Pitfalls of Current Diagnostic Criteria of Tumor Lysis Syndrome.

BACKGROUND: Tumor Lysis syndrome (TLS) is a well-recognized medical emergency in patients with cancer diagnosis. The diagnostic criteria of TLS have been revised many times since it was recognized, but still have many drawbacks limit diagnosis accuracy. SUMMARY: Autopsy studies in patients with perimortem diagnoses of TLS have shown that they may not have actually had TLS. Therefore, many cancer patients who are at risk for TLS, clinical and laboratory criteria may be fulfilled due to other causes of acute kidney injury. In this review, we aim to cast a spotlight on the shortcomings and pitfalls of the current diagnostic criteria for TLS, and propose a roadmap for developing a more rigorous criteria that improve on the diagnostic accuracy. KEY MESSAGES: Causes of AKI in patients with cancer other than TLS should be considered. Because current diagnostic criteria may miss those differential diagnosis, specific biomarkers that can tell when TLS is the underlying process is an important need, besides appropriate criteria that can jump over the pitfalls in the current criteria and enhance the recognition of TLS among other causes.

Hyponatremia Demystified: Integrating Physiology to Shape Clinical Practice.

Hyponatremia is one of the most common problems encountered in clinical practice and one of the least-understood because accurate diagnosis and management require some familiarity with water homeostasis physiology, making the topic seemingly complex. The prevalence of hyponatremia depends on the nature of the population studied and the criteria used to define it. Hyponatremia is associated with poor outcomes including increased mortality and morbidity. The pathogenesis of hypotonic hyponatremia involves the accumulation of electrolyte-free water caused by either increased intake and/or decrease in kidney excretion. Plasma osmolality, urine osmolality, and urine sodium can help to differentiate among the different etiologies. Brain adaptation to plasma hypotonicity consisting of solute extrusion to mitigate further water influx into brain cells best explains the clinical manifestations of hyponatremia. Acute hyponatremia has an onset within 48 hours, commonly resulting in severe symptoms, while chronic hyponatremia develops over 48 hours and usually is pauci-symptomatic. However, the latter increases the risk of osmotic demyelination syndrome if hyponatremia is corrected rapidly; therefore, extreme caution must be exercised when correcting plasma sodium. Management strategies depend on the presence of symptoms and the cause of hyponatremia and are discussed in this review.

Spurious Electrolyte and Acid-Base Disorders in the Patient With Cancer: A Review.

Electrolyte and acid-base disorders are frequently encountered in patients with malignancy, either due to cancer itself or as a complication of its therapy. However, spurious electrolyte disorders can complicate the interpretation and management of these patients. Several electrolytes can be artifactually increased or decreased such that the serum electrolyte values do not correspond to their actual systemic levels, potentially resulting in extensive diagnostic investigations and therapeutic interventions. Examples of spurious derangements include pseudohyponatremia, pseudohypokalemia, pseudohyperkalemia, pseudohypophosphatemia, pseudohyperphosphatemia, and artifactual acid-base abnormalities. Correctly interpreting these artifactual laboratory abnormalities is imperative for avoiding unnecessary and potentially harmful interventions in cancer patients. The factors influencing these spurious results also must be recognized, along with the steps to minimize them. We present a narrative review of commonly reported pseudo electrolyte disorders and describe strategies to exclude erroneous interpretations of these laboratory values and avoid pitfalls. Awareness and recognition of spurious electrolyte and acid-base disorders can prevent unnecessary and harmful treatments.

Safety of Stromal Vascular Fraction Cell Therapy for Chronic Kidney Disease of Unknown Cause (Mesoamerican Nephropathy).

