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Pregnancy and Renal Disease
 

Pregnancy and Renal Disease

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    Pregnancy and Renal Disease Pregnancy and Renal Disease Presentation Transcript

    •  
    • & DR.A.NILAVAN PG II YEAR
    •  
    • Anatomic changes
    • PHYSIOLOGICAL CHANGES
      • SYSTEMIC HEMOYNAMIC CHANGES
      • # plasma volume increase by 50 to 60%
      • # c.o increase by 40to 50%
      • # hypo tension ( 10 mm hg decrease)
    • RENAL HEMODYNAMICS
      • GLOMERULAR CHANGES
      • # RPF increases by 60%
      • # GFR increases by 50%
      • # sr creatinine decreases
      • inspite of these changes
      • Intraglomerular blood pr is
      • unchanged and this has long
      • term effect on renal function
    • TUBULAR CHANGES
    • Cont…. Pre-pregnancy Pregnancy Uric acid(mg/dl) 4 3.2 (early) 4.3 (late) Sodium(mmol/l) 140 135 Pottasium(mmol/l) Slight increase BUN(mg/dl) 12.7 9.3 Urea(mmol/l) 4.5 3.3 Vitamin/ amino acid decreases Protein(g/dl) 7 6(proteinuria) glucose glucosuria ca decreases Osmolality(mosm/kg) 285 275
    • Common changes in pregnancy Pre-pregnancy pregnancy Hematocrit% 41 33 Plasma protein(g/dl) 7 6 Plasma osmolality(mosm/kg) 285 275 Plasma sodium(mmol/l) 140 135 Plasma creatinine(mg/dl) 0.8 0.5 BUN(mg/dl) 12.7 9.3 Plasma urea(mmol/l) 4.5 3.3 pH 7.40 7.44 PCO2(mmhg) 40 30 Hco3(mmol) 25 20 SBP(mmhg) 115 105 DBP(mmhg) 70 60
    • Renal complications in pregnancy
      • UTI & Asymptomatic bacteriuria
      • Hypertensive disorders of pregnancy
      • Acute renal failure
      • Renal calculi
      • Abnormal urinalysis
    • Urinary Tract Infection
        • 1-2 % of pregnancy
        • Assosiated with SGA , IUD, premature labour, Hypertension and anemia
        • Persistant leukocyturia (2-3 wbc/HPF)
      Significant bacteriuria 10 5
      • 10 2 with symptoms
      • cystitis/ pyelonephritis
    • Cont…
      • Pyelonephritis
        • 70% have asymptomatic bacteriuria
        • Mostly in second trimester
        • Symptoms – Pain, fever, dysuria
        • Complication – Endotoxic Shock, DIC, ARF
        • Treatment
          • Hydration
          • IV Antibiotics for 24 – 48 hours
          • Change to oral antibiotics for 10-14 days
    • Cont…
      • Cystitis
        • Symptoms – Urgency, frequency and dysuria without systemic signs
        • Culture may be negative
        • Recurrence is 17%
        • Usually doesnot progress to pyelonephritis
      • Asymptomatic Bacteriuria
        • 2-7%
        • Without pyuria
        • 30% will progress to pyelonephritis
        • Increases risk of premature labour and low birhtweight
        • urine culture
      Repeat culture in high risk patient ( repeated UTI and anomalies) Treatment : Cephalosporins for 3-7 days (pyelonephritis risk reduced to 3%) Recheck culture after 2-3 weeks ( recurrence 35%) 2 or more repeated infection Supressive therapy with nitrafurantoin and cephalosporins
    • Safety of antibiotics category Antibiotic A. Drugs taken by large no of pregnant women with out any proven harm Amox, ampi,cefalexin, Cephalothin,nitrofurantoin,penicillin B1 Taken by limited no of pregnant women with out proven harm; animal studies show no increase in fetal harm Aztreonam, ceftazidime,cefataxime, cefaclor, amox/clavulanic acid,piperacillin B2 As B1, but animal data unavailable Vancomycin B3 As B1,but animal studies show an increase in fetal damage Cipro, norfloxacin, ofloxacin,imipenem, Trimethoprim C Drugs whose pharmalogic effects are suspected of causing harm Sulphonamides, Cotrimoxazole, fusidic acid D Proven to cause fetal harm Tetracycline, gentamycin, Chloramphenicol
