Insulin resistance is a central component of the metabolic dysregulation observed in obesity, which puts one at risk for the development of type 2 diabetes and complications related to diabetes such as chronic kidney disease. Insulin resistance and compensatory hyperinsulinemia place one at risk for other risk factors such as dyslipidemia, hypertension, and proteinuria, e.g., development of kidney disease. Our traditional view of insulin actions focuses on insulin-sensitive tissues such as skeletal muscle, liver, adipose tissue, and the pancreas. However, insulin also has distinct actions in kidney tissue that regulate growth, hypertrophy, as well as microcirculatory and fibrotic pathways which, in turn, impact glomerular filtration, including that governed by tubuloglomerular feedback. However, it is often difficult to discern the distinct effects of excess circulating insulin and impaired insulin actions, as exist in the insulin resistance individual, from the associated effects of obesity or elevated systolic blood pressure on the development and progression of kidney disease over time. Therefore, we review the experimental and clinical evidence for the distinct impact of insulin resistance on kidney function and disease.

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity?

Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation It commonly occurs in patients with other metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods This classification can help clinicians determine the etiology and provide the appropriate management for these complex patients Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation Transplant renal artery stenosis (TRAS) and obstructive sleep apnea (OSA) are recognized but common and treatable causes of resistant hypertension post-transplantation During late post-transplant period, chronic renal allograft dysfunction becomes an additional cause of hypertension As these patients develop more substantial chronic kidney disease affecting their allografts, fibroblast growth factor 23 (FGF23) increases and is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients The exact relationship between increased FGF23 and post-transplant hypertension remains poorly understood Blood pressure (BP) targets and management involve both non-pharmacologic and pharmacologic treatment and should be individualized Until strong evidence in the kidney transplant population exists, a BP of <130/80 mmHg is a reasonable target Similar to complete renal denervation in non-transplant patients, bilateral native nephrectomy is another treatment option for resistant post-transplant hypertension Native renal denervation offers promising outcomes for controlling resistant hypertension with no significant procedure-related complications This review addresses the epidemiology, pathogenesis, and specific etiologies of post-transplant hypertension including TRAS, calcineurin inhibitor effects, OSA, and failed native kidney The cardiovascular and survival outcomes related to post-transplant hypertension and the utility of 24-h blood pressure monitoring will be briefly discussed Antihypertensive medications and their mechanism of actions relevant to kidney transplantation will be highlighted A summary of guidelines from different professional societies for BP targets and antihypertensive medications as well as non-pharmacological interventions, including bilateral native nephrectomy and native renal denervation, will be reviewed

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Approach and Management of Hypertension After Kidney Transplantation.

Hypophosphatemia in critically ill adults and children - A systematic review.

Obstructive sleep apnoea (OSA) is frequently associated with comorbidities that include metabolic, cardiovascular, renal, pulmonary and neuropsychiatric. There is considerable evidence that OSA is an independent risk factor for many of these comorbidities but, more recently, there is evidence that some of these comorbidities may predispose to the development of OSA. Thus, there is growing evidence of a bidirectional relationship between OSA and comorbidity, especially for heart failure, metabolic syndrome and stroke. Potential mechanisms of bidirectional relationships differ in individual comorbidities with fluid retention and redistribution being especially important in heart failure and end-stage renal disease, whereas neural mechanisms may be more important in diabetes mellitus and stroke. The evidence for other comorbidities, such as hypertension and atrial fibrillation, support these being more a consequence of OSA with limited evidence to support a bidirectional relationship. The present review explores the evidence for such bidirectional relationships with a particular perspective on comorbidities that may predispose to OSA. The impact of therapy in bidirectional relationships is also reviewed, which highlights the clinical importance of accurate diagnosis. This aspect is especially true of COPD, where the identification of co-existing OSA has important implications for optimum therapy. Obstructive sleep apnoea (OSA) is an independent risk factor for comorbidity, especially cardiometabolic. However, some comorbidities may be risk factors for OSA, supporting a bidirectional relationship that may have important implications for treatment. https://bit.ly/3BbJy6V

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Bidirectional relationships of comorbidity with obstructive sleep apnoea

