Decrease in platelet count in patients with AKI and its association with major adverse kidney events.

INTRODUCTION: A reduction in platelet count in critically ill patients is a marker of severity of the clinical condition. However, whether this association holds true in acute kidney injury (AKI) is unknown. We analyzed the association between platelet reduction in patients with AKI and major adverse kidney events (MAKE). METHODS: In this retrospective cohort, we included AKI patients at the Hospital Civil of Guadalajara, in Jalisco, Mexico. Patients were divided according to whether their platelet count fell >21% during the first 10 days. Our objectives were to analyze the associations between a platelet reduction >21% and MAKE at 10 days (MAKE10) or at 30-90 days (MAKE30-90) and death. RESULTS: From 2017 to 2023, 400 AKI patients were included, 134 of whom had a > 21% reduction in platelet count. The mean age was 54 years, 60% were male, and 44% had sepsis. The mean baseline platelet count was 194 x 103 cells/µL, and 65% of the KDIGO3 patients met these criteria. Those who underwent hemodialysis (HD) had lower platelet counts. After multiple adjustments, a platelet reduction >21% was associated with MAKE10 (OR 4.2, CI 2.1-8.5) but not with MAKE30-90. The mortality risk increased 3-fold (OR 2.9, CI 1.1-7.7, p = 0.02) with a greater decrease in the platelets (<90 x 103 cells/µL). As the platelets decreased, the incidence of MAKE was more likely to increase. These associations lost significance when accounting for starting HD. CONCLUSION: In our retrospective cohort of patients with AKI, a > 21% reduction in platelet count was associated with MAKE. Our results are useful for generating hypotheses and motivating us to continue studying this association with a more robust design.

A reduction in platelet count in critically ill patients has been associated with a worse prognosis, but it is not yet known whether this relationship also exists in patients with acute kidney injury, who are more susceptible to platelet decrease due to the syndrome or due to the onset of hemodialysis. In our study of acute kidney injury patients, we found that those whose platelet count decreased >21% during the first days were more likely to experience a major kidney event. In addition, the greater the decrease in platelet count was, the more likely these events were to occur. The significance of this association was lost in patients who start hemodialysis. Our conclusions could serve to generate hypotheses about this interesting relationship.

Systolic Blood Pressure and the Risk of Kidney Replacement Therapy and Mortality in Patients with Chronic Kidney Disease Stages 4-5.

INTRODUCTION: In patients with chronic kidney disease stages 4 and 5 (CKD stages 4-5) without dialysis and arterial hypertension, it is unknown if the values of systolic blood pressure (SBP) considered in control (<120 mm Hg) are associated with kidney replacement therapy (KRT) and mortality. METHODS: In this retrospective cohort study, hypertensive CKD stages 4-5 patients attending the Renal Health Clinic at the Hospital Civil de Guadalajara were enrolled. We divided them into those that achieved SBP <120 mm Hg (controlled group) and those who did not (>120 mm Hg), the uncontrolled group. Our primary objective was to analyze the association between the controlled group and KRT; the secondary objective was the mortality risk and if there were subgroups of patients that achieved more benefit. Data were analyzed using Stata software, version 15.1. RESULTS: During 2017-2022, a total of 275 hypertensive CKD stages 4-5 patients met the inclusion criteria for the analysis: 62 in the controlled group and 213 in the uncontrolled group; mean age 61 years; 49.82% were male; SBP was significantly lower in the controlled group (111 mm Hg) compared to the uncontrolled group (140 mm Hg); eGFR was similar between groups (20.41 mL/min/1.73 m2). There was a tendency to increase the mortality risk in the uncontrolled group (HR 6.47 [0.78-53.27]; p = 0.082) and an association by the Kaplan-Meir analysis (Log-rank p = 0.043). The subgroup analysis for risk of KRT in the controlled group revealed that patients ≥61 years had a lower risk of KRT (HR 0.87 [95% CI, 0-76-0.99]; p = 0.03, p of interaction = 0.005), but no differences were found in the subgroup analysis for mortality. In a follow-up of 1.34 years, no association was found in the risk of KRT according to the controlled or uncontrolled groups in a multivariate Cox analysis. CONCLUSION: In a retrospective cohort of patients with CKD stages 4-5 and hypertension, SBP >120 mm Hg was not associated with risk of KRT but could be associated with the risk of death. Clinical trials are required in this group of patients to demonstrate the impact of reaching the SBP goals recommended by the KDIGO guidelines.

Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery.

