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.

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem.

INTRODUCTION: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. METHODS: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. RESULTS: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. CONCLUSION: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial.

AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

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.

Blood transfusion reactions and risk of acute kidney injury and major adverse kidney events.

BACKGROUND: Blood transfusion reactions may have a negative impact on organ function. It is unknown whether this association holds true for acute kidney injury (AKI). Therefore, we conducted a cohort study to assess the association between transfusion reactions and the incidence of AKI and major adverse kidney events. METHODS: In this retrospective cohort study, we included patients who received transfusion of blood products during hospitalization at the Hospital Civil of Guadalajara. We analyzed them according to the development of transfusion reactions, and the aim was to assess the association between transfusion reactions and AKI during long-term follow-up. RESULTS: From 2017 to 2021, 81,635 patients received a blood product transfusion, and 516 were included in our study. The most common transfusion was red blood cell packaging (50.4%), fresh frozen plasma (28.7%) and platelets (20.9%); of the 516 patients, 129 (25%) had transfusion reactions. Patients who had transfusion reactions were older and had more comorbidities. The most common type of transfusion reaction was allergic reaction (70.5%), followed by febrile nonhemolytic reaction (11.6%) and anaphylactoid reaction (8.5%). Most cases were considered mild. Acute kidney injury was more prevalent among those who had transfusion reactions (14.7%) than among those who did not (7.8%), p = < 0.01; those with AKI had a higher frequency of diabetes, vasopressors, and insulin use. Transfusion reactions were independently associated with the development of AKI (RR 2.1, p = < 0.02). Major adverse kidney events were more common in those with transfusion reactions. The mortality rate was similar between subgroups. CONCLUSION: In our retrospective cohort of patients who received blood product transfusions, 25% experienced transfusion reactions, and this event was associated with a twofold increase in the probability of developing AKI and some of the major adverse kidney events during long follow-up.

A Pilot Trial on the Effect of Levothyroxine on Proteinuria in Patients With Advanced CKD.

INTRODUCTION: Thyroid hormones can directly affect kidney function; elevated levels of thyroid-stimulating hormone (TSH) and chronic kidney disease (CKD) are associated with proteinuria, decreased estimated glomerular filtration rate (eGFR), and progression to end-stage renal disease. Our hypothesis is that in patients with CKD and TSH at levels considered to be in the low subclinical hypothyroidism (SCH) range, lowering TSH with levothyroxine (LVX) improves the clinical parameters of renal function. METHODS: This was a double-blind, randomized, pilot clinical trial in patients with proteinuric CKD (eGFR <60 ml/min per 1.73 m2 and proteinuria >150 mg/d) performed at the Hospital Civil de Guadalajara, with the intention of lowering TSH (levels of 1.25-2.5 µIU/l) in patients with TSH (levels of 2.6-9.9 µIU/ml with FT4 in the range of 0.7-1.8 ng/dl). Patients were randomized 1:1 to receive LVX or placebo for 12 weeks. The primary objective was to evaluate absolute levels of proteinuria at the beginning compared to the end of the study and, as a secondary objective, the changes in serum creatinine (sCr), eGFR, cholesterol, triglycerides, low-density lipoprotein (LDL), and blood pressure, and to assess the tolerability and safety of LVX. RESULTS: Between March and November 2018, a total of 163 patients were assessed for eligibility; 119 patients did not meet the inclusion criteria or were excluded, and 32 patients were randomized. The demographic and clinical characteristics of the 2 study groups were essentially not different. Subjects were 66.87 (SD 12.19) years of age, 62.5% were female, 75% were diabetes mellitus, eGFR was 23.55 (±12.91) ml/min per 1.73 m2, TSH was 5.37 ± 2.13 µIU/ml, proteinuria in 24-hour urine collection was 1.52 ± 1.12, and all of them were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Proteinuria at 12 weeks in the LVX group was 0.89 SD ± 1.28 g/d, and in the placebo group it was 1.35 SD ± 0.85 g/d; when compared to placebo, LVX showed a significant decrease in proteinuria of 1.1 g/d (P = 0.0011). The eGFR in the LVX group showed an improvement of 4 ml/min/1.73 m2 (P = 0.049); in the placebo group, there was a decrease of 1.98 ml/min per 1.73 m2. The sCr, cholesterol, triglycerides, low-density lipoprotein, systolic blood pressure, and diastolic blood pressure were not different between groups. Adverse events were reported in the LVX group in 7.14% of patients and in 11.11% of patients in the placebo group; none left the study because of adverse effects, and there were no serious adverse events. CONCLUSION: This single-center, randomized, double-blind, placebo-controlled pilot clinical trial in patients with advanced proteinuric CKD who already used ACEIs or ARBs demonstrated that administering LVX to obtain a TSH range close to 2.5 µIU/ml decreased proteinuria and improved eGFR. Future research is needed to confirm our results and to determine whether our findings generalize to patient groups not explicitly enrolled in this small pilot trial.