BMC Nephrology

Cardiovascular morbidity and mortality are highly prevalent in patients with end-stage renal disease, and osteoprotegerin (OPG) may be an important link between bone loss and vascular calcification. This study was conducted to evaluate the relationship between central arterial stiffness and serum OPG levels in hemodialysis (HD) patients. Blood samples were collected from 120 HD patients, and the carotid–femoral pulse wave velocity (cfPWV) value was measured using a validated tonometry system. The cfPWV value of > 10 m/s was used to define the high artery stiffness group. Serum OPG levels were analyzed categorically into tertiles. Of the 120 HD patients, 53 (44.2%) were defined as the high arterial stiffness group, who had higher values of systolic blood pressure (p = 0.038), serum calcium (p = 0.007), and OPG (p <  0.001) levels and a higher prevalence of diabetes mellitus (DM, p = 0.001). Increasing tertiles of serum OPG levels were significantly associated with greater height (p = 0.011), male gender (p = 0.008), higher cfPWV values (p = 0.020), and lower intact parathyroid hormone (iPTH, p = 0.049) levels. Multivariable linear regression analysis showed that cfPWV value was independently associated with DM (β = 1.83, p = 0.008) and increasing tertiles of serum OPG levels (β = 0.89 and 1.63 for tertile 2 and tertile 3, respectively, p for trend = 0.035) in HD patients. Multivariable logistic regression analysis revealed that, in addition to age, DM, low iPTH levels, and high serum calcium levels, increasing tertiles of serum OPG levels (OR = 5.34 for tertile 2; OR = 7.06 for tertile 3; p for trend = 0.002) were an independent predictor of high arterial stiffness in HD patients. Serum calcium levels positively correlated with cfPWV value only in the highest OPG tertile group (r = 0.408, p = 0.009). A positive association was detected between serum OPG levels and central arterial stiffness in HD patients, and patients with high serum OPG levels may have greater influence of calcium load on central arterial stiffening.

The aim of this systematic review and meta-analysis was to summarize the association of obstructive sleep apnea (OSA) with renal outcome. Our study followed the PRISMA guidelines. Two independent reviewers searched for relevant articles in the databases of Pubmed, the Web of Science and CENTRAL, and conducted study selection and quality assessment. A random-effect model was used to estimate the effects. A total of 1240 articles were initially identified (Pubmed = 568, Web of Science = 640, CENTRAL = 32). After removal of duplicate articles (n = 415) and irrelevant articles (n = 788), 37 were selected for full-text review, and 18 were finally included in the analysis. Overall, patients diagnosed with OSA were found to have a higher odds ratio (OR) of a poorer renal outcome, with a pooled OR of 1.77 (95% C.I.: 1.37–2.29). The significant association between OSA and a poorer renal outcome was not affected by the medical condition of diabetes mellitus (DM). In addition, we found that OSA was consistently associated with higher albuminuria/proteinuria and a lower estimated glomerular filtration rate (eGFR), with a pooled OR of 1.84 (95% C.I.: 1.24–2.73) and 1.60 (95% C.I.: 1.19–2.16), respectively. A greater OSA severity was also found to be related to a higher OR, with a mild group OR of 1.45 (95% C.I.: 1.19–1.77) and a moderate and severe group OR of 2.39 (95% C.I.: 1.96–2.90). Our study demonstrated that OSA is significantly associated with poorer renal function.

The degree to which genetic or environmental factors are associated with early kidney damage among African Americans (AAs) is unknown. Among 462 AAs in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, we examined the cross-sectional association between apolipoprotein L1 (APOL1) risk variants and income with: 1) mildly reduced eGFR (<75 mL/min/1.73 m2, creatinine-cystatin C equation) and 2) elevated urine albumin-to-creatinine ratio (ACR) (≥17 in men and ≥25 mg/g in women). High risk APOL1 status was defined by 2 copies of high-risk variants; low risk if 0 or 1 copy. Income groups were dichotomized as < $14,000/year (lowest income group) or ≥ $14,000/year. Logistic regression models were adjusted for age, sex, and % European ancestry. Overall, participants’ mean age was 47 years and 16% (n = 73) had high risk APOL1 status. Mean eGFR was 99 mL/min/1.73 m2. Mildly reduced eGFR was prevalent among 11% (n = 51). The lowest income group had higher adjusted odds (aOR) of mildly reduced eGFR than the higher income group (aOR 1.8, 95% CI 1.2-2.7). High-risk APOL1 was not significantly associated with reduced eGFR (aOR 1.5, 95% CI 0.9-2.5). Among 301 participants with ACR data, 7% (n = 21) had elevated ACR. Compared to low-risk, persons with high-risk APOL1 had higher odds of elevated ACR (aOR 3.8, 95% CI 2.0-7.3). Income was not significantly associated with elevated ACR (aOR 1.8, 95% CI 0.7-4.5). There were no significant interactions between APOL1 and income. Both genetic and socioeconomic factors may be important determinants of early kidney damage among AAs.

