Pregnancy Related Acute Renal Failure in a Tertiary Care Hospital in Bangladesh

Background: Pregnancy related acute renal (PRARF)failure is more commom in deverloping countries than developed country. Improved antenatal care and obstretic care reduce PRARF in developed country. In Bangladesh maternal mortality rate is 3.8/1000 population of which 25% account foracute renal failure. We try to find out cause, risk factor and out come of pregnancy related acute renal failure. Materials and Methods: A prospective obsevational study was done to observe the status of ARF in pregnancy inNephrology Department of Dhaka Medical College during 2007-2008. All patients were undergone detail histoty, clinical examination and investigation and follow up during hospital stay. Data recorded in predesigned case record form., Statistical analysis was done with SPSS soft ware 12.5 pakage. All data presented as mean or percentage. The Chi square test or Fisher’s exact test was used to compare differences in the frequency of clinical manifestations among cases. P value <0.05 count as significant. Results: Among 57 women, the mean age was 27±6.6 years range from 17-43 years.Sixty seven percent were multrigravidae, 51%(29) was on irregular antenatal care, and 67% below primary level of education. Renal failure occur mainly in 3 trimester of pregnancy (31.4±7.4 weeks). Common presentation is with generalized swelling (51%)and oligouria (52%) with reduce haemoglobin and leucocytosis. The mean creatinine was 6.7±3mg/dl in this series. Lower uterine caeserian section (LUCS) done in 23% cases. 56.1% had severe renal failure and 47% patients required dialysis. Complete recovery was seen in 63%cases while, 31% died and 6% patient have incomplete recovery with persistent dialysis dependent status. Septicaemia (43%) and eclampsia (19%) were the main cause of PRARF, others causes were PPH, APH, ruptured ectopic pregnancy. In 3% patients, actual cause was not identified. Poor antenatal care(p-0.027 ), severity of renal failure(p-0.066), patient requiring dialysis(p-0.025), LUCS(0.028), septicaemia(p-0.026) and low level of education(0.036) have significant effect on outcome. Conclusion: Pregnancy related acute renal failure is common with inceased mortality in our study due to poor antenatal care, low level of education and multiple pregnancy. Improve obstretical care and Nephrological care may reduce Pregnancy related acute renal failure and mortality. 1. Assistant Profesor, Department of Nephrology, Enam Medical College, Savar, Dhaka. 2. Assistant Professor, Department of Nephrology, Dhaka Medical College, Dhaka. 3. Assistant Professor, Department of Medicine, Dhaka Medical College. 4. Medical officer, 250 Bedded hospital, Sadar, gopalgonj 5. Professor of Nephrology, National Institute of Kidney Disease and urology. Correspondence : Dr. Ratan Das Gupta, Assistant Professor, Department of Nephrology, Dhaka Medical College. Email:dasgupta_ratan@yahoo.com maternal mortality rate is about 3.8/1000 population.2 of which 25% is account for acute renal failure3. In healthy pregnancy marked changes occurs in physiology and anatomy of renal system. Renal blood flow increases upto 70%,GFR increases 50%, blood pressure and creatinine fall.4,5 More over pregnancy related hypertension, eclampsia are important complicating factors during pregnancy. Even normal level of creatinine is regarded as renal failure during pregnancy. Pregnancy related acute renal failure is about 20% of totalAcute Renal failure( ARF) with 50% mortality in india. 6 Pre-eclampsia and eclampsia is the most common cause(14.5-23%) of of ARF related to pregnancy.6 Other causes are septic abortion, antepartum and postpartum haemorrhage, ischemic acute tubular necrosis, acute fatty liver of pregnancy, puerperal sepsis and thrombotic microangiopathies and pyelonephritis.7 Improved antenatal care and obstetric practices in developed countries markedly Introduction: Pregnancy related acute renal failure is the important cause of maternal mortality. In developing country it is more common than developed countries as a result of improved antenatal care and obstetric practice.1 In Bangladesh reduced pregnancy related acute renal failure in last 50 years.3 Acute renal failure related to pregnancy is about 5% and 1/ 10000 of all pregnancy in developed countries.3 Although in Bangladesh as well as in other developing country it is declining but still it remains high and leading to increase maternal mortality. Data from eastern India, 11.6% of acute renal failure patient recurring dialysis were due to pregnancyrelated. 