| Abstract|| |
Pregnancy-related acute kidney injury (PRAKI) and urological complications can significantly increase the maternal morbidity and mortality, and morbidly adherent placenta (MAP) has been found to increase the risk of both. This is a four-year prospective study, conducted on patients with MAP. Baseline parameters (demographic/antenatal/perinatal), operative details (obstetric/urological/hemostatic), peri-operative complications (AKI/urological), and maternal/fetal outcomes were studied till six weeks after delivery. Statistical analysis was done using IBM SPSS Statistics version 21.0, and P <0.05 was considered statistically significant. Out of the 5475 deliveries conducted in the study period, 64 had adherent placentation. AKI occurred in 39.1% of patients, with severe AKI (AKIN-2, 3) in 10.9%, and significantly higher incidence in placenta percreta (P = 0.021, relative risk [RR] - 2.34), urological injuries (P = 0.001, RR - 2.86), and high blood loss (P = 0.001) on univariate analysis, but placenta percreta was the most statistically significant factor P = 0.049) on multivariate analysis. Urological involvement/injuries requiring intervention were encountered in 22 patients, with statistically significantly high incidence in placenta previa (P = 0.023, RR - 1.62), placenta percreta (P = 0.000, RR - 17.18), and patients undergoing hysterectomy (P = 0.000, RR - 2.01) on univariate analysis, but placenta percreta was most statistically significantly implicated on multivariate analysis (P = 0.017). AKI and urological injuries significantly increased the need for intensive care and days of hospitalization. On six-week follow-up, all AKI patients recovered completely; no urinary leak or vesico-vaginal fistula was seen in urologically intervened patients and no maternal mortality occurred. There is an alarmingly high incidence of PRAKI and urological complications in MAP, posing a great threat to their worldwide improving statistics. Awareness of this condition among renal fraternity can significantly improve the maternal renal and overall prognosis.
|How to cite this article:|
Chahal HS, Juneja SK, Kaur S, Kochar B, Sharma S, Makkar V. Pregnancy-related acute kidney injury and urological comorbidities in morbidly adherent placenta: A potential challenge to AKI-0by25. Saudi J Kidney Dis Transpl 2020;31:368-79
|How to cite this URL:|
Chahal HS, Juneja SK, Kaur S, Kochar B, Sharma S, Makkar V. Pregnancy-related acute kidney injury and urological comorbidities in morbidly adherent placenta: A potential challenge to AKI-0by25. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 May 25];31:368-79. Available from: http://www.sjkdt.org/text.asp?2020/31/2/368/284011
| Introduction|| |
Pregnancy-related acute kidney injury (PRAKI) is an unexpected adverse turn of events in an otherwise normal maternity and is a major cause of perinatal morbidity and mortality in developing countries. Obstetric hemorrhage is among the major cause of PRAKI, and morbidly adherent placenta (MAP) causes the severest of hemorrhages, but the incidence of PRAKI in MAP has not been studied systematically. MAP is a rare form of placental mal-adherence, due to defect in decidua basalis, resulting in abnormal invasion of the placenta into the substance of the uterus and absence of a plane of cleavage between the two. Depending on severity, the condition is classified as placenta accreta (the chorionic villi reaching the uterine myo- metrium), placenta increta (invading into the uterine myometrium), and placenta percreta (chorionic villi penetrating the uterine serosa and beyond). It occurs due to absence/deficiency of Nitabuch’s layer. This aberrant invasion can extend beyond the uterus into the surrounding pelvic structures, with urinary bladder being the most common, besides involving the ureters, gut, and rarely abdominal wall.,, The lacunae in antenatal care in developing countries leading to the diagnosis of MAP in peripartum period and lack of awareness regarding the potential risk of AKI and urological involvement make the scenario even more challenging.
This study highlights the incidence of AKI and urological complications with MAP and their impact on maternal morbidity.
| Materials and Methods|| |
This was a prospective study done over a period of four years (January 1, 2014, to December 31, 2017) at a tertiary care center in North India. The study was approved by the institutional ethical committee. Pregnant patients delivered in our hospital, diagnosed antenatally or peri-partum to have MAP, with normal baseline renal function and no past history of renal disease or diabetes, were included in this study. Proper informed consent was taken from the patients for inclusion in the study. Patients with pre-eclampia/ eclampia, a history of urological surgery in the past, and those refusing consent for inclusion were excluded from the study.
