Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel

Andrew S Bomback1, James A Tumlin2, Joel Baranski3, James E Bourdeau4, Anatole Besarab5, Alice S Appel1, Jai Radhakrishnan1, Gerald B Appel11Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, NY, USA; 2Department of Internal Medicine, Division of Nephrology, University of Tennessee College of Medicine in Chattanooga, Chattanooga, TN, USA; 3Balboa Nephrology Medical Group, San Diego, CA, USA; 4Nephrology Specialists of Oklahoma, Tulsa, OK, USA; 5Department of Medicine, Division of Nephrology and Hypertension, Henry Ford Health System, Detroit, MI, USAPurpose: A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.Patients and methods: Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.Results: Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.Conclusion: ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.Keywords: nephrotic syndrome, membranous nephropathy, chronic kidney diseas

Disordered aldosterone-volume relationship in end-stage kidney disease

Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship

Dysglycemia but not lipids is associated with abnormal urinary albumin excretion in diabetic kidney disease: a report from the Kidney Early Evaluation Program (KEEP)

BACKGROUND: The relationship between glycemic control and lipid abnormalities with urinary albumin-creatinine ratio (ACR) in chronic kidney disease (CKD) patients with diabetes mellitus (DM) is unknown. We sought to investigate the association of dyslipidemia and glycemic control with levels of albuminuria in the National Kidney Foundation (NKF) Kidney Early Evaluation Program (KEEP) participants with DM and CKD stage 3 or higher. METHODS: We performed a cross-sectional study of 6639 eligible KEEP patients with DM and CKD Stage 3 to 5 from June 2008 to December 2009. Multivariate logistic regression was used to evaluate the association of lipid parameters (per 10 mg/dl change in serum level) and glycosylated hemoglobin (HbA1c) values with three degrees of albuminuria normo (<30 mg⁄g), micro (30 to 300 mg⁄g) and macro (>300 mg⁄g). RESULTS: 2141 KEEP participants were included. HbA1c levels were strongly associated with micro-albuminuria (compared to normo-albuminuria) and macro-albuminuria (compared to normo-albuminuria and micro-albuminuria). Each 1.0% increase in HbA1c increased the odds of micro-albuminuria by 32% (OR 1.32, 95% CI 1.23-1.42) and the odds of macro-albuminuria (vs. microalbuminuria) by 16% (OR 1.16, 95% CI 1.05-1.28). Only increases in serum HDL were associated with decreased odds of micro-albuminuria; otherwise, the association between other components of the serum lipid profile with urinary ACR did not reach statistical significance. CONCLUSION: In this cross-sectional study of 2141 KEEP participants with DM and CKD stages 3–5, overall glycemic control but not lipids were associated with abnormal urinary albumin excretion, a marker of increased risk for progressive disease

A Hypertension Risk Score for Middle-Aged and Older Adults

Determining which demographic and medical variables predict the development of hypertension could help clinicians stratify risk in both prehypertensive and nonhypertensive persons. Subject-level data from 2 community-based biracial cohorts were combined to ascertain the relationship between baseline characteristics and incident hypertension. Hypertension, defined as diastolic blood pressure ≥90 mm Hg, systolic blood pressure ≥140 mm Hg, or reported use of medication known to treat hypertension, was assessed prospectively at 3, 6, and 9 years. Internal validation was performed by the split-sample method with a 2:1 ratio for training and testing samples, respectively. A scoring algorithm was developed by converting the multivariable regression coefficients to integer values. Age, level of systolic or diastolic blood pressure, smoking, family history of hypertension, diabetes mellitus, high body mass index, female sex, and lack of exercise were associated with the development of hypertension in the training sample. Regression models showed moderate to high capabilities of discrimination between hypertension vs nonhypertension (area under the receiver operating characteristic curve 0.75–0.78) in the testing sample at 3, 6, and 9 years of follow-up. This risk calculator may aide health care providers in guiding discussions with patients about the risk for progression to hypertension

Sodium Phosphate Does Not Increase Risk for Acute Kidney Injury After Routine Colonoscopy, Compared With Polyethylene Glycol

Oral sodium phosphate (OSP) is a common bowel purgative administered before colonoscopy; the Food and Drug Administration has warned against its use because of concerns about acute kidney injury (AKI) from the absorbed phosphate and dystrophic calcification. However, it is not clear if OSP is associated with AKI in the general population or in high-risk subgroups undergoing colonoscopy. We estimated the risk of AKI among patients undergoing a screening colonoscopy using OSP vs polyethylene glycol (PEG) for bowel cleansing in a large, US-based claims database

Sugar-sweetened soda consumption, hyperuricemia, and kidney disease

The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead to elevations in uric acid levels. Here we determined whether soda drinking is associated with hyperuricemia and, as a potential consequence, reduced kidney function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities Study completed a dietary questionnaire and had measurements of their serum creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds ratios from logistic regressions for binary outcome of hyperuricemia and chronic kidney disease (eGFR less than 60 ml/min per 1.73 m2) were evaluated. Compared to participants who drank less, consumption of over one soda per day was associated with increased odds of prevalent hyperuricemia and chronic kidney disease. The odds ratio for chronic kidney disease significantly increased to 2.59 among participants who drank more than one soda per day and had a serum uric acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than one soda per day was not associated with hyperuricemia or chronic kidney disease. Neither preexistent hyperuricemia nor development of hyperuricemia modified the lack of association between soda drinking and incident chronic kidney disease. Thus our study shows that high consumption of sugar-sweetened soda was associated with prevalent but not incident hyperuricemia and chronic kidney disease

A Simple Algorithm to Predict Incident Kidney Disease

Despite the growing burden of chronic kidney disease (CKD), there are no algorithms (to our knowledge) to quantify the effect of concurrent risk factors on the development of incident disease

Association of C-Reactive Protein and Microalbuminuria (from the National Health and Nutrition Examination Surveys, 1999 to 2004)

Chronic kidney disease and cardiovascular disease share many risk factors. Injury to the vascular endothelium, measured by elevated levels of serum C-reactive protein (CRP), may play a role in kidney and cardiovascular disease. We therefore examined the association of CRP with microalbuminuria, a marker of early kidney injury. We conducted a cross-sectional analysis of a nationally representative, population-based survey. Weighted multiple logistic regression was used to study the association between CRP and microalbuminuria, adjusting for well-known risk factors. CRP was analyzed by a continuous variable and two categorized variables using quartiles and clinically recommended cutpoints. CRP concentration was positively associated with microalbuminuria. In the multivariate model, a one unit (in milligrams per liter) increase in CRP concentration was associated with a 2% increased odds of microalbuminuria (odds ratio 1.02, 95% confidence interval [CI] 1.01 to 1.02, p = 0.0003). When CRP concentrations were stratified by clinically recommended cutpoints, compared with persons with CRP concentrations 3 mg/L were 1.15 times (95% CI 0.94 to 1.42) and 1.33 times (95% CI 1.08 to 1.65) more likely to have microalbuminuria, respectively. In subgroup analyses, the strength of association was comparable or stronger. In conclusion, elevated CRP levels were associated with microalbuminuria in a large, nationally representative data set. Vascular inflammation, as measured by CRP, may be a common contributor to early heart and kidney disease

Gestational Diabetes Mellitus Alone in the Absence of Subsequent Diabetes Is Associated With Microalbuminuria: Results from the Kidney Early Evaluation Program (KEEP)

OBJECTIVE Women with gestational diabetes mellitus (GDM) maintain a higher risk for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for development of chronic kidney disease (CKD), but GDM alone, without subsequent development of overt diabetes, may also pose a risk for CKD

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies