Incorporating genetic testing into a routine kidney clinic.

Incorporating genetic testing in routine outpatient nephrology clinic can improve on chronic kidney disease (CKD) diagnosis and utilization of precision medicine. We sent a genetic test on patients with atypical presentation of common kidney diseases, electrolytes derangements, and cystic kidney diseases. We were able to identify a gene variant contributing to patients' kidney disease in more than half of our cohort. We then showed that patients with ApoL1 risk allele have likely worse kidney disease, and we were able to confirm genetic focal segmental glomerulosclerosis (FSGS) in 2 patients and avoid unnecessary immunosuppression. Genetic testing has also improved our operation to establish a polycystic kidney disease excellence center by confirming our diagnosis, especially in patients without a well-defined family history. In conclusion, utilizing genetic testing in a routine outpatient renal clinic did not cause any burden to either patients or nephrologists, with minimal administrative effort and no financial cost to our patients. We expect that genetic testing in the right setting should become routine in nephrology to achieve a patient-centered precision medicine with less invasive means of kidney disease diagnosis.

Prevention of Intradialytic Hypotension in Hemodialysis Patients: Current Challenges and Future Prospects.

Intradialytic hypotension, defined as rapid decrease in systolic blood pressure of greater than or equal to 20 mmHg or in mean arterial pressure of greater than or equal to 10 mmHg that results in end-organ ischemia and requires countermeasures such as ultrafiltration reduction or saline infusion to increase blood pressure to improve patient's symptoms, is a known complication of hemodialysis and is associated with several potential adverse outcomes. Its pathogenesis is complex and involves both patient-related factors such as age and comorbidities, as well as factors related to the dialysis prescription itself. Key factors include the need for volume removal during hemodialysis and a suboptimal vascular response which compromises the ability to compensate for acute intravascular volume loss. Inadequate vascular refill, incorrect assessment or unaccounted changes of target weight, acute illnesses and medication interference are further potential contributors. Intradialytic hypotension can lead to compromised tissue perfusion and end-organ damage, both acutely and over time, resulting in repetitive injuries. To address these problems, a careful assessment of subjective symptoms, minimizing interdialytic weight gains, individualizing dialysis prescription and adjusting the dialysis procedure based on patients' risk factors can mitigate negative outcomes.

A Critical Review of Medication Adherence in Hypertension: Barriers and Facilitators Clinicians Should Consider.

Hypertension is a global public health problem, and its prevalence is increasing worldwide. Impacting all human societies and socioeconomic strata, it remains the major modifiable risk factor for global burden of cardiovascular disease all-cause mortality and the leading cause of loss of disability-adjusted life years. Despite increased awareness, the rate of blood pressure control remains unsatisfactory, particularly in low- to middle-income countries. Apparent treatment-resistant hypertension is associated with worse adverse health outcomes. It includes both true resistant and pseudo-resistant hypertension, which requires out-of-office blood pressure monitoring to exclude white-coat effect and confirmation of adherence to the agreed recommended antihypertensive therapy. The depth of medication non-adherence remains poorly recognized among medical practitioners, thus presenting an underestimated modifiable risk factor. Medication non-adherence is a complex and multidimensional variable with three quantifiable phases: initiation, implementation, and discontinuation, collectively called persistence. Non-adherence can be both intentional and non-intentional and usually involves several interconnected factors. Persistence declines over time in the treatment of chronic diseases like hypertension. The risk is higher in patients with new diagnosis, poor insurance status, polypharmacy, and multiple comorbidities, particularly psychiatric disorders. The World Health Organization divides the contributing factors impacting adherence into five categories. Screening and detection for medication non-adherence are challenging due to its dynamic nature and potential white-coat effect. Easy-to-conduct screening methods have low reliability and validity, whereas more reliable and valid methods are costly and difficult to perform. Medication non-adherence is associated with poor clinical outcome and potential negative impact on health-care costs. Evaluation of adherence should become an integral part of assessment of patients treated for hypertension. Medication adherence can significantly improve with a patient-centered approach, non-judgmental communication skills, and collaborative multidisciplinary management, including engagement of the patients in their care by self-blood pressure monitoring.

