Cases Of End-stage Renal Disease Research Articles

Spontaneous bilateral femoral neck fracture in a man with end-stage renal disease and severe secondary hyperparathyroidism

Medical treatment is the primary recommended method for in the management of severe secondary hyperparathyroidism (SHPT) in pre-dialysis individuals. This paper reports a case of end-stage renal disease (ESRD) and severe SHPT with pathologic bilateral hip fractures. A 61-year-old man, as a known case of ESRD, with radial osteoporosis and persistent SHPT ( intact PTH >2000 pg/mL) and hypercalcemia with appropriate level of phosphorus and 25(OH) D who did not respond to medical treatment referred to hospital with multiple fractures. The patient referred for subtotal parathyroidectomy. One month after parathyroidectomy, parathyroid hormone (PTH) level significantly diminished from its preoperative values. Serum calcium and phosphorus returned to normal values and muscle weakness progressively improved until the patient became able to walk again. Parathyroidectomy in patients with severe secondary hyperparathyroidism (persistent serum levels of intact PTH>800 pg/mL) is suggested, particularly when is associated with severe hypercalcemia and/or hyperphosphatemia, and progressive and debilitating hyperparathyroidism bone disease, that are refractory and resistant to medical therapy.

GLOBAL CHALLENGE OF EARLY DETECTION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE

C hronic Kidney Disease (CKD) is a global health burden with a high economic cost to the health system and is an independent risk factor for cardiovascular disease (CVD), not only in the developed country but also in developing country like Indonesia. 1,2 The incidence and prevalence of CKD are increasing every year. The global prevalence of CKD is about 11-13% with the majority in stage III. 1 CKD stage V or End Stage Renal Disease (ESRD) needs a complicated management including renal replacement treatment such as hemodialysis, continuous ambulatory peritoneal dialysis (CAPD) or renal transplantation that are very high cost and limited in some centers. 1-3 The incidence rate of ESRD per million populations in Indonesia from 2002-2006 was increasing from 10.2, 11.7, 13.8, 18.4 to 23.4. 3 There were 117,162 new cases of ESRD reported in United States of America by the end of 2013 and the unadjusted incidence rate was 363 per million/year. 4

Bamboo leaf extract ameliorates diabetic nephropathy through activating the AKT signaling pathway in rats

Diabetic nephropathy (DN) is one of the most severe diabetic complication and it is becoming become a worldwide epidemic, accounting for approximately one-third of all case of end-stage renal disease. However, the underlying mechanism and strategy to alleviate renal injury remain unclear. In the present study, we assessed the protective effect of bamboo leaf extract on the DN, and investigated the underlying mechanism by which bamboo leaf extract ameliorating DN. Diabetic rats were induced by 4 weeks high sugar and high fat diet, and then injected a single dose of STZ (35mg/kg) into abdominal cavity. Different dose of bamboo extract (50mg/kg, 100mg/kg and 200mg/kg) were orally administered every day for a period of 12 weeks. Body weight, blood glucose, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and 24-hour urinary protein (24 h-UP) were assessed. Total superoxide dismutase (T-SOD) activity and MDA (methane dicarboxylic aldehyde, MDA) level were tested by assay kit. Microstructural changes were observed by hematoxylin–eosin (HE) staining and electron microscopy. Expression of phosphorylated ser/thr protein kinase (P-AKT), phosphorylated glycogen synthase kinase-3 beta (P-GSK-3β), B cell lymphoma/leukemia 2-associated X protein (BAX) and cleaved-cysteinyl aspartate-specific proteinase-3 (Cleaved Caspase-3) were measured by Western-Blotting (WB). Results showed that diabetic rats had weight loss, high blood glucose, HbAlc, BUN, Scr and 24-UP and T-SOD activity were increased and MDA level was decreased in diabetic rats. Moreover, hyperglycemia could injury renal tissue ultrastructure, inhibit P-AKT level and increase P-GSK-3β, BAX and Cleaved Caspase-3 levels in rats. However, bamboo leaf extract treatment could reduce body weight loss, BUN, Scr, 24 h-UP and MDA level, improve T-SOD activity and alleviate renal injury in diabetic rats. Furthermore, bamboo leaf extract increased P-AKT level, decreased P-GSK-3β, BAX and Cleaved Caspase-3 levels in STZ-diabetic rats. In conclusion, our study suggested that bamboo leaf extract ameliorated DN in diabetic rats, and this protective effect is possibly related to suppressing oxidative stress through activating AKT signaling pathway. Bamboo leaf extract treatment may be a potential promising therapy for DN.

