Cancer therapy in patients with reduced kidney function.

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

Assessment of Glomerular Filtration Rate in Patients with Cancer: A Statement from the American Society of Onco-Nephrology.

Accurate assessment of glomerular filtration rate (GFR) is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of cancer patients have baseline chronic kidney disease (CKD), and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface-area (BSA)-adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD-EPI equations, with 2,508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (8 studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the ASON Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.

Long-Term Cardiovascular Outcomes in Children and Adolescents With Hypertension.

Importance: Hypertension affects 6% of all children, and its prevalence is increasing. Childhood hypertension tracks into adulthood and is associated with subclinical cardiovascular disease; however, there is a lack of evidence linking childhood hypertension to cardiovascular outcomes, which may contribute to underdiagnosis and undertreatment. Objective: To determine the long-term associated risk of major adverse cardiac events (MACE) among children diagnosed with hypertension. Design, Setting, and Participants: This was a population-based, retrospective, matched cohort study conducted from 1996 to 2022. The study included all children (aged 3-18 years) alive in Ontario, Canada, from 1996 to 2021, who were identified using provincial administrative health databases. Children with prior kidney replacement therapy were excluded. Exposure: Incident hypertension diagnosis, identified by validated case definitions using diagnostic and physician billing claims. Each case was matched with 5 controls without hypertension by age, sex, birth weight, maternal gestational hypertension, prior comorbidities (chronic kidney disease, diabetes, cardiovascular surgery), and a propensity score for hypertension. Main Outcomes and Measures: The primary outcome was MACE (a composite of cardiovascular death, stroke, hospitalization for myocardial infarction or unstable angina, or coronary intervention). Time to MACE was evaluated using the Kaplan-Meier method and Cox proportional hazards regression. Results: A total of 25 605 children (median [IQR] age, 15 [11-17] years; 14 743 male [57.6%]) with hypertension were matched to 128 025 controls without hypertension. Baseline covariates were balanced after propensity score matching, and prior comorbidities were uncommon (hypertension vs control cohort: malignancy, 1451 [5.7%] vs 7908 [6.2%]; congenital heart disease, 1089 [4.3%] vs 5408 [4.2%]; diabetes, 482 [1.9%] vs 2410 [1.9%]). During a median (IQR) of 13.6 (7.8-19.5) years of follow-up, incidence of MACE was 4.6 per 1000 person-years in children with hypertension vs 2.2 per 1000 person-years in controls (hazard ratio, 2.1; 95% CI, 1.9-2.2). Children with hypertension were at higher associated risk of stroke, hospitalization for myocardial infarction or unstable angina, coronary intervention, and congestive heart failure, but not cardiovascular death, compared with nonhypertensive controls. Conclusions and Relevance: Children diagnosed with hypertension had a higher associated long-term risk of MACE compared with controls without hypertension. Improved detection, follow-up, and control of pediatric hypertension may reduce the risk of adult cardiovascular disease.

Capacity for the management of kidney failure in the International Society of Nephrology Middle East region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems.

Approach to Diagnosis and Management of Hypertension: A Comprehensive and Combined Pediatric and Adult Perspective.

The global prevalence of primary hypertension has been increasing both in children and in the adolescent and adult populations and can be attributed to changes in lifestyle factors with an obesity epidemic, increased salt consumption, and sedentary lifestyles. Childhood blood pressure is the strongest predictor of adult hypertension. Although hypertension in adults is associated strongly with an increased risk for cardiovascular disease, chronic kidney disease, and mortality, outcomes in children are defined less clearly. In adults, major guidelines agree on a threshold of less than 120/80 mm Hg as the optimal blood pressure (BP) and recommend a target of less than 130/80 mm Hg for treatment in most cases. In children, international pediatric guidelines recommend using thresholds based on the normative distribution of BP in healthy normal-weight children. Out-of-office BP assessment is extremely useful for confirming the diagnosis of hypertension and monitoring response to treatment. Lifestyle modifications are instrumental whether coupled or not with pharmacologic management. New agents such as nonsteroidal mineralocorticoid-receptor antagonists, aminopeptidase A inhibitors, aldosterone synthase inhibitors, and dual endothelin antagonists hold significant promise for resistant hypertension. The transition from pediatric to adult care can be challenging and requires careful planning and effective coordination within a multidisciplinary team that includes patients and their families, and pediatric and adult providers.

Sustainable Development Goals: Challenges and the Role of the International Society of Nephrology in Improving Global Kidney Health.

The United Nations 2030 agenda for sustainable development includes 17 sustainable development goals (SDGs) that represent a universal call to end poverty and protect the planet, and are intended to guide government and private sector policies for international cooperation and optimal mobilization of resources. At the core of their achievement is reducing mortality by improving the global burden of noncommunicable diseases (NCDs), the leading causes of death and disability worldwide. CKD is the only NCD with a consistently rising age-adjusted mortality rate and is rising steadily up the list of the causes of lives lost globally. Kidney disease is strongly affected by social determinants of health, with a strong interplay between CKD incidence and progression and other NCDs and SDGs. Tackling the shared CKD and NCD risk factors will help with progress toward the SDGs and vice versa . Challenges to global kidney health include both preexisting socioeconomic factors and natural and human-induced disasters, many of which are intended to be addressed through actions proposed in the sustainable development agenda. Opportunities to address these challenges include public health policies focused on integrated kidney care, kidney disease surveillance, building strategic partnerships, building workforce capacity, harnessing technology and virtual platforms, advocacy/public awareness campaigns, translational and implementation research, and environmentally sustainable kidney care.

