Diagnosis and Management of Immune Checkpoint Inhibitor-Associated Nephrotoxicity: A Position Statement from the American Society of Onco-nephrology.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of renal immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), though glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms and clinicopathological features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for re-challenge with ICI following AKI episodes. In addition, we explore ICI use in special populations such as kidney transplant recipients and propose key areas of focus for future research and clinical investigation.

Cancer therapy in patients with reduced kidney function.

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

Structures for quality assurance and measurements for kidney replacement therapies: A multinational study from the ISN-GKHA.

AIM: Optimal care for patients with kidney failure reduces the risks of adverse health outcomes, including cardiovascular events and death. We evaluated data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to assess the capacity for quality service delivery for kidney failure care across countries and regions. METHOD: We explored the quality of kidney failure care delivery and the monitoring of quality indicators from data provided by an international survey of stakeholders from countries affiliated with the ISN from July to September 2022. RESULTS: One hundred and sixty seven countries participated in the survey, representing about 97.4% of the world's population. In countries where haemodialysis (HD) was available, 81% (n = 134) provided standard HD sessions (three times weekly for 3-4 h per session) to patients. Among countries with peritoneal dialysis (PD) services, 61% (n = 101) were able to provide standard PD care (3-4 exchanges per day). In high-income countries, 98% (n = 62) reported that >75% of centers regularly monitored dialysis water quality for bacteria compared to 28% (n = 5) of low-income countries (LICs). Capacity to monitor the administration of immunosuppression drugs was generally available in 21% (n = 4) of LICs, compared to 90% (n = 57) of high-income countries. There was significant variability between and within regions and country income groups in reporting the quality of services utilized for kidney replacement therapies. CONCLUSION: Quality assurance standards on diagnostic and treatment tools were variable and particularly infrequent in LICs. Standardization of delivered care is essential for improving outcomes for people with kidney failure.

Renal AA amyloidosis: presentation, diagnosis, and current therapeutic options: a review.

Amyloid A amyloidosis is thought to be the second most common form of systemic amyloidosis behind amyloidosis secondary to monoclonal Ig. It is the result of deposition of insoluble fibrils in the extracellular space of tissues and organs derived from the precursor protein serum amyloid A, an acute phase reactant synthesized excessively in the setting of chronic inflammation. The kidney is the most frequent organ involved. Most patients present with proteinuria and kidney failure. The diagnosis is made through tissue biopsy with involvement of the glomeruli in most cases, but also often of the vessels and the tubulointerstitial compartment. The treatment usually targets the underlying etiology and consists increasingly of blocking the inflammatory cascade of cytokines with interleukin-1 inhibitors, interleukin-6 inhibitors, and tumor necrosis factor-α inhibitors to reduce serum amyloid A protein formation. This strategy has also shown efficacy in cases where an underlying etiology cannot be readily identified and has significantly improved the prognosis of this entity. In addition, there has been increased interest at developing effective therapies able to clear amyloid deposits from tissues, albeit with mitigated results so far.

Anxiety, depression and post-traumatic stress disorder in patients on hemodialysis in the setting of the pandemic, inflation, and the Beirut blast: a cross-sectional study.

BACKGROUND: In 2020, Lebanon has witnessed its worst economic crisis, exacerbated by the COVID-19 pandemic and a massive explosion of its capital. Amidst these stressors, this study aims at assessing the prevalence of depression, anxiety, suicidality, post-traumatic stress disorder (PTSD) and cognitive impairment in patients undergoing hemodialysis in an academic hospital destroyed by the explosion. METHODS: This cross-sectional study conducted 6 months after the blast included adults on hemodialysis, with no previous diagnoses of dementia or intellectual disability. It explores prevalence rates of psychiatric disorders, in addition to other medical and psychosocial variables such as frailty, malnutrition, sarcopenia, quality of life and religiosity. RESULTS: Forty two patients (mean age 66.1; SD: 11.2 years) undergoing hemodialysis for 6.12 years (SD:7.22 years) were included. Anxiety and depression rates reached 54.8% and 57.1% using cut-offs of 6 and 7 respectively on the Hospital Anxiety and Depression rating Scale. 9.5% of the patients reported being in the hospital at the time of the blast and 7.1% reported being injured. 33.3% screened positively for PTSD using a cut-off of 23 on the PCL-5. 26.2% had passive death wishes and 7.1% had suicide plans, however no one had attempted it. 23.8% were found cognitively impaired as shown by the Mini-Cog (<3). Around two-third of participants were moderately to severely malnourished per the GLIM criteria. One third suffered from frailty, according to the FRAIL screening tool. Around 60% suffered from sarcopenia, based on handgrip strength measures. These findings contrast with "acceptable to good" quality of life subjectively reported by participants on the Short Form 36 (SF-36) Health Survey. While one-third of participants participated in organizational religious activities, 88% reported significant subjective meaning of religion in their heart. CONCLUSIONS: Rates of depression, anxiety, PTSD, suicidality, and cognitive impairment were found to be alarming in the setting of an urban dialysis unit following a major explosion. Psychiatric disorders were found to be compounded with increased prevalence of malnutrition, frailty, and sarcopenia. These findings urge healthcare providers to implement early diagnostic and intervention strategies to improve both mental and physical wellbeing of this vulnerable population, in similar settings.

