Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Reverse Epidemiology for Lipid Disorders in Hemodialysis-Dependent Patients: Role of Dilutional Hypolipidemia.

Introduction: Atherosclerotic cardiovascular disease is a major cause of mortality and morbidity in dialysis patients. Compared to general population, dialysis patients have lower lipid levels and higher vascular events. This paradox is popularly known as reverse epidemiology. Present study is an attempt to understand reasons for low lipids in dialysis patients. Subjects and Methods: This was a prospective observational multicentric study involving three stages across six dialysis units with Care Hospitals, Hyderabad. Maintenance hemodialysis patients were studied with fasting lipid profiles [TC, LDL-c, HDL-c, and TG], pre- and post-dialysis blood lipids and effluent water lipid profiles. Other parameters studied were use of statins, interdialytic weight gain, and ultrafiltration. All patients had uniform dialysis protocols regarding filter used and dialysis duration. Results: Of the 91 patients studied, we observed significant rise in post-dialysis TC, LDL, and HDL [P < 0.01] and lower lipids [P < 0.01] just before the next dialysis. Lipids were least filtered across the membrane except HDL, which was found in effluent water for more than 60% of patients. Single use of dialyser was associated with higher rise in post dialysis lipids as well as HDL getting filtered in effluent [P = 0.24]. Rosuvastatin was associated with lower lipid values [P = 0.08] and BMI [P = 0.19]. Conclusions: Low lipid levels in dialysis patients are due to dilutional hypolipidemia and needs correction with an equation proposed in present study. Corrected lipids should be used for risk stratification and deploying treatment.

ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy.

Acute kidney injury (AKI) is a complex syndrome with a high incidence and considerable morbidity in critically ill patients. Renal replacement therapy (RRT) remains the mainstay of treatment for AKI. There are at present multiple disparities in uniform definition, diagnosis, and prevention of AKI and timing of initiation, mode, optimal dose, and discontinuation of RRT that need to be addressed. The Indian Society of Critical Care Medicine (ISCCM) AKI and RRT guidelines aim to address the clinical issues pertaining to AKI and practices to be followed for RRT, which will aid the clinicians in their day-to-day management of ICU patients with AKI. How to cite this article: Mishra RC, Sodhi K, Prakash KC, Tyagi N, Chanchalani G, Annigeri RA, et al. ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy. Indian J Crit Care Med 2022;26(S2):S13-S42.

CRRT in developing world.

Continuous renal replacement therapy (CRRT) has become a mainstay therapy in the intensive care unit (ICU) and its utilization continues to increase in developed countries. The wide variations of CRRT practice, however, are evident in developing countries while clinicians in these resource-limited countries encounter various barriers such as a limited number of nephrologists and trained staff, a gap of knowledge, machine unavailability, cultural and socioeconomic aspects, high-cost therapy without reimbursement, and administrative as well as governmental barriers. In this article, we demonstrate the situation of CRRT and discuss the barriers of CRRT in a resource-limited setting. We also discuss the strategies to improve CRRT practice. These recommendations can serve as a fundamental guideline for clinicians to implement CRRT in low-resource settings.

Acute Kidney Injury Recognition in Low- and Middle-Income Countries.

Acute kidney injury (AKI) is increasingly common around the world. Because of the low availability of effective therapies and resource limitations, early preventive and therapeutic measures are essential to decrease morbidity, mortality, and cost. Timely recognition and diagnosis of AKI requires a heightened degree of suspicion in the appropriate clinical and environmental context. In low- and middle-income countries (LMICs), early detection is impaired by limited resources and low awareness. In this article, we report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on how to improve recognition of AKI. We expect these recommendations will lead to an earlier and more accurate diagnosis of AKI, and improved research to promote a better understanding of the epidemiology, etiology, and histopathology of AKI in LMICs.

Acute Kidney Injury Risk Assessment: Differences and Similarities Between Resource-Limited and Resource-Rich Countries.

