|Year : 2020 | Volume
| Issue : 2 | Page : 99-103
Spectrum and short-term outcome of acute kidney injury in renal allograft recipients: A single-center experience of Northwest India
Shyam Sundar Nowal, Gaurav Shekhar Sharma, Manish Sharma, Dhananjai Agarwal, Rajesh Jhorawat, Rakesh Kumar Gupta, Sanjeev Kumar Sharma, Pankaj Beniwal, Vinay Malhotra
Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
|Date of Submission||23-Sep-2019|
|Date of Acceptance||15-Mar-2020|
|Date of Web Publication||06-Jul-2020|
Dr. Rajesh Jhorawat
Department of Nephrology, Sawai Man Singh Medical College and Hospital, Jaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
Introduction: Acute kidney injury (AKI) episodes in postrenal transplant are important determinants of short- and long-term graft survival. Renal allograft recipients (RARs) are more vulnerable for AKI and differ in risk factor, etiology, and outcome compared to community-setting AKI. The aim of this study was to evaluate the spectrum and the impact of AKI episode on RARs. Materials and Methods: This was a single-center, prospective observational study on 72 RARs (live and cadaveric) with a total of 93 AKI episodes, who were admitted with AKI (as defined by Kidney Disease Improving Global Outcome [KDIGO] criteria) between October 2016 and September 2018 and were followed for 3 months after AKI episodes. Results: A total of 93 AKI episodes occurred in 72 RARs during the study period. The mean age was 36.32 ± 12.03 years and mean serum creatinine at AKI episode was 2.59 ± 0.85 mg/dl. The etiologies of AKI were infections (n = 67, 72.04%), biopsy-proven rejection (n = 10, 10.75%), calcineurin inhibitor toxicity (n = 9, 9.67%), biopsy-proven acute tubular necrosis (n = 3, 3.22%), recurrence of native kidney disease (n = 2, 2.15%), and miscellaneous causes (n = 2, 2.15%). The majority (n = 53, 57.98%) of AKI episodes developed in the 1st year of transplant, 14 (15.05%) between 1st and 2nd year posttransplant, while the rest 26 (27.95%) beyond 2 years. Sixty-nine (74.2%) AKI episodes were in the KDIGO Stage 1, 18 (19.4%) were in Stage 2, and 6 (6.5%) episodes were in Stage 3. At 3 months of follow-up, various factors associated with nonrecovery of renal functions, including multiple AKI episode (P = 0.006), AKI requiring dialysis (P = 0.027), AKI Stage II or III (P = 0.003), and noninfectious etiology (P = 0.027). Overall, AKI had significant impact on renal allograft function at 3 months (P = 0.045). Pulmonary infection (P = 0.016) and need for dialysis (P = 0.001) were associated with increased risk of mortality in RARs after AKI. Conclusion: AKI in RARs had significant impact on renal allograft function and recovery.
Keywords: Acute kidney injury, calcineurin inhibitor toxicity, infection, rejection, renal allograft recipients
|How to cite this article:|
Nowal SS, Sharma GS, Sharma M, Agarwal D, Jhorawat R, Gupta RK, Sharma SK, Beniwal P, Malhotra V. Spectrum and short-term outcome of acute kidney injury in renal allograft recipients: A single-center experience of Northwest India. Indian J Transplant 2020;14:99-103
|How to cite this URL:|
Nowal SS, Sharma GS, Sharma M, Agarwal D, Jhorawat R, Gupta RK, Sharma SK, Beniwal P, Malhotra V. Spectrum and short-term outcome of acute kidney injury in renal allograft recipients: A single-center experience of Northwest India. Indian J Transplant [serial online] 2020 [cited 2020 Aug 9];14:99-103. Available from: http://www.ijtonline.in/text.asp?2020/14/2/99/289043
| Introduction|| |
Acute kidney injury (AKI) is estimated to occur in about 20–200 per million population in the community, 7%–18% of patients in the hospital, and approximately 50% of patients admitted to the intensive care unit.,, AKI in renal allograft recipients (RARs) is different from that seen in the general population as the denervated allograft is susceptible for hemodynamic instability, use of nephrotoxic drugs, especially calcineurin inhibitors (CNIs), immune-mediated injury, and predisposition to opportunistic infections. The incidence of AKI in RARs has been found to be highly variable in the available studies, ranging from 11% to 80%.,,,,
Etiology of AKI in renal-transplant setting can be divided into prerenal, renal, and postrenal causes. Transplant-specific causes of prerenal AKI are volume depletion, hypotension, and CNI effects. Specific renal causes include acute tubular necrosis (ATN), acute rejection either cellular- or antibody-mediated injury, recurrence of primary kidney disease, and infections such as urinary tract infection (UTI) and polyomavirus (BK). The common postrenal causes after transplant are obstruction due to lymphocele, ureteral stricture, urine leak, hematoma, and abscess.,, However, literature is limited especially from developing world regarding occurrence, etiology, and outcome of AKI in RARs; hence, we design this study.