Background: Cardiac surgery is a leading cause of acute kidney injury (AKI). Such AKI patients may develop progressive chronic kidney disease (CKD). Others, who appear to have sustained no permanent loss of function (normal serum creatinine), may still lose renal functional reserve (RFR). Methods: We extended the follow-up in the observational 'Preoperative RFR Predicts Risk of AKI after Cardiac Surgery' study from hospital discharge to 3 months after surgery for 86 (78.2%) patients with normal baseline estimated glomerular filtration rate (eGFR), and re-measured RFR with a high oral protein load. The primary study endpoint was change in RFR. Study registration at clinicaltrials.gov Identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759. Results: At 3 months, three patients developed new CKD. All remaining patients continued to have a normal eGFR (93.3 ± 15.1 mL/min/1.73 m2). However, when stratified by post-operative AKI and cell cycle arrest (CCA) biomarkers, AKI patients displayed a significant decrease in RFR {from 14.4 [interquartile range (IQR) 9.5 - 24.3] to 9.1 (IQR 7.1 - 12.5) mL/min/1.73 m2; P < 0.001} and patients without AKI but with positive post-operative CCA biomarkers also experienced a similar decrease of RFR [from 26.7 (IQR 22.9 - 31.5) to 19.7 (IQR 15.8 - 22.8) mL/min/1.73 m2; P < 0.001]. In contrast, patients with neither clinical AKI nor positive biomarkers had no such decrease of RFR. Finally, of the three patients who developed new CKD, two sustained AKI and one had positive CCA biomarkers but without AKI. Conclusions: Among elective cardiac surgery patients, AKI or elevated post-operative CCA biomarkers were associated with decreased RFR at 3 months despite normalization of serum creatinine. Larger prospective studies to validate the use of RFR to assess renal recovery in combination with biochemical biomarkers are warranted.

Optimizing a kidney stress test to evaluate renal functional reserve.

BACKGROUND: Renal function reserve (RFR) describes the capacity of the kidney to increase glomerular filtration rate (GFR) in response to physiological or pathological stimuli. The scope of our study was to evaluate the optimal level of stimulation using different doses of protein load (PL) for a standard renal stress test (RST). METHODS: 18 young healthy individuals were given sessions of PL with 1 and 2 g/kg body weight. Endogenous creatinine clearance was calculated. Baseline GFR (bGFR) and stress GFR (sGFR) (post-PL) were obtained; RFR is the difference between stress and baseline GFR. A p-value < 0.05 was considered statistically significant. RESULTS: Mean bGFR was 107.97 ± 12.33 mL/min/1.73m2. sGFR with 1 and 2 g PL were significantly higher than bGFR in all subjects. The sGFR after 2 g PL (141.75 ± 19.90 mL/min/1.73m2) was not statistically different from the sGFR after 1 g PL (142.37 ± 22.35 mL/min/1.73m2). sGFR and therefore RFR were independent from the value of bGFR. CONCLUSIONS: We found no difference between 1 and 2 g/kg body weight PL to elicit sGFR. RST may be useful to predict susceptibility and risk of developing acute kidney injury and/or progression to chronic kidney disease. RST uncovers the possible loss of renal functional mass when this condition is not manifested clinically. Further studies are needed to set this hypothesis.

Fabry's disease: an example of cardiorenal syndrome type 5.

Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry's disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors-and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

Initiation of renal replacement therapy in the intensive care unit in Vicenza (IRRIV) score.

INTRODUCTION: One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT. METHODS: A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT. RESULTS: We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT. CONCLUSIONS: We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT.

High cutoff membrane to reduce systemic inflammation due to differentiation syndrome: a case report.

BACKGROUND: Differentiation syndrome is a life-threatening complication of therapy that is carried out with agents used for acute promyelocytic leukemia. Its physiopathology comprehends the production of inflammatory mediators by differentiating granulocytes, endothelial and alveolar cells due to stimulation by all-trans retinoic acid and leading to sustained systemic inflammation. METHODS: Treatment with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD) was performed to reduce the circulating mediators of systemic inflammation. RESULTS: After 52 h of treatment, an important reduction was observed in inflammatory mediators (IL-1ß: from 10 to 2 pg/ml; IL-8: from 57 to 40 pg/ml; TNF-α: from 200 to 105 pg/ml; IL-6: from 263 to 91 pg/ml), as well as in anti-inflammatory mediators (IL-10: from 349 to 216 pg/ml). CONCLUSIONS: HCO-CVVHD should be explored as a part of treatment in systemic inflammation states other than sepsis (e.g., differentiation syndrome). Furthermore, its immunomodulatory effects could be particularly useful in immunocompromised patient treated with corticosteroids.

