KDIGO- 2025 IgAN Clinical Practice Guidelines

 Sept 2025- KDIGO released yet another IgAN Guidelines. The last one was in 2021. Since 2021, several new trials were published with novel agents to be used in IgAN-- from Nefecon, Sparsenten, Atrasenten and Iptacopan.  Which ones made this new guideline?

This is the main figure from the guidelines.

The key takeaways

1. In all patients, treatment of the immunological side of IgAN and the CKD side, at the same time
2. Addition of Nefecon as an alternative to Steroids
3. Addition of DEARA and SGLT2i to the main CKD treatment option.
4. Lower proteinuria goal of 0.5g/day or lower and ideally 0.3g/day. and a stable eGFR 
5. Early renal biopsy encouragement
6. Still consider clinical trials in the right cases. 

Few misses

1. Pure endothlin antagonists -- will they have a role?
2. Why did complement inhibition not make this cut... perhaps waiting for long-term data
3. APRIL inb soone to be approved and may even add a dent to this strategy above.

Topic Discussions: Auto antibodies in diffuse podocytopathies

Recent advances have reshaped how we view nephrotic syndrome moving from descriptive pathology to a mechanism-based model. A growing body of evidence shows that circulating autoantibodies against key slit diaphragm proteins—nephrin, podocin, and Kirrel1—play a central role in many cases of autoimmune podocytopathy. This was also confirmed in pediatric literature. 

These discoveries promise earlier, less invasive diagnosis and more precise, personalized treatment.

Yet, translating these insights into clinical practice is far from straightforward. The antibodies are often present at very low or transient levels, disappearing into the urine during active disease. Their titers fluctuate with relapses and remissions, complicating the timing of tests. Moreover, NS is heterogeneous: while many patients have anti-nephrin antibodies, others harbor antibodies to podocin or Kirrel1, and some exhibit overlapping profiles through “epitope spreading.”

Technical challenges also hamper detection. Assay performance depends on antigen fragment choice, expression system, and protein modifications—especially for the heavily glycosylated nephrin. To improve reliability, researchers emphasize combined strategies, pairing ELISA with high-resolution biopsy techniques like super-resolution microscopy.

The article proposes a roadmap: develop multiplex assays, standardize antigen design, integrate biopsy validation, and pursue longitudinal studies. Success could enable precision diagnostics and tailored therapy, transforming care for children and adults with nephrotic syndrome.

Is it time for targeted therapies for Glomerular Diseases?

Concept Map: How I treat Glomerular Diseases in the Older patients

 

Based on CJASN article published in 2025

Women in Nephrology 2025 Meeting at Northwell Health

Please see the announcement below for a very special conference taking place September 13 and 14^th  2025. The WIN Leadership Conference is a 2-day interactive program that brings together speakers who are well-known international leaders in Nephrology to provide sessions related to finding and succeeding in leadership roles. It includes context, tools, and knowledge pertinent to careers in private practice, industry, and academia as well as the different career tracks within academia.

 

Please join us for a wonderful event!!!

Here is the eventbrite link:

https://www.eventbrite.com/e/2025-women-in-nephrology-leadership-conference-tickets-1384242549729?aff=oddtdtcreator

Plasma Cell Dyscrasias and Kidney Transplantation- a consensus report

A multidisciplinary consensus report by specialists in nephrology, hematology/oncology, and pathology addresses the complex intersection of plasma cell dyscrasias (PCD), such as multiple myeloma, AL amyloidosis, and monoclonal gammopathy of renal significance, and end-stage kidney disease (ESKD), exploring candidacy and strategies for kidney transplantation. 

Patients with PCD face disproportionately high rates of ESKD, severely impacting survival and quality of life. Although a kidney transplant can offer meaningful benefits, its use has been historically limited by concerns regarding disease recurrence and suboptimal outcomes. In light of evolving PCD therapies that improve disease control and extend survival, a collaborative expert panel evaluated current evidence to redefine selection criteria and care pathways for PCD-ESKD patients eligible for kidney transplant. 