8 This increased in acute renal failure is due to poor antenatal, postnatal and obstetrical care. Proper identification of causes and risk factors of pregnancy related acute renal failure may help to prevent pregnancy related ARF and thus reduce maternal mortality. Materials and Methods: This was a Prospective observational study done in Nephrology department of Dhaka medical college during 2007-2008. Study population included all pregnancy related acute renal failure patients admitted or consulted by Nephrology department after excluding chronic kidney disease or pre-existing renal disease and SLE. Informed written consent was taken from enrolled patients. Patients were carefully observed and pertinent clinical and laboratory data recorded daily on a standard form. All patients underwent detailed history and examination and laboratory investigations of routine urine examination, blood urea, seum creatinine, ultrasonography, complete blood count, liver function test was done. All patients was followed up daily during hospital stay and every fifteen day intervail for at lest three months who fail to recover completely. All test were done in Dhaka Medical College laboratory and ultrsonography was done in radiology department. Creatinine reacts with Alkaline picrate proceding an orange red complex. The speed of absorbence change is proportional to the creatinine concentration. This test were done by Hitachi 912 (Germany) and reagents were also supplied by Hitachi. The outcome measurement were seen as Death, complete recovery and incomplete recovery. ARF was diagnosed on basis of clinical and laboratory findings. Sudden oliguria (urine less than 400 ml in 24 hrs) or anuria or serum creatinine increased above 1.5mg/dl was defined as ARF Complete recovery was defined as renal function (s. creatinine) returning to normal. Whereas, partial improvement was defined when serum Creatinine decreased below 2 mg/ dl and patient was not dialysis dependent. Irreversible renal failure was defined when the patient remained dialysis dependent after 3 months of enrollment. Acute tubular necrosis (ATN) was suspected with history of hypovolemia, APH, PPH, abruption placentae, hypotension and transfusion reaction with increased creatinine value(>2mg/dl). Sepsis was diagnosed in presence of fever > 38.5 C, respiratory rate >20/min, pulse rate>90/min, WBC counts > 12000 cells/mL ± DIC, positive blood cultures, retained products of conception and/ or organ hypoperfusion. Preeclampsia was diagnosed if hypertension and proteinuria occurred after 20 weeks of gestation, progressing to eclampsia when seizures occurred. Indications for dialysis were volume overload, hyperkalemia, metabolic acidosis, uremic encephalopathy, severe uremia. Data was recorded in predesigned case record form. Data analysis were done using SPSS version 12.5 chicago illianois. All parameter are presented as mean ± SD or percentage. Chi-square test applied for compares between groups and p value <.05 count as significant. Results: During the period of 2007-2008, 57 women with pregnancy related acute renal failure were observed with mean age 27±6.6 years and range from 17-43 years. Most of the patient were on irregular antenatal care 51%(29), and 67% were multrigravidae. Acute renal failure occur mainly in 3rd trimester of pregnancy with mean age of gestation was 31.4±7.4 weeks. 67% of patients were below primary level of education. Table-I shows baseline characteristics of population. Table-I Base line characteristic of study population Mean ± SD (range) / percentage(n) Age (years) 27.6± 6.6 ( 17-43) Antenatal care Regular 23%(13) Irregular 51%(29) No 26%(15) Number of Primi 33%(19) pregnancy Multrigravidae 67%(38) Duration of 1st trimester 14%(8) pregnancy 2nd trimester 9%(5) 3rd trimister 77%(44) Weeks of pregnancy 31.4±10.3 Education Below primary 53%(30) Below HSC 41% Above HSC 6% Pregnancy Related Acute Renal Failure in a Tertiary Care Hospital in Bangladesh JM Vol. 13, No. 2


I. Introduction
There are several significant physiological changes that occur during pregnancy.Increased blood volume, reduced vascular resistance, and other anatomical and physiological changes which might affect kidney function and, in some cases, can cause renal failure [1,2,3] .