The diagnosis of MAP was based on the absence of plane of cleavage between the placenta and uterus, resulting in heavy bleeding from the site of implantation on forced/piecemeal removal, making manual removal partially or totally impossible. Histo- pathological confirmation was done in patients undergoing hysterectomy. A detailed history of the patients was recorded including demographic parameters, past obstetric history (number of previous normal or cesarean deliveries, abortions, and any other gynecological procedures), and complete medical and personal history. History pertaining to the present gestation included antenatal history and follow-up, antenatal/perinatal radiological diagnosis of adherent placentation, and the time of first presentation to our hospital (on antenatal follow-up from here or outside) were recorded. Baseline investigations including complete blood count, renal function, urine microscopy and dipstick, liver function tests, coagulation parameters, and ultrasonography were done in all patients. The details of present delivery (normal or cesarean, elective or emergency procedure), presence of bladder invasion and/or injury, and type of obstetric and urological procedures were noted in detail. The estimated blood loss and number of blood transfusions and methods adopted to achieve hemostasis [deep suturing of the placental bed, internal iliac artery ligation (IAL) (unilateral or bilateral), and uterine artery embolization [UAE]) during perioperative period were recorded. Patients were closely monitored peri-operatively and post-operatively for urine output (hourly) and renal function (daily). AKI was diagnosed and staged based on the Acute Kidney Injury Network (AKIN) classification/ staging system. The need for renal replacement therapy, intensive care (with or without ventilator support), and days of hospital stay were noted for each patient. After discharge, each patient was followed up weekly for six weeks, for complications related to obstetric and urological procedures, with renal functions repeated at each visit. A check radio- cystogram was done at three weeks after delivery in all patients undergoing bladder repair/surgery. Final renal, urological, and overall maternal and neonatal outcomes were analyzed at the end of six weeks.
| Statistical Analysis|| |
The data were described in terms of range, mean ± standard deviation, frequencies (number of cases), and relative frequencies (percentages) as appropriate for univariate analysis. Comparison of quantitative variables between the st udy groups was done using Student’s t-test and Mann-Whitney U-test for independent samples for parametric and non- parametric data, respectively. For comparing categorical data, Chi-square (%2) test was performed, and Fisher’s exact test was used when the expected frequency is <5. P <0.05 was considered statistically significant. Relative risk (RR) was calculated for various parameters. Variables which were <0.05 at uni- variate analysis were taken for binary logistic regression for multivariate analysis. All statistical calculations were made using IBM SPSS Statistics for Microsoft Windows version 21.0 (IBM Corp., Armonk, NY, USA).
| Results|| |
A total of 5475 deliveries were conducted in the hospital during the four-year study period, out of which, there were 2047 normal vaginal deliveries and 3428 cesarean deliveries. Out of these, 64 patients were diagnosed to have MAP. The incidence of MAP thus calculated from our study was one in 86 deliveries (i.e., 12.8/1000 deliveries).
The mean age of the patients was 30.98 ± 4.09 years (range 24-45), and the mean gestation was 32.69 ± 5.05 weeks (range 1639 weeks). None of the patients had preexisting renal disease or diabetes or any other exclusion criteria. Most of the patients (n = 58, 90.6%) were multigravida (G2 - 9, G3 - 23, G4 - 17, G5 - 3, and G6 - 6). Fifty-five patients (85.9%) had a history of previous cesarean deliveries and 28 (43.8%) had a history of abortions in the past. One patient had a history of laparotomy twice for ectopic pregnancies and another one had a history of having tried medical termination with oral pills thrice in the present pregnancy.
Twenty-four patients (37.5%) were diagnosed to have MAP on antenatal ultrasound, many of them in early stage of labor on hospital admission. Forty-three (67.2%) had presented to the emergency room, most of which were antenatally undiagnosed cases n = 34) referred from outside in advanced labor with severe complications such as antepartum hemorrhage, hematuria (n = 2), hemoperi- toneum (n = 1), sepsis (n = 2), and disseminated intravascular coagulation (DIC) (n = 2).
In the peri-operative findings, 31 patients (48.4%) had placenta accreta, 13 (20.3%) had placenta increta, and 20 (31.3%) had placenta percreta. Thirty-seven (57.8%) had placenta previa (PP). Urological injuries were encountered in 22 patients (34.4%). The mean estimated blood loss was 2157 ± 1843 mL (range 200-7300 mL), and 56/64 (87.5%) required blood transfusion (mean 3.1 ± 2.8 transfusions; range 1-11 units). Hemostasis was achieved by deep suturing of the placental bed after manual removal of the placenta followed by packing in 11/64 (17.2%), internal IAL in 20 patients (31.3%), and UAE in 10 (15.6%) patients. Five patients needed ultrasound-guided evacuation of the placenta, however one of these patients had post- procedure sepsis and required total abdominal hysterectomy on day 3. Total (n = 38) or subtotal n = 3) hysterectomy was needed in 41 patients (64.1%).