Chronic kidney disease of unknown cause (CKDu), also known as Mesoamerican nephropathy, typically presents as an ischemic nephropathy with chronic tubulointerstitial fibrosis in normotensive patients, rapidly progressing to kidney failure. In this first-in-human, open-label, safety study, we followed 18 patients with CKDu (stages 3-5) for 36 months after receiving a single infusion of angiogenic/anti-fibrotic autologous adipose-derived stromal vascular fraction (SVF) cells into their kidneys bilaterally via renal artery catheterization. SVF therapy was safe and well tolerated. There were no SVF-related serious adverse events and no procedural complications. Color Doppler evaluation at 2 months demonstrated increased perfusion to the interlobar and/or arcuate artery levels in each kidney evaluated (36/36) with a reduction in resistance index at the hilar artery (35/36) kidneys. Beyond 12 months, patients with initial eGFR <30 mL/minute/1.73 m2 deteriorated, whereas those ≥30 mL/minute/1.73 m2 further sustained their renal function, suggesting a possible renal protective effect in that group.

Sodium and Potassium Dysregulation in the Patient With Cancer.

Sodium and potassium disorders are pervasive in patients with cancer. The causes of these abnormalities are wide-ranging, are often primary or second-order consequences of the underlying cancer, and have prognostic implications. The approach to hyponatremia should focus on cancer-related etiologies, such as syndrome of inappropriate antidiuretic hormone, to the exclusion of other causes. Hypernatremia in non-iatrogenic forms is generally due to water loss rather than excessive sodium intake. Debilitated or dependent patients with cancer are particularly vulnerable to hypernatremia. Hypokalemia can occur in patients with cancer due to gastrointestinal disturbances, resulting from decreased intake or increased losses. Renal losses can occur as a result of excessive mineralocorticoid secretion or therapy-related nephrotoxicity. The approach to hyperkalemia should be informed by historical and laboratory clues, and pseudohyperkalemia is particularly common in patients with hematological cancers. Hyperkalemia can be seen in primary or metastatic disease that interrupts the adrenal axis. It can also develop as a consequence of immunotherapy, which can cause adrenalitis or hypophysitis. Tumor lysis syndrome (TLS) is defined by the development of hyperkalemia and is a medical emergency. Awareness of the electrolyte abnormalities that can befall patients with cancer is vital for its prompt recognition and management.

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy.

Novel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all types of cancers. Immune-related adverse events have been associated with immunotherapies. AKI has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations, including immune checkpoint inhibitor-induced parathyroid hormone-related peptide production, sarcoid-like granulomas, and hyperprogression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor-induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy-associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.

Hypomagnesemia in Patients With Cancer: The Forgotten Ion.

Magnesium is crucial for various cellular and enzymatic processes, yet it often is overlooked or underappreciated. Hypomagnesemia, a deficiency of magnesium in the blood, is a frequent problem in cancer patients and can lead to severe symptoms and morbidity. In this review, we provide an in-depth analysis of the physiology and regulation of magnesium, and signs and symptoms of hypomagnesemia in cancer patients. We also examine the causes and mechanisms of magnesium imbalances in cancer patients, specifically focusing on cancer-specific therapies that can lead to hypomagnesemia. Finally, we provide updates on the management of hypomagnesemia, including oral and parenteral supplementation, as well as the role of drugs in cases that are resistant to treatment. This review aims to raise awareness among health care providers caring for cancer patients about the significance of monitoring magnesium levels in cancer patients and function as a guide. Future clinical studies should focus on magnesium monitoring, its impact on cancer progression, and its potential for preventing acute kidney injury.

Hypophosphatemia in cancer patients.

Dysregulation of phosphorus homeostasis resulting in hypophosphatemia is common in cancer patients and can result in serious complications and impact outcomes. Several factors, including critical illness, nutritional status, cancer type and therapy, influence the development of hypophosphatemia. Hypophosphatemia can develop as a result of phosphaturic mesenchymal tumors or as a paraneoplastic phenomenon. The clinical presentation for hypophosphatemia varies depending on the duration and severity of the hypophosphatemia and affects several organ systems. Among other serious effects, hypophosphatemia can impair tissue oxygenation and can cause hemolysis, leukocyte and platelet dysfunction, encephalopathy, seizures, arrhythmias, cardiomyopathy, rhabdomyolysis and coma. Multiple studies have demonstrated that hypophosphatemia is an adverse prognostic marker in inpatients with increased in-hospital stay, mortality and postoperative complications. The phosphate level is homeostatically regulated and maintained in a narrow range by three main hormones: parathyroid hormone, fibroblast growth factor 23 and 1,25-dihydroxyvitaminD3. Together, these hormones regulate how the intestine, kidneys and bones traffic phosphorus. Several hematological malignancies and cancer therapies are associated with proximal tubular dysfunction (Fanconi syndrome), resulting in phosphaturia. Caution should be taken with parenteral administration of phosphate salts, because secondary complications can develop, principally due to hypocalcemia. The general approach to hypophosphatemia should target the underlying cause. Early recognition and prevention are essential and the approach to hypophosphatemia in the cancer patient, because of the nuances and complexity, should be multidisciplinary.

