Vascular calcification in kidney stone formers: the impact of age and stone composition.

An increased prevalence of vascular calcification (VC) has been reported in kidney stone formers (KSFs), along with an elevated cardiovascular risk. The aim of the current study is to assess whether VC in these patients develops at a younger age and is influenced by stone composition. This single-center, matched case-control study included KSFs with uric acid or calcium oxalate stones (diagnosed based on stone analysis) and age- and sex-matched controls without a history of nephrolithiasis. The prevalence and severity of abdominal aortic calcification (AAC) and bone mineral density (BMD) were compared between KSFs and non-KSFs. In total, 335 patients were investigated: 134 with calcium oxalate stones, 67 with uric acid stones, and 134 controls. Overall, the prevalence of AAC was significantly higher among calcium stone formers than among the controls (67.9% vs. 47%, p = 0.002). In patients under 60 years of age, those with calcium oxalate stones exhibited both a significantly elevated AAC prevalence (61.9% vs. 31.3%, p = 0.016) and severity (94.8 ± 15.4 vs. 30.3 ± 15.95, p = 0.001) compared to the controls. Within the age group of 40-49, osteoporosis was identified only in the KSFs. Multivariate analysis identified age, smoking, and the presence of calcium stones as independent predictors of AAC. This study highlights that VC and osteoporosis occur in KSFs at a younger age than in non-stone-formers, suggesting potential premature VC. Its pathogenesis is intriguing and needs to be elucidated. Early evaluation and intervention may be crucial for mitigating the cardiovascular risk in this population.

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.

Pseudohyperkalemia in chronic lymphocytic leukemia: Prevalence, impact, and management challenges.

The term pseudohyperkalemia refers to a false elevation in serum potassium levels due to potassium release from cells in vitro. Falsely elevated potassium levels have been reported in patients with thrombocytosis, leukocytosis, and hematologic malignancies. This phenomenon has been particularly described in chronic lymphocytic leukemia (CLL). Leukocyte fragility, extremely high leukocyte counts, mechanical stress, higher cell membrane permeability related to an interaction with lithium heparin in plasma blood samples, and metabolite depletion due to a high leukocyte burden have been reported to contribute to pseudohyperkalemia in CLL. The prevalence of pseudohyperkalemia is up to 40%, particularly in the presence of a high leukocyte count (>50 × 109/L). The diagnosis of pseudohyperkalemia is often overlooked, which may result in unnecessary and potentially harmful treatment. The use of whole blood testing and point-of-care blood gas analysis, along with thorough clinical evaluation, may help differentiate between true and pseudohyperkalemic episodes.

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.

Incidence, risk factors, and recognition of pseudohyperkalemia in patients with chronic lymphocytic leukemia.

Pseudohyperkalemia, a false elevation of potassium level in vitro, can be observed in chronic lymphocytic leukemia (CLL) patients due to fragility of leukocytes along with a high leukocyte count. This retrospective, observational study included all patients diagnosed with CLL at our hospital who had at least one leukocyte count ≥ 50.0 × 109/L during the years 2008-2018. All hyperkalemic episodes (including when leukocyte count was below 50.0 × 109/L) during this period were assessed. Pseudohyperkalemia was defined as when a normal potassium level was measured in a repeated blood test or when known risk factors and ECG changes typical of hyperkalemia were absent. Of the 119 episodes of hyperkalemia observed, 41.2% were considered as pseudohyperkalemia. Pseudohyperkalemia episodes were characterized by significantly higher leukocyte counts as well as higher potassium and LDH levels compared to true hyperkalemia. Pseudohyperkalemia was documented in medical charts only in a minority of cases (n = 4, 8.1%). Treatment was administered in 17 of 49 (34.7%) cases and caused significant hypokalemia in 6 of those cases. The incidence of pseudohyperkalemia in this study was rather high, suggesting that physicians should be more aware of this phenomenon in patients with CLL.

Labile plasma iron levels in chronic hemodialysis patients treated by intravenous iron supplementation.

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.

Outcomes of transcatheter aortic valve implantation compared with surgical aortic valve replacement in geriatric patients with chronic kidney disease
.

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.
.

Hyponatremia Predicts Poor Outcomes in Patients With Chronic Kidney Disease Undergoing Heart Operation.

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 < 0.0001), decreasing values of sodium (HR 1.14. 95% CI: 1.07 to 1.2, p = 0.0002), and decreasing values of GFR (HR 1.01, 95% CI: 1.003 to 1.03, p = 0.007). Sodium less than 135 mEq/L was independently associated with increased need for dialysis (HR 1.3, 95% CI: 1.1 to 1.7, p = 0.0008). By linear regression, decreasing values of preoperative sodium were proportionate to the incidence of operative mortality (p < 0.0001) and need for dialysis (p < 0.0001). 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.

Preoperative aldosterone receptor blockade and outcomes of cardiac surgery in patients with chronic kidney disease
.

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.
.

Neutrophil-Lymphocyte Ratio: Prognostic Impact in Heart Surgery. Early Outcomes and Late Survival.

BACKGROUND: 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. METHODS: 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. RESULTS: The cutoff value for elevated NLR was 2.6. Patients with elevated NLR were older (p < 0.0001), had a higher incidence of cardiac comorbidity (p < 0.0001), and higher European System for Cardiac Operative Risk Evaluation score (p < 0.0001). 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, p < 0.0001); 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; p < 0.0001). CONCLUSIONS: 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.

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.

Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy.

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.

What is nephrocalcinosis?

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.