| Materials and Methods|| |
This is a prospective observational study, conducted in the Department of Nephrology, Sawai Man Singh (SMS) Medical College and Hospital, Jaipur, Rajasthan, India, between October 2016 and September 2018. All the RARs who were at least 1 month postrenal transplantation and were admitted in the Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, with AKI during the above-mentioned study period were included in our study. Those patients who do not met the above inclusion criteria and those who were lost to follow-up were excluded from the study.
The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. The study has been approved by Institutional ethics committee of Sms Medical College and Attached Hospital (3009/MC/EC/2017).
All patients received triple-immunosuppressant, i.e., corticosteroids, tacrolimus, and mycophenolate sodium, in standard doses. Induction therapy was given in high-risk cases (RARs with cadaveric- and live-unrelated donors) with basiliximab (20 mg intravenous infusion 4 h before the transplant surgery and on the 4th day posttransplant) or Antithymoglobin (ATG) 4.5 mg/kg or 1.5 mg/kg/day for 3 days.
AKI was defined, based on the Kidney Disease Improving Global Outcome [KDIGO] 2012 guidelines, as increase in serum creatinine by 0.3 mg/dl within 48 h or increase in serum creatinine to 1.5 times from baseline which is known or presumed to have occurred within the prior 7 days or urine volume <0.5 ml/kg/h for 6 h., The graft function was assessed by eGFR calculation using creatinine-based CKD Epidemiology Collaboration equation using stable baseline serum creatinine and stable creatinine after 3 months of AKI episode.
The severity of AKI was categorized by the KDIGO 2012 guidelines. Acute rejection, recurrence of native kidney disease, and de novo glomerulonephritis were diagnosed by graft biopsy. Acute CNI toxicity was considered if elevated trough level with graft dysfunction and/or graft biopsy. After AKI, complete recovery was defined when baseline eGFR achieved at 3 months or difference is <5 ml/min/1.73 m2. Incomplete recovery was defined when eGFR at 3 months is <60 ml/min/1.73 m2 or difference was or ≥5 ml/min/1.73 m2. CKD is defined as when eGFR <60 ml/min/1.73 m2 at 3 months or more.
The statistical analysis was performed using the SPSS 20 software (IBM SPSS 20 software, Chicago, IL, USA). Results were expressed as mean and standard deviation for continuous variables and values and percentage for categorical variables. Student's t-test was used to assess the differences between two groups. Chi-square test was used for comparison of categorical data. P < 0.05 was considered statistically significant.
| Results|| |
A total of 93 AKI episodes occurred in 72 RARs enrolled, among which 54 (58.06%) patients had single episode of AKI, 15 (16.13%) patients each had two episodes, and 3 (3.22%) patients each had three episodes of AKI. The mean age was 36.32 ± 12.03 years. Male: female ratio was 3.2:1. Mean serum creatinine at the time of discharge after renal transplant was 1.33 ± 0.40 mg/dl. Some form of induction therapy was received by 32 (34.4%) patients, while no induction was given to 61 (65.6%) patients. Baseline characteristics and donor profile are shown in [Table 1].