    • HYPERTENSION
    •  
    • PRE ECLAMPSIA
      • New onset hypertension(140/90mmhg) & proteinuria after 20 weeks( PC ratio 0.3 μ g/ mg creatinine)
      • Edema
      • Uric acid >5.5mg/dl
      • PATHOGENESIS
      • wide spread endothelial dysfunction and
      • micro angio pathy in mother
    • Severe preeclampsia BP 160/110 Urine PC ratio >5 μ g/mg or proteinuria >5g/24 h urine Oliguria CVA , seizures, visual disturbance Pulmonary edema Epigastric or rt upper quadrant pain Hepato cellular injury Sr LDH >600 iu/l Thrombocytopenia < 100000(HELLP syndrome) IUGR
      • Natural History
        • Proteinuria and hypertension usually will disappear within days or weeks, sometimes may take maximum of six months
        • Renal Biopsy – Proteinuria for more than six months , Deteriorating renal function, Presence of Urinary Sediments
        • Predicts future hypertension 7-37% and future cardiovascular risk
      • Prevention
        • 75-80 mg Aspirin
        • Calcium
        • Vit C and E do not protect
    • Management
      • Bed rest
      • Weight loss & salt restriction not recommended
      • Anti hyper tensive
      • ACE inhibitors& ARB contraindicated .
      • Diuretics should be used carefully .
      • Alfa methyl dopa is the drug of choice.
      • Hydralazine is drug of choice in emergencies.
      • β blockers can be used.
      • CCB may cause tocolysis in third trimester
    • Management of preeclampsia PROBLEM MANAGEMENT Control blood pr Acute Rx if BP >170/110 Chronic Rx if BP>140/90 Eclampsia Diazepam 10-20mg to terminate convulsion Magnesium sulfate for neurological sign 4 g IV over 20 minutes then 1.5 g/hr for 48 hrs Volume expander therapy 500-1000 ml of colloid over 4-6 hr for persistent oliguria Supportive therapy Platelet infusion if count <20000-40000 FFP for micro angiopathy Dialysis for ARF Progressive decline in renal, hepatic or clotting function or fetal growth Delivery
    • Type of hyper tension drug Rx given Acute Hydralazine 5 mg bolus every20- 30 min (max 20 mg) then infusion at 5-10 mg/hr Labetolol 50 mg 20 every min (max 300mg) Nifidipine 20 mg oral Chronic first line Methyl dopa 500-2000mg/day PO Clonidine 0.2-0.8 mg /day PO Labetolol 200-1200mg/day PO Atenolol 50- 100 mg/day PO Second line Hydralazine 25-200 mg/day PO Prazosin 1-10 mg/day PO Nifidipine sr 40-100 mg/day PO
    • Acute renal failure in pregnancy
      • Renal failure in early pregnancy
      • Prerenal azotemia
        • Causes
          • Hyperemesis gravidarum
          • Hemorrhage associated with spontaneous abortion
      • Acute tubular necrosis
        • Causes
          • Severe volume depletion (hyperemesis gravidarum, hemorrhage from spontaneous abortion, or shock secondary to septic abortion )
    • Cont….
      • Renal Cortical Necrosis
        • Cause
          • The disorder is most likely initiated by primary disseminated intravascular coagulation in the setting of severe renal ischemia
        • It is more commonly associated with pregnancy.
        • C/F- gross hematuria, flank pain, and severe oliguria/anuria following an obstetric catastrophe (abruptio placentae, septic abortion, retained fetus, amniotic fluid embolism).
