Acute Renal Failure in Pregnancy in a Developing Country: Twenty Years of Experience

Abstract

Acute renal failure (ARF) has become a rare complication of pregnancy in developed countries. The aim of this study was to describe changing trends in pregnancy-related acute renal failure (PR-ARF) in two successive periods; 1982–1991 and 1992–2002. From July1982 to December 2002, 190 cases of PR-ARF were observed in Eastern India (11.6% of total number of ARF needing dialysis). Obstetrical complications were causative factors for ARF in 15% (65/426) and 10% (125/1201) of patients in the two periods, respectively. The incidence of PR-ARF fell from 15% in 1982–1991 to 10% in 1992–2002, with respect to the total number of acute renal failure cases. Post-abortal ARF showed a declining trend, 9% in the 1980s to 7% in the 2000s, of the total number of ARF cases. Preeclampsia-eclampsia was the cause of obstetrical ARF in 23% (1982–1991) and 14.4% (1992–2002) of cases in these two periods. The percentage of total ARF due to eclampsia declined from 3.5% during the period 1982–1991 to 1.4% in 1992–2002. Puerperal sepsis contributed to 0.8% of total ARF in recent years, compared to 2.4% in the earlier period. The incidence of cortical necrosis decreased significantly (p < 0.001) from 17% in 1982–1991 to 2.4% in the 2000s. The maternal mortality reduced to 6.4% in 1992–2002 from initial high mortality of 20% in the period of 1982–1991. Conclusion. PR-ARF which remained high in the initial period has decreased in recent years. This is associated with a declining trend in post‐abortal ARF and a reduction in maternal mortality as well. We noted a significant decrease (p < 0.001) in the incidence of cortical necrosis in PR-ARF. The reasons for this favorable outcome in obstetrical ARF seem to be due to improved medical care, decrease in the number of septic abortions, effective care of obstetrical complications, and legalization of abortion.

Keywords:

• pregnancy
• renal cortical necrosis
• acute renal failure
• septic abortion
• dialysis

INTRODUCTION

The incidence of pregnancy-related acute renal failure (PR-ARF) in western countries with respect to the total number of cases of acute renal failure (ARF) has markedly decreased over the last few decades, from 20–40% in the 1960s to 2–3% in the 1980s.[1–3] In the same period, the frequency of PR-ARF vs. the total number of pregnancies has fallen from about 1/3,000 to 1/15,000–1/20,000.[1–4] This dramatic decrease of PR-ARF in industrialized countries reflects the virtual disappearance of septic abortion and improved prenatal care.[[1]], [[2]] Obstetrical complications constituted 15–25% of total cases of ARF in India in the 1970s and 1980s, and septic abortion was the most common cause of ARF in pregnancy.[[5]], [[6]] Since 1970, ARF in pregnancy in India has shown declining trends and obstetrical causes constitute 9–13% of total cases of ARF.[[7]], [[8]] In recent years, ARF has become a rare (1 in 20,000 pregnancies) complication in pregnancy in developed nations, in contrast to the still high incidence of PR-ARF in developing countries.[[5]], [[9]], [[10]]

The purpose of this study was to describe the changing trends in PR-ARF over a period of 20 years and compare the results of our observations in two periods, namely 1982–1991 and 1992–2002, with respect to evaluating epidemiology, nature of renal damage, and outcome in PR-ARF.

PATIENTS AND METHODS

This study was conducted at the Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India, between 1982–2002. The patients with ARF following obstetrical complications form the subject load of the present study. The comparison was made between all cases of PR-ARF needing dialytic treatment between 1982–2002 and the number of patients with ARF on dialysis in our unit over the same period. Two 10-year periods were compared: 1982–1991 and 1992–2002. The causes of PR-ARF were classified according to their obstetrical complications: 1) post-abortal, 2) preeclampsia-eclampsia (PE-E) (according to the diagnostic criteria of the American College of Obstetrics & Gynecology), 3) Postpartum hemorrhage, 4) puerperal sepsis, and 5) antepartum hemorrhage (Table 1).