AKI occurred in 25 (39.1%) of MAP deliveries, with AKIN-1 in 11 (17.2%), AKIN-2 in nine (14.1%), and AKIN-3 in five (7.8%) patients. One patient had acute tubular necrosis, with oliguria for eight days and required renal replacement therapy (2 sessions of slow low-efficacy dialysis, on day 6 and day 10 post-delivery at a serum creatinine of 7.32 mg/dL and 8.48, respectively), with subsequent improvement in urine output and renal function, and had a serum creatinine of 3.92 mg/dL on discharge at day 22 post- delivery and normal renal function by six weeks and hence, no kidney biopsy was contemplated for her. None of the other AKIN-3 patients had long-lasting oligo-anuric state requiring renal replacement therapy or renal biopsy. On comparing the group suffering AKI (MAP-AKI) from those without kidney injury (MAP-No-AKI) [Table 1] and [Table 2], there was no statistically significant difference in age (P = 0.372), but AKI was high in patients presenting in early gestation (P = 0.002). AKI occurred more often in ante- natally undiagnosed [RR - 1.15, 95% confidence interval (CI): 0.79-1.68] and emergency cases (RR - 1.23, 95% CI: 0.89-1.72). There was statistically significantly increased risk in placenta percreta (P = 0.021, RR - 2.34, 95% CI: 1.12-4.91) than increta (RR - 0.69, 95% CI: 0.24-2.01) and accreta (RR - 0.64, 95% CI: 0.35-1.15). Patients having AKI had a statistically significantly higher peri- operative blood loss (3086.4 ± 1993.8 vs. 1561.5 ± 1479.6, P = 0.001) and had required significantly higher number of transfusions P = 0.003). AKI was encountered in 50% of patients undergoing IAL (RR - 1.56, 95% CI: 0.76-3.2), 30% with UAE (RR - 0.67, 95% CI: 0.19-2.35) and 27.3% of patients undergoing deep suturing of placental bed (RR - 0.59, 95% CI: 0.71-1.99). Hysterectomy increased the risk (RR - 1.35, 95% CI: 0.951.92) and so did urological interventions (P = 0.001, RR - 2.87, 95% CI: 1.55-5.28). AKI was seen in almost all patients requiring both hysterectomy and bladder repair (14/15). The occurrence of AKI statistically significantly correlated with need for intensive care unit (ICU) care (P = 0.001, RR - 3.64, 95% CI: 1.61-8.22) and increased the number of days of hospitalization significantly (14.4 ± 8.5 vs. 8.4 ± 5.1 days, 95% CI: 2.6-9.5, P = 0.001).
|Table 1: Comparison of patients with morbidly adherent placenta suffering acute kidney injury with those not having acute kidney injury.|
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|Table 2: Comparison of patients with morbidly adherent placenta with acute kidney injury with those not having acute kidney injury.|
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Urological injuries requiring intervention were encountered in 22 patients (34.4%). Patients mostly underwent surgical repair of bladder for bladder tears or rupture, but few needed only adhesiolysis (n = 2) and cystos- copic evaluation with retrograde pyelography (n = 1), with two of them requiring radiopaque polyurethane (double-J) ureteric stent insertion. Indwelling per-urethral catheter was left in situ following bladder repair in all these patients, with additional suprapubic catheteri- zation in four of them with extensive bleeding from the bladder mucosa. None of the patients required complete or partial resection of the bladder. Two patients also required laparo- tomy for accompanying small gut involvement, one of them presenting with hemo- peritoneum and shock. The patients suffering urological complications (MAP-Ur, n=22) were compared to those with no urological injuries (MAP-Non-Ur, n = 42) [Table 3] and [Table 4]. Urological complications occurred more in antenatally undiagnosed patients (RR - 1.27, 95% CI: 0.88-1.84), especially those operated as emergency cases (RR - 1.38, 95% CI: 1.001.89). Most of them were multigravida. Presence of placenta percreta P = 0.000, RR- 17.18, 95% CI: 4.38-67.39) and PP (P = 0.023, RR - 1.62, 95% CI: 1.09-2.39) significantly correlated with the need for bladder repair. There was statistically significantly more blood loss (3898.2 ± 1736.5 mL vs. 1245.2 ± 1094.2 mL, 95% CI: 1944.6-3361.3, P = 0.000) and more requirement of blood transfusions in MAP-Ur patients (5.5 ± 3.0 vs. 1.88 ± 1.5, 95% CI: 2.5-4.8, P = 0.000). Hysterectomy was performed in 95.5% of patients (21/22) with bladder invasion versus 47.6% (20/42) in those without bladder injury (P = 0.000, RR - 2.01, 95% CI: 1.44-2.79). Ten patients in MAP-Ur required IAL, one required UAE, and one required deep suturing of placental bed for hemostasis. Statistically significantly higher number (15/22) had AKI in MAP-Ur (P = 0.001, RR 2.87, 95% CI: 1.55-5.28), with AKIN-1 in 6, AKIN-2 in 4, AKIN-3 in 5, and a significantly higher number needed ICU care (with or without ventilatory support) (P = 0.000, RR: 7.64, 95% CI: 2.91-20.08). The occurrence of urological injuries significantly increased the hospital stay (15.8 ± 8.63 vs 8.1 ± 4.6 days; 95% CI: 4.5-11.1, P = 0.000).