The incidence of acute kidney injury (AKI) among acutely ill patients is reportedly very high and has vexing consequences on patient outcomes and health care systems. The risks and impact of AKI differ between developed and developing countries. Among developing countries, AKI occurs in young individuals with no or limited comorbidities, and is usually due to environmental causes, including infectious diseases. Although several risk factors have been identified for AKI in different settings, there is limited information on how risk assessment can be used at population and patient levels to improve care in patients with AKI, particularly in developing countries where significant health disparities may exist. The Acute Disease Quality Initiative consensus conference work group addressed the issue of identifying risk factors for AKI and provided recommendations for developing individualized risk stratification strategies to improve care. We proposed a 5-dimension, evidence-based categorization of AKI risk that allows clinicians and investigators to study, define, and implement individualized risk assessment tools for the region or country where they practice. These dimensions include environmental, socioeconomic and cultural factors, processes of care, exposures, and the inherent risks of AKI. We provide examples of these risks and describe approaches for risk assessments in the developing world. We anticipate that these recommendations will be useful for health care providers to plan and execute interventions to limit the impact of AKI on society and each individual patient. Using a modified Delphi process, this group reached consensus regarding several aspects of AKI risk stratification.

Use of biomarkers to assess prognosis and guide management of patients with acute kidney injury.

Several new biomarkers of kidney damage have been characterized and are being validated in clinical studies. These damage biomarkers complement existing conventional biomarkers of kidney function (e.g. serum creatinine, serum urea, and urine output) that are currently utilized to diagnose and stage acute kidney injury (AKI). Both functional and damage biomarkers provide an opportunity to identify patients with AKI who are at risk for a less favorable prognosis in terms of worsening damage or further declines in kidney function and likelihood of need for renal replacement. We performed a systemic search and review of the available literature pre-conference. Our workgroup presented the findings in multiple rounds to the ADQI conference members and a final summary and review was refined in an iterative approach. The specific clinical situations of renal or liver transplantation, or cirrhosis/hepatorenal syndrome were not included. Overall, multiple AKI biomarkers have been well characterized for utilization for AKI prognosis. These functional and damage markers can be used to assist in decisions related to triage of patients with AKI and identifying patients with who are at risk for progression. Set cut-offs for various biomarkers and their bedside utility are forthcoming and will be in part determined by regulatory intended use guidelines, platform standardization, and inter-laboratory calibration. There remain many unresolved areas of AKI biomarker use in selected syndromes of AKI (e.g. cardiorenal syndrome, hepatorenal syndrome). As clinicians gain experience with AKI biomarkers, clinical care plans that incorporate them into routine care will shortly follow.

Impact of preoperative renal dysfunction on outcomes of off-pump coronary artery bypass grafting.

BACKGROUND: This study assessed whether preoperative renal insufficiency predisposes patients undergoing off-pump coronary artery revascularization to postoperative dialysis. METHODS: From August 2004 through June 2009, 2,275 patients undergoing off-pump coronary artery bypass were categorized into five groups (stages) by glomerular filtration rate (GFR). Of these, 1,855 patients had renal insufficiency: stage 2: 1,406; stage 3: 428; stage 4: 21, and 414 had normal renal function, stage 1. Excluded were 6 patients with end-stage renal disease (stage 5). Preoperative variables and postoperative outcomes were compared among groups. RESULTS: Preoperative patient characteristics were similar; however, patients with normal renal function were younger (p = 0.001). Serum creatinine rose significantly above baseline on the first postoperative day in the renal insufficiency groups (p = 0.001). The GFR groups had similar inotrope use, reexploration rate, duration of postoperative mechanical ventilation, postoperative stroke, wound infection, and mortality rate. Stage 4 patients had a higher incidence of postoperative myocardial infarction (p = 0.002). Stage 3 and 4 patients had an increased need for postoperative dialysis vs stage 1 patients (p = 0.002). CONCLUSIONS: Nonparametric contingency analysis showed patients with low preoperative GFR (stage 3 and 4, p < 0.0001) and a history of smoking (p = 0.04) were at increased risk for postoperative dialysis. Patients who required postoperative inotropic support tended toward requiring postoperative dialysis (p = 0.06). Low preoperative ejection fraction (p = 0.83), class III or IV angina (p = 0.069), and postoperative blood transfusions were not associated with the need for postoperative dialysis in patients undergoing off-pump revascularization.

Peritoneal dialysis in acute kidney injury: lessons learned and applied.

