Metabolomic analysis of uremic pruritus in patients on hemodialysis.

Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform's chemical library. A role for uremic solutes in pruritus remains to be established.

Vitamin D and parathyroid hormone status in community-dwelling elderly patients with mild-to-moderate kidney impairment.

INTRODUCTION: Evidence on vitamin D and parathyroid hormone (PTH) status in patients with early kidney impairment is limited. We aimed to determine the associations among kidney function, vitamin D, and PTH status in community-dwelling elderly patients with mild-to-moderate kidney impairment. METHODS: Community-dwelling elderly patients were enrolled in this Institutional Review Board approved cross-sectional study. The eligibility criteria were as follows: age > 60 years, no recent hospitalization within the past 12 months, no conditions that affect vitamin D status including vitamin D supplementation, and eGFR > 30 mL/min/1.73 m2. Serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels were assessed. RESULTS: A total of 226 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 26.61 ± 10.44 ng/mL and the mean serum PTH was 50.67 ± 22.67 pg/mL. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] and secondary hyperparathyroidism [PTH > 65 pg/mL] were 25.3% and 18.1%, respectively. Patients with eGFR 30- < 60 mL/min/1.73m2 had significantly higher prevalence of 25(OH)D < 20 ng/mL (33.7% versus 19.4%, p < 0.05) than patients with eGFR ≥ 60 mL/min/1.73 m2. Multiple regression analysis showed independent negative association of serum PTH level with eGFR (mL/min/1.73 m2, ß: - 0.261, 95% CI [- 0.408, - 0.114]) and serum 25(OH)D (ng/mL, ß: - 0.499, 95% CI [- 0.775, - 0.223], adjusted for possible confounders). CONCLUSIONS: The prevalence of vitamin D deficiency was higher in patients with eGFR 30 - < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. Both decreased serum 25(OH)D levels and decreased eGFR were independently associated with increased serum PTH levels among these patients.

Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes.

BACKGROUND/AIMS: Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage. METHOD: Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800 mg/kg bw), ML (700 mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined. RESULTS: ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats. CONCLUSION: MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.

Elevated serum creatinine in the context of HIV - who is the culprit? Over-the-counter supplements vs. antiretrovirals.

We present a case of a 53-year-old male living with well-controlled HIV who, as part of routine monitoring, was noted to have an unexpected decline in renal function. His antiretrovirals were switched accordingly. It subsequently transpired that he had recently started taking creatine supplements in order to build muscle mass. He underwent specialist renal review and further investigation with a chromium-labelled scan which revealed his renal function was, in fact, stable. He continues under renal and HIV follow-up. It is now more widely recognised that creatine can affect renal function, and result in difficulty in interpretation of traditional renal blood tests. However, the further investigations that may be undertaken in such settings and HIV treatment considerations are not as widely reported. This case serves as a reminder to ensure over-the-counter and herbal supplements are part of routine questioning in HIV clinics, and outlines the specialist investigations that may be undertaken in cases of apparent renal decline.

Effect of branched chain amino acid supplementation on dialysis adequacy and nutritional parameters in hemodialysis patients.

Malnutrition in hemodialysis (HD) patients is caused by deficient nutrient and protein intake and has a negative impact on patient outcomes. The assessment of dialysis adequacy in these patients depends to a large extent on the calculation of urea clearance using dialyzer clearance of urea (K) multiplied by the duration of the dialysis treatment (t, in minutes) divided by the volume of distribution of urea in the body (V, in mL); Kt/V. This study aims to detect the effect of branched-chain amino acid (BCAA) supplementation on Kt/V and other nutritional parameters such as serum albumin as well as body mass index. Forty-six patients from the HD Unit of Mostafa Mahmoud Hospital were included in this study. Daily intake of BCAA was continued for three months. At the start of the study, before the intervention, and at the end of the 3rd month, we measured serum albumin, valine, leucine, iso-leucine, and Kt/V. Analysis of data was performed using paired and independent t-test. We found that BCAA has a highly significant effect on increasing the level of albumin, leucine, isoleucine, valine, and Kt/V in HD patients (P <0.001) (Paired t-test). BCAA supplements could be used in this patient population to improve dialysis adequacy and outcome.

Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial.

BACKGROUND: Acute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone. METHODS: The Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analysis assessed the effects of study therapy within tertiles of baseline estimated glomerular filtration rate (eGFR) and subgroups at heightened risk for diuretic resistance. RESULTS: Across eGFR tertiles, there was no incremental benefit of high-dose spironolactone on any efficacy endpoint, including changes in log N-terminal pro-B-type natriuretic peptide and signs and symptoms of congestion (all P for interaction ≥ 0.06). High-dose spironolactone had no significant effect on N-terminal pro-B-type natriuretic peptide reduction regardless of blood pressure, diabetes mellitus status, and loop diuretic dose (all P for interaction ≥ 0.38). In-hospital changes in serum potassium and creatinine were similar between treatment groups for all GFR tertiles (all P for interaction ≥ 0.18). Rates of inpatient worsening HF, 30-day worsening HF, and 60-day all-cause mortality were numerically higher among patients with lower baseline eGFR, but relative effects of study treatment did not differ with renal function (all P for interaction ≥ 0.27). CONCLUSIONS: High-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance. In-hospital initiation or continuation of spironolactone was safe during the inpatient stay, even when administered at high doses to patients with moderate renal dysfunction.

Hemogram and iron indices in renal anemia and the amelioration with Carica papaya leaf extract applied on albino rat model.

The present study was designed to look at the hematological disorders in gentamicin nephrotoxicity model, as kidney is considered as one of the hemopoietic organs. In a previous study, novel and classical kidney injury biomarkers were utilized to evaluate the nephroprotective potential of Carica papaya leaf extract (CPLE) in the same model in albino rats. Gentamicin (100 mg/kg, subcutaneously, for 21 consecutive days) resulted in significant decreases in red blood cell (RBC) count, hemoglobin concentration (HGB), and packed cell volume (PCV) value, with minimal alterations in erythrocytic indices. Leucogram showed leukocytosis, granulocytosis, and thrombocytopenia. Erythropoietin (EPO) levels were also drastically decreased by the end of the experimental course. Serum iron, unsaturated iron-binding capacity (UIBC), total iron binding capacity (TIBC), transferrin saturation %, and serum transferrin concentration values were significantly decreased in contrast to ferritin, which was increased. When concurrently administered with gentamicin, CPLE (150 and 300 mg/kg, orally via gastric tube, for 21 days) significantly protected against the drastic effects of the former on the blood profile with improving potentials on erythrogram, leukogram, thrombocytes, EPO, iron and its indices, in a dose-dependent manner. These data may suggest CPLE as an appreciated blood homeostatic and nephroprotective agent from a natural source that could be a good remedy in conditions associated with blood disorders.

Effect of amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing on the treatment of renal failure and hypertension by the PI3K/AKT pathway.

To study the effect and molecular mechanisms of amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing on the treatment methods of renal failure and hypertension. A total of 60 cases of renal failure hypertension were randomly divided into the Control group and the Treatment group. The control group was treated with amlodipine besylate, while the treatment group was treated with amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing. A rat model of renal failure hypertension was established. Rats were divided into the sham group, model group, NC group (treated with amlodipine besylate) and treatment group (treated with amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing). Rats were given drugs at 10­20 weeks of age to observe their general condition and detect changes of blood pressure, blood biochemical indices and urine index. The pathological changes of renal tissue were examined by hematoxylin and eosin staining, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)9 were detected by immunohistochemistry. Reverse transcription­quantitative polymerase chain reaction was used to determine mRNA expression of phosphoinositide 3­kinase (PI3K), protein kinase B (AKT) and endothelin (ET)­1 and western blotting was used to detect the expression of phosphorylated (p)­PI3K/PI3K, p­AKT/AKT and p­nuclear factor (NF)­κB p65/NF­κB p65 protein. Systolic and diastolic blood pressures in Treated group patients were significantly lower compared with in Control group patients. The systolic and diastolic blood pressure of rats were significantly decreased and blood urea nitrogen (BUN), carbapenem­resistant Enterobacteriaceae (CRE), N­acetyl­ß­D­glucosaminidase (NAG), urine protein (UP) and blood urea protein (BUP), contents were significantly decreased following amlodipine besylate treatment. The expression of VEGF and matrix metallopeptidase 9 protein were significantly decreased, but the expression of PI3K, AKT mRNA and p­PI3K/PI3K, p­AKT/AKT protein were significantly increased. ET­1 mRNA and p­NF­κB p65/NF­κB protein were significantly increased. The pathological alterations of renal tissue were improved and the pathological changes of glomerulus, tubule and interstitium were alleviated. Amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing can effectively reduce the systolic pressure and diastolic pressure of patients, and improve the symptoms and signs of patients, which may be associated with the regulation of the expression of PI3K/AKT pathway, so as to regulate the expression of BUN, CRE, UP, BUP and NAG.

