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Acid-base balance is maintained by kidney excretion of titratable acids and bicarbonate reabsorption. Metabolic alkalosis is uncommon in dialysis-treated patients. The aim of this retrospective study was to assess the rate of metabolic alkalosis in pediatric patients treated with peritoneal dialysis.Medical records of children treated with peritoneal dialysis in Shaare Zedek Medical Center from January 2000 to June 2021 were reviewed and compared with young adults currently treated with peritoneal dialysis. Demographic, clinical, and peritoneal dialysis characteristics were extracted from the medical records.Thirty chronic peritoneal dialysis patients were included in our study, seven under 2 years, 13 between 2 and 18 years, and 10 adults. 90.3% of the measurements in infants showed metabolic alkalosis compared to 32.3% in the 2-18-year group and none in the adult group. Higher size-adjusted daily exchange volume, lack of urine output, and high lactate-containing dialysate were associated with metabolic alkalosis. Alkalosis was not explained by vomiting, diuretic therapy, or carbonate-containing medications. High transport membrane, low dietary protein, and malnutrition, all previously reported explanations for metabolic alkalosis, were not found in our study.Metabolic alkalosis is common in infants treated with peritoneal dialysis as opposed to older children and adults. High lactate-containing dialysate is a possible explanation. Higher size-adjusted daily dialysate exchange volume, which may reflect higher bicarbonate absorption, is another independent predictor of alkalosis. Acid-base status should be closely followed in infants, and using a dialysis solution with lower bicarbonate or lactate level should be considered. A higher resolution version of the graphical abstract is available as Supplementary Information.

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.

Keratin-based hair straightening treatment is a popular hair styling method. The majority of these products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe AKI following use of hair-straightening treatment occurring in Israel over the past several years.Case series.We retrospectively identified 26 patients from 14 medical centers in Israel who developed severe AKI and reported prior treatment with hair-straightening products between 2019 and 2022.The 26 patients described had a median age of 28.5 years (range, 14-58) and developed severe AKI following hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients developed a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies that demonstrated intra-tubular calcium oxalate deposition in six and microcalcification in tubular cells in one. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in four cases. Three patients required temporary dialysis.Retrospective uncontrolled study, small number of kidney biopsies.This study describes cases of acute kidney injury with prior exposure to hair straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential under-recognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.

Intravenous (IV) fluid is frequently used to treat patients who have been admitted with an acute infection; among these patients, some will experience pulmonary congestion and will need diuretic treatment. Consecutive admissions to the Internal Medicine Department of patients with an acute infection were included. Patients were divided based on IV furosemide treatment within 48 h after admission. A total of 3556 admissions were included: In 1096 (30.8%), furosemide was administered after ≥48 h, and in 2639 (74.2%), IV fluid was administered within 48 h after hospital admission. In-hospital mortality was higher in patients with furosemide treatment (15.9% vs. 6.8%, p < 0.001). Treatment with furosemide in patients admitted with an infection was found to be associated with prolonged hospital stay and increased in-hospital mortality.

Introduction Since infammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifer of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients. Objective and methods We investigated the efect modifcation by systemic infammation (serum CRP) on the relationship between a surrogate of the flling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantifed by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model. Results At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r=0.23, P

AIM The aim of the present study was to evaluate the incidence, risk factors, clinical characteristics and outcomes of acute kidney injury (AKI) in octogenarians admitted to the emergency room, and to compare these parameters with those in a younger group of patients admitted in the same period. METHODS This is a prospective, observational, single-center study that enrolled adult patients admitted to the emergency room of Shaare Zedek Medical Center, Jerusalem, Israel. Patients were stratified by age (≥80 years or

Sodium–glucose cotransporter-2 (SGLT-2) inhibitors are effective antihyperglycemic agents with proven cardiovascular and renal benefits.1 2 The risk for acute kidney injury (AKI) in patients on SGLT-2 inhibitors is considered to be relatively low. However, there have been postmarketing reports of episodes of AKI, some requiring hospitalisation and even dialysis in patients receiving SGLT-2 inhibitors.3 This phenomenon may be related to volume contraction and haemodynamic changes, particularly in patients with other risk factors (such as patients on renin–angiotensin–aldosterone system blocking agents or non-steroidal anti-inflammatory drugs, patients with chronic kidney disease).4 Here, we present a case of acute interstitial nephritis (AIN) and acute tubular necrosis likely related to a SGLT-2 inhibitor. A 67-year-old woman was admitted with weakness, dizziness and abdominal pain. Her medical history was remarkable for hypertension, diabetes mellitus, ischaemic heart disease and peripheral vascular disease. Her medications …