        • The diagnosis can usually be confirmed by demonstrating a radiolucent rim in the cortex , using computed tomography (CT) scanning.
        • Recovery typically requires months, and renal functional recovery is usually incomplete.
    • Cont….
      • Pyelonephritis
      • Thrombotic thrombocytopenic purpura(TTP)
        • While TTPand hemolytic uremicsyndrome represent a spectrum that includes microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, TTP is more likely to occur in the first trimester and generally does not cause severe renal failure.
        • Patients may have a severe deficiency of ADAMTS-13.
        • Plasma exchange is the primary treatment
    • Renal failure in late pregnancy
      • Causes
      • Preeclampsia and the associated disorders (eclampsia and HELLP)
      • Acute tubular necrosis
        • causes- Preeclampsia,
        • HELLP syndrome
        • Uterine hemorrhage with abruptio
      • Acute fatty liver of pregnancy
    • Cont…
      • 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 aspartate aminotransferase and alanine aminotransferase levels also occurring. 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
    • Postpartum renal failure
      • Hemolytic uremic syndrome
        • severe hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.
        • Postpartum acute renal failure usually presents days to weeks following a normal delivery and may be related to retained placental fragments
        • Hemolytic uremic syndrome can be difficult to differentiate from severe preeclampsia or HELLP syndrome and may require renal biopsy for diagnosis(presence of schistocytes may be help ful)
    • Other causes of acute renal failure in pregnancy
      • Obstructive Uropathy
        • moderate or severe dilatation of the collecting system in women with oliguria or anuria
        • Etiologies of obstructive uropathy include gravid uterus, polyhydramnios, kidney stones, and enlarged uterine fibroids.
        • Obstructive uropathy usually resolves with delivery, although ureteral stenting may be required preterm .
      • Nephrolithiasis
      • Antiphospholipid syndrome
        • All pregnant women with lupus should be screened for antiphospholipid antibodies and lupus anticoagulant.
        • These women are at increased risk for fetal loss and worsening of renal function .
        • Treatment with low-dose aspirin or heparin depends on antibody levels and previous obstetric history of early fetal loss and/or thrombo
    • Management ARF
      • Restoration of fluid nvolume
      • Appropriate antibiotics
      • Delivery of baby as early as possible
      • DIALYSIS – individualised
      • - sr. creatinine ≥3.5 mg/dl
    • URINALYSIS
      • Hematuria
      • Proteinuria
      • Pyuria
    • Hematuria
      • Microscopic Hematuria
        • 20 % of normal pregnancy
        • Lupus Nephritis
        • Ig A Nephropathy
        • TMD
        • Calculi
        • Polycystic Kidney Disease
        • Sickle cell trait
      • Macroscopic Hematuria
        • Hemorrhagic bacterial cystitis
        • Neoplasm
        • Calculi
    • Proteinuria
      • More than 300mg/day or Urine PC ratio 0.3 mg per milligram of creatinine
      • DD
        • Renal Calculi
        • Preeclampsia
        • New Onset glomerular disease
    • Pyuria
      • May be due to infection or contamination of Vagina
    • Nephrolithiasis
      • Decrease risk of calcium stone
      • Though calciuria/ dilatation/ stasis, there is increased excretion of inhibitor of stone formation( magnesium, citrate, nephrocalcin)
      • Decreased risk of uric acid &cystine stone
      • due to gestational bicarbonateamia and alkalanisation of urine
      • Xanthine oxidase and d-pencillamine avoided especially during Ist trimester
      • Complication
      • preterm rupture of membranes
      • UTI-Management : treatment for longer period followed by antibiotic prophylaxis
      • Ultrasonography is the primary diagnostic imaging modality .
      • Ureteral stenting may be necessary if the stones cannot be passed.
