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Infections can trigger immune-mediated glomerular injury, leading to infection-related glomerulonephritis. Pathogens that can trigger immune-mediated glomerular damage include bacteria, viruses, and parasites. Previously, poststreptococcal glomerulonephritis, the prototype for infection-related glomerulonephritis, was the most common cause of this condition, especially in Western countries. Other triggers for bacterial-associated infection-related glomerulonephritis have evolved, including staphylococcal infection-associated glomerulonephritis, and infection-related glomerulonephritis due to other causes, such as subacute bacterial endocarditis, shunt nephritis, indwelling central venous catheters, and visceral abscesses. Bacterial infection is by far the most common cause. The damage primarily results from the deposition of immune complexes. This activity reviews the epidemiology, etiology, pathogenesis, evaluation, and management of infection-related glomerulonephritis, highlighting the role of the interprofessional team in evaluating and treating patients with this condition. Objectives: Identify the epidemiology, etiology, and pathophysiology of infection-related glomerulonephritis. Evaluate methods for assessing patients with infection-related glomerulonephritis. Apply appropriate treatment and management strategies for patients with infection-related glomerulonephritis. Implement interprofessional team strategies to improve care coordination and communication, enhancing outcomes for patients with infection-related glomerulonephritis. Access free multiple choice questions on this topic.

Glomerulonephritis results from immune dysregulation-mediated glomerular injury. Many infections can trigger glomerulonephritis, including endocarditis; enterocolitis; pneumonia; intraventricular shunt infections; viral infections, such as hepatitis B and C, HIV, and SARS-CoV-2; and parasitic infections, such as malaria, filariasis, and schistosomiasis.[1][2][3] Previously, poststreptococcal glomerulonephritis was the leading cause of bacterial infection-related glomerulonephritis. During the past few decades, other triggers for bacterial-associated infection-related glomerulonephritis have evolved, including staphylococcal infection-associated glomerulonephritis, subacute bacterial endocarditis, shunt nephritis, indwelling central venous catheters, and visceral abscesses.[1] For simplification, bacterial infection-related glomerulonephritis can be divided into: Poststreptococcal glomerulonephritis Staphylococcal infection-associated glomerulonephritis Other bacterial infection-associated glomerulonephritis, including shunt nephritis, subacute bacterial endocarditis, central venous catheter infections, and visceral abscesses. Nonbacterial causes, including viruses, fungi, and parasites

The etiology of infection-related glomerulonephritis depends on the cause. As previously discussed, several infections can trigger glomerulonephritis, including endocarditis; enterocolitis; pneumonia; intraventricular shunt infections; viral infections, such as hepatitis B and C, HIV, and SARS-CoV-2; and parasitic infections, such as malaria, filariasis, and schistosomiasis.[1][2] The vast majority of infection-related glomerulonephritis is associated with bacterial infections. Infection-related glomerulonephritis can be divided into the following: Poststreptococcal glomerulonephritis is characterized by the rapid deterioration of kidney function due to an inflammatory response (type III hypersensitivity reaction) following streptococcal infection.[4][5] This condition results from nephrogenic strains of group A beta-hemolytic streptococci, also known as nephrogenic streptococci. The disease affects the glomeruli and the small blood vessels of the kidneys. Poststreptococcal glomerulonephritis most frequently presents in children aged 1 to 2 weeks after a sore throat or 6 weeks after a skin infection (impetigo).[6] Nephritis-associated plasmin receptor and streptococcal pyrogenic exotoxin B are the 2 common antigens associated with the pathogenesis of poststreptococcal glomerulonephritis.[7] These antigens not only activate the alternative complement pathway, resulting in hypocomplementemia, but they also have an affinity for plasmin and glomerular proteins. Key risk factors for streptococcal outbreaks include poor hygiene, overcrowding, and low socioeconomic status, which contribute to the higher incidence of poststreptococcal glomerulonephritis in resource-limited countries. Genetic factors are expected to predispose to the condition since almost 40% of patients with poststreptococcal glomerulonephritis gave a positive family history.[2]

Poststreptococcal glomerulonephritis is characterized by the rapid deterioration of kidney function due to an inflammatory response (type III hypersensitivity reaction) following streptococcal infection.[4][5] This condition results from nephrogenic strains of group A beta-hemolytic streptococci, also known as nephrogenic streptococci. The disease affects the glomeruli and the small blood vessels of the kidneys. Poststreptococcal glomerulonephritis most frequently presents in children aged 1 to 2 weeks after a sore throat or 6 weeks after a skin infection (impetigo).[6] Nephritis-associated plasmin receptor and streptococcal pyrogenic exotoxin B are the 2 common antigens associated with the pathogenesis of poststreptococcal glomerulonephritis.[7] These antigens not only activate the alternative complement pathway, resulting in hypocomplementemia, but they also have an affinity for plasmin and glomerular proteins. Key risk factors for streptococcal outbreaks include poor hygiene, overcrowding, and low socioeconomic status, which contribute to the higher incidence of poststreptococcal glomerulonephritis in resource-limited countries. Genetic factors are expected to predispose to the condition since almost 40% of patients with poststreptococcal glomerulonephritis gave a positive family history.[2] Staphylococcal infection-associated glomerulonephritis results from Staphylococcal infections, including those caused by Staphylococcus aureus and coagulase-negative S epidermidis. Acute staphylococcal infections, such as skin infections, osteomyelitis, staphylococcal endocarditis, and pneumonia, can lead to bacteremia with immune dysregulation, which in turn can cause glomerulonephritis. The occurrence of staphylococcal infection-associated glomerulonephritis has surged, especially in Western countries, due to the evolution of drug-resistant forms of Staphylococci, such as methicillin-resistant S aureus and methicillin-resistant S epidermidis. Intravenous drug abuse is a significant risk factor for the development of staphylococcal infection-associated glomerulonephritis and bacterial endocarditis-associated glomerulonephritis.