Spectrum, pattern, and etiology of acute kidney injury
The median period from the date of transplant to AKI episode (vintage period) was 11 ± 51.34 months. The mean serum creatinine at presentation of AKI episode was 2.59 ± 0.85 mg/dl. The majority (n = 53, 57.98%) of AKI episodes occurred within the 1st year of transplant, of which 19 (20.43%) episodes occurred within first 3 months, 18 (19.35%) episodes in the period between 3 and 6 months, 16 (17.20%) in the period beyond 6 months up to 1 year, while the remaining episodes 14 (15.05%) occurred in the period beyond 1st year up to 2 years posttransplant and the rest 26 (27.95%) beyond 2 years [Table 2]. Most of the AKI episodes (n = 69, 74.2%) were in KDIGO Stage 1 at the time of admission, while the remaining 18 (19.4%) and 6 (6.5%) episodes were in Stage 2 and Stage 3, respectively.
Infections were the most common etiology (n = 67, 72.04%), followed by biopsy-proven rejection (n = 10, 10.75%) and CNI toxicity (n = 9, 9.67%) as detailed in [Table 2]. Among infectious, pneumonia was found in 21.5% (n = 20), UTI in 20.43% (n = 19), and acute gastroenteritis in 19.35% (n = 18) of patients. Nine (9.67%) cases were due to other infectious of which four patients were found to have tubercular etiology, three had Cytomegalovirus infection, and two had varicella-zoster virus infection.
The second most common cause was biopsy-proven rejection (n = 10, 10.75%), followed by acute CNI toxicity occurred in n = 9, 9.67% cases, ATN (n = 3,3.22%) and recurrence of native kidney disease (n=2,2.15% i.e in one FSGS and another C3 GN). The miscellaneous causes (n = 2, 2.15%) included transplant renal artery thrombosis in one and unexplained thrombotic microangiopathy (TMA) in one patient. One patient had graft loss due to transplant renal artery thrombosis.
Eight patients require dialysis support during the illness. AKI in four patient who required dialysis had infection (three had pneumonitis and one had acute gastroenteritis) and rest four patients had AKI due to non-infection etiology i.e antibody mediated rejection (AMR, 1 patient), recurrence of basic disease (C3GN, 1 patient), TMA (1 patient), and iatrogenic postprocedure perirenal hematoma (1 patient). Total mortality in our study was 5 (5.37%); four patients had bilateral pneumonitis and one had buccal cavity squamous cell carcinoma with secondary bacterial pneumonitis. Moreover, of those who required dialysis, three patients had died.
Etiology of acute kidney injury with duration of renal transplant
The most common etiology of AKI in the 1st year of transplant was infection (n = 34, 64.15%) followed by rejection (n = 8, 15.09%) and CNI toxicity (n = 8, 15.09%) [Figure 1]. During the 1st year posttransplant, both rejection and CNI toxicity are in equal proportion. In between 1 and 2 years and more than 2 years, infections still dominate; however, the proportion of rejection and CNI toxicity gradually decrease after 1 year postrenal transplant in our study, as shown in [Figure 1].
Risk factor and acute kidney injury outcome at 3 months
At 3 months of follow-up, we found that the patients who have multiple episode of AKI are likely to have low GFR at 3 months. Other factors were found to be associated with nonrecovery or incomplete recovery was those who require dialysis during the illness, higher AKI stage, i.e., II or III. The patients who had noninfectious etiology were likely to have incomplete recovery in renal function, and even among noninfectious acute CNI toxicities have better renal recovery compared to rejection. When we compare the renal function with duration of AKI, both AKI <1 year and AKI > 1 year have equal impact at 3 months (P = 0.59). However, the distribution of etiology of AKI, especially noninfection, was more before 1 year posttransplantation [Figure 1]. However, in subcategorization, noninfection is likely to contribute incomplete recovery at 3 months during the 1 year period. However, after 1 year, infection and noninfection etiology equally contribute to nonrecovery or incomplete recovery at 3 months [Table 3]. The mean baseline serum creatinine and eGFR were 1.45 ± 0.34 mg/dl and 61.11 ± 14.78 ml/min, respectively, and at 3 months after AKI episode, the mean serum creatinine was 1.61 ± 0.79 mg/dl and mean eGFR was 55.57 ± 16.61 ml/min (P = 0.045) [Figure 2].
