Patients with Alport syndrome present with hematuria in early childhood. Proteinuria develops during teenage years, with nephrotic syndrome in 30%-40%. Male patients with X-linked Alport progress to end-stage kidney disease, usually in adulthood. Female carriers of X-linked classic Alport syndrome usually have only hematuria, but may develop progressive kidney disease as middle-aged or older adults. Carriers of rare autosomal recessive variants of Alport syndrome also have hematuria. Gradual deafness develops in about half of adult men with Alport syndrome, with eye defects in about one-third, most commonly anterior lenticonus.

Antibiotic therapy has decreased the incidence of glomerulonephritis related to subacute bacterial endocarditis (SBE). Kidney involvement may be the initial manifestation of SBE in about 20% of patients. Hematuria and mild proteinuria are commonly present. Hypertension and nephrotic syndrome are rare. Serum complement levels may be low. Gross hematuria may be present in patients with renal infarctions related to embolic events. The degree of GFR loss correlates with the severity of glomerulonephritis; diffuse glomerulonephritis causes moderate GFR loss, and necrotizing glomerulonephritis with crescents can cause a rapid GFR decline.

Karyomegalic nephropathy is a rare autosomal recessive disease due to mutation in the FAN1 gene, resulting in low-grade proteinuria and slowly progressive GFR loss starting in the third decade of life, culminating in end-stage kidney disease.

Sarcoidosis is a systemic disease of middle-aged patients, with an incidence of 15-20 per 100,000. African Americans are affected much more commonly than those of European ancestry, with the exception of increased incidence in patients of Scandinavian ancestry; there is a slight female preponderance. Organs most commonly involved include lung, lymph nodes (particularly hilar), eyes, and skin. Kidney disease develops in up to a third of patients, and may present as acute kidney injury related to hypercalcemia, or GFR decline and low-level proteinuria due to granulomatous parenchymal injury.

Sickle cell disease is an autosomal recessive disease that occurs most commonly in individuals of African ancestry, with an incidence of 1 in 500 African Americans. Kidney disease has varying manifestations, with microalbuminuria in childhood, progressing to overt proteinuria in 20%-25% and nephrotic syndrome in about 5%, and progressive GFR loss after age 20 years in 5%-8% of all sickle cell patients. Patients often show hyposthenuria and hematuria as well. Some patients develop papillary necrosis and acute kidney injury due to sickle cell crisis.

Acute interstitial nephritis (AIN) describes a lesion with interstitial edema with a mononuclear cell infiltrate invading the interstitium and tubules, composed mostly of T lymphocytes. There are scattered plasma cells and macrophages, occasionally with non-necrotizing granulomas, and variable presence of eosinophils. When inflammation is due to infection, the lesion is diagnosed according to the specific pathogen involved (eg, bacterial, viral, or fungal). AIN commonly manifests clinically as acute kidney injury, with rapid decline in glomerular filtration rate, often with fever, eosinophilia, hematuria, sterile pyuria, and non-nephrotic proteinuria.

Tubular atrophy is a general term that describes several patterns of chronic tubular injury with thickened tubular basement membranes, and clinically manifests as chronic kidney disease with decreased glomerular filtration rate. Increased extent of tubular atrophy and accompanying interstitial fibrosis correlates with worse prognosis. Proteinuria is variable, depending on cause.

Toxic acute tubular injury describes a lesion with frank necrosis of tubules, which commonly manifests clinically as acute kidney injury, with a rapid decline in glomerular filtration rate, often oliguria, and granular casts and low-level proteinuria. In some settings (eg, with industrial/environmental toxin exposures), the onset may be gradual with a slow decline in glomerular filtration rate and loss of concentrating ability. Toxic acute tubular injury may occur at any age, with varying underlying causality.