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Effect of pregnancy on the kidney. Increased plasma volume Increased intravascular volume Increased GFR Increased intraglomerular pressure Hyponatremia is frequently seen Hypokalemia can be seen . Pregnancy and renal disease. Hormonal changes contribute to these changes
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Effect of pregnancy on the kidney • Increased plasma volume • Increased intravascular volume • Increased GFR • Increased intraglomerular pressure • Hyponatremia is frequently seen • Hypokalemia can be seen
Pregnancy and renal disease • Hormonal changes contribute to these changes • Pregnant ladies gain 12 to 16 kilograms of weight mostly fluids • Serum creatinine and BUN decreases in pregnancy • Normal serum creatinine can be a sign of a significant renal disease • Pregnancy affect renal disease and renal disease affect the outcome of pregnancy
Pregnancy and renal disease • Pregnancy is associated in a decline in renal function in 1 -- 10% of cases when GFR is mildly reduced at the beginning of pregnancy Cr less than 1.5 mg/dl • The rise in Cr is seen at the third trimester • Transient decline in renal function may be seen
Moderate renal impairment • Women with moderate renal insufficiency ( Cr between 1.5 and 2.9 mg/dl ) • In these patients there is a decline of Cr in the first trimester but rise above base line level as the pregnancy progress
3rd trimester First trimester 76 women with pregnancy and moderate renal impairment Jones etal New Eng J 1996 335 : 226
Some patients may have permanent decline in renal function • In the previous study 10% of the women progressed to end stage renal disease • The risk was highest in patients with a serum Cr above 2 mg/dl • The risk of permanent decline in renal function is highest in the presence of uncontrolled hypertension
Once serum creatinine exceed 3 mg /dl most women have amenorrhea or anovulatory cycles making the likelihood of pregnancy very small • Some studies showed some link between the type of renal disease and outcome being worse in MPGN and reflux nephropathy
Effect of kidney disease on pregnancy • Fetal survival is lowest with uncontrolled hypertension • The relative risk of fetal death tenfold higher in women with a mean blood pressure greater than 105 mmHg • The risk of prematurity is increased when serum creatinine exceed 1.4 mg/dl • Preterm delivery is not uncommon
There is an increased risk of pre-eclampsia with increased fetal and maternal morbidity • Pre-eclampsia might be more difficult to diagnose in the presence of baseline proteinuria and hypertension • In this situation worsening of proteinuria and hypertension might be a clue to the diagnosis
Pregnancy in the dialysis patient • The frequency of conception in this group is .3 to 1.5 % per year • There is increase fetal wastage in this group • Blood pressure and anemia may become more difficult to control in this group
Hou an his group surveyed 1281 women of childbearing age on dialysis • 1.5% became pregnant over tow years time • 52% had surviving infants Total no Survivng infants Hou,SH pregnancy in women on dialysis AM J Kid Dis 1994 23 60
Pregnancy and dialysis • Bogan in Belgium surveyed 1472 women of child bearing age on dialysis • 1.5% became pregnant over tow years time • 50% had successful out come of pregnancy Bagon etal pregnancy and dialysis Am J of Kid disease 1998 , 31 ; 766
Dialysis and pregnancy • There is improvement in the survival compared to old reports because of • More intense dialysis with BUN below 17 mmol/l 50 mg/dl ( almost daily dialysis ) • Higher dose of EPO is required to provide adequate red cell mass • Metabolic acidosis and hypocalcaemia should be corrected
Pregnancy and dialysis • Careful uterine and fetal monitoring during dialysis and through out the whole pregnancy • Avoid hypotension during dialysis since this may provoke uterine contraction and fetal loss • Nutritional status and dry weight should be assessed on frequent bases since intradialytic weight gain can be confused with the usual weight gain in pregnancy
Dialysis and fetal size • In spite of optimal therapy mothers are at increased risk of sever hypertension and premature delivery with a mean gestational age of 30 weeks • If the patient is a good potential candidate for transplant it is better to delay pregnancy tell she is transplanted
Case presentation • A 24 year old saudi lady found to have raised creatinine when she was evaluated for primary infertility and a diagnosis of ESRD was made • Her renal function continued to deteriorate and she was put on regular hemodialysis • A cadaver transplant was done
Case presentation • The transplant was successful and her serum Cr was around 1.2 mg/dl • She was maintained on azathioprine steroids and cyclosporine • She became pregnant 18 months post transplant with a full term twins • Serum Cr post delivery was 1.3 mg • One year later her serum Cr was 1.4 • She became pregnant
Case presentation • Hb before gestation was 9.4 gm • Hb decreased to 7.8 gm with more symptoms • EPO was added and her anemia improved with Hb of 11 at the time of delivery • The outcome of the pregnancy was successful
