Oxalate nephropathy and chronic turmeric supplementation: a case report.

We present a case of a 69-year-old man who presented for routine check-up and was incidentally found to have kidney failure with an initially unrevealing history and bland urinary sediment. He was diagnosed with oxalate nephropathy in the setting of chronic turmeric supplementation and chronic antibiotic therapy with associated diarrhea. Our case provides several key insights into oxalate nephropathy. First, the diagnosis requires a high index of clinical suspicion. It is uncommonly suspected clinically unless there is an obvious clue in the history such as Roux-en-Y gastric bypass or ethylene glycol poisoning. Diagnosis can be confirmed by histopathologic findings and corroborated by serum levels of oxalate and 24-hour urinary excretion. Second, the diagnosis can often be missed by the pathologist because of the characteristics of the crystals unless the renal pathologist has made it a rule to examine routinely all H&E sections under polarized light. This must be done on H&E, as the other stains dissolve the crystals. Third, one oxalate crystal in a routine needle biopsy is considered pathologic and potentially contributing to the AKI or to the CKD in an important way. Fourth, secondary oxalosis can be largely mitigated or prevented in many cases, especially iatrogenic cases. This can come through the surgeon or the gastroenterologist providing proper instructions to patients on an oxalate-restricted diet or other specific dietary measures. Lastly, this case highlights the success that results from cooperation and communication between the pathologist and the treating physician.

Traditional herbal medicine use doubled the risk of multi-organ dysfunction syndrome in children: A prospective cohort study.

BACKGROUND: Traditional herbal medicine (THM) is frequently used in pediatric populations in many low-income countries as a form of healthcare and has been associated with a range of adverse events, including liver toxicity, renal failure, and allergic reactions. Despite these concerns, its impact on multi-organ dysfunction syndrome (MODS) risk has not been thoroughly investigated. OBJECTIVE: This study aimed to investigate the incidence and predictors of MODS in a pediatric intensive care unit (PICU) in Ethiopia, with a focus on the association between THM use and the risk of MODS. METHODS: This was a single-center prospective cohort study conducted at a PICU in the university of Gondar Comprehensive Specialized hospital, Northwest Ethiopia. The study enrolled eligible patients aged one month to 18 years admitted to the PICU during the study period. Data on demographic characteristics, medical history, clinical and laboratory data, and outcome measures using standard case record forms, physical examination, and patient document reviews. The predictors of MODS were assessed using Cox proportional hazards models, with a focus on the association between traditional herbal medicine use and the risk of MODS. RESULTS: A total of 310 patients were included in the final analysis, with a median age of 48 months and a male-to-female ratio of 1.5:1. The proportion and incidence of MODS were 30.96% (95% CI:25.8, 36.6) and 7.71(95% CI: 6.10, 9.40) per 100-person-day observation respectively. Renal failure (17.74%), neurologic failure (15.16%), and heart failure (14.52%) were the leading organ failures identified. Nearly one-third of patients (32.9%) died in the PICU, of which 59.8% had MODS. The rate of mortality was higher in patients with MODS than in those without. The Cox proportional hazards model identified renal disease (AHR = 6.32 (95%CI: 3.17,12.61)), intake of traditional herbal medication (AHR = 2.45, 95% CI:1.29,4.65), modified Pediatric Index of Mortality 2 (mPIM 2) score (AHR = 1.54 (95% CI: 1.38,1.71), and critical illness diagnoses (AHR = 2.68 (95% CI: 1.77,4.07)) as predictors of MODS. CONCLUSION: The incidence of MODS was high. Renal disease, THM use, mPIM 2 scores, and critical illness diagnoses were independent predictors of MODS. A more than twofold increase in the risk of MODS was seen in patients who used TMH. Healthcare providers should be aware of risks associated with THM, and educate caregivers about the potential harms of these products. Future studies with larger sample sizes and more comprehensive outcome measures are needed.

Experimental Characteristics of Patients with Newly Diagnosed Multiple Myeloma.