Staphylococcal infection-associated glomerulonephritis results from Staphylococcal infections, including those caused by Staphylococcus aureus and coagulase-negative S epidermidis. Acute staphylococcal infections, such as skin infections, osteomyelitis, staphylococcal endocarditis, and pneumonia, can lead to bacteremia with immune dysregulation, which in turn can cause glomerulonephritis. The occurrence of staphylococcal infection-associated glomerulonephritis has surged, especially in Western countries, due to the evolution of drug-resistant forms of Staphylococci, such as methicillin-resistant S aureus and methicillin-resistant S epidermidis. Intravenous drug abuse is a significant risk factor for the development of staphylococcal infection-associated glomerulonephritis and bacterial endocarditis-associated glomerulonephritis. Other bacterial infection-associated glomerulonephritis includes subacute bacterial endocarditis-associated glomerulonephritis, shunt nephritis, central venous catheter-associated glomerulonephritis, and glomerulonephritis secondary to deep-seated visceral abscesses. Subacute bacterial endocarditis results from the infection of damaged heart valves by bacteria such as Streptococcus viridans, Streptococcus mutans, and gram-negative bacilli, including the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella species).[8][9] Shunt nephritis results from immune-mediated damage of the glomeruli due to the infection of ventriculo-atrial and ventriculo-peritoneal shunts used in the treatment of hydrocephalus. Infected central venous catheters and visceral abscesses can also trigger infection-related glomerulonephritis.[1] Viral and parasitic causes (rarer) are detailed below.

Previously, poststreptococcal glomerulonephritis was the dominant form of bacterial-associated glomerulonephritis. However, over the past few decades, the incidence of poststreptococcal glomerulonephritis has declined significantly in developed countries due to the evolution of antibiotic therapy, improved hygiene, higher living standards, and increased access to health care.[10] In contrast, poststreptococcal glomerulonephritis is more common in developing countries due to an increased risk of infections, antibiotic resistance, and limited access to health care. The annual incidence of new cases of poststreptococcal glomerulonephritis in developing countries ranges from 8.5 to 28.5 per 100,000 individuals.[11] Poststreptococcal glomerulonephritis is the most common cause of glomerulonephritis in children worldwide.[2] In adults, this condition is reported mainly in the older population.[12] With the increasing incidence of hospital- and community-acquired staphylococcal infections, staphylococcal infection-associated glomerulonephritis has emerged as the most common cause of infection-related glomerulonephritis in the Western world.[1] The incidence of staphylococcal infection-associated glomerulonephritis peaks after the fifth decade of life; however, younger adults can be affected, especially in intravenous drug abuse-related endocarditis-associated glomerulonephritis.[13] Central venous catheter-associated glomerulonephritis has become more common, especially in critically ill patients on parenteral nutrition.[14] The incidence of shunt nephritis has declined since the introduction of ventriculoperitoneal shunts for the treatment of hydrocephalus.[1] The epidemiology of virus-associated glomerulonephritis varies in the literature. Up to 5% of patients affected by hepatitis B virus (HBV) and hepatitis C virus (HCV) develop nephropathy, including membranous nephropathy, membranoproliferative glomerulonephritis, and cryoglobulinemia.[15] Approximately 6% to 30% of patients with HIV develop proteinuria due to glomerular damage.[15] COVID-19 is known to cause glomerular diseases, with collapsing glomerulopathy occurring in 36.1% of cases.[16]

The epidemiology of virus-associated glomerulonephritis varies in the literature. Up to 5% of patients affected by hepatitis B virus (HBV) and hepatitis C virus (HCV) develop nephropathy, including membranous nephropathy, membranoproliferative glomerulonephritis, and cryoglobulinemia.[15] Approximately 6% to 30% of patients with HIV develop proteinuria due to glomerular damage.[15] COVID-19 is known to cause glomerular diseases, with collapsing glomerulopathy occurring in 36.1% of cases.[16] Regarding parasitic infections, autopsy-proven glomerulopathy has been reported in approximately 10% to 12% of patients infected with Schistosoma in endemic areas.[17] The epidemiology of malaria-associated glomerular damage is less described in the literature. Amoura et al biopsied 23 patients with malaria infection and acute kidney injury. Twenty-one patients had focal segmental glomerular sclerosis, with 18 patients showing collapsing lesions.[18] Filarial glomerulopathy has been reported in India, although its exact prevalence is currently unknown.[19]