Hypertension Related to Obesity: Pathogenesis, Characteristics and Factors for Control.

The World Health Organization (WHO) refers to obesity as abnormal or excessive fat accumulation that presents a health risk. Obesity was first designated as a disease in 2012 and since then the cost and the burden of the disease have witnessed a worrisome increase. Obesity and hypertension are closely interrelated as abdominal obesity interferes with the endocrine and immune systems and carries a greater risk for insulin resistance, diabetes, hypertension, and cardiovascular disease. Many factors are at the interplay between obesity and hypertension. They include hemodynamic alterations, oxidative stress, renal injury, hyperinsulinemia, and insulin resistance, sleep apnea syndrome and the leptin-melanocortin pathway. Genetics, epigenetics, and mitochondrial factors also play a major role. The measurement of blood pressure in obese patients requires an adapted cuff and the search for other secondary causes is necessary at higher thresholds than the general population. Lifestyle modifications such as diet and exercise are often not enough to control obesity, and so far, bariatric surgery constitutes the most reliable method to achieve weight loss. Nonetheless, the emergence of new agents such as Semaglutide and Tirzepatide offers promising alternatives. Finally, several molecular pathways are actively being explored, and they should significantly extend the treatment options available.

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review.

BACKGROUND: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. SUMMARY: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.

Current State of Immunosuppression: Past, Present, and Future.

The success of solid-organ transplantation was made possible by recognizing that destruction of the graft is caused by an alloimmune-mediated process. For the past decade, immunosuppressive protocols have used a combination of drugs that significantly decreased the rate of acute organ rejection. Despite advances in surgical and medical care of recipients of solid-organ transplants, long-term graft survival and patient survival have not improved during the past 2 decades. Current immunosuppression protocols include a combination of calcineurin inhibitors, such as tacrolimus, and antiproliferative agents (most commonly mycophenolate mofetil), with or without different dosing regimens of corticosteroids. Mammalian target of rapamycin inhibitors were introduced to be used in combination with cyclosporine-based therapy, but they did not gain much acceptance because of their adverse event profile. Belatacept, a costimulatory inhibitor, is currently being studied in different regimens in an effort to replace the use of calcineurin inhibitors to induce tolerance and to improve long-term outcomes. Induction therapy is now being used in more than 90% of kidney transplants and more than 50% cases of other solid-organ transplantation such as lung, heart, and intestinal transplants. As a result of these combination immunosuppressive (IS) therapy protocols, not only the incidence but also the intensity of episodes of acute rejection have decreased markedly, and at present 1-year graft and patient survival is almost 98% for kidney transplant recipients and approximately greater than 80% for heart and lung transplants. Evolving concepts include the use of donor-derived bone marrow mesenchymal cells to induce tolerance, to minimize the use of maintenance IS agents, and to prevent the development of adverse events associated with long-term use of maintenance IS therapy.

A Western dietary pattern is associated with overweight and obesity in a national sample of Lebanese adolescents (13-19 years): a cross-sectional study.

Adolescent obesity is associated with both immediate and longer-term health implications. This study aims to identify dietary patterns among a nationally representative sample of Lebanese adolescents aged between 13 and 19 years (n 446) and to assess the association of these patterns with overweight and obesity. Through face-to-face interviews, socio-demographic, lifestyle and anthropometric variables were collected. Dietary intake was assessed using a sixty-one-item FFQ. Dietary patterns were derived by factor analysis. The following two dietary patterns were identified: Western and traditional Lebanese. The Western pattern was characterised by high consumption of red meat, eggs and fast-food sandwiches. The traditional Lebanese pattern reflected high intakes of fruits and vegetables, legumes and fish. Female sex and a higher maternal education level were associated with a greater adherence to the traditional Lebanese pattern. As for the Western pattern, the scores were negatively associated with crowding index, physical activity and frequency of breakfast consumption. After adjustment, subjects belonging to the 3rd tertile of the Western pattern scores had significantly higher odds of overweight compared with those belonging to the 1st tertile (OR 2·3; 95% CI 1·12, 4·73). In conclusion, two distinct dietary patterns were identified among adolescents in Lebanon: the traditional Lebanese and the Western, with the latter pattern being associated with an increased risk of overweight. The findings of this study may be used to guide the development of evidence-based preventive nutrition interventions to curb the obesity epidemic in this age group.