The effectiveness and safety of angiotensin-converting enzyme inhibition or receptor blockade in vascular diseases in patients with hemodialysis.

Patients with end-stage renal disease (ESRD) who are on hemodialysis have high risk of vascular diseases. Our study sought to examine whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs) could reduce the frequencies of cardiovascular and cerebrovascular events in patients receiving hemodialysis using the medication possession ratio (MPR) method of analysis.This retrospective cohort study identified cases of ESRD with dialysis from the National Health Insurance Research Database between 1999 and 2006, and used Cox-regression methods to evaluate risk of poor outcomes. Primary outcomes, including death from any cause, and secondary outcomes, including admission for stroke, myocardial infarction, and heart failure, were examined.Compared to the nonuser group, the adjusted HRs for mortality of the nonadherence group and the adherence group were 0.81 (95% CI: 0.76–0.86) and 0.98 (95% CI: 0.86–1.13), respectively. Cardiovascular events were more frequent in patients with ESRD receiving ACEIs /ARBs than in nonusers. Compared with nonusers, the hazard of secondary outcome significantly increased in the nonadherence group or adherence group in 10 years follow-up.Compared with patients with diabetes or chronic kidney disease, patients on hemodialysis may not experience the same cardiovascular and cerebrovascular benefits from ACEIs/ARBs use.

Vital Signs: Decrease in Incidence of Diabetes-Related End-Stage Renal Disease among American Indians/Alaska Natives - United States, 1996-2013.

BackgroundAmerican Indians and Alaska Natives (AI/AN) have the highest diabetes prevalence among any racial/ethnic group in the United States. Among AI/AN, diabetes accounts for 69% of new cases of end-stage renal disease (ESRD), defined as kidney failure treated with dialysis or transplantation. During 1982–1996, diabetes-related ESRD (ESRD-D) in AI/AN increased substantially and disproportionately compared with other racial/ethnic groups.MethodsData from the U.S. Renal Data System, the Indian Health Service (IHS), the National Health Interview Survey, and the U.S. Census were used to calculate ESRD-D incidence rates by race/ethnicity among U.S. adults aged ≥18 years during 1996–2013 and in the diabetic population during 2006–2013. Rates were age-adjusted based on the 2000 U.S. standard population. IHS clinical data from the Diabetes Cares and Outcomes Audit were analyzed for diabetes management measures in AI/AN.ResultsAmong AI/AN adults, age-adjusted ESRD-D rates per 100,000 population decreased 54%, from 57.3 in 1996 to 26.5 in 2013. Although rates for adults in other racial/ethnic groups also decreased during this period, AI/AN had the steepest decline. Among AI/AN with diabetes, ESRD-D incidence decreased during 2006–2013 and, by 2013, was the same as that for whites. Measures related to the assessment and treatment of ESRD-D risk factors also showed more improvement during this period in AI/AN than in the general population.Conclusion and implications for public health practiceDespite well-documented health and socioeconomic disparities among AI/AN, ESRD-D incidence rates among this population have decreased substantially since 1996. This decline followed implementation by the IHS of public health and population management approaches to diabetes accompanied by improvements in clinical care beginning in the mid-1980s. These approaches might be a useful model for diabetes management in other health care systems, especially those serving populations at high risk.

Palliation Versus Dialysis for End-Stage Renal Disease in the Oldest Old: What are the Considerations?