The incidence of pregnancy related acute renal failure (PRARF) has declined over the past few years.The incidence of pregnancy related acute renal failure ranges from 5-15% in developing countries with a much lesser percentage in developed countries.The reasons for the decline are multifactorial owing to better understanding and pathophysiology, decreased septic abortion cases due to abortion laws, judicious and early termination in severe pre-eclampsia and others [4,5] .
Causes of pregnancy related acute renal failure can be divided into pre renal ARF, Intrinsic ARF and post renal ARF.Pre renal is the most common form of ARF, the causes of which include hemorrhage, infections, septic abortion, severe pre-eclampsia and eclampsia, abruptio placenta and severe dehydration.Intrinsic renal causes are ischemia, toxins, renal disease, DIC and others [3] .
During the reversible stages of Anuria, the clinical condition can be divided into four phases: Incipient stage, phase of anuria, phase of diuresis and phase of recovery.Phase of anuria can last from few hours to few weeks.Initially asymptomatic, gradually patients might develop anorexia, vomiting and diarrhea.And in the later stages, patient looks toxic with raised blood pressure, mental confusion and finally delirium followed by coma might be the end result if not managed [3,4] .
There is gradual increase in the concentration of plasma urea, potassium, creatinine and phosphate as a result of endogenous protein catabolism.Rise in phosphate leads to lowering of plasma calcium.The fall in calcium with rise in potassium might have an adverse effect on cardiac function [6] .
Though the incidence of the pregnancy related acute renal failure is declining but still it's an important medical condition which must be diagnosed and promptly managed.It is therefore essential to understand the changes to make a proper interpretation of the clinical and laboratory findings in pregnancy.
The objective of the study was to determine the prevalence, clinical profile, management and outcome of patients with pregnancy related acute renal failure.

II. Material and methods
The present study was based on the retrospective analysis of hospital case records of Department of Nephrology in Government General Hospital, Guntur Medical College, Guntur.It was intended to bring out the profile of the pregnancy related acute renal failure (PR-ARF) cases in pregnancy admitted in the hospital from 2010 to 2018.
Inclusion criteria: Pregnant women who had developed acute renal failure with oliguria (urine output <400ml in 24 hours and serum creatinine >1.5 mg/dL during antepartum and postpartum period Exclusion criteria: History of any renal disease prior to pregnancy including renal stones or any medical history of hypertension or diabetes before the pregnancy were excluded from the study.
Patients were monitored carefully and managed accordingly.Hemodialysis was performed according to the standard protocols.
ARF is a clinical syndrome that indicates an abrupt decline in glomerular filtration rate (GFR) to a sufficient amount to decrease the excretion of nitrogenous waste products (urea and creatinine) and other uremic toxins [4,7] .PR-ARF was diagnosed on the basis of clinical and laboratory findings.Sudden oliguria (urine <400 mL in 24 h) or anuria or serum creatinine increased above 1.5 mg/dL was defined as ARF [8] .
A predesigned proforma was used to get the information from the case records.The basic demographic data, clinical and laboratory details of all the patients were recorded properly.Statistical analysis was done by using Microsoft Excel 2007 and EPI INFO 7 version.Data was presented in percentages and proportions.

III. Results
A total of 5788 patients were admitted in the department of Nephrology at our institute over 9 years period (2010 to 2018).Out of the 5788 admissions, 2236 admitted cases were due to Acute Renal Failure (ARF).Among the total ARF cases, pregnancy related acute renal failure cases were 248 (11.09%), hence the prevalence of PRARF in the present study was 11.09%.A complete review of the hospital case records was done among these 248 PRARF cases.
