Nephrotic Syndrome for the Internist.

Nephrotic syndrome (NS) is a key clinical entity for the internist to recognize and understand. A wide range of infectious, metabolic, malignant, and autoimmune processes drive nephrosis, leading to a syndrome defined by proteinuria, edema, and hypoalbuminemia. NS occurs due to increased permeability to proteins at the level of the glomerulus, which allows for passage of albumin and other proteins into the urine. Proteinuria leads to a cascade of clinical complications characterized by fluid accumulation, kidney inflammation, and dysregulation of coagulation and immunity. In this article, the authors review the clinically important etiologies of NS that should inform an initial clinical evaluation.

Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease.

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

Infective Endocarditis-Associated Pauci-Immune Glomerulonephritis in a Patient With Cryoglobulinemia.

Small-vessel vasculitis has a broad differential with similar clinical presentation and laboratory abnormalities, including petechial rashes, neurologic symptoms, glomerulonephritis, and abnormal inflammatory markers. Biopsy-based diagnosis is critical as the treatment varies by etiology. We report a case of a 41-year-old man with diagnosed cryoglobulinemia and hepatitis C presenting with a petechial rash, altered mental status, and acute kidney injury and ultimately found to have proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis secondary to infective endocarditis. Skin biopsy was consistent with resolving, but nonspecific vasculitis and MRI showed foci of hemosiderin deposition concerning vasculitic lesions. Blood cultures grew Enterococcus faecalis, and he was treated with IV antibiotics. Kidney biopsy showed pauci-immune necrotizing focal segmental glomerulonephritis (GN) and diffuse acute tubular necrosis (ATN). After blood cultures cleared, he was initially treated with mycophenolate for worsening renal function. When the patient stopped antibiotics unexpectedly, his kidney function worsened and improved only after immunosuppression was stopped and antibiotics were restarted. This case highlights the importance of renal biopsy in patients with multiple potential etiologies of GN. The case resolution also reinforces that patients with infective endocarditis causing ANCA-associated GN should be treated with antibiotics in addition to, and possibly instead of, immunosuppression.

Supportive Care and Symptom Management for Patients With Immunoglobulin Light Chain (AL) Amyloidosis.

Immunoglobulin light chain (AL) amyloidosis is a disorder of clonal plasma cells characterized by deposition of amyloid fibrils in a variety of tissues, leading to end-organ injury. Renal or cardiac involvement is most common, though any organ outside the central nervous system can develop amyloid deposition, and symptomatic presentations may consequently vary. The variability and subtlety of initial clinical presentations may contribute to delayed diagnoses, and organ involvement is often quite advanced and symptomatic by the time a diagnosis is established. Additionally, while organ function can improve with plasma-cell-directed therapy, such improvement lags behind hematologic response. Consequently, highly effective supportive care, including symptom management, is essential to improve quality of life and to maximize both tolerance of therapy and likelihood of survival. Considering the systemic nature of the disease, close collaboration between clinicians is essential for effective management.

Kidney thrombotic microangiopathy in lupus nephritis: Impact on treatment and prognosis.

INTRODUCTION: Lupus nephritis (LN) may present with thrombotic microangiopathy (TMA) on kidney biopsy, the impact of which on outcomes is unclear. This study examined the prognostic importance of LN with TMA on kidney biopsy, including response to therapy and long-term outcomes. METHODS: We conducted a single-center, retrospective study of all cases of LN with concomitant TMA on kidney biopsy in the Glomerular Disease Collaborative Network database. Controls were individuals with LN without TMA matched to cases based on demographic and clinical variables. Outcomes were remission at 6- and 12-months, end-stage kidney disease (ESKD) and death. Logistic regression and Cox proportional hazards models were used to ascertain the risks for outcomes, with adjustment for serum creatinine and proteinuria. RESULTS: There were 17 cases and 28 controls. Cases had higher creatinine, higher proteinuria and greater chronicity on biopsy at baseline compared to controls. The rates of remission at 6-months and 12-months were similar between cases and controls (6-months 53.9% vs 46.4%, adjusted OR 2.54, 95% CI 0.48, 13.37; 12-months 53.9% vs 50.0%, adjusted OR 2.95, 95% CI 0.44, 19.78). Cases were at greater risk for ESKD in univariate analysis (HR 3.77; 95% CI 1.24, 11.41) but not when adjusting for serum creatinine and proteinuria (HR 2.20; 95% CI 0.63, 7.71). There was no significant difference in the risk of death between cases and controls. CONCLUSION: Lupus nephritis with renal TMA likely responds to therapy similarly to those without TMA; risk for ESKD is not significantly increased, although the influence of renal function and proteinuria in larger samples is needed.