Key recommendations emphasize achieving and confirming robust hematologic response before kidney transplant, tailoring immunosuppression to balance rejection risk with infection and recurrence, and adopting biomarker-driven risk stratification. The report also emphasizes the importance of ongoing multidisciplinary collaboration and targeted post-transplant surveillance tailored to PCD. 

One classic example of this is PGNMID or C3GN, which has a high recurrence rate post-transplant. Below is a potential pre-transplant treatment strategy to prevent recurrence. 

Together, this consensus guidance aims to broaden kidney transplant access for patients with PCD-ESKD while safeguarding graft survival and long-term outcomes.

Guest Post by Naoka Murakami, MD

In the NEWS: Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression

We know that Type 1 DM is a tough condition to have. Type 1 DM is an autoimmune condition where the immune system destroys the insulin-producing beta cells, resulting in a total lack of insulin, without which the body can’t regulate blood sugar. 

The “obvious solution”  would be to replace these lost cells, but transplantation introduces another problem: the immune system attacks any foreign cells, requiring toxic immunosuppression that comes with significant risks. We know this from our world in pancreas and kidney transplantation. 

In a brief report in NEJM, a group in Europe showed how edited cells that survived transplantation by becoming completely invisible to the immune system—a development that circumvents the immune rejection hurdle—and potentially removes the need for hostile immunosuppression. What the investigators did was to make the transplanted cells INVISIBLE to the immune system. They used CRISPR technology to remove HLA markers and then a viral technology to increase levels of CD47-- don't attack me signal. This made foreign cells look like your own.  What a clever idea.. The exact opposite of immunotherapy for cancer. 

They then went on to test this in a 42-year-old individual with Type 1 DM. And injected these edited cells into his forearm muscle with NO immunosuppression drugs and monitored him for 12 weeks. What happened?-- Edited cells SURVIVED and are not visible to the immune system, and started producing insulin within days. The patient responded to meals and was glucose responsive, and PET scans showed living functioning grafts. This is a fascinating move in science. They only used 7% of the possible dose, so the person still needed insulin. But this was a fascinating proof of concept we may be able to use in other autoimmune diseases, and introducing gene editing cells without the need for immunosuppression.

In the NEWS: Obesity Related CKD

Obesity-related Chronic Kidney Disease (Ob-CKD) encompasses a wide range of manifestations in persons with chronic kidney disease (CKD), from cases without known structural damage (hyperfiltration or albuminuria) to more advanced stages with obesity-related glomerulopathy (glomerular hypertrophy, podocytopathy, mesangial matrix expansion, focal and segmental glomerulosclerosis, tubulointerstitial fibrosis, tubular atrophy, and vascular lesions). Ob-CKD can also coexist with other kidney diseases, affect persons on dialysis, and in kidney transplant recipients.

In response to this complexity, Spanish Society of Nephrology (S.E.N.), Latin American Society of Nephrology and Hypertension (SLANH), and Spanish Society for the Study of Obesity (SEEDO) developed a consensus report proposing a classification system based on renal alterations and CKD stage (non-dialysis, dialysis, or transplant), aiming to standardize terminology and guide clinical management.  One of our principal aims is to diagnose individuals with obesity and CKD, classify, and subsequently individualize their treatment. What remains undiagnosed will remain untreated.

The effective treatment of Ob-CKD requires a multidisciplinary approach involving nutritional therapy, physical activity, pharmacological treatment, and bariatric surgery when indicated. The consensus also emphasizes the role of incretin-based therapies, which have been shown to promote weight loss and improve cardiorenal outcomes, including reductions in cardiovascular events and mortality in persons with Ob-CKD.

This was published in Kidney International 

See a sample below of cases related to Ob-CKD

Guest Post by

Dr. Maria J Soler