Introduction: The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target. Aim: We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients. Materials and Methods: We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects. Results: Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin (p = 0.018 and p = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; p = 0.03 and p = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD (p = 0.026) or with LPD and inulin (p = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-α) (p = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) (p = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1β (p = 0.529) and IL-6 (p = 0.828) in the two groups. Conclusions: LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.

BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents ( P =0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P =0.022) and adrenalectomy (72% versus 54%; P =0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01234220.

Background: Methylmalonic Aciduria (MA) without homocystinuria (or isolated MA) is a group of rare inherited metabolic disorders which leads to the accumulation of methylmalonic acid (MMA), a toxic molecule that accumulates in blood, urine, and cerebrospinal fluid, causing acute and chronic complications including metabolic crises, acute kidney injury (AKI), and chronic kidney disease (CKD). Detailed Case Description: Herein, we report a case of a 39-year-old male with MA and stage IV CKD who experienced acute metabolic decompensation secondary to gastrointestinal infection. The patient underwent a single hemodialysis (HD) session to correct severe metabolic acidosis unresponsive to medical therapy and to rapidly remove MMA. The HD session resulted in prompt clinical improvement and shortening of hospitalization. Discussion: MMA accumulation in MA patients causes acute and life-threatening complications, such as metabolic decompensations, and long-term complications such as CKD, eventually leading to renal replacement therapy (RRT). Data reported in the literature show that, overall, all dialytic treatments (intermittent HD, continuous HD, peritoneal dialysis) are effective in MMA removal. HD, in particular, can be useful in the emergency setting to control metabolic crises, even with GFR > 15 mL/min. Kidney and/or liver transplantations are often needed in MA patients. While a solitary transplanted kidney can be rapidly affected by MMA exposure, with a decline in renal function even in the first year of follow-up, the combined liver–kidney transplantation showed better long-term results due to a combination of reduced MMA production along with increased urinary excretion. Conclusions: Early diagnosis, multidisciplinary management and preventive measures are pivotal in MA patients to avoid recurrent AKI episodes and, consequently, to slow down CKD progression.

Introduction: Vascular access recirculation during hemodialysis is associated with reduced effectiveness and worse survival outcomes. To evaluate recirculation, an increase in pCO₂ in the blood of the arterial line during hemodialysis (threshold of 4.5 mmHg) was proposed. The blood returning from the dialyzer in the venous line has significantly higher pCO₂, so in the presence of recirculation, pCO2 in the arterial blood line may increase (ΔpCO₂) during hemodialysis sessions. The aim of our study was to evaluate ΔpCO₂ as a diagnostic tool for vascular access recirculation in chronic hemodialysis patients.Methods: We evaluated vascular access recirculation with ΔpCO₂ and compared it with the results of a urea recirculation test, which is the gold standard. ΔpCO₂ was obtained from the difference in pCO₂ in the arterial line at baseline (pCO₂T1) and after 5 min of hemodialysis (pCO₂T2). ∆pCO₂ = pCO₂T2–pCO₂T1.Findings: In 70 hemodialysis patients (mean age: 70.52 ± 13.97 years; hemodialysis vintage of 41.36 ± 34.54, KT/V 1.4 ± 0.3), ∆pCO₂ was 4 ± 4 mmHg, and urea recirculation was 7% ± 9%. Vascular access recirculation was identified using both methods in 17 of 70 patients, who showed a ∆pCO₂ of 10 ± 5 mmHg and urea recirculation of 20% ± 9%; time in months of hemodialysis was the only difference between vascular access recirculation and non‐vascular access recirculation patients (22 ± 19 vs. 46 ± 36, p: 0.05). In the non‐vascular access recirculation group, the average ΔpCO₂ was 1.9 ± 2 (p: 0.001), and the urea recirculation % was 2.8 ± 3 (p: 0.001). The ΔpCO₂ correlated with the urea recirculation % (R: 0.728; p < 0.001).Discussion: ΔpCO₂ in the arterial blood line during hemodialysis is an effective and reliable diagnostic tool for identifying recirculation of the vascular access but not its magnitude. The ΔpCO₂ test application is simple and economical and does not require special equipment.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

Cisplatin (cis-diclorodiamminoplatin, CDDP) is a common chemotherapeutic agent for solid tumors, but its use is limited by severe side effects such as ototoxicity and nephrotoxicity. Variability in CDDP dosing and administration, along with high mortality and sensitivity in animal models, complicates experimental approaches. This study aimed to evaluate ototoxic damage in rats by comparing a single bolus versus three divided CDDP injections, also considering nephrotoxic effects. Twenty-four Sprague-Dawley rats were divided into three groups: eight received a single intraperitoneal injection of CDDP (14 mg/kg), eight received three injections (4.6 mg/kg/day), and eight were untreated controls. All CDDP-treated rats showed significant high-frequency hearing loss and morphological damage, including cochlear outer hair cell loss and renal glomerular atrophy with proximal tubule necrosis. Oxidative stress markers (nitrotyrosine and SOD1 expression) confirmed cochlear and renal alterations. Notably, the single bolus group had a 25% mortality rate and significant weight loss among survivors, unlike the other groups. This study introduces the novel finding that cumulative administration of three doses reduces mortality and weight loss while maintaining similar ototoxic and nephrotoxic effects. Therefore, cumulative administration is recommended for future studies to mitigate ototoxic and nephrotoxic damage, offering a potentially improved protocol for the administration of cisplatin.