As the US population continues to age, new cases of end-stage renal disease (ESRD) in individuals, aged 85 years or older (the oldest old), are increasing. Many patients who begin hemodialysis despite questionable benefit may struggle with high symptom burden and rapid functional decline. This article reviews the history regarding the funding and development of the Medicare ESRD program, reviews current approaches to the oldest old with ESRD, and considers strategies to improve the management approach of this vulnerable population.

Analysis of patients with end-stage renal disease on dialysis in Tabuk City, Saudi Arabia: A single-center, three-year retrospective study.

This study was performed to analyze various demographic data such as age, gender, nationality, status of the patients, and the causes of end-stage renal disease (ESRD) of 349 patients who were undergoing hemodialysis (HD) during the period from January 2013 to December 2015 at the Dialysis Center of King Khalid Hospital in Tabuk City. One hundred and fifty-two patients (43.6%) were on HD in 2015. Age of the patients ranged from 9 to 93 years and the mean age was 51.3 ± 17.6 years. Majority of the patients, i.e., 140 (40.1%) were in the age group of 40-59 years, followed by the age group of 60-79 years by 27.8% (97 patients). Saudis constituted 84.2% (294) and non-Saudis accounted 15.8% (55) of the patients over the years studied. There were 198 males (56.7%) and 151 females (43.3%). The death rate in 2014 was 6.2%, whereas it increased in 2015 to 10.5%. The high escape rate (10.3%) of patients was in 2014. Diabetic nephropathy was the most common cause of ESRD, accounting for 30.4% of all cases, followed by unknown etiologies accounting for 25.2%. Nearly 22.6% of all ESRD cases had hypertension. Primary glomerular disease was seen in 8.9% and obstructive uropathy in 3.7%. Other causes constituted 7.4% of the cases. The data of ERSD patients in Tabuk City are comparable with that of other regions of the Kingdom of Saudi Arabia. We conclude that analysis studies of HD centers help to understand the problems and the needs of the patients, find the solutions, and create a connection between the consumers and health-care providers.

Peritoneal Dialysis or Hemodialysis: Present and Future Trends in the United States.

In 2013, 88.4% of all incident end-stage renal disease (ESRD) patients began renal replacement therapy with hemodialysis (HD) while 9.0% began with peritoneal dialysis (PD). The remaining 2.6% received a preemptive kidney transplant. In the US, outpatient HD units are widely distributed and economy of scale has resulted in HD being the most common ESRD modality. Use of PD and preemptive kidney transplant were relatively more common in younger groups and relatively less common among Black and Hispanic patients. Of note is that the new Medicare reimbursement system, known as the 'bundle', provides substantial financial incentives to do PD as opposed to in-center HD. By the end of 2013, 63.9% of all prevalent ESRD cases were receiving HD, 6.9% were being treated with PD, and 29.3% had a functioning kidney transplant. Distributions of modality use by patient characteristics generally mirror those for incident patients. PD and kidney transplant were more commonly used among patients who were younger and were more likely to be non-Hispanic Whites. Differences in the use of home dialysis (PD and HD) are largely driven by differences among individual dialysis centers or groups of centers, rather than by large-scale regional effects. Thus, the future use of PD or home HD will be driven by the proclivities of the largest dialysis providers, which, in turn, are driven by financial reimbursement.

Dietary polyunsaturated fatty acids and incidence of end-stage renal disease in the Southern Community Cohort Study.