Urinary tract obstructions (UTO) induce tubular injury. The hypothesis explored in this study is that UTO can cause transient proteinuria. The aims of this study were to determine whether patients with UTO have a higher incidence/severity of proteinuria compared with catheterized patients without UTO and whether proteinuria resolves at short term follow-up.This was a prospective, matched case control study that included 100 patients; 50 with acute UTO and 50 controls. Proteinuria was quantified using three consecutive 24-hour urinary collections during a week of hospitalization and its incidence, severity, and quantitative changes were compared between the study groups.Groups were similar by age (83.12±7.94 versus 84.48±9.39 (p=0.44)), major comorbidities, chronic medical treatment and causes of hospitalization. Abnormal proteinuria was observed in all patients with UTO and 94% of the control group. The degree of proteinuria was similar between the groups in the first, second and third 24-hour urine collections (638±419, 828±743, 728±944 vs. 620±639, 648±741, 732±841 mg/24 hours; p=0.88, 0.23 and 0.99, respectively). Proteinuria did not change significantly during a week of in-hospital follow-up in either study group (p=0.19 for trend).This study demonstrated a very high incidence of significant proteinuria in a cohort of hospitalized patients either with or without acute UTO. Proteinuria does not resolve in the early period after the relief of UTO. Future study with longer follow-up is needed to determine if this proteinuria resolves or persists following hospital discharge and if it has long-term prognostic significance.

Background and Aims SGLT-2 inhibitors are effective anti-hyperglycemic agents with proved cardiovascular and renal benefits. However, there have been post marketing reports of episodes of acute kidney injury (AKI), some requiring hospitalization and even dialysis in patients receiving SGLT2 inhibitors. This phenomenon may be related to volume contraction and hemodynamic changes, particularly in patients with other risk factors (such as patients on RAAS blocking agents or NSAIDS, patients with CKD). We present a case of acute interstitial nephritis (AIN) and acute tubular necrosis related to an SGLT2-inhibitor. Method Case report description. Results A 67-year-old women was admitted with weakness, dizziness and abdominal pain. Her medical history was remarkable for hypertension, diabetes mellitus, ischemic heart disease and peripheral vascular disease. Her medications included bisoprolol, losartan, amlodipine, sitagliptin and aspirin. Two months prior the current presentation, empagliflozin was prescribed by her primary physician for her diabetes mellitus. However, several days after initiation of empgliflozin she felt weak and dizzy and empagliflozin was discontinued. A week before the current presentation, empagliflozin was re-initiated by her cardiologist. The patient reported no recent illness, fevers, rash, arthralgias, respiratory symptoms or bone pain. She denied exposure to other new medications (including NSAIDS and antibiotics). On admission, blood pressure was 165/76 mm Hg. The rest of the physical examination was unremarkable. Laboratory studies revealed acute kidney injury (creatinine 3.19 mg/dL, BUN 28 mg/dL, baseline creatinine 0.9 mg/dL). Complete blood count demonstrated no eosinophilia or thrombocytopenia. Urinalysis showed a few leukocytes but no red cells or casts. The urine protein to creatinine ratio was 5160 mg of protein per gram creatinine. Abdominal ultrasonography showed normal-size kidneys and no hydronephrosis. Immunologic and infectious serologies were unremarkable. over several days the patient became oligo-anuric and creatinine peaked to 9.22 mg/dL and hemodialysis was initiated. Empiric treatment with prednisone was given and a renal biopsy was performed. Four glomeruli were seen on light microscopy. The glomeruli were normocellular. An interstitial infiltrate of lymphocytes and small numbers of eosinophils were seen. Thining of the renal tubular brush border with intra-tubular necrotic content was a also seen. Immunofluorescence was negative. The findings were compatible with acute interstitial nephritis and acute tubular necrosis (Figure 1). The patient was discharged with a regimen of intermittent hemodialysis and steroid therapy. Three months later, urine output and kidney function improved, and the patient was weaned off dialysis. Conclusion In this case report, we describe previously unreported histologically proven AIN likely related to empagliflozin exposure. Although SGLT2 inhibitors have been reported to be associated with AKI it has been supposed to be related to volume contraction and hemodynamic changes. As virtually any drug can cause AIN, further proof of the drug's causation in our case was an onset of renal dysfunction with re- institution of empagliflozin, biopsy-proven AIN and absence of other drugs, infection or systemic disease that might cause AIN. With the dramatic increase in use of SGLT-2 inhibitors worldwide, treating physicians should be aware of AIN as a possible cause of AKI in this context.

Objectives:Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients.Methods:All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed.Results:Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52–76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD.Conclusions:Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.

