Sayna Norouzi, MD, is an assistant professor of medicine, clinical nephrologist, and founder and director of the glomerular disease and polycystic kidney disease clinics at Loma Linda University Medical Center.

Sayna Norouzi, MD

Pathophysiology of IgAN

This episode focuses on the underlying biology of IgA nephropathy, particularly the “multi-hit hypothesis.” The panel explains that the disease is driven not by a single event but by several interconnected immune steps, beginning with the production of galactose-deficient IgA1, followed by the formation of circulating autoantibodies, immune complex deposition in the kidney, and subsequent inflammatory injury. They discuss how each of these biological stages represents a potential therapeutic target. The clinicians emphasize that understanding the mechanism helps guide treatment choices, especially as newer agents are designed to intervene earlier in the disease pathway. They contrast older, broad immunosuppressive drugs with emerging therapies that more selectively modulate specific immune steps. This mechanistic framing helps reinforce why some patients continue to worsen even when proteinuria is controlled: the deeper immune dysregulation may remain active. The segment helps connect pathophysiology directly to clinical decision-making.

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This episode focuses on the underlying biology of IgA nephropathy, particularly the “multi-hit hypothesis.”

Optimizing Supportive Care for IgAN

In this segment, the panel focuses on what “optimized supportive care” truly means for patients with IgA nephropathy. They emphasize that supportive therapy is not passive; it involves aggressively reducing proteinuria and protecting kidney function. The clinicians outline a structured approach that begins with maximizing RAAS blockade using ACE inhibitors or ARBs at the highest tolerated doses, alongside strict blood pressure control. They discuss incorporating SGLT2 inhibitors as a 

 of supportive care, noting that emerging evidence shows meaningful reductions in proteinuria and slower eGFR decline. Lifestyle modifications—such as dietary sodium restriction, weight management, and smoking cessation—are also highlighted. The group stresses that clinicians must confirm supportive therapy is fully optimized before escalating to immunosuppressive or targeted treatments. Yet, they acknowledge that if proteinuria remains elevated or eGFR continues to fall despite these measures, disease-modifying therapies become necessary. This segment underscores that supportive care is foundational, structured, and closely monitored—not simply a “waiting” phase.

In this segment, the panel focuses on what “optimized supportive care” truly means for patients with IgA nephropathy.

The panel discusses how clinicians assess progression in IgA nephropathy and the importance of recognizing high-risk patients early. They emphasize that proteinuria is a central prognostic marker, and that achieving sustained reduction is critical. However, they note that ongoing eGFR decline, even when proteinuria appears improved, signals continued immune-mediated injury and should prompt re-evaluation. The group then addresses diagnostic challenges, including the fact that many patients first present after significant kidney damage has already occurred. To improve early detection, they support lowering the biopsy threshold to persistent proteinuria around 0.5 g/day, particularly when accompanied by hematuria. Increased awareness among primary care clinicians is highlighted as essential for earlier referral. Finally, the discussion includes the role of the RaDaR Registry, which collects long-term real-world data to help identify progression patterns and refine risk stratification. Overall, the segment underscores the need for early diagnosis and vigilant monitoring.

RaDaR Insights on Proteinuria, eGFR Decline, and Diagnostic Challenges in IgAN

In this segment, the panelists discuss IgA Nephropathy, a glomerular disease primarily affecting young adults in their 20s and 30s. The condition has a slight predilection for males and Southeast Asians. Patients typically present asymptomatically with blood or protein in urine, or with gross hematuria following a respiratory tract infection. Less commonly, patients may develop severe nephrotic syndrome. Clinicians are most concerned with proteinuria and kidney function. Patients with proteinuria exceeding 0.5 grams are considered at risk for disease progression. The panel emphasizes that diagnoses often occur too late, with patients already having lost nearly half their kidney function. This is particularly critical because these young patients have decades ahead of them, and even small annual kidney function losses can lead to end-stage kidney disease, potentially requiring dialysis. The early detection and monitoring of these patients are crucial for preserving long-term kidney health.

Clinical and Laboratory Findings Suggestive of IgA Nephropathy (IgAN)

In this segment, the panelists discuss IgA Nephropathy, a glomerular disease primarily affecting young adults in their 20s and 30s. The condition has a slight predilection for males and Southeast Asians. Patients typically present asymptomatically with blood or protein in urine, or with gross hematuria following a respiratory tract infection. Less commonly, patients may develop severe nephrotic syndrome.

Clinicians are most concerned with proteinuria and kidney function. Patients with proteinuria exceeding 0.5 grams are considered at risk for disease progression. The panel emphasizes that diagnoses often occur too late, with patients already having lost nearly half their kidney function. This is particularly critical because these young patients have decades ahead of them, and even small annual kidney function losses can lead to end-stage kidney disease, potentially requiring dialysis. The early detection and monitoring of these patients are crucial for preserving long-term kidney health.

In this segment, the panelists discuss IgA Nephropathy, a glomerular disease primarily affecting young adults in their 20s and 30s. The condition has a slight predilection for males and Southeast Asians. Patients typically present asymptomatically with blood or protein in urine, or with gross hematuria following a respiratory tract infection. Less commonly, patients may develop severe nephrotic syndrome.
Clinicians are most concerned with proteinuria and kidney function. Patients with proteinuria exceeding 0.5 grams are considered at risk for disease progression. The panel emphasizes that diagnoses often occur too late, with patients already having lost nearly half their kidney function. This is particularly critical because these young patients have decades ahead of them, and even small annual kidney function losses can lead to end-stage kidney disease, potentially requiring dialysis. The early detection and monitoring of these patients are crucial for preserving long-term kidney health.


Sayna Norouzi, MD

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