Topic Discussion: Futball and the Kidney ( soccer)

What happens to the kidneys during a soccer match?

With the 2026 FIFA World Cup approaching, it's the perfect time to remember that soccer doesn't just challenge the heart and muscles—it also places unique physiological stress on the kidneys. A review in Kidney Medicine explores the fascinating intersection of sports nephrology and soccer. 

⚽ Top 5 Kidney Takeaways

Most kidney changes are physiologic—not pathologic.
Transient rises in serum creatinine, exercise-induced proteinuria, microscopic hematuria, and reductions in eGFR are common after intense matches and usually resolve within 24–72 hours.

Hydration is kidney protection.

Maintaining hydration before, during, and after matches minimizes tubular stress and limits increases in biomarkers such as NGAL and KIM-1, especially during play in heat.

Creatinine isn't the whole story.
Because muscle injury elevates serum creatinine, biomarkers such as cystatin C, NGAL, and KIM-1 may better distinguish physiologic adaptation from true kidney injury in athletes.

Avoid unnecessary NSAIDs.
Dehydration, heat stress, rhabdomyolysis, and NSAID use together substantially increase the risk of acute kidney injury during competition.

Soccer remains kidney-safe for most athletes.
With appropriate hydration, individualized risk assessment, and avoidance of nephrotoxins, even many athletes with CKD, a solitary kidney, or a kidney transplant can safely participate.

Bottom line: Soccer challenges the kidneys—but in healthy athletes these changes are usually adaptive, transient, and reversible. Understanding these physiologic responses helps clinicians avoid overdiagnosis while recognizing the rare athlete who truly needs evaluation.

Figure from paper

Consult Rounds: Mantle Cell Lymphoma and the Kidney

Mantle Cell Lymphoma Isn't Just Renal Infiltration

In a paper published in KI Reports, various GNs were reported with Mantle Cell lymphoma. When we think of kidney disease in mantle cell lymphoma (MCL), we often think about direct lymphomatous infiltration. This multicenter series reminds us that immune-mediated glomerular diseases are actually common and frequently improve with lymphoma-directed therapy.

Study Highlights

• 30 patients with MCL who underwent kidney biopsy from multiple centers.

• 20 had active MCL at biopsy.

• Among those with active disease:

  • 70% had kidney lesions attributable or potentially attributable to MCL.

  • 55% had immune complex (IC) or complement-mediated glomerular disease.

  • 40% had renal lymphomatous infiltration, often coexisting with glomerular lesions.

Interestingly, renal Pathology Was Remarkably Diverse. The spectrum included:

• PGNMID (including IgG3κ cases)

• C3 glomerulonephritis

• Secondary membranous nephropathy

• Lupus-like immune complex GN

• Tubular basement membrane immune deposits

• Concurrent lymphomatous infiltration in many patients.

Perhaps the most important finding: Patients with PGNMID, C3GN, and membranous nephropathy who received lymphoma-directed therapy experienced remission of both their hematologic disease and kidney disease, with marked improvements in creatinine and proteinuria.

Unlike many monoclonal gammopathy-associated kidney diseases, most glomerular lesions were polyclonal rather than monoclonal, suggesting that immune dysregulation and complement activation—rather than direct deposition of a circulating monoclonal protein—may drive kidney injury in MCL.

In summary, Kidney injury in MCL extends far beyond direct lymphoma infiltration.  Consider kidney biopsy in MCL patients with AKI, proteinuria, or hematuria.  Successful treatment of the lymphoma can result in remission of the glomerular disease, emphasizing the importance of multidisciplinary care between nephrology, pathology, and hematology.

Consult Rounds: Histotripsy associated AKI

 

Histotripsy is an emerging non-invasive, non-thermal ablative technology that uses focused ultrasound pulses to mechanically destroy tumors through acoustic cavitation. Approved by the FDA in late 2023 for treatment of liver tumors, histotripsy has generated excitement because it can fragment tissue without surgical incisions, ionizing radiation, or traditional thermal injury. Early studies have also suggested potential downstream immunomodulatory effects beyond localized tumor destruction.

