Chronic Kidney Disease-An Underestimated Risk Factor for Antimicrobial Resistance in Patients with Urinary Tract Infections.

(1) Background: Chronic kidney disease (CKD), as well as antimicrobial resistance (AMR) represent major global health problems, with important social and economic implications. It was reported that CKD is a risk factor for antimicrobial resistance, but evidence is scarce. In addition, CKD is recognized to be a risk factor for complicated urinary tract infections (UTIs). (2) Methods: We conducted an observational study on 564 adult in-hospital patients diagnosed with urinary tract infections. The aim of the study was to identify the risk factors for AMR, as well as multiple drug resistance (MDR) and the implicated resistance patterns. (3) Results: The mean age was 68.63 ± 17.2 years. The most frequently isolated uropathogens were Escherichia coli strains (68.3%) followed by Klebsiella species (spp. (11.2%). In 307 cases (54.4%)), the UTIs were determined by antibiotic-resistant bacteria (ARBs) and 169 cases (30%) were UTIs with MDR strains. Increased age (≥65) OR 2.156 (95% CI: 1.404−3.311), upper urinary tract obstruction OR 1.666 (1.083−2.564), indwelling urinary catheters OR 6.066 (3.919−9.390), chronic kidney disease OR 2.696 (1.832−3.969), chronic hemodialysis OR 4.955 (1.828−13.435) and active malignancies OR 1.962 (1.087−3.540) were independent risk factors for MDR UTIs. In a multivariate logistic regression model, only indwelling urinary catheters (OR 5.388, 95% CI: 3.294−8.814, p < 0.001), CKD (OR 1.779, 95% CI: 1.153−2.745, p = 0.009) and chronic hemodialysis (OR 4.068, 95% 1.413−11.715, p = 0.009) were risk factors for UTIs caused by MDR uropathogens. (4) Conclusions: CKD is an important risk factor for overall antimicrobial resistance, but also for multiple-drug resistance.

Acute kidney injury in moderate and severe COVID-19 patients: Report of two university hospitals.

Acute kidney injury (AKI) is one of the most severe complications of SARS-CoV-2 infection. In a retrospective study, we aimed to describe the influence of COVID-19-related factors on the severity, outcome and timing of AKI in 268 patients admitted in two large COVID-19-designated university hospitals over a period of 6 months. In the univariate analysis, there was a significant relationship between KDIGO stage and the extension of COVID-19 pneumonia on computed tomography (CT), need for oxygen supplementation, serum levels of ferritin, interleukin-6, and procalcitonin, but none of these variables had a value for predicting KDIGO stage in multinomial regression. The odds of recovery of renal function were significantly diminished by d-dimer values. Lack of immunomodulatory treatment was found to be correlated with increased need for renal replacement therapy (RRT). Compared with AKI at admission, hospital-acquired AKI was predicted by the severity of lung damage on CT, evolved more frequently with incomplete recovery of renal function, and was significantly associated with antiviral therapy.

Combination of cranberry extract and D-mannose - possible enhancer of uropathogen sensitivity to antibiotics in acute therapy of urinary tract infections: Results of a pilot study.

Uncomplicated lower urinary tract infections are extremely common in women. Antibiotic treatment for acute episodes and for recurrence prophylaxis has its drawbacks and alternative therapies are sought in order to reduce the antimicrobial resistance phenomenon and the intestinal dismicrobism expansion. There are few studies on the effect of combination of cranberry extract with D-mannose in acute urinary tract infection management. In a pilot, randomized study 93 non-pregnant, otherwise healthy women, were enrolled with mean age of 39.77±10.36, diagnosed with uncomplicated lower urinary tract infection. Medical history, clinical examination, urine culture and a list of complaints were noted at the baseline visit. In a first phase of the study, treatment with either guideline recommended antibiotic alone or in association with the investigated product (cranberry extract plus D-mannose) was prescribed and all patients were clinically examined at day 7. All ameliorated and cured patients received in a second phase of the study, in a double-blind manner, prophylaxis with the investigated product or placebo for another 21 days, then a second clinical examination and a check of the list of complaints were performed. The cure rates were higher at day 7 when investigated product was added to antibiotic (91.6 vs. 84.4%). In resistant strains, a significantly higher cure rate was shown when the investigated product was added to antibiotic prescribed (88.8 vs. 37.5%, P<0.0001). The effect of cranberry extract plus D-mannose combination in acute urinary tract infection episodes seems to be promising. The significant cure rate registered in the patients with antibiotic-resistant urine cultures may be explained by a beneficial influence of the product on the antimicrobial sensitivity. Further studies are needed on this subject.