Background Preoperative hyponatremia adversely affects outcomes of cardiothoracic operation. However, in patients with chronic kidney disease, the association of sodium levels on postoperative events has never been evaluated. We investigated the impact of preoperative hyponatremia on outcomes after cardiac operation in patients with non–dialysis-dependent chronic kidney disease. Primary end points were operative mortality and acute kidney injury that required dialysis. Secondary end points were major infection and long-term survival. Methods The study is observational and includes all patients with stage III to IV chronic kidney disease (non-dialysis) undergoing cardiac operation between February 2000 and January 2016. Patients were stratified into two groups by preoperative sodium levels: sodium less than 135 mEq/L and sodium of 135 mEq/L or more. Results There were 1,008 patients (mean estimated glomerular filtration rate [GFR]: 43 ± 14 mL • min−1 • 1.73 m−2) with 92 patients (9%) in the low-sodium group. Patients with low sodium had higher operative mortality (p = 0.0004), need for new dialysis (p = 0.0008), and infection (p = 0.002). Predictors of operative mortality were European System for Cardiac Operative Risk Evaluation (EuroSCORE) (hazard ratio [HR] 1.03. 95% confidence interval [CI]: 1.02 to 1.05, p Conclusions Preoperative hyponatremia is a predictor of increased mortality and other adverse events in patients with non–dialysis-dependent chronic kidney disease undergoing cardiac operation. These findings are similar to those in hyponatremic patients without kidney disease.

The factors that determine prognosis in elderly patients with dialysis-requiring acute kidney injury (AKI-D) is uncertain. The purpose of this study was to examine predictors of in-hospital mortality in these patients.A retrospective, single-center study of hospitalized patients ≥ 70 years old with AKI-D. Clinical and demographic variables were compared between survivors and non-survivors, independent predictors of hospital mortality were identified by logistic regression.Among 137 eligible patients, hospital mortality was 66%; 59% of survivors were dialysis dependent at hospital discharge and 43% of initial survivors died within 1 year post discharge. There was no significant difference in age between survivors (80.2) and non-survivors (80.5) (p = 0.829). Non-survivors had higher rates of altered mental status (68.2 vs. 22.2%, p0.001), hypotension (29.5 vs. 13.6%, p = 0.048), leucopenia/leukocytosis (62.6 vs. 42.2%, p = 0.024), ICU admission (59.3 vs. 34.8%, p = 0.007), mechanical ventilation (64 vs. 21.7% p0.001), hepatic dysfunction (46.2 vs. 21.7%, p = 0.005), a diagnosis of sepsis (64.8 vs. 26.3%, p = 0.04), and treatment with vasopressors (69.8 vs. 35.6%, p0.001). The presence of ≥ 5 of these conditions was associated with90% mortality. Logistic regression showed altered mental status (OR = 7.4, 95% CI = 3.0 - 18.2) and mechanical ventilation (OR = 6.0; 95% CI = 2.5 - 14.6, p0.001) to independently predict hospital mortality.Elderly patients with AKI-D have a very high rate of hospital mortality or dialysis-dependent survival. Acute illness severity predicts poor outcome despite dialysis. The decision to dialyze patients in this setting should not be based on age alone but consider prognosis and expected quality of life. .

Background Transcatheter aortic valve implantation (TAVI) is a less invasive treatment modality for patients with severe aortic valve stenosis (AS) who are at a higher risk if they have surgery. Preoperative chronic kidney disease (CKD) influences outcomes of cardiac surgery and is associated with a higher mortality and more complicated hospital course. The aims of our study were to evaluate the comparative outcomes of TAVI versus surgical aortic valve replacement (SAVR) in geriatric patients with preoperative CKD. Materials and methods We prospectively collected data on patients > 75 years of age who underwent either SAVR or TAVI at Shaare Zedek Medical Center, Jerusalem, Israel. The outcomes studied were postoperative acute kidney injury (AKI), in-hospital and long-term mortality, and major neurologic and infectious morbidity. Results A total of 318 patients were analyzed, of those, 199 and 119 underwent SAVR and TAVI, respectively. In patients with CKD, there was no statistically significant difference in postoperative AKI. SAVR patients had significantly higher in-hospital mortality (OR 5.9; 95% CI 1.6 - 29.6, p = 0.02), postoperative infection (OR 4.2; 95% CI 1.6 - 12.4, p = 0.005), and longer duration of hospital stay. Mortality at 1 and 2 years was lower in the SAVR group, although the difference was not statistically significant (p = 0.059). Conclusion For elderly patients with CKD who are at a higher risk if they have surgery. TAVI offers a good alternative with lower procedural risk. .

