in the first trimester and generally .does not cause severe renal failurePatients may have a severe deficiency of ADAMTS- .13 .Plasma exchange is the primary treatment
Renal failure in late pregnancy.Pre-eclampsia &eclampsia- 1.HELLP syndrome-2.Acute tubular necrosis-3 .Acute fatty liver of pregnancy-4
Acute fatty liver of pregnancyAcute fatty liver of pregnancy (or hepaticlipidosis of pregnancy) usually manifests inthe third trimester of pregnancy, but mayoccur any time in the second half ofpregnancy or in the the period immediately .after delivery
:-CausesIt is thought to be caused by a disorderedmetabolism of fatty acids by mitochondria inthe mother, caused by deficiency in theLCHAD((long-chain 3-hydroxyacyl-coenzyme . A dehydrogenase) enzyme
Clinical manifestationsThe usual symptoms in the mother are non-.specific including nausea ,vomiting , anorexia.and abdominal painJaundice and fever may occur in 70% of.patientsIn patients with more severe disease pre- .eclampsia may occur
This may progress to involvement of additionalsystems, including acute renal failure,hepatic.encephalopathy and pancreatitisThere have also been reports of diabetes .insipidus complicating this condition
Diagnosis.Elevation of liver enzymes*Bilirubin is elevated *Alkaline phosphatase is often elevated in *pregnancy due to production from the.placentaElevated white blood cell count. *.*disseminated intravascular coagulation.Hypoglycemia*
DiagnosisAbdominal ultrasound may show fat depositionin the liver but, as the hallmark of thiscondition is microvesicular steatosis this maynot be seen on ultrasound Rarely, thecondition can be complicated by rupture ornecrosis of the liver, which may be identified by ultrasound
TreatmentInitial treatment involves supportive management withintravenous fluids, intravenous glucose and bloodproducts, including fresh frozen plasma and.cryoprecipitate to correct DICThe fetous should be monitored with cardiotocography.After the mother is stabilized, arrangements areusually made for delivery. This may occur vaginally,but, in cases of severe bleeding or compromise ofthe mothers status, a caesarian section may be . needed
Liver transplantation is rarely required fortreatment of the condition, but may beneeded for mothers with severe DIC, thosewith rupture of the liver, or those with severe.encephalopathy
Postpartum renal failurePostpartum acute renal failure usually presentsdays to weeks following a normal deliveryand may be related to retained placental .fragments
DIFFERENTIAL DIAGNOSIS OF MICROANGIOPATHIC :-SYNDROMES DURING PREGNANCY HELLP AFLP TTP HUSHypertension 80% 25-50% occasional presentRenal Mild to Moderate Mild to Severeinsufficiency moderate moderateFever, neurologicsymptoms 0 0 ++ 0onest 3rd trimester 3rd trimester Any time PostpartumPlt count Low to very low Low to very low Low to very low Low to very lowPTT Normal to high High Normal NormalLiver function test High to very high High to extremely Usually normal Usually normalAntithrombin III Low Low Normal Normal
Relationship between pregnancy and.kidney disease Effects of pregnancy Effects of kidney on kidney disease disease on pregnancy Worsening proteinuria Infertility Loss of kidney function Preterm delivery Hypertension and IUGR preeclampsia Decreased fetal survival Preeclampsia
High grade proteinuria and severe*4hypertensionalso important risk factors for progression of –.renal disease in pregnancy, worse outcomes
CKD and pregnancy – diabeticnephropathyof pregnant women with type I DM have overt 6%diabetic nephropathy (<20/40: U prot>300mg/d,macroalbuminuria >300mg/d, alb/creat. ratio)>0.3mg/mgMicroalbuminuria also associated with an increased• risk of adverse fetal-maternal outcomesEffect of nephropathy on pregnancy:•.prematurity(22%), IUGR(15%), pre-eclampsia
Effect of pregnancy on nephropathy:•.exacerbation of proteinuria and hypertensionReturn to baseline post-partum with well.preserved renal functionPre-eclampsia is the most frequent*complication of pregnancy in women with.diabetic nephropathy
CKD and pregnancy - ADPKDExacerbation of HTN, increased risk of pre-.eclampsiaPrenatal genetic testing for PKD1 disease.(C16) – availableNo increased incidence of simple UTI during.pregnancy
