Successful treatment with daratumumab of a patient with monoclonal lambda light chain disease presenting as nephrotic syndrome and crescentic glomerulonephritis.

Monoclonal immunoglobulin deposition disease (MIDD) are a group of systemic diseases, characterized by deposition of monoclonal immunoglobulin predominantly in the kidney. In the absence of overt hematologic disease, MIDD are classified as a part of monoclonal gammopathy of renal significance. Patients with MIDD may present with a nephrotic syndrome and kidney function impairment. Treatment usually include anti-plasma cell therapy. Here we report a case of a 54-year-old female who presented with nephrotic syndrome related to light chain deposition disease of lambda type. Due to a complicated clinical course (including cardiac injury and thromboembolic stroke), plasma-cell targeted therapy was stopped. A few months later, the patient presented with severe acute kidney injury. Kidney biopsy revealed crescentic glomerulonephritis, and immunofluorescence staining was positive for lambda chain. Treatment with daratumumab was initiated resulting in stabilization of kidney function and partial nephrotic syndrome remission.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening 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 acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a 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 experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI 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 underrecognized 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.

Dialysis modality, humoral response to vaccine, and SARS-CoV-2 infection risk: Comparative prospective evaluation.

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.

Humoral Response and SARS-CoV-2 Infection Risk following the Third and Fourth Doses of the BNT162b2 Vaccine in Dialysis Patients.

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.

Metabolic alkalosis in infants treated with peritoneal dialysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prospective determination of the incidence and severity of hyponatraemia in older hospitalised patients with acute urinary tract obstruction.

INTRODUCTION: acute urinary tract obstruction (aUTO) is a common finding in older hospitalised patients. Anecdotal reports described hyponatraemia in patients with aUTO, which subsides rapidly with relief of the obstruction.The aim of this study was to determine the incidence, severity and subsequent correction of hyponatraemia in patients with aUTO. METHODS: this is a prospective, single-centre, observational study including inpatients in the internal medicine and geriatric wards. A total of 204 patients were investigated, 104 with aUTO and 100 controls. The prevalence, severity and associations of hyponatraemia between aUTO and control patients were compared. RESULTS: the incidence of hyponatraemia was similar in aUTO and control groups 28% versus 22%, respectively (P = 0.42). However, the incidence of severe hyponatraemia was significantly higher in the study group 7% versus 1% (P = 0.04). Mean sodium level was lower in hyponatremic patients with aUTO 127.7 ± 5.9 mEq/l versus 130.8 ± 3 mEq/l (P = 0.013). Serum sodium remained largely unchanged in the control group (∆Na 1.5 ± 2.3 mEq/l) but increased significantly within 48 hours following catheter insertion in patients with urinary retention (∆Na 5.3 ± 4.2 mEq/l overall in the aUTO group and 9.6 ± 3 mEq/l in those with urinary retention and severe hyponatraemia (P = 0.002)).

A randomized multicenter trial on a lung ultrasound-guided treatment strategy in patients on chronic hemodialysis with high cardiovascular risk.

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.

[PROTEINURIA IN PATIENTS WITH ACUTE URINARY TRACT OBSTRUCTION].

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Preoperative aldosterone receptor blockade and outcomes of cardiac surgery in patients with chronic kidney disease
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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 < 0.008) was significantly higher in the SPL group. Propensity score matching analyses yielded similar results. CONCLUSIONS: Although SPL is usually administered to significantly sicker patients, its use is not associated with increased major postoperative complications. However, the modulating effect of SPL in this clinical study remains to be elucidated in a prospective randomized trial.
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Outcomes of transcatheter aortic valve implantation compared with surgical aortic valve replacement in geriatric patients with chronic kidney disease
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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.
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Outcomes of very elderly treated with dialysis for acute kidney injury
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BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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%, p < 0.001), 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% p < 0.001), 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%, p < 0.001). The presence of ≥ 5 of these conditions was associated with > 90% 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, p < 0.001) to independently predict hospital mortality. CONCLUSION: 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.
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Next-generation sequencing in patients with advanced cancer: are we ready for widespread clinical use? A single institute's experience.

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.

Selective screening for distal renal tubular acidosis in recurrent kidney stone formers: initial experience and comparison of the simultaneous furosemide and fludrocortisone test with the short ammonium chloride test.

BACKGROUND: 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 (KSFs). However, a diagnosis of dRTA, especially when 'incomplete', can be missed and needs to be confirmed by a urinary acidification (UA) 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 UA tests were performed: 124 F+F and 34 NH4Cl; both tests were completed in 34 patients. RESULTS: The mean age was 45.4 ± 15 years, and 49% of patients were male. The prevalence of complete and incomplete dRTAs was 7 and 13.7%, respectively. Of the 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 80-100), specificity 24% (95% CI 7-50), positive predictive value 57% (95% CI 37-75), negative predictive value 100% (95% CI 40-100)]. 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.