Background Mineralocorticoid receptor antagonists ( MRA s) have emerged as potential atrial fibrillation ( AF ) preventive therapy, but inconsistent results have been reported. We aimed to examine the effects of MRA s on AF occurrence and explore factors that could influence the magnitude of the effect size. Methods and Results PubMed, Embase, and Cochrane Central databases were used to search for randomized clinical trials and observational studies addressing the effect of MRA s on AF occurrence from database inception through April 03, 2018. We performed a systematic review and random effects meta‐analyses to compute odds ratios with 95% CI s. Meta‐regression was then applied to explore the sources of between‐study heterogeneity. We included 24 studies, 11 randomized clinical trials and 13 observational cohorts, representing a total number of 7914 patients (median age: 64.2 years; median left ventricular ejection fraction: 49.7%; median follow‐up: 12.0 months), 2843 (35.9%) of whom received MRA therapy. Meta‐analyses showed a significant overall reduction in AF occurrence in the MRA ‐treated patients versus the control groups (15.0% versus 32.2%; odds ratio, 0.55; 95% CI , 0.44–0.70 [ P AF episodes ( odds ratio , 0.42; 95% CI , 0.31–0.59 [ P I 2 =54%; P =0.0008). Meta‐regression analyses showed that effect size was significantly associated with older studies and higher AF occurrence rate in the control groups. Conclusions MRA s seem to be effective in AF prevention, especially regarding recurrent AF episodes.

BACKGROUND AND AIMS Recent clinical evidence demonstrates that chronic low-dose mineralocorticoid receptor antagonists (MRA), when added to optimal treatment, result in reductions in cardiovascular mortality. However, continuation of MRAs before cardiac surgery in patients with CKD has never been evaluated and its potential benefit or harm in this specific clinical setting is largely unknown. MATERIALS AND METHODS This is an observational study that included adult CKD patients undergoing cardiac surgery. Patients were divided into two groups according to preoperative use of spironolactone (SPL). The studied outcomes were postoperative acute kidney injury (AKI) requiring dialysis, mortality, and major morbidities (cardiovascular, neurologic, and infectious). RESULTS Data on 698 patients with preoperative CKD stage III and IV were analyzed: 99 received SPL preoperatively and 599 did not. At baseline, patients on SPL had higher EuroScore and had more complicated surgery. No significant differences in the incidence of postoperative AKI, myocardial infarction (MI), cardiovascular accident (CVA), sepsis, and mortality were detected between groups in both univariate and multivariate analyses. However, incidence of postoperative low cardiac output state (p

The neutrophil-lymphocyte ratio (NLR) is a recognized marker of inflammation associated with poor outcomes in various clinical situations. We analyzed the prognostic significance of preoperative elevated NLR in patients undergoing cardiac surgery.We performed a retrospective review of 3,027 consecutive patients undergoing cardiac surgery. Receiver-operating-characteristic was used to determine the cutoff value for elevated NLR. Multivariate regression was used to determine the predictive value of preoperative NLR on clinical outcomes. Cox proportional hazards functions were used to determine predictors of late events. Late survival data to 16 years was obtained from the Ministry of Interior.The cutoff value for elevated NLR was 2.6. Patients with elevated NLR were older (p0.0001), had a higher incidence of cardiac comorbidity (p0.0001), and higher European System for Cardiac Operative Risk Evaluation score (p0.0001). An elevated NLR emerged as an independent predictor of operative mortality (hazard ratio [HR] 2.15, 95% confidence interval [CI]: 1.51 to 3.08, p0.0001); pleural effusion (HR 1.42, 95% CI: 1.13 to 1.80, p = 0.003); low output syndrome (HR 1.54, 95% CI: 1.23 to 1.93, p = 0.0002); prolonged ventilation (HR 1.49, 95% CI: 1.23 to 1.82, p = 0.0001); or composite outcomes (HR 1.61, 95% CI: 1.36 to 1.91, p 0.0001). The NLR emerged as an independent predictor of late mortality (HR 1.19, 95% CI: 1.11 to 1.28; p0.0001).Elevated NLR is associated with a higher incidence of adverse outcomes after cardiac surgery. It is a predictor of operative as well as late mortality. Further studies are warranted to determine whether prophylactic treatment with antiinflammatory agents can prevent such outcomes. It may be warranted to include the baseline NLR as another variable in risk stratification of patients about to undergo cardiac surgery.

The increased usage of intravenous iron in hemodialysis patients during recent years has led to increasing concern over the potential development of iron overload. Current methods for detecting iron overload, transferrin saturation, and serum ferritin are neither sensitive nor specific. Labile plasma iron (LPI) represents a component of nontransferrin-bound iron and may be a more accurate indicator of impending iron overload. We studied whether LPI measured can serve as an early indicator of impending iron overload and mortality in hemodialysis patients. Chronic hemodialysis patients from two medical centers in Israel and Poland who received intravenous iron were included. Baseline clinical and laboratory parameters were recorded. LPI was measured before and 48 hours after a single IV administration. Correlation of positive LPI with laboratory parameters and 2-year mortality was evaluated. One hundred and one hemodialysis patients were included in the study. LPI became positive post-administration in 18 (17.8%) patients. Ferritin levels >526 ng/mL and monthly iron doses >250 mg were associated with positive LPI after intravenous iron. At a 2-year follow-up, higher mortality was observed in the positive LPI group (61.1% compared to 25.3%, P ≤ .05), although this effect was not statistically significant after multivariate adjustment. A substantial number of hemodialysis patients have positive LPI after intravenous iron administration. LPI positively correlates with laboratory parameters that are currently in routine clinical use for detecting iron overload and with higher intravenous iron dose. Further studies should be conducted to establish the clinical implications of LPI monitoring in hemodialysis patients.