Bone turnover correlates with bone quantity but not bone microarchitecture in chronic hemodialysis.

INTRODUCTION: In chronic hemodialysis, high-turnover bone disease was associated with decreased bone mineral density (BMD), poor bone quality (chemical and structural), and increased fracture risk. Our aim was to correlate bone turnover markers (BTMs) with bone microarchitecture measured by trabecular bone score (TBS) before and after correction for BMD. MATERIALS AND METHODS: We measured lumbar spine (LS), femoral neck, and 1/3 radius BMD and LS TBS by dual X-ray absorptiometry in 81 patients on permanent hemodialysis. Bone turnover was assessed using serum parathyroid hormone, osteocalcin, C-terminal crosslaps of type 1 collagen, procollagen 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). No patient had any partial or total parathyroidectomy and no previous or current treatment with anti-osteoporotic drugs. RESULTS: All BTMs correlated significantly with each other. Univariate regressions showed significant negative correlations between BTMs and BMD (best r = - 0.53, between P1NP and 1/3 radius Z-score) or BTMs and TBS (best r = - 0.27, p < 0.05 between ALP and TBS T-score). TBS correlated significantly with BMD at all three sites (best r = 0.5, between LS BMD and TBS T-score). Multivariate regression showed that TBS, crude or adjusted, correlated with LS BMD. No model retained any of the BTMs as independent variables due to the better prediction of BMD and multicollinearity. CONCLUSION: We showed a progressively impaired bone microarchitecture with increasing bone turnover in chronic hemodialysis. However, this correlation is no longer present when controlling for bone mass. This suggests that impaired bone microarchitecture and increased fracture risk are dependent upon factors other than high bone turnover.

Chronic hemodialysis is associated with lower trabecular bone score, independent of bone mineral density: a case-control study.

We measured trabecular bone score (TBS) in 98 patients on permanent hemodialysis (HD) and 98 subjects with similar bone mineral density and normal kidney function. TBS was significantly lower in HD patients, indicating deteriorated bone microarchitecture, independent of bone mass. This might partially explain the increased fracture risk in HD. PURPOSE: In the general population, trabecular bone score (TBS) was shown to predict fracture independent of bone mineral density (BMD). In end-stage renal disease patients on hemodialysis (HD), the value of TBS is beyond that of BMD in currently unclear. Our aim was to assess lumbar spine (LS) TBS in HD patients compared with subjects with normal kidney function matched for age, sex, and LS BMD. METHODS: We assessed TBS and LS and femoral neck (FN) BMD in 98 patient on permanent HD (42.8% males; mean age 57.5 ± 11.3 years; dialysis vintage 5.5 ± 3.8 years) and 98 control subjects (glomerular filtration rate > 60 mL/min) using DXA. We simultaneously controlled for sex, age (± 3 years), and LS BMD (± 0.03 g/cm2). RESULTS: HD patients had significantly lower LS TBS (0.07 [95% CI 0.03-0.1]; p = 0.0004), TBS T-score (0.83 SD [95% CI 0.42-1.24]; p = 0.0001)) and TBS Z-score (0.81 SD [95% CI 0.41-1.20]; p = 0.0001) than matched controls. TBS significantly correlated with LS BMD in both HD patients (r = 0.382; p = 0.001) and controls (r = 0.36; p = 0.002). The two regression lines had similar slopes (0.3 vs. 0.28; p = 0.84) with different intercepts (0.88 vs. 0.98). TBS adjustment significantly increased the 10-year fracture risk from 3.7 to 5.3 for major osteoporotic fracture and from 0.9 to 1.5 for hip fracture. CONCLUSIONS: HD patients have lower TBS than controls matched for LS BMD, indicating altered bone microarchitecture. Also, the magnitude of TBS reduction in HD patients is constant at any LS BMD. Adjustment for TBS partially corrects the absolute 10-year fracture risk.

