Glomerular Diseases: New Guidelines Unpacked!

On March 24, 2026, new guideline updates and an expanded overview of glomerular diseases were published for the nephrology community in the United States. These updates addressed classification systems, diagnostic strategies, clinical manifestations, and management recommendations for glomerular diseases. The revised recommendations respond to the rising burden of glomerular diseases as a major cause of end-stage kidney disease, and they reflect advances in diagnostic technology, targeted therapies, and risk stratification for both adult and pediatric patients.

Glomerular diseases remain the third leading cause of end-stage kidney disease, or ESKD, in the United States, accounting for approximately 10,000 new cases annually. Only diabetes and hypertension contribute more cases to the national ESKD burden. This number gives a sense of scale: 10,000 new diagnoses each year translates to more than 27 people every day in the United States alone who progress to irreversible kidney failure due to glomerular disease. The guideline committees recognized that these disorders have a significant public health impact, especially since their progression may be slowed or altered with timely and precise intervention.

The new guidelines emphasize a dual classification system for glomerular diseases. Primary glomerular diseases are those that arise intrinsically from the kidney’s own tissue. Secondary glomerular diseases develop as a consequence of systemic illnesses, with systemic lupus erythematosus, certain infections, and malignancies being the most commonly cited triggers. This classification is foundational because it guides the diagnostic workup and downstream treatment. For instance, a patient with new-onset proteinuria and hematuria who also has a known systemic autoimmune disease may undergo a very different set of laboratory and biopsy evaluations than a patient with isolated kidney findings and no systemic symptoms.

The glomerular filtration barrier, the primary site of injury in these diseases, is made up of three crucial layers: fenestrated endothelial cells, a specialized basement membrane, and interdigitating podocytes. Each of these structures plays a distinct role in filtering the blood. When any part of this barrier is damaged, proteins and red blood cells that are normally retained in the bloodstream can leak into the urine. This manifests as proteinuria—an excess of protein in the urine—or hematuria, which is the presence of blood in the urine. The amount and type of urinary abnormalities give clues about the location and severity of the barrier injury. For example, severe podocyte injury typically leads to massive proteinuria, while basement membrane disruption can cause both proteinuria and hematuria.

Diagnosis of glomerular disease is multifaceted. The guidelines continue to recommend kidney biopsy as the gold standard in many cases. A biopsy is generally advised for patients who present with nephrotic or nephritic syndrome, unexplained kidney dysfunction, or have positive blood serologies for systemic diseases such as lupus. The decision to biopsy balances the benefit of obtaining a definitive diagnosis and guiding treatment against the risk of procedural complications, primarily bleeding. However, the 2025 guideline updates, incorporated into the 2026 overview, introduce important nuances. In selected situations, biopsy can be omitted. For example, in patients with membranous nephropathy who test positive for PLA2R antibodies and have stable kidney function, or in those with ANCA-positive vasculitis with classic clinical features, the diagnosis can be made without tissue confirmation. This reduces exposure to biopsy risks, especially in children and patients with bleeding diatheses.

The guidelines specify that diagnosis should combine clinical findings, serology, and imaging when possible to avoid unnecessary biopsies. This marks a change from previous protocols, where kidney biopsy was reflexively performed for most cases. The focus has shifted towards diagnostic efficiency and safety, particularly for pediatric patients and those with classic disease presentations.

Nephrotic syndrome is one of the cardinal clinical syndromes arising from glomerular disease. It is defined by urine protein excretion greater than 3500 milligrams over 24 hours, or a protein-creatinine ratio exceeding 3500 milligrams per gram. Other features include hypoalbuminemia—low blood albumin—hypercholesterolemia, the presence of edema, and a tendency toward hypercoagulability, which means an increased risk for blood clots. These findings are not simply laboratory curiosities; they reflect the loss of protein through the glomerular barrier, the liver’s compensatory increase in cholesterol production, and changes in the balance of blood clotting factors.

Patients with nephrotic syndrome, especially those with membranous nephropathy whose albumin drops below 2.5 grams per deciliter, face a substantially increased risk of thrombosis. Renal vein thrombosis is a particularly dreaded complication. Studies cited in the guidelines report that up to 25 percent of patients with membranous nephropathy may develop some form of thrombotic event. The mechanism is primarily the loss of anticoagulant proteins in the urine and increased hepatic synthesis of prothrombotic factors. Early identification and risk stratification are now built into the guideline recommendations.

For nephrotic syndrome, conservative therapy is foundational. It includes renin-angiotensin system blockers, either ACE inhibitors or ARBs, to reduce proteinuria and slow kidney function loss. Statins are used to address hypercholesterolemia, while diuretics help manage edema. SGLT2 inhibitors are recommended for patients with chronic kidney disease coexisting with nephrotic syndrome, reflecting an expanded role for these agents beyond diabetes. These therapies are now considered standard for all nephrotic syndrome cases involving chronic kidney disease, as stipulated in the 2025 guideline update.

The guidelines also address specific primary nephrotic syndromes, such as focal segmental glomerulosclerosis, or FSGS. FSGS can be primary, driven by immunologic mechanisms, or secondary to factors like obesity, sickle cell disease, or chronic drug exposure including lithium. Diagnosis depends on kidney biopsy, which reveals characteristic segmental scarring in the glomeruli. The worst prognosis is seen in the collapsing variant, while the tip lesion variant carries the best outlook. Conservative therapy is used for those with subnephrotic proteinuria, while high-dose glucocorticoids are first-line for primary nephrotic cases. Calcineurin inhibitors serve as second-line agents if steroid resistance develops.

