Khadke B*, Prasad M**, Gupta AS***.
(* First year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth G S Medical College and K E M Hospital, Mumbai, India.)
A case of pregnancy associated with chronic renal disease, management of pregnancy and possible outcomes in women with chronic kidney disease, managed with erythropoietin injection is presented here.
Chronic kidney disease is classified in five stages. All five stages are associated with increased risk of preterm labor, pre-eclampsia and intra uterine growth restriction, 86% preterm deliveries occur in women with serum creatinine above 2.5 mg/dl and more than 40% pregnancies are associated with pre-eclampsia. Pregnant woman with high level of serum creatinine have more decline in renal function than non-pregnant woman with the same level of creatinine. Approximately 30 % have increased risk of fetal loss when serum creatinine ranges between 1.6 to 5.5 mg/dl, 50% women with serum creatinine more than 1.5mg/dl have decline in glomerular filtration rate, and among them 20% developed end stage renal disease in the postpartum period.
A 19 year old primigravida married for 1 year presented to the outpatient department at 28 weeks of gestation with diagnosed chronic kidney disease. Approximately 2 months before conception, she had developed an episode of fever which was diagnosed as enteric fever by the positive Widal test showing infection with Salmonella typhi O and H. She was treated with antibiotics for the same. Ultrasonography (done by a practitioner in a remote rural area) revealed hepato-splenomegaly, but no specific comment on any abnormality in the kidneys was mentioned in the report. However, in view of continuing abdominal pain, vomiting, low grade fever and multiple joint pains, she presented to our tertiary care hospital for further evaluation, 2 months after this initial episode. Investigations showed raised serum creatinine of 2.33 mg/ dl, raised blood urea of 86.7 mg % and raised blood urea nitrogen as 40.35 mg % for which she was evaluated. Ultrasonography showed renal parenchymal disease (grade III in right kidney and grade II in left kidney) and left moderate hydronephrosis. Investigations also showed anemia (hemoglobin 8.8 gm%) and proteinuria (2+) on urine routine examination. Diagnosis of chronic kidney disease with renal anemia was made, and she was managed on outpatient basis by nephrology department. There was no requirement for dialysis, but was advised close follow up.
She was given injection iron carboxymaltose 1000 mg and injection erythropoietin 2000 IU two doses; tablet sodium bicarbonate 1 gram thrice a day and multivitamin tablets twice a day. She was advised further work up but did not comply and was lost to follow up. Five months later she visited the nephrology department and reported amenorrhea for the prior 5 months. Pregnancy was diagnosed and she was referred for antenatal registration. She and her relatives were counseled about risk involved in pregnancy with kidney disease and was advised admission. However, she got admitted two months later, at 33 weeks. She was comfortable, mild pallor was present, there was no facial puffiness, pedal edema, anasarca or ascites. Blood pressure was 140/90 mm Hg, urine albumin was 1+, systemic examination was otherwise unremarkable and uterine size was corresponding to period of gestation.
Nephrologist reviewed her. Salt intake of only 2 grams per day, protein intake of 0.8 grams per day, maintaining an input corresponding to the output, abdominal girth monitoring and daily weight monitoring were initiated. Tablet acetylsalicylic acid 75 mg once a day, tablet sodium bicarbonate 1 gm thrice a day, calcium and iron supplements were started and continued. Her serum TSH value was 5.31 IU/ml and tablet levothyroxine 50 mcg was started.
As part of evaluation of multiple joint pains, levels of ANA, serum PTH, vitamin D were checked and found to be normal. Radiological evaluation of joints was also normal. Ophthalmologist excluded chronic changes in her retina. The investigations at the time of admission were blood urea nitrogen of 41 mg%, creatinine of 2.5 mg%, SGOT 32 U/L, SGPT 22 U/L, sodium 132 mEq/l, potassium 4.2 mEq/l, chloride 107 mEq/l, and 24 hour urine protein of 760 mg. In view of persistent anemia, which was of renal origin, nephrologists advised injection erythropoietin 2000 IU twice a week for a total of 3 weeks; which was given. Multivitamin injections were also continued.
Fetal growth parameters were monitored and the fetal growth was appropriate for gestational age. At 37 weeks, she went into spontaneous labor and LSCS was required due to thick meconium stained amniotic fluid with fetal distress in the first stage of labor. General anesthesia was given and intraoperative blood pressure rose to 180/120 mm of Hg that was controlled by intravenous labetalol. Male child of 2.316 kg was delivered, and postoperative period was otherwise uneventful. The neonate was evaluated and was found to have absent right kidney, but was discharged since there was no decrease in urine output. Outpatient follow up with pediatric nephrologist was advised.
The mother was continued on levothyroxine, iron and calcium supplements and sodium bicarbonate.
Our patient did not know that she was suffering from chronic renal disease just prior to pregnancy. How long she had renal disease prior to its identification during pregnancy is not known. Webster et al opine that pregnancy is an opportunity to identify renal disease. Despite advice of regular follow-up, she did not comply. It has been shown that accurate diagnosis and intensive follow-up with specialist nephrologist increases the maternal survival and neonatal outcomes. Despite poor follow-up, our patient had a blood urea nitrogen level of 40 mg%, which is within the target; 50 mg% is preferred among patients with chronic kidney disease and on dialysis.