Background: Multiple myeloma (MM), a malignant plasma cell proliferative disease, makes up to 1% of all cancers and somewhat exceeds 10% of all hematological cancers. Since it affects many organs, the signs and symptoms of myeloma vary greatly. This investigation was carried out to identify the clinical and laboratory characteristics of MM. Method: From January 1, 2014, to June 30, 2020, 169 in-patients who received a MM diagnosis for the first time at China-Japan Friendship Hospital in Beijing had their medical information examined. Results: Among 169 newly diagnosed patients, the median age was 60 years (26-84 years). Seven patients were younger than 40 years, and 16.0% (27/169) were 70 years or older. 40.8% (69/169) had IgG M-protein and 27.2% (46/169) had IgA. 84% (142/169) of patients were in the Durie Salmon stage 3. The major sign and symptoms at diagnosis were fatigue (100/169, 59.2%), bone pain (96/169, 56.8%), and weight loss (34/169, 20.1%). Anemia was present initially in 94.0% (159/169), high erythrocyte sedimentation rate in 92.7% (101/109), and thrombocytopenia in 26.6% (45/169). Similarly, hypercalcemia, renal insufficiency, and hypoalbuminemia were observed in 19.3% (31/161), 27.8%, and 75.7% respectively. Immunoparesis was found in 94% (110/117) of IgG, IgA, or IgM patients, and in 87% (33/38) of light chain myeloma patients. A localized band was found in 78.3% (123/157) of patients upon serum protein electrophoresis while monoclonal protein was detected by immunofixation in 91.5% (139/152) of patients. 4.1% (7/169) of the patients had non-secretory myeloma. The prevalence of light chain myeloma was 22.5% (38/169), and these individuals were more likely than other myeloma patients to have renal insufficiency (50% versus 21%, P < .05). In 84.8% of patients, the bone marrow had 10% or more plasma cells. Conclusion: The notable features that can be concluded from this study are the early onset of myeloma in the Chinese population and an advanced disease stage at the time of diagnosis with most of them accompanying anemia, hypoalbuminemia, and immunoparesis.

Feasibility and Safety of Adjuvant Chemotherapy for Resected Colorectal Cancer in Patients With Renal Insufficiency: A Pooled Analysis of Individual Patient Data from Five Japanese Large-scale Clinical Trials.

BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

Imaging Patients with Kidney Failure.

The approach to imaging a patient with kidney failure continues to evolve. Overstatement of the risk of iodinated contrast material-induced (ie, contrast-induced) acute kidney injury and new guidelines for administration of gadolinium-based contrast media affect screening and the choice of contrast material. Treatment of kidney failure requires dialysis or a kidney transplant. Pretransplant imaging includes assessment for the feasibility of performing a transplant and evaluation for underlying malignancy and peripheral vascular disease. Patients with kidney failure are at high risk for renal cell carcinoma. Subtypes that occur exclusively or more commonly in patients with kidney failure, such as acquired cystic kidney disease, renal cell carcinoma, and clear cell papillary renal cell carcinoma, have specific clinical-pathologic characteristics, with indolent behavior. Performing US for dialysis planning increases the success of placement of an arteriovenous fistula, while postoperative US evaluation is essential in assessment of access dysfunction. Systemic manifestations in patients with kidney failure are multifactorial and may relate to the underlying cause of renal failure or may be secondary to treatment effects. Disturbances in mineral and bone metabolism and soft-tissue and vascular calcifications are seen in patients with chronic kidney disease and mineral bone disorder. Neurologic and cardiothoracic complications are also common. The authors provide a comprehensive overview of imaging considerations for patients with kidney failure, including the appropriate use of CT, MRI, and US with their respective contrast agents; the use of imaging in transplant workup and dialysis assessment; and the common renal and extrarenal manifestations of kidney failure. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Clinical features and risk factors of renal dysfunctions in thalassemic patients.