BackgroundWhether polyunsaturated fatty acids (PUFA) are associated with end-stage renal disease (ESRD) in populations with a high burden of risk factors for kidney disease is unknown. We sought to determine whether PUFA intake is associated with ESRD.MethodsWe conducted a nested case–control study of ESRD within the Southern Community Cohort Study (SCCS), a prospective cohort of low-income blacks and whites in the southeastern US (2002–2009). Through 2012, 1,074 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3,230 controls by age, sex and race. Dietary intake of total, n-3 or n-6 PUFA was assessed from a validated food frequency questionnaire administered at baseline. Odds ratios (ORs) and 95 % confidence intervals (CIs) were computed from logistic regression models that included matching variables, body mass index, smoking, diabetes, hypertension, education, income, total energy intake and percent energy from protein and saturated fat.ResultsThe mean (SD) age of participants was 55 (9) years. Most participants were women (55 %), black (87 %), with hypertension (67 %) and on average obtained 8 % of their energy from PUFA. Higher PUFA intake was marginally associated with a lower risk of ESRD in adjusted analyses. The adjusted odds ratios (95 % confidence intervals) for ESRD for the 5th vs. 1st quintile of PUFA were 0.79 (0.60–1.05; P trend = 0.06) for total PUFA, 0.81 (0.61–1.06; P trend = 0.04) for n-6 PUFA and 0.93 (0.71–1.21; P trend = 0.45) for n-3 PUFA.ConclusionsWe observed a marginally significant inverse trend between dietary PUFA intake and ESRD incidence, mainly driven by n-6 fatty acid intake. Our findings require replication but suggest that a diet rich in n-6 PUFA may prevent ESRD development in a population with a high burden of kidney disease risk factors.

Preeclampsia and ESRD: The Role of Shared Risk Factors

Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors. Population-based nested case-control study. The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or≥4). Preeclamptic pregnancy, confirmed by medical record review. ESRD. Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension. There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37). The limited number of ESRD cases and missing data for prepregnancy kidney function. Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.

Risk of end-stage renal disease in Japanese patients with chronic kidney disease increases proportionately to decline in estimated glomerular filtration rate

Predominantly based on North American and European studies, 30% to 40% declines in estimated glomerular filtration rate (eGFR) over a few years are strongly associated with the risk of end-stage renal disease (ESRD) and have been proposed as surrogate endpoints of ESRD for clinical research. However, this association has not been systematically quantified in Asian populations. To do this we studied adult Japanese patients with baseline eGFR 10-59 ml/min/1.73m2. Changes in eGFR from baseline measured by centrally assessed serum creatinine were linked to subsequent ESRD in 2410 patients after one year and in 2079 patients after year 2. After year 1, 1.4% experienced a 53% decrease in eGFR (equivalent to doubling of serum creatinine), whereas 4.3% and 9.7% had eGFR decrease of 40% or 30% or more, respectively. The corresponding numbers after 2 years were 4.2%, 10.9%, and 19.3%, respectively. After year 1 baseline period, 498 patients developed ESRD over a median follow-up of 2.9 years (365 ESRD cases over a median follow-up of 2 years after year 2). In year 1, after accounting for potential confounders, a strong linear association was found between eGFR declines and subsequent ESRD, with adjusted hazard ratios of 20.7 (95% confidence interval 14.3-30.1) for a 53% decrease, 9.6 (7.4-12.5) for a 40% decrease, and 5.3 (4.1-6.9) for a 30% decrease compared to no change. Corresponding hazard ratios for year two analysis were 17.3 (11.8-25.3), 6.5 (4.7-9.1), and 3.1 (2.2-4.4), respectively. The associations were consistent across demographics and kidney diseases. Thus, 30% to 40% declines in eGFR are strongly associated with the riskof ESRD in Japanese patients with reduced eGFR, broadening global implications as a surrogate endpoint inclinical research.

Incidence, mortality, and prevalence of end-stage chronic renal disease in the Bajo Lempa region of El Salvador: A ten-year community registry

The Bajo Lempa is an impoverished rural coastal region of El Salvador affected by the chronic kidney disease (CKD) epidemic known as Mesoamerican nephropathy. The local community organisation Fondo Social de Emergencia para la Salud (FSES) (Emergency social fund for health) is helping to fight the epidemic in 42 communities of the region (19,223 inhabitants; average age 26.7 years; 48.5% male; 40.2% <18 years). ObjectivesTo report annual rates of end-stage renal disease (ESRD) incidence and patient mortality in these communities during a 10-year period (2004–2013), and the prevalence of patients receiving renal replacement therapy (RRT) as of 31 December 2013. MethodsThe FSES recorded new ESRD cases, basic patient history, form of RRT if received and patient deaths. ResultsWe registered 271 new ESRD cases (annual average 27.1; 89% male; average age 55.6 years, four <18 years). Average annual ESRD incidence rate: 1409.8 per million population (pmp). Two-thirds did not report diabetes or hypertension. 94 patients (34.7%) received RRT: 58 in the Ministry of health, 26 in private services, 9 in social security and 1 in the military health system. 246 patients died (annual average 24.6 deaths; 89.4% male; average age 56.1 years; 92.3% at home). Average annual mortality rate: 128/100,000 population. Prevalence of patients receiving RRT in 2013: 1300.5pmp (N=25; 84% male; average age 51 years). ConclusionsThis region has a high incidence of ESRD. Few receive RRT. Patient mortality is high even with RRT. Most patients are male (9:1). Social determinants influence the high mortality.

Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets.

Increasing incidences of obesity and diabetes have made diabetic kidney disease (DKD) the leading cause of chronic kidney disease and end-stage renal disease worldwide. Despite current pharmacological treatments, including strategies for optimizing glycemic control and inhibitors of the renin-angiotensin system, DKD still makes up almost one-half of all cases of end-stage renal disease in the United States. Compelling and mounting evidence has clearly demonstrated that immunity and inflammation play a paramount role in the pathogenesis of DKD. This article reviews the involvement of the immune system in DKD and identifies important roles of key immune and inflammatory mediators. One of the most recently identified biomarkers is serum amyloid A, which appears to be relatively specific for DKD. Novel and evolving treatment approaches target protein kinases, transcription factors, chemokines, adhesion molecules, growth factors, advanced glycation end-products, and other inflammatory molecules. This is the beginning of a new era in the understanding and treatment of DKD, and we may have finally reached a tipping point in our fight against the growing burden of DKD.

Ultrasound evaluation of coexistent thyroid and parathyroid lesions in end stage renal disease cases

Ultrasound evaluation of coexistent thyroid and parathyroid lesions in end stage renal disease cases

End-stage renal disease in patients with rheumatoid arthritis.

To determine the frequency of end-stage renal disease (ESRD) in patients with rheumatoid arthritis (RA), the causes of ESRD, and the treatment of RA in the setting of ESRD. Cross-sectional study of RA (N = 3754) and non-RA (N = 326,776) patients in the United States Renal Data System (USRDS) during 2011 (N = 330,530). The epidemiology of ESRD in RA was determined and the etiology of ESRD in patients with and without RA was compared. The frequency of patients with RA with at least one filled prescription for prednisone/prednisolone, a DMARD, and/or a biologic in 2011 was determined. The prevalence of RA with ESRD in the USRDS in 2011 was 1.1%. There were significant differences in age, race, sex, and BMI category between the groups (p < 0.01). Diabetes (33.5%) and hypertension (30.6%) were the most common primary causes of ESRD in patients with RA. Amyloidosis, vasculitis, and analgesic nephropathy combined accounted for less than 10% of cases of ESRD. Prednisone was the most commonly filled medication that could be used to treat RA (45.9% of RA patients). Hydroxychloroquine was the most frequently filled DMARD (13.5%); biologics were uncommon (etanercept 2.5%, adalimumab 1.5%; golimumab, infliximab, anakinra, and abatacept <1%). The co-occurrence of RA with ESRD was 1.1% in the USRDS by 2011. Physicians should be aware of the critical impact of the comorbidities of diabetes and hypertension in causing ESRD in RA patients. Use of DMARDS other than hydroxychloroquine and biologics to treat RA in the setting of ESRD appears to be infrequent. Further prospective studies of treatment strategies for RA in ESRD are needed.

Higher protein intake is associated with increased risk for incident end-stage renal disease among blacks with diabetes in the Southern Community Cohort Study

Background and aimsDiabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes. Methods and resultsWe conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002–2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (±SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 ± 3.3 vs. 15.1 ± 3.1%, P < 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02–1.10) for blacks with diabetes, 1.02 (0.98–1.06) for blacks without diabetes, 0.99 (0.90–1.09) for whites with diabetes and 0.94 (0.84–1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17–2.65). ConclusionOur results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed.

