Diagnosis and Management of Nephrotic Syndrome in Adults: A Comprehensive Guide

Introduction

Nephrotic syndrome (NS) in adults is a complex clinical condition characterized by a quartet of hallmark features: significant proteinuria, hypoalbuminemia, hyperlipidemia, and edema. This syndrome arises from an increased permeability of the glomerular basement membrane within the kidneys, leading to the excessive leakage of protein into the urine. This glomerular dysfunction can stem from primary kidney diseases or occur secondary to a range of systemic conditions, including infections, diabetes mellitus, systemic lupus erythematosus (SLE), malignancies, and certain medications. Understanding the etiology, pathophysiology, and clinical presentation of nephrotic syndrome is crucial for effective diagnosis and management, requiring a multidisciplinary approach to optimize patient outcomes.

Nephrotic-range proteinuria, a defining characteristic, is typically quantified as urinary protein excretion exceeding 3 grams per 24 hours, or a protein-to-creatinine ratio of 2 g/g on a spot urine sample. While nephrotic syndrome can manifest at any age, the presentation in adults often differs from that in children. Adults commonly present with edema in dependent areas of the body, such as the legs and ankles, while children may initially exhibit facial swelling.

It’s important to distinguish nephrotic syndrome from nephritic syndrome. While both involve glomerular disease, nephritic syndrome is characterized by glomerular inflammation leading to hematuria (blood in urine) and impaired kidney function, features that are less prominent in typical nephrotic syndrome, although overlap can occur. This article delves into the diagnosis and management of nephrotic syndrome specifically in adults, providing a comprehensive overview for healthcare professionals.

Etiology of Nephrotic Syndrome in Adults

The causes of nephrotic syndrome in adults are broadly categorized into primary and secondary glomerular diseases.

Primary Glomerular Diseases

Primary causes involve intrinsic kidney pathologies, where the kidney is the primary organ affected. These include:

• Membranous Nephropathy (MN): The most common primary cause of nephrotic syndrome in White adults. MN is characterized by thickening of the glomerular basement membrane due to the deposition of immune complexes. Idiopathic MN, accounting for the majority of cases, is often associated with antibodies to the phospholipase A2 receptor (PLA2R) on podocytes. Secondary forms can be triggered by malignancy, infections (hepatitis B, lupus), and drugs.
• Focal Segmental Glomerulosclerosis (FSGS): While more prevalent in African American populations as a primary cause, FSGS is also seen in adults of all ethnicities. FSGS is defined by scarring (sclerosis) in segments of some glomeruli. It can be primary (idiopathic) or secondary to genetic mutations affecting podocyte proteins (like nephrin, podocin), hypertension, obesity, reflux nephropathy, and HIV infection.
• Minimal Change Disease (MCD): Though more common in children, MCD can occur in adults, particularly in association with Hodgkin’s lymphoma, NSAID use, or allergic reactions. Renal biopsy shows minimal changes on light microscopy, hence the name, but electron microscopy reveals effacement of podocyte foot processes.

Secondary Causes of Nephrotic Syndrome

Secondary nephrotic syndrome arises as a complication of systemic diseases. Common secondary causes in adults include:

• Diabetes Mellitus: Diabetic nephropathy is a leading cause of secondary nephrotic syndrome globally. Chronic hyperglycemia leads to glomerular damage, resulting in proteinuria and eventually nephrotic syndrome.
• Systemic Lupus Erythematosus (SLE): Lupus nephritis, kidney involvement in SLE, is a significant cause of nephrotic syndrome, particularly in women. Immune complex deposition in glomeruli leads to inflammation and proteinuria.
• Amyloidosis: Various forms of amyloidosis, including AL amyloidosis (primary amyloidosis associated with plasma cell dyscrasias) and AA amyloidosis (secondary amyloidosis associated with chronic inflammation), can deposit amyloid fibrils in the glomeruli, disrupting their function and causing nephrotic syndrome.
• Infections: Certain chronic infections can lead to nephrotic syndrome. These include:
  • Hepatitis B and C: Viral antigens can trigger immune complex glomerulonephritis.
  • Human Immunodeficiency Virus (HIV): HIV-associated nephropathy (HIVAN), particularly in individuals with African ancestry carrying APOL1 risk alleles, can cause FSGS and nephrotic syndrome.
  • Syphilis: Secondary syphilis can rarely present with nephrotic syndrome.
• Malignancies: Certain cancers, particularly Hodgkin’s lymphoma and solid tumors, can be associated with membranous nephropathy as a paraneoplastic syndrome.
• Medications: Several drugs can induce nephrotic syndrome, including:
  • Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Can cause minimal change disease or membranous nephropathy.
  • Gold Salts and Penicillamine: Historically used for rheumatoid arthritis, can cause membranous nephropathy.
  • Lithium: Rarely, can induce nephrotic syndrome.
  • Bisphosphonates: Case reports link some bisphosphonates to FSGS.
  • Interferon: Interferon therapy has been associated with FSGS.
• Preeclampsia: In pregnant women, particularly in the third trimester, preeclampsia can manifest with nephrotic-range proteinuria.