    • PREGNANCY WITH PRE-EXISTING KIDNEY DISEASE Effects on Renal disease Effects on Pregnancy outcome RENAL FUNCTION: Mild: Serum creatinine < 1.4 GFR >50 ml/min Mild/ no deterioration of renal function Preterm labour Moderate: Serun Creatinine 1.5-1.9 GFR 25-50ml/min 40% decline in renal function, but 50% will have recovery 2%----ESRD Preterm labour Preeclampsia IUGR Severe: Serum Creatinine >2 GFR <25ml/min 2/3----rapid decline 1/3-----ESRD Preterm labour Preeclampsia IUGR
    • Cont… Effects on Renal Disease Effects on Pregnancy Outcome PROTEINURIA >500mg /24hr urine
      • Thromboembolism
      • Risk for chronic hypertension
      • Poor long term renal prognosis
      Preterm labour Preeclampsia IUGR HYPERTENSION >Rapid decline in renal function Preterm labour Preeclampsia IUGR Increased perinatal mortality ( from 4% t 23 %) UTI Pyelonephritis Preterm Labour Low Birth Weight REDUCED PLASMA VOLUME IUGR HYPERGLYCAEMIA Large for gestational age
    • MANAGEMENT OF WOMEN WITH CKD DURING PREGNANCY PREPREGNANCY Advise- Increased risk of Pregnancy complications |( IUGR, Preeclampsia,pretem labour) Adivise – increased risk of deteriorating maternal renal function Discontinue inappropriate medication- STATINS, ACE INHIBITORS, ARB Aspirin 75 m/dl Folic acid 5 mg/dl
      • PRENATAL MONITORING
      • Urine |Culture every 4-6 weeks- after one infection , keep urine sterile with prophylactic antibiotics
      • Proteinuria more than 3g/24hr-thrombosis prophylaxis with LMW heparin
      • Proteinuria 1-3g/24hr- prophylaxis if other risk factors ( smoking , matrenal age> 35 yrs, obesity, immobilty)
      • Haematuria- if red cell cast suggesting active parenchymal disease, consider renal biopsy or delivery if > 32 weeks
      • Blood Pressure – maintain BP at or below 140/90 mm Hg with antihypertensive medication
      • Serum Creatinine, BUN- recognise acute or chronic renal impairment and need for dialysis
      • FBC and iron status’-use iron or EPO if necessary to keep Hb 10-11g/dl
      • Baseline renal ultrasound ( pelvicalyceal dimensions)
      • POST NATAL
      • Close monitoring of BP and fluid balance
      • Continue LMW heparin for 6 weeks
      • Return to nonpregnant medication regimen over 2 weeks
    • Management of woman on maintainance dialysis during pregnancy
      • PREGNANCY
      • Woman on dialysis have reduced fertility(0.5—3%)
      • Pregnancy is more likely if optimun Hb and iron status
      • Pregnancy is more likely to be successful with HD rather than PD
      • Advise increased risk of adverse pregnancy outcome (preterm labour, IUGR and pre-eclampsia)
      • Discontinue inapporporiate medications- statins, ACE inhibitors, ARB
      • PRENATAL
      • HD regimen to mimic physiological renal changes of pregnancy
      • after first trimester increase dialysis regimen to almost daily( 20-24hrs per week) to keep predialysis BUN < 50 mg/dl, serum urea< 17 mmol/L
      • Increase EPO and Iron to keep Hb 10-11g/dl
      • Recognise gestational weight gain, approximately 0.5kg/week in 2 nd and 3 rd trimster
      • Recognise hypertension might be caused by fluid overload before using anti-hypertensive medication
      • Give Aspirin 75 mg and Folic acid 5mg daily throughout pregnancy.