Infection-related glomerulonephritis primarily results from immune-mediated glomerular damage triggered by systemic infections. Bacterial, viral, and parasitic antigens trigger the formation of antibodies, which in turn form immune complexes that deposit in the glomerular capillary tufts, leading to the activation of the complement system, glomerular inflammation, and injury. In poststreptococcal glomerulonephritis, immune complexes are formed peripherally in the blood or in situ in kidney tissues when antibodies bind to antigens deposited in the glomerular basement membrane. Alternatively, they may arise from antibody reactions against glomerular components that cross-react with streptococcal antigen due to molecular mimicry.[2][20] The time needed for the formation of immune complexes could explain the latency between the time of infection and the onset of clinical manifestations, resembling a type III hypersensitivity reaction.[1] The presence of immune complexes activates the alternative complement pathway, leading to the infiltration of leukocytes and the proliferation of mesangial cells in the glomerulus. These changes impair the capillary perfusion and glomerular filtration rate, leading to kidney failure (oliguria or anuria), acid-base imbalance, electrolyte abnormalities, volume overload, edema, and hypertension.[1] Target antigens thought to play a role in the pathogenesis of poststreptococcal glomerulonephritis include the bacterial cell membrane protein known as M protein, endostreptocin; nephritis strain-associated protein, also known as streptococcal pyogenic exotoxin B; nephrin plasma-binding protein; and nephritis-associated plasmin receptor.[1][21] In staphylococcal infection-associated glomerulonephritis, superantigens such as the staphylococcal enterotoxins C, A, and toxic shock syndrome toxin-1 are thought to activate T cells by binding to major histocompatibility complex class II molecules, leading to B- and T-cell proliferation and glomerular damage.[22] Neutrophil activation and the formation of neutrophil extracellular traps in response to infections are also thought to play a role in stimulating the immune system and mediating glomerular damage in staphylococcal infection-associated glomerulonephritis.[23][24]

In staphylococcal infection-associated glomerulonephritis, superantigens such as the staphylococcal enterotoxins C, A, and toxic shock syndrome toxin-1 are thought to activate T cells by binding to major histocompatibility complex class II molecules, leading to B- and T-cell proliferation and glomerular damage.[22] Neutrophil activation and the formation of neutrophil extracellular traps in response to infections are also thought to play a role in stimulating the immune system and mediating glomerular damage in staphylococcal infection-associated glomerulonephritis.[23][24] The glomerular targets and antigens involved in the pathogenesis of glomerulonephritis associated with viral and parasitic infections are summarized in Table 1.[25][26][16][27][28] Table Table 1. Clinical Presentations, Histopathological Hallmarks, and Glomerular Targets of Viral and Parasitic Infection-Related Glomerulonephritis. Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; IgG, immunoglobulin G; FSGS, focal segmental glomerulosclerosis; APOL1, apolipoprotein L1; AKI, acute kidney injury.

Histopathology of Infection-Related Glomerulonephritis The histopathological findings of viral- and parasite-associated glomerulonephritis are summarized in Table 1.[29][30][31][32] Key histopathological findings associated with bacterial infection-related glomerulonephritis are discussed below (see Images Histopathology Showing Poststreptococcal Glomerulonephritis and Histopathology Showing Staphylococcal Infection-Associated Glomerulonephritis). Light microscopy findings: Glomerular enlargement Glomeruli are diffusely, segmentally, or globally enlarged, with endocapillary and mesangial hypercellularity, creating a lobular configuration. Infiltration and proliferation Initially, neutrophilic infiltration predominates, leading to an exudative glomerulonephritis, which is followed by mononuclear cell infiltration. Mesangial and endothelial cell proliferation, as well as mesangial edema, obstruct the capillary lumina by inflammatory cells. Capillary basement membranes The capillary basement membranes typically appear of normal thickness. Occasional findings Rare glomerular fibrinoid necrosis, microthrombosis, and cellular crescents may be observed, especially in cases of rapidly progressive glomerulonephritis. Chronic evolution Over time, neutrophilic infiltration diminishes, and the endocapillary hypercellularity transitions to mesangial hypercellularity. Mild mesangial cellularity and matrix expansion may persist for several years but eventually resolve, resulting in a normal-appearing glomerulus. Interstitial and tubular changes Prominent interstitial and tubular leukocyte infiltration may be present. Tubules often contain red blood cells and may include eosinophilic, cast-like material. Immunofluorescence findings: Immunoglobulin and complement deposition Small, irregular, coarse granular deposits of polyclonal IgG and C3 along the glomerular capillary walls, with scattered mesangial deposits. IgM and IgA: Generally absent or minimal, except in cases associated with staphylococcal infection, where IgA may be predominant. C1q and C4 Typically absent. Properdin: May be present in some cases. Patterns of staining Described patterns include starry sky, garland, and mesangial patterns, which are commonly observed in poststreptococcal glomerulonephritis. Electron microscopy findings: Cellular changes Marked endocapillary hypercellularity with frequent neutrophils present in the glomerular tuft. Deposit characteristics

May be present in some cases. Patterns of staining Described patterns include starry sky, garland, and mesangial patterns, which are commonly observed in poststreptococcal glomerulonephritis. Electron microscopy findings: Cellular changes Marked endocapillary hypercellularity with frequent neutrophils present in the glomerular tuft. Deposit characteristics Occasional mesangial and small subendothelial deposits may be observed. The hallmark finding is the presence of large, hump-type subepithelial deposits, which occur without a significant reaction from the glomerular basement membrane. Chronic phase In the chronic stage of the disease, mesangial deposits become more prominent. Endocapillary proliferation is typically reduced, with mesangial deposits dominating the pathology. Table 2 highlights the salient histopathological features of poststreptococcal glomerulonephritis, staphylococcal-associated glomerulonephritis, and other bacterial infection-associated glomerulonephritis, as determined by light microscopy, immunofluorescence, and electron microscopy.[29][30][31][32] Table Table 2. Histopathological Characteristics of Bacterial Infection-Related Glomerulonephritis. Abbreviation: IgG, IgG, immunoglobulin G.