Coronary risk score for mineral bone disease in chronic non-diabetic hemodialysis patients: results from a prospective pilot study.

INTRODUCTION: Chronic kidney disease-mineral bone disorder enhances coronary artery impairment (often occult and difficult to diagnose) in hemodialysis (HD) patients. The aim of the study was to correlate biochemical and imagistic parameters of MBD with the degree of documented coronary artery disease (CAD) in non-diabetic HD patients, in order to obtain a MBD-coronary risk score as a screening algorithm. METHODS: A 3-year prospective study was conducted on 168 non-diabetic HD patients, evaluating MBD biochemical parameters along with pulse wave velocity (PWV) determination and valve/coronary calcification assessment; coronary angiography was performed in symptomatic patients. Correlations between noninvasive parameters and the degree of coronary obstruction were assessed using IBM SPSS Statistics 20 software, Chi-square test and the determination of odds ratio. RESULTS: Significant differences in serum calcium (p < 0.001), phosphates (p = 0.03), bicarbonate (p < 0.001), albumin and iPTH (p = 0.002), percentage of deviations from PWV normal values (p = 0.004), average doses of phosphate binders and vitamin D and the number of vascular/valve calcifications were noted between the study group (angina, n = 17) and control group (asymptomatic, n = 151). After applying MBD-coronary risk score in control group, coronary angiography was performed in high-score patients. CONCLUSION: A noninvasive screening algorithm for early diagnosis of CAD in asymptomatic HD patients with altered MBD parameters is necessary. Applying MBD-coronary risk score might be an important step in the prevention of major coronary episodes by extending the indication for further investigations, early diagnosis and treatment management.

Very low protein diets supplemented with keto-analogues in ESRD predialysis patients and its effect on vascular stiffness and AVF Maturation.

BACKGROUND: Native arteriovenous fistula (AVF) is the most appropriate type of vascular access for chronic dialysis. Its patency rates depend on vascular wall characteristics. Ketoacid analogues of essential amino acids (KA/EAA) are prescribed in end-stage renal disease (ESRD) pre-dialysis patients to lower toxic metabolic products generation and improve nutritional status. We hypothesized that very-low protein diet (VLPD) supplemented with KA/EAA may influence arterial wall stiffness and affect AVF maturation rates and duration in pre-dialysis ESRD patients. METHODS: In a prospective, cohort, 3 years study we enrolled 67 consecutive non-diabetic early referral ESRD patients that underwent AVF creation in our hospital. Patients were divided in two groups based on their regimen 12 months prior to surgery: a VLPD supplemented with KA/EAA study group versus a low protein diet non-KA/EAA-supplemented control group. For each patient we performed serum analysis for the parameters of bone mineral disease, inflammation and nutritional status, one pulse wave velocity (PWV) measurement and one Doppler ultrasound (US) determination prior the surgery, followed by consequent Doppler US assessments at 4, 6, 8 and 12 weeks after it. Rates and duration of mature AVF achievement were noted. We used logistic regression to analyze the association between AVF maturation and KA/EAA administration, by comparing rates and durations between groups, unadjusted and adjusted for systolic blood pressure, C-reactive protein, PWV, phosphorus values. All parameters in the logistic model were transformed in binary variables. A p-value < α = 0.05 was considered significant; data were processed using SPSS 16 software and Excel. RESULTS: In the study group (n = 28, aged 57 ± 12.35, 13 females) we registered better serum phosphate (p = 0.022) and C-reactive protein control (p = 0.021), lower PWV (p = 0.007) and a higher percent of AVF creation success (33.3 % versus 17.8 %, p < 0.05). AVF maturation duration was lower in study group (5.91 versus 7.15 weeks, p < 0.001). CONCLUSIONS: VLPD supplemented with KA/EAA appear to improve the native AVF primary outcome, decreasing the initial vascular stiffness, possible by preserving vascular wall quality in CKD patients through a better serum phosphate levels control and the limitation of inflammatory response.