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Intensive Care Unit Admission Diagnosis: A Prospective Cohort Study.

Background: Acute kidney injury (AKI) is most commonly caused by tubular injury and is associated with a wide variety of critical illnesses. It is well known that urinary biomarkers can lead to the early identification of AKI. However, the ability of urinary biomarkers to distinguish between different types of critical illness has been less studied. Methods: In this prospective cohort study, urinary neutrophil gelatinase-associated lipocalin (uNGAL) was measured in 107 patients consecutively admitted to the ICUs in our tertiary medical center. uNGAL samples were collected within 3-6 hours of admission to an ICU and measured by ELISA. All data were analyzed using R statistical software, and univariate analysis was used to determine the correlations of uNGAL levels with AKI stage, admission diagnoses, and ICU course. Results: uNGAL level increased by a mean of 24-fold (SD 10-59) in ICU patients with AKI and demonstrated a significant correlation with the different AKI stages. uNGAL predicted the need for RRT, with values increased by more than 15-fold (P<0.05) in patients needing RRT, and remained a useful tool to predict AKI in ICU patients with a urinary tract infection. uNGAL level was correlated with certain ICU admitting diagnoses whereby uNGAL levels were lower in ICU patients with cardiogenic shock compared with other admission diagnoses (ß=-1.92, P<0.05). Conclusions: uNGAL can be used as an early predictor of AKI and its severity in patients admitted to the ICU, including the need for RRT. uNGAL may also help in distinguishing patients with cardiogenic shock from those with other critical illnesses and identifying those at risk for poor outcomes irrespective of the presence of AKI.

Approach to Hypertension in Adolescents and Young Adults.

PURPOSE OF REVIEW: The prevalence of hypertension in adolescents and young adults has increased in part due to the obesity epidemic. The clinical impact and future cardiovascular risk of this underestimated public health problem is an evolving field. RECENT FINDINGS: The development of hypertension is predicted by tracking of elevated blood pressure from childhood to adulthood. Young hypertensive individuals have lower awareness, slower diagnosis rates, and poorer blood pressure control than older patients. Increased awareness, appropriate screening, early identification, and individualized treatment approaches for elevated blood pressure could prevent development of hypertension in adulthood and cardiovascular events in later life. The optimal blood pressure management for young adults with a low 10-year risk of atherosclerotic cardiovascular disease of < 10% remains challenging due to lack of randomized controlled trials. Evidence-based recommendations are needed to implement appropriate measures for time of treatment initiation, preferred antihypertensive drug class to be used and optimal target blood pressure level from childhood through young adulthood.

Hyperkalemia and Hypertension Post Organ Transplantation - A Management Challenge.

Potassium is the most important intracellular cation and the kidneys play a pivotal role in potassium homeostasis. Potassium disorder is a common electrolyte abnormality and it increases the risk of death from any cause, particularly cardiovascular events. Hyperkalemia is a common electrolyte abnormality encountered post organ transplantation. The etiology is multifactorial, and includes drugs such as calcineurin inhibitors. In certain regards, the clinical picture of post-transplantation hyperkalemia and hypertension resembles that of Gordon syndrome or familial hyperkalemic hypertension, a disorder characterized by over activity of thiazide-sensitive sodium chloride cotransporter. Effective and safe management of chronic hyperkalemia can be challenging in this special patient population. Despite the significant short-term and long-term side effects, fludrocortisone (a potent synthetic oral mineralocorticoid receptor agonist) has emerged as the default drug of choice for treatment of refractory hyperkalemia in many organ transplant recipients. However, the long-term efficacy and safety of fludrocortisone for management of hyperkalemia in organ transplant recipients remains unknown. This review discusses potassium homeostasis, including the role of the kidneys, and focuses on calcineurin inhibitor-induced hyperkalemia and on the under-appreciated role of thiazide-type diuretic use in management of hyperkalemia and hypertension. We present an illustrative case of post-transplantation hyperkalemia and hypertension with relevant literature.

Hypertension in Premenopausal and Postmenopausal Women.