During the procedure, patients typically undergo general anesthesia in an interventional radiology suite or hybrid operating room. Real-time ultrasound guidance is used to localize the lesion and define the treatment field. High-amplitude ultrasound pulses generate dense cavitation bubble clouds that rapidly expand and collapse, mechanically fractionating tissue into acellular debris while largely sparing surrounding structures. Treatment is delivered sequentially in a raster-like pattern across the lesion with continuous imaging feedback.( see above figure created via AI)

While the oncology potential of histotripsy is substantial, nephrologists should be aware of a possible emerging complication: histotripsy-associated acute kidney injury (H-AKI). In a recent brief report published in KI Reports, a patient developed AKI with hematuria shortly after hepatic histotripsy in the absence of alternative clear insults, with improvement following hydration and supportive care.

To further explore whether this represented an isolated event or a broader signal, post-marketing review of the FDA MAUDE database identified additional cases of renal impairment following hepatic histotripsy. Reported patients were often older females with larger treatment volumes (>90 cc). Some required dialysis, while others recovered with conservative management and intravenous fluids. However, MAUDE data remain hypothesis-generating and limited by underreporting, lack of adjudication, and incomplete clinical detail.

Additional support for this phenomenon comes from an abstract presented at the Society of Interventional Radiology describing multiple cases of histotripsy-induced AKI. Interestingly, several reports described dark or discolored urine, raising the possibility of pigment-mediated tubular injury.

At present, no biopsy-proven mechanism has been reported. Proposed pathophysiologic mechanisms include hemolysis with pigment nephropathy, release of cellular debris after extensive tissue fractionation, hemodynamic injury, inflammatory cytokine release, or immune-mediated interstitial injury. Larger treatment fields may increase systemic exposure to hemoglobin, heme pigments, and intracellular contents.

Why does this matter? Histotripsy is rapidly expanding beyond hepatic tumors into renal and other solid organ malignancies. As use increases, nephrologists, oncologists, and interventional radiologists should recognize AKI as a potential procedural complication requiring early identification and supportive management. Future studies are needed to better define incidence, mechanisms, biomarkers, and preventive strategies for H-AKI.

Detective Nephron: Poem Style

 Here is the next detective nephron but a poetic version

https://www.kidneynews.org/view/journals/kidney-news/18/4/article-p12_8.xml

KDIGO updates another IgAN guideline- 2026

 

Since the 2025 IgA nephropathy (IgAN) guideline update, three major therapies have reshaped the treatment landscape. Atrasentan, an endothelin A receptor antagonist, received accelerated approval for patients at high risk of progression (uPCR ≥1.5 g/g) based on the ALIGN trial. Added on top of RAS inhibition, it achieved a 38.1% reduction in proteinuria versus 3.1% with placebo, a significant 36.1% treatment difference.

Later in 2025, sibeprenlimab, an anti-APRIL monoclonal antibody targeting B-cell–mediated IgA production, was approved following the VISIONARY trial. It demonstrated a 50.2% reduction in proteinuria versus a 2.1% increase with placebo (difference 51.2%). Importantly, it also showed robust biologic effects, reducing pathogenic Gd-IgA1 by ~70% along with significant reductions in total IgA, IgM, and IgG.

Most recently, iptacopan, a complement factor B inhibitor, showed strong long-term outcomes. Over two years, it significantly slowed eGFR decline and reduced kidney failure events (HR 0.57), with an overall safety profile similar to placebo, though with higher rates of serious infections.

Together, these therapies target distinct pathways—hemodynamic, immunologic, and complement—marking a new era of mechanism-driven IgAN treatment.