Erythropoietin Therapy in a Pregnant Post-Renal Transplant PatientSaad Al ShohaibDepartment of Medicine, King Khalid National Guard Hospital, Jeddah, Kingdom of Saudi Arabia Address of Corresponding Author Nephron 1999;81:81-83 (DOI: 10.1159/000045251)
Renal transplant • Fertility return after transplant with a pregnancy success rate of more than 90% after the first trimester • There is slight increase in spontaneous abortion and intrauterine growth retardation • Pregnancy has no important early effect on renal function and affected by the same factors in pregnancy in patients with renal impairment
Renal transplant • Women are advised to wait one year after living related transplant and tow years post cadaver transplant to avoid complications arising from rejection • Neither low dose prednisolone or azathioprine appear to have adverse effect on the fetus • The obstetrician should review the operative notes to confirm the location of the graft
cyclosporine • Cyclosporine may aggravate or induce hypertension during pregnancy • Cyclosporine does not appear to be a major teratogen • Cyclosporine metabolism is increased during pregnancy and higher doses may be required to achieve adequate levels however there is controversy regarding adjusting the dose
Mycophenolate mofetil • MMF should not be used in pregnancy as animal studies showed adverse effect on the fetus • Patient that are welling to get pregnant should be converted to azathioprine
Sirolimus (Rapamycin ) • Sirolimus is contraindicated in pregnancy and should discontinued at least 12 weeks prior to pregnancy • Cyclosporine should be used during gestation but once delivered sirolimus can be restarted
Tacrolimus (prograf ) • Kains reviewed 100 pregnancies in 84 women treated on prograf • 27% were renal transplant recipients • 68% progressed to alive birth • Four babies had malformations
Obstetrical mangement • Increase frequency of prenatal visit • Early treatment of a symptomatic bacteriuria • Monthly renal function • Close monitoring for the development of pre eclampsia
SLE • SLE occur frequently in women in child bearing age • SLE patients are usually as fertile as other patients but their pregnancy is associated with more complication • The prognosis is best for both the mother and fetus if SLE is quiescent for at least 6 months
SLE • Exacerbation of the disease • Fetal loss • Neonatal lupus • Breast feeding
Exacerbation of the disease • 50% of patients will exacerbate their disease during pregnancy • Flares occur in all three trimester and in the immediate postpartum period
Ruiz prospectively evaluated 40 pregnancies in 37 patients with SLE • Flare up occurred in 24 cases 60% • Compared to the rates of flare up post delivery the rate is higher • Flare up mainly as nephritis and arthritis Ruiz etal increased rate of lupus flare up during pregnancy Br J Rheum 1996 35:133
Lupus nephritis • There is increased risk of fetal loss • Increased risk of worsening renal function as well as other manifestations of the disease • Sever renal impairment requiring dialysis may occur • Pre existing hypertension and azotemia are associated with worse prognosis
SLE following transplant • The outcome is similar to other transplant patients
Comparison between SLE and Non SLE post renal transplant pregnancy outcome Live birth abortion Therapeutic termination Mccy Groy etal pregnancy outcome Am J Transp 2003 3:35
pre eclampsia and SLE P • Preeclampsia is a frequent complication of SLE 13% • It might be difficult to distinguish between preeclamsia and lupus nephritis • Active urinary sediment is suggestive of lupus nephritis
Pre eclampsia and SLE • Complement C3 C4 are low in lupus nephritis but normal in preeclamsia • Anti DNA titer is increased in lupus nephritis • Thrombocytopenia and raised liver enzymes are suggestive of preecalmpsia
Fetal loss and SLE risk factors • Hypertension • Lupus nephritis • Low C3 high DNA • Antiphospholipid antibody
Fetal loss and SLE Petri etal fetal outcome of lupus pregnancy J Rheum 1993 20 650
Hypertension and pregnancy • Preeclamsia eclampsia • Chronic hypertension (present before 20 weeks of pregnancy • Preeclampsia superimposed on underlying hypertension • Gestational hypertension (hypertension in after 20 weeks without prteinuria
Hypertension preeclampsia • Labetalol is the is the preferred therapy for sever hypertension • Hydralazine is an acceptable alternative • Methyldopa and labetalol the first line oral therapy • Atenolol should be avoided in early pregnancy
Hypertension and pregnancy • ACE inhibitors and ARBs are contraindicated during pregnancy since uterine and placental ischemia may occur • Nitroprusside should be avoided (fetal cyanide poisinig)
Breast feeding • Beta blockers and calcium channel blockers enter breast milk but are safe during lactation • ACE inhibitors and ARBs should be avoided • Diuretics reduce milk volume and should be avoided
Preexisting hypertension • Has a strong on fetal and maternal outcome • Preeclampsia 10– 20% • Preterm birth 12—34% • Growth retardation 8—16% • The higher the blood pressure the worse the outcome
ARF in pregnancy • HUS TTP • HELLP syndrome • Renal cortical necrosis • Acute pyelonephritis • Acute fatty liver of pregnancy