Obtaining a detailed history and performing a thorough physical examination are crucial in evaluating patients with suspected infection-related glomerulonephritis. Lower extremity edema, frothy urine, hematuria, and recent infection all support a diagnosis of infection-related glomerulonephritis. A recent viral prodrome characterized by fatigue, low-grade fever, and upper respiratory complaints may indicate a virus-associated infection-related glomerulonephritis.[33] In contrast, recent travel to an endemic area may indicate an underlying parasite infection-related glomerulonephritis.[34] Intravenous drug use should raise suspicion for HBV-, HCV-, or HIV-associated infection-related glomerulonephritis.[33] Below are specific findings in the most common causes of bacterial infection-related glomerulonephritis: Poststreptococcal glomerulonephritis: Poststreptococcal glomerulonephritis primarily affects children, with approximately 50% of cases being asymptomatic and discovered through routine urinalysis. The classic triad includes hematuria, edema, and hypertension, often following a recent streptococcal infection, such as pharyngitis, tonsillitis, or impetigo. Gross hematuria is the most common presenting symptom, characterized as smoky, tea-colored, or cola-colored urine, which occurs in 30% to 50% of cases.[35] Kidney involvement is generally transient, with recovery typically occurring within 1 to 2 weeks. Up to 80% of patients experience hypertension, which resolves in most cases within 10 days. Edema, particularly periorbital edema, is observed in 65% to 90% of cases, with generalized edema often indicating more severe disease.[35][36]

Poststreptococcal glomerulonephritis: Poststreptococcal glomerulonephritis primarily affects children, with approximately 50% of cases being asymptomatic and discovered through routine urinalysis. The classic triad includes hematuria, edema, and hypertension, often following a recent streptococcal infection, such as pharyngitis, tonsillitis, or impetigo. Gross hematuria is the most common presenting symptom, characterized as smoky, tea-colored, or cola-colored urine, which occurs in 30% to 50% of cases.[35] Kidney involvement is generally transient, with recovery typically occurring within 1 to 2 weeks. Up to 80% of patients experience hypertension, which resolves in most cases within 10 days. Edema, particularly periorbital edema, is observed in 65% to 90% of cases, with generalized edema often indicating more severe disease.[35][36] Staphylococcal infection-associated glomerulonephritis: Adults with this condition typically present with concurrent staphylococcal infections, such as endocarditis, cellulitis, or osteomyelitis. Common kidney-related manifestations include hematuria, proteinuria, elevated serum creatinine, and edema. The clinical course may vary from mild microscopic hematuria to full-blown nephritic syndrome. About 26% to 30% of older adult patients with staphylococcal infection-associated glomerulonephritis may present with or develop new-onset heart failure due to the combined impact of cardiovascular disease and fluid overload. Staphylococcal infection-associated glomerulonephritis may also mimic vasculitis, with some patients developing cutaneous vasculitis resembling IgA vasculitis or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.[1][37] Other bacterial infection-associated glomerulonephritis: Patients with glomerulonephritis due to other bacterial infections (eg, endocarditis, deep-seated abscesses, and shunt infections) typically present with signs of infection alongside kidney-related manifestations. Hematuria and proteinuria are common, with some patients presenting with nephritic syndrome or nephrotic-range proteinuria. Hypertension and peripheral edema may be present. Kidney function impairment often correlates with the severity of infection and may resolve as the infection is treated.[9]

In all cases of infection-related glomerulonephritis, urine analysis, urine microscopy, and kidney function tests are required. Urine analysis and urine microscopy may demonstrate hematuria, proteinuria, dysmorphic red blood cells, and red blood cell casts. Proteinuria should be quantified by the urine protein-to-creatinine ratio and the urine albumin-to-creatinine ratio, and confirmed with a 24-hour urine protein collection. Blood urea nitrogen and serum creatinine may be elevated, especially in severe cases with oliguria or anuria. Neutrophilia, lymphocytosis, and eosinophilia may signify underlying bacterial, viral, or parasitic infection, respectively.[38] Imaging studies, such as a kidney ultrasound, may be used to assess kidney size and rule out obstructive nephropathy. Chest x-rays are indicated in patients with suspected heart failure, pulmonary involvement, or volume overload.[39] Diagnostic Tests and Findings According to the Underlying Cause of Infection-Related Glomerulonephritis Poststreptococcal glomerulonephritis: Diagnosis involves a combination of clinical assessment and laboratory evaluation.[36] Streptococcal antibody titers: Anti-streptolysin O, anti-DNAse B, and anti-hyaluronidase antibodies help confirm recent streptococcal infection. Elevated anti-streptolysin O titers are commonly observed after pharyngitis. Serum complement (C3): C3 levels are typically low during the acute phase and return to normal within 6 to 8 weeks. Kidney function tests: Blood urea nitrogen and serum creatinine may be elevated, especially in severe cases with oliguria or anuria. Kidney biopsy is generally not required unless atypical features are present, such as rapidly progressive glomerulonephritis, normal complement levels, or no rise in antistreptococcal antibodies.[36] Staphylococcal-associated glomerulonephritis (SAGN): Evaluation of SAGN includes both infection-specific and kidney-focused diagnostics.[1][37] Blood cultures: Essential for identifying the causative staphylococcal species, particularly in cases of endocarditis or osteomyelitis. Serum complement levels: C3 levels are typically low in SAGN, consistent with an immune-complex process. Transesophageal echocardiography: Performed to evaluate for staphylococcal endocarditis.

