Pregnancy & Kidney Prof. (Dr.) Iffat Yazdani Aga Khan University Hospital / Clifton Kidney & General Hospital.

Pregnancy & Kidney

Prof. (Dr.) Iffat YazdaniAga Khan University Hospital /

Clifton Kidney & General Hospital

Normal Renal Alterations in Pregnancy

Changes in G.F.R.

• GFR and RBF rise markedly • Glomerular hyperfiltration results in normal reduction

in the plasma creatinine concentration to about 0.4 to 0.5 mg/dL

• Blood urea nitrogen (BUN) and uric acid levels fall for the same reason

Before PregnancyWomen with chronic kidney

disease often have amenorrhoea but may still occasionally ovulate

and thus conceive

• Contraceptive measures that consider clinical comorbidities should be taken by those who do not wish to become pregnant.

• Folic acid 400 μg, until 12 weeks’ gestation.

• Low dose aspirin (50-150 mg/day) reduces the risk of pre-eclampsia

• Fetotoxic drugs - such as ACE inhibitors and angiotensin II receptor blockers—should be stopped.

2 questions, when a woman with underlying kidney disease

becomes pregnant:

• What is the effect of pregnancy on the kidney disease ?

• What is the effect of the kidney disease on pregnancy ?

1. Pregnancy in mild to moderate Kidney Disease

2. Pregnancy in Dialysis Patients3. Pregnancy in Renal Transplant4. Pregnancy in Diabetic Nephropathy5. Pregnancy in Lupus Nephropathy6. Pregnancy in Glomerulonephritis

Renal Function may decline as a result of Pregnancy among patients with renal disease, determined in part by the severity of underlying renal disease.

Effect of Pregnancy on Renal Function

GRF Mildly reduced Plasma Creatinine < 1.5 mg % Permanent decline in Renal Function 0-10%Others Transient Decline

GFR moderately reduced Plasma Creatinine 1.6-2.9 mg % SCreatinine rises as pregnancy progresses40% of women decline in renal function

Risk of Irreversible loss of GRF exceed s in patients who have uncontrolled hypertension

During PregnancyCare of Women with Chronic Kidney Disease

Urine Blood Pressure

Renal Function Full Blood Count

Ultrasound of Renal Tract

4 – 6 WeeksCheck(1) Prophylactic antibiotics, (2) proteinuria – thromboprophylaxis with low molecular weight heparin if > 1g proteinuria /24 h (3) haematuria – perform microscopy

Aim to keep it between120/70 & 140/90 mm Hg

Check serum creatinine & Urea depending on the stage of the disease. More frequently for disease stages 3-5 and in the second half of pregnancy.

Keep Haemoglobin at 10-11 g/l

Perform Base line renal ultrasound – 12 weeks

CKD in mild to moderate kidney diseaseNevis IF American Society of Nephrology - 2011

– Mother• Gestational HTN• Pre Eclampisa / Eclampsia (2nd trimester)

– Child• Preterm Birth• Small for age• Still birth

Frequency of conception among women of

childbearing age on dialysis ranges from 0.3 - 1.5 % per

year.

• Intensification of dialysisKeep B.U.N. ↓ 50 mg/dl to avoid polyhydramnios.

slow rate U.F. hypotension5 to 7, Hemodialysis minimal heparinization to avoid sessions with bicarbonate buffer volume contraction

• Adequate supply of calories and protein

Protein intake should be - 1 g/kg per day - Additional 20 g/day for fetal growth. - Supplemented with water soluble vitamins and zinc

• Antihypertensive regimen

Acceptable antihypertensives include labetalol, Nifedipine XL, methyldopa, and metoprolol.Avoidable antihypertensives Diuretics, ACE inhibitors, ARBs.

• Correction of AnemiaGive Erythropoietin with Iron & Folic Acid supplemented. Keep Hb % > 10.

• Treatment of premature labor

The use of β agonists is preferred & NSAIDs should be avoided.

• Avoidance of metabolic acidosis

• Prevention of hypocalcemia

• Reinforced fetal monitoring as soon as viability is reached

Management of Pregnant Dialysis Patient

Common Themes in Dialysing Pregnant Patients

1. Keeping BUN < 502. Increasing dialysis time and frequency3. BP control4. Managing anemia with increasing doses of ESA5. Fetal monitoring once viability reached

Women who Start Dialysis During Pregnancy

• Likelihood of infant surviving is good• Termination of a pregnancy after renal function has

begun to deteriorate rarely rescues the kidneys• NEJM, Jones and Hayslett, 1996, looked at 82

pregnancies in 67 women w/CRI, only 15% of those w/deteriorating renal function had a return of renal function to baseline in 6 mths post partum

Medications

Comments Safety issues Common medications in CKD/ESRD

Limited data. Safe to use 1 .Erythropoietin

Low dose intravenous iron recommended

Safe to use 2 .Iron

Limited data. Widely used 3 .Vitamin D

Minimize dose of heparin

Safe to use 4 .Heparin

Renal Transplant & Pregnancy

Women are advised to wait at least one year after living, related-donor transplantation and two years after deceased transplantation to avoid complications. The renal allograft should be functioning well, with a stable serum creatinine level <1.5 mg/dL (132 micromol/L) and urinary protein excretion <500 mg/day.

