Renal Disease in Pregnancy

Registrar Teaching November 2014Dr Sarah Pixton

Talk outline• 1. Renal embryology- How the renal system

develops• 2. Physiology in Pregnancy- How the renal system

changes with pregnancy• 3. CHRONIC – Overview of How pregnancy effects CRD– How CRD affects pregnancy– Specific conditions in CRD

• 4. ACUTE– Acute renal disease in pregnancy

1. Renal EmbryologyA. The Pronephros:Is the cranialmost set of tubes, which mostly regress begins 4th week & disappears by day 24 or 25B. The mesonephros:Is located along the midsection of the embryo and develops into mesonephric tubules and the mesonephric duct (Wolffian duct). These tubules carry out some kidney function at first, but then many of the tubules regress. However, the mesonephric duct persists and opens to the cloaca at the tail of the embryo. C. The metanephros:Gives rise to the definitive adult kidney. Develops from an outgrowth of the caudal mesonephric duct, the ureteric bud, and from a condensation of nearby renogenic intermediate mesoderm, the metanephric blastema

Renogenesis

Cranial-caudal patterning establishes a “renogenic” region within the intermediate mesoderm in the tail of the embryo –this renogenic mesoderm is the METANEPHRIC BLASTEMA The METANEPHRIC BLASTEMA secretes growth factors that induce growth of the URETERIC BUD from the caudal portion of the mesonephric duct. The URETERIC BUD proliferates and responds by secreting growth factors that stimulates proliferation and then differentiation of the metanephric blastema into glomeruli and kidney tubules

Ascent of the kidneys and associated malformations

2. Physiological Changes in Pregnancy

• Blood volume and red cell mass increase by up to 50%, systemic vascular resistance falls and cardiac output increases by up to 30%. These cardiovascular adaptations have a profound effect on kidney

• Increase in the GFR and renal plasma flow (30-50% by T2 persist till term)

• Fall in serum creatinine (by 20-30%)• Increased protein excretion= 300mg/24hrs upper limit. PCR

30mg/mmol• Physiological hydronephrosis=

– increase in size of kidney by 1.5cm– Dilatation of renal pelvis and ureter occurs R>LSmooth muscle relaxation due to progesterone effect. Gravid uterus

dextrorotation to right

3. Chronic/ Pre existing renal Disease

• CKD is rare in pregnant patients, affecting 0.15% of pregnancies, and most patients have early stages of CKD.

• In the general population, diabetes mellitus and hypertension are the commonest causes of CKD.

Effect of Pregnancy on Chronic Renal Disease CRD

• Mod-severe renal impairment = 25-50% accelerated decline in renal function…

• Most with severe CRD fail to return to pre pregnancy baseline renal function…

• 1 in 3 women with Cr >180 will require dialysis during pregnancy or within 6 months post partum..

Renal Impairment

MILD (Cr <125)

MOD (Cr <170)

SEVERE (Cr <220)

Cr >220

Loss of Function

2% 40% 65% 75%

Postpartum deterioration

20% 50% 60%

ESRF 2% 33% 40%

Previous incidence• Mild disease: Approximately 16% of the patients showed a decline in renal

function. Most of the latter returned to pre-pregnancy levels of renal function during the postpartum period; however, 6% progressed to end-stage renal disease

A.I. Katz, J.M. Davison, J.P. Hayslett, et al. Pregnancy in women with kidney disease Kidney Int, 18 (1980), p. 192

• Severe disease (Cr >250): seem to be at significant risk for a decline in function following pregnancy. Jones and Hayslett reported that 4 of 12 progressed to end-stage renal disease within 1 year. Cunningham reported that 5 of 11 patients (45%) progressed to end-stage renal disease.

D.C. Jones, J.P. Hayslett Outcome of pregnancy in women with moderate or severe renal insufficiency N Engl J Med, 335 (1996), p. 226

F.G. Cunningham, S.M. Cox, T.W. Harstad, et al. Chronic renal disease and pregnancy outcomeAm J Obstet Gynecol, 163 (1990), p. 453

Effect of CRD on Pregnancy

• Miscarriage• Gestational Hypertension in 50%• PET (If mild CRD risk = 20%, if severe cr >180 =

60%)• IUGR (if severe 65%)• PTD (if severe 90%)• LSCS• Fetal death (with urea >20-25 mmol/l 10%)

Effect CRD on Pregnancy cont..

• Black dots = mild to mod Red dots= severe

Exam /Investigations

Blood pressure;Hypertension is strongly related to decline of renal function and adverse pregnancy outcomes. Check each visitRoutine antenatal tests;G&H, rubella, HIV, syphilis, hepatitis B & C, HIV serology, urine m/c/s, pap smear. Regular screen for asymptomatic bacturiaFBC and iron studies;Baseline assessment of Hb and potential anaemiaUrea and creatinine;Baseline renal function which allows assessment of pregnancy riskCalcium and vitamin D;Assessment of renal bone diseaseSpot urine protein creatinine ratio or 24 hour urine protein collection;Baseline function which allows assessment of pregnancy risk. Do Urinalysis each visit- if pos do PCR.Consider CT head to exclude intracranial aneurysms for those with FHx or known PCKDEarly and 26-28/40 GTT if on corticosteroid use eg in renal transplant

Management• Pre pregnancy counselling

essential• Role of aspirin in prevention

of PET ( see NICE Guidelines)

