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Acute kidney injury (AKI) is a growing global health problem with increased mortality and morbidity. Cisplatin is achemotherapy drug first introduced in 1978, and since then, it became one of the most widely used and successful anti-cancer medication. However, there are risks associated with cisplatin administration, such as nephrotoxicity. Mechanisms of nephrotoxicity include proximal tubular injury, DNA damage, apoptosis, inflammation, oxidative stress, and vascular injury. Although various protocols are being used in clinical practice in nephrotoxicity prevention due to cisplatin, there are no clear guidelines regarding this approach. Most recommendations include hydration and avoiding additional nephrotoxic drugs. To prevent nephrotoxicity, future perspectives could rely on natural products, such as flavonoids or saponins or pharmacological products, such as aprepitant, but data are scarce in this direction. Repetitive administration of cisplatin could cause subclinical kidney injury, which over time, leads to chronic kidney disease (CKD). Therefore, more studies are needed to determine possible ways to prevent nephrotoxicity and avoid the burden of CKD worldwide.

The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high-sensitivity C-reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD).We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations.350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle-brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 220 ng/mL was a predictor of cardiovascular events, while the EF 50% was a predictor for renal outcomes. For CKD patients with PCSK9 220 ng/mL and hsCRP 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers.The results of this study show that PCSK9 220 ng/mL was predictor for cardiovascular events, while EF 50% was predictor for CKD progression to ESRD. PCSK9 220 ng/mL and hsCRP 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994–2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.

Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking.In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management.Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88-10.26, P 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68-9.29, P 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE.Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.

There is evidence that serum iron levels, regardless of the presence of anemia, directly impact outcomes in congestive heart failure (CHF) including quality of life, hospitalization rate and overall survival. Despite modern medical treatments, the prognosis of CHF remains grim. Ironically, simple iron replenishment may serve as a powerful tool in the armamentarium. This review will start from fundamental concepts of iron in oxygen delivery and analyze evidence-based outcomes in CHF iron-directed therapeutic trials. Imaging rationale that dovetails with this pathophysiology will also be detailed in a clinician-directed fashion.

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients. In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)—including death, stroke, and myocardial infarction. During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64–1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio—0.81, 95% CI 0.68–0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio—1.26, 95% CI 1.16–1.37). This study shows that a LUS–bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.

The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis.This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria 0.3 g per 24 h (urinary protein-creatinine rate 300 mg/g [ 30 mg/mmol]]; partial remission (proteinuria 0.3 but 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events.At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance.Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

The aim of the study was to evaluate the correlation between electrocardiographic parameters and heart rate variability with cardiovascular events and mortality among chronic hemodialysis patients. In this prospective study, we enrolled 116 asymptomatic patients in whom we performed ambulatory 24-h electrocardiographic Holter monitoring and before and after hemodialysis electrocardiographs. We measured the interval (PR, QRS, QTc, QTc dispersion) differences on the surface electrocardiographs and obtained frequency-domain measures from Holter monitoring (VLF, LF, HF and the LF/HF ratio). During the follow-up period, 13 participants died (11.2 %) and 16 (13.8 %) patients experienced a cardiovascular event. The pre–post-dialysis difference in QTc interval was the best predictor for cardiovascular events (95 % CI 0.453–0.786), while pre-dialysis QRS interval was the predictor for all-cause mortality (95 % CI 1.134–3.136). Also, both outcomes were predicted by pre–post-dialysis difference in PR interval and VLF. Interval changes during hemodialysis are predictive for cardiovascular events and mortality. Autonomic dysfunction and changes in PR should be monitored routinely, particularly in patients with suspected coronary artery disease.

In the last decade, despite constant investigation, no current single treatment has been able to decrease the incidence of diabetic nephropathy and to significantly reduce progression of diabetic CKD. Patients with type 2 diabetes mellitus and proteinuria (>0.5 g/day) after a screening and treatment optimization phase were randomly assigned to receive silymarin or placebo. The primary outcome was a composite outcome: mortality, decline of eGFR > 50% and renal replacement therapy. Secondary outcomes were a composite renal outcome (defined as a decline of eGFR ≥ 50% or ESRD) and also to test the effect of silymarin on the change in eGFR and proteinuria. We also assessed the adverse effects (hospitalizations, headache or gastrointestinal symptoms) during the study. One hundred and two patients were included in the study. There were no significant differences between the two study groups regarding the primary and renal outcomes (HR 0.62, 95% CI 0.3–1.2, p = 0.15; HR 0.56, 95% CI 0.26–1.24, p = 0.16, respectively). At study end, eGFR declined significantly in both arms (p

Periodontal disease is a chronic infectious disease. Individuals with end-stage kidney disease (ESKD) experience impaired quality of life (QoL) and low oral health. This is the first comprehensive study which aimed to explore the link between periodontal disease and quality of life, assessed with the Short Form 36-Item Health Survey in hemodialysis patients. In total, 101 patients (57 females) with ESKD were recruited from two Romanian dialysis centers. Periodontal disease assessment included the measurement of periodontal disease index, with its three components: the gingival and periodontal index (GP), the bacterial plaque index (PI) and the calculus index (CI). For assessing QoL, we used the Short Form 36-Item Health Survey (SF-36), with its two components: physical component (PCS) and mental component (MCS). The mean age was 52.5 ± 14.3 years. The dialysis vintage was 6.7 ± 5.6 years. According to periodontal status, the mean value of GP was 4.0 ± 1.3, mean PI was 1.8 ± 0.9, and mean CI was 1.3 ± 0.7. Regarding the QoL, the means for PCS and MCS were 38.0 ± 17.3 and 45.0 ± 16.3, respectively. In univariate analysis, the physical and mental components of QoL were significantly associated with the gingival and periodontal index, the bacterial plaque index and the calculus index. In the multivariable linear regression, only the gingival and periodontal index remained significantly associated with physical component (β = −3.26, p = 0.04, 95% CI −6.39 to −0.13) and mental component (β = −5.57, p = 0.001, 95% CI −8.74 to −2.41) of QoL. Our study shows a high prevalence and severity of periodontal disease. The gingival and periodontal index was associated with low QoL, both on physical and on mental components.