Table 1 Obstetrical complications causing ARF

	Study period
Complications	1982–1991 (n = 65)	1992–2002 (n = 125)
Post-abortal	40 (61.5%)	90 (72%)
Eclampsia	15 (23%)	18 (14.4%)
Puerperal sepsis	06 (9.23%)	10 (8%)
APH	02 (3%)	04 (3.2%)
PPH	02 (3%)	03 (2.4%)

Pre- and post-dialysis biochemical investigation included measure of blood urea, serum creatinine, uric acid sodium, and potassium. The other biochemical investigations included serum calcium, phosphorous, alkaline phosphatase, serum protein, albumin, and SGOT/SGPT. The hematological and coagulation studies were done by standard technique to rule out disseminated intravascular coagulation (DIC) and hemolytic uremic syndrome (HUS). Kidney size was assessed by ultrasonography prior to biopsy. The renal tissue was obtained by percutaneous biopsy and studied using light microscopy to check for renal cortical necrosis in selected cases.

RESULTS

One hundred ninety patients with obstetrical ARF were studied over 20 years between 1982–2002. The obstetrical complications leading to ARF are shown in Table 1. Post-abortal ARF remains the dominant cause of PR-ARF in the two periods. The various categories of obstetrical ARF, with respect to the total number of cases of ARF, are shown in Figures 1 and 2. The fall in PR-ARF during the second period was solely due to an increase in the number of total cases of ARF treated by dialysis. Overall, the causes of PR-ARF in the two periods show little or no differences (Figures 1 and 2). On comparison of PR-ARF with respect to the total number of cases of ARF, we observed prevalence of obstetrical ARF fell from 15% in 1982–1991 to 10% in 1992–2002. The post-abortal ARF had a declining tendency; 9% in 1982–1991 and 7% in 1992–2002. The maternal mortality reduced to 6.4% from an initial high mortality of 20% (Table 2). There is a significant reduction in the incidence of cortical necrosis in 1992–2002 in contrast to very high incidence (17%) in 1982–1991 (Figure 3). The acute tubular necrosis was the dominant renal lesion in obstetrical ARF in both early and late pregnancy. However, the incidence of renal cortical necrosis was nearly equal in early and late pregnancy. The acute tubular necrosis (ATN) was the clinical diagnosis in the majority of cases (Table 3).

Table 2 Comparative data for ARF in two study periods

	Study period
Parameters	1982–1991	1992–2002
Prevalence of obst. ARF	15%	10%
Post-abortal ARF	9%	7%
Maternal mortality	20%	6.4%
Cortical necrosis	17%	2.4%
Puerperal sepsis	2.4%	0.85%
Eclampsia	3.5%	1.4%
Uterine hemorrhage (APH + PPH)	0.92%	0.58%

Table 3 Renal histology of ARF

Phase of pregnancy	Total patients	1982–1991		Totalpatients	1992–2002
		ATN	ACN		ATN	ACN
ARF in early pregnancy	40	33 (82.5)	07 (17.5)	90	88 (99.7)	02 (0.2)
ARF in late pregnancy	25	21 (84)	04 (16)	35	34 (97)	01 (2.9)

Figure in parentheses represents percentage.

ATN—acute tubular necrosis.

ACN—acute cortical necrosis.

Figure 1 Obstetrical ARF with respect to total ARF (1982–1991).

Figure 2 Obstetrical ARF with respect to total ARF (1992–2002).

Figure 3 Comparative analysis of renal histology.

Renal biopsy was performed in patients with persistent anuria (>4 week) and with clinical suspicion of cortical necrosis. A renal tissue was obtained for biopsy in 18 cases and was evaluated by light microscope. Biopsy revealed cortical necrosis in 14 cases and tubular necrosis in 4 cases.

DISCUSSION

Although there has been a decline in the incidence of ARF from obstetrical causes in recent years in India, complications related to pregnancy continue to be an important cause of ARF in our country. In the Chandigarh study, ARF due to septic abortion, which constitutes 13.7% of total ARF during 1965–1974, had declined to 3.5% by 1981–1986. The overall incidence of obstetric causes leading to ARF decreased from 22.0% to 9.2% in the same period.[[7]] In economically advanced countries, the current estimates of the incidence of ARF in pregnancy are less than 0.01%.[[2]], [[3]] We noted ARF due to obstetrical complication decreased from 15% in 1982–1991 to 10% in 1992–2002 with a declining trend in post-abortal ARF from 9% to 7% in the same period.