Anxiety, depression and post-traumatic stress disorder in patients on hemodialysis in the setting of the pandemic, inflation, and the Beirut blast: a cross-sectional study.

BACKGROUND: In 2020, Lebanon has witnessed its worst economic crisis, exacerbated by the COVID-19 pandemic and a massive explosion of its capital. Amidst these stressors, this study aims at assessing the prevalence of depression, anxiety, suicidality, post-traumatic stress disorder (PTSD) and cognitive impairment in patients undergoing hemodialysis in an academic hospital destroyed by the explosion. METHODS: This cross-sectional study conducted 6 months after the blast included adults on hemodialysis, with no previous diagnoses of dementia or intellectual disability. It explores prevalence rates of psychiatric disorders, in addition to other medical and psychosocial variables such as frailty, malnutrition, sarcopenia, quality of life and religiosity. RESULTS: Forty two patients (mean age 66.1; SD: 11.2 years) undergoing hemodialysis for 6.12 years (SD:7.22 years) were included. Anxiety and depression rates reached 54.8% and 57.1% using cut-offs of 6 and 7 respectively on the Hospital Anxiety and Depression rating Scale. 9.5% of the patients reported being in the hospital at the time of the blast and 7.1% reported being injured. 33.3% screened positively for PTSD using a cut-off of 23 on the PCL-5. 26.2% had passive death wishes and 7.1% had suicide plans, however no one had attempted it. 23.8% were found cognitively impaired as shown by the Mini-Cog (<3). Around two-third of participants were moderately to severely malnourished per the GLIM criteria. One third suffered from frailty, according to the FRAIL screening tool. Around 60% suffered from sarcopenia, based on handgrip strength measures. These findings contrast with "acceptable to good" quality of life subjectively reported by participants on the Short Form 36 (SF-36) Health Survey. While one-third of participants participated in organizational religious activities, 88% reported significant subjective meaning of religion in their heart. CONCLUSIONS: Rates of depression, anxiety, PTSD, suicidality, and cognitive impairment were found to be alarming in the setting of an urban dialysis unit following a major explosion. Psychiatric disorders were found to be compounded with increased prevalence of malnutrition, frailty, and sarcopenia. These findings urge healthcare providers to implement early diagnostic and intervention strategies to improve both mental and physical wellbeing of this vulnerable population, in similar settings.

Monoclonal gammopathy of renal significance: Multidisciplinary approach to diagnosis and treatment.

Monoclonal gammopathy of renal significance (MGRS) is a hemato-nephrological term referring to a heterogeneous group of kidney disorders characterized by direct or indirect kidney injury caused by a monoclonal immunoglobulin (MIg) produced by a B cell or plasma cell clone that does not meet current hematologic criteria for therapy. MGRS-associated kidney diseases are diverse and can result in the development of end stage kidney disease (ESKD). The diagnosis is typically made by nephrologists through a kidney biopsy. Many distinct pathologies have been identified and they are classified based on the site or composition of the deposited Mig, or according to histological and ultrastructural findings. Therapy is directed towards the identified underlying clonal population and treatment decisions should be coordinated between hematologists and nephrologists in a multidisciplinary fashion, depend on the type of MGRS, the degree of kidney function impairment and the risk of progression to ESKD.

Renal AA amyloidosis: presentation, diagnosis, and current therapeutic options: a review.

Amyloid A amyloidosis is thought to be the second most common form of systemic amyloidosis behind amyloidosis secondary to monoclonal Ig. It is the result of deposition of insoluble fibrils in the extracellular space of tissues and organs derived from the precursor protein serum amyloid A, an acute phase reactant synthesized excessively in the setting of chronic inflammation. The kidney is the most frequent organ involved. Most patients present with proteinuria and kidney failure. The diagnosis is made through tissue biopsy with involvement of the glomeruli in most cases, but also often of the vessels and the tubulointerstitial compartment. The treatment usually targets the underlying etiology and consists increasingly of blocking the inflammatory cascade of cytokines with interleukin-1 inhibitors, interleukin-6 inhibitors, and tumor necrosis factor-α inhibitors to reduce serum amyloid A protein formation. This strategy has also shown efficacy in cases where an underlying etiology cannot be readily identified and has significantly improved the prognosis of this entity. In addition, there has been increased interest at developing effective therapies able to clear amyloid deposits from tissues, albeit with mitigated results so far.

Hypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control.

The World Health Organization (WHO) refers to obesity as abnormal or excessive fat accumulation that presents a health risk. Obesity was first designated as a disease in 2012 and since then the cost and the burden of the disease have witnessed a worrisome increase. Obesity and hypertension are closely interrelated as abdominal obesity interferes with the endocrine and immune systems and carries a greater risk for insulin resistance, diabetes, hypertension, and cardiovascular disease. Many factors are at the interplay between obesity and hypertension. They include hemodynamic alterations, oxidative stress, renal injury, hyperinsulinemia, and insulin resistance, sleep apnea syndrome and the leptin-melanocortin pathway. Genetics, epigenetics, and mitochondrial factors also play a major role. The measurement of blood pressure in obese patients requires an adapted cuff and the search for other secondary causes is necessary at higher thresholds than the general population. Lifestyle modifications such as diet and exercise are often not enough to control obesity, and so far, bariatric surgery constitutes the most reliable method to achieve weight loss. Nonetheless, the emergence of new agents such as Semaglutide and Tirzepatide offers promising alternatives. Finally, several molecular pathways are actively being explored, and they should significantly extend the treatment options available.