IgA nephropathy (IgAN) is one of the world’s most common glomerular diseases. Hyperuricemia was recently defined as risk factor for chronic kidney disease. We aimed to investigate the impact of baseline serum uric acid levels on progression of IgAN. A total of 93 patients with IgAN were screened. Demographic information and biochemical data were recorded. eGFR (using the CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration formula) was used as renal function marker. Baseline and sixth month eGFR values were calculated. Progression of renal disease was defined as the difference between baseline eGFR and sixth month eGFR (delta eGFR). Mean age of the patients was 40 ± 11 years (60 % were males). Baseline mean eGFR was 77.9 ± 30.2 mL/min, and baseline mean serum uric acid was 5.65 ± 1.68 mg/dL. Importantly, baseline serum uric acid levels were found to be associated with the change in eGFR (r = 0.252, p = 0.01). In multivariate analysis (adjusted R 2 = 0.171, p = 0.031), adjusting for age, gender, baseline eGFR, blood pressure, baseline albumin concentration and ACEI and/or ARB use revealed that the baseline serum uric acid levels significantly predicted the change in eGFR. Baseline serum uric acid concentration is directly proportional to the rate of decline in renal functions in patients with IgAN. Uric acid-lowering treatments may be beneficial for the prevention of progression of IgAN. However, randomized controlled studies are needed for this purpose.

Elevated vasopressin may increase systemic vascular resistance and pulmonary capillary wedge pressure, subsequently decrease stroke volume and cardiac output. Vasopressin receptor antagonists may counteract these effects and improve outcomes in heart failure. We aimed to assess benefits and harms of vasopressin receptor antagonists (VRAs) versus placebo in addition to standard care in adults with heart failure (HF).We conducted a systematic review of randomized controlled trials with searches of CENTRAL and MEDLINE to January 2014 and reference lists without language restriction. Meta-analysis using a random-effects model was done for all-cause and cardiovascular mortality, hospitalization for heart failure, changes in clinical assessment of HF, serum sodium concentration (Na), kidney function and treatment-specific side effects.We identified 13 trials and 5,525 participants. In 10 trials, participants received standard therapy for HF. In low-quality evidence, VRAs in patients with HF had no effect on all-cause mortality risk ratios (RR 0.98; CI 0.88-1.08), cardiovascular mortality (RR 1.03; CI 0.91-1.16) or change in creatinine mean difference (MD -0.01; CI -0.10 to 0.09 mg/dL), but reduced body weight by 0.8 kg from baseline (MD -0.83; CI -1.10 to -0.55 kg) and increased Na (MD 2.61; 95 % CI 1.88-3.35 mmol/L). Compared with placebo, VRAs increased the risk of adverse events by 14 % (RR 1.14; CI 1.04-1.26). Studies were generally limited to short-term follow-up with limited data available on patient important outcomes.Vasopressin receptors antagonists may reduce body weight and increase Na but do not improve all-cause mortality, cardiovascular mortality or kidney function. In addition, acceptability of long-term treatment side effects and hospitalization appears problematic.

Chronic volume overload is very frequent in hemodialysis (HD) patients and is directly associated with hypertension, increased arterial stiffness, left ventricular hypertrophy (LVH), heart failure and ultimately with higher mortality and morbidity. One major issue is that presently there are very few comparative studies of the various methods (clinical, bioimpedance, inferior cava vein diameter (ICV) and Brain Natriuretic Peptide (NT-proBNP)) for volume status evaluation and their correlation with cardiovascular disease.In 160 patients treated by chronic HD in our center, euvolemic according to clinical assessment, we performed evaluation of volume status through bioimpedance spectroscopy (BIS), ICV and NT-proBNP, as well as echocardiography, to estimate the left ventricle structure and function.Despite appearing clinically euvolemic, severe fluid overload, as defined by a relative tissue hydration (RTH)--i.e. fluid overload over extracellular water ratio (FO/ECW)--above 15% was found in 25.6% of patients. Four categories of patients were considered according to pre-HD BP and BIS values. Forty-five percent of patients (group A) had a reasonable control of BP and volume (SBP150 mmHg and RTH15%), 29.3% (group B) were classified as hypertensive (SBP150 mmHg and RTH15%), 16.7% (group C) had high blood pressure and marked volume expansion, (SBP150 mmHg and RTH15%), while 9% (group D) had SBP150 mmHg despite RTH15%. Assuming that BIS is the most accurate and validated method to assess hydration status, we calculated the positive predictive value for ICV-based evaluation--18%, with a sensitivity of 67% and an important proportion of false negative cases (45%). NT-proBNP was even less accurate: PPV of only 26%, with a sensitivity of 60% and a specificity of only 45% and an extremely high proportion of false positive cases (73%). Group A patients had the best cardio-vascular profile: lowest LV mass and NT-proBNP levels.Using multi-frequency body impedance spectroscopy, we found a large group of hypertensive and/or fluid-overloaded patients despite apparently being at "dry weight" on clinical evaluation and a marked discrepancy between clinical appearance and fluid status. Of the 4 different methods, assuming BCM "gold standard", there were major disagreements and discrepancies between the other three methodologies. BCM is a valuable and simple bed-side tool for the correct management of BP and risk stratification in HD patients as it allows for excellent discriminators of more abnormal cardiac and vascular profiles.