PURPOSE OF REVIEW: To examine available clinical data on the differences between premenopausal and postmenopausal women with hypertension (HTN). Clinical conditions related to HTN and reproductive status differ in younger women compared with older women. Due to recent changes in the definition of HTN, the prevalence of HTN has increased significantly in all women. Rising rates of obesity among women of all ages increase the risk for HTN. RECENT FINDINGS: Among younger women, long-term vascular consequences of preeclampsia, the under-reported prevalence of fibromuscular dysplasia, and widespread use of oral contraceptive pills in women with contraindications confer unique risks for HTN-related cardiovascular risk. For older women, insights on vascular aging and hormonal changes with menopause are shown to be gender-specific causal factors for HTN. Assessment of risk factors unique to premenopausal and postmenopausal women can facilitate the management of HTN and improve long-term outcomes. Further studies in women are needed to accurately stratify women risk based on these risk factors.

New diagnosis of bullous pemphigoid after withdrawal of immunosuppressive therapy in a failed renal transplant recipient on hemodialysis.

The occurrence of the autoimmune blistering disease, bullous pemphigoid (BP), in patients with failed renal allograft is rare and the few reported cases suggest various provocative factors without reaching a consensus. Here we report the case of a patient presenting with bullous lesions soon after the complete discontinuation of immunosuppressant therapy following renal allograft failure. Skin biopsy confirmed the diagnosis of BP. Administration of systemic corticosteroid controlled the occurrence of BP lesions in our patient. Increased clinical suspicion is warranted in cases of patients with renal transplant failure, since withdrawal of the immunosuppressant therapy could lead to unmasking the underlying autoimmune skin disease.

Management of Hypertension in Patients with Chronic Kidney Disease.

Hypertension is the leading factor in the global burden of disease. It is the predominant modifiable risk factor for stroke, heart disease, and kidney failure. Chronic kidney disease (CKD) is both a common cause and sequel of uncontrolled hypertension. The pathophysiology of CKD-associated hypertension is complex and multi-factorial. This paper reviews the key pathogenic mechanisms of CKD-associated hypertension, the importance of standardized blood pressure (BP) measurement in establishing the diagnosis and management plus the significance of ambulatory BP monitoring for assessment of diurnal BP variation commonly seen in CKD. The optimal BP target in CKD remains a matter of discussion despite recent clinical trials. Medical therapy can be difficult and challenging. In addition to lifestyle modification and dietary salt restriction, treatment may need to be individualized based on co-morbidities. Combination of antihypertensive drugs, including appropriate diuretic choice and dose, is of great significance in hypertension management in CKD.

Hypertension in Chronic Kidney Disease.

Hypertension, a global public health problem, is currently the leading factor in the global burden of disease. It is the major modifiable risk factor for heart disease, stroke and kidney failure. Chronic kidney disease (CKD) is both a common cause of hypertension and CKD is also a complication of uncontrolled hypertension. The interaction between hypertension and CKD is complex and increases the risk of adverse cardiovascular and cerebrovascular outcomes. This is particularly significant in the setting of resistant hypertension commonly seen in patient with CKD. The pathophysiology of CKD associated hypertension is multi-factorial with different mechanisms contributing to hypertension. These pathogenic mechanisms include sodium dysregulation, increased sympathetic nervous system and alterations in renin angiotensin aldosterone system activity. Standardized blood pressure (BP) measurement is essential in establishing the diagnosis and management of hypertension in CKD. Use of ambulatory blood pressure monitoring provides an additional assessment of diurnal variation in BP commonly seen in CKD patients. The optimal BP target in the treatment of hypertension in general and CKD population remains a matter of debate and controversial despite recent guidelines and clinical trial data. Medical therapy of patients with CKD associated hypertension can be difficult and challenging. Additional evaluation by a hypertension specialist may be required in the setting of treatment resistant hypertension by excluding pseudo-resistance and treatable secondary causes. Treatment with a combination of antihypertensive drugs, including appropriate diuretic choice, based on estimated glomerular filtration rate, is a key component of hypertension management in CKD patients. In addition to drug treatment non-pharmacological approaches including life style modification, most important of which is dietary salt restriction, should be included in the management of hypertension in CKD patients.