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Amyloidosis and the Kidney: An Update.

Various types of systemic amyloidosis can wreak havoc on the architecture and functioning of the kidneys. Amyloidosis should be suspected in patients with worsening kidney function, proteinuria, and multisystem involvement, but isolated kidney involvement also is possible. Confirming the amyloidosis type and specific organ dysfunction is of paramount importance to select the appropriately tailored treatment and aim for better survival while avoiding treatment-associated toxicities. Amyloid renal staging in light chain amyloidosis amyloidosis helps inform prognosis and risk for end-stage kidney…

Magnesium reabsorption in the kidney.

Mg2+ is essential for many cellular and physiological processes, including muscle contraction, neuronal activity, and metabolism. Consequently, the blood Mg2+ concentration is tightly regulated by balanced intestinal Mg2+ absorption, renal Mg2+ excretion, and Mg2+ storage in bone and soft tissues. In recent years, the development of novel transgenic animal models and identification of Mendelian disorders has advanced our current insight in the molecular mechanisms of Mg2+ reabsorption in the kidney. In the proximal tubule, Mg2+ reabsorption is dependent on paracellular permeability by claudin-…

Autoinflammatory diseases and the kidney.

The kidney represents an important target of systemic inflammation. Its involvement in monogenic and multifactorial autoinflammatory diseases (AIDs) vary from peculiar and relatively frequent manifestations to some rare but severe features that may end up requiring transplantation. The pathogenetic background is also very heterogeneous ranging from amyloidosis to non-amyloid related damage rooted in inflammasome activation. Kidney involvement in monogenic and polygenic AIDs may present as renal amyloidosis, IgA nephropathy, and more rarely as various forms of glomerulonephritis (GN), namely se…

Genomics in the kidney clinic.

Inherited diseases are a frequent cause of end-stage kidney disease and often seen in the kidney clinic. Clinical genomic testing is increasingly available in the UK and eligible patients in England can be referred through the NHS Genomic Medicine Service. Testing is useful for diagnosis, prognostication and management of conditions such as autosomal dominant polycystic kidney disease (ADPKD), Alport syndrome, autosomal dominant tubulointerstitial kidney disease (ADTKD) and focal segmental glomerulosclerosis (FSGS). As more patients undergo genomic testing and newer technologies such as whole …

Therapeutics in rheumatology and the kidney.

The field of rheumatology has advanced significantly in recent years to provide rheumatologists with an extensive array of medications to combat rheumatic joint conditions. In contrast to an older era, when NSAIDs and other nephrotoxic agents were the mainstay of treatment, modern DMARDs vary considerably in their nephrotoxic potential and their use is not always precluded in populations with pre-existing chronic kidney disease (CKD). This review will explore in detail the safety and efficacy profiles of medications used to treat rheumatologic disease, specifically in the setting of CKD. Speci…

Amyloidosis of the Heart and Kidney.

Amyloidosis encompasses a collection of disorders of pathological protein folding. The extracellular location where these "amyloid fibril" proteins are deposited determines the clinical presentation of the disease. The abnormal architecture of these fibrils makes them insoluble and not easily removed, leading to disruption of normal tissue structure and interference with normal physiology. Amyloidosis of the heart and kidney can be inherited, secondary to unrelated diseases, or due to a plasma cell disorder. This review will focus on immunoglobulin light chain amyloidosis, which is life-threat…

Development of the metanephric kidney.

The kidney plays an integral role in filtering the blood-removing metabolic by-products from the body and regulating blood pressure. This requires the establishment of large numbers of efficient and specialized blood filtering units (nephrons) that incorporate a system for vascular exchange and nutrient reabsorption as well as a collecting duct system to remove waste (urine) from the body. Kidney development is a dynamic process which generates these structures through a delicately balanced program of self-renewal and commitment of nephron progenitor cells that inhabit a constantly evolving ce…

Ischemic Preconditioning of the Kidney.