Non-Immunoglobulin Amyloidosis-Mediated Kidney Disease: Emerging Understanding of Underdiagnosed Entities.

Amyloidosis is a complex group of rare disorders characterized by the deposition of misfolded proteins in the extracellular space of various tissues and organs, leading to progressive organ dysfunction. The kidneys constitute a very common site affected, most notably by immunoglobulin-mediated (light chain, heavy chain, and light and heavy chain amyloidosis), but other types that include serum amyloid A (AA) amyloidosis and leukocyte chemotactic factor 2 amyloidosis, along with mutant proteins in several hereditary forms of amyloidosis such as transthyretin, fibrinogen α-chain, gelsolin, lysozyme, and apolipoproteins AI/AII/AIV/CII/CIII amyloidosis have been incriminated as well. The clinical presentation is variable and can range from minimal proteinuria for leukocyte chemotactic factor 2 amyloidosis to a full-blown nephrotic syndrome for AA amyloidosis. Clinical correlation, genetic analysis, and adequate tissue typing through a kidney biopsy are essential to make the correct diagnosis, especially when a family history of amyloidosis is absent. Except for AA and transthyretin amyloidosis, the treatment is usually purely supportive. Kidney transplantation is an acceptable form of treatment for end-stage kidney disease in all types of non-Ig-mediated renal amyloidosis.

Case report: Successful treatment of renal-limited thrombotic microangiopathy secondary to chronic lymphocytic leukemia.

Thrombotic microangiopathy (TMA) is a rare renal complication of patients with chronic lymphocytic leukemia (CLL) and is often associated with peripheral features. We present the first case of CLL patients with renal-limited TMA. A 70-year-old female patient with a history of well-controlled type 2 diabetes and baseline albuminuria of 87.2 mg/g 1 year prior and CLL was on active surveillance only. Her baseline white blood cell (WBC) was 202.6 x 103/µl. She presented with nephrotic syndrome with proteinuria of 10 g/g and a subsequent unremarkable serologic work-up. A kidney biopsy revealed diabetic glomerulosclerosis and chronic TMA. Initially, she was treated conservatively with angiotensin receptor blockade and sodium glucose cotransporter-2 inhibition but progressed with increased proteinuria of 17 g/g. Complement functional panel testing was pursued and showed dysregulation of the classical and alternative complement pathways. We decided to treat CLL which was suspected to be the culprit. At 9 months post-ibrutinib initiation, there was a 90% reduction in the WBC as well as a 94% reduction in proteinuria (17 g/g to 0.97 g/g). This case emphasizes the role of complement dysregulation in the pathogenesis of TMA in CLL patients. Treatment of CLL can restore complement dysregulation and improve renal outcomes.

Long-Term Cardiovascular Outcomes in Children and Adolescents With Hypertension.

Importance: Hypertension affects 6% of all children, and its prevalence is increasing. Childhood hypertension tracks into adulthood and is associated with subclinical cardiovascular disease; however, there is a lack of evidence linking childhood hypertension to cardiovascular outcomes, which may contribute to underdiagnosis and undertreatment. Objective: To determine the long-term associated risk of major adverse cardiac events (MACE) among children diagnosed with hypertension. Design, Setting, and Participants: This was a population-based, retrospective, matched cohort study conducted from 1996 to 2022. The study included all children (aged 3-18 years) alive in Ontario, Canada, from 1996 to 2021, who were identified using provincial administrative health databases. Children with prior kidney replacement therapy were excluded. Exposure: Incident hypertension diagnosis, identified by validated case definitions using diagnostic and physician billing claims. Each case was matched with 5 controls without hypertension by age, sex, birth weight, maternal gestational hypertension, prior comorbidities (chronic kidney disease, diabetes, cardiovascular surgery), and a propensity score for hypertension. Main Outcomes and Measures: The primary outcome was MACE (a composite of cardiovascular death, stroke, hospitalization for myocardial infarction or unstable angina, or coronary intervention). Time to MACE was evaluated using the Kaplan-Meier method and Cox proportional hazards regression. Results: A total of 25 605 children (median [IQR] age, 15 [11-17] years; 14 743 male [57.6%]) with hypertension were matched to 128 025 controls without hypertension. Baseline covariates were balanced after propensity score matching, and prior comorbidities were uncommon (hypertension vs control cohort: malignancy, 1451 [5.7%] vs 7908 [6.2%]; congenital heart disease, 1089 [4.3%] vs 5408 [4.2%]; diabetes, 482 [1.9%] vs 2410 [1.9%]). During a median (IQR) of 13.6 (7.8-19.5) years of follow-up, incidence of MACE was 4.6 per 1000 person-years in children with hypertension vs 2.2 per 1000 person-years in controls (hazard ratio, 2.1; 95% CI, 1.9-2.2). Children with hypertension were at higher associated risk of stroke, hospitalization for myocardial infarction or unstable angina, coronary intervention, and congestive heart failure, but not cardiovascular death, compared with nonhypertensive controls. Conclusions and Relevance: Children diagnosed with hypertension had a higher associated long-term risk of MACE compared with controls without hypertension. Improved detection, follow-up, and control of pediatric hypertension may reduce the risk of adult cardiovascular disease.

