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Nephronophthisis and Medullary Cystic Kidney Disease

Nephronophthisis (NPHP) and medullary cystic kidney disease (MCKD) represent a set of rare genetic kidney diseases with a similar kidney histopathology, which includes interstitial fibrosis with tubular atrophy, changes in the tubular basement membrane (TBM), and cyst formation. These two diseases can be distinguished clinically by their inheritance pattern and often by their age of onset. NPHP has an autosomal recessive inheritance pattern and results in…

Polycystic and Other Cystic Kidney Diseases

Autosomal Dominant Polycystic Kidney Disease Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, occurring in 1 of 400 to 1000 live births. It is the most common of all hereditary cystic disorders ( Table 39.1 ). ADPKD affects all ethnic groups equally, and it has been reported worldwide. It accounts for approximately 5% of the end-stage kidney disease (ESKD) population in the…

Sickle Cell Nephropathy

Sickle cell anemia is the most common monogenic disorder in the world and is caused by the homozygous inheritance of the sickle β-globin gene (HbSS), produced by a single-point mutation in chromosome 11. The resultant β chain of the hemoglobin molecule possesses a substitution of valine for glutamic acid at position 6, leading to an unstable form of hemoglobin (hemoglobin S). Under conditions of low-oxygen tension,…

Genetically Based Kidney Transport Disorders

The coming of age of clinical chemistry in the latter half of the 20th century, bringing with it the routine measurement of electrolytes and minerals in patient samples, produced descriptions of distinct inherited syndromes of abnormal tubular transport in the kidney. Clinical investigation led to speculation, often ingenious and sometimes controversial, regarding the underlying causes of these syndromes. More recently, the tools of molecular biology made…

APOL1-Mediated Kidney Disease

Ancestry and Chronic Kidney Disease Racial disparities in the incidence rates of chronic kidney disease (CKD) are widely appreciated. Compared to Americans of European descent, Americans of African descent face approximately a 4-fold higher risk for developing end-stage kidney disease (ESKD) with an estimated lifetime risk for ESKD approaching 8% (versus 2%–3% in European Americans). Although lower socioeconomic status and poorer access to healthcare contribute to…

Principles of Drug Therapy in Patients With Decreased Kidney Function

Decreased kidney function may be observed in many settings, including patients with chronic kidney disease (CKD), the elderly with age-related decline in glomerular filtration rate (GFR), and patients with acute kidney injury (AKI). In adults, these conditions are associated with high medication use, making these patients particularly vulnerable to the accumulation of a drug or its active or toxic metabolites. Clinicians must have a thorough understanding…

Kidney Disease Caused by Therapeutic Agents

Medications are an essential intervention to provide appropriate patient care, and new agents are being introduced into clinical practice at a rapid pace. Although most drugs are well tolerated, kidney injury remains an unfortunate and relatively frequent adverse consequence. Some kidney toxicity is idiosyncratic, while some individuals possess risk factors that predispose them to these syndromes. Not unexpectedly, the general population is regularly exposed to various…

Acute Interstitial Nephritis

In 1898, W. T. Councilman defined acute interstitial nephritis (AIN) as “an acute inflammation of the kidney characterized by cellular and fluid exudation in the interstitial tissue, accompanied by, but not dependent on, degeneration of the epithelium; the exudation is not purulent in character, and the lesions may be both diffuse and focal.” This was seen on postmortem examination of patients with scarlet fever and, less…

Acute Tubular Injury and Acute Tubular Necrosis

Acute tubular injury (ATI) characterizes damage to renal tubular epithelial cells and is the leading cause of acute kidney injury (AKI) in hospitalized patients. ATI is defined by a sudden decline in kidney function from ischemic or toxic insults and can occur at any epithelial segment along the nephron but is typically most profound in the proximal tubule. Packed with mitochondria and dependent on oxidative phosphorylation,…

Clinical Approach to the Diagnosis of Acute Kidney Injury

Pathophysiology The main causes of acute kidney injury (AKI) are associated with decreased kidney perfusion. A decrease in oxygen delivery severe or prolonged enough to impair cellular function can cause tubular or vascular endothelial dysfunction. The mismatch between oxygen delivery and demand is more prominent in certain regions of the kidney because variations in blood flow are characteristic of the kidney circulation. Because the kidneys receive…

