A 39-year-old G3P2⁺⁰, Nigerian housewife with one living child, presented at the accident and emergency department of Abuja Clinics Limited Maitama with weakness and haematuria at 32 weeks gestation. She was not booked for prenatal care in our facility and presented without any formal referral. Prior to presentation, she had received sought prenatal care in another tertiary level healthcare facility. There was associated dizziness, epigastric pain, generalized body and abdominal pains, anasarca, heartburn and diarrhoea but no blurred vision. There was reduced urinary output. Pregnancy had progressed uneventfully until the thirtieth week of gestation when she noticed above symptoms. She was a known hypertensive patient diagnosed two years earlier, and on medical management before the onset of the index pregnancy. Her blood group is O rhesus “D” positive, and haemoglobin genotype is AA. Her routine ante natal tests were essentially normal (she was negative to Human immunodeficiency virus I & II, Hepatitis B Surface antigen (HBsAg), Hepatitis C Virus (HCV) and Venereal Disease research laboratory (VDRL) screening tests) [1-5].

Her first pregnancy at the age of 34 years was complicated with severe preeclampsia. This resulted in the caesarean delivery of a 2.5 kg female baby who is alive and well. She received blood transfusions during the procedure. Her second pregnancy 2 years later was unsuccessful and ended with spontaneous abortion of a set of twins. Other aspects of the history were essentially normal.

Physical examination revealed an anxious looking, middle aged woman, who was pale, anicteric, afebrile, with puffy face and bilateral pedal oedema. Her pulse rate was 80 beats per minute (bpm), regular and full volume while her blood pressure (BP) was – 150/90 mmHg. Her heart sounds were normal and there was no murmur. Abdominal examination showed a low transverse scar, Symphysis-fundal height (SFH) of 34 cm, and cephalic presentation. The fetal heart rate was 140 bpm. Investigations results were as follows urinalysis – proteinuria, no cast, triphosphate ++; haemoglobin concentration – 6 g/dl, packed cell volume (PCV) – 18%; red blood cell - 2.92×106; white blood cell (WBC) – 5,500/mm3, neutrophil 75%, lymphocyte 18%, Eosinophil – 6%, Basophil – 0; platelet 68×103cells/ml; fasting blood sugar (FBS)– 4.6 mmol/L serum creatinine 1092 μmol/L, urea – 52 mmol/L, blood urea nitrogen – 73 mg/dL, Sodium (Na) – 139 meq/L, Chloride (Cl) – 102 meq/L, Potasium (K) – 3.2 meq/L, Bicarbonate (HCO3) – 3.1 meq/L, calcium – 2.5 mmol/L, inorganic phosphate - 1.1 mmol/L; liver function test (LFT) – normal – serum glutamate-oxaloacetic acid, (SGOT) – 11 units/liter, serum glutamate pyruvate transaminase (SGPT ) – 9 unit/ liter, Alanine phosphatase (ALP) – 254 units/liter, total bilirubin – 0.18 mg/dl, direct bilirubin - 0.15 mg/dl. Other results were low density lipoprotein (LDL) - 1.2 mmol/l, high density lipoproteins 1.9 mmol/l, cholesterol 2.7 mmol/l, triglyceride 1.0 mmol/L; prothrombin time – 17.5 second, international normalization ratio (INR) – 1.3; uric acid – 674 mmol/L, total serum protein – 57 g/dl and serum albumin – 34 g/ dl. Electrocardiogram and echocardiogram were normal.

Ultrasound scan showed a single viable and active fetus in cephalic presentation. The fetal heart rate was 125 bpm. The fetal kicks and movements were well demonstrated. The placenta was anteriorly located, calcified and Grade III. The liquor volume was reduced. The estimated fetal weight (EFW) was 1.2 kg and the estimated gestational age (EGA) was – 29 weeks. Umbilical artery Doppler showed an increase in peak systolic/end diastolic (PS/ED) ratio. The kidneys, liver and pancreas showed cystic lesions which were more numerous in the kidneys (Figures 1-3). The portal veins were also dilated. Ascites was noted in the peritoneal cavity. The bowels showed normal peristalsis but appeared compromised by the enlarged kidneys. Impressions of viable singleton at 29 weeks gestation with possible intrauterine growth restriction (IUGR) and autosomal dominant polycystic kidney disease were made. Urine culture grew Klebsiella spp sensitive to amoxicillin clavulanic acid.