Alt text: Diagram illustrating the various causes of nephrotic syndrome, categorized into primary glomerular diseases (Membranous Nephropathy, FSGS, Minimal Change Disease) and secondary causes (Diabetes, Lupus, Amyloidosis, Infections, Drugs, Malignancy).

Epidemiology of Nephrotic Syndrome in Adults

Nephrotic syndrome affects adults across all age groups, genders, and ethnicities. However, the incidence and underlying causes vary across populations.

• Age: While nephrotic syndrome can present at any age in adulthood, certain causes are more common at specific ages. For instance, membranous nephropathy is more frequent in older adults, while FSGS and MCD can occur across the adult age spectrum.
• Gender: There is a slight male predominance in nephrotic syndrome overall, similar to the general trend in chronic kidney disease. However, lupus nephritis, a significant cause of secondary nephrotic syndrome, is more common in women.
• Race and Ethnicity: Racial and ethnic disparities exist in the etiology of nephrotic syndrome. Membranous nephropathy is the most common primary cause in White adults. In contrast, focal segmental glomerulosclerosis is disproportionately prevalent as a cause of nephrotic syndrome in African Americans and Hispanics, often linked to genetic factors like APOL1 risk alleles and socioeconomic disparities affecting access to healthcare and management of conditions like hypertension and diabetes. Diabetic nephropathy is also more common in these populations due to higher rates of diabetes.
• Global Variation: The epidemiology of nephrotic syndrome varies geographically. In developed countries, diabetic nephropathy and primary glomerular diseases are leading causes. In some regions of the Middle East and Africa, infectious causes, although less common than previously thought, may still play a role. Schistosomal glomerulopathy, once considered a significant cause in certain tropical regions, is now less prevalent due to improved public health measures.

Pathophysiology of Nephrotic Syndrome

The fundamental defect in nephrotic syndrome is increased glomerular permeability to proteins. To understand this, it’s essential to review the normal glomerular filtration barrier.

The Glomerular Filtration Barrier

The glomerular filtration barrier is a complex three-layered structure designed to prevent the passage of large proteins while allowing water and small solutes to filter from the blood into the urine. The layers are:

1. Fenestrated Endothelium: The inner layer, composed of endothelial cells lining the glomerular capillaries, contains pores (fenestrations) that are relatively large but still restrict cells and large molecules.
2. Glomerular Basement Membrane (GBM): A meshwork of extracellular matrix proteins, including collagen and laminin. The GBM provides structural support and size-selective filtration, restricting molecules larger than approximately 70 kDa.
3. Podocytes: The outermost layer, specialized epithelial cells that envelop the GBM. Podocytes have foot processes that interdigitate, forming filtration slits bridged by slit diaphragms. These diaphragms are crucial for charge-selective filtration, as they are negatively charged and repel negatively charged proteins like albumin.

Mechanisms of Proteinuria

In nephrotic syndrome, damage to any component of this filtration barrier can disrupt its integrity, leading to massive proteinuria.