• Diagnosing superimposed PET :– BP >160/110 sudden

worsening when previous good control

– >2g proteinuria or rapid increase in proteinuria

– Cr >110– +/- additional feature of PET

• Multidisciplinary team

NICE Guidelines 2010

• 1) Assess RF• 2) Commence Aspirin if:one HIGH risk factor

OR>= 2 MODERATE risk

factorsTo commence low dose

aspirin (75-100mg/ day) at 12 weeks

Risk factors for pre-eclampsia:

Moderate: First pregnancy Age ≥ 40 years Pregnancy interval > 10 years BMI ≥ 35 kg/m2 at first visit Family history of pre-eclampsia Multiple pregnancy

High: Hypertensive disease during previous pregnancy Chronic kidney disease Autoimmune disease such as SLE or APLS Type 1 or type 2 diabetes Chronic hypertension

Specific Conditions

In most cases the renal function rather than aetiology is what impacts fetal outcome...Except if due to UTI increased risk PTL, SLE or Diabetes which can have negative impact on fetal outcome independent of renal function.

Glomerulopathiesthe kidney esp the glomerulus and its capillaries, is subject to a large number

of acute and chronic diseases,

• There are several distinct clinical glomerulopathic syndromes: acute nephritic, pulmonary-renal, nephrotic, basement membrane, glomerulovascular and infectious disease syndromes.

1) Acute Nephritic SyndromePresents with hypertension, haematuria, red cell casts, pyuria and proteinuria

In some patients rapidly progressive glomerulonephritis leads to end stage renal failure, in others chronic glomerulonephritis develops

Systemic Lupus Erythematosus SLE

• Lupus nephritis often enters a phase of quiescence during pregnancy as a result of increased endogenous corticosteroids

• flares can often occur in the puerperium

• If lupus flares do occur during pregnancy they can be difficult to

• distinguish fromPET: HTN, proteinuria and decline in renal function, often with thrombocytopaenia.

• The presence of invisible haematuria, depressed serum complement levels, a rise in anti-double-stranded DNA titre and cutaneous manifestations of SLE support a diagnosis of a lupus flare

IgA Nephropathy

• also known as Berger disease

• most common form of acute glomerulonephritis worldwide.

• Its primary form is an immune-complex disease. Henoch- Schönlein purpura may be a systemic form of the disease

2) Nephrotic Syndrome

• When nephrosis complicates pregnancy, the maternal and fetal prognosis depends on the underlying cause and severity of the disease. Where possible a renal biopsy may indicated to determine cause.

• Perinatal mortality may be 40% if it develops during T1

• Spectrum of renal disorders, proteinuria is the hallmark

• =Proteinuria >3g/24hr, Serum albumin <30g/L and oedema

• Defect in the glomerular capillary wall allowing excessive filtration of plasma proteins

PCKD

• Autosomal Dominant• Incidence 1:800 live births• 10% ESRF is due to PCKD• 85% cases due to mutation

of PKD1 gene on Ch16• 15% due to mutation PKD2

on Ch 4.• Usually asymptomatic till

30s or 40s• Hypertension develops in

75%• Progression to renal failure

is a major problem

• Superimposed ARF may develop from infection or obstruction from cyst displacement (kink ureter)

• Other organ involvement includes liver with 1/3 pt asymptomatic hepatic cysts

• Increased incidence cardiovalvular lesions esp Mitral valve prolapse (13 fold increase)

• Approx 10% die from ruptured intracranial berry aneurysms

Acute renal Disease during Pregnancy

• Pyelonephritis=– Asymptomatic bacturia on screening in T1 should

be treated and MSU repeated. – Renal tract dilatation and urinary stasis results in

increased rates of pyelonephritis

Acute Renal Injury (AKI)

Avoiding Acute Tubular Necrosis• 1 Prompt and vigorous replacement of blood in instances of massive

hemorrhage, such as in placental abruption, placenta previa, uterine rupture, and postpartum uterine atony

• 2. Termination of pregnancies complicated by severe preeclampsia or eclampsia and careful blood replacement if loss is excessive

• 3. Close observation for early signs of sepsis syndrome and shock in women with pyelonephritis, septic abortion, chorioamnionitis, or sepsis from other pelvic infections

• 4. Avoidance of potent diuretics to treat oliguria before initiating appropriate efforts to ensure that cardiac output is adequate for renal perfusion

• 5. Avoidance of vasoconstrictors to treat hypotension, unless pathological vasodilation is unequivocally the cause of the hypotension

References• Embryology Learning Resources-Duke University Medical School

https://web.duke.edu/anatomy/embryology/urogenital/urogenital.html• Renal Disease In Pregnancy Curtis L. Sanders, MD, Michael J. Lucas,

MD.Obstetrics and Gynecology Clinics of North America Volume 28, Issue 3, 1 September 2001, Pages 593–600

• Renal Disease in Pregnancy by Nelson-Piercy, Catherine. Journal of Renal Nursing, ISSN 2041-1448, 07/2012, Volume 4, Issue 4, pp. 168 – 169

• Renal Disease in Pregnancy Matt Hall, Nigel J Brunskill. “The Pink Journal” Obstetrics, Gynaecology and Reproductive Medicine 20:5 2010• NICE Guidelines August 2010. Hypertension in pregnancy: The

management of hypertensive disorders during pregnancy• Williams Obstetrics Chapter 48 Renal and Urinary Tract Disorders