Cross-sectional evaluation of the relationship between vitamin D status and supplement use across levels of kidney function in adults.

OBJECTIVES: The objective of this study was to assess vitamin D status of US non-pregnant adults using a standardised assay across 15 mL/min/1.73 m2 increments of kidney function, report the use of dietary supplements containing vitamin D and assess relationships between vitamin D and markers of bone resorption. DESIGN: This study is a cross-sectional evaluation. SETTING: The study is from the US National Health and Nutrition Evaluation Survey in 2001-2012. PARTICIPANTS: The participants were non-institutionalised, non-pregnant adults, age ≥20 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was serum 25OHD evaluated using liquid chromatography-tandem mass spectroscopy traceable to international reference standards. Secondary outcome measures were use of dietary supplements containing vitamin D and the serum intact parathyroid hormone and bone-specific alkaline phosphatase in a subset of participants. RESULTS: The median 25OHD concentration in 27 543 US non-pregnant adults was 25.7 ng/mL (range, 2.2-150.0 ng/mL). Vitamin D supplements were used by 38.0%; mean (SE)=757 (43) international units/day. The range of 25OHD concentration across groups, stratified by kidney function, was 23.0-28.1 ng/mL. The lowest concentration of 25OHD observed was in people with higher kidney function (23.0 ng/mL for estimated glomerular filtration rate >105 mL/min/1.73 m2). Only 24% of people not taking a dietary supplement had a 25OHD concentration >30 ng/mL. Serum intact parathyroid hormone inversely correlated with 25OHD within all kidney function groups. Bone-specific alkaline phosphatase was also negatively associated with 25OHD concentration. CONCLUSIONS: These data indicate that 25OHD concentrations and supplement use may be suboptimal in a significant proportion of the population, across all kidney function levels. The response of bone resorption markers further suggests that 25OHD levels could be improved. Together, these data support a re-evaluation of the 25OHD concentration associated with health in adults.

Shrunken pore syndrome, preeclampsia, and markers of NO metabolism in pregnant women during the first trimester.

Shrunken pore syndrome (SPS) is a condition that manifests itself as the decreased renal clearance of low-molecular-weight proteins but normal clearance of creatinine. Pregnant women with evidence of SPS during the first trimester have an increased risk of developing preeclampsia (PE). The nitric oxide (NO) metabolism markers arginine and ADMA, especially their ratio (Arg/ADMA), are recognized markers of endothelial dysfunction. The aim of this nested case-control study was to establish first-trimester reference intervals (RI) for markers of NO metabolism and to study these markers in women with evidence of SPS at the end of the first trimester. Seventy-four women were stratified in the first trimester according to evidence of SPS (SPS + or SPS-) and the occurrence of PE during subsequent pregnancy (PE + or PE-), as follows: SPS-/PE-, SPS+/PE-, SPS-/PE+, and SPS+/PE+. RIs were determined according to the CLSI EP28-A3c guidelines. Serum Arg and ADMA levels were analyzed. The Arg and ADMA concentrations did not differ among the four groups. However, women in the SPS+/PE + group had a significantly lower Arg/ADMA ratio than those in the other 3 groups (p = .02). In conclusion, we defined the first-trimester RI of Arg, ADMA and the Arg/ADMA ratio as markers of NO metabolism. Our results suggest that SPS in the first trimester predicts a pathophysiological hallmark of subsequent PE, i.e. lower NO production leading to increased vessel tone. Early identification of women at risk for later PE could lead to adaptive prophylactic interventions, such as supplementation with Arg or an NO-donor drug in order to mitigate the risk of developing PE.