The Devil Is in the Details A 75-year-old woman was admitted to the hospital with a 4-month history of weight loss (total weight loss, 8 kg) and night sweats. She reported no fever, arthralgias, co...

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

Several previous studies have reported an increase in Hounsfield unit density of the renal papillae in patients with nephrolithiasis compared with controls. Kidney stone formers (KSF) were found to have higher papillary and cortical density in both kidneys, irrespective of which side had calculi, and it was proposed that this might be related to the presence of underlying hypercalciuria. The current study was designed: (1) to determine whether recurrent KSF do have higher papillary density compared with healthy controls; (2) to test an association between higher renal papillary density and the presence of hypercalciuria in KSF. This retrospective case-matched controlled study was carried out at the Royal Free Hospital, London, UK. We investigated 111 patients, 57 of whom were KSF and 54 healthy controls. The CT attenuation values were measured within a 0.2 cm(2) area of the renal papilla in the upper, middle, and lower segments of each kidney, and were compared between KSF and non-stone formers, and between KSF with and without hypercalciuria. There were no significant differences in age and sex between groups. Papillary density was significantly higher in KSF by both crude and adjusted analyses (p 0.001). However, there was no association between higher papillary density and hypercalciuria in KSF. The papillary density measured by CT is a useful, non-invasive tool to differentiate between KSF and healthy controls. The absence of any correlation between papillary density and hypercalciuria suggests that the presence of clinically significant underlying renal stone disease, rather than urinary metabolic abnormalities, correlates with radiologically detectable increased papillary density.

Purpose Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients. Materials and Methods We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy. Results The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9±2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002). Conclusions Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab.

The available publications on nephrocalcinosis are wide-ranging and have documented multiple causes and associations of macroscopic or radiological nephrocalcinosis, most often located in the renal medulla, with various metabolic and genetic disorders; in fact, so many and various are these that it is difficult to define a common underlying mechanism. We have reviewed nephrocalcinosis in relation to its definition, genetic associations, animal models, and putative mechanisms. We have concluded, and hypothesized, that nephrocalcinosis is primarily a renal interstitial process, resembling metastatic calcification, and that it may have some features in common with, and pathogenic links to, vascular calcification.

Recent epidemiologic studies have provided evidence for an association between nephrolithiasis and cardiovascular disease, although the underlying mechanism is still unclear. Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and the hypothesis explored in this study is that VC is more prevalent in calcium kidney stone formers (KSFs). The aims of this study were to determine (1) whether recurrent calcium KSFs have more VC and osteoporosis compared with controls and (2) whether hypercalciuria is related to VC in KSFs.This is a retrospective, matched case-control study that included KSFs attending an outpatient nephrology clinic of the Royal Free Hospital (London, UK) from 2011 to 2014. Age- and sex-matched non-stone formers were drawn from a list of potential living kidney donors from the same hospital. A total of 111 patients were investigated, of which 57 were KSFs and 54 were healthy controls. Abdominal aortic calcification (AAC) and vertebral bone mineral density (BMD) were assessed using available computed tomography (CT) imaging. The prevalence, severity, and associations of AAC and CT BMD between KSFs and non-stone formers were compared.Mean age was 47±14 years in KSFs and 47±13 in non-stone formers. Men represented 56% and 57% of KSFs and non-stone formers, respectively. The prevalence of AAC was similar in both groups (38% in KSFs versus 35% in controls, P=0.69). However, the AAC severity score (median [25th percentile, 75th percentile]) was significantly higher in KSFs compared with the control group (0 [0, 43] versus 0 [0, 10], P0.001). In addition, the average CT BMD was significantly lower in KSFs (159±53 versus 194 ±48 Hounsfield units, P0.001). A multivariate model adjusted for age, sex, high BP, diabetes, smoking status, and eGFR confirmed that KSFs have higher AAC scores and lower CT BMD compared with non-stone formers (P0.001 for both). Among stone formers, the association between AAC score and hypercalciuria was not statistically significant (P=0.86).This study demonstrates that patients with calcium kidney stones suffer from significantly higher degrees of aortic calcification than age- and sex-matched non-stone formers, suggesting that VC may be an underlying mechanism explaining reported associations between nephrolithiasis and cardiovascular disease. Moreover, bone demineralization is more prominent in KSFs. However, more data are needed to confirm the possibility of potentially common underlying mechanisms leading to extraosseous calcium deposition and osteoporosis in KSFs.