Sepsis and acute renal failure are much more common following illegal than legal abortions.[[11]], [[12]] The legalization of abortion in India in 1972 has led to a fall in the incidence of post-abortal acute renal failure. ARF in early pregnancy is almost always due to septic abortion, and in the vast majority of cases (85%) abortion is conducted by unauthorized and self-trained personnel under unhygienic conditions. The legalization of abortion was followed by a substantial decrease in the percentage of septic abortion related acute renal failure in several developing countries.[[13]] In addition, we have noted the majority of pregnant women are multigravida—seeking abortion for limitation of family size in our study.[[8]] Therefore, the avoidance of unwanted pregnancy and prevention of septic abortion are keys to eliminating ARF associated with septic abortion in early pregnancy.

Obstetric complications such as eclampsia, abruptio placenta, intrauterine fetal death, ante/post-partum hemorrhage, and puerperal sepsis may cause ARF in late pregnancy.[[8]], [[14]], [[15]] The prevalence of obstetric ARF was 38.5% in 1982–1991 and decreased to 28% in 1992–2002 in late pregnancy. This decrease is due to better obstetric management in the latter period of studies. A similar observation was noted in another study.[[7]] The improvement in operative technique, availability of potent antibiotics, decline in the use of the traditional midwife (dai) for deliveries, and overall improvement in obstetric care have lead to a reduction of more than 50% in the incidence of acute renal failure due to postpartum hemorrhage and puerperal sepsis in late pregnancy.[[16]] The incidence of puerperal sepsis associated ARF has decreased to 0.8% in recent years from 1.4% in 1982–1991. Similarly, incidence of acute renal failure following eclampsia has decreased to 1.4% from 3.5% in 1982–1991. These favorable responses in the latter period reflect overall improvement in obstetric care at our center.

The main cause of obstetric ARF in late pregnancy is preeclampsia-eclampsia. Renal hypoperfusion is a major factor responsible for ARF in these patients. Decreased glomerular filtration rate and decreased sodium excretion are characteristic of preeclampsia. However, frank ARF is unusual, unless complications such as abruption-placenta is superimposed on preeclampsia or preeclampsia progresses to develop hemolysis with elevated liver enzyme and low platelet count (HEELP) syndrome.[[17]]

Renal cortical necrosis (RCN) is an uncommon entity that accounts for only 2% of all cases of ARF. Obstetric cause accounts for RCN in 56% and 65.2% of patients reported in two Indian studies.[[18]], [[19]] The overall incidence of renal cortical necrosis in obstetric ARF was 25% in our previous series.[[20]] However, the incidence of renal cortical necrosis ranges between 10–30% of all cases of obstetric ARF. The incidence of renal cortical necrosis has declined from 17% in 1982–1991 to 2.4% in 1992–2002 in obstetric ARF. Thus, we observed a significant reduction in the incidence of cortical necrosis in PR-ARF in the present study. This change is mainly due to the reduction in the number of septic abortions, improved care of sepsis, and better management of puerperal sepsis.

Maternal mortality was as high as 33% in the previous study; sepsis being the most common (48%) cause of death.[[8]] The maternal mortality reduced to 6.4% in 1992–2002 from initial high mortality of 20% in the period of 1982–1991. It appears ARF in pregnancy is largely preventable because it is usually the result of obstetric complications and not intrinsic renal disease. The elimination of septic abortion is the key step in preventing post-abortal ARF. With this in mind, pregnancy-related acute renal failure could be viewed as a public health problem rather than a nephrological problem.

In conclusion, pregnancy-related ARF, which remained high in the initial period, has decreased in recent years. This is associated with a declining trend in post-abortal ARF and a reduction in maternal mortality. We also observed a significant fall (P < 0.001) in the incidence of cortical necrosis in obstetric ARF. These changing trends in obstetrical ARF were mainly due to decreases in the number of septic abortions, puerperal sepsis, the legalization of abortion, and improved care of obstetrical complications.

ACKNOWLEDGMENTS

This work was presented as free communication in a symposium “Kidney in Pregnancy” in the ERA-EDTA/ISN, World Congress of Nephrology, June 8–12, 2003, Berlin, Germany. The abstract was ranked within the top 20 scores in the Berlin World Congress of Nephrology (WCN 2003).

Notes

9. Prakash J, Tripathi K, Usha, Srivastava PK. Pregnancy related acute renal failure is still high in India (Abstract). Proceeding of the 11th International Congress of Nephrology. Tokyo, 1990;15A.