Common Medications in Kidney Transplantation

Fetal adrenal insuffi ciency

Safe to use 1 .Prednisone

IUGR Safe to use 2 .Cyclosporine

Severe IUGR, renal failure, hyperkalemia

Not safe to use 3 .Tacrolimus

Teratogenic in animals Not safe to use 4.Mycophenolate mofetil

Fetal neutropenia, teratogenic in high doses

Widely used 5 .Azathioprine

Very limited data Not safe to use 6 .Polyclonal antibodies

C.K.D. and Pregnancy – Diabetic Nephropathy

• 6% of pregnant women with type I DM have :– overt diabetic nephropathy (<20/40: U prot>300mg/d– macroalbuminuria >300mg/d– alb/creat. ratio >0.3mg/mg)

• Effect of nephropathy on pregnancy– prematurity(22%)– IUGR(15%), pre-eclampsia

Pregnant women with diabetes & risk of developing kidney

diseasesWith normal albumin ↓ low risk

With microalbuminuria and normal kidney function

↓ low risk

With poorly controlled HTN or reduced G.F.R. and S.Cr. > 1.5 mg/dL, proteinuria >3 g in 24 hours)

↑ high risk

Ekbom P, Damm (Diabetes Care 2001) /Young EC, Pires ML / Carr DB, Koontz GL, Gardella C. Am J Hypertens / Yogev Y, Chen R, Ben-Haroush (Neonatal Med 2010; 23:999) / Nielsen LR, Damm P, Mathiesen ER. (Diabetes Care 2009; 32:38)

Maternal Complications in Pregnancies Complicated by

Diabetic Nephropathy (2001 to 2012)

• Pregnant women with diabetes, microalbuminuria, and normal kidney function appear to be at low risk for loss of kidney function, but may have a transient increase in albuminuria

• Women with poorly controlled hypertension or reduced glomerular filtration rate (GFR) and increased proteinuria (serum creatinine level >1.5 mg/dL, proteinuria >3 g in 24 hours) at the onset of pregnancy are at risk of permanent kidney damage, including end-stage kidney disease.

• Recommended B.P. 110-129/ 65-79 mm Hg

Diabetic Kidney Disease Complications

• Fetal growth restriction• Abnormal antenatal fetal assessment• Preeclampsia, even in women with good

glycemic control.

The occurrence of these pregnancy complications may necessitate preterm delivery and increases the chance of cesarean birth

C.K.D. 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 > 6 months pre-conception, low incidence of clinical flare during pregnancy.

• Women with intracranial aneurysms may be at increased risk of subarachnoid hemorrhage

during labor.

Lupus Flare-up Versus Preeclampsia

PE SLE

+ + Proteinuria

+ + Hypertension

- + RBCs cast

+ + Azotemia

- + Low C3, C4

+/- - Abnormal liver function test results

+/- + Low platelet count

- + Low leukocyte count

Causes of Proteinuria in PregnancyPrimary renal diseases• IgA nephropathy

• Minimal change disease

• Membranous nephropathy

• Focal segmental glomerulosclerosis

• Primary glomerulonephritis

• Allergic interstitial nephritis

• Polycystic kidney disease

Systemic causes• Preeclampsia

• Diabetic nephropathy

• Lupus nephritis (diffuse proliferative, focal proliferative, membranous)

• Hypertensive nephrosclerosis

• Thrombotic thrombocytopenic purpura (TTP)

• Infection-associated glomerular disease (eg, HIV, hepatitis B/C)

• Systemic vasculitis

• Multiple myeloma

• Chronic vesicoureteral reflux

• Antiphospholipid syndrome

• Symptomatic urinary tract obstruction

• Preeclampsia is the most common cause of proteinuria in pregnancy and must be excluded in all women with proteinuria first identified after 20 weeks of gestation.

• If preeclampsia is excluded, then the presence of primary or secondary renal disease should be considered.

Criteria for the diagnosis of preeclampsiaSystolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on two occasions at least four hours apart after 20 weeks of gestation in a previously normotensive patient

If systolic blood pressure is ≥160 mmHg or diastolic blood pressure is ≥110 mmHg, confirmation within minutes is sufficient

and

Proteinuria ≥0.3 grams in a 24-hour urine specimen or protein (mg/dL)/creatinine (mg/dL) ratio ≥0.3

Dipstick 1+ if a quantitative measurement is unavailable

In patients with new-onset hypertension without proteinuria, the new onset of any of the following is diagnostic of preeclampsia:

Platelet count <100,000/microliter

Serum creatinine >1.1 mg/dL or doubling of serum creatinine in the absence of other renal disease

Liver transaminases at least twice the normal concentrationsPulmonary edemaCerebral or visual symptoms

Adapted from: Hypertension in pregnancy: Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122:1122.Graphic 79977 Version 9.0

Women with Nephrotic Syndrome

• Discomfort from severe leg edema can be managed with sodium restriction (1.5 g, approximately 60 mEq), bedrest, and leg elevation.

• Prophylactic anticoagulation is reasonable in pregnant women with nephrotic syndrome and severe hypoalbuminemia (serum albumin <2.0 mg/dL, or <2.8mg/dL in membranous nephropathy), especially if another risk factor (eg, bedrest) is present.

• Bile acid sequestrants and fibrates can be safely used in pregnancy to treat severe hyperlipidemia due to nephrotic syndrome; statins should be avoided.

Kidney Biopsy During Pregnancy

• There are few Indications for Kidney Biopsy s• May be performed if there is a sudden

unexplained deterioration in renal function or markedly symptomatic nephrotic syndrome occurring before 32 weeks gestation.

• Biopsy after week 32 is not recommended.

The Treatment for Pregnancy Associated AKI

• Preeclampsia-associated AKI is an indication for delivery. Delivery generally results in completely recovery of renal function, although moderately increased albuminuria may persist.

• TTP-HUS-associated AKI is primarily treated with plasma exchange.

• AFLP-associated AKI includes the treatment of disseminated intravascular coagulation (DIC) and delivery of the fetus.

Hypertension

• In women with chronic primary or secondary hypertension or previous pregnancy-related hypertension, low-dose aspirin from the 12th week of gestation until delivery is suggested, but should be determined on a case-by-case basis.

Thank You