Membranous nephropathy is another condition highlighted in the guideline updates. Around 75 percent of cases are primary, often marked by the presence of anti-PLA2R antibodies, while the remaining quarter are secondary to systemic diseases like lupus, hepatitis B, or certain tumors. The risk of thrombosis is particularly high in this group, estimated at up to 25 percent, with renal vein thrombosis being a major concern. A key management change is the emphasis on anti-PLA2R antibody testing. If a patient with membranous nephropathy tests positive and maintains a normal glomerular filtration rate, a kidney biopsy may be avoided. Observation with conservative therapy is recommended for 6 to 12 months to allow for possible spontaneous remission. Immunosuppression is reserved for persistent nephrotic-range proteinuria.

Minimal change glomerulopathy, the most common nephrotic syndrome in children and 10 to 15 percent of cases in adults, is characterized by sudden-onset nephrotic syndrome. It is diagnosed by biopsy, which shows normal light microscopy but reveals podocyte foot process effacement on electron microscopy. Glucocorticoids induce remission in over 80 percent of adults and over 90 percent of children.

Nephritic syndrome, or glomerulonephritis, represents a different clinical spectrum. It is defined by the presence of hematuria, usually with dysmorphic red blood cells or red cell casts in the urine. Proteinuria is also present, though typically less than in nephrotic syndrome. Other features may include hypertension, edema, and evidence of impaired kidney function. The clinical spectrum is broad, ranging from asymptomatic microscopic hematuria that may be found incidentally, to rapidly progressive glomerulonephritis, or RPGN, which is marked by a swift decline in kidney function over days to weeks.

RPGN is defined by a 50 percent drop in estimated glomerular filtration rate over a short period, often accompanied by crescent formation on kidney biopsy. ANCA-associated vasculitis, lupus nephritis, and anti-glomerular basement membrane disease are common causes. Prompt intervention is essential but often leaves patients with chronic kidney disease, even if acute lesions are reversed. In anti-GBM disease, more than half of patients also have lung involvement, known as Goodpasture syndrome. Diagnosis rests on linear IgG staining on biopsy, while treatment combines plasmapheresis, glucocorticoids, and cyclophosphamide.

The guidelines review immune complex-mediated glomerulonephritides as well. IgA nephropathy is the most frequent primary glomerular disease worldwide. It presents with either asymptomatic hematuria or gross hematuria that follows upper respiratory infections. About one-third of patients progress to end-stage kidney disease within 15 years. The new guidelines adopt a dual-target strategy for IgA nephropathy: preventing the formation of IgA-containing immune complexes and treating kidney damage due to nephron loss. Sparsentan, a dual endothelin-angiotensin receptor antagonist, and SGLT2 inhibitors are now recommended for progressive disease. Budesonide, in a targeted-release formulation, is FDA-approved as an antiproteinuric therapy. The guidelines also include specific recommendations for pregnancy planning and for children with IgA nephropathy.

IgA vasculitis is considered the systemic form of IgA nephropathy. It classically presents with a tetrad of rash, joint pain, abdominal pain, and kidney disease. The disease is more severe in adults, with treatment involving glucocorticoids and cyclophosphamide in rapidly progressive cases.

Lupus nephritis affects up to 75 percent of individuals with systemic lupus erythematosus. Diagnosis is by kidney biopsy, which classifies the disease into six categories. Conservative therapy with RAS blockers is used for classes I and II. Immunosuppression with mycophenolate mofetil is preferred for classes III, IV, and V. In class VI, where chronic changes predominate, kidney replacement therapy is considered. The 2025 update incorporates emerging data supporting newer agents such as belimumab and voclosporin as add-on therapies for patients with refractory lupus nephritis. Personalized risk stratification based on serology and biopsy findings now informs therapy selection and intensity.

Infection-related glomerulonephritis, or IRGN, classically follows streptococcal infections in children, but in adults, it is often linked to ongoing infections with Staphylococcus aureus or gram-negative bacteria. Supportive therapy and infection control remain the focus, but the guidelines now provide more specific indications for glucocorticoid use. For example, glucocorticoids are considered when patients have persistent nephrotic syndrome or rapid deterioration in kidney function despite 4 to 6 weeks of infection control. Adults with IRGN are monitored more closely for progression to chronic kidney disease, since their prognosis is worse than that of children.

Membranoproliferative glomerulonephritis, though rare and most common in children and young adults, is treated with immunosuppression when nephrotic-range proteinuria or kidney dysfunction is present.

The updated guidelines also cover diabetic kidney disease, the leading cause of chronic kidney disease and ESKD worldwide. Between 20 and 40 percent of people with diabetes develop diabetic kidney disease. Screening is recommended yearly: patients with type 2 diabetes should be screened at diagnosis, and those with type 1 diabetes should be screened after five years. Treatment involves maximizing RAS blockade, adding SGLT2 inhibitors when kidney function allows, and considering finerenone for persistent albuminuria despite optimal RAS therapy. The guidelines warn against combining multiple RAS agents due to risk of hyperkalemia and acute kidney injury.

The guidelines specify that for children with nephrotic syndrome, early referral to pediatric nephrologists is essential. Rituximab is now considered earlier in the treatment course for steroid-dependent cases, reflecting a move toward personalized, risk-stratified care.

The 2026 overview makes clear that the landscape of glomerular disease management is shifting toward more nuanced, risk-based, and patient-centered care. The new recommendations incorporate advanced serological and imaging markers, promote diagnostic efficiency, and expand the armamentarium of therapies for both nephrotic and nephritic syndromes. The scale of glomerular disease—10,000 new cases of ESKD per year in the United States alone—underscores the urgency of these changes. The risk of thrombosis in patients with membranous nephropathy and an albumin less than 2.5 grams per deciliter is so pronounced that up to one in four may experience a thrombotic event, often in the renal vein, making recognition and prevention a central focus of clinical practice.