Here is the most recent KDIGO update
Above cartoon was created using AI for illustrating a battle of the new class of agents for IgAN treatment

Perspective : Not All AKI in Cancer Is ATN: A Diagnostic Wake-Up Call

AKI is increasingly common in patients with cancer. Between sepsis, volume depletion, contrast exposure, and nephrotoxic therapies, it is often tempting—and convenient—to attribute kidney injury to acute tubular necrosis. 

But what if we are wrong more often than we think?

The Problem: Diagnostic Anchoring in Onconephrology

Cancer patients represent one of the most complex populations we manage. They are exposed to multiple therapies, experience rapid physiologic changes, and frequently have overlapping clinical syndromes. Despite this, many cases of AKI are still labeled as “ATN” early in the course, often without further evaluation. This diagnostic anchoring creates a critical blind spot—one that risks missing treatable and potentially reversible causes of kidney injury.

What Are We Missing?

Several important entities can mimic ATN in patients with cancer:

Immune checkpoint inhibitor–associated acute interstitial nephritis (AIN):
With the widespread use of PD-1, PD-L1, and CTLA-4 inhibitors, AIN is increasingly recognized. It is often delayed in onset, subtle in presentation, and highly responsive to corticosteroids. Without biopsy, it is frequently missed.

Thrombotic microangiopathy (TMA):
TMA can occur in association with VEGF inhibitors, hematologic malignancies, transplantation, and even cancer itself. Importantly, it may present without classic hematologic features. Complement-mediated mechanisms are increasingly implicated. Renal limited TMA is so common and often gets missed due to lack of heme parameters. 

Light chain–mediated kidney disease:
Cast nephropathy, light chain deposition disease, and other monoclonal protein–related injuries are not always immediately recognized, particularly outside specialized hematologic settings. Often this is missed in the setting of lymphoma and NON plasma cell based heme cancers. 

Drug-induced tubulointerstitial injury:
Proton pump inhibitors, antibiotics, and targeted cancer therapies can all contribute to kidney injury. These often coexist with immunotherapy, further complicating the clinical picture.

Non Dilated Obstruction:

This is definitely missed. We see this in Onconephrology all the time and especially in retroperitoneal mets cancers and or RP masses. Renal sonogram will show NO hydronephrosis but it is still hydronephrosis and b/l PCNs improve the renal function. 

Why This Matters

Multiple studies comparing clinical diagnoses with kidney biopsy findings have demonstrated significant discordance. A substantial proportion of cases initially presumed to be ATN are reclassified after biopsy—many into diagnoses that would change management.

Despite this, kidney biopsy is often deferred due to concerns about procedural risk, patient acuity, or the perception that it will not alter treatment decisions. Increasingly, however, that assumption does not hold true.

A Practical Framework: When to Pause and Reconsider

Before assigning a diagnosis of ATN in a patient with cancer, it is worth pausing and asking whether the full differential has been considered.

Red flags that should prompt further evaluation include:

• Recent or ongoing immunotherapy

• Exposure to VEGF inhibitors or novel targeted agents ( often most folks don't do a good detailed oncology history of meds)

• Underlying or suspected hematologic malignancy

• Lack of kidney recovery despite supportive care

• Presence of proteinuria or active urine sediment

Key questions to consider:

• Would identifying AIN change management (e.g., initiation of steroids)?

• Could this represent TMA requiring targeted or complement-directed therapy?

• Would a kidney biopsy meaningfully guide treatment decisions?

• Would this patient benefit from PCN as clinically seems to have hydronephrosis but no signs on imaging?

In this setting, labeling AKI as “ATN” without careful consideration is no longer sufficient.

AKI in patients with cancer is often more than just ATN. It may reflect immune-mediated injury, complement dysregulation, or monoclonal protein–related disease.

Recognizing these possibilities is essential to delivering the right treatment at the right time.

How often are you performing kidney biopsies in patients with cancer and AKI?
Have biopsy findings changed your management in unexpected ways?
Are we underutilizing kidney biopsy in this population?