• Podocyte Injury: Podocyte damage is central to most primary glomerular diseases causing nephrotic syndrome. Effacement (flattening) of podocyte foot processes, detachment of podocytes from the GBM, and reduction in podocyte density are common findings. These changes reduce the size selectivity and charge selectivity of the filtration barrier, allowing albumin and other proteins to leak through.
• GBM Abnormalities: In membranous nephropathy, immune complex deposition thickens the GBM and alters its structure and function. In other glomerulopathies, GBM may be thinned or structurally altered.
• Endothelial Cell Dysfunction: Endothelial injury can contribute to proteinuria, although its role is less prominent in primary nephrotic syndrome compared to conditions like thrombotic microangiopathies.

Pathogenesis of Edema in Nephrotic Syndrome

Edema, a hallmark of nephrotic syndrome, arises from complex mechanisms, with two main hypotheses proposed:

1. Underfill Hypothesis: This classic theory posits that massive proteinuria leads to hypoalbuminemia. Reduced serum albumin concentration decreases plasma oncotic pressure. This oncotic pressure drop leads to fluid shifting from the intravascular space into the interstitial space, causing edema. The reduced intravascular volume then triggers renal sodium and water retention to compensate, further contributing to edema.
2. Overfill Hypothesis: This more recent theory suggests that primary sodium retention by the kidneys is the initiating event. It proposes an intrinsic renal tubular defect that increases sodium reabsorption, possibly due to the effects of filtered proteins on renal tubules. This primary sodium retention leads to volume expansion and edema. Evidence supporting this includes observations that sodium retention can precede hypoalbuminemia, and some nephrotic patients have normal or even increased intravascular volume.

In reality, edema formation in nephrotic syndrome likely involves a combination of both underfill and overfill mechanisms, with individual variations based on the specific underlying disease and patient physiology.

Hyperlipidemia and Hypercoagulability

Besides proteinuria and edema, nephrotic syndrome is associated with hyperlipidemia and hypercoagulability, contributing to increased cardiovascular and thromboembolic risks.

• Hyperlipidemia: The liver increases lipoprotein synthesis in response to hypoalbuminemia and reduced oncotic pressure. This leads to elevated levels of total cholesterol, LDL cholesterol, triglycerides, and lipoprotein(a). Impaired catabolism of lipoproteins due to decreased levels of enzymes like lipoprotein lipase also contributes.
• Hypercoagulability: Nephrotic syndrome increases the risk of thromboembolism, both venous and arterial. Several factors contribute:
  • Loss of anticoagulant proteins in urine, such as antithrombin III, protein C, and protein S.
  • Increased hepatic synthesis of procoagulant factors, including fibrinogen and factors V, VII, VIII, and X.
  • Increased platelet aggregation and endothelial dysfunction.
  • Hemoconcentration due to fluid shifts.

Alt text: Diagram illustrating the pathophysiology of nephrotic syndrome, showing the cascade from glomerular damage leading to proteinuria, hypoalbuminemia, edema, hyperlipidemia, and hypercoagulability.

Histopathology of Nephrotic Syndrome

Renal biopsy and histopathological examination are critical in diagnosing the underlying cause of nephrotic syndrome, especially in adults, to guide treatment. Different glomerular diseases exhibit distinct histological patterns.

• Minimal Change Disease (MCD): Light microscopy typically appears normal (hence “minimal change”). Immunofluorescence is negative. Electron microscopy is essential for diagnosis, revealing diffuse effacement of podocyte foot processes.
• Focal Segmental Glomerulosclerosis (FSGS): Light microscopy shows segmental sclerosis (scarring) within some glomeruli, which may progress to global glomerulosclerosis. Immunofluorescence is usually negative but may show non-specific IgM and C3 in sclerotic areas. Electron microscopy reveals podocyte foot process effacement, similar to MCD, but also shows segmental GBM collapse and sclerosis.
• Membranous Nephropathy (MN): Light microscopy shows diffuse thickening of the GBM. Immunofluorescence demonstrates granular deposits of IgG and C3 along the GBM. Electron microscopy is characteristic, showing subepithelial immune deposits and “spikes” of GBM material projecting outwards between the deposits (“spike and dome” pattern). PLA2R staining is often positive in idiopathic MN.
• Membranoproliferative Glomerulonephritis (MPGN): Light microscopy shows mesangial proliferation, GBM thickening, and often “double contouring” of the GBM (“tram-track” appearance). Immunofluorescence patterns vary depending on the type of MPGN (immune complex vs. complement-mediated). Electron microscopy shows subendothelial and/or intramembranous deposits.
• Diabetic Nephropathy: Light microscopy initially shows GBM thickening and mesangial expansion. Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) is a later, more specific finding. Immunofluorescence may show non-specific staining for albumin and immunoglobulins. Electron microscopy shows GBM thickening and mesangial expansion.
• Lupus Nephritis: Histological patterns in lupus nephritis are varied and classified (Class I to VI) based on the extent and location of glomerular lesions (mesangial, focal, diffuse, membranous, sclerosing). Immunofluorescence is typically strongly positive for immunoglobulins (IgG, IgA, IgM), complement (C3, C1q), and immune complexes in a “full house” pattern. Electron microscopy reflects the specific class of lupus nephritis.
• Amyloidosis: Light microscopy shows amorphous, eosinophilic deposits in glomeruli and blood vessels, which stain positively with Congo red and exhibit apple-green birefringence under polarized light. Immunofluorescence is usually negative. Electron microscopy reveals characteristic non-branching fibrils.