Serial serum urea, blood urea nitrogen and creatinine showed persistently rising values. Her blood pressure varied between 150/90 mmHg and 210/130 mmHg. She received blood transfusions, subcutaneous erythropoietin 4000 IU weekly, tablets methyldopa and nifedipine, tablet amoxicillin clavulanic acid, oral rehydration salt (ORS) and Gestid suspension. She was also given injection dexamethasone 8mg hourly for 24hrs. She was on continuous fetomaternal monitoring.

On the fourth day of admission she showed signs of fetal distress and worsening kidney disease and therefore had dialysis and emergency caesarean section. A live 0.95 kg female baby was delivered. The operation was complicated with massive blood loss that necessitated subtotal hysterectomy. She required mechanical ventilation for a period of 10days and received inotropes, multiple blood and platelet transfusions and intensive low efficiency dialysis. While in ICU she developed septicaemia due to enterobacteriacea and received intravenous amoxicillin with flucloxacillin. The expanded spectrum beta-lactamase positive (ESBL) Klebsiella on the skin was treated with twice daily povidone Iodine wash. She also developed severe post partum depression for which she received mirtazapine and olanzepine. She was eventually discharged from admission after about 4months. However, she is on regular follow-up with the renal unit of the hospital, receiving renal replacement therapy pending conclusion of arrangements for kidney transplant.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. It is a multisystem disorder characterized by multiple, bilateral renal cysts, as well as cysts in other organs like liver, pancreas, arachnoid membranes [1,2]. ADPKD affects both males and females. Some of the anomalies documented in men with ADPKD include Criptozoopermia (1×106 sperm cells/ ml) [3] necrospermia, immotile sperm, seminal vesicle cysts and ejaculatory duct cysts [2]. It affects approximately 1 in 400 to 1000 live births [4]. It usually presents between the 3^rd and 4^th decades of life [5]. Approximately half of the patients progress to end-stage kidney disease (ESKD) by age of 60 [6]. It has been estimated that ADPKD is responsible for 10% of chronic renal failure [3]. The effect of ADPKD on fertility and pregnancy outcomes depends on the renal function of the kidneys. More often than not, pregnancy outcome is good and fertility is not affected by ADPKD in patients with normal renal function [2,7-9].

In this report we presented a 39 year old multiparous Nigerian woman who presented at 32 weeks gestation with features of end-stage kidney disease (ESKD). She was on medical management for chronic hypertension before the onset of the index pregnancy. Although she was not formally referred to us, history obtained suggests that she had been without symptoms prior to the onset of index pregnancy up until the 3rd trimester of her gestation. The fact that she was initially without symptoms but developed worsening symptoms of kidney disease during the third trimester of this index pregnancy is typical of chronic kidney diseases in pregnancy. We therefore suspect that she may be suffering from undiagnosed chronic kidney disease long before presenting to us. The kidney disease however progressed to ESKD later in the course of the pregnancy. This trend has been noted to be common in patients with ADPKD with underlying hypertension. Early hypertension and subsequent progression to renal failure is due to massive enlargement of the cysts and fibrosis which are the hallmark of the disease. ADPKD accounts for 5-10% of cases requiring renal replacement therapy [4,9].

For several decades, the prognosis of pregnancies complicated with chronic kidney disease end stage kidney disease (ESKD) has been poor. Termination of pregnancy with sterilization was once advocated for all patients with ESKD. The fertility of patients with ESKD is often reduced with associated menstrual and ovulatory disorders. However, fertility may be preserved in some patients. Fertility rate is better in patients without advanced renal insufficiency (serum creatinine >3 mg/ dL) and without treatment with cytotoxic alkylating agent.

Chronic kidney disease (CKD) is estimated to be seen in approximately 4% of women of reproductive age [10]. The relationship between kidney disease and pregnancy is complex as pregnancy affects the maternal disease progression to end-stage kidney disease (ESKD). In addition, kidney disease and its treatment affect pregnancy and fetal development. We suspect from her clinical course that the kidney disease in our patient could have been present but was asymptomatic before the onset of pregnancy but later became symptomatic in the course of the pregnancy. Adverse pregnancy outcomes are noted to be more common in patients with acute on chronic kidney disease and advanced renal insufficiency [11].