INTRODUCTION: Chronic anemia, iron overload, and iron chelation therapy are the main contributing factors for renal complications in thalassemia, e.g., nephrolithiasis, glomerular disease, and renal tubular dysfunction. The prevalence and associated factors for developing renal dysfunctions in Thai patients with thalassemia, however, remained limited. This study aimed to determine the prevalence and risk factors of renal dysfunctions in patients with thalassemia. METHODS: A cross-sectional study was conducted on adult patients with thalassemia disease at Srinagarind Hospital, Khon Kaen University, Thailand. All patients were evaluated for complete blood count, blood chemistry, urinalysis, and urine biochemistry. Renal tubular dysfunction was defined as existing in at least one of the following parameters including; proteinuria, hypercalciuria, hypouricemia with uricosuria, or hypophosphatemia with phosphaturia. Logistic regression analysis was used to identify associated factors for renal dysfunctions. RESULTS: Of 105 patients, renal tubular dysfunction was found in 60 patients (57.1%). In multivariate analysis of the clinical risk factors for renal tubular dysfunction in thalassemia patients, age per 10 year increase (adjusted odds ratio [AOR] = 1.4, 95% CI: 1.0-2.0, p value 0.01) and Hb E/beta-thalassemia (AOR = 3.6, 95% CI: 1.3-10.3, p value 0.01) were statistically proven to be associated with renal tubular dysfunction. Hyperuricosuria was a significantly associated factor for microhematuria. (AOR = 2.9, 95% CI: 1.1-8.0, p value 0.03). CONCLUSIONS: Renal dysfunctions are prevalent in thalassemia patients, with older age and Hb E/beta-thalassemia genotype as significant risk factors for renal tubular dysfunction. Hyperuricosuria is a risk factor for microhematuria. Renal dysfunctions should be recognized and monitored in aging patients with Hb E/beta-thalassemia.

Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Upacicalcet, a positive allosteric modulator of the calcium-sensing receptor, prevents vascular calcification and bone disorder in a rat adenine-induced secondary hyperparathyroidism model.

Secondary hyperparathyroidism (SHPT) is a major comorbidity of chronic kidney disease (CKD). Chronic elevation of PTH levels is associated with cortical bone deterioration and increase in the risk of fractures in CKD patients. Here, we evaluated the effect of repeated administration of upacicalcet, a novel positive allosteric modulator of the calcium-sensing receptor, in a rat model of adenine-induced renal failure, by determining serum levels of intact PTH (iPTH), calcium, phosphorus, creatinine, and urea nitrogen. Furthermore, parathyroid hyperplasia (parathyroid gland weight and Ki-67-positive cell density), ectopic calcification (calcium content in the thoracic aorta, kidney and heart and positive von Kossa staining in the thoracic aorta), and bone morphometry parameters (cortical porosity and fibrosis volume) were evaluated. Rats treated with either 0.2 mg/kg or 1 mg/kg upacicalcet exhibited significantly lower serum iPTH levels than CKD-control rats, as early as 7 days after the first dose. Repeated administration of upacicalcet reduced serum iPTH levels and inhibited parathyroid hyperplasia in rats with adenine-induced severe renal failure. Moreover, it suppressed ectopic calcification and cortical pore formation. In contrast, serum calcium and phosphorus levels were not significantly affected, suggesting a low risk of hypocalcemia, which often occurs with SHPT treatment. In conclusion, repeated administration of upacicalcet decreased serum iPTH levels and suppressed parathyroid hyperplasia in the adenine-induced CKD rat model of SHPT. Furthermore, ectopic calcification and cortical pore formation were suppressed without significant changes in blood mineral parameters. Upacicalcet safely inhibited the progression of SHPT in an adenine-induced CKD rat model.

Nephroprotective effects of polyherbal extract via attenuation of the severity of kidney dysfunction and oxidative damage in the diabetic experimental model.

In view of many complications of diabetes, kidney failure is considered as one of the main complications. The oxidative stress-induced due to persistent hyperglycemic conditions is the major cause of kidney disease. The present study was designed to explore the nephroprotective efficacy of polyherbal (PH) extract in a diabetic model induced by streptozotocin (STZ). STZ (55 mg/kg body weight, intraperitoneal) was injected in overnight fasting rats to develop the diabetic experimental model. Effect on kidney injury was evaluated by investigating biochemical and histological evidences in renal tissue after 56 days of treatment of PH extract. Results showed the high glucose level in STZ treated rats that suggested hyperglycemia persistence along with the successful establishment of nephropathy in diabetic rats with altered renal function, inflammatory cytokines level as well as oxidative and nitrosative stress. Administration of PH extract significantly improved the glycemic condition, glomerular function and proximal reabsorptive markers. Further, elevated pro-inflammatory cytokines levels and disturbed redox status were restored. Moreover, findings were fostered and substantiated by histopathological examinations. Our work strongly proposes that the nephroprotective effect of the PH extract on renal damage could be attributed due to its anti-inflammatory and antioxidant properties. Thus, PH extract could have potential as a pharmaceutical drug for diabetes mellitus (DM). Additional long-term study or clinical trial is required for further investigations.