History and Physical Examination in Adult Nephrotic Syndrome

A detailed history and physical exam are essential for initial assessment and to guide diagnostic workup.

History

• Presenting Symptoms:
  • Edema: Location, onset, and progression of edema (dependent edema in legs/ankles, periorbital edema, ascites, pleural effusions).
  • Frothy Urine: Due to proteinuria.
  • Weight Gain: From fluid retention.
  • Fatigue and Malaise: Non-specific symptoms.
  • Loss of Appetite: May occur due to edema and systemic effects.
• Past Medical History:
  • Diabetes Mellitus: Duration, control, and complications.
  • Systemic Lupus Erythematosus (SLE) or other autoimmune diseases.
  • History of Cancer.
  • Chronic Infections: Hepatitis B, Hepatitis C, HIV.
  • Amyloidosis or Plasma Cell Dyscrasias.
  • Kidney Disease History: Prior proteinuria or kidney problems.
• Medication History: Detailed review of all medications, including NSAIDs, supplements, and over-the-counter drugs.
• Family History: Family history of kidney disease, nephrotic syndrome, or autoimmune diseases.
• Social History: Risk factors for HIV, hepatitis, and substance abuse.

Physical Examination

• Vital Signs: Blood pressure (hypertension is common, but hypotension can occur with volume depletion), heart rate, respiratory rate.
• General Appearance: Assess for signs of systemic illness.
• Edema Assessment:
  • Peripheral Edema: Examine for pitting edema in ankles, legs, and sacrum. Grade severity.
  • Periorbital Edema: Swelling around the eyes, especially in the morning.
  • Ascites: Abdominal distention, shifting dullness, fluid wave.
  • Pleural Effusions: Decreased breath sounds, dullness to percussion.
• Cardiovascular Exam: Assess for signs of volume overload (jugular venous distention, S3 gallop).
• Abdominal Exam: Assess for ascites, hepatomegaly, splenomegaly.
• Skin Exam: Rashes (malar rash in SLE), signs of chronic liver disease (spider angiomata, jaundice).
• Neurological Exam: Peripheral neuropathy (in diabetic nephropathy), signs of systemic illness.
• Fundoscopic Exam: Diabetic retinopathy (in diabetic nephropathy).

Evaluation and Diagnosis of Nephrotic Syndrome in Adults

The diagnosis of nephrotic syndrome involves laboratory testing, imaging, and often renal biopsy to determine the underlying cause.

