Background. Acute kidney injury (AKI) is an underreported but major cause of morbidity and mortality among patients undergoing major surgical interventions in sub-Saharan Africa (SSA). Whereas AKI is often seen following major cardiac surgery in high-income countries, a similar spectrum of surgical diseases and interventions is not seen in developing countries. The impacts on surgical outcomes have also not been well characterized in SSA. This study aimed at identifying risk factors, incidence and determinants and short-term outcomes of AKI among patients undergoing major surgery. Methods. This was a cohort study of adult patients undergoing major surgery at the University College Hospital, Ibadan, Nigeria. Data obtained were sociodemographic details, risk factors for AKI, details of surgery, anaesthesia and intra- operative events and short-term outcomes. Blood samples were obtained for pre-operative (pre-op) full blood count, serum electrolytes, blood urea and creatinine (SCr). Post-operatively (Post-op) SCr was determined at 24 h, Day 7 post-op and weekly until each patient was discharged. Results. A total of 219 subjects who had major surgery (86.3% elective) were enrolled. The median age of the patients was 46 (range 18–73) years and 72.6% were females. The surgeries performed were mostly simple mastectomies (37.4%), exploratory laparotomies (22.8%) and total thyroidectomies (16.4%). The incidences of AKI were 18.7% at 24 h and 17.4% at Day 7 post-op, while cumulative AKI incidence was 22.5% at 1-week post-op. Pre-op elevated SCr [odds ratio (OR) 3.86], sepsis (OR 2.69), anaemia (OR 2.91) and duration of surgery >120 min (OR 1.75) were independently associated with AKI. In- patient mortality was 20.4% in individuals with AKI and 5.3% in those without AKI (P< 0.01). Conclusion. Peri-operative risk factors for AKI are common among patients undergoing major surgery in SSA hospitals. The cumulative incidence of AKI was high and independently associated with pre-op sepsis, anaemia, pre-existing kidney dysfunction and duration of surgery >120 min. Key words: acute kidney injury (AKI), incidence, risk factors, sub-Saharan Africa, surgery Received: June 21, 2017. Editorial decision: November 20, 2017 V C The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/443/4788819 by Ed 'DeepDyve' Gillespie user on 07 August 2018 444 | Y.R. Raji et al. use of multiple antibiotics and analgesics], lifestyle, medical Background histories, clinical diagnosis, types and duration of surgery, epi- Acute kidney injury (AKI) is a major cause of morbidity and sodes of hypotension and details of anaesthesia. Pre-, intra- and mortality among patients undergoing major surgical interven- post-op serum electrolytes, urea and creatinine and full blood tions worldwide and contributes to prolonged hospital stays count were carried out while noting the vital signs, intra-op and increased cost of treatments [1, 2]. The epidemiology of AKI blood loss, fluid input and output, use of inotropic agents and appears different between high-income countries (HICs) and the need for blood transfusion. Post-op blood samples were also low- and middle-income countries (LMICs) [3, 4]. Whereas it is collected for serum creatinine (SCr) within 24 h of surgery, Day 7 often seen following major cardiac surgery in the former, this is post-op and weekly until participants were discharged home. not the case in LMICs [4–6]. AKI was defined and graded in accordance with the Kidney A review by Adu et al.  estimated the incidence of AKI Disease: Improving Global Outcomes (KDIGO) 2012 criteria among hospitalized patients in the sub-Saharan Africa (SSA) (Table 1), while pre-existing kidney dysfunction, anaemia, sepsis, region to be 1.9%. In contrast, a recent study by Evans et al.  hypertension, intra-op hypertension and hypotension, diabetes reported the incidence of AKI among 892 cases of medical mellitus, prolonged and major surgery and recovery of kidney admissions in a Malawian hospital to be 17.2%, with an in- function are defined as shown in Table 1. hospital mortality rate of 44.4%. The outcome of AKI