A high incidence and adverse outcomes of cognitive impairment in dialysis patients have recently become recognized. Classical risk factors, uremia, anemia, metabolic disturbances, and hemodynamic instability during dialysis accelerate vascular cognitive impairment.To evaluate laboratory factors that influence cognitive function in consecutive chronic hemodialysis (CHD) patients over a 2-year period.Between June 2010 and June 2011 we conducted a prospective, single-center trial that evaluated cognitive function in adult chronic hemodialysis (HD) patients. A battery of cognitive function tests was used: modified mini mental state (3MS), trailmaking tests A (trails A) and B (trails B). The 15-item geriatric depression scale (GDS) and the activities of daily living (ADL) test were used, respectively, for assessing symptoms of depression and global functional status. All tests were performed twice at yearly intervals in consecutive HD patients. Global cognitive impairment was defined as a 3MS80 and impaired executive function as a Trails A performance time75 seconds and Trails B180 seconds.56 chronic HD patients aged 65.00 ± 17.8 years were studied; 57% of them were males. 86% suffered from hypertension (HTN), 40% were diabetics and ~ 1/3 had ischemic heart disease, congestive heart failure (CHF), and dyslipidemia. Average plasma calcium, phosphorus, and PTH were within the recommended range. No features suggestive of malnutrition, severe anemia, inflammation, or inadequate dialysis were detected. 14 patients (24%) had mild chronic hyponatremia (Na ranges 131 - 135 meq/L). Significant disturbances in global cognitive and executive function were detected in the study patients. In 2010, 50% had 3MS80, 71% and 91% had severely impaired trails A and B tests (respectively), 54% had symptoms of depression and 50% suffered from impaired ADL. Retesting of the survivors in 2011 revealed increased prevalence of cognitive and functional declines along with worsening depression scoring. Univariate analysis demonstrated significant correlation between cognitive decline and age, female gender, education, poor executive and functional status, inadequate dialysis dose (Kt/V1.2, p = 0.023), high plasma phosphorus levels (p6 mg/dL, p = 0.034), and hyponatremia (Na135 mEq/L, p = 0.001). Multivariate stepwise logistic regression analysis revealed statistically significant associations between hyponatremia and impaired ADL (p = 0.043) and impaired ADL and mortality (p = 0.002).A high prevalence of global cognitive and executive impairment was detected in our hemodialysis cohort. We found an association between mild chronic hyponatremia and impaired functional status. Whether treatments aimed at modifying hyponatremia could mitigate functional decline or mortality remains to be elucidated.

Meir Nitzan,1 Itzchak Slotki,2 Linda Shavit2 1Department of Applied Physics/Electro-Optics, Jerusalem College of Technology, 2Department of Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel Abstract: The commonly used techniques for systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurement are the auscultatory Korotkoff-based sphygmomanometry and oscillometry. The former technique is relatively accurate but is limited to a physician’s office because its automatic variant is subject to noise artifacts. Consequently, the Korotkoff-based measurement overestimates the blood pressure in some patients due to white coat effect, and because it is a single measurement, it cannot properly represent the variable blood pressure. Automatic oscillometry can be used at home by the patient and is preferred even in clinics. However, the technique’s accuracy is low and errors of 10–15 mmHg are common. Recently, we have developed an automatic technique for SBP measurement, based on an arm pressure cuff and a finger photoplethysmographic probe. The technique was found to be significantly more accurate than oscillometry, and comparable to the Korotkoff-based technique, the reference-standard for non-invasive blood pressure measurements. The measurement of SBP is a mainstay for the diagnosis and follow-up of hypertension, which is a major risk factor for several adverse events, mainly cardiovascular. Lowering blood pressure evidently reduces the risk, but excessive lowering can result in hypotension and consequently hypoperfusion to vital organs, since blood pressure is the driving force for blood flow. Erroneous measurement by 10 mmHg can lead to a similar unintended reduction of SBP and may adversely affect patients treated to an SBP of 120–130 mmHg. In particular, in elderly patients, unintended excessive reduction of blood pressure due to inaccurate SBP measurement can result in cerebral hypoperfusion and consequent cognitive decline. By using a more accurate technique for automatic SBP measurement (such as the photoplethysmographic-based technique), the optimal blood pressure target can be achieved with lower risk for hypotension and its adverse events. Keywords: oscillometry, hypotension, cognitive impairment, photoplethysmography