The diagnosis of ADPKD was made in this index pregnancy. The diagnosis of ADPKD as was done in this case is primarily by imaging studies of the kidneys using ultrasound scan (Figures 1-3), computer tomography scan (CT scan) (Figures 4 and 5), and/or magnetic resonance imaging (MRI). The ultrasound scan done during pregnancy and computed tomography scan taken after her delivery showed bilaterally enlarged kidneys filled with variously sized multiple cysts along with cysts in the liver and pancreas (Figure 2). Ultrasound scan is reliable, inexpensive and readily available. MRI and CT are highly sensitive methods of diagnosing APDKD but they are expensive and sparsely available in our environment. Both modalities can pick up cysts as small as 2 mm [12].

Figure 1: Ultrasound scan picture showing multiple variously sized cysts in the liver and right kidney.

Figure 2: Ultrasound scan picture showing multiple variously sized cysts in the spleen and left kidney.

Figure 3: Ultrasound scan picture showing multiple variously sized cysts in the pancreas.

Figure 4: CT scan image showing multiple cysts (stars) within the Liver.

Figure 5: CT scan image showing Bilateral Enlarged Polycystic Kidneys (Large Block Arrows), Liver Cyst (Curved arrow) and stones within the Gallbladder (Small Arrow).

Clinical and laboratory parameters facilitated the diagnosis of ESKD in our patient. The reduction in urinary output, worsening preexisting hypertension, proteinuria, sustained progressively elevated serum creatinine, urea and blood urea nitrogen (BUN) were the marks of worsening kidney disease. She could be classified to be in Landesman and Sherr group C at presentation. The clinical and laboratory profile depicts complication with pre-eclampsia. Pregnancy is normally associated with low serum creatinine concentration due to the physiological increase in glomerular filtration (GFR) by 50%. Therefore serum creatinine levels considered normal for non pregnant women may indeed indicate an underlying kidney disease in pregnancy.

The most common symptom in ADPKD patients is pain which may be in form of lower back pain, radiculopathy or abdominal pain. Cyst rupture, haemorrhage, infected cysts and nephrolithiasis are the frequently suspected aetiologies [13]. The enlarged kidney, liver and pancreas may be responsible for the persistent abdominal pain reported by our patient due to their mass effect. This mass effect can also lead to compression of surrounding structures, indigestion, oesophageal reflux, malnutrition and ascites. The massively enlarged kidneys could have occupied the abdominal and pelvic cavities causing the disparity between the estimated gestational age (EGA) and symphysis-fundal height (SFH) noted in the clinical findings. The ascites may also be as a result of reduced oncortic pressure due to proteinuria. Haematuria may be related to stones, hypertension, cyst rupture or haemorrhage.

There is no specific treatment so far available for ADPKD. Management of women with ADPKD in pregnancy involves adequate control of hypertension, control of dyslipidaemia, dietary modification, and dietary protein restriction, control of acidosis and prevention of hyperphosphatemia. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) are the drugs of choice for the treatment of hypertension in patients with ADPKD. However these are contraindicated in pregnancy. In situations where a patient had been on these drugs preconception, the drug regimen should be reviewed and changed to other antihypertensive drugs which are relatively safe in pregnancy. Long term administration of nephrotoxic drugs, caffeine, use of oestrogen and smoking should be avoided.

Women affected by ADPKD with preexisting hypertension and or renal failure can develop varied complications. Sometimes the fatal outcome may be poor. Anaemia, haematuria, nephrolithiasis, recurrent urinary tract infections (UTI), preeclampsia, oligohydramnios, intrauterine growth restriction (IUGR) are some of the maternal and fetal complications noted in this case. Other possible complications include fetal congenital anomalies, dyslipidaemia, cholelithiasis, intracranial aneurysm, diverticulosis, hernia, miscarriage and prematurity [14]. The risk factors for renal failure in patients with ADPKD include, black race, diagnosis of ADPKD and first episodes of haematuria before age 35 years, hyperlipaemia, low level of highdensity lipoproteins and sickle cell trait. Others include age >30 yrs, male gender, preeclampsia and severity of the kidney disease. Most of these risk factors were however present in this patient.

Hypertension and anaemia are the most commonly reported maternal complications and usually require aggressive management. She received antihypertensive medications, higher doses of injected erythropoietin, haematinics and repeated blood and blood product transfusions. The blood pressure should be maintained below 140/90 mmHg and haemoglobin levels of 100 – 110 g/l should be the target [15,16]. The antihypertensive drugs of choice in pregnancy include methyl dopa, calcium channel blockers, hydrallazine, beta blocker and labetalol. ACEI or ARB drugs should be avoided. Diuretics should be used cautiously to prevent hypovolemia.