We explored the association between health literacy and self-care behaviors among low-income patients with chronic kidney disease (CKD). We used baseline data from the Kidney Awareness Registry and Education trial (n = 137 patients with CKD) and multivariable logistic regressions to cross-sectionally examine the association between health literacy, defined by a validated questionnaire, and healthy behaviors. Study participants had a mean age of 55 years, were racially diverse (6% White, 36% Hispanic, 43% Black, 15% Asian) and 26% had low health literacy. Over one-third (38%) had hypertension, 51% had diabetes, and 67% had CKD stage 3 or 4. Compared to individuals with adequate health literacy, those with low health literacy had non-statistically significant higher tobacco use (adjusted odds ratio [aOR] = 2.33; 95% CI 0.90–6.06) and lower consumption of sugary beverages (aOR = 0.50; 0.20-1.23) and statistically significant decreased fast food intake (aOR = 0.38; 0.16-0.93). Health literacy was not associated with differences in medication adherence (0.84; 0.38-1.89) or physical activity (aOR = 2.39; 0.54-10.53). Health literacy was not uniformly associated with all self-care behaviors important for CKD management. A more nuanced understanding of the association of health literacy and self-care may be necessary to promote participation in behaviors known to slow CKD progression.

Diet can markedly affect acid-base status and it significantly influences chronic kidney disease (CKD) and its progression. The relationship of dietary acid load (DAL) and CKD has not been assessed on a population level. We examined the association of estimated net acid excretion (NAEes) with CKD; and socio-demographic and clinical correlates of NAEes. Among 12,293 U.S. adult participants aged >20 years in the National Health and Nutrition Examination Survey 1999–2004, we assessed dietary acid by estimating NAEes from nutrient intake and body surface area; kidney damage by albuminuria; and kidney dysfunction by eGFR < 60 ml/min/1.73m2 using the MDRD equation. We tested the association of NAEes with participant characteristics using median regression; while for albuminuria, eGFR, and stages of CKD we used logistic regression. Median regression results (β per quintile) indicated that adults aged 40–60 years (β [95% CI] = 3.1 [0.3–5.8]), poverty (β [95% CI] = 7.1 [4.01–10.22]), black race (β [95% CI] = 13.8 [10.8–16.8]), and male sex (β [95% CI] = 3.0 [0.7- 5.2]) were significantly associated with an increasing level of NAEes. Higher levels of NAEes compared with lower levels were associated with greater odds of albuminuria (OR [95% CI] = 1.57 [1.20–2.05]). We observed a trend toward greater NAEes being associated with higher risk of low eGFR, which persisted after adjustment for confounders. Higher NAEes is associated with albuminuria and low eGFR, and socio-demographic risk factors for CKD are associated with higher levels of NAEes. DAL may be an important target for future interventions in populations at high risk for CKD.

Endothelin-1 (ET-1) inhibition of vasopressin (AVP)-stimulated water reabsorption by the inner medullary collecting duct (IMCD) is associated with reduced cAMP accumulation. To determine the effect of ET-1 deficiency, AVP-stimulated cAMP responsiveness was assessed in IMCD from mice with collecting duct-specific deletion of ET-1 (CD ET-1 KO) and from control animals. Cyclic AMP production, adenylyl cyclase (AC) mRNA, and AC protein were measured in acutely isolated IMCD. CD ET-1 KO IMCD had enhanced AVP-stimulated cAMP accumulation. Inhibition of calcium-stimulated AC using BAPTA did not prevent enhanced AVP responsiveness in CD ET-1 KO IMCD. Factors known to be modified by ET-1, including nitric oxide, cyclooxygenase metabolites, and superoxide did not affect the increased AVP responsiveness of CD ET-1 KO IMCD. Differential V2 receptor or G-protein activity was not involved since CD ET-1 KO IMCD had increased cAMP accumulation in response to forskolin and/or cholera toxin. CD ET-1 KO did not affect mRNA or protein levels of AC3, one of the major known collecting duct AC isoforms. However, the other known major collecting duct AC isoform (AC5/6) did have increased protein levels in CD ET-1 KO IMCD, although AC5 (weak signal) and 6 mRNA levels were unchanged. ET-1 deficiency increases IMCD AC5/6 content, an effect that may synergize with acute ET-1 inhibition of AVP-stimulated cAMP accumulation.

Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate. Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function. 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment. Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN. This trial is registered with EudraCTN2008–001009-41 . Trial registration date 2008-10-08.