Neutrophil-to-lymphocyte ratio (NLR) is considered a readily available biomarker of systemic inflammation. An association between elevated NLR and adverse outcomes in a variety of medical and surgical conditions including CKD has been demonstrated in several studies. In this study, we evaluated the accuracy of single Emergency Department (ED) measurement of NLR for early diagnosis of acute kidney injury (AKI). We prospectively studied 294 patients aged 71.6 ± 17. We measured NLR at presentation to the ED. AKI is defined as a new-onset 1.5-fold or more increase in serum creatinine or a 25% decrease in estimated GFR sustained for at least 3 days despite volume resuscitation. The primary outcome is AKI. Secondary outcome is in-hospital mortality. A multivariate model and ROC analysis were performed to evaluate the association and eventual predictive capacity of NLR for the outcomes. 36 patients (12.2%) developed AKI and 26 (9%) died, 8 (22%) of the AKI group and 17 patients (7%) of the non-AKI group. The Mean NLR is significantly higher in AKI compare to non-AKI patients (11.7 ± 15.2 vs 6.45 ± 7.19, p = 0.048). A multivariate model adjusted for age, gender, blood pressure, plasma albumin and hemoglobin levels confirms that the NLR is higher in AKI patients (p = 0.031). Receiver operating characteristics curve reveals an AUC of 0.715 (95% CI 0.63–0.8) sensitivity 0.78, specificity 0.65, and OR 6.423 (CI 2.659–16.026) for a cutoff value of NLR 5.5. The relation between NLR and in-hospital mortality is not statistically significant (p = 0.92). Single ED measurement of NLR might be a useful tool for early diagnosis of AKI. This finding is particularly important in light of the low cost and widespread availability of NLR, especially compared with other biomarkers currently under study in the context of AKI.

Background and objectives Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. Design, setting, participants, & measurements In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound–guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre– and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. Results Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ -statistics ( κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. Conclusions Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

Background Vitamin D (Vit D) deficiency plays a central role in the pathogenesis of chronic kidney disease (CKD) complications, both skeletal and nonskeletal. The purpose of this study was to examine whether 25(OH)D levels and supplementation with oral cholecalciferol (Vitamin D3 (Vit D3)) are associated with morbidity and mortality among patients with significant CKD. Methods CKD patients attending the nephrology clinic at Shaare Zedek Medical Center between July 1, 2008 and January 31, 2012, tested at least twice for 25(OH)D levels, were enrolled. Primary endpoints included death, end-stage renal disease (ESRD) requiring start of dialysis, a rise of at least 50% in serum creatinine, or composite endpoints of the above. Results A total of 516 patients were studied, of whom 178, 257, and 81 patients had baseline vitamin D levels 30 ng/mL, respectively. We found an association between baseline 25(OH)D level below 15 ng/mL and renal outcomes (start of dialysis or a rise of at least 50% in serum creatinine) in both crude and multivariate analyses (hazard ratio (HR) 3.17, 95% CI 1.12 - 8.94). Vit D3 supplementation demonstrated beneficial effects on combined renal outcomes and death in univariate analyses (p = 0.02). Moreover, an increment of 10 ng/mL in 25(OH)D levels was associated with a 25% reduction in mortality (HR 0.755 (95% CI 0.54 - 1.00), in crude but not adjusted analyses. Conclusions Significant Vit D deficiency in CKD can serve as a biological marker indicating patients in whom adverse renal outcomes can be anticipated. Moreover, Vit D3 supplementation and rise of serum 25(OH)D levels may have beneficial influence on hard renal outcomes. .

The next-generation sequencing (NGS) assay targeting cancer-relevant genes has been adopted widely for use in patients with advanced cancer. The primary aim of this study was to assess the clinical utility of commercially available NGS. We retrospectively collected demographic and clinicopathologic data, recommended therapy, and clinical outcomes of 30 patients with a variety of advanced solid tumors referred to Foundation Medicine NGS. The initial pathologic examination was performed at the pathology department of the referring hospital. The comprehensive clinical NSG assay was performed on paraffin-embedded tumor samples using the Clinical Laboratory Improvement Amendments-certified FoundationOne platform. The median number of genomic alterations was 3 (0-19). The median number of therapies with potential benefit was 2 (0-8). In 12 cases, a comprehensive clinical NGS assay did not indicate any therapy with potential benefit according to the genomic profile. Ten of the 30 patients received treatments recommended by genomic profile results. In six of the 10 cases, disease progressed within 2 months and four patients died within 3 months of treatment initiation. Three of the 30 patients benefited from a comprehensive clinical NGS assay and the subsequent recommended therapy. The median PFS was 12 weeks (95% confidence interval 10-57) in patients treated with molecularly targeted agents chosen on the basis of tumor genomic profiling versus 48 weeks (95% confidence interval 8-38) in the control group treated with physician choice therapy (P=0.12). Our study suggests that NGS can detect additional treatment targets in individual patients, but prospective medical research and appropriate clinical guidelines for proper clinical use are vital.