She had a successful pregnancy and caesarean delivery of a small for gestational age 0.98 kg female baby under general anaesthesia. The baby spent about two months in special care baby unit (SCBU) but as at the time of this report, has thrived well. Similar fetal complication has been corroborated in other studies in pregnant women with ADPKD with preexisting renal failure and hypertension [17-19]. Successful pregnancy in women with ADPKD has also been reported by other researchers [14,15].

The IUGR may have resulted from high levels of blood urea nitrogen (BUN), acidosis, limited intra-abdominal space as a result of the massively enlarged polycystic kidney and uteroplacental insufficiency from poorly controlled hypertension. The surgery was complicated by massive blood loss which led to subtotal hysterectomy and acute-on-chronic kidney failure. The blood loss might have been as a result of poor blood indices, intrinsic uterine factors (uterine atony) and disseminated intravascular coagulopathy (DIC). Uremic toxins cause functional platelet defects and prolonged bleeding time. Thrombocytopenia may have resulted from peripheral destruction of platelets [19] and is also a complication of preeclampsia.

She was admitted and managed in the intensive care unit as a result of acute-on-chronic kidney failure. It has been posited that pregnant women with acute-on-chronic kidney failure should be managed in intensive care unit (ICU) using a multi-disciplinary team approach made up of the gynecologist, intensivist, nephrologist, hematologist, nurses and nutritionists. She had slow long extended daily dialysis (SLEDD) or sustained low-efficiency dialysis as it is thought to be more suitable for her because of her hemodynamic instability and massive blood loss [20]. Other dialysis modalities that can be employed include intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT). Sustained low- efficiency dialysis is a hybrid form of renal replacement therapy. It shares the advantages of both IHD and CRRT. Simple procedure, flexibility scheduling, fluid removal without adverse effect, good metabolic control, no increased risk of bleeding with the use of citrate and use of standard haemodialysis machine are some of the advantages of SLEDD [21,22]. Nutritional support is very important in managing these patients. Early aggressive enteral, parenteral or combined nutritional support is paramount in management [23].

The depression she suffered may be due to prolonged hospital admission, her disease condition and concern about her baby’s chance of survival.

Initially her family history seemed negative for ADPKD due to inadequate information about her lineage from her and her relatives but during evaluation of her relatives for kidney transplant her 2 sisters were discovered/noted to have polycystic kidneys. Her available relatives were also evaluated for the disease using ultrasonography.

Her children were referred to the pediatrician for follow up because of the quoted 50% risk of inheriting ADPKD by the offspring of women with ADPKD [24]. It has been noted that about 95% of individuals with ADPKD have an affected parent and each child of an affected individual has a 50% chance of inheriting the pathogenic variant [24]. Pre-implantation genetic diagnosis (PGD) may be an option for some families with high risk of ADPKD. The follow up of her children should among other things include early blood pressure monitoring, screening for aneurysm and cardiovascular complications.

Although we did not see this patient before conception, preconception counseling should be an integral part of the management of women of reproductive age with hypertension, CKD and ADPKD. They should be cautioned on the possibility of becoming pregnant and the need to plan their pregnancy to occur when they are in optimal health. They should be made to understand the risk of the renal disease progressing to ESKD during pregnancy especially in those with moderate to severe disease. They should understand that the most important factor affecting fetal and maternal prognosis is the degree of renal function at conception.

On the other hand although not applicable to this case since she had undergone a hysterectomy, women with landesman and Sherr class C who are considering further pregnancy should be counseled on the risk of pregnancy, possible need for dialysis, risk of inheriting ADPKD for the unborn baby, and the need for prenatal genetic diagnosis (where available).

Prenatal diagnosis can be done using prenatal ultrasonography. The diagnosis of fetal ADPKD is suspected when the ultrasound scan shows intrauterine sonographic finding of hyperechogenic enlarged fetal kidney.

Efficient collaboration and communication between the related specialties and sub-specialties is very essential to ensure the best possible care for patients. Continuous training and retraining of the teams involved in managing such high risk pregnancy should be instituted and maintained. With widespread availability of dialysis centers and anticipated increase in survival of renal patients, Resident doctors’ exposure to the management of renal diseases in pregnancy should be increased by organizing postings in renal units. Where the patient is already on these drugs before the onset of pregnancy the drug regimen should be reviewed and changed to other antihypertensive drugs which are relatively safe in pregnancy. Centers for the management of kidney disease in pregnancy should be established to help improve on the experiences of physician and allow for proper equipment, and training of residents and ancillary services.