Observation of year wise distribution of the PRARF cases found that highest number of cases were seen in 2018 and lowest in 2014 & 2017 years respectively.Mean age of the study population was 23 years.With regards to causes of pregnancy related acute renal failure, the most common cause in the present study was toxemias of pregnancy which was seen in more than one third cases (37.1%).Next common causes were postpartum hemorrhage which was seen in 32 cases (12.9%), puerperal sepsis (10.5%), ante partum hemorrhage (9.2%).Other causes were Acute Gastroenteritis (5.2%), Acute viral hepatitis (4.8%), Septic abortion (4.4%).Post LSCS Hemodynamic and Thrombotic Micro Angiopathies were seen in 9 cases each respectively.Out of the total 248 cases, majority (64.1%, n=159) were treated on hemodialysis and rest 89 cases (35.9%) were managed conservatively.A complete recovery was seen in majority of the patients (91.1%, n=226) followed by partial recovery in 14 cases (5.7%).
In the 9 years study period, there were 8 patients (3.2%) who expired due to pregnancy related ARF.

IV. Discussion
Acute Renal failure is alife-threatening complication in pregnancy.The present study had been conducted in a tertiary care institute with an objective to determine the prevalence, clinical profile, management and outcome of patients with pregnancy related acute renal failure.A retrospective analysis of hospital case records was done with an intention to bring out the profile of the pregnancy related acute renal failure (PR-ARF) cases in pregnancy admitted in the hospital from 2010 to 2018.In the present study, the prevalence of pregnancy related acute renal failure was found to be 11.09%.Slightly lower incidence of PRARF was seen in study by Goplani K R et al [4] where incidence was 9.06%.
A systemic review by Zynab Karimi et al [3] on prevalence of pregnancy-related Acute Renal Failure in Asia observed that the prevalence ranged from 0.1% in China to 21.6% in Bangladesh.Another study from India revealed 19.3% developed acute kidney failure in the first trimester, 10.5% in the second, and 70.2% during the puerperium period.
Sivakumar et al [9] reported that out of 1,353 cases with ARF seen between 1999 and 2009, 59 (4.36%) were pregnancy-related.The prevalence rates of ARF during different trimesters pregnancy were as follows: 1.7% in the first trimester, 6.7% in the second trimester, 16.9% in the third trimester, and 74.6% in the postpartum period.With regards to causes related PRARF, present study found that the most common cause was toxemias of pregnancy (37.1%) followed by postpartum hemorrhage (12.9%), puerperal sepsis (10.5%) and ante partum hemorrhage (9.2%).
A changing picture of acute kidney injury in pregnancy study from 33 years observation by J.Prakash et al [12] observed post abortal AKI as the commonest cause followed by puerperal sepsis, hypertensive disorders and haemorrhage (ante partum & postpartum).In the present study, about two thirds were managed with hemodialysis and rest conservatively.A complete recovery was seen in majority of the patients (91.1%) followed by partial recovery in 5.7%.In the 9 years study period, there were 8 patients (3.2%) who expired due to pregnancy related ARF.
A single centre experience by Najar MS et al [13] observed that about one third patients were given hemodialysis, peritoneal dialysis in 15% and both modalities in 12.5%.Only medical treatment was given in majority (40%) of the cases.About three fourth of patients recovered completely.A higher mortality was found in this study (20%) compared to the present study.

V. Conclusion
Though the prevalence of pregnancy related ARF has been declining over the years, but the present 9 years hospital based retrospective study found a higher prevalence of 11.09% with toxemias in pregnancy being the most common cause followed by postpartum hemorrhage and sepsis.Two thirds of them were managed through hemodialysis.Prognosis was good with majority of them recovered completely.Therefore, a good quality of ante natal care with accurate diagnosis would be an important factor in reducing the burden.