Concept Map: APOL1 Mediated Kidney Disease (AMKD)

 

Consult Rounds: the Heart Failure, hyponatremia and no clues on physical exam???-- Detective Nephron style

The Heart Failure That Left No Clues on Physical Exam

Patient: Severe heart failure

Exam: Shockingly normal
Question: Where did the signs go?

CLUE #1: The Missing Congestion

• No crackles

• No JVD

• No edema

What may be happening?
Chronic HF adapts. Lymphatics drain. Veins stretch. Congestion hides.

CLUE #2: The Resting Alibi

• Looks fine in bed

• Symptoms only with exertion

What really is happening?
The exam interrogates patients at rest—CHF commits its crimes on exertion.

CLUE #3: Masked by Modern Therapy

• Diuretics

• ARNI / MRA

• SGLT2 inhibitors

What is possible?
Congestion is controlled. The disease is not.

CLUE #4: The Low-Output Plot Twist

• Poor perfusion

• Fatigue, weakness

• No obvious volume overload

This is Low-output HF leaves few visible footprints.

CLUE #5: Body Habitus Interference

• Obesity

• Thick chest wall

Strange: Classic signs are present—but physically undetectable.

What a nephrologist can do to get FORENSIC EVIDENCE 

What solves the case when the exam fails:

• Echocardiography -- looking also at IVC

• BNP / NT-proBNP

• Lung ultrasound (B-lines > crackles)

• Hemodynamics when needed ( RHC)

Severe heart failure with a silent physical exam

Verdict: The bedside exam detects overt congestion, not chronic compensation or low-output physiology. Use POCUS wisely!

HSCT -TA-TMA, the Kidney, and Complement-Targeted Therapies: Where We Are Now

Hematopoietic Stem Cell Transplant-associated thrombotic microangiopathy (TA-TMA) is a devastating complication of hematopoietic stem cell transplantation characterized by endothelial injury, microvascular thrombosis, and multiorgan dysfunction. The kidney is the most commonly and severely affected organ, with patients frequently developing acute kidney injury, proteinuria, hypertension, and long-term CKD. Renal involvement strongly predicts poor survival.

A figure from a recent review summarizes the challenges we have to diagnose TA-TMA and the limited treatment options of steroids, rituximab, and maybe eculizumab in certain cases.

Mounting evidence implicates complement dysregulation, particularly beyond the terminal C5 pathway, in TA-TMA pathogenesis. The strongest clinical data to date support narsoplimab, a monoclonal antibody targeting MASP-2 in the lectin pathway. Across multiple expanded-access and real-world case series—including the largest global cohort—narsoplimab demonstrated markedly improved 1-year survival in both adults and children, many with baseline renal dysfunction. Outcomes were best when used early, and safety signals were acceptable. These data culminated in FDA approval in December 2025 for TA-TMA in adults and children ≥2 years.

Beyond MASP-2 inhibition, upstream complement blockade is emerging. Iptacopan (factor B inhibitor) has been reported in small adult case series with improvement in hematologic markers and reduction in proteinuria, supporting a role for alternative pathway inhibition. Pegcetacoplan (C3 inhibitor) has been described in pediatric off-label cases and is under prospective investigation, reflecting interest in broader complement control for refractory disease.

Together, these studies suggest that earlier, upstream complement inhibition may provide better protection for the renal microvasculature and improve outcomes in TA-TMA compared with C5-only strategies.

HTN and TMA- Topic Discussion

Malignant hypertension with AKI or AKD is a life-threatening emergency that demands rapid blood-pressure control and carries a high risk of permanent kidney damage. When thrombotic microangiopathy (TMA) is present, diagnostic challenges intensify. Although complement-mediated TMA frequently presents with severe hypertension, malignant hypertension itself can cause TMA-like vascular injury. This has been a point of debate for many years. Does the TMA cause HTN or is HTN a cause of TMA as well? 