Blood cultures: Essential for identifying the causative staphylococcal species, particularly in cases of endocarditis or osteomyelitis. Serum complement levels: C3 levels are typically low in SAGN, consistent with an immune-complex process. Transesophageal echocardiography: Performed to evaluate for staphylococcal endocarditis. Kidney biopsy: Indicated when the diagnosis is unclear or when the patient exhibits rapidly progressive glomerulonephritis or crescentic glomerulonephritis. Findings often include endocapillary hypercellularity, mesangial proliferation, and immune-complex deposition.[1][37] Other bacterial infection-associated glomerulonephritis: Diagnosis is driven by identifying the underlying infection and correlating kidney-related symptoms.[9] Blood cultures: Necessary for identifying bacterial pathogens, especially in patients with endocarditis or deep-seated infections. Echocardiography: Particularly useful in diagnosing endocarditis-associated glomerulonephritis. Complement levels: C3 may be low in cases of immune complex glomerulonephritis. Kidney biopsy: May be indicated in cases with uncertain etiology or where there is suspicion of a vasculitic process.[9] Viral infection-related glomerulonephritis: Serum complement levels: May be reduced in cases of cryoglobulinemia.[40] Serologies: COVID testing is required if COVID is suspected. HIV, HBV, and HCV serologies are required to help differentiate between current and past infections.[33] Viral polymerase chain reaction (PCR) helps quantify active viral load.[41] Liver enzymes: May be elevated in viral hepatitis.[33] Kidney biopsy: May be indicated in cases with uncertain etiology or where there is suspicion of a vasculitic process.[9] Parasitic infection-related glomerulonephritis: Schistosomiasis: Diagnosis includes microscopic examination of eggs in the urine, serologies, and PCR.[34] Kidney biopsy: May show membranoproliferative, membranous, mesangioproliferative patterns of injury or focal segmental glomerulosclerosis.[42]

Kidney biopsy: May be indicated in cases with uncertain etiology or where there is suspicion of a vasculitic process.[9] Parasitic infection-related glomerulonephritis: Schistosomiasis: Diagnosis includes microscopic examination of eggs in the urine, serologies, and PCR.[34] Kidney biopsy: May show membranoproliferative, membranous, mesangioproliferative patterns of injury or focal segmental glomerulosclerosis.[42] Malaria: Diagnosis involves a complete blood count, which reveals anemia and thrombocytopenia, and a Giemsa-stained blood smear, which shows Plasmodia at various stages of development.[43] PCR may be required for diagnosis. Increased indirect and total bilirubin or lactate dehydrogenase indicate hemolysis.[43] A kidney biopsy may reveal minimal change disease, a membranoproliferative pattern, or focal segmental glomerulosclerosis.[42] Filariasis: Serological antibody testing, circulating antigen assays, and blood smears help confirm diagnosis.[44] A kidney biopsy may reveal membranous nephropathy or focal segmental glomerulosclerosis.[42]

Treatment of poststreptococcal glomerulonephritis, staphylococcal infection-associated glomerulonephritis, other bacterial infection-associated glomerulonephritis, and viral- and parasite-associated glomerulonephritis all require supportive care to manage hypervolemia, hypertension, and the effects of kidney dysfunction, in addition to specific therapies. Management of Hypervolemia and Hypertension Restriction of dietary sodium intake and loop diuretics may be used to manage hypervolemia and hypertension. Calcium channel blockers can be added for additional blood pressure control. Angiotensin-converting enzyme inhibitors are avoided in the acute phase of kidney injury to prevent further reduction of glomerular filtration rate and hyperkalemia. Patients with hypertensive emergencies may need parenteral antihypertensive medications.[35][3] Kidney Replacement Therapy Dialysis may be required in cases with severe kidney dysfunction to manage electrolyte and acid-base imbalances. Specific Considerations Individualized management strategies for each condition are described below. Poststreptococcal glomerulonephritis: Poststreptococcal glomerulonephritis is often a self-limiting condition that requires supportive treatment. Antibiotics are not indicated, as the infection usually resolves by the time kidney injury develops. Prophylactic antibiotics should be considered for close contacts of patients with group A Streptococcal infection in areas of high disease prevalence and transmission. However, there is no significant risk reduction in developing poststreptococcal glomerulonephritis after antibiotic therapy; however, it may prevent the spread of infection.[3][35] Based on current data, there is no definite recommendation for the use of immunosuppressive therapies. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines,[26] the risks and benefits of immunosuppression should be carefully weighed in patients with severe kidney impairment,  especially in the older population with several comorbidities. Some studies suggest that corticosteroids may be beneficial in severe cases of poststreptococcal glomerulonephritis to suppress acute inflammation and reduce the risk of long-term kidney damage.[1]