Evaluation of the relationship between serum carnitine levels and intradialytic complications in children with kidney failure.

BACKGROUND: Carnitine plays a crucial role in the metabolism of fatty acids as well as energy production. Previous research has suggested a significant decrease in carnitine levels in patients with kidney failure and those undergoing hemodialysis. Therefore, we designed this study to assess the prevalence and characteristics of carnitine deficiency and its association with hemodialysis complications in the pediatric population. METHODS: This research was a pilot study of 29 children undergoing hemodialysis. Before hemodialysis, a 5-mL blood sample was drawn from each patient through a peripheral vein to measure serum-free carnitine levels, complete blood count with differential, blood urea nitrogen (BUN), creatinine, and electrolytes. Each patient was observed for intradialytic complications, including muscle cramps and hypotension, during 12 sessions of hemodialysis. RESULTS: We included 26 participants with a mean age of 14.23 years undergoing hemodialysis. Carnitine deficiency was revealed in 54.8% of our participants. Also, there was no significant correlation between carnitine deficiency and age, gender, and BUN levels (P = 0.698, P = 0.43, and P > 0.05, respectively). Intradialytic complications, including episodes of hypotension and muscle cramps, were more frequent in patients with carnitine deficiency (P = 0.02, P = 0.01, respectively). Other reasons for muscle cramps, such as fluid overload, nutritional status, dialysis regimen, and other important lab results (phosphorus, magnesium, etc.), were ruled out. CONCLUSION: In conclusion, we found a higher prevalence of carnitine deficiency in pediatric hemodialysis patients. Carnitine deficiency was significantly associated with increased intradialytic symptoms, including muscle spasms and hypotension. Our results could support a potential role of carnitine supplementation in pediatric patients with kidney failure for controlling intradialytic complications, but this requires further investigation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure.

BACKGROUND: Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. METHODS: We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. RESULTS: The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. CONCLUSION: In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Augmented Renal Clearance Following Traumatic Injury in Critically Ill Patients Requiring Nutrition Therapy.

The intent of this study was to ascertain the prevalence of augmented renal clearance (ARC) in patients with traumatic injuries who require nutrition therapy and identify factors associated with ARC. Adult patients admitted to the trauma intensive care unit from January 2015 to September 2016 who received enteral or parenteral nutrition therapy and had a 24 h urine collection within 4 to 14 days after injury were retrospectively evaluated. Patients with a serum creatinine concentration > 1.5 mg/dL, required dialysis, or had an incomplete urine collection were excluded. ARC was defined as a measured creatinine clearance > 149 mL/min/1.73 m2. Two hundred and three patients were evaluated. One hundred and two (50%) exhibited ARC. A greater proportion of patients with ARC were male (86% vs. 67%; p = 0.004), had traumatic brain injury (33% vs. 9%; p = 0.001), a higher injury severity score (30 ± 11 vs. 26 ± 12; p = 0.015), were younger (36 ± 15 vs. 54 ± 17 years; p = 0.001), had a lower serum creatinine concentration (0.7 ± 2 vs. 0.9 ± 0.2 mg/dL; p = 0.001) and were more catabolic (nitrogen balance of -10.8 ± 13.0 vs. -6.2 ± 9.2 g/d; p = 0.004). The multivariate analysis revealed African American race and protein intake were also associated with ARC. Half of critically ill patients with traumatic injuries experience ARC. Patients with multiple risk factors for ARC should be closely evaluated for dosing of renally-eliminated electrolytes, nutrients, and medications.

Metabolomic analysis of uremic pruritus in patients on hemodialysis.

Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform's chemical library. A role for uremic solutes in pruritus remains to be established.

Chronotherapy with a Renin-angiotensin System Inhibitor Ameliorates Renal Damage by Suppressing Intrarenal Renin-angiotensin System Activation.