in the SSA region is poor compared with HICs. Olowu et al.  reported that Statistical analysis only 64% of 1042 children and 33% of 178 adults with AKI across Statistical analyses were done using the Statistical Package for many studies received dialysis when needed. While the overall Social Sciences (SPSS) version 20 (IBM, Armonk, NY, USA). mortality was 34% in children and 32% in adults, the mortality Continuous variables are expressed as means or medians and rose to 73% in children and 86% in adults when dialysis was categorical variables are expressed as proportions. Paired t-test needed but not received . Most of the reports from the SSA was used to test for association between continuous variables region are on community-acquired AKI, while reports on the that were normally distributed and continuous variables that epidemiology of AKI among individuals undergoing surgery are were not normally distributed were compared using the Mann– sparse. With the increase in volume of surgical procedures per- Whitney U-test. Associations between categorical variables formed in SSA , it has been hypothesized that most cases of were compared using the chi-square test or Fisher’s exact test surgery-related [peri-operative (peri-op)] AKI are underdetected. as appropriate. Linear and multiple logistic regression analyses The impact of delayed or undetected AKI is enormous in were conducted to identify factors that were independently patients undergoing surgical interventions and it is associated associated with the development of AKI. Associations between with increased morbidity and mortality, prolonged hospital stay variables were considered to be significant for P-values <0.05. and higher cost of treatment [11, 12]. Despite peri-op AKI being a preventable disease with enor- Ethical approval mous benefits of early detection and intervention, which is fea- sible through identification of risk factors and prompt This study adhered to the Declaration of Helsinki and ethical institution of appropriate treatment during the peri-op period, approval was obtained from the Joint University of Ibadan and very limited data are available on the incidence of AKI and its University College Hospital, Ibadan Institutional Review Board. risk factors among patients undergoing surgery in the SSA All participants gave written informed consent. region. The primary objective of this study was to identify peri- op risk factors and determine the pattern of AKI among patients Results undergoing major surgery in a leading tertiary hospital in Nigeria and the secondary objective was to determine the short- Clinical characteristics of the participants term outcomes of AKI among the participants. A total of 219 participants who had major surgery were recruited into the study; the median age of the patients was 46 Materials and methods (range 18–73) years and 159 (72.6%) were females. The median duration of surgery was 100 (range 30–433) min and the median Study design and participants pre-op systolic blood pressure (SBP) and diastolic blood pressure This was a short-term follow-up study of 219 adult patients (DBP) was 120 (range 70–190) mmHg and 80 (range 50– undergoing major surgical interventions at the University 150) mmHg, respectively. A total of 189 (86.3%) participants College Hospital, Ibadan, Nigeria. Consecutively presenting underwent elective surgery while 30 (13.7%) had emergency sur- patients requiring elective or emergency surgery were enrolled gical interventions. The medians were significantly higher in the study between 1 October 2015 and 31 January 2016. among the participants with AKI compared with those without Inclusion criteria were individuals 18–74 years of age while AKI for the duration of surgery and pre-op, 24-h and 1-week exclusion criteria were individuals with <18 or >74 years of age, post-op SCr, while the median estimated glomerular filtration primarily obstructive urological disease, end-stage renal disease rate (eGFR) was significantly lower in the participants with AKI (ESRD) or on renal replacement therapy (RRT). Standard case compared with those without AKI (Table 2). In addition, AKI at report forms were used to collect data from the participants. the end of 1 week was significantly associated with gender. The Data obtained included sociodemographic details, risk factors spectrums of surgical diseases among the participants were for AKI [pre-operative (pre-op) sepsis, diabetes mellitus, pre- predominantly breast carcinoma, simple multinodular goitre, existing kidney disease, presence of comorbidity, anaemia, abdominal ventral hernia and acute appendicitis (Table 2). The emergency surgery, prolonged duration of anaesthesia, pro- surgical interventions carried out were mainly simple mastecto- longed duration of surgery, intra-op blood loss, intra-operative mies, exploratory laparotomies, total thyroidectomies, appen- (intra-op) hypotension, intra-op hypertension, post-operative dectomies and wide excision of soft tissue sarcomas and the (post-op) sepsis, post-op fluid loss through the surgical drain, proportions were similar in participants with and without AKI Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/443/4788819 by Ed 'DeepDyve' Gillespie user on 07 August 2018 AKI among adult patients in Nigeria | 445 Table 1. Deﬁnitions of diagnostic criteria Variable Definition AKI Increase in serum creatinine by 0.3 mg/dL (26.5 mmol/L) within 48 h OR increase in SCr to >1.5 times baseline that is known or presumed to have occurred within the prior 7 days OR urine volume <0.5 mL/ kg/h for 6 h  Pre-existing kidney dysfunction eGFR <60 mL/min/1.73 m  Anaemia Haemoglobin <11 g/dL  Sepsis The presence of conﬁrmed (culture) or presumed identiﬁable microbes with two or more features of SIRS. Features of SIRS include fever (temperature >38 C) or hypothermia (temperature <36 C), tachycardia (pulse rate >90/min), tachypnoea (respiratory rate 6 3 6 3 >20/min) and leucocytosis (WBC >11 10 /mm ) or leucopenia (WBC <4 10 /mm )[16, 17] Hypertension SBP 140 mmHg or diastolic DBP 90 mmHg, presence of hypertension previously diagnosed by a physi- cian or use of antihypertensive medications to control BP  Diabetes mellitus Fasting plasma glucose >7 mmol/L, diabetes mellitus diagnosed previously by a physician or use of anti- diabetic medications to control blood sugar  Intra-operative hypotension Increase in mean arterial BP > 20% from the baseline, lasting 5–10 min. Intra-op hypotension was deﬁned as absolute SBP <80 mmHg or a drop in the baseline SBP of >20% lasting at least 5–10 min [20, 21] Major surgery Any surgical procedure that required at least a regional or general anaesthesia, surgery that lasts >120 min in duration or surgery requiring in-hospital care Full recovery of kidney function SCr return to baseline value or below  Partial recovery of kidney function Change from higher AKI severity stage to a lower one but not below Stage I or a reduction in SCr of> 25% from the highest value attained  Prolonged surgery Surgical interventions lasting >120 min  KDIGO staging of AKI Stage I Increased SCr 1.5–1.9 times from the baseline OR urine output <0.5 mL/kg/h for 6–12 h Stage II Increased SCr 2.0–2.9 times from baseline OR urine output <0.5 mL/kg/h for 12 h Stage III Increased absolute SCr to> 4.0 mg/dL (>353.6 mmol/L) OR initiation of RRT OR increased SCr 3.0 times from baseline OR 0.3 mL/kg/h for 24 h OR anuria for 12 h  SIRS, systemic inﬂammatory response syndrome; WBC, white blood cell count. (Table 2). General anaesthesia was administered to 198 (90.4%) Factors associated with AKI patients while spinal anaesthesia was the choice in the remain- On multivariate analysis, only pre-existing kidney dysfunction, ing [21 (9.6%)] participants (Table 2). pre-op sepsis, anaemia and duration of surgery >120 min inde- pendently predicted AKI at the end of the 1-week post-op period (Table 5). Peri-op risk factors Outcome data Pre-op sepsis, pre-op anaemia, pre-existing kidney dysfunction and emergency cases were observed to be significantly higher Of the 219 participants enrolled, 49 (22.5%) had AKI; at the end among participants with AKI on bivariate analysis, while diabe- of 30 day, 33 (67.3%) and 16 (32.7%) of those