|Table 3: Comparison of patients with morbidly adherent placenta undergoing urological intervention with those requiring no urological intervention.|
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|Table 4: Comparison of patients with morbidly adherent placenta undergoing urological intervention with those requiring no urological intervention|
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On follow-up, all patients with AKI recovered well and none had loss of renal function or urinary sediment and hence the need for kidney biopsy. All MAP-Ur patients underwent radiocystography at three weeks post- surgery, which was found to be normal, with no urinary leak, vesico-vaginal, or uretero- vaginal fistula formation. Five cases of fetal losses at gestation ages 16, 18, 20, 23, and 34 weeks (intra-uterine death of one of the twins in an in-vitro fertilization pregnancy), one neonatal death (on day 6) in a pre-term (26 weeks), and one loss to follow-up after 10 days were encountered. There was no maternal mortality in 63 patients followed-up for six weeks; however, one did not come for follow- up after discharge against medical advice 10 days after delivery.
| Discussion|| |
PRAKI is a leading cause of peri-partum morbidity and mortality. A large number of studies on PRAKI from the developing countries reveal a decrease in its incidence over the last few decades. The incidence in India has steadily declined from 22% in the 1960s to 9% in the 1980s, 3% to 7% in the early 2000s,, and a further down to 1.56% in 2017. South Africa showed improvement from 25% to less than 16% over a period of 15 years. A study in Turkey also demonstrated a declination of PRAKI primarily due to reduction in septic abortion by 30% in the last 20 years. The incidence in different provinces in China ranged from 0.02% to 1.84%. These improved statistics in developing countries are attributed to the improved socioeconomic situation, early detection of PRAKI, and proper management of obstetric complications. However, the levels continue to remain higher than those seen in developed countries (1 in 20,000 pregnancies). In developing countries, sepsis and hemorrhage account for ≥50% of cases of PRAKI, in contrast to developed countries where chronic hypertension, renal disease, and preeclamp- sia/eclampsia are important causes., None of the studies have systematically studied the risk of PRAKI in MAP, the rising incidence of which is a matter of concern for both developing and developed countries.
MAP with its growing incidence poses a great threat to the physiology of parturition. The gravity of danger posed by MAP can be assessed from its incidence, which has increased from one in 2562 in the 1970s, one in 53-3 in a retrospective series from 1982 to 2002, one in 275 in 2008-2010, to a high of 1 in 86 deliveries in our study. This trend largely correlates with rise in the number of cesarean deliveries and the higher incidence of PP as both these conditions are harbinger of adherent placentation. The normal vaginal delivery (NVD) to cesarean section ratio in our study too was 1.67:1, a sharp skewing toward cesarean because of ours’ being a referral hospital catering to high-risk and complicated cases. Other clinical conditions associated with MAP are grand multiparity, prior uterine surgery, myomectomy, curettage, uterine irradiation, endometrial ablation, Asherman syndrome, uterine leiomyomata, uterine anomalies, hypertensive disorders of pregnancy, and smoking. MAP can lead to life-threatening hemorrhage, AKI, bladder and bowel involvement, sepsis, DIC, and rarely amniotic fluid embolism, thus significantly increasing the risk of maternal and fetal morbidity and mortality. Studies have reported maternal mortality of 6%-7% and a perinatal mortality of 24% with MAP. This study unfolds the strong correlation between PRAKI and urolo- gical complications with MAP.