Racial-ethnic differences in health-related quality of life among adults and children with glomerular disease.

INTRODUCTION: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships between race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease. METHODS: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: 1. Missed school or work due to kidney disease; 2. Responses to Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression. RESULTS: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than White or Asian participants. Black adults missed work or school most frequently due to kidney disease (30% versus 16-23% in the other three groups, p=0.04), and had the worst self-reported global physical health (median score 44.1 versus 48.0-48.2, p<0.001) and fatigue (53.8 versus 48.5-51.1, p=0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status were associated with HRQOL. CONCLUSIONS: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by Black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.

Chronic Kidney Disease as a Predictor of Postoperative Choroidal Effusions After Glaucoma Surgery.

PRCIS: Patients with chronic kidney disease (CKD) are at increased risk for choroidal effusion development following glaucoma surgery. PURPOSE: Choroidal effusion is a postoperative complication of glaucoma surgery that results from a transudative fluid collection in the suprachoroidal space. Kidney disease alters bodily fluid dynamics through a variety of mechanisms. The relationship between CKD and choroidal effusion following glaucoma surgery has not previously been studied. The purpose of this study was to determine the relationship between CKD and choroidal effusion development after glaucoma surgery. PATIENTS AND METHODS: This retrospective cohort study consisted of 86 eyes from 86 patients who received glaucoma filtering surgery or transscleral cyclophotocoagulation within the study timeframe. Forty-three patients had CKD, and 43 patients did not have kidney disease. The main outcome of this study was the development of choroidal effusion measured by the Pearson χ2 test and multivariate analysis using a binomial regression with a log link. RESULTS: Ten patients (23.3%) in the CKD group developed choroidal effusion, while 2 patients (4.7%) in the no-kidney disease group developed choroidal effusion (relative risk, 5.0; 95% confidence interval: 1.16-21.5; P=0.013). The association between CKD and choroidal effusion showed mixed results in the multivariate analysis, with some analyses showing a significant association and others showing no significant association. CONCLUSIONS: In both the univariate and multivariate analyses, CKD was found to be significantly associated with choroidal effusion after glaucoma surgery.

Antiphospholipid Syndrome Nephropathy and Other Thrombotic Microangiopathies Among Patients With Systemic Lupus Erythematosus.

Antiphospholipid syndrome (APS) and other causes of thrombotic microangiopathy (TMA) negatively impact the renal outcomes of patients with systemic lupus erythematosus (SLE) and lupus nephritis. Here we review the diagnosis and management of occlusive renal vascular lesions due to APS and other TMAs, with a focus on patients with SLE and lupus nephritis. The presence of a thrombotic event, unexplained hypertension, thrombocytopenia, or hemolytic anemia should prompt consideration for TMA syndromes. The differential diagnosis of a TMA in a patient with SLE includes APS, thrombocytopenic purpura, complement-mediated or infection-associated hemolytic uremic syndrome, drug-mediated TMA (particularly due to calcineurin inhibitor toxicity), and malignant hypertension. Treatment of APS with a documented thrombotic event focuses on anticoagulation to reduce the risk for further thrombotic events. Treatment of classic presentations of thrombocytopenic purpura and hemolytic uremic syndrome in the SLE population is the same as in patients without SLE. Treatment of APS nephropathy or TMA when it is diagnosed by biopsy with concomitant lupus nephritis presents a challenge to clinicians because there is no clear standard of care. Small and retrospective studies suggest potential benefit of complement inhibition, mammalian target of rapamycin (mTOR) inhibition, B cell depleting therapy, and plasma exchange therapy for patients with lupus nephritis and TMA, and prospective investigation of these therapies should be a research priority.

Mediastinal choriocarcinoma presenting with syncope.

Mediastinal choriocarcinomas are rare germ-cell tumors that occur almost exclusively in young males. These tumors grow rapidly, causing compression of mediastinal structures, and are usually associated with a poor prognosis. We report herein a unique case documenting syncope as initial clinical presentation of a mediastinal choriocarcinoma causing a superior vena cava (SVC) syndrome. The patient was treated with a standard chemotherapy triplet, with normalization of the tumor markers after the first chemotherapy cycle. He remains with no evidence of disease relapse 18 months later. Clinicians should consider the diagnosis of a mediastinal germ-cell tumor in a younger male patient presenting with a syncopal episode.