Nephrology Commons^™

Endothelin Receptor Antagonists In Resistant Hypertension And Proteinuric Kidney Disease: Receptor Strategy And Volume Management, Corey Keith Goldman, Jesse M. Goldman

Division of Nephrology Faculty Papers

This narrative review examines how endothelin receptor antagonists (ERAs) can be used at the intersection of difficult-to-control hypertension, chronic kidney disease (CKD), and albuminuria or proteinuria. For clinicians, the central question is not receptor selectivity alone, but whether a specific agent, indication, dose, background therapy, and monitoring plan can deliver meaningful blood-pressure or kidney benefit without unacceptable fluid retention. Pulmonary arterial hypertension established the pharmacology and major safety liabilities of the class; the current implementation questions for hypertension and kidney specialists arise in systemic hypertension and proteinuric kidney disease. Aprocitentan is the first and only ERA approved for hypertension; in …

Target Trial Of Glucagon-Like Peptide-1 Agonists Versus Dipeptidyl Peptidase-4 Inhibitors And Mortality In Hemodialysis, Dustin Le, Duncan Kilpatrick, Walter K. Kraft, Morgan E. Grams, Bernard G. Jaar, Jung-Im Shin

Division of Nephrology Faculty Papers

INTRODUCTION: The comparative effectiveness of glucagon-like peptide-1 (GLP-1) agonists (GLP-1s) versus dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4s) in hemodialysis is unknown.

METHODS: Using 2011 to 2021 US Renal Data System and Medicare claims data, we emulated a target trial comparing new users of GLP-1s versus DPP-4s with patients who survived ≥ 90 days on in-center hemodialysis before medication initiation. We used inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs).

RESULTS: We identified 3671 GLP-1 and 12,039 DPP-4 users. After IPTW, mean age was 63 years, 52% male, 63% White, and mean body mass …

Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, And Treatment, Edward J. Filippone, John L. Farber

Division of Nephrology Faculty Papers

Primary membranoproliferative glomerulonephritis (MPGN) is an ultrarare disease characterized by immunofluorescence microscopy as either immune-complex mediated (IC-MPGN) or C3 glomerulopathy (C3), the latter subdivided by electron microscopy to C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both IC-MPGN and C3G typically have obvious C3 staining differentiating them from other causes of MPGN histology. Secondary causes must be excluded, including infections, autoimmune disease, and neoplasia. Clinical presentations are variable, including urinary sediment abnormalities, nephrotic syndrome, or a rapidly progressive course. The prognosis is unfavorable with about 50% reaching kidney failure by 10 years. Recurrence following transplantation is frequent, and allograft survival …

Primary Care Use And Clinical Outcomes In A Prevalent Cohort Of Patients Receiving Hemodialysis, Dustin Le, Hatem Najar, Zoheb Backer, Rohanit Singh, Byoungjun Kim, Morgan E. Grams, Laura Plantinga, Bernard G. Jaar

Division of Nephrology Faculty Papers

Rationale & Objective - Primary care is associated with improved health outcomes, but whether this is true for patients receiving dialysis is unclear. We evaluated the association of primary care use in the previous year and clinical outcomes using a prevalent cohort of patients receiving hemodialysis.

Study Design - Retrospective cohort study.

Setting & Participants - United States Renal Data System registry of prevalent patients requiring maintenance in-center on January 1, 2019, linked with Medicare claims data.

Exposure - Primary care use was defined as ≥ 1 outpatient visit to a provider with the specialty of Family, General, Geriatric, or …

Serum Factors In Primary Podocytopathies, Edward J. Filippone, John L. Farber

Division of Nephrology Faculty Papers

Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include …

Parvovirus B19 Infection In Kidney Transplant Recipients, Hatem Najar, Kiran Goli, Maria P. Martinez Cantarin

Division of Nephrology Faculty Papers

On August 14, 2024, the Centers for Disease Control issued a Health Alert Network (HAN) health advisory due to a surge in Parvovirus B19 (B19V) infections in the United States. Our report presents two cases of suspected donor-derived Parvovirus B19 infection in kidney transplant patients. Both cases had refractory anemia requiring treatment with intravenous immunoglobulin. These cases highlight the importance of awareness and monitoring of B19V infection in the context of recent epidemiologic trends to improve clinical outcomes in kidney transplant recipients.

