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Approach to Proteinuria in Pregnancy with DM �& �Risks of Preeclampsia

Dr S M Suhail

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Renal Consult – proteinuria in pregnancy in a case of DM

  • DM for 2 years
  • 32 weeks gestation
  • UTP 7.48 gm, increased from 2.9 gm, and oedema
  • BP 160/100 on Labetolol
  • No HELLP
  • Uric acid 430 from 351 µmol/l
  • Creatinine 70 from 56 µmol/l
  • Is this truly Preeclampsia?
  • Should we consider any other diagnosis?
  • Should we start her on steroids?
  • Risks of preeclampsia to the kidney

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A case of�proteinuria, pregnancy and preeclampsia

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  • Obviously
    • Management comes first
      • For safety of mother and the faetus,
    • Delivery cures preeclampsia.
  • If not
    • Eclampsia and maternal + fetal risk.

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Management Issue

Diagnostic Issue

Follow-up Issue

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Diagnostic issues- � proteinuria and pregnancy

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  • 31 weeks gestation
  • UTP 7.48 gm, oedema and DM for 2 years
  • BP 160/100 on Labetolol
  • No HELLP
  • Uric acid 430 from 351 umol/l
  • Creatinine 74 from 56 umol/l
  • Is this truly Preeclampsia?
  • Should we consider any other diagnosis?
  • Should we start her on steroids?
  • Risks of preeclampsia to the kidney

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Diagnostic issues-� proteinuria in pregnancy.

  • Protein-to-creatinine ratio ~ 24 hrs UTP
    • UPCR >3.0 mg/mg ~ UTP>3.0 g/24 hr
    • UPCR< 0.2 mg/mg ~ UTP< 0.2 g/24 hr.

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  • In pregnancy, this is not true
    • Haemodynamic alterations lead to variation of protein excretion on hourly basis in relation to creatinine.
    • 24 hours estimation is gold standard.

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Proteinuria in general -� causes

  • Primary Glomerulonephritis
  • SLE/Secondary glomerulonephritis and vasculitis
  • Diabetic nephropathy
  • Transplant glomerulopathy
  • Multiple myeloma/Amyloidosis/Paraproteinaemia
  • Other causes
    • Orthostatic, CCF, exercise induced, UTI, chyluria etc

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Proteinuria in pregnancy-� causes

  • Gestational proteinuria
  • Preeclampsia
  • Glomerulonephritis, primary/secondary/other diseases
    • Pre-existing
    • New onset
  • Diabetic nephropathy
  • UTI
  • Physiological

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Diabetic nephropathy – natural history

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RETINOPATHY

8

Years

Index case of proteinuria

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Diabetic nephropathy and pregnancy …Audience response

  • Is this a case of

diabetic nephropathy?

    • Yes
    • No
    • Not sure

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Diabetic nephropathy and pregnancy …Audience response

  • Is this a case of

diabetic nephropathy?

    • Yes
    • No
    • Not sure

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Glomerulonephritis in pregnancy

  • Urinalysis
    • Dysmorphic RBC with/without granular cast is the hallmark of GN

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Glomerulonephritis in pregnancy…

  • Primary Glomerulonephritis
  • SLE- lupus nephritis flaire
  • Secondary glomerulonephritis and vasculitis
  • Worsening of Preexisting GN

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Glomerulonephritis in pregnancy�

Relevant investigations

    • 24 hours Urine protein
    • Immunological
      • ANA/Anti DS-DNA/ANCA
      • Anti GBM
      • C3,C4, CH50
      • Anti Phospholipid Ab
      • HBsAg/AntiHCVAb/HIV screen
      • Myeloma screen

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US Kidney

Doppler renal vessels

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? Renal Biopsy

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Increase of proteinuria in pregnancy-

  • Early preeclampsia (proteinuria less than 5g)
    • Proteinuria is not mandatory for preeclampsia (ACOG current guideline1)
  • Progression to preeclampsia
  • Worsening of GN

Case series2

  • Proteinuria cases followed up in Pregnancy:
    • 33% of cases developed preeclampsia
    • Less than 0.3% cases were gestational proteinuria
    • Remaining were not biopsied antenatal, managed as GN with biopsy deferred postpartum

1. www.acog.org/Task Force and Work Group Reports/Hypertension in Pregnancy.

2. Ekiz A, et al. J Matern Fetal Neonatal Med. 2015 Jul 28:1-5

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Glomerulonephritis in pregnancy-

Presentation:

  • Nephrotic syndrome
  • Nephritic syndrome
  • Rapidly progressive GN
  • Asymptomatic urinary abnormalities

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Renal Biopsy in pregnancy

  • Multitude of difficulties
  • Relative contraindication, particularly in the third trimester.

A Case Series--

  • 18 renal biopsies in pregnancy.
    • 15 antepartum period and 3 postpartum
    • Classic glomeruloendotheliosis of preeclamptia confirmed in 5.
    • Complications:
      • 7 renal hematomas
      • 2 patients required blood transfusion.
      • 4 intrauterine fetal deaths - presumed that none were a result of the biopsy.