The detrimental association between fear of falling and motor performance in older cancer patients with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) are at increased risk of falls and developing fear of falling (FoF). Although FoF may continue to impair motor performance and increase the risk of falling even further, this association remains unexplored in CIPN. RESEARCH QUESTION: Does high FoF in patients with CIPN further deteriorate motor performance beyond the impairment from CIPN-related sensory deficits? METHODS: In this secondary analysis of data collected from two clinical trials, gait parameters during habitual walking condition and postural sway parameters during 30-second quiet standing (eye-open and eyes-closed) were compared among older participants (≥ 65 years) with CIPN and high FoF (CIPN FoF+; n=16), older participants with CIPN and low FoF (CIPN FoF-; n=19) and normal older controls (i.e., non-cancer, non-diabetic, non-neurologic, and non-orthopedic; n=16). We measured gait and postural sway parameters using wearable sensors (BioSensics, Newton, MA, USA), and FoF severity using the Falls Efficacy Scale-International. RESULTS: The largest between-group differences were found in gait speed. The CIPN FoF + group had significantly slower gait speed (0.78 ± 0.21 m/s) than the CIPN FoF- (0.93 ± 0.17 m/s) and normal control groups (1.17 ± 0.13 m/s) (all p < .05; effect sizes = 0.79 and 2.23, respectively). We found a significant association between gait speed and FoF severity (R2 = 0.356; p < .001) across all participants with CIPN. Among participants with CIPN, no significant differences in postural sway parameters were found between the CIPN FoF+and CIPN FoF- groups. SIGNIFICANCE: Our results suggest that gait performance further deteriorates in patients with CIPN and high FoF beyond the impairment from CIPN-related sensory deficits. Our results also suggest further research is needed regarding FoF, and fall risk, as FoF is a simple tool that healthcare providers can use in clinical practice.

Harnessing digital health to objectively assess cancer-related fatigue: The impact of fatigue on mobility performance.

OBJECTIVE: Cancer-related fatigue (CRF) is highly prevalent among cancer survivors, which may have long-term effects on physical activity and quality of life. CRF is assessed by self-report or clinical observation, which may limit timely diagnosis and management. In this study, we examined the effect of CRF on mobility performance measured by a wearable pendant sensor. METHODS: This is a secondary analysis of a clinical trial evaluating the benefit of exercise in cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN). CRF status was classified based on a Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score ≤ 33. Among 28 patients (age = 65.7±9.8 years old, BMI = 26.9±4.1kg/m2, sex = 32.9%female) with database variables of interest, twenty-one subjects (75.9%) were classified as non-CRF. Mobility performance, including behavior (sedentary, light, and moderate to vigorous activity (MtV)), postures (sitting, standing, lying, and walking), and locomotion (e.g., steps, postural transitions) were measured using a validated pendant-sensor over 24-hours. Baseline psychosocial, Functional Assessment of Cancer Therapy-General (FACT-G), Falls Efficacy Scale-International (FES-I), and motor-capacity assessments including gait (habitual speed, fast speed, and dual-task speed) and static balance were also performed. RESULTS: Both groups had similar baseline clinical and psychosocial characteristics, except for body-mass index (BMI), FACT-G, FACIT-F, and FES-I (p<0.050). The groups did not differ on motor-capacity. However, the majority of mobility performance parameters were different between groups with large to very large effect size, Cohen's d ranging from 0.91 to 1.59. Among assessed mobility performance, the largest effect sizes were observed for sedentary-behavior (d = 1.59, p = 0.006), light-activity (d = 1.48, p = 0.009), and duration of sitting+lying (d = 1.46, p = 0.016). The largest correlations between mobility performance and FACIT-F were observed for sitting+lying (rho = -0.67, p<0.001) and the number of steps per day (rho = 0.60, p = 0.001). CONCLUSION: The results of this study suggest that sensor-based mobility performance monitoring could be considered as a potential digital biomarker for CRF assessment. Future studies warrant evaluating utilization of mobility performance to track changes in CRF over time, response to CRF-related interventions, and earlier detection of CRF.