Early evaluation must therefore exclude secondary hypertension and secondary TMAs, which require etiology-specific treatment. Because a definitive distinction between essential hypertension and complement-mediated TMA relies on genetic testing that takes weeks, clinicians must use clinical and histologic clues to guide early complement-blocker therapy. Significant gaps remain in understanding pathogenesis, diagnosis, and treatment. A recent paper in KI really takes this to a better understanding. 

Some key messages from the review article

1. Malignant hypertension can directly cause a true TMA.
Severely elevated blood pressure can injure small vessels, leading to endothelial damage, platelet consumption, hemolysis, and classic TMA findings. This is not simply “secondary hemolysis”—it is a bona fide microangiopathic process.
2. Distinguishing hypertensive TMA from other TMAs is critical.
Hypertensive TMA can mimic HUS/TTP and complement-mediated TMA. Misdiagnosis can delay the correct therapy. The clinical context (markedly high BP, long-standing HTN, LVH, retinal changes) is key.
3. Treatment hinges on rapid but careful blood-pressure control.
The cornerstone is controlled BP reduction—typically in the ICU—with parenteral antihypertensives. This alone often reverses hematologic abnormalities and improves renal function.
4. ADAMTS13 and complement studies help guide management but should not slow treatment.
Work-up is important, especially when features are atypical or improvement is slower than expected. But initial management should start immediately based on clinical suspicion.
5. Kidney recovery varies widely—follow-up matters.
Some patients experience near-complete recovery; others progress to CKD or ESRD, especially when treatment is delayed. Long-term blood-pressure control is essential to prevent recurrence and preserve renal function.

     An important component is the heme component of TMA and it's presence in the systemic form of TMA. The figure( similar to the paper in KI) suggests that the complement-mediated TMA had most likely to have heme parameters of TMA as well followed by drug induced TMA and systemic diseases.  HTN is not that common. 

 

Next Detective Nephron

 Enjoy the journey of hypomagnesemia in the next DN in ASN Kidney News.

In the NEWS: Unmasking PGNMID: Is it Truly Monoclonal, or Are We Misclassifying Kidney Disease?

 

    Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a severe kidney disease, traditionally classified under Monoclonal Gammopathy of Renal Significance (MGRS). This classification implies that the kidney damage is caused by a single, abnormal B-cell or plasma cell clone producing a "monoclonal" antibody. However, a long-standing puzzle in nephrology has been the surprisingly low rate at which these supposed disease-causing clones are actually detected in PGNMID patients. This discrepancy has fueled a debate: is PGNMID always truly monoclonal, or are we sometimes misattributing its cause?

    A recent study published in Kidney International, led by Javaugue, Pascal, and colleagues, delves into this question using advanced diagnostic tools. They analyzed 56 PGNMID patients, employing highly sensitive immunoglobulin repertoire sequencing (RACE-RepSeq) on bone marrow samples and specialized immunofluorescence on kidney biopsies to scrutinize the nature of the deposited immunoglobulins. The findings challenge conventional understanding. Only 23% of the patients had a detectable bone marrow clone consistent with their kidney deposits. The predominant subtype, PGNMID-IgG3, accounted for 73% of cases and was the main reason for the low clone detection rate; a mere 9.8% of these IgG3 cases showed a clonal B-cell proliferation. 

Crucially, in clone-negative PGNMID-IgG3 kappa patients, kidney biopsies revealed that the immunoglobulin deposits were *oligoclonal* or *polyclonal*, not truly monoclonal as the "monotypic" appearance on standard immunofluorescence might suggest.

Patients with clone-negative PGNMID showed distinct characteristics compared to clone-positive patients. Although diagnosed younger, they presented with more severe symptoms at diagnosis, including significantly higher proteinuria, but, interestingly, showed a lower prevalence of hypocomplementemia. Since IgG3 is the most frequent isotype and is known to be highly effective to bind and activate complement components, this finding is somehow surprising. However, compared to clone-positive patients with an elevated circulating monoclonal Ig, serum IgG3 levels in this subgroup remain normal which could explain the absence of hypocomplementemia. The study also hinted at potential infectious triggers in clone-negative cases, observing increased IgG1 and highly mutated light chain repertoires.