|Table 3: Risk factor for progression or non-recovery and mortality post-AKI|
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|Figure 2: (a) Change is serum creatinine at 3 months postacute kidney injury episode. (b) Change in estimated glomerular filtration rate at 3 months postacute kidney injury. Different time interval represented with different color line (P = 0.045)|
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| Discussion|| |
The higher incidence of AKI in the transplant setting can be explained by several factors. These include ischemia–reperfusion injury that occurred during the kidney-transplant surgery, presence of single functioning kidney, risk of developing opportunistic infections due to immunosuppressed state, nephrotoxicity produced by immunosuppressive medications, slow or delayed graft function, rejection episodes, graft vessel thrombosis, surgical complications, etc., In our study, we analyzed various factors contributing to AKI in postrenal transplantation. We found various risk factors contributing to nonrecovery of renal parameters including the risk of mortality in such subgroup of patients.
The etiology of AKI in RARs is different from that seen in the community. The most common cause of AKI in the general as well as in the critically ill population has been found to be ATN (50% of cases in a large prospective multicenter inpatient study)., On the other hand, UTI has been found to be the most common cause of AKI in RARs in previous studies.,, The immunosuppressed state, along with the possibility of urinary reflux from the anastomotic site, may contribute to a higher incidence of UTI in this set of patients. Consistent with these results, even we found infections (n = 66, 70.96%) as the most common cause of AKI; however, pneumonia, UTI, and acute gastroenteritis were found almost in equal proportion (around 20%) followed by rejection (10.75%, n = 10), CNI toxicity (9.67%, n = 9), and recurrence of native kidney disease (3.22%, n = 3) in our study.
Majority of AKI episodes in our study have occurred within the 1st year of transplantation i.e., around 57% of AKI episodes. This is consistent with the previous study by Nagarajan et al. and a large study based on the USRD system conducted by Snyder et al., Majority of AKI episodes in our study (i.e., 74.2%, n = 69) were in Stage 1 at the time of presentation similar to previous studies., Of total, eight patients (8.6%) required dialysis support and mortality rate was 5.37%. Moreover, pneumonitis was the predominant cause. This higher mortality can be explained as our patient had more lung infection compared to other studies where urosepsis dominates.
In our study, many factors were found to be associated with incomplete recovery of renal function at 3 months post-AKI [Table 3]. Factors such as multiple AKI episode, AKI requiring dialysis, KDIGO Stage II or III, and noninfection etiology such as rejection were more likely associated with incomplete recovery of renal function after AKI. Duration of AKI after renal transplant was not associated with renal recovery in our study. However, after 1 year, etiology of AKI skewed toward infection that appears to have impact on renal recovery as shown in [Figure 2].
At follow-up, it was found that progression of renal dysfunction was more in patients having multiple episodes of AKI than those with single episodes, patients those who require dialysis during the course of AKI, and patients who had rejection as etiology of the AKI. These findings were consistent with the studies by Nagarajan et al. and Avgustin et al. In our study, patients with AKI Stage II or III were associated with incomplete recovery. Overall AKI episode in our study affects the renal outcome as shown in [Figure 2]. In infection, pulmonary infections were not associated with incomplete recovery; however, pneumonitis was the most common cause of death in our study. Dialysis during AKI episode and pneumonitis were the risk factors for mortality in our study [Table 3].
Limitation of our study was that it was a single-center study with limited number of recipients. Follow-up period was short to make any definitive relation of AKI episode to long-term patient and allograft survival. Hence, larger and multicenter studies with longer follow-up are required to better correlate patient and allograft outcomes with AKI episodes.
| Conclusion|| |
Most of the episodes of AKI in RARs occurred in the 1st year posttransplant, and majority had Stage 1 at presentation. Infections were the most common causes followed by rejection and CNI toxicity. Many factors such as multiple episodes of AKI, need for dialysis, higher stage of AKI, and noninfectious etiology appear to affect the renal recovery at 3 months post-AKI in RARs. Overall, AKI episode impacts the renal outcome in RARs.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]