The latest medical research on Nephrology

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Moderate aging does not exacerbate cisplatin-induced kidney injury or fibrosis despite altered inflammatory cytokine expression and immune cell infiltration.

American journal of physiology. Renal physiology

Aging is a risk factor for certain forms of kidney injury due to normal physiological changes, but the role aging plays in cisplatin-induced kidney...

ADAMTS13 protects mice against renal ischemia/reperfusion injury by reducing inflammation and improving endothelial function.

American journal of physiology. Renal physiology

Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disi...

Blood Pressure Goals in Patients with Chronic Kidney Disease: A Review of Evidence and Guidelines.

Clinical journal of the American Society of Nephrology : CJASN

Hypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade...

Medicare's New Prospective Payment System on Facility Provision of Peritoneal Dialysis.

Clinical journal of the American Society of Nephrology : CJASN

Peritoneal dialysis is a self-administered, home-based treatment for ESKD associated with equivalent mortality, higher quality of life, and lower costs compared with hemodialysis. In 2011, Medicare implemented a comprehensive prospective payment system that makes a single payment for all dialysis, medication, and ancillary services. We examined whether the prospective payment system increased dialysis facility provision of peritoneal dialysis services and whether changes in peritoneal dialysis provision were more common among dialysis facilities that are chain affiliated, located in nonurban areas, and in regions with high dialysis market competition.

We conducted a longitudinal retrospective cohort study of n=6433 United States nonfederal dialysis facilities before (2006-2010) and after (2011-2013) the prospective payment system using data from the US Renal Data System, Medicare, and Area Health Resource Files. The outcomes of interest were a dichotomous indicator of peritoneal dialysis service availability and a discrete count variable of dialysis facility peritoneal dialysis program size defined as the annual number of patients on peritoneal dialysis in a facility. We used general estimating equation models to examine changes in peritoneal dialysis service offerings and peritoneal dialysis program size by a pre- versus post-prospective payment system effect and whether changes differed by chain affiliation, urban location, facility size, or market competition, adjusting for 1-year lagged facility-, patient with ESKD-, and region-level demographic characteristics.

We found a modest increase in observed facility provision of peritoneal dialysis and peritoneal dialysis program size after the prospective payment system (36% and 5.7 patients in 2006 to 42% and 6.9 patients in 2013, respectively). There was a positive association of the prospective payment system with peritoneal dialysis provision (odds ratio, 1.20; 95% confidence interval, 1.13 to 1.18) and PD program size (incidence rate ratio, 1.27; 95% confidence interval, 1.22 to 1.33). Post-prospective payment system change in peritoneal dialysis provision was greater among nonurban (P<0.001), chain-affiliated (P=0.002), and larger-sized facilities (P<0.001), and there were higher rates of peritoneal dialysis program size growth in nonurban facilities (P<0.001).

Medicare's 2011 prospective payment system was associated with more facilities' availability of peritoneal dialysis and modest growth in facility peritoneal dialysis program size.

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Home-Based Kidney Care, Patient Activation, and Risk Factors for CKD Progression in Zuni Indians: A Randomized, Controlled Clinical Trial.

Clinical journal of the American Society of Nephrology : CJASN

The burden of CKD is greater in ethnic and racial minorities and persons living in rural communities, where access to care is limited.

A 12-month clinical trial was performed in 98 rural adult Zuni Indians with CKD to examine the efficacy of a home-based kidney care program. Participants were randomized by household to receive usual care or home-based care. After initial lifestyle coaching, the intervention group received frequent additional reinforcement by community health representatives about adherence to medicines, diet and exercise, self-monitoring, and coping strategies for living with stress. The primary outcome was change in patient activation score, which assesses a participant's knowledge, skill, and confidence in managing his/her own health and health care.

Of 125 randomized individuals (63 intervention and 62 usual care), 98 (78%; 50 intervention and 48 usual care) completed the 12-month study. The average patient activation score after 12 months was 8.7 (95% confidence interval, 1.9 to 15.5) points higher in the intervention group than in the usual care group after adjusting for baseline score using linear models with generalized estimating equations. Participants randomized to the intervention had 4.8 (95% confidence interval, 1.4 to 16.7) times the odds of having a final activation level of at least three ("taking action") than those in the usual care group. Body mass index declined by 1.1 kg/m2 (P=0.01), hemoglobin A1c declined by 0.7% (P=0.01), high-sensitivity C-reactive protein declined by 3.3-fold (P<0.001), and the Short-Form 12 Health Survey mental score increased by five points (P=0.002) in the intervention group relative to usual care.

A home-based intervention improves participants' activation in their own health and health care, and it may reduce risk factors for CKD in a rural disadvantaged population.

Sleep Quality and Sleep Duration with CKD are Associated with Progression to ESKD.

Clinical journal of the American Society of Nephrology : CJASN

Shorter or longer sleep duration and poor sleep quality are risk factors for numerous cardio-metabolic diseases, cardiovascular disease, and mortality in subjects with normal kidney function. The association of sleep duration and sleep quality with health outcomes in patients with CKD remains uncertain.