Laboratory Evaluation

• Urine Studies:
  • Urinalysis: Dipstick testing for protein (3+ or 4+ indicates nephrotic-range proteinuria). Microscopic exam for casts (hyaline, granular, fatty, waxy, epithelial cell casts), hematuria. Lipiduria (free lipid or lipid in casts/tubular cells).
  • 24-hour Urine Protein Excretion: Gold standard for quantifying proteinuria (≥ 3 grams/24 hours for nephrotic range).
  • Spot Urine Protein-to-Creatinine Ratio (UPCR): Convenient alternative to 24-hour collection (UPCR ≥ 2 g/g is nephrotic range).
• Blood Tests:
  • Serum Albumin: Low levels (< 3.5 g/dL) are a hallmark of nephrotic syndrome.
  • Serum Creatinine and Blood Urea Nitrogen (BUN): Assess kidney function. Elevated levels indicate renal impairment.
  • Estimated Glomerular Filtration Rate (eGFR): Calculated from serum creatinine, age, gender, and race, provides a measure of kidney function.
  • Lipid Panel: Elevated total cholesterol, LDL cholesterol, triglycerides.
  • Complete Blood Count (CBC): May show anemia.
• Serologic Studies (to investigate secondary causes):
  • Serum Glucose and Hemoglobin A1c (HbA1c): Screen for and assess diabetes control.
  • Antinuclear Antibodies (ANA), Anti-dsDNA, Complement Levels (C3, C4): Evaluate for SLE.
  • Hepatitis B and C Serology: Screen for viral hepatitis.
  • HIV Antibody Test: Screen for HIV infection.
  • Serum and Urine Protein Electrophoresis with Immunofixation: Evaluate for monoclonal gammopathies and amyloidosis.
  • Cryoglobulins: Evaluate for cryoglobulinemia.
  • Rheumatoid Factor (RF) and Anti-cyclic Citrullinated Peptide (anti-CCP): Evaluate for rheumatoid arthritis.
  • Antineutrophil Cytoplasmic Antibodies (ANCA): Evaluate for ANCA-associated vasculitis.
  • Anti-glomerular Basement Membrane (anti-GBM) Antibodies: Evaluate for Goodpasture’s syndrome.
  • Phospholipase A2 Receptor (PLA2R) Antibodies: Specific for idiopathic membranous nephropathy. Positive PLA2R antibodies can support the diagnosis of primary MN without biopsy in some cases.

Imaging Studies

• Renal Ultrasound: Assess kidney size, echogenicity, and rule out hydronephrosis. Increased echogenicity may suggest chronic kidney disease. Useful to exclude obstruction and assess kidney size before biopsy.

Renal Biopsy

Renal biopsy is often crucial in adults with nephrotic syndrome to:

• Establish the specific histopathological diagnosis: Identify the type of glomerulonephritis (MCD, FSGS, MN, MPGN, etc.).
• Determine the etiology: Differentiate primary from secondary glomerular disease.
• Assess disease severity and prognosis: Evaluate the extent of glomerular damage, chronicity, and interstitial fibrosis.
• Guide treatment: Tailor immunosuppressive therapy based on the biopsy findings.

Indications for Renal Biopsy in Adults with Nephrotic Syndrome:

• Nephrotic syndrome in adults is generally an indication for biopsy, as the likelihood of secondary causes and the need for specific therapy are higher than in children.
• Atypical presentations (e.g., nephrotic syndrome with significant hematuria or rapid decline in kidney function).
• Suspected secondary cause where biopsy is needed for confirmation or to assess the extent of kidney damage (e.g., lupus nephritis, amyloidosis).
• Steroid resistance (if MCD is suspected clinically, but no response to initial steroid therapy).

Alt text: Image of a renal biopsy needle, illustrating the medical procedure used to obtain a kidney tissue sample for diagnosis.

Treatment and Management of Nephrotic Syndrome in Adults

Management of nephrotic syndrome in adults is multifaceted, aiming to:

1. Treat the underlying cause: If secondary nephrotic syndrome, addressing the primary disease is paramount.
2. Reduce proteinuria: To alleviate symptoms and slow kidney disease progression.
3. Manage edema: To improve patient comfort and reduce complications.
4. Treat hyperlipidemia and prevent thromboembolism: To reduce cardiovascular risk.
5. Manage complications: Infections, acute kidney injury, etc.