MAP patients are predisposed to AKI due to excessive bleeding, increased risk of sepsis, DIC, co-existent organ invasions, and need for extensive and sometimes multiple surgical interventions. The incidence of PRAKI in our study was as high as one-third of MAP deliveries (39.1%), with 10% having severe AKI. The incidence was higher in early gestation, possibly because these patients had more severe placental invasions, causing early antepartum hemorrhages, sepsis, DIC, etc. AKI was seen more in patients with placenta percreta and presence of bladder invasion, possibly due to excessive hemorrhage, extensive surgical intervention required, need for blood products, increased sepsis, and DIC in these patients. There was no difference in the incidence of AKI with different hemostatic techniques (deep suturing, UAE, and IAL) or hysterectomy, however concomitant bladder repair statistically significantly increased the risk (P = 0.001). AKI also increased the need for ICU care (with or without ventilator support, P = 0.001) and the number of recuperation days statistically significantly (P = 0.001). Another study also showed increased need and longer stay in ICU [weighted mean difference, 2.13 days (95% CI: 1.43-2.83 days)] in PRAKI compared with those without AKI.
Besides AKI, bladder involvement increases the morbidity significantly in MAP. After the first case of bladder involvement in MAP, reported in 1969, only 27 cases were reported till 2000, but we encountered 22 such cases in our study of 64 patients. In cases reported from developing countries, bladder involvement was recognized only at the time of delivery. Ideally, MAP and the accompanying bladder involvement can be diagnosed on antenatal ultrasound and confirmed by MRI in doubtful cases. Sometimes, gross hematuria also leads to antenatal diagnosis. Most of the cases in the present study were antenatally undiagnosed (62.5%), who presented to us for the first time in the peri-partum period“with impending or established complications of adherent placenta,” and some of them were diagnosed intra-operatively during an attempt at removal of placenta, a scenario seconded by other studies from developing countries., In such cases, urologists are usually consulted after a life-threatening emergency situation has already arisen. At our center, urologists were always kept in loop in patients with antenatally diagnosed MAP (24/64); however, in unsuspected emergency cases, the urology team was called in after the intra-operative diagnosis. This is in sharp contrast to that of developed nations, like in a 12-year retrospective series from Utah, the USA, in which all women had at least one antenatal ultrasound and almost half of those with an antenatal suspicion of MAP underwent pelvic MRI. Antenatal diagnosis allowed for pre-operative ureteric stenting and scheduled cesarean hysterectomy, without attempts at placental removal, in the Utah study, both of which appeared to reduce maternal morbidity and significantly lower mean blood loss compared with women undergoing emergency delivery. However, cystotomy was still required in 29% of their patients. A Turkish study too had ultrasound mapping of the placental area for all the patients before surgery, with emergency cesarean hysterectomy in 15.6% and the remaining underwent planned cesarean hysterectomy, and only 8.6% had urological injury. Royal Women’s Hospital, UK, have had a different experience, where as many as 73.5% underwent urological interventions. In the presence of bladder wall invasion and uncontrolled uterine bleeding following delivery, every attempt should be made to maintain hemodynamic stability and preserve the bladder and ureters. Reconstructive surgery, if necessary, may be postponed until after the patient is hemodynamically stabilized. Although resection of the bladder base with the distal ureters has been advocated if invasion is found at the time of delivery, it causes heavy bleeding and resultant AKI, and also an increased risk of coagulopathy, transfusion reaction, sepsis, adult respiratory distress syndrome, multi-organ failure due to aggressive blood transfusion, and vesicovaginal fistulas due to extensive surgery.
This is the first attempt from a developing country to prospectively study the incidence of AKI and urological complications in the rare maternal condition of MAP. The study has its own limitations. Although the study cohort was the largest among the other MAP studies from the region, the number may be insufficient to identify differences in renal and other complications with different management strategies. Each patient with AKI had multiple implicating factors which could not be studied individually. The incidence of hypotension at different time of hospital stay could not be correlated to AKI. Ours being a tertiary care hospital with multispecialty back-up, the data may underestimate the challenges faced at the primary care facilities in the management of such patients in developing countries. Multi- centric studies from developing and developed world can make us wiser in this regard.
| Conclusion|| |
The study emphasizes the need for the renal fraternity to identify morbidly adherent placenta as a potential challenge to the improving statistics of PRAKI worldwide. There is a need to check the rising trend of cesarean deliveries, which is resulting in a higher incidence of MAP. The need for a good antenatal program in developing countries to diagnose such conditions pre-emptively is also emphasized. The condition when faced needs a multidisciplinary team approach, and the associated renal complications, morbidity, and mortality can be reduced when managed well. It is strongly advocated to manage MAP deliveries in tertiary care facilities, well equipped to handle unforeseen maternal, nephro-urological, and other complications.
Conflict of interest: None declared.
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Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab
[Table 1], [Table 2], [Table 3], [Table 4]