A 4-year prospective cohort study in 17 nephrology centers in Japan, the CKD Japan Cohort (CKD-JAC) Study, assessed an association of self-reported sleep duration and sleep quality, on the basis of the Pittsburgh Sleep Quality Index (PSQI) questionnaire, with incidence of ESKD in 1601 patients with eGFR 10-59 ml/min per 1.73 m2 using multivariable-adjusted Cox proportional hazards models.

Baseline sleep duration and PSQI global score for the 1601 patients were mean±SD 7.0±1.3 hours and median 4 (interquartile range, 3-7), respectively. Poor sleep quality (PSQI global score ≥6) was common (n=588 [37%]). During a median of 4.0 (2.6-4.3) years of the follow-up period, 282 (18%) patients progressed to ESKD. After adjusting for age, sex, eGFR, urinary albumin excretion, smoking status, body mass index, history of diabetes and cardiovascular disease, systolic BP, blockade of the renin-angiotensin system, use of hypnotics, and Beck depression inventory score, both shorter (≤5 hour) and longer (>8 hour) sleep duration were associated with ESKD (adjusted hazard ratios [95% confidence intervals] for ≤5.0, 5.1-6.0, 6.1-7.0, 7.1-8.0, and ≥8.0 hours were 2.05 [1.31 to3.21], 0.98 [0.67 to 1.44], 1.00 [reference], 1.22 [0.89 to 1.66], and 1.48 [1.01 to 2.16]), suggesting a U-shaped relationship between sleep duration and ESKD. PSQI global score ≥6 was also associated with incidence of ESKD (adjusted hazard ratios [95% confidence intervals] for PSQI global score ≤5 and ≥6 were 1.00 [reference] and 1.33 [1.03 to 1.71]).

Shorter (≤5 hour) and longer (>8 hour) sleep duration and poor sleep quality (PSQI global score ≥6) were associated with ESKD in patients with CKD.

This article contains a podcast at

Association of Monoclonal Gammopathy with Progression to ESKD among US Veterans.

Clinical journal of the American Society of Nephrology : CJASN

Whether patients with monoclonal protein are at a higher risk for progression of kidney disease is not known. The goal of this study was to measure the association of monoclonal protein with progression to ESKD.

This was a retrospective cohort study of 2,156,317 patients who underwent serum creatinine testing between October 1, 2000 and September 30, 2001 at a Department of Veterans Affairs medical center, among whom 21,898 had paraprotein testing within 1 year before or after cohort entry. Progression to ESKD was measured using linked data from the US Renal Data System.

Overall, 1,741,707 cohort members had an eGFR≥60 ml/min per 1.73 m2, 283,988 had an eGFR of 45-59 ml/min per 1.73 m2, 103,123 had an eGFR of 30-44 ml/min per 1.73 m2 and 27,499 had an eGFR of 15-29 ml/min per 1.73 m2. The crude incidence of ESKD ranged from 0.7 to 80 per 1000 person-years from the highest to lowest eGFR category. Patients with low versus preserved eGFR were more likely to be tested for monoclonal protein but no more likely to have a positive test result. In adjusted analyses, a positive versus negative test result was associated with a higher risk of ESKD among patients with an eGFR≥60 ml/min per 1.73 m2 (hazard ratio, 1.67; 95% confidence interval, 1.22 to 2.29) and those with an eGFR of 15-29 ml/min per 1.73 m2 (hazard ratio, 1.38; 95% confidence interval, 1.07 to 1.77), but not among those with an eGFR of 30-59 ml/min per 1.73 m2. Progression to ESKD was attributed to a monoclonal process in 21 out of 76 versus seven out of 174 patients with monoclonal protein and preserved versus severely reduced eGFR at cohort entry.

The detection of monoclonal protein provides little information on ESKD risk for most patients with a low eGFR. Further study is required to better understand factors contributing to a positive association of monoclonal protein with ESKD risk in patients with preserved and severely reduced levels of eGFR.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

Clinical journal of the American Society of Nephrology : CJASN

There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial.

Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects.

The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids.

ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT.

Clinical journal of the American Society of Nephrology : CJASN

The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD.

We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m2 at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control.

The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m2. Median PTH was 48 (interquartile range [IQR], 35-67) pg/ml and FGF23 was 66 (IQR, 52-88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular (P-interaction=0.01) and heart failure (P-interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention.

SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.

Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts.

American journal of physiology. Renal physiology

Hypertonicity increases water permeability, independently of vasopressin, in the inner medullary collecting duct (IMCD) by increasing aquaporin-2 (...

Characterization of renal NaCl and oxalate transport in Slc26a6-/- mice.

American journal of physiology. Renal physiology

The apical membrane chloride-oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in m...

SGLT2 inhibition and renal urate excretion: the role of luminal glucose, GLUT9 and URAT1.

American journal of physiology. Renal physiology

Inhibitors of the sodium-glucose cotransporter SGLT2 enhance urinary glucose and urate excretion and lower plasma urate levels. The mechanisms rema...