Elderly hemodialysis patients have a higher rate of mortality than nonelderly hemodialysis patients. Recent studies shown that the serum uric acid to creatinine ratio (SUA/Scr) was associated with all-cause mortality in general adults. The purpose of the present study was to investigate the association between the SUA/Scr and all-cause and cardiovascular disease mortality among elderly hemodialysis patients. A total of 222 patients (≥ 60 years) who received hemodialysis more than 8 h per week at Taizhou Second People’s Hospital for at least 3 months were enrolled in the present study from January 2015 to December 2019. Clinical characteristics including age, sex and height et. al, were obtained from the hemodialysis database. The laboratory data, including albumin (ALB), total cholesterol (TC), serum uric acid (SUA), serum creatinine (Scr) and so on, were collected before hemodialysis and analyzed by automatic biochemical analyzer. Survival information was recorded during the follow-up period. Multiple Cox regression was carried out to analyze the association between SUA/Scr and all-cause mortality. The survival rate of each group was calculated by the Kaplan–Meier method, and the ratio of survival curves was analyzed by the log-rank test. The contribution of SUA/Scr for predicting all-cause mortality risk was evaluated by net reclassification improvement (NRI). During the 19-month observation period, 78 patients died. Individuals in the nonsurviving group had significantly older ages (P < 0.001), body mass index (BMI) (P = 0.004), serum creatinine (P = 0.005) and prealbumin (P = 0.006) than surviving patients. After adjusting for age, sex, BMI, prealbumin, dialysis vintage, dialysis frequency, single-pool Kt/V (spKt/V), DM, hypertension and comorbidities, a higher ratio of SUA/Scr was independently associated with a higher risk of all-cause mortality (HR: 1.292; 95% CI: 1.013–1.648; P = 0.039). The predict value on all-cause mortality of SUA/Scr was superior to SUA (additive NRI = 0.214, P = 0.015) and Scr (additive NRI = 0.476, P < 0.001) among elderly hemodialysis patients. The serum uric acid to creatinine ratio is strongly associated with all-cause mortality in elderly hemodialysis patients which is more predictive than SUA or Scr alone.

Nonadherence to medications by patients requiring hemodialysis (HD) leads to unfavorable clinical outcomes. Limited data exist to demonstrate the effect of incorporating patient-centered interventions using concepts of medication therapy management and motivational interview by pharmacists on pharmacoadherence in patients requiring HD. Therefore, we assessed the impact of patient-centered pharmacist care on pharmacoadherence and its outcomes in patients requiring HD. Adult patients who had received outpatient HD for at least 3 months were enrolled. The study was conducted from October 2016 to April 2017. Pharmacists interviewed the patients at month 1, 2, 4 and 6, and the intervention (comprehensive review) occurred at months 3 and 5. The primary outcome was the change in pharmacoadherence as assessed by pre-HD serum phosphate levels and the differences in the number of medications between patient’ self-report and medications records at the electronic healthcare records (EHRs). The secondary outcomes included changes in systolic blood pressure (SBP), glycosylated hemoglobin levels, serum low-density lipoprotein (LDL) levels, and the prevalence and types of medication-related problems (MRPs). Seventy-two patients were enrolled. Their median age was 59 (interquartile range: 47–67.5) years, and 53% were men. Pre- and post-intervention pharmacoadherence, as indicated by serum phosphate levels and the differences in the number of medications between patient’ self-report and the medication records at the EHRs, did not significantly differ (p = 0.682 and 0.348, respectively). Mean SBP and mean LDL did not significantly change post-intervention. The median number of MRPs declined between Months 3 and 5 (p = 0.002): the prevalence of MRPs at Month 3 was 44.9% (95 confidence interval [CI]: 40.4–49.3) and decreased to 29.8% (95 CI: 25.6–34.3) at Month 5. Drug use without indication was the most frequent MRP (23.9%). Patient-centered pharmacist care did not result in significant changes in pharmacoadherence. However, its clinical utility as a tool to identify and mitigate MRPs in patients requiring HD is indisputable. ClinicalTrials.gov identifier: NCT03576404 (retrospectively registered on July 3rd, 2018).

Renal evaluation studies are rare in American Cutaneous Leishmaniasis (ACL). The aim of this study is to investigate whether specific treatment reverts ACL-associated renal dysfunction. A prospective study was conducted with 37 patients with ACL. Urinary concentrating and acidification ability was assessed before and after treatment with pentavalent antimonial. The patients mean age was 35.6 ± 12 years and 19 were male. Before treatment, urinary concentrating defect (U/Posm <2.8) was identified in 27 patients (77%) and urinary acidification defect in 17 patients (46%). No significant glomerular dysfunction was observed before and after specific ACL treatment. There was no reversion of urinary concentrating defects, being observed in 77% of the patients before and in 88% after treatment (p = 0.344). Urinary acidification defect was corrected in 9 patients after treatment, reducing its prevalence from 40% before to only 16% after treament, (p = 0.012). Microalbuminuria higher than 30 mg/g was found in 35% of patients before treatment and in only 8% after treatment. Regarding fractional excretion of sodium, potassium, calcium, phosphorus and magnesium, there was no significant difference between pre and post-treatment period. As previously described, urinary concentrating and acidification defects were found in an important number of patients with ACL. Present results demonstrate that only some patients recover urinary acidification capacity, while no one returned to normal urinary concentration capacity.