Poststreptococcal glomerulonephritis: Poststreptococcal glomerulonephritis is often a self-limiting condition that requires supportive treatment. Antibiotics are not indicated, as the infection usually resolves by the time kidney injury develops. Prophylactic antibiotics should be considered for close contacts of patients with group A Streptococcal infection in areas of high disease prevalence and transmission. However, there is no significant risk reduction in developing poststreptococcal glomerulonephritis after antibiotic therapy; however, it may prevent the spread of infection.[3][35] Based on current data, there is no definite recommendation for the use of immunosuppressive therapies. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines,[26] the risks and benefits of immunosuppression should be carefully weighed in patients with severe kidney impairment,  especially in the older population with several comorbidities. Some studies suggest that corticosteroids may be beneficial in severe cases of poststreptococcal glomerulonephritis to suppress acute inflammation and reduce the risk of long-term kidney damage.[1] Staphylococcal infection-associated glomerulonephritis: The management of SAGN focuses on identifying and treating the ongoing infection, as well as providing supportive care, similar to that in poststreptococcal glomerulonephritis. A thorough evaluation to identify the infection is vital. Timely initiation of empiric antibiotics while waiting for microbial culture and sensitivity results is essential. Prolonged antibiotic therapy is often necessary. Immunosuppressive therapy is contraindicated given the risk of worsening of infection.[1][3]

Staphylococcal infection-associated glomerulonephritis: The management of SAGN focuses on identifying and treating the ongoing infection, as well as providing supportive care, similar to that in poststreptococcal glomerulonephritis. A thorough evaluation to identify the infection is vital. Timely initiation of empiric antibiotics while waiting for microbial culture and sensitivity results is essential. Prolonged antibiotic therapy is often necessary. Immunosuppressive therapy is contraindicated given the risk of worsening of infection.[1][3] Other bacterial infection-associated glomerulonephritis: Apart from supportive measures, it is crucial to differentiate endocarditis-associated glomerulonephritis with positive ANCA serology from true ANCA-associated glomerulonephritis, as the latter requires aggressive immunosuppressive therapy. Immunosuppression is generally contraindicated in acute endocarditis-associated glomerulonephritis; however, there have been case reports of endocarditis-associated glomerulonephritis treated with steroids, either after eradication of the underlying bacterial infection or concurrently with antibiotics.[45] Valve replacement may be necessary in severe cases of endocarditis-related glomerular nephritis.[1][3] HBV-associated infection-related glomerulonephritis: Antiviral therapy is essential for preserving kidney function in patients with HBV-related glomerulonephritis. The KDIGO recommends treating HBV-related glomerulonephritis in patients with HBeAg positivity and or HBV DNA levels greater than 2000 IU/mL using nucleoside or nucleotide analogues. Immunosuppression is generally avoided to prevent HBV flares. The choice of antiviral agent depends on factors such as age, pregnancy, HIV co-infection, and kidney function. In HBV/HIV co-infection, tenofovir disoproxil fumarate is preferred for its dual activity. For patients on dialysis, tenofovir alafenamide or entecavir is recommended and administered after dialysis. The KDIGO also recommends plasma exchange in patients with symptomatic vasculitis and cryoglobulin levels higher than 500 mg/dL.[46][47][48]

HBV-associated infection-related glomerulonephritis: Antiviral therapy is essential for preserving kidney function in patients with HBV-related glomerulonephritis. The KDIGO recommends treating HBV-related glomerulonephritis in patients with HBeAg positivity and or HBV DNA levels greater than 2000 IU/mL using nucleoside or nucleotide analogues. Immunosuppression is generally avoided to prevent HBV flares. The choice of antiviral agent depends on factors such as age, pregnancy, HIV co-infection, and kidney function. In HBV/HIV co-infection, tenofovir disoproxil fumarate is preferred for its dual activity. For patients on dialysis, tenofovir alafenamide or entecavir is recommended and administered after dialysis. The KDIGO also recommends plasma exchange in patients with symptomatic vasculitis and cryoglobulin levels higher than 500 mg/dL.[46][47][48] HCV-associated infection-related glomerulonephritis: Direct-acting antiviral agents have transformed the management of HCV infection. These agents are used in combination over a 12-week course and are associated with viral response rates of greater than 95%. The KDIGO guidelines recommend the use of direct-acting antiviral agents for HCV-associated glomerulonephritis in patients with stable kidney function or non-nephrotic proteinuria. However, in cases of acute cryoglobulinemic vasculitis, nephrotic syndrome, cryoglobulinemic flare, or rapidly progressive renal failure, viral suppression alone may be insufficient due to the 4- to 8-week delay in viral clearance. In such cases, adjunctive immunosuppressive therapies—including corticosteroids, rituximab, and plasmapheresis—may be warranted. Emerging data suggest that recurrence or de novo glomerulonephritis may occur despite sustained virologic response, potentially linked to persistent polyclonal or monoclonal B-cell activation. Rituximab is currently suggested as first-line therapy for these cases.[49][47][48][47]