Specific Treatment Based on Etiology

• Primary Glomerular Diseases:
  • Minimal Change Disease (MCD): Corticosteroids (prednisone) are the first-line treatment. Most adults with MCD are steroid-responsive.
  • Focal Segmental Glomerulosclerosis (FSGS): Treatment is more challenging. Initial therapy often includes corticosteroids, but response rates are lower than in MCD. Immunosuppressants like cyclosporine, tacrolimus, mycophenolate mofetil (MMF), and rituximab may be used, especially for steroid-resistant FSGS. ACE inhibitors or ARBs are crucial for proteinuria reduction.
  • Membranous Nephropathy (MN): Treatment strategies are risk-stratified based on proteinuria levels and risk of progression to kidney failure. Low-risk patients may be monitored. Moderate- to high-risk patients require immunosuppression. First-line options include rituximab or cyclophosphamide alternating with corticosteroids (Ponticelli regimen). Calcineurin inhibitors (cyclosporine or tacrolimus) are also effective. PLA2R antibody levels can guide treatment and monitor response.
• Secondary Nephrotic Syndrome:
  • Diabetic Nephropathy: Optimal glycemic control, blood pressure management (ACE inhibitors or ARBs are first-line), and lifestyle modifications are crucial. SGLT2 inhibitors have shown renal protective benefits in diabetic kidney disease.
  • Lupus Nephritis: Immunosuppressive therapy tailored to the class of lupus nephritis, typically including corticosteroids and immunosuppressants like mycophenolate mofetil or cyclophosphamide. Rituximab may be used in certain cases.
  • Amyloidosis: Treatment focuses on the underlying amyloidogenic disorder (e.g., chemotherapy for AL amyloidosis, treatment of chronic inflammatory conditions for AA amyloidosis).
  • Drug-Induced Nephrotic Syndrome: Discontinue the offending medication.

General Management Strategies

• Edema Management:
  • Sodium Restriction: Low-sodium diet (< 2 grams/day) is essential.
  • Diuretics: Loop diuretics (furosemide, bumetanide) are first-line to promote sodium and water excretion. Thiazide diuretics or potassium-sparing diuretics (spironolactone) may be added for synergistic effect or to manage potassium balance. Metolazone can be used for diuretic resistance.
  • Albumin Infusion: May be considered in severe, symptomatic edema unresponsive to diuretics, but the benefit is often transient, and it’s not routinely recommended.
• Proteinuria Reduction:
  • ACE Inhibitors or Angiotensin Receptor Blockers (ARBs): First-line agents to reduce proteinuria, even in the absence of hypertension. They reduce intraglomerular pressure. Titrate to maximum tolerated doses.
• Hyperlipidemia Management:
  • Statins: First-line to lower LDL cholesterol and reduce cardiovascular risk.
  • Fibrates or other lipid-lowering agents: May be added if triglycerides remain elevated despite statin therapy.
• Anticoagulation:
  • Prophylactic anticoagulation (low-molecular-weight heparin or warfarin): Consider in patients with serum albumin < 2.5 g/dL, especially with other thromboembolic risk factors (immobility, prior thromboembolism). Risk-benefit assessment is needed.
• Dietary Management:
  • Adequate Protein Intake: Historically, low-protein diets were recommended, but current guidelines suggest normal protein intake (0.8-1.0 g/kg/day) to prevent malnutrition. Higher intake may be considered during active protein loss.
  • Low-Sodium Diet: As mentioned for edema management.
  • Potassium Monitoring: Diuretics can affect potassium levels.
  • Vitamin D Supplementation: May be needed due to urinary loss of vitamin D-binding protein.
• Infection Prevention:
  • Pneumococcal Vaccination: Recommended due to increased risk of pneumococcal infections.
  • Influenza Vaccination: Annually recommended.
  • Prompt treatment of infections: Increased susceptibility to infections due to immunosuppression and loss of immunoglobulins in urine.

Long-Term Monitoring

• Regular follow-up with nephrologist to monitor kidney function (serum creatinine, eGFR, proteinuria), serum albumin, lipids, and medication side effects.
• Blood pressure monitoring.
• Monitoring for steroid toxicity in patients on long-term corticosteroids.
• Assessment for thromboembolic events.
• Patient education on medication adherence, diet, and recognizing signs and symptoms of complications.

Differential Diagnosis of Nephrotic Syndrome

Several conditions can mimic nephrotic syndrome or present with edema and proteinuria, requiring careful differential diagnosis.