with AKI had full tes mellitus and hypertension were not associated with AKI and partial recovery of their kidney function, respectively. Six (Table 3). Pre-op sepsis was significantly higher among partici- participants (12.2%) among those with AKI required and had pants who had emergency surgery [8 (26.7%)] compared with haemodialysis. The crude mortality rates (30 days post-op) elective cases [17 (8.9%); P< 0.01]. A duration of surgery among those with AKI and those without AKI were 10 (20.4%) >120 min, a duration of anaesthesia >120 min and the need for and 9 (5.3%), respectively (P< 0.01). intra-op blood transfusion were the identified intra-op AKI risk factors that were significantly higher among the individuals Discussion with AKI (Table 3), while the post-op risk factors for AKI were The incidence of AKI (22.5%) in our study was higher than the similar in individuals with AKI and those without AKI (Table 3). 1.9% reported among hospitalized adult patients by Adu et al. . Our finding was similar to the 17.2% reported by Evans et al. and 16.7% by Bagasha et al.  among adult hospitalized patients Incidence of AKI in a Ugandan and a Malawian hospital, respectively. Also, the AKI The incidences of AKI were 18.7% (n¼ 41) and 17.4% (n¼ 38) within incidence in our study agreed with the 16.3% reported by Skinner 24 h and Day 7 post-op, respectively, while the cumulative AKI et al.  among South African patients admitted with trauma. Of incidence at 1-week post-op was 22.5% (n¼ 49). The proportion of note is that the case mix of sepsis and trauma differs from ours diagnosed AKI varied with the diagnostic criteria employed; the because of specialty bias. The low incidence of AKI reported by highest incidence (22.5%) was observed when either SCr or urine Adu et al.  in their review is probably due to underestimation of output–based criteria was used (Table 4). The severity of AKI using the true incidence of AKI in SSA, as the low incidence might have KDIGO grading among participants with AKI showed 32 (65.3%) in resulted from the non-uniformity of definition of AKI across the Stage I, 11 (22.4%) in Stage II and 8 (16.2%) in Stage III. studies included in their review. Supporting this explanation Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/443/4788819 by Ed 'DeepDyve' Gillespie user on 07 August 2018 446 | Y.R. Raji et al. Table 2. Baseline characteristics of patients who underwent major surgical interventions Peri-op AKI No peri-op AKI Variables (n¼ 49) (n¼ 170) P-value Gender, n (%) Female 29 (59.2) 129 (76.3) 0.02* Male 20 (40.8) 41 (23.7) Age (years), median (range) 49 (19–73) 46 (18–74) 0.23 SBP (mmHg), median (range) 120 (70–180) 120 (80–190) 0.96 DBP (mmHg), median (range) 80 (52–150) 80 (50–115) 0.75 Duration of primary surgical illness (months), median (range) 6 (1–96) 10.5 (1–205) 0.12 Duration of surgery (min), median (range) 105 (45–433) 96 (30–350) 0.03* Pre-op SCr (mmol/L), median (range) 106 (44.5–371.3) 79.6 (61.7–97.2) 0.01* 24-h post-op SCr (mmol/L), median (range) 106 (30.4–344.8) 88.4 (23.2–132.5) 0.01* Day 7 post-op SCr (mmol/L), median (range) 105 (32.0–319.5) 92 (34.6–138.3) 0.01* eGFR (mL/min/1.73 m ), median (range) 77 (39.7–160.4) 96 (73.4 6153.0) 0.01* Haemoglobin (g/dL), mean6 SD 7.461.6 7.261.4 0.86 Types of surgery, n (%) Emergency 14 (28.6) 16 (9.4) 0.01* Elective 35 (71.4) 154 (90.6) Presence of at least one comorbidity, n (%) 15 (30.6) 56 (32.9) 0.76 Surgical diagnoses, n (%) Breast carcinoma 17 (34.5) 63 (37.1) 0.86 Thyroid tumour 10 (20.4) 26 (15.2) Abdominal wall hernia 4 (8.9) 10 (5.8) Acute appendicitis 3 (6.1) 11 (64.7) Intestinal obstruction 3 (6.1) 7 (4.1) Pancreatic carcinoma 2 (4.1) 7 (4.1) Soft tissue sarcoma 0 (0) 8 (4.7) Colorectal carcinoma 1 (2.0) 5 (2.9) Enterocutaneous ﬁstula 1 (2.0) 4 (2.4) Others 8 (16.3) 29 (17.1) Surgical interventions, n (%) Mastectomy 21 (42.9) 59 (34.7) 0.38 Exploratory laparotomy 13 (26.5) 40 (23.5) Thyroidectomy 2 (4.1) 34 (20.0) Appendectomy 5 (10.2) 6 (3.5) Wide excision (sarcoma) 1 (2.0) 10 (5.9) Herniorrhaphy 1 (2.0) 9 (5.3) Axillary clearance 2 (4.1) 1 (0.6) Cholecystectomy 