Cytokine removal with high cut-off membrane: review of literature.

During the last decade, blood purification therapies have been proposed as an effective therapy to control the cytokines dysregulation in systemic inflammatory syndromes. Among them, the treatment with high cut-off membranes is characterized by larger pore size and more effective clearance for middle molecular weight molecules (cytokines). In this paper, we performed a thoughtful review of the literature on HCO being used for blood purification indications in all systemic inflammation syndromes. Clinical and experimental studies show that the use of high effluent flows in a pure diffusive treatment effectively removes serum cytokines with a safe profile in albumin clearance. In clinical studies, the removal of these inflammatory mediators is associated with a significant improvement in hemodynamic condition, oxygenation indices, and organ dysfunction.

SGLT2i treatment during AKI and its association with major adverse kidney events.

Background: The association between the administration of sodium-glucose cotransporter 2 inhibitors (SGLT2is) during acute kidney injury (AKI) and the incidence of major adverse kidney events (MAKEs) is not known. Methods: This retrospective cohort study included patients with AKI and compared the outcomes for those who were treated with SGLT2is during hospitalization and those without SGLT2i treatment. The associations of SGLT2i use with MAKEs at 10 and 30-90 days, each individual MAKE component, and the pre-specified patient subgroups were analyzed. Results: From 2021 to 2023, 374 patients were included in the study-316 without SGLT2i use and 58 with SGLT2i use. Patients who were treated with SGLT2is were older; had a greater prevalence of diabetes, hypertension, chronic heart failure, and chronic kidney disease; required hemodialysis less often; and presented stage 3 AKI less frequently than those who were not treated with SGLT2is. Logistic regression analysis with nearest-neighbor matching revealed that SGLT2i use was not associated with the risk of MAKE10 (OR 1.08 [0.45-2.56]) or with MAKE30-90 (OR 0.76 [0.42-1.36]). For death, the stepwise approach demonstrated that SGLT2i use was associated with a reduced risk (OR 0.08; 0.01-0.64), and no effect was found for kidney replacement therapy (KRT). The subgroups of patients who experienced a reduction in the risk of MAKEs in patients with AKI treated with SGLT2is were those older than 61 years, those with an eGFR >81, and those without a history of hypertension or DM (p ≤ 0.05 for all). Conclusion: The use of SGLT2is during AKI had no effect on short- or medium-term MAKEs, but some subgroups of patients may have experienced benefits from SGLT2i treatment.

Clinical evaluation of peripheral tissue perfusion as a predictor of mortality in sepsis and septic shock in the intensive care unit: Systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. DESIGN: Systematic review and meta-analysis. SETTING: Intensive care unit. PATIENTS AND PARTICIPANTS: Patients with sepsis and septic shock. INTERVENTIONS: Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases. MAIN VARIABLES OF INTEREST: The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model. RESULTS: Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%-86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91-14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80-4.72) and 0.39 (95% CI, 0.30-0.51), respectively. CONCLUSIONS: Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock. REGISTRATION: PROSPERO CRD42019134351.

Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation.

BACKGROUND: Although acute kidney injury (AKI) frequently complicates cardiac operations, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiologic stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI. METHODS: We enrolled 110 patients with normal resting glomerular filtration rates undergoing elective cardiac operation. Preoperative RFR was measured by using a high oral protein load test. The primary end point was the ability of preoperative RFR to predict AKI within 7 days of operation. Secondary end points included the ability of a risk prediction model, including demographic and comorbidity covariates, RFR, and intraoperative variables to predict AKI, and the ability of postoperative cell cycle arrest markers at various times to predict AKI. RESULTS: AKI occurred in 15 patients (13.6%). Preoperative RFR was lower in patients who experienced AKI (p < 0.001) and predicted AKI with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% confidence interval [CI]: 0.70 to 0.96). Patients with preoperative RFRs not greater than 15 mL · min-1 · 1.73 m-2 were 11.8 times more likely to experience AKI (95% CI: 4.62 to 29.89 times, p < 0.001). In addition, immediate postoperative cell cycle arrest biomarkers predicted AKI with an AUC of 0.87. CONCLUSIONS: Among elective cardiac surgical patients with normal resting glomerular filtration rates, preoperative RFR was highly predictive of AKI. A reduced RFR appears to be a novel risk factor for AKI, and measurement of RFR preoperatively can identify patients who are likely to benefit from preventive measures or to select for use of biomarkers for early detection. Larger prospective studies to validate the use of RFR in strategies to prevent AKI are warranted. ClinicalTrials.gov identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759.