Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome.

BACKGROUND: In adults with primary focal segmental glomerulosclerosis (FSGS), daily prednisone may induce complete remissions (CR) and partial remissions (PR), but relapses are frequent and adverse events are common. METHODS: We carried out 2 open-label, uncontrolled trials to explore the efficacy and tolerability of pulse oral dexamethasone as an alternative to daily prednisone. We enrolled adult patients with proteinuria > 3.5 g/day despite the use of renin-angiotensin-aldosterone blockade. In the first trial, we enrolled 14 subjects with FSGS and administered 4 dexamethasone doses (25 mg/m2) daily for 4 days, repeated every 28 days over 32 weeks. The second trial involved a more intensive regimen. Eight subjects received 4 dexamethasone doses of 50 mg/m2 every 4 weeks for 12 weeks, followed by 4 doses of 25 mg/m2 every 4 weeks for 36 weeks; subjects were randomized to 2 doses every 2 weeks or 4 doses every 4 weeks. RESULTS: In the first trial, we enrolled 13 subjects with FSGS and 1 with minimal change disease and found a combined CR and PR rate of 36%. In the second trial, we enrolled 8 subjects. The combined CR and PR rate was 29%. Analysis combining both trials showed a combined CR and PR rate of 33%. Adverse events were observed in 32% of subjects, with mood symptoms being most common. There were no serious adverse events related to the study. CONCLUSION: We conclude that high dose oral dexamethasone is well tolerated by adults with idiopathic nephrotic syndrome and may have some efficacy.

Dietary Habits and Risk of Kidney Function Decline in an Urban Population.

OBJECTIVE: Explore the association between following a Dietary Approaches to Stop Hypertension (DASH)-accordant diet and kidney end points among urban adults. DESIGN: Prospective cohort study. SETTING: Healthy Aging in Neighborhoods of Diversity across the Life Span study. SUBJECTS: A total of 1,534 urban dwelling participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/minute/1.73 m2. INTERVENTION: DASH diet accordance determined via a score based on nine target nutrients. MAIN OUTCOME MEASURE: Rapid kidney function decline (eGFR decline >3 mL/minute/1.73 m2 per year), incident chronic kidney disease (CKD) (follow-up eGFR <60 mL/minute/1.73 m2), and eGFR decline >25%. RESULTS: Participants' mean age was 48 years, and 59% were African-American. Median DASH score was 1.5 (range, 0-8). Over a median of 5 years, 13.4% experienced rapid eGFR decline, including 15.2% among participants not following a DASH-accordant diet (score ≤1) and 12.0% with higher accordance (score >1) (P = .08). Outcomes varied by hypertension status. In multinomial logistic regression models, following adjustment for sociodemographic and clinical factors, including total energy intake, low DASH diet accordance was associated with rapid eGFR decline among participants with hypertension (risk ratio, 1.68; 95% confidence interval: 1.17-2.42) but not among those without hypertension (risk ratio, 0.83; 95% confidence interval: 0.56-1.24; P interaction .001). There was no statistically significant association between DASH diet accordance and incident CKD or eGFR decline >25%. Results were similar when DASH diet accordance was analyzed in tertiles. CONCLUSIONS: Among urban adults, low accordance to a DASH-type diet was not associated with incident CKD, but was associated with higher risk of rapid eGFR decline among those with hypertension, yet not among those without hypertension. Further study of dietary patterns as a potential target for improving kidney outcomes among high-risk populations is warranted.

Genetics of focal segmental glomerulosclerosis and human immunodeficiency virus-associated collapsing glomerulopathy: the role of MYH9 genetic variation.

Until recently, knowledge of genetic causes of glomerular disease was limited to certain rare or uncommon inherited diseases, and to genes, either rare or with small effect, identified in candidate gene studies. These genetic factors accounted for only a very small fraction of kidney disease. However, the striking differences in frequency of many forms of kidney disease between African Americans and European Americans, which could not be explained completely by cultural or economic factors, pointed to a large unidentified genetic influence. Because focal segmental glomerulosclerosis (FSGS) and human immunodeficiency virus-associated collapsing glomerulopathy have striking racial disparities, we performed an admixture mapping study to identify contributing genetic factors. Admixture mapping identified genetic variants in the nonmuscle myosin heavy chain 9 gene (MYH9) as having a major influence on both FSGS and human immunodeficiency virus-associated collapsing glomerulopathy, with odds ratios from 4 to 8 and attributable fractions of 70% to 100%. Previously identified, rare, inherited MYH9 disorders point to a mechanism by which MYH9 variation disrupts the actin-myosin filaments responsible for maintaining the structure of podocytes, the cells that provide one of three filtration barriers in the glomeruli. MYH9 variation has a smaller but still highly significant effect on nondiabetic kidney disease, and a weaker but significant effect on diabetic kidney disease; it is unclear whether underlying cryptic FSGS is responsible for the MYH9 association with these diseases. The strong predicted power of MYH9 variation for disease indicates a clear role for genetic testing for these variants in personalized medicine, for assessment of genetic risk, and potentially for diagnosis.