The phenomenon of ischemic preconditioning was discovered in 1986 in experiments with the heart, and then it was observed in almost all organs, the kidneys included. This phenomenon is underlain by conditioning of the tissues with short ischemia/reperfusion cycles intended for subsequent exposure to pathological ischemia. Despite the kidneys are not viewed as so vital organs as the brain or the heart, the acute ischemic injury to kidneys is a widespread pathology responsible for the yearly death of almost 2 million patients, while the number of patients with chronic kidney disease is estimated…

Heart Disease and the Kidneys.

Clinical Background: The heart can cause kidney disease, and the kidney can cause heart disease. As an example of the first situation, we can mention dilated cardiomyopathies, which can lead to renal failure of the pre-renal type due to the state of renal hypoflow. As an example of the second situation, we can remember that renal failure is a risk factor for cardiovascular diseases, such as coronary heart disease, due to the acceleration in the process of atherosclerosis that it promotes. Epidemiology: In this chapter, we will address what we consider to be the two main aspects of the interrel…

Multiple Myeloma and the Kidney.

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… MM can affect the kidney function in several ways, either as monoclonal gammopathy of renal significance (MGRS) or as acute kidney injury (AKI) as in light chain cast nephropathy (LCCN). Surprisingly, renal complications in MM are not mentioned throughout the paper. … Management of acute kidney injury in symptomatic multiple myeloma. Kidney Int . 2021 ; 99 : 570 – 580 33440212 10.1016/j.kint.2020.11.010 3. Cancarini G Terlizzi V Garatti A . Supportive treatment for cast nephropathy in patients with multiple myeloma; a pilot study. …

Neuroimmune Communication in the Kidney.

Recent studies have clarified the interaction between nervous systems and immunity regarding the manner in which local inflammation is regul … ry bowel disease. Moreover, emerging studies have revealed that vagus nerve stimulation ameliorates kidney damage in an animal model of acute kidney injury. These studies suggest that the link between the nervous system and kidneys is associated with the pathophysiology of kidney injury. Here, we review the current knowledge of the neuroimmune circuit an …

Pathology of the kidney allograft.

The kidney biopsy still represents the best approach to diagnose renal transplant complications. It is considered the gold standard in the diagnosis of rejection and non-rejection complications. Although invasive, it is a safe procedure with a very low complication rate. With adequate sampling, changes related to antibody-mediated rejection (ABMR) and T-cell mediated rejection (TCMR) can be identified. However, the pathologist needs to be aware of the many other complications, not related to rejection, that can affect the allograft function. Examples include viral infections, drug toxicity, sy…

HIV, drugs and the kidney.

Human immunodeficiency virus (HIV) affects over 36 million people worldwide. Antiretroviral therapy (ART) is expanding and improving HIV viral suppression, resulting in increasing exposure to drugs and drug interactions. Polypharmacy is a common complication as people are living longer on ART, increasing the risk of drug toxicities. Polypharmacy is related not only to ART exposure and medication for opportunistic infections, but also to treatment of chronic lifestyle diseases. Acute kidney injury (AKI) is frequent in HIV and is commonly the result of sepsis, dehydration and drug toxicities. Fu…

Oxygenation of the Transplanted Kidney.

Although kidney oxygen tensions are heterogenous, and mostly below renal vein level, the nephron is highly dependent on aerobic metabolism for active tubular transport. This renders the kidney particularly susceptible to hypoxia, which is considered a main characteristic and driver of acute and chronic kidney injury, albeit the evidence supporting this assumption is not entirely conclusive. Kidney transplants are exposed to several conditions that may interfere with the balance between oxygen supply and consumption, and enhance hypoxia and hypoxic injury. These include conditions leading to an…

Thrombotic Microangiopathy and the Kidney.

Thrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and

Antiphospholipid Syndrome and the Kidney.

The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis, p … y of patients with APS, eventually will develop features of SLE. Because SLE and APS can target the kidneys independently or at the same time, discriminating between inflammatory or thrombotic lesions is crucial in planning therapy. We provide an overview of the renal manifestations associated with the presence of aPL in patients with SLE, and discuss th …