An overview of permanent vascular access in hemodialyzed patients.

In the last decade, because of significant number of end-stage renal disease individuals in need of renal therapy replacement and permanent quest of nephrologist to optimize kidney disease patients' quality of life, there is an increased interest in achieving a suitable permanent vascular access, essential for an efficient dialysis. Furthermore, it is of high importance to preserve arteriovenous fistula in optimal condition and therefore, it is vital to correctly understand the histopathology and pathophysiological mechanisms implicated in maturation and well function of dialysis vascular access.

Intra-peritoneal chronic loculation in peritoneal dialysis patients - a new medical management approach.

Peritoneal dialysis (PD) limitation as renal replacement therapy is mostly due to peritonitis and complications. Formation and persistence of intra-abdominal loculations is often under-diagnosed. Encapsulated peritoneal sclerosis (EPS) is a life-threatening complication, but malnutrition, recurrent peritonitis and early membrane failure are insidious enemies that need to be emphasized. It is important to highlight the persistence of intra-abdominal fluid collection after clinical resolution of peritonitis in PD patients and to indicate a new medical management approach for an early diagnosis. During five years, we selected PD peritonitis cases followed by a six months interval free of infections. Ninety-seven subjects were followed at six months and one year after the first peritonitis. Tomography had been performed to patients presenting a positive inflammatory state without a specific infectious cause. Subjects presenting documented localized fluid collection (31 cases) were divided into: drug-treated group and those undergoing laparoscopy by a new surgery technique (seven patients); a comparison regarding the clinical state and biohumoral parameters was assessed in both groups. The prevalence of intra-abdominal loculation following an apparent resolved peritonitis was high (31.9%). The cases undergoing laparoscopy presented a better evolution - improved clinical status (p=0.001), higher hemoglobin values (p=0.06), significant lower doses of erythropoietin requirement (p=0.03), improved dialysis adequacy (p=0.005) and inflammatory state. In cases with confirmed fluid encapsulated loculation, an active attitude (screening imaging protocol and laparoscopic exploration) appears to be mandatory, decreasing the risk of EPS, a serious complication which pathology and treatment are incompletely understood.

Oral treatment of metabolic acidosis in hemodialyzed patients and the implications on the hemodynamic status.

UNLABELLED: Metabolic acidosis slowly develops during renal impairment natural evolution towards ESRD and represents an important contributing factor of CKD progression. Although, several clinical and experimental trials reported the major impact of metabolic acidosis on CKD evolution, the pathophysiology mechanism remains a matter of debate. Furthermore, international guidelines do not impose a specific treatment scheme for metabolic acidosis in CKD patients, and metabolic acidosis is not fully compensated once hemodialysis starts. Therefore, the aim of our study was to determine an adequate follow-up of metabolic acidosis therapy benefits and risks in HD patients. PATIENTS AND METHODS: 164 HD patients were evaluated according to the following protocol: bioumoral laboratory tests, the measure of different important parameters (residual diuresis, UF, BP, LVMI, volemia status). The assessed data were statistic analyzed using non-paired Student's t-test for continuous variables and chi-square (χ²) test for qualitative parameters (p-value <0.05 was considered statistically significant). RESULTS: HD individuals were followed-up depending on their predialysis-alkaline reserve value. After therapy started, predialysis-alkaline reserve mean level increased from 19.4 mEq/L to 22.6 mEq/L (p<0.001). Furthermore, we observed a significant decrease of nitrogenous waste products values (T=10.87<1.66) and intradialytic hypotension events (p<0.001). CONCLUSIONS: Our findings emphasize the beneficial effects of correcting metabolic acidosis using the proposed treatment scheme with direct impact on hemodynamic status improvement.