This research strongly suggests that PGNMID is a heterogeneous condition. The authors conclude that most PGNMID-IgG3 cases are driven by oligoclonal or polyclonal IgG3 production and do not arise from an underlying monoclonal B-cell disorder. They propose that such cases should no longer be classified as MGRS, and suggest the term "proliferative glomerulonephritis with monotypic deposits" to accurately reflect their origin. This distinction is critical, as it has profound implications for how these patients are diagnosed and, ultimately, treated. The study underscores the power of advanced molecular techniques in refining our understanding and management of complex kidney diseases.

In the News: B cell and plasma cell therapies in Glomerular Diseases

Glomerular diseases often result from loss of immune tolerance, leading to the production of autoantibodies by plasmablasts/plasma cells. Besides secreting antibodies, B cells contribute to T cell activation through antigen presentation and the secretion of pro-inflammatory cytokines. Standard immunosuppression works broadly but has many side effects, and many patients remain refractory. Thus, there is growing interest in therapies that more precisely target B cells and plasma cells. This review in JASN 2025 really is a very nicely done summary of the topic. 

B cells develop through naïve, activated, memory, plasmablast, to plasma cell stages. Memory B cells and long-lived plasma cells are particularly important in sustaining autoantibody production. 

Differential expression of surface markers (e.g. CD20 present on many B cells but lost in plasma cells) and dependency on survival signals (such as BAFF, APRIL) define what makes some cells resistant to certain therapies. 

Some challenges are that some plasma cell populations are long-lived and reside in protected niches (e.g. bone marrow), making them resistant to many therapies. Risk of depleting beneficial B cell subsets (e.g. those with regulatory functions). Heterogeneity of disease: different glomerular diseases (IgA nephropathy, lupus nephritis, membranous nephropathy, vasculitis etc.) have varying dependence on B cells vs plasma cells.

Therapies targeting B cells and plasma cells have shown promise in trials for various glomerular diseases. See the table below. Novel tools (like CAR-T, bispecifics) may help overcome resistance and target plasma cells more effectively.

Lupus Nephritis has trials ongoing with BAFF inhibition, Anti CD20+BAFF, BTK inhibitor, Anti CD38, CAR-T and bispecifics.  ANCA vasculitis has trials ongoing in Anti CD20 with BAFF-APRIL, and CAR-T.  Membranous Nephropathy has trials ongoing in anti-CD-20, BAFF, BTK inhibitors and Anti CD-38.  MCD/FSGS has trials ongoing in Anti CD-20 and BTK inhibitors. IgAN has trials in APRIL, APRIL+BAFF, Anti CD38 and CAR-T as well. 

Table: Therapies Targeting B-Cell and Plasma Cell Lineages in Glomerular Disease

Target / Stage	Examples of Therapeutics	Notes
Naïve / Mature B Cells	Anti-CD20 mAbs (rituximab, obinutuzumab, ofatumumab)	Deplete most circulating B cells, but not plasma cells
B Cell Survival Signals	BAFF inhibitors (belimumab), BAFF/APRIL dual inhibitors (telitacicept)	Block trophic support for B cells and plasmablasts
BCR Signaling	BTK inhibitors (ibrutinib, acalabrutinib)	Reduce activation and differentiation
Plasmablasts / Short-lived PCs	Proteasome inhibitors (bortezomib, carfilzomib)	Induce apoptosis of antibody-secreting plasmablasts
Long-lived Plasma Cells	Anti-CD38 mAbs (daratumumab, isatuximab); anti-BCMA agents	Direct depletion, even in bone marrow niches
Novel Cellular Immunotherapy	CAR-T cells (anti-CD19, anti-BCMA); bispecific T-cell engagers	Potent but experimental; risk of profound immunosuppression
Regulatory B Cells (Bregs)	Indirectly affected by the above agents	Their depletion may worsen immune dysregulation—needs careful monitoring

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