Our patient had anemia with hemoglobin of 8.8 gm% which did not improve with oral hematinics. The incidence of anemia in patients with chronic renal disease can be as high as 80 %. A hemoglobin level of less than 9 gm% despite three weeks of oral hematinics is considered an indication for erythropoietin.
A total of 6 doses of erythropoietin (2000 IU each dose) was required in our patient during pregnancy. The requirement of erythropoietin in pregnancy is higher than that required in non-pregnant state. The accurate dose of erythropoietin during pregnancy has not been definitively determined. Other factors such as nutritional status, duration of disease and type of vascular access ports appear to be determinants. Erythropoietin does not cross the placenta, and is a FDA category C drug, approved for use in pregnancy when indicated for maternal indication. The therapeutic value of this drug lies in compensating for the reduced renal production of erythropoietin in renal disease.[5,6]
Our patient developed severe intrapartum hypertension. The occurrence of hypertension can be related to the kidney disease itself, or it may be secondary to the use of erythropoietin, and this is difficult to distinguish. However, the hypertension was transient.[7,8]
Our patient had hypothyroidism, which was also detected during pregnancy, but did not appear to be the main cause of renal disorder. There have been case reports of severe hypothyroidism being the sole cause of renal disorder in pregnancy.
The neonate weighed 2.3 kilograms. The occurrence of IUGR in mothers with kidney disease is well known. However, we would like to highlight the fact that recent research is being conducted to look at determinants of future chronic kidney disease. Newsome et al have recently opined that being born as an IUGR baby is in itself a risk factor for future development of renal disease as an adult, consistent with the theory of “fetal origin of adult disease”.
In our patient, the neonate, surprisingly had a single kidney. An entity of hereditary renal dysplasia/ aplasia which has the features of absent kidney in the fetus and renal problems in the mother had been initially described by Buchta et al. Though evaluation was being planned on a later date, the significance of this is not known.
Chronic renal disease may be first identified during pregnancy. There is a need to emphasize and counsel patients about rigorous follow-up. Anemia during pregnancy in renal disease may necessitate erythropoietin injection, and its use is safe.
- Webster P, Webster LM, Cook HT, Horsfield C, Seed PT, Vaz R, et al. A Multicenter Cohort Study of Histologic Findings and Long-Term Outcomes of Kidney Disease in Women Who Have Been Pregnant. Clin J Am Soc Nephrol. 2017;12(3):408–16.
- Reddy SS, Holley JL. The importance of increased dialysis and anemia management for infant survival in pregnant women on hemodialysis. Kidney Int. 2009; 75(11):1133–4.
- Sachdeva M, Barta V, Thakkar J, Sakhiya V, Miller I. Pregnancy outcomes in women on hemodialysis: a national survey. Clin Kidney J. 2017; 10(2):276–81.
- Cyganek A, Pietrzak B, Kociszewska-Najman B, Sanko-Resmer J, Paczek L, Wielgos M. Anemia Treatment With Erythropoietin in Pregnant Renal Recipients. Transplant Proc. 2011 Oct; 43(8):2970–2.
- Wolfson GH, Vargas E, Browne VA, Moore LG, Julian CG. Erythropoietin and Soluble Erythropoietin Receptor: A Role for Maternal Vascular Adaptation to High-Altitude Pregnancy. J Clin Endocrinol Metab. 2017; 102(1):242–50.
- Ifudu O. Patient characteristics determining rHuEPO dose requirements. Nephrol Dial Transplant. 2002; 17 Suppl 5:38–41.
- Piccoli GB, Cabiddu G, Castellino S, Gernone G, Santoro D, Moroni G, et al. A best practice position statement on the role of the nephrologist in the prevention and follow-up of preeclampsia: the Italian study group on kidney and pregnancy. J Nephrol. 2017; 30(3):307–17.
- Kashiwagi M, Breymann C, Huch R, Huch A. Hypertension in a pregnancy with renal anemia after recombinant human erythropoietin (rhEPO) therapy. Arch Gynecol Obstet. 2002; 267(1):54–6.
- Bora A, Madhva Prasad S, Gupta AS. Severe hypothyroidism causing minimal change nephropathy in early pregnancy. JPGO 2017. Volume 4 No.9. Available from: http://www.jpgo.org/2017/08/severe-hypothyroidism-causing-minimal.html
- Newsome AD, Davis GK, Ojeda NB, Alexander BT. Complications during pregnancy and fetal development: implications for the occurrence of chronic kidney disease. Expert Rev Cardiovasc Ther. 2017; 15(3):211–20.
- Rodriguez MM. Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT). Fetal Pediatr Pathol. 2014; 33(5–6):293–320.
Khadke B, Prasad M, Gupta AS. Pregnancy With Chronic Renal Anemia. JPGO 2018. Volume 5 No.6. Available from: http://www.jpgo.org/2018/06/pregnancy-with-chronic-renal-anemia.html