CKD and pregnancy - Lupus Rate of relapse not different between pregnant women and concurrent controls (9-60%). Major factor determining a pregnancy related exacerbation is the stability of the disease before conception If in remission for >6mths pre-conception, low incidence of clinical flare during pregnancy. Women with intracranial aneurysms may be at increased risk of subarachnoid hemorrhage. during labor
the frequency of exacerbations duringpregnancy was higher for women withmembranous nephropathy than for those.with diffuse proliferative glomerulonephritis
Antiphospholipid antibody syndrome in:-pregnancyThe presence of antiphospholipid antibodies or thelupus anticoagulant is associated with increased fetal;loss, particularly in the second trimester;increased risk of arterial and venous thrombosismanifestations of vasculitis such as thromboticmicroangiopathy; and an increased risk of. preeclampsiaTreatment consists of anticoagulation with heparin and.aspirin
ESRD requiring dialysis is associated with amarked decrease in fertility. Pregnancy,however, occurs in approximately 1% ofpatients, usually within the first few years of .starting dialysis
The fetal outcome is quite poor. Only 23-55% ofpregnancies result in surviving infants, and a largenumber of second-trimester spontaneous abortionsoccur. In addition, surviving infants have significantmorbidities. Approximately 85% of surviving infantsare born premature, and 28% are born SGA.Maternal complications occur as well. Severalmaternal deaths have been reported. Hypertensionworsens in more than 80% of pregnant females on .dialysis and is a major concern
:-RecommendationsSome general recommendations apply to patients who become pregnantwhile receiving dialysis. Place the patient on a transplant list (if not onalready) because outcomes with allograft transplant patients aremarkedly better. During hemodialysis, uterine and fetal monitoring andmake every attempt to avoid dialysis-induced hypotension. Someevidence indicates that the use of erythropoietin may improve fetalsurvival; however, no findings from randomized studies supports this.Erythropoietin can also increase hypertension and must be usedcautiously. Increased frequency of dialysis may improve mortality andmorbidity. Aggressive dialysis to keep BUN levels less than 50 mg/dLmay be need daily dialysis. Controlling uremia in this fashion mayavoid polyhydramnios, control hypertension, and improve the mothers.nutritional status
MedicationsCommon Safety issues Commentsmedications inCKD/ESRDErythropoietin. 1 Safe to use .Limited dataIron. 2 Safe to use Low dose intravenous iron recommendedVitamin D. 3 Widely used .Limited dataHeparin. 4 Safe to use Minimize dose of heparin
Guidelines for pregnancy in kidney:-transplant recipient Two years post-transplant, with good general health and serum creatinine less than 2.0 mg/dL (preferably <1.5 mg/dL(. No recent or ongoing rejection . Normotension, or minimal antihypertensives Absent or minimal proteinuria No evidence of pelvicalyceal dilation on renal ultrasonogram
:-Immunosuppression Prednisone - Less than 15 mg per day Azathioprine - Less than or equal to 2 mg/kg/d Calcineurin inhibitor–based therapy - Therapeutic levels Mycophenolate mofetil and sirolimus - Discontinue 6 weeks prior to conception Methylprednisolone - The preferred agent for treatment of rejection during pregnancy
Common medications in kidneytransplantationPrednisone. 1 Safe to use Fetal adrenal insuffi ciencyCyclosporine. 2 Safe to use IUGRTacrolimus. 3 Not safe to use Severe IUGR, renal failure, hyperkalemiaMycophenolate.4 Not safe to use Teratogenic in animalsmofetilAzathioprine. 5 Widely used Fetal neutropenia, teratogenic in high dosesPolyclonal. 6 Not safe to use Very limited dataantibodies
:-Complication Risks Immunosuppressive agents increase the risk of hypertension during pregnancy. Preeclampsia occurs in approximately one-third of transplant recipients. Almost 50% of pregnancies in these women end in preterm delivery due to hypertension. Blood levels of calcineurin inhibitors need to be frequently monitored due to changes in volumes of distribution of extracellular volume. There is an increased risk of infection included cytomegalovirus, toxoplasmosis, and herpes infections, and bacterial infection which arouse concern for the fetus.