Objective The intrarenal renin-angiotensin system (RAS) is activated in chronic kidney disease (CKD) patients and is not suppressed at night in CKD patients showing nocturnal hypertension, contributing to renal damage. Furthermore, changes in RAS inhibitor administration from morning to evening, namely chronotherapy, ameliorates renal damage at night. We attempted to clarify whether or not chronotherapy ameliorates renal damage by suppressing the intrarenal RAS activity. Methods We recruited 34 CKD patients with RAS inhibitors in the morning. We conducted ambulatory blood pressure (BP) monitoring and urine collection and evaluated urinary albumin (Alb) and angiotensinogen (AGT), which are surrogate markers for intrarenal RAS activity during the day and at night, respectively. The same experiments were conducted after changing the administration time. The ratio of values associated with morning versus evening dosing was defined as the morning to evening (M/E) ratio. Results The M/E ratio of urinary Alb had a significant and positive relationship with that of urinary AGT during the day and at night in all CKD patients. However, no significant relationships were found between the M/E ratios of urinary Alb and AGT using multiple linear regression analyses. Conversely, there was a significant and positive relationship between the M/E ratios of urinary Alb and AGT at night but not during the day in CKD patients whose estimated glomerular filtration rate was <45 mL/min/1.73 m2 and whose night-to-day ratio of systolic BP was >0.90, even after adjustment. Conclusion This study indicated that chronotherapy with RAS inhibitors improved the renal damage via intrarenal RAS suppression, especially in CKD patients with an impaired renal function and nocturnal hypertension.

[Peculiarities of the treatment of venous thromboembolism with direct oral anticoagulants in challenging patients: senile age, renal failure, fragility]. / Osobennosti terapii venoznykh tromboembolicheskikh oslozhnenii pryamymi oral'nymi antikoagulyantami u oslablennykh patsientov: starcheskii vozrast, pochechnaya nedostatochnost', khrupkost'.

The paper is a narrative review of the literature on the use of direct oral anticoagulants (DOACs) for the VTE treatment in challenging patients: senile age (≥75 years), impaired renal function (estimated glomerular filtration rate ≤50 ml/min), fragility (one of the previous characteristics and/or bodyweight ≤50 kg). The paper discusses the studies of EINSTEIN DVT and PE (rivaroxaban), AMPLIFY (apixaban), HOKUSAI-VTE (edoxaban), RE-COVER I and II (dabigatran) in the focus of the secondary analysis in the pre-specified patient's subgroups, as well as their pooled analyzes and meta-analyzes. Based on the results of this review, it was concluded that in a subgroup of senile age patients, dabigatran increases the risk of major bleeding by 4.8 times and has no advantages over vitamin K antagonists (VKA); rivaroxaban and apixaban retain superiority over VKA on the safety outcomes and reduce the risk of major bleeding by 73% and 77%. In the subgroup of patients with impaired renal function, the use of apixaban and dabigatran is associated with an increase in the risk of major bleeding by 6.5 and 7.3 times, and these DOACs do not have advantages over VKA; rivaroxaban retains its superiority over VKA and reduces the risk of major bleeding by 78%. For fragile patients, a secondary analysis is available only for rivaroxaban, which remains superior to VKA on safety endpoints and reduces the risk of major bleeding by 73%. In the absence of direct comparisons between the available DOACs, the presented data can be used as a rational approach for the choice of appropriate treatment for VTE in challenging patients.

A pilot study on secondary anemia in "frailty" patients treated with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability.

OBJECTIVE: Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. PATIENTS AND METHODS: In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. RESULTS: Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. CONCLUSIONS: Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

Comparison of Anti-factor Xa Activity Among Three Different Factor Xa Inhibitors in Non-valvular Atrial Fibrillation Patients with Renal Impairment.