Hypomagnesemia in the Cancer Patient.

Hypomagnesemia is a common medical problem that contributes to the morbidity and mortality of patients with cancer. This review summarizes magnesium physiology and highlights the mechanisms underlying magnesium disturbances due to cancer and cancer treatment. The causes of hypomagnesemia can be categorized according to the pathophysiologic mechanism: decreased intake, transcellular shift, gastrointestinal losses, and kidney losses. Patients with cancer are at risk for opportunistic infections, frequently experience cardiovascular complications, and often receive classes of medications that cause or exacerbate hypomagnesemia. Also, cancer-specific therapies are responsible for hypomagnesemia, including platinum-based chemotherapy, anti-EGF receptor mAbs, human EGF receptor-2 target inhibitors (HER2), and calcineurin inhibitors. Urinary indices, such as the fractional excretion of magnesium, can provide useful information about the etiology. The management of hypomagnesemia depends on the magnitude of hypomagnesemia and the underlying cause. We recommended checking serum magnesium at the beginning of treatment and as part of routine monitoring throughout cancer treatment. Opportunities exist for potential research and practice improvement, including further characterization of hypomagnesemia regarding the clinical effect on cancer outcomes, preventing hypomagnesemia in patients receiving high-risk anticancer agents, and developing effective therapeutic strategies.

Healthy Eating Index of Living Donor Renal Transplantation Recipients During the First Year Posttransplant.

BACKGROUND: The aim of this study was to examine the relationship between diet quality and weight gain in kidney transplant recipients from pretransplant baseline through posttransplant at 3 months and 1 year. METHODS: Data from a prospective, observational cohort study of kidney transplant patients (n = 26) were analyzed. Participants were adult (aged 18-65 years), living donor kidney transplant recipients who were participating in a prospective body composition study. Body weight, body mass index, dietary intake, and Healthy Eating Index scores were used to assess changes in weight, nutrient intake, and diet quality. FINDINGS: At the time of kidney transplantation, 42% (n = 11) were obese and 27% (n = 7) were overweight. Weight significantly increased from transplantation to 12 months (mean [SD]: 83 [18] kg and 90 [18] kg, respectively; mean change 8.4%, P = .002). At 12 months posttransplant, dietary fat intake significantly increased (P = .033). Body weight was strongly correlated with total dietary fat intake (r = 0.56, P = .003). The Healthy Eating Index total scores at baseline and 1-year posttransplant were not significantly different (45.75 [14.99] and 42.59 [12.70]). Likewise, component scores did not change from pretransplant to posttransplant. DISCUSSION: Diet quality of transplant recipients was poor both before and after transplantation. Using the Healthy Eating Index confirmed that improvements in food intake are needed. Further research is warranted to identify dietary recommendations for the prevention of excessive weight gain and the potential adverse health complications following kidney transplantation.

Hyponatremia in the cancer patient.

Hyponatremia is a common electrolyte disorder observed in a wide variety of malignancies and is associated with substantial morbidity and mortality. Newer cancer therapies have improved patient outcomes while contributing to new cases of hyponatremia. Patients should be monitored closely for the development of vasopressin- and non-vasopressin-mediated hyponatremia. Acute and symptomatic forms of hyponatremia require urgent intervention, and recent findings support the correction of chronic "asymptomatic" hyponatremia. Optimizing hyponatremia may reduce medical costs, and improve cancer survival likelihood and quality of life. In this article, we review the epidemiology, pathophysiology, etiology, diagnosis, and treatment of hyponatremia in the cancer patient.