HCV-associated infection-related glomerulonephritis: Direct-acting antiviral agents have transformed the management of HCV infection. These agents are used in combination over a 12-week course and are associated with viral response rates of greater than 95%. The KDIGO guidelines recommend the use of direct-acting antiviral agents for HCV-associated glomerulonephritis in patients with stable kidney function or non-nephrotic proteinuria. However, in cases of acute cryoglobulinemic vasculitis, nephrotic syndrome, cryoglobulinemic flare, or rapidly progressive renal failure, viral suppression alone may be insufficient due to the 4- to 8-week delay in viral clearance. In such cases, adjunctive immunosuppressive therapies—including corticosteroids, rituximab, and plasmapheresis—may be warranted. Emerging data suggest that recurrence or de novo glomerulonephritis may occur despite sustained virologic response, potentially linked to persistent polyclonal or monoclonal B-cell activation. Rituximab is currently suggested as first-line therapy for these cases.[49][47][48][47] HIV-associated infection-related glomerulonephritis: The KDIGO recommends the immediate initiation of antiretroviral therapy (ART) in all HIV-positive patients with kidney disease, irrespective of CD4 count. Effective immunovirological control is essential to reduce the risk of acute kidney injury and HIV-associated kidney complications. Combination regimens typically involve 2 or more agents across 4 major classes of ART, each targeting distinct stages of the viral life cycle. HIV-related glomerulonephritis results directly from viral replication; consequently, ART-induced viral suppression is linked to slowing of glomerular filtration rate decline and histological improvement, including restoration of normal podocyte morphology within affected glomeruli. On the other hand, immune reconstitution inflammatory syndrome may manifest shortly after ART initiation, presenting as acute kidney injury secondary to acute interstitial nephritis or immune complex glomerulonephritis. HIV immune complex kidney disease often fails to respond to ART, likely due to irreversible damage to the glomerular basement membrane from immune complex deposition. Impaired kidney function influences the selection and dosing of renally excreted antiretrovirals, many of which carry specific nephrotoxic risks, necessitating vigilant monitoring of kidney function.[50][51][48]

HIV-associated infection-related glomerulonephritis: The KDIGO recommends the immediate initiation of antiretroviral therapy (ART) in all HIV-positive patients with kidney disease, irrespective of CD4 count. Effective immunovirological control is essential to reduce the risk of acute kidney injury and HIV-associated kidney complications. Combination regimens typically involve 2 or more agents across 4 major classes of ART, each targeting distinct stages of the viral life cycle. HIV-related glomerulonephritis results directly from viral replication; consequently, ART-induced viral suppression is linked to slowing of glomerular filtration rate decline and histological improvement, including restoration of normal podocyte morphology within affected glomeruli. On the other hand, immune reconstitution inflammatory syndrome may manifest shortly after ART initiation, presenting as acute kidney injury secondary to acute interstitial nephritis or immune complex glomerulonephritis. HIV immune complex kidney disease often fails to respond to ART, likely due to irreversible damage to the glomerular basement membrane from immune complex deposition. Impaired kidney function influences the selection and dosing of renally excreted antiretrovirals, many of which carry specific nephrotoxic risks, necessitating vigilant monitoring of kidney function.[50][51][48] COVID-19-associated infection-related glomerulonephritis: COVID-19-associated acute kidney injury and glomerular disease can occur due to direct viral effects, cytokine storm, endothelial damage, thrombotic microangiopathy, or systemic complications. In addition to supportive therapy, antiviral therapy helps in reducing viral load. In certain cases, immunomodulators such as dexamethasone and tocilizumab, an interleukin-6 blocker, may be required to control the inflammatory response. Accurate assessment and management of fluid status, as well as the management of a hypercoagulable state, are essential components of care. Early initiation of treatment is crucial. Remdesivir, nirmatrelvir/ritonavir, and molnupiravir have also been used in patients with advanced kidney disease. Dosing modifications for kidney function and drug interaction checks are recommended with each of these agents.[52][53][54]

COVID-19-associated infection-related glomerulonephritis: COVID-19-associated acute kidney injury and glomerular disease can occur due to direct viral effects, cytokine storm, endothelial damage, thrombotic microangiopathy, or systemic complications. In addition to supportive therapy, antiviral therapy helps in reducing viral load. In certain cases, immunomodulators such as dexamethasone and tocilizumab, an interleukin-6 blocker, may be required to control the inflammatory response. Accurate assessment and management of fluid status, as well as the management of a hypercoagulable state, are essential components of care. Early initiation of treatment is crucial. Remdesivir, nirmatrelvir/ritonavir, and molnupiravir have also been used in patients with advanced kidney disease. Dosing modifications for kidney function and drug interaction checks are recommended with each of these agents.[52][53][54] Parasite-associated infection-related glomerulonephritis: These conditions more prevalent in tropical and developing nations can cause severe acute illness. Early detection of the pathogen, along with targeted anti-infective therapy and supportive care, remains the mainstay of treatment even with kidney involvement. Antiparasitic therapy such as praziquantel, ivermectin, chloroquine, hydroxychloroquine, or primaquine may be required to hasten treatment.[44][43][34]