      • Adjust phosphate binders and vitamin D according to serum chemistry
      • Aim for protein intake 1.2 to 1.8 g/kg/day
      • LABOUR AND DELIVERY
      • Cesarean Section most likely
      • Women on PD will need temporary HD ( for 72 hours)
      • POS TNATAL
      • Close monitoring of BP and Fluid balance
      • Gradually return to non-pregnant dialysis regimen over 2 weeks
      • PREPREGNANCY
      • Advise to delay pregnancy until 2 years post-transplantation
      • Advise of increased risk of adverse pregnancy outcome according to BP, proteinuria and GFR
      • Discontinue and substitute inappropriate medications including statins, ACE inhibitors , ARB, mycophenolate and sirolimus
      • PRENATAL
      • Aspirin 75 mg once daily
      • Folic acid 5mg daily
      • Keep maintenance CNIs at lower end of therapeutic levels
      • Be aware of the dilutional fall in CNI levels in pregnancy
      • Monitor BP, renal function, Proteinuria and urine culture every 4-6 weeks throughout pregnancy
      MANAGEMENT OF RENAL TRANSPLANT RECEPIENTS DURING PREGNANCY
      • LABOUR
      • peri-partum prophylactic antibiotics
      • Spontaneous vaginal delivery, usually possible despite pelvis kidney
      • Temporary increase in steroid dose to cover the stress of delivery
      • POSTNATAL
      • re-adjust CNIs dose
      • Breastfeeding while taking azathioprine and cyclosporine unlikely to be harmful but should probably be limited to < one month
    • Glomerulonephritis
      • Clinical parameters like Hypertension/proteinuria/ development of renal impairment/ UTI more important than histological type
      • Biopsy-
      • sudden renal impairment with serum creatinine >1.4 mg/dl
      • New onset heavy proteinuria ( >5g/24hrs)
      • Active urinary sediment with red cell cast (32 weeks)
    • Ig A Nephropathy
      • Women with normal renal function&BP have successful uncomplicated pregnancy
      • Pre-existing HT- risk factor for pre-eclampsia and fetal prematurity
      ADPKD
      • High risk for recurrent proteinuria/Hypertension during pregnancy
      • Pregnancy has triggered recurrent HSP
    • Reflux Nephropathy
      • 1. Complications
      • Superimposed pre-eclampsia
      • Recurrent UTI
      • Deteriorating renal function
      • Chronic Hypertension
      • Increased fetal mortality
      • 2. Antenatal period
      • Urine culture every 4-6 weeks throughout pregnancy
      • 3. Women with persistent VUR should be corrected befire planning for pregnancy .
    • Upper Urinary Tract Obstruction
      • ANTENATAL PERIOD
      • Renal function assessment
      • Urine culture and BP
      • USG -at end of first trimester
      • repeat if symptoms of infectionor rise in sr creatinine occurs
    • LUPUS NEPHRITIS
        • The best outcomes occur in women who have had stable, inactive lupus for 6 months or longer prior to conception.
          • Renal flares in pregnancy usually present with proteinuria, hypertension, and falling GFR, making distinction from preeclampsia very difficult. Low complement levels may be helpful in distinguishing between women with preeclampsia and patients with active lupus nephritis.
          • These patients should all be screened for anti-SSA, due to the risk of congenital heart block
    • Cont… MANAGEMENT
      • low dose steroids
      • azathioprine
      • hydroxychloroquine
      • relapse- iv methyl prednisolone 500mg daily for 3 days
      • increased oral prednisolone
      • antihyper tensive
      • low dose aspirin
      • LMWH
      • peripartum flare up - steroids
    • Diabetic nephropathy
      • Pregnant women with diabetic nephropathy may also develop worsening proteinuria and hypertension
      • Complication - preeclampsia
      • still birth
      • good control of blood glucose & blood pressure before and during pregnancy improves perinatal & maternal out come
    •  
        • Guidelines for pregnancy in kidney transplant recipient:
          • Two years posttransplant, 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
        • 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 cytomegalovirus, toxoplasmosis, and herpes infections, which arouse concern for the fetus.