Peritoneal dialysis (PD) is a simple, safe, gentle, and efficient renal replacement therapy (RRT) method. It is able to correct acute kidney injury (AKI)-induced metabolic, electrolytic, and acid-base disorders and volume overload both in and out the intensive care unit setting. Some PD modalities, such as high-volume PD and continuous flow PD, can provide RRT doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for children, patients with refractory heart failure or hemodynamically instable, conditions where systemic anticoagulation should be avoided, patients with difficulty for vascular access and hypo- and hyperthermia conditions. In the following manuscript, PD technical aspects and the possible advantages and limitations of this RRT method will be discussed, and the more recent literature on clinical experience with PD for treatment of AKI will be reviewed.

The contrasting characteristics of acute kidney injury in developed and developing countries.

Acute kidney injury (AKI) has become increasingly prevalent in both developed and developing countries, and is associated with severe morbidity and mortality, especially in children. Uncertainty regarding the true incidence of AKI limits awareness of the problem, thereby reducing political visibility of the disorder and hampering efforts to prevent its occurrence. In developed countries, AKI occurs predominantly in urban intensive care units and is associated with multiorgan failure and sepsis, high mortality, and occurrence in older populations. While cases of AKI in urban areas of the developing world have similar characteristics to those in the developed world, AKI in rural regions commonly develops in response to a single disease and specific conditions (e.g. gastroenteritis) or infections (e.g. severe malaria, leptospirosis, or hemolytic-uremic syndrome) and in younger otherwise healthy individuals. Many causes of AKI in rural settings, such as diarrhea, poisoning, malaria, or septic abortion, can be prevented by interventions at the individual, community, and regional levels. Treatment with dialysis is often unavailable or too costly in developing regions, so there must be community-wide efforts to eradicate causes of AKI, expedite diagnosis, and aggressively manage prerenal conditions and specific infections. We have reviewed recent literature on AKI, identified differences and similarities in the condition between developed and developing areas, analyzed the practical implications of the identified differences, and made evidence-based recommendations for study and management.

Coronary artery bypass grafting with or without cardiopulmonary bypass in patients with preoperative non-dialysis dependent renal insufficiency: a randomized study.

OBJECTIVE: Preoperative renal insufficiency is a predictor of acute renal failure in patients undergoing coronary artery revascularization with cardiopulmonary bypass. Off-pump coronary artery bypass grafting has been shown to be less deleterious than on-pump bypass in patients with normal renal function, but the effect of this technique in patients with non-dialysis dependent renal insufficiency in a randomized study is unknown. METHODS: From August 2004 through October 2005, 116 consecutive patients with preoperative non-dialysis-dependent renal insufficiency (glomerular filtration rate measured using the Modification of Diet in Renal Disease equation [MDRD GFR] < or = 60 mL x min(-1) x 1.73 m(-2)) undergoing primary coronary artery bypass grafting were randomized to on-pump (n = 60) and off-pump (n = 56) groups. MDRD GFR and serum creatinine levels were measured preoperatively and postoperatively at days 1 and 5. The changes in renal function and clinical outcomes were compared between the two groups. RESULTS: Preoperative characteristics were comparable between the two groups. The repeated-measures analysis of variance was performed on the data that showed worsening of renal function in the on-pump group compared with the off-pump group (serum creatinine, P < .000; glomerular filtration rate, P < .000). Further analysis of subgroups of patients with diabetes alone, hypertension alone, and combined hypertension and diabetes also showed significant deterioration renal function in the on-pump group compared with the off-pump group. In covariate analysis, diabetes has emerged as a significant covariate by serum creatinine criteria while compromised left ventricular function has emerged as a significant covariate by glomerular filtration rate criteria. These analyses showed that the use of cardiopulmonary bypass is significantly associated with adverse renal outcome (P < .000). Three patents required hemodialysis in the on-pump group and none in the off-pump group. The mean number of grafts per patient was 3.85 +/- 0.86 and 3.11 +/- 0.89 in the on-pump and off-pump groups, respectively (P < .001), but the indices of completeness of revascularization, 1.00 +/- 0.08 for off-pump coronary bypass and 1.01 +/- 0.08 for on-pump coronary bypass, were similar (P = .60). CONCLUSIONS: This study suggests that on-pump as compared with off-pump coronary artery bypass grafting is more deleterious to renal function in diabetic patients with non-dialysis dependent renal insufficiency. MDRD GFR is a more sensitive investigation than serum creatinine levels to assess renal insufficiency in patients undergoing coronary bypass.