Vascular calcifications in chronic kidney disease--clinical management.

Chronic kidney disease (CKD) patients could present various types of calcifications causing different pathological conditions that would contribute to the renal disease progression and high risk of mortality. Extra-skeletal calcifications represent a common consequence of mineral bone disorders in CKD patients. Vascular calcifications represent a complex systemic manifestation caused by phospho-calcium homeostasis disorders, by imbalance among promoters and inhibitors of calcification and the presence of various arterial diseases and other risk factors. Consequently, vascular calcification can be considered an active pathological process that resembles osteogenesis. Therefore, before starting a suitable therapy for the prevention or delay of vascular calcifications, our recommendations are: to perform lateral abdominal radiography or CT-based techniques in CKD stages 3-5 patients for an early vascular calcification detection, to assess thoroughly patients presenting hyperphosphatemia, hyperparathyroidism, vitamin D deficiency and to understand clearly the pathophysiology of arterial calcification and calciphylaxis.

Potassium level changes--arrhythmia contributing factor in chronic kidney disease patients.

UNLABELLED: As the renal function progressive decline is often correlated to diuresis impairment, potassium level changes represent a major pathophysiological factor in monitoring chronic kidney disease. Even more, potassium level imbalance could lead to life-threatening situations with the risk of severe rhythm disorders appearance. The aim of the study was to determine in which degree the serum potassium changes are implicated in arrhythmias development in CKD patients. PATIENTS AND METHODS: We included 678 CKD patients (predialysis and dialysed patients) to whom we recorded biohumoral and clinical features in correlations with the possibility of arrhythmias genesis. RESULTS: we noticed, in our predialysis group, an important correlation between hyper-/hypokalemia and arrhythmias appearance, more frequent during hypokalemia episodes (OR=4.04, respectively OR=7.5). The same situation was observed in chronic dialysis group. CONCLUSIONS: Hypokalemia is a stronger risk factor than hyperkalemia, but all together, any minimal changes in serum potassium levels could determine arrhythmia in CKD patients.

Evolution of chronic hypertensive nephropathies treated with ACE inhibitors on patients in pre-dialysis stage.

Arterial hypertension (HT), being the main factor of negative evolution for chronic nephropathies, has imposed a careful adjustment of pharmacological treatment. The widespread use of angiotensin conversion enzyme inhibitors (ACE inhibitors) has brought into attention the side effects of this class of antihypertensive drugs. The study focuses on the clinical and paraclinical evaluation of these elements, by means of detecting variations in serum creatinine, natriuresis and diuresis levels factors. In addition, cardiac cavity measurements have been made and the results have lead to the conclusion that the decision to administer ACE inhibitors has to be well founded, and patients should be closely monitored in order to prevent complications of the primary disease.

[Role of ACE inhibitors in the management of arterial hypertension of hemodyalised patients]. / Rolul inhibitorilor de enzima de conversie în managementul hipertensiunii arteriale la hemodializati.

By establishing the renal supleetion procedure, the patients with cronic renal failure also have an acceleration of arterial hypertension. The management of this situation calls for the understanding of the generating mechanisms (hipervolemia by the reduction of natriuresis and hiperreninemia) and the adaptation of the therapeutical approach for every patient. It imposes an individualized dialization prescription taking into account the residual renal function and an antihypertension treatment, in which the role of the conversion enzyme inhibitors is intensely debated.

Arterial hypertension management with conversion enzyme inhibitors in hemodialysis patients.

By establishing the renal suppletion procedure, the patients with chronic renal failure also have an acceleration of arterial hypertension phenomena. The management of this situation calls for the understanding of the ethological mechanisms (hypervolemia by the reduction of Na excretion and high rennin secretion) and the adaptation of the therapeutic approach to every patient. An individualized dialysis prescription is imposed, taking into account the residual renal function and an anti-hypertension treatment, in which the role of the conversion enzyme inhibitors (ACE inhibitor) is intensely debated.