The Road Ahead: Emerging Therapies For Primary Iga Nephropathy, Edward J. Filippone, Rakesh Gulati, John Farber

Division of Nephrology Faculty Papers

Primary IgA nephropathy (IgAN) is the most common form of primary glomerulopathy. A slowly progressive disease presenting in the young to middle-aged, most patients with reduced eGFR or proteinuria will progress to end-stage kidney disease (ESKD) in their lifetimes. The pathogenesis involves increased production of galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes that deposit in the glomerulus, eliciting mesangial cell proliferation, inflammation, and complement activation. The backbone of therapy is supportive, including lifestyle modifications, strict blood pressure control, and renin-angiotensin system inhibition targeting proteinuria < 300 mg/day. Sodium-glucose transporter 2 inhibitors are indicated for persisting proteinuria or declining eGFR. Sparsentan is indicated for persisting proteinuria. Immunosuppression should be considered for all patients at risk for progression (persisting proteinuria and/or declining eGFR). To reduce Gd-IgA1 production, targeted-release budesonide is approved. Agents targeting B cell survival factors APRIL or BAFF/APRIL have significantly reduced Gd-IgA1 production and proteinuria in phase 2 trials but await phase 3 data for approval. To reduce inflammation, high-dose steroids are ineffective and toxic in Caucasian patients, although lower-dose regimens may be effective in Chinese patients. Complement inhibition is being actively studied. The factor B inhibitor iptacopan has conditional approval. The terminal pathway inhibitors cemdisiran and ravulizumab show promise in phase 2 studies. Our current approach for those requiring immunosuppression involves combining the reduction of Gd-IgA1 (nefecon) with suppressing the effects of inflammation (iptacopan). The optimal duration of such therapy is uncertain. Clearly, there is more to be learned with many trials underway.

Contemporary Review Of Iga Nephropathy, Edward Filippone, Rakesh Gulati, John Farber

Division of Nephrology Faculty Papers

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%–50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate …

Real-Life Experience On The Effect Of Sglt2 Inhibitors Vs. Finerenone Vs. Combination On Albuminuria In Chronic Kidney Disease, Mohamad Hanouneh, Dustin Le, Bernard G. Jaar, Christina Tamargo, C. Elena Cervantes

Division of Nephrology Faculty Papers

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting.

METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m² and a urine albumin-to-creatinine ratio (UACR) ≥ …

Prevention Of Intradialytic Hypotension In Hemodialysis Patients: Current Challenges And Future Prospects, Seyed Mehrdad Hamrahian, Salem Vilayet, Johann Herberth, Tibor Fülöp

Division of Nephrology Faculty Papers

Intradialytic hypotension, defined as rapid decrease in systolic blood pressure of greater than or equal to 20 mmHg or in mean arterial pressure of greater than or equal to 10 mmHg that results in end-organ ischemia and requires countermeasures such as ultrafiltration reduction or saline infusion to increase blood pressure to improve patient’s symptoms, is a known complication of hemodialysis and is associated with several potential adverse outcomes. Its pathogenesis is complex and involves both patient-related factors such as age and comorbidities, as well as factors related to the dialysis prescription itself. Key factors include the need for volume removal …

Adipose Tissue Metabolic Changes In Chronic Kidney Disease, Eurico Serrano, Prashamsa Shenoy, Maria Paula Martinez Cantarin

Division of Nephrology Faculty Papers

Adipose tissue is a complex organ whose functions go beyond being an energy reservoir to sustain proper body energy homeostasis. Functioning as an endocrine organ, the adipose tissue has an active role in the body's metabolic balance regulation through several secreted factors generally termed as adipokines. Thus, adipose tissue dysregulation in chronic kidney disease (CKD) can have a deep impact in the pathophysiology of diseases associated with metabolic dysregulation including metabolic syndrome, insulin resistance (IR), atherosclerosis, and even cachexia. CKD is a progressive disorder linked to increased morbidity and mortality. Despite being characterized by renal function loss, CKD is accompanied …