• Non-Nephrotic Range Proteinuria: Benign proteinuria, orthostatic proteinuria, transient proteinuria.
• Other Causes of Edema:
  • Cardiac Edema: Heart failure.
  • Hepatic Edema: Cirrhosis, liver failure.
  • Gastrointestinal Edema: Protein-losing enteropathy, malnutrition.
  • Lymphatic Edema: Lymphedema.
  • Venous Insufficiency: Chronic venous insufficiency.
  • Idiopathic Edema.
• Conditions with Proteinuria but not Nephrotic Syndrome:
  • Nephritic Syndrome: Glomerular inflammation with hematuria and acute kidney injury.
  • Tubulointerstitial Nephritis: May have proteinuria, but usually not in nephrotic range.
  • Polycystic Kidney Disease: May have proteinuria.
  • Hypertensive Nephrosclerosis: Proteinuria due to chronic hypertension.

Staging and Prognosis of Nephrotic Syndrome

Nephrotic syndrome itself is a clinical syndrome, not staged in the traditional sense. However, the underlying glomerular disease is the primary determinant of prognosis.

• Prognosis varies widely depending on the etiology.
• Minimal Change Disease (MCD): Excellent prognosis with steroid therapy. Most patients achieve remission, although relapses can occur. Long-term kidney failure is rare.
• Focal Segmental Glomerulosclerosis (FSGS): Prognosis is less favorable. Higher risk of steroid resistance and progression to end-stage renal disease (ESRD). Recurrence after kidney transplantation is common.
• Membranous Nephropathy (MN): Variable prognosis. Spontaneous remission occurs in some patients. Others progress to ESRD. PLA2R antibody levels can help predict prognosis. Immunosuppressive therapy improves outcomes in higher-risk patients.
• Diabetic Nephropathy: Progression to ESRD is common, but ACE inhibitors/ARBs and SGLT2 inhibitors can slow progression.
• Lupus Nephritis: Prognosis depends on the class of lupus nephritis and response to immunosuppression.
• Amyloidosis: Prognosis is often guarded, depending on the type and extent of amyloid deposition and response to treatment of the underlying amyloidogenic disorder.

Factors Associated with Poorer Prognosis:

• Older age at onset.
• African American race.
• Severe proteinuria at presentation.
• Hypertension.
• Impaired kidney function at presentation.
• Steroid resistance.
• Specific histopathological diagnoses (FSGS, membranous nephropathy, certain classes of lupus nephritis).

Complications of Nephrotic Syndrome

Nephrotic syndrome and its treatment can lead to various complications:

• Infections: Increased susceptibility to bacterial infections (pneumonia, peritonitis, cellulitis) due to loss of immunoglobulins and immunosuppressive therapy.
• Thromboembolism: Increased risk of venous thromboembolism (deep vein thrombosis, pulmonary embolism) and arterial thrombosis.
• Acute Kidney Injury (AKI): Can be precipitated by volume depletion, infection, or progression of underlying glomerular disease.
• Chronic Kidney Disease (CKD) and ESRD: Progression of glomerular disease can lead to irreversible kidney damage and need for dialysis or transplantation.
• Hyperlipidemia and Cardiovascular Disease: Increased risk of atherosclerosis and cardiovascular events.
• Hypocalcemia and Bone Disease: Vitamin D deficiency and calcium malabsorption can lead to metabolic bone disease.
• Malnutrition: Protein loss and anorexia can contribute to malnutrition.
• Anemia: Chronic kidney disease-associated anemia may develop.
• Steroid-Related Complications: In patients treated with long-term corticosteroids (weight gain, hyperglycemia, hypertension, osteoporosis, cataracts, infections).

Enhancing Healthcare Team Outcomes

Optimal management of nephrotic syndrome requires an interprofessional team approach, involving:

• Nephrologists: Lead diagnosis, treatment, and long-term management.
• Primary Care Physicians: Early detection, referral, and ongoing care coordination.
• Nurses: Patient education, medication management, monitoring, and symptom management.
• Pharmacists: Medication reconciliation, drug interaction checks, and patient counseling on medications.
• Dietitians: Dietary counseling on sodium restriction, protein intake, and lipid management.
• Social Workers: Address psychosocial needs and access to resources.

Effective communication and collaboration among team members are crucial to improve patient outcomes, reduce complications, and enhance quality of life for adults with nephrotic syndrome. Patient education and shared decision-making are also essential components of successful management.

References

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Disclosure: Carolina Tapia declares no relevant financial relationships with ineligible companies.

Disclosure: Khalid Bashir declares no relevant financial relationships with ineligible companies.