A Randomized Trial of Cyclosporine in Patients with Steroid-Resistant Focal Segmental Glomerulosclerosis

Background A clinical trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis (FSGS) was conducted. Despite the fact that it is the most common primary glomerulonephritis to progress to renal failure, treatment trials have been very limited. Methods We conducted a randomized controlled trial in 49 cases of steroid-resistant FSGS comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 200 weeks, and the short- and long-term effects on renal function were assessed. Results Seventy percent of the treatment group versus 4% of the placebo group (P < 0.001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 40% of the remitters by 52 weeks and 60% by week 78, but the remainder stayed in remission to the end of the observation period. Renal function was better preserved in the cyclosporine group. There was a decrease of 50% in baseline creatinine clearance in 25% of the treated group compared with 52% of controls (P < 0.05). This was a reduction in risk of 70% (95% CI, 9 to 93) independent of other baseline demographic and laboratory variables. Conclusions These results suggest that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of FSGS. Although a high relapse rate does occur, a long-term decrease in proteinuria and preservation of filtration function were observed in a significant proportion of treated patients

Gene Expression Profiling on Global cDNA Arrays Gives Hints Concerning Potential Signal Transduction Pathways Involved in Cardiac Fibrosis of Renal Failure

Cardiac remodelling with interstitial fibrosis in renal failure, which so far is only poorly understood on the molecular level, was investigated in the rat model by a global gene expression profiling analysis. Sprague–Dawley rats were subjected to subtotal nephrectomy (SNX) or sham operation (sham) and followed for 2 and 12 weeks, respectively. Heart-specific gene expression profiling, with RZPD Rat Unigene-1 cDNA arrays containing about 27 000 gene and EST sequences revealed substantial changes in gene expression in SNX compared to sham animals. Motor protein genes, growth and differentiation markers, and extracellular matrix genes were upregulated in SNX rats. Obviously, not only genes involved in cardiomyocyte hypertrophy, but also genes involved in the expansion of non-vascular interstitial tissue are activated very early in animals with renal failure. Together with earlier findings in the SNX model, the present data suggest the hypothesis that the local renin–angiotensin system (RAS) may be activated by at least two pathways: (a) via second messengers and Gproteins (short-term signalling); and (b) via motor proteins, actins and integrins (longterm signalling). The study documents that complex hybridization analysis yields reproducible and promising results of patterns of gene activation pointing to signalling pathways involved in cardiac remodelling in renal failure. The complete array data are available via http://www.rzpd.de/cgi-bin/services/exp/viewExpressionData.pl.cg

Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis

<p>Abstract</p> <p>Background</p> <p>Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis.</p> <p>Methods</p> <p>This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC).</p> <p>Results</p> <p>Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy.</p> <p>Conclusions</p> <p>A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.</p

A multidisciplinary program for achieving lipid goals in chronic hemodialysis patients

BACKGROUND: There is little information on how target lipid levels can be achieved in end stage renal disease (ESRD) patients in a systematic, multidisciplinary fashion. METHODS: We retrospectively reviewed a pharmacist-directed hyperlipidemia management program for chronic hemodialysis (HD) patients. All 26 adult patients on chronic HD at a tertiary care medical facility were entered into the program. A clinical pharmacist was responsible for laboratory monitoring, patient counseling, and the initiation and dosage adjustment of an appropriate 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) using a dosing algorithm and monitoring guidelines. The low-density lipoprotein (LDL) cholesterol goal was ≤ 100 mg/dl. A renal dietitian provided nutrition counseling and the nephrologist was notified of potential or existing drug interactions or adverse drug reactions (ADRs). Patients received a flyer containing lipid panel results to encourage compliance. Data was collected at program initiation and for 6 months thereafter. RESULTS: At the start of the program, 58% of patients were at target LDL cholesterol. At 6 months, 88% had achieved target LDL (p = 0.015). Mean LDL cholesterol decreased from 96 ± 5 to 80 ± 3 mg/dl (p < 0.01), and mean total cholesterol decreased from 170 ± 7 to 151 ± 4 mg/dl (p < 0.01). Fifteen adjustments in drug therapy were made. Eight adverse drug reactions were identified; 2 required drug discontinuation or an alternative agent. Physicians were alerted to 8 potential drug-drug interactions, and appropriate monitoring was performed. CONCLUSIONS: Our findings demonstrate both feasibility and efficacy of a multidisciplinary approach in management of hyperlipidemia in HD patients

Association of dialysis facility-level hemoglobin measurement and erythropoiesis-stimulating agent dose adjustment frequencies with dialysis facility-level hemoglobin variation: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>A key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation.</p> <p>Methods</p> <p>This was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation.</p> <p>Results</p> <p>First to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges.</p> <p>Conclusions</p> <p>Frequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.</p

Chronic kidney disease and use of dental services in a united states public healthcare system: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>As several studies have shown an association between periodontal disease and chronic kidney disease (CKD), regular dental care may be an important strategy for reducing the burden of CKD. Access to dental care may be limited in the US public health system.</p> <p>Methods</p> <p>In this retrospective cohort study of 6,498 adult patients with (n = 2,235) and without (n = 4,263) CKD and at least 12 months of follow-up within the San Francisco Department of Public Health Community Health Network clinical databases, we examined the likelihood of having a dental visit within the observation period (2005-2010) using Cox proportional hazards models. To determine whether dental visits reflected a uniform approach to preventive service use in this setting, we similarly examined the likelihood of having an eye visit among those with diabetes, for whom regular retinopathy screening is recommended. We defined CKD status by average estimated glomerular filtration rate based on two or more creatinine measurements ≥ 3 months apart (no CKD, ≥ 60 ml/min/1.73 m²; CKD, < 60 ml/min/1.73 m²).</p> <p>Results</p> <p>Only 11.0% and 17.4% of patients with and without CKD, respectively, had at least one dental visit. Those with CKD had a 25% lower likelihood of having a dental visit [HR = 0.75, 95% CI (0.64-0.88)] than those without CKD after adjustment for confounders. Among the subgroup of patients with diabetes, 11.8% vs. 17.2% of those with and without CKD had a dental visit, while 58.8% vs. 57.8% had an eye visit.</p> <p>Conclusions</p> <p>Dental visits, but not eye visits, in a US public healthcare setting are extremely low, particularly among patients with CKD. Given the emerging association between oral health and CKD, addressing factors that impede dental access may be important for reducing the disparate burden of CKD in this population.</p