Obstructive sleep apnea (OSA) is regarded as an independent risk factor for hypertension. The possible mechanism includes oxidative stress, endothelial injury, sympathetic excitement, renin–angiotensin–aldosterone system activation, etc. Clinical studies have found that there is a high coexistence of OSA and primary aldosteronism in patients with hypertension and that elevated aldosterone levels are independently associated with OSA severity in resistant hypertension. The underlying mechanism is that aldosterone excess can exacerbate OSA through increasing overnight fluid shift and affecting the mass and function of upper airway muscles during the sleep period. Thus, a bidirectional influence between OSA and aldosterone exists and contributes to hypertension in OSA patients, especially resistant hypertension.

https://www.frontiersin.org/articles/10.3389/fendo.2021.801689/pdf

The Role of Aldosterone in OSA and OSA-Related Hypertension

Obstructive sleep apnea (OSA), hypertension, and chronic kidney disease (CKD) are different entities and are generally managed individually most of the time. However, CKD, OSA, and hypertension share many common risk factors and it is not uncommon to see this complex triad together. In fact, they share similar pathophysiology and have been interlinked with each other. The common pathophysiology includes chronic volume overload, hyperaldosteronism, increased sympathetic activity, endothelial dysfunction, and increased inflammatory markers. The combination of this triad has significant negative impact on the cardiovascular health, and increases the mortality and morbidity in this complicated group of patients. On one hand, progression of CKD can lead to the worsening of OSA and hypertension; similarly, worsening sleep apnea can make the hypertension difficult to treat and enhance the progression of CKD. This review article highlights the bidirectional interlink among these apparently different disease processes which share common pathophysiological mechanisms and emphasizes the importance of treating them collectively to improve outcomes.

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The Triad of Sleep Apnea, Hypertension, and Chronic Kidney Disease: A Spectrum of Common Pathology

Peritoneal dialysis is an important dialysis modality used in the management of the patients with end stage renal disease. Success of the peritoneal dialysis depends on obtaining and maintaining a good access to the peritoneal cavity. Obtaining a peritoneal access with longer survival, reduced catheter related infections and complications are crucial for effective peritoneal dialysis. The introduction of Missouri Swan neck pre-sternal catheters gave whole new dimension to the world of peritoneal dialysis. These catheters are not only associated with reduced catheter associated complications but also reduced exit site and tunnel infections, peri-catheter leaks, catheter tip migration, cuff extrusion and peritonitis. Further, patients with ostomies and obesity also do better with the pre-sternal catheters. Overall, patient’s acceptance of pre-sternal exit site is better. These catheters have a coiled intra-abdominal segment; a titanium adaptor joins the abdominal segment to the upper segment. The upper segment has two cuffs, one on either side of pre-sternal swan-neck segment. The present chapter describes the advantages of pre-sternal swan neck catheters over conventional abdominal peritoneal dialysis catheters with various methods of implantation of pre-sternal catheters.

Pre-sternal and Extended Catheters

Nutritional deficiencies are very common among the patient on chronic hemodialysis. But they can be easily overlooked or misdiagnosed. Deficiencies of trace elements and phosphorous is rare among this patient population but if neglected can lead to catastrophic effects. We describe a case report of a patient with ESRD recently started on outpatient maintenance hemodialysis, who presented with life threatening muscular weakness with respiratory failure requiring prolonged mechanical ventilation. On initial workup, it was unclear what the cause of her weakness was, however, further investigations showed undetectable phosphorous levels as well as very low levels of trace elements. Replacement of these compounds to normal levels led to marked improvement in the clinical picture. On further evaluation, the patient was also found to be profoundly depressed with poor appetite even prior to initiation of hemodialysis. This case report highlights the importance of early diagnosis of depression and malnutrition in patients on chronic hemodialysis, as severe depression can contribute to malnutrition and life threatening deficiencies of organic as well as inorganic compounds, which may cause life threatening complications as evidenced in this patient.

Fahad Aziz

Papers

The Triad of Sleep Apnea, Hypertension, and Chronic Kidney Disease: A Spectrum of Common Pathology

Pre-sternal and Extended Catheters

Life threatening nutritional deficiencies in a dialysis patient.

Role of Peritoneal Dialysis in Acute Kidney Injury