Liver Disease, Acute Kidney Dysfunction, and the Hepatorenal Syndrome

Systemic homeostasis is normally maintained by a neurohumoral communication-feedback loop between major organs. Any dysregulation of this organ cross talk can contribute to organ dysfunction during times of illness; that is, injury to one organ can have direct or indirect (via medical therapies) deleterious repercussions on the other. There are few circumstances in which this link is as extensive as it is between the kidneys and…

Cardiorenal Syndrome

Cardiorenal syndrome (CRS) is a heterogenous disorder that is broadly characterized as interrelated dysfunction of the heart and kidneys. It is predominantly thought of as an entity that occurs in the setting of heart failure, although other cardiac abnormalities such as coronary artery disease, valvular disease, and arrythmias are often present. The specific kidney pathophysiologies that encompass CRS include abnormalities of filtration, sodium and water handling,…

Myeloma, Amyloid, and Other Dysproteinemias

Paraproteinemic kidney diseases are typically the result of deposition of immunoglobulins or immunoglobulin fragments (heavy chains and light chains; Fig. 28.1 ) in specific parts of the nephron, and they can be divided generally into those diseases that manifest primarily as glomerular or as tubulointerstitial injury ( Box 28.1 ). Glomerular diseases include AL-type amyloidosis (amyloid composed of light chains), AH-type amyloidosis (amyloid composed of heavy…

Onconephrology

Onconephrology is a growing field within nephrology, with many malignancies and their treatments affecting the kidneys and kidney disease impacting the management of many cancers. Although patients with malignancy can develop kidney diseases similar to other acutely and chronically ill patients, they are also at risk for unique kidney syndromes because of either the cancer itself or its treatment. Understanding these unique disorders is a prerequisite…

Pathogenesis, Pathophysiology, and Treatment of Diabetic Kidney Disease

## Diabetic kidney disease (DKD) is the leading cause of kidney failure in adults. In the United States, approximately half of patients initiating dialysis have diabetes mellitus, and most of these have type 2 diabetes; patients with youth-onset type 2 diabetes, as shown in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, exhibit a particularly high risk of progressive DKD after…

Systemic Lupus Erythematosus and the Kidney

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organs, including the skin, joints, brain, peripheral nervous system, heart, gastrointestinal tract, and kidneys. Kidney involvement in SLE, generally termed lupus nephritis (LN) , is a major contributor to SLE-associated morbidity and mortality. Up to 50% of SLE patients have clinically evident kidney disease at presentation, and, during follow-up, kidney involvement occurs in…

Viral Nephropathies: Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus, and SARS-CoV-2

## Human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) are the most important causes of viral-related kidney disease in the world. Several mechanisms are involved in the pathogenesis of virus-related kidney disease, including tropism of the virus in the kidney, direct cytopathic effects, and immune response to the virus including production of immune complexes. These lead to a spectrum of glomerular…

Infection-Related Glomerulonephritis

In previous editions, this chapter was titled “Post-infectious Glomerulonephritis,” which aptly describes classic post-streptococcal glomerulonephritis (PSGN) but is a misnomer for the increasingly recognized forms of glomerulonephritis (GN) that are manifestations of ongoing infection. Indeed, infection has a much broader role in the development of GN, sometimes serving as a trigger for a variety of common autoimmune responses including lupus, antineutrophil cytoplasmic antibody (ANCA) vasculitis, and…

Complement-Mediated Glomerulonephritis and Thrombotic Microangiopathy

## The complement system is a group of proteins that provide an important part of the immune defense against infection. Many components of the complement system circulate as inactive proteins in the plasma. Activation of the complement system generates peptide fragments that serve as ligands for several receptors and complete a multimeric complex (C5b-9) that forms pores in membranes resulting in cell lysis. As with all…

Immunoglobulin A Nephropathy and Related Disorders

## Immunoglobulin A nephropathy (IgAN) was first described in 1968 by the Parisian pathologist Jean Berger, and at one time it was known as Berger’s disease . It is the most common pattern of glomerulonephritis (GN) identified in areas of the world where kidney biopsy is widely performed. IgAN is defined by mesangial IgA deposition often accompanied by a mesangial proliferative GN, and it is an…