1 (2.0) 2 (1.2) Others 3 (6.1) 11 (1.8) Types of anaesthesia used, n (%) GA with isoﬂurane plus propofol 36 (73.4) 134 (78.8) 0.43 GA with halothane 7 (14.3) 20 (11.8) GA with ketamine 1 (2.0) 3 (1.8) Spinal anaesthesia 5 (10.3) 13 (7.6) BP, blood pressure; GA, general anaesthesia; SD, standard deviation. *P-value less than 0.05. Exploratory laparotomy in 30 cases (13.7%) were with additional surgical procedures such as bowel resection, appendectomy, splenectomy or adhesiolysis. further is the similarity of the AKI incidence in our study to those mastectomies with axillary clearance, exploratory laparotomies reported by Evans et al.  and Skinner et al.  among patients and total thyroidectomies were the predominant surgical proce- who were admitted for medical- and trauma-related AKI, respec- dures, unlike in HICs where cardiopulmonary surgery was the tively. The general increase in the volume of surgical procedures leading surgical procedure causing peri-op AKI [29–32]. may have also contributed to the increasing incidence of peri-op Most of the identified AKI risk factors were modifiable and AKI in the SSA region, where mostly medical AKI had been previ- therefore preventive strategies for their early identification and ously reported [7, 9, 26]. prompt treatment should be part of the protocol for managing The incidence of AKI in our study is similar to the pattern patients undergoing major surgical interventions to reduce the observed from the HICs among patients who underwent surgi- burden of AKI in this group of patients. Pre-op anaemia was cal interventions [27–30]. Although the incidence of AKI in our observed to be associated with an increased risk of peri-op AKI study is similar to the reports from HICs, the spectrum of surgi- by 3-fold. This is in agreement with the observations by cal procedures performed was different in our cohort. Simple Karkouti et al.  and De Santo et al., who also reported Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/443/4788819 by Ed 'DeepDyve' Gillespie user on 07 August 2018 AKI among adult patients in Nigeria | 447 Table 3. Peri-op characteristics of participants with AKI and those without AKI Peri-op AKI No peri-op AKI Risk factors (n¼ 49) (n¼ 170) P-value Pre-op risk factors, n (%) Age >60 years 8 (16.3) 20 (11.8) 0.69 Pre-op sepsis 12 (28.6) 12 (7.1) 0.01* Presence of at least one co-morbidity 16 (32.6) 56 (32.9) 0.76 Elevated pre-op BP 16 (32.5) 62 (36.5) 0.60 Hypertension 9 (18.4) 40 (23.5) 0.48 Diabetes mellitus 4 (8.1) 10 (5.9) 0.56 Proteinuria 11 (22.5) 20 (11.8) 0.06 Pre-op anaemia 22 (44.9) 40 (23.5) 0.01* Pre-op leucocytosis 7 (14.2) 12 (7.1) 0.09 Pre-existing kidney dysfunction 13 (26.6) 6 (3.5) 0.02* Intra-op risk factors6 Prolonged duration of surgery >120 min 32 (65.3) 29 (17.1) 0.01* Prolonged duration of anaesthesia >120 min 33 (67.3) 40 (23.5) 0.01* Intra-op hypotension 4 (4.1) 9 (5.3) 0.23 Intra-op hypertension 2 (2.1) 6 (3.5) EBL >500 mL 15 (30.6) 31 (18.2) 0.09 Intra-op blood transfusion 28 (57.1) 34 (20.0) 0.02* Need for >3 L intra-op 12 (24.5) 23 (13.5) 0.07 Need for inotropic support 1 (2.0) 2 (1.2) 0.65 Post-op risk factors6 Drain >500 mL/day 10 (20.4) 28 (16.5) 0.52 Had 2 or more post-op antibiotics 11 (22.5) 46 (27.1) 0.53 Post-op analgesic 47 (95.9) 166 (97.6) 0.67 Post-op sepsis 11 (22.5) 46 (27.1) 0.53 Post-op blood transfusion 47 (95.9) 166 (97.6) 0.67 BP, blood pressure; EBL, estimated blood loss. *P-value less than 0.05. dysfunction and apoptosis [37, 38]. Prompt treatment of severe Table 4. Incidence of AKI based on different KDIGO diagnostic sepsis prior to surgery using the international guideline for criteria management of sepsis (Surviving Sepsis Campaign Guideline) is n (%) recommended . This aggressive treatment of sepsis prior to KDIGO criteria for AKI diagnosis (total; N¼ 219) surgical procedures is a cost-effective way of preventing peri-op AKI and its attendant outcomes, most especially in emergency Increased serum creatinine >26.7 mmol/L 28 (12.7) cases, which are at higher risk of developing sepsis. SCr criteria >1.5-fold from baseline 36 (16.2) For surgery