INTRODUCTION: Distal renal tubular acidosis (dRTA) is associated with renal stone disease and it often needs to be considered and excluded in some recurrent calcium kidney stone formers (KSF). However, a diagnosis of dRTA, especially when ‘incomplete’, can be missed and needs to be confirmed by a urinary acidification test. The ‘gold standard’ reference test is still the short ammonium chloride (NH4Cl) test, but it is limited by gastrointestinal side effects and occasionally failure to ingest sufficient NH4Cl. For this reason, the furosemide plus fludrocortisone (F+F) test has been proposed as an easier and better-tolerated screening test. The aim of the present study was to assess the usefulness of the F+F test as a clinical screening tool for dRTA in a renal stone clinic. METHODS: We studied 124 patients retrospectively in whom incomplete dRTA was suspected: 71 had kidney stones only, 9 had nephrocalcinosis only, and 44 had both. A total of 158 urinary acidification tests were performed: 124 F+F and 34 NH4Cl; both tests were completed in 34 patients. RESULTS: Mean age was 45.4 ± 15 years and 49% of patients were male. The prevalence of complete and incomplete dRTA was 7% and 13.7 %, respectively. Of 34 patients tested using both tests, 17 (50%) were abnormal and 4 (12%) were normal. Thirteen (39%) patients were abnormal by F+F, but normal by NH4Cl (sensitivity 100% [95% CI 80% to 100%], specificity 24% [95% CI 7% to 50%]; positive predictive value 57% [95% CI 37% to 75%], negative predictive value 100% [95% CI 40% to 100%]). CONCLUSIONS: The F+F test is characterized by an excellent sensitivity and negative predictive value, and the diagnosis of incomplete dRTA can be excluded reliably in a patient who acidifies their urine normally with this test. However, its lack of specificity is a drawback, and if there is any doubt, an abnormal F+F test may need to be confirmed by a follow-up NH4Cl test. Ideally, a prospective blinded study in unselected KSFs is needed to accurately assess the reliability of the F+F test in diagnosing, rather than excluding, dRTA.

Implantable Port-a-Cath System Insertion in Patients with Metastatic Colon Cancer Receiving Bevacizumab-Based Chemotherapy Combination of bevacizumab with continuous 5- fluoracil (5-FU)-based regimens are considered to be the backbone of colorectal cancer (CRC) systemic therapy. Administration of these continuous intravenous regimens requires insertion of an indwelling central venous catheters and implantable port systems. Certain aspects of the toxicity profile of Bevacizumab could interfere with implantable port-a-cath insertion. The aim of present study was to evaluate the safety port-a-cath insertion shortly before or during bevacizumab treatment in patients with metastatic colon cancer.

Background: Kidney stone disease has an estimated prevalence of around 10%. Genetic as well as environmental factors are thought to play an important role in the pathogenesis of renal stones. Aim: The aim of our study was to analyse and report the main characteristics of patients with kidney stones attending a large UK metabolic stone clinic in London between 1995 and 2012. Design: A cross-sectional study. Methods: Analysis of data from stone formers attending the University College and Royal Free Hospitals’ metabolic stone clinic from 1995 to 2012. Demographic, clinical, dietary and biochemical characteristics have been summarized and analysed for men and women separately; trends over time have also been analysed. Results: Of the 2861 patients included in the analysis, 2016 (70%) were men with an average age of 47 years (range 18–87 years) and median duration of disease of 6 years (range 0–60 years). The prevalence of low urine volume, hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia was 5.6%, 38%, 7.9%, 18% and 23%, respectively. The prevalence of several risk factors for stones increased over time. The majority of stones were mixed, with around 90% composed of calcium salts in varying proportion. Conclusion: Our findings in a large cohort of patients attending a London-based stone clinic over the past 20 years show differences in distributions of risk factors for stones for men and women, as well as metabolic profiles and stone composition. The impact of most risk factors for stones appeared to change over time.

BACKGROUND The prevalence and incidence of kidney stone disease have increased markedly during the past several decades, and studies have demonstrated that inappropriate dietary habits are leading to more obesity and overweight (OW) in children and adults, which may be important in stone formation. Obese and OW patients share most of the same risk factors for cardiovascular morbidity, while the impact of being OW, rather than obese, on urinary metabolic parameters of kidney stone formers (KSF) is less well known. The aims of this study were to investigate urinary metabolic parameters, stone composition and probability of stone formation (Psf) in OW KSF when compared with normal weight (NW) and obese KSF. METHODS The kidney stone database for KSF attending a large metabolic stone clinic was investigated. Patients with a recorded BMI, confirmed diagnosis of kidney stone disease and full metabolic evaluation were divided into three categories: BMI ≤25.0 kg/m(2) (NW group), BMI 25-30 kg/m(2) (OW group) and BMI >30.0 kg/m(2) (obese group). Twenty-four hour urinary volume (U.Vol), pH (U.pH), calcium (U.Ca), oxalate (U.Ox), citrate (U.Cit), uric acid (U.UA), magnesium (U.Mg), sodium (U.Na) and potassium (U.K) excretions, along with stone composition and Psf, were then compared among the groups. RESULTS A total of 2132 patients were studied, of whom 833 (39%) were NW, 863 (40.5%) were OW and 436 (20.5%) were obese. OW and obese KSF were older (mean age 43 ± 15 in NW, 48 ± 13 in OW and 50 ± 12 years in obese; P for trend