BACKGROUND: Factor-Xa inhibitors (FXaIs) are widely used for the treatment of non-valvular atrial fibrillation (NVAF). Although we have previously reported the distribution of the anti-factor Xa activity (AXA) values of three different FXaIs in NVAF patients, the differences in the distribution of AXA values among the different FXaIs in patients with renal impairment (RI) have not been fully elucidated. METHODS: Trough and peak AXA values were measured in 94 patients taking rivaroxaban, 124 patients taking apixaban, and 66 patients taking edoxaban. Of them, we identified 26 patients with moderate RI [creatinine clearance (CrCl) 30-49 mL/min] and 17 patients with severe RI (CrCl 15-29 mL/min) in the rivaroxaban cohort, 37 patients with moderate RI and 17 patients with severe RI in the apixaban cohort, and 21 patients with moderate RI and 9 patients with severe RI in the edoxaban cohort. AXA values were measured using chromogenic AXA assays. Both trough and peak AXA values were compared between patients with moderate RI and those with severe RI in each cohort, and differences in the peak-to-trough ratio among the different drugs were assessed. RESULTS: In the rivaroxaban cohort, the peak AXA value was significantly higher in patients with severe RI than in those with moderate RI. In the apixaban cohort, neither the trough nor peak AXA values significantly differed between patients with moderate RI and those with severe RI. In the edoxaban cohort, the trough AXA value was significantly higher in patients with severe RI than in those with moderate RI, and peak AXA tended to be higher in patients with severe RI. The peak-to-trough ratio of AXA values was significantly lower in patients taking apixaban than in those taking rivaroxaban and edoxaban. CONCLUSION: Among Japanese NVAF patients with RI, the peak or trough AXA values were higher in patients with severe RI than in those with moderate RI when taking rivaroxaban and edoxaban, whereas both the peak and trough AXA values were similar between patients with severe RI and those with moderate RI when taking apixaban. The peak-to-trough ratio of AXA values was the lowest in patients taking apixaban.

[The 473rd case: renal failure, abdominal pain, and mental abnormality].

A 43-year-old male presented with elevated serum creatinine for 4 years and developed abdominal pain for 3 days. He started peritoneal dialysis 2 months ago. Dialysis-related peritonitis was ruled out and acute gastroenteritis was diagnosed. The patient was administrated with ertapenem 500 mg/d. An acute mental abnormality developed 3 days later. After excluded organic encephalopathy, ertapenem was discontinued for the suspicion of antibiotic-related encephalopathy. The frequency of peritoneal dialysis was increased to accelerate the clearance of antibiotics. However, the metal abnormality became even more severe. Then a diagnosis of Wernick-Korsakoff syndrome was considered. After the administration of high dose vitamin B(1), the mental disorder dramatically relieved. Vitamin B(1) 30 mg/d is maintained during peritoneal dialysis and the mental disorder does not relapse.

[Nutrition in children with continuous renal replacement therapy]. / Nutrición en niños tratados con técnicas de depuración extrarrenal continua.

INTRODUCTION: The aim of this study was to analyse the nutritional state, diet and gastrointestinal complications of children that require continuous renal replacement therapy (CRRT). MATERIAL AND METHODS: A retrospective analysis of a database, which included the information about patients who required CRRT between the years 2013 and 2017. Data were collected on the replacement technique, type of nutrition, calorie and protein intake, gastrointestinal complications, and clinical course. RESULTS: A total of 65 children (61.5% male) were treated with CRRT, and 24 patients (37%) also needed ECMO support. Just over one-quarter (27.7%) of patients had a weight less than P3, and 48.4% of them a height less than P3. At the beginning of the technique, 31 children (47.7%) received enteral nutrition, at the end, there were 52 patients receiving enteral nutrition (80%). The transpyloric tube was used to provide nutrition in 76% of the cases. The median caloric intake was 63kcal/kg/day, and the protein intake was 1.6g/kg/day. There were gastrointestinal difficulties during the process in 48 patients (73.8%), with 29 (44.6%) patients being diagnosed with gastric distension or excessive gastric remains, 22 (33.8%) with constipation, 8 (12.3%) with vomiting, and 4 (6.1%) diarrhoea. One patient treated with ECMO presented with intestinal ischaemia. Enteral nutrition was cancelled in 3 patients (4.6%) due to the complications. There was no relationship between complications and type of diet or ECMO assistance. CONCLUSIONS: A high percentage of children treated with CRRT showed undernutrition but they had adequate tolerance to the enteral nutrition. Although the gastrointestinal complications percentage was high in few subjects, these complications are the reason why enteral nutrition was stopped.