Awareness of the different entities that may present similarly to infection-related glomerulonephritis is essential, as treatment modalities vary based on the etiology of infection versus autoimmunity. Poststreptococcal glomerulonephritis versus SAGN: Distinguishing poststreptococcal glomerulonephritis from SAGN is crucial, as SAGN requires treatment of ongoing infection with antibiotics, whereas in poststreptococcal glomerulonephritis, the infection has often resolved before the kidney dysfunction manifests. No IgA deposits are observed on direct immunofluorescence in cases of poststreptococcal glomerulonephritis. IgA nephropathy, IgA vasculitis, or incidental IgA deposits: IgA nephropathy is the most common glomerulonephritis in the world. This disease typically occurs after an upper respiratory tract infection. The presence of low C3 levels may help distinguish SAGN from IgA Nephropathy. SAGN and IgA vasculitis can both present with a skin rash due to leukocytoclastic vasculitis. Stronger C3 staining as compared to IgA on direct immunofluorescence may help steer the diagnosis towards SAGN. In case of incidental IgA deposits, there are mild IgA deposits with no accompanying C3 noted on direct immunofluorescence. ANCA vasculitis: Evidence suggests that infection may contribute to the development of ANCA-associated granulomatosis and polyangiitis, which poses a treatment dilemma.[55] Some studies have also described ANCA staining in the SAGN biopsy sample. In such cases, SAGN could be mistaken for ANCA-associated glomerulonephritis.[1] As mentioned previously, the distinction between these 2 conditions is essential for choosing the proper treatment. Lupus nephritis: The presence of positive antinuclear antibody, double-stranded DNA, cytopenia, and multi-organ involvement may help differentiate lupus nephritis from infection-related glomerulonephritis. C3 glomerulopathy: Typically, in C3 glomerulopathy, there is no active ongoing infection; the disease course may be protracted with intermittent flares, and the low C3 levels are persistent. Some authors have also described infection as a second hit in patients with underlying abnormalities in the alternative complement pathway, leading to C3 glomerulonephritis.[1][56][57][56]

C3 glomerulopathy: Typically, in C3 glomerulopathy, there is no active ongoing infection; the disease course may be protracted with intermittent flares, and the low C3 levels are persistent. Some authors have also described infection as a second hit in patients with underlying abnormalities in the alternative complement pathway, leading to C3 glomerulonephritis.[1][56][57][56] Henoch-Schönlein purpura: Typically presents with palpable purpura, kidney failure, and gastrointestinal and musculoskeletal manifestations, with normal complement levels. Hemolytic uremic syndrome: Hemolysis, bloody diarrhea, thrombocytopenia, and stool culture positive for Escherichia coli O157:H7. Although Streptococcal and Staphylococcal infections are the most common causes of infection-related glomerulonephritis, several other bacterial, parasitic, and viral organisms are implicated in the development of glomerulonephritis and may be considered as potential etiologies of infection-related glomerulonephritis when appropriate.

In general, the prognosis of bacterial, viral, or parasitic infection-related glomerulonephritis depends on the presentation, pathogen, baseline kidney function, the presence or absence of rapidly progressive glomerulonephritis, and the timing of treatment.[3] Poststreptococcal glomerulonephritis typically has a favorable prognosis, with complete recovery observed in the majority of children. Kidney outcomes in the adult population are worse than in children. Residual hypertension and chronic kidney disease may be noted in 30% to 50% of affected adults. Kidney recovery is guarded in staphylococcal infection-associated glomerulonephritis. Some studies report up to 77% of patients with sustained chronic kidney disease. Progression to end-stage kidney disease needing dialysis may occur in about 43% of patients with risk factors such as diabetes mellitus, moderate-to-severe interstitial fibrosis and tubular atrophy, and advanced age. In other bacterial infection-associated glomerulonephritis, kidney function outcomes are poor, with complete recovery occurring in only about one-third of patients.[3] Parainfectious glomerulonephritis caused by non-streptococcal organisms and drug-resistant bacteria is associated with a poor prognosis.[58]

Complications of infection-related glomerulonephritis during the acute phase are hypertensive emergency and related conditions such as encephalopathy, fluid overload, and acute kidney failure needing kidney replacement therapy. Heart failure due to valvular heart disease may be observed in endocarditis-related glomerular nephritis and may further increase the risk of kidney dysfunction.

Avoiding overcrowded environments and maintaining personal hygiene are crucial measures that patients should take to reduce the risk of streptococcal infections, especially in areas with high population density and a high prevalence of disease. Prompt diagnosis and treatment of throat or skin infections is vital in preventing spread and possibly kidney complications. Vaccinations, especially before traveling to endemic areas, are essential for preventing viral and parasitic infection-related glomerulonephritis.

Management of infection-related glomerulonephritis requires a multidisciplinary approach involving internists, nephrologists, infectious disease consultants, intensivists, pharmacists, and nursing staff, all working together to provide excellent care for their patients. At the individual patient level, fluid and salt intake, edema, blood pressure, serum creatinine, and potassium levels, as well as urine output, require close monitoring. Avoiding nephrotoxic medication and medication adherence for antibiotics and antihypertensives are crucial. At the community level, encouraging the screening of all close contacts and family members to rule out an acute infection is key. Early recognition of kidney injury and consultation with a nephrologist can lead to improved outcomes.[59] A strategic approach is equally crucial, involving evidence-based strategies to optimize treatment plans and minimize adverse effects. Ethical considerations must guide decision-making, ensuring informed consent and respecting patient autonomy in treatment choices. Each healthcare professional must be aware of their responsibilities and contribute their unique expertise to the patient's care plan, fostering a multidisciplinary approach. Effective interprofessional communication is crucial, as it enables seamless information exchange and facilitates collaborative decision-making among team members. Care coordination plays a pivotal role in ensuring that the patient's journey from diagnosis to treatment and follow-up is well-managed, minimizing errors and enhancing patient safety. By embracing these principles of skill, strategy, ethics, responsibilities, interprofessional communication, and care coordination, healthcare professionals can deliver patient-centered care, ultimately improving patient outcomes and enhancing team performance in the management of infection-related glomerulonephritis.