Jeffrey A. Kuller, et al. Am J of Obs and Gyn, 2001, 184(6): 1093–1096

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Steroid in pregnancy--

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  • 31 weeks gestation
  • UTP 7.48 gm, and oedema
  • BP 160/100 on Labetolol
  • No HELLP
  • Uric acid 430 from 351 umol/l
  • Creatinine 74 from 56 umol/l
  • Is this truly Preeclampsia?
  • Should we consider any other diagnosis?
  • Should we start her on steroids?
  • Risks of preeclampsia to the kidney

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Should we start her on steroids?

Case report in MRI renal unit:

  • Nephrotic syndrome suspected during pregnancy
  • UTP of 26 gm at 3rd trimester
    • With renal biopsy contraindicated

(Prof Lau in Renal lab used to do this)

    • Urine protein selectivity test,
      • a largely significant test
      • predicting steroid-responsiveness of nephrotic syndrome,

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SI <0.2 steroid-responsive nephrotic syndrome

<0.2 steroid-non-responsive

Hamilton P, et al.Clin Kidney J. 2014 Dec;7(6):595-8. doi: 10.1093/ckj/sfu103. Epub 2014 Oct

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CHMW

CLMW

SI =

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Steroid and immunosuppressant for GN� -MRI case report

  • Steroid was started (SI<0.2)
  • NS went into remission during the pregnancy
  • Preeclampsia and fetal complications were prevented.

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  • Other Immunosuppressive medicines like Cyclosporine, Tacrolimus, Azathioprine are safe to continue in pregnancy. MMF cannot be started, but continuation is in general discouraged.

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Hamilton P, et al.Clin Kidney J. 2014 Dec;7(6):595-8. doi: 10.1093/ckj/sfu103. Epub 2014 Oct

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Renal Consult- � Proteinuria in pregnancy

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  • 31 weeks gestation
  • UTP 7.48 gm, and oedema
  • BP 160/100 on Labetolol
  • No HELLP
  • Uric acid 430 from 351 umol/l
  • Creatinine 74 from 56 umol/l
  • Is this truly Preeclampsia?
  • Should we consider any other diagnosis?
  • Should we start her on steroids?
  • Risks of preeclampsia to the kidney

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Pregnancy and the kidney – in general

  • Renal length increased by 1 to 1.5 cm
    • Physiologic dilatation of the ureters
    • hydronephrosis
  • Marked alterations in renal haemodynamics:
    • GFR and effective renal plasma flow (ERPF) increase by 50%
    • Total protein excretion (TPE) and urinary albumin excretion (UAE) significantly elevated after 20 weeks gestation.
    • Estrogen and progesterone and prostaglandin E2, elevated.
  • eGFR
    • MDRD eGFR underestimates by>40 ml/min
    • CCG eGFR overestimates by >20 ml/min
  • Gold standard is 24 hours urine mGFR

Sharon E, et al. JASN, 2009, 20:14-22

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Preeclapmsia and kidney

  • Placental dysfunction,
  • Anti-angiogenic and other factors,

into the maternal circulation

  • Impaired VEGF/PDGF and TGF-β

signaling,

  • Endothelial dysfunction
  • Preeclampsia and other systemic

effects.

Sharon E, et al.Kid International, 2005, 67:2101-13

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Preeclampsia and renal pathology-� Glomerular endotheliosis instead of Glomerulonephritis

Case report:

  • Biopsy at 33 weeks with UPCR of 26 gm/gm showed glomerular endotheliosis instead of glomerulonephritis

Sharon E, et al.Kid International, 2005, 67:2101-13

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Effects of Preeclampsia on kidney

  • Glomerular capillary Endothelial dysfunction lead to proteinuria and thrombotic microangiopathy.
  • Patient with mild renal impairment, normal BP, and little or no proteinuria have good maternal and fetal outcomes,
  • Patient with a serum creatinine >2.5 mg/dl, >40% develop preeclampsia, preterm delivery, and high (33%) likelihood of decline in renal function
  • Proteinuria can persist after pregnancy in patients with preeclampsia, therefore follow up by nephrologist is needed.

Sharon E, et al.Kid International, 2005, 67:2101-13

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Follow up post pregnancy-� For proteinuria

In a long-term observational study:

  • 463 patients with preeclampsia with proteinuria
  • Proteinuria persisted in 34 women (0.7 %) after pregnancy
    • 71% were diagnosed with underlying renal disease (MGN, MPGN, IgAN, FSGS).
    • 29% were diagnosed with idiopathic preeclampsia glomerular endotheliosis

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Unverdi S, et al. Wien Klin Wochenschr. 2013; 125(3-4):91-5

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Proteinuria and pregnancy-� Conclusion

    • Persistent proteinuria is a predictor of underlying renal disease.

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    • All patients with preeclampsia should be evaluated with respect to continuing proteinuria, persistent hematuria, or impaired renal functions after postpartum period.

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    • Percutaneous renal biopsy should be performed in these patients post natal.

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Case Description continued .....

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  • Patient was delivered at 32 weeks by caesarean section in view of the Severe Preeclampsia
  • BW: 1735 gm, No neonatal hypoglycaemia
  • Baby was in neonatal care for 2 weeks

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Concluding remarks

Being diabetic and Pregnant : Is it safe for the Mother and the Baby? : YES

� 1. Pre-pregnancy counselling:

DM (HbA1c <7%) and no significant end organ

damage, safety of medications

2. Anti-natal :

Good DM control

Monitoring of the fetus

Watch out for complications such as Preeclampsia

3. Postpartum advice :

Contraception and planning for the next

pregnancy

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TQ

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