Since the completion of the Human Genome Project in 2003, an expanding understanding of the genetic basis of diseases has allowed us to target disease mechanisms at the molecular level. One example of the application of precision medicine in nephrology targets the mammalian target of rapamycin (mTOR) complex in the multisystem disease of tuberous sclerosis (TSC). Affecting roughly 1 in 6000 live births, TSC is a rare but significant cause of kidney disease in children (1). About one-half of patients with TSC are at risk of chronic kidney disease, which is the leading cause of morbidity and mortality
Once the decision to pursue peritoneal dialysis (PD) is made, two primary modalities are available from which patients can choose: continuous ambulatory PD (CAPD) and ambulatory PD (APD). CAPD involves manually performed exchanges using gravity to fill and drain the peritoneal cavity, and APD involves exchanges that are performed using a cycler over several hours, typically during the night. The selection of a PD modality is dependent on an individual's lifestyle because there is no difference in patient and technique survival (1).
Subtypes of APD include continuous cycling PD (CCPD), nightly intermittent PD (NIPD), and tidal PD (TPD)
Kidney involvement is a major complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), manifesting clinically as rapid decline in glomerular filtration rate and histologically by Pauci-immune crescentic (Figure 1) and necrotizing (Figure 2) glomerulonephritis.
Extracapillary proliferation causes glomerular tuft deflation with disappearance of normal glomerular structure and occlusion of capillary lumina. This is better shown by Jones methenamine silver (JMS) staining (A) and periodic acid−Schiff (PAS) staining (B). (Image courtesy Paride Fenaroli)
Glomerular fibrinoid necrosis at Jones methenamine silver (JMS) staining
Silver staining hallmarks glomerular basement membranes (GBMs) and allows
C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), collectively known as C3 glomerulopathy (C3G), are rare glomerular diseases presenting with microscopic hematuria, proteinuria, and often, abnormal kidney function. Low serum C3 is present in 70%−80% of patients with DDD and 50% with C3GN (1). Effective therapies are lacking, and prognosis is poor (2). Disease recurrence after kidney transplantation is common and leads to graft loss in 30%−40% of affected patients (3, 4).
Pathogenesis of C3G
C3G is characterized by dysregulation of the alternative complement pathway and defined by C3-dominant staining on immunofluorescence
As the coronavirus infectious disease 2019 (COVID-19) pandemic unleashed through the world, we found that patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) had a wide range of direct and indirect effects culminating in a variety of end-organ injuries. Acute kidney injury (AKI) was found in as many as 80% of patients admitted to the intensive care unit with severe illness.
The most common histopathologic equivalent of clinical AKI was acute tubular injury or necrosis in biopsy and autopsy studies in these patients. However, COVID-19 can affect all compartments of the kidney parenchyma, including the glomerulus, interstitium, and vasculature.
Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerular disease worldwide. Despite being initially described over 50 years ago by Dr. Jean Berger, there remains no disease-specific treatment. Its underlying pathogenesis is a dysregulation of the IgA immune system, which is characterized by elevated circulating levels of polymeric IgA1 that lack terminal galactose residues within the hinge region (termed “poorly galactosylated IgA1”) and the presence of IgA1-specific IgG and IgA antibodies (Figure 1). This leads to the formation of IgA-containing immune complexes that deposit within the glomerular mesangium, triggering mesangial cell proliferation, complement activation, inflammation,
Fibrillary glomerulonephritis and immunotactoid glomerulonephritis represent two of the kidney diseases characterized by organized fibrillar deposits. In 1977, the first case of fibrillary glomerulonephritis was described in a patient with nephrotic syndrome whose kidney biopsy showed amyloid-like deposits that did not stain with Congo red (1). The term “fibrillary glomerulonephritis,” however, did not appear in the literature until 1987 (2). Immunotactoid glomerulonephritis was first used to describe the kidney biopsy of a patient with nephrotic syndrome in 1980 (3). For years, whether immunotactoid and fibrillary glomerulonephritis denoted two separate entities or different presentations of
Drugs cause approximately 20% of community- and hospital-acquired episodes of acute kidney failure (1–3). Among older adults, the incidence of drug-induced nephrotoxicity may be as high as 66% (4). Drug-induced nephrotoxicity may account for 20% of acute kidney injury (AKI), including both acute and chronic kidney disease. Prospective cohort studies of AKI have documented the frequency of drug-induced nephrotoxicity to be approximately 14%−26% in intensive care unit cohorts (5–7).
A growing body of literature highlights the potential for drugs to induce not only AKI but also glomerular diseases, termed drug-induced
Minimal change disease (MCD) is one of the major causes of idiopathic nephrotic syndrome, accounting for up to 70%−90% of cases in children and approximately 15% of cases in adults (1). The characteristic appearance of MCD on a kidney biopsy is normal glomeruli on light microscopy with diffuse effacement of the epithelial foot processes on electron microscopy. The pathogenesis of MCD is not fully elucidated, but systemic T cell dysfunction producing increased levels of a glomerular permeability factor has been implicated (2, 3). Although the pathogenesis remains uncertain, similar to focal segmental glomerulosclerosis, a
Membranous nephropathy (MN) is a common cause of nephrotic syndrome, attributed to approximately 25% of adult patients with nephrotic-range proteinuria or nephrotic syndrome (1). This number is significantly less in children with nephrotic syndrome. The clinical course of MN is insidious, with variable degrees of proteinuria, hypoalbuminemia, and hyperlipidemia that can lead to significant edema and in extreme cases, a rapid loss of kidney function, anasarca, acute kidney injury, and thromboembolic events. The clinical presentation is the resulting immune complex formation on the epithelia side of the glomerular basement membrane (GBM).