One-Year Historical Cohort Study of the Phosphate Binder Sucroferric Oxyhydroxide in Patients on Maintenance Hemodialysis.

OBJECTIVE: The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. DESIGN: Historical cohort analyses of de-identified electronic medical records. SUBJECTS: In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. MAIN OUTCOME MEASURES: Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5 mg/dL) and mean number of PB pills/day. RESULTS: Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P < .0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P < .0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women). CONCLUSION: Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status.

Renal Tubular Dysfunction Fully Accounts for Plasma Biochemical Abnormalities in Type 1A Pseudohypoparathyroidism.

Context: Type 1A pseudohypoparathyroidism (PHP-1A) is characterized by target organ resistance to PTH. Patients can present with various dysmorphic features; however, renal failure has not been classically described. Case Description: A female patient came to our attention at the age of 7 years with characteristic signs of PTH resistance (i.e., hypocalcemia, hyperphosphatemia, and high serum PTH levels). She also presented with hypothyroidism, early-onset obesity, short metacarpal bones, and multiple subcutaneous ossifications, leading to a clinical diagnosis of pseudohypoparathyroidism. In addition to her genetic condition, she had bilateral renal hypodysplasia that was slowly progressing to end-stage kidney disease. She received a kidney transplant at the age of 16 years and, after transplantation, experienced rapidly normalized calcium, phosphate, and PTH levels, allowing f withdrawal of vitamin D supplementation. Conclusions: To the best of our knowledge, ours is the first report of a patient with PHP-1A undergoing kidney transplantation. Normalization of biochemical parameters after the procedure demonstrated that renal tubular resistance to PTH is sufficient to explain the calcium/phosphate abnormalities observed in PHP-1A.

Lipid peroxidation diminishing perspective of isolated theaflavins and thearubigins from black tea in arginine induced renal malfunctional rats.

BACKGROUND: Recently oxidative stress induced maladies have amplified owing to sedentary lifestyle and monotonous diet. Introduction of plant based biomolecules may be a suitable strategy to cope with the lipid peroxidation. In this context, black tea polyphenols (theaflavin & thearubigins) are in fame among the scientific community as cost effective therapeutic agents owing to their safety, economics, structural diversity and ability to modulate various lipid peroxidation responses by halting the expression of different metabolic targets. METHODS: The mandate of present investigation was to first time check the synergism among the isolated theaflavins & thearubigins against lipid peroxidative indicators both in vitro and in vivo. Purposely, theaflavins and thearubigins were isolated from black tea through solvent partition methods by using different solvents (Aqueous ethanol, Aqueous methanol & Water) and time intervals (30, 60 & 90 min) and subjected to in vitro characterization through different antioxidant indices to access the in vitro lipid peroxidation shooting effect of these bioactive moieties. Moreover, individual theaflavins contents also estimate through HPLC. For evaluation of in vivo antioxidant effect, renal malfunction was induced through arginine and forty rats were divided in four groups (10 each after power analysis) and 04 types of diets were given i.e. T0 (control diet without supplementation), T1 (Basic experimental Diet+ theaflavins supplementation @ 1 g), T2 (Basic experimental Diet+ Thearubigins supplementation @ 1 g) & T3 (Basic experimental Diet+ Supplementation of theaflavins+ thearubigins @ 0.5 + 0.5 g, respectively) for the period of 56 days. Alongside, a control study was also carried out for comparison by involving normal rats fed on arginine free diet. The body weight, lipid profile, glycemic responses, Renal function test, liver function test, antioxidant indices and hematological parameters were estimated at the termination of study. RESULTS: The results indicated that theaflavins and thearubigins isolation was significantly affected by time of extraction and solvent. In this context, aqueous ethanol at 60 min extraction interval caused maximum extraction. Likewise, theaflavins isolate exhibited more antioxidant activity as compared to thearubigins. Moreover, the theaflavins and thearubigins based experimental diets imparted significant reduction in Lipid profile, glucose content, renal function tests and TBARS with enhancement in insulin, HDL and hematological parameters. In this context, theaflavin based diet caused maximum reduction in lipid profile and TBARS better as compared to thearubigins and theaflavins + thearubigins based. However, theaflavin+ thearubigins based diet caused highest glucose, urea & creatinine decline and maximum insulin increase & antioxidant indices as compared to other nutraceuticals. CONCLUSIONS: It was deduced that theaflavins & thearubigins have strong antioxidative potential both in in vitro as well as in vivo to tackle the menace associated with lipid peroxidation.