Successful Kidney Transplantation Is Associated With Weight Gain From Truncal Obesity and Insulin Resistance.

OBJECTIVE: The objective of this study is to compare changes in body composition, lifestyle factors, and metabolic responses occurring in living kidney transplant recipient patients after transplantation. DESIGN AND METHODS: The study was a single-site, prospective, observational study. To identify metabolic responses during the initial years after transplantation, we obtained state-of-the-art, high-resolution measurements of body composition from a 4-compartment model using dual-energy X-ray absorptiometry, air displacement plethysmography, and total body potassium and nitrogen counters. We also assessed dietary recalls and actigraphy before transplantation and 3- and 12-month after transplantation. The study was conducted at a quaternary care hospital outpatient transplant center and a United States Department of Agriculture Agricultural Research Service center. Thirty-one adults receiving a living donor kidney allograft were studied. The main outcome measures were change in body composition at 3 months and 1 year after transplantation, and this was correlated with the occurrence of insulin resistance. RESULTS: In patients receiving a successful kidney transplant from living donors treated with standard immunosuppression, significant increases in body weight were detected at 3 and 12 months after transplantation (2.2 kg, P = .03 and 6.6 kg, P < .0001, respectively). Weight gain was principally due to adipose tissue accumulation in the truncal region. There was no increase in muscle mass or fluid accumulation. Weight gain was not associated with changes in resting energy expenditure or physical activity. Notably, increases in visceral and subcutaneous adipose tissue were positively correlated with insulin resistance. CONCLUSION: Successful transplantation was associated with increased insulin resistance and weight gain without increases in muscle or fluid. This metabolic pattern suggests potential interventions that could prevent or mitigate the consequences of adipose tissue accumulation in transplant recipients.

Using wearables to screen motor performance deterioration because of cancer and chemotherapy-induced peripheral neuropathy (CIPN) in adults - Toward an early diagnosis of CIPN.

OBJECTIVE: An essential component for optimizing quality of life in adults with cancer is determining the degree to which therapy may negatively impact motor-performance, so that patients can maintain their quality of life and independence. This study examined whether instrumented gait and balance could determine the magnitude of deterioration in motor-performance from chemotherapy-induced peripheral neuropathy (CIPN). METHODS: We recruited 84 adults with cancer (age = 71.1 ±â€¯9.7 years old, BMI = 26.8 ±â€¯6.2 kg/m2, gender = 56%female) and 57 age-matched non-cancer patients (age = 69.5 ±â€¯9.8 years old, BMI = 27.1 ±â€¯6.0 kg/m2, gender = 79%female). Based on clinical screening, the group with cancer was classified into two groups: participants with CIPN (CIPN+) and without CIPN (CIPN-). Gait and balance were quantified using validated wearables. The Vibration Perception Threshold (VPT) test was used to stratify the CIPN+ group into mild (Mild-CIPN) and severe (Severe-CIPN) subgroups. RESULTS: All gait and balance parameters were deteriorated in the group with cancer compared to non-cancer group with the largest effects observed for stride-time (11%, Cohen's effect size d = 1.00, p < 0.001) and eyes-closed ankle sway (94%, d = 0.49, p = 0.001). The same trend was observed when the Severe-CIPN subgroup was compared to the Mild-CIPN. VPT correlates significantly with motor deterioration, with the largest correlation found in stride-time (Rho = 0.37, p = 0.007). Severe-CIPN subjects were significantly older and overall had more deterioration in the majority of motor-performance parameters after adjusting for age (p < 0.050). CONCLUSION: These results confirmed the negative impact of CIPN on motor-performance with the largest effects on ankle stability and stride-time. VPT is a predictor of motor deterioration and may be used to determine the severity of CIPN symptom.