Assessment of GFR in Patients with Cancer: A Statement from the American Society of Onco-Nephrology.

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.

Capacity for the management of kidney failure in the International Society of Nephrology Middle East region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems.

Sustainable Development Goals: Challenges and the Role of the International Society of Nephrology in Improving Global Kidney Health.

The United Nations 2030 agenda for sustainable development includes 17 sustainable development goals (SDGs) that represent a universal call to end poverty and protect the planet, and are intended to guide government and private sector policies for international cooperation and optimal mobilization of resources. At the core of their achievement is reducing mortality by improving the global burden of noncommunicable diseases (NCDs), the leading causes of death and disability worldwide. CKD is the only NCD with a consistently rising age-adjusted mortality rate and is rising steadily up the list of the causes of lives lost globally. Kidney disease is strongly affected by social determinants of health, with a strong interplay between CKD incidence and progression and other NCDs and SDGs. Tackling the shared CKD and NCD risk factors will help with progress toward the SDGs and vice versa . Challenges to global kidney health include both preexisting socioeconomic factors and natural and human-induced disasters, many of which are intended to be addressed through actions proposed in the sustainable development agenda. Opportunities to address these challenges include public health policies focused on integrated kidney care, kidney disease surveillance, building strategic partnerships, building workforce capacity, harnessing technology and virtual platforms, advocacy/public awareness campaigns, translational and implementation research, and environmentally sustainable kidney care.

Monoclonal gammopathy of renal significance: Multidisciplinary approach to diagnosis and treatment.

Monoclonal gammopathy of renal significance (MGRS) is a hemato-nephrological term referring to a heterogeneous group of kidney disorders characterized by direct or indirect kidney injury caused by a monoclonal immunoglobulin (MIg) produced by a B cell or plasma cell clone that does not meet current hematologic criteria for therapy. MGRS-associated kidney diseases are diverse and can result in the development of end stage kidney disease (ESKD). The diagnosis is typically made by nephrologists through a kidney biopsy. Many distinct pathologies have been identified and they are classified based on the site or composition of the deposited Mig, or according to histological and ultrastructural findings. Therapy is directed towards the identified underlying clonal population and treatment decisions should be coordinated between hematologists and nephrologists in a multidisciplinary fashion, depend on the type of MGRS, the degree of kidney function impairment and the risk of progression to ESKD.

Approach to Diagnosis and Management of Hypertension: A Comprehensive and Combined Pediatric and Adult Perspective.

The global prevalence of primary hypertension has been increasing both in children and in the adolescent and adult populations and can be attributed to changes in lifestyle factors with an obesity epidemic, increased salt consumption, and sedentary lifestyles. Childhood blood pressure is the strongest predictor of adult hypertension. Although hypertension in adults is associated strongly with an increased risk for cardiovascular disease, chronic kidney disease, and mortality, outcomes in children are defined less clearly. In adults, major guidelines agree on a threshold of less than 120/80 mm Hg as the optimal blood pressure (BP) and recommend a target of less than 130/80 mm Hg for treatment in most cases. In children, international pediatric guidelines recommend using thresholds based on the normative distribution of BP in healthy normal-weight children. Out-of-office BP assessment is extremely useful for confirming the diagnosis of hypertension and monitoring response to treatment. Lifestyle modifications are instrumental whether coupled or not with pharmacologic management. New agents such as nonsteroidal mineralocorticoid-receptor antagonists, aminopeptidase A inhibitors, aldosterone synthase inhibitors, and dual endothelin antagonists hold significant promise for resistant hypertension. The transition from pediatric to adult care can be challenging and requires careful planning and effective coordination within a multidisciplinary team that includes patients and their families, and pediatric and adult providers.

Weber-Christian disease associated with the tip variant of focal segmental glomerulosclerosis: a case report.

Weber-Christian disease (W-CD) is associated with relapsing nodular panniculitis and a variety of systemic findings. Renal parenchymal involvement has been rarely reported. The authors describe a case of nephrotic syndrome in an African-American man with a W-CD flare. The patient had chills and low-grade fever with painful lower extremity skin lesions. A renal biopsy demonstrated the tip variant of focal segmental glomerulosclerosis (FSGS). The kidney biopsy also suggested parenchymal involvement by W-CD disease, with supportive ultrastructural findings. The synchronous W-CD flare and biopsy-proven FSGS and the rapid and sustained response of both to limited treatment suggest a causative association.