Lithiase rénale de l’adulte : des mécanismes au traitement médical préventif

Nephrolithiasis is a very common (prevalence around 10 to 12% in France) and recurrent disorder. Nephrolithiasis is associated to chronic kidney disease and is responsible for 2 to 3% of cases of end-stage renal disease, mainly if it is associated to nephrocalcinosis or to a monogenic disorder (1.6% of nephrolithiasis in adults, among them 1% of cystinuria). To understand the underlying pathophysiological processes, stone analysis (morphology and using infrared spectrophotometry) as well as minimal biological assessment including urine crystal research are required. The calcic nephrolithiasis is the more frequent subtype (>80%). Its medical treatment relies on simple dietary rules: non-alkaline hyperdiuresis>2 liters/day, calcium intake normalization (1 gram per day divided between the three principal meals), normalization of sodium (6 to 7 grams per day) and protein intake (1g/kg of theoretical body weight/day), and eviction of foods rich in oxalate. In case of persistent hypercalciuria (>0.1mmol/kg of theoretical body weight/day on free diet), a thiazide diuretic can be started while being aware to correct iatrogenic decrease in plasma potassium and urine citrate excretion. Measurement of bone mineral density must systematically be performed in patients with high 24 h-urinary calcium excretion. The medical treatment of uric acid nephrolithiasis relies on alkaline hyperdiuresis (goal of urine pH: 6.2 to 6.8). The use of allopurinol is justified only if urine uric acid is over 4mmol/day. Thanks to a well-managed preventive medical treatment, one can expect to stop the activity of nephrolithiasis in more than 80% of cases, making it one of the most accessible renal pathologies to preventive medical treatment.

Prediction of susceptible biomarkers for end stage renal disease among North Indians.

Involvement of pro-inflammatory genes has been correlated with basic kidney diseases and end stage renal disease (ESRD). However, results at odds were often noted from such independent association studies. This study proposes a genome wide analysis approach to predict ESRD risk associated genes. We included 42 single nucleotide polymorphisms (SNPs) showing association among north Indian ESRD cases and controls. ESRD cases comprised chronic glomerulonephritis (CGN), chronic interstitial nephritis (CIN), hypertension (HTN) and autosomal dominant polycystic kidney disease (ADPKD). Genotyping data obtained from our prior published reports were compared with Genome-Wide Association Studies (GWAS) SNPs retrieved from HapMap and GWASCentral databases using R-statistical package SNPAssoc. Linkage disequilibrium (LD), gene-gene interaction, classification and regression tree (CART) and pathway analysis were carried out in the present study supplemented with IL-6 and TNF-α levels estimation using enzyme linked immunosorbent assay (ELISA). Comparison of genotyping data with GWAS SNPs revealed significant associations for interleukin (IL)1-RN, IL-6, MTHFR, tumour necrosis factor-α (TNF-α) and CCR3 genes with ESRD. Nine SNPs were commonly associated with CGN, CIN, HTN, ADPKD and ESRD. LD (D = 0.9) and gene-gene interaction (P = 0.0002) analyses revealed significant associations for IL-6 and TNF-α genes. In a consistent manner, CART analysis and functional analysis servers predict predisposing effects for TNF-α and IL-6 with ESRD. Finally, higher body circulating levels were observed for mutant TNF-α and IL-6 alleles among ESRD. The study indicates significance for IL-6 and TNF-α gene with basic kidney diseases and ESRD. Extensive statistical tests, pathway analysis and functional assays also reflect attenuated level of significance for these SNPs. In future these may be brought from bench side to clinical practice as diagnostic biomarkers upon external and prospective replication and confirmation among other cohorts.

Risk prediction to inform surveillance of chronic kidney disease in the US Healthcare Safety Net: a cohort study.

BackgroundThe capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net.MethodsWe conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996–2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies.ResultsOverall, 1730 persons progressed to end-stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83–94 %, 74–95 %, and 75–82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42–71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC ≥0.80) when evaluated using traditional criteria.ConclusionsRecently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0272-0) contains supplementary material, which is available to authorized users.

Nuove opzioni terapeutiche per la malattia renale policistica

Abstract non disponibile