lasting >120 min, adequate fluid balance both Urine output criteria alone: urine volume 11 (5.0) prior to and during surgery must be ensured, in addition to opti- <0.5 mL/kg/h for 6 h Combination of both SCr and urine output– 21 (9.6) mal BP control to prevent episodes of intra-op hypotension and based criteria hypertension. These steps will reduce the risk of AKI in patients Diagnosis based on either SCr or urine out- 49 (22.4) undergoing major surgery. put–based criteria Pre-existing kidney dysfunction was identified as a predictor of AKI among our patients, although we couldn’t establish whether the pre-existing kidney dysfunction was chronic kid- ney disease (CKD) or AKI. This is because most of the partici- anaemia as a predictor of peri-op AKI among patients who had pants had no baseline urinalysis and SCr records that were at cardiac surgery and coronary artery bypass graft, respectively. least 3 months prior to admission for the surgical procedures. Optimizing the haemoglobin concentration prior to and during The existence of pre-existing kidney dysfunction in our study surgery has the potential of reducing the incidence of peri-op increased the risk of developing peri-op AKI by 4-fold. This find- AKI and this can be achieved through pre-op blood transfusion ing is in keeping with previous reports that classified CKD as a in emergency settings or during surgery and using erythropoie- risk factor for AKI . Although CKD may not be reversible, sis stimulating agents in elective cases. Intra-op blood transfu- prompt identification of modifiable peri-op risk factors for AKI sion is a common occurrence in SSA, particularly in emergency and instituting preventive measures may safeguard against surgical procedures [35–36]; not surprisingly, a quarter of our development of AKI, which is a known risk factor for CKD pro- cohort required intra-op blood transfusions while 12.8% gression. Also, early involvement of nephrologists in the opti- required further post-op blood transfusions. mal care of at-risk patients prior to surgery will go a long way in Another factor that was associated with AKI in our study reducing the burden of AKI among individuals undergoing sur- was sepsis. Sepsis causes AKI through multipronged injury gical interventions. pathways that include ischaemia–reperfusion injury, direct This study is not without limitations, and these include inflammatory injury, coagulation and endothelial cell the definition of pre-existing kidney dysfunction as eGFR Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/443/4788819 by Ed 'DeepDyve' Gillespie user on 07 August 2018 448 | Y.R. Raji et al. Table 5. Logistic regression analysis of factors predicting AKI Risk factors Odds ratio 95% CI P-value Female gender 0.83 0.3949–1.0574 0.71 Pre-op sepsis 2.67 1.1198–7.3341 0.03* Pre-existing kidney dysfunction 3.86 1.8075–9.7942 0.01* Pre-op anaemia 2.91 1.0829–5. 2254 0.02* Duration of anaesthesia >120 min 1.03 0.7324–5.9186 0.12 Duration of surgery >120 min 1.75 1.3912–11.4267 0.04* Emergency surgery 1.44 0.5269–3.9106 0.48 Need for blood intra-op blood transfusion 0.93 0.8594–4.1937 0.65 *P-value less than 0.05. <60 mL/min/1.73 m , given that eGFR is not accurate when the 4. Lameire NH, Bagga A, Cruz D et al. Acute kidney injury: an kidney function is near normal. Second, due to limited funds, increasing global concern. Lancet 2013; 382: 170–179 SCr was only measured pre-op, 24 h post-op, 7 days post-op and 5. Cerda ´ J, Lameire N, Eggers P et al. Epidemiology of acute kid- weekly until patients were discharged and thus some cases of ney injury. 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Rocha PN, Rocha AT, Palmer SM et al. Acute renal failure inherent risk factor for acute kidney injury? Clin J Am Soc after lung transplantation: incidence, predictors and impact Nephrol 2010; 5: 1690–1695 Downloaded from https://academic.oup.com/ckj/article-abstract/11/4/443/4788819 by Ed 'DeepDyve' Gillespie user on 07 August 2018
Clinical Kidney Journal – Oxford University Press
Published: Aug 1, 2018
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