Hypoparathyroidism: Less Severe Hypocalcemia With Treatment With Vitamin D2 Compared With Calcitriol.

Context: Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism. Objective: Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol. Design, Setting, and Patients: A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records. Main Outcome Measures: Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia. Results: D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones. Conclusion: We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.

Effects of Hyperbaric Oxygen Treatment on Renal System.

INTRODUCTION: Hyperbaric oxygen (HBO) treatment is steadily increasing as a therapeutic modality for various types of diseases. Although good clinical outcomes were reported with HBO treatment for various diseases, the multisystemic effects of this modality are still unclear. This study aimed to investigate the renal effects of HBO experimentally. MATERIALS AND METHODS: Fourteen New Zealand White rabbits were divided into 2 groups randomly as the control group and the study group. The study group received HBO treatment for 28 days (100% oxygen at 2.5 atmospheres for 90 minutes daily) and the control group was used to obtain normal renal tissue of the animal genus. After the intervention period, venous blood samples were obtained, and renal tissue samples were harvested for comparisons. RESULTS: Normal histological morphology was determined with Masson trichrome staining and periodic acid-Schiff staining in the control group. Atrophic glomerular structures, vacuolated tubule cells, and degeneration were detected in the renal samples of the study group with Masson trichrome staining. Additionally, flattening was observed on the brush borders of the proximal tubules, and tubular dilatation was visualized with periodic acid-Schiff staining. The histopathologic disruption of renal morphology was verified with detection of significantly elevated kidney function laboratory biomarkers in the study group. CONCLUSIONS: Our findings suggests that HBO has adverse effects on renal glomerulus and proximal tubules. However, the functional effects of this alteration should be investigated with further studies.

Massive copper and selenium losses cause life-threatening deficiencies during prolonged continuous renal replacement.

OBJECTIVE: Several trace elements are essential for immunity and wound healing, particularly after major burns. Continuous renal replacement therapy (CRRT), which is used to treat renal failure, causes significant trace elements losses. The aim of the present review is to update the current literature and draw attention to this type of complication, as copper deficiency is rarely suspected and diagnosed in clinical conditions and may occur in chronic critically ill patients. METHODS: This is an emblematic case report and review of literature. RESULTS: Major copper and selenium deficiencies were documented in a patient with major burns complicated by renal failure. The main cause was effluent loss during prolonged CRRT. The copper deficit resulted in life-threatening bradycardia and the alteration of lipid metabolism with severe hypertriglyceridemia. The published data are scarce, but trace element losses with effluent have been previously documented, as has the affect of copper deficiency on cardiac rhythm. CONCLUSION: The literature regarding the specific requirements for chronically critically ill patients is limited. During prolonged CRRT, copper and selenium levels decrease and probably should be monitored during prolonged therapy. Research in this area is required.

Nephrology consultations incorporated into HIV care - non-compliance is an important issue.

Although infrequent, kidney disease is a potentially serious co-morbidity among human immunodeficiency virus (HIV)-infected patients. The spectrum of renal impairment is very wide from clinically insignificant to end stage renal disease and often requires nephrologist's consultation. Therefore, we established combined renal and HIV care in the HIV Out-Patient Clinic in Warsaw. Medical records of patients consulted by nephrologist from March 2014 to March 2015 were included in analyses. Patients changing medication without consulting the physician or persistently not coming for follow-up visits were defined as non-compliant. In statistical analyses, non-parametric tests and logistic regression models were used as appropriate. In total, 100 patients were consulted by a nephrologist during the study period. All patients were white Europeans, 88 (88%) male, 42 (42%) infected through men having sex with men and 16 (16%) through intravenous drug users. Fifteen (15%) patients had hepatitis C virus (HCV) infections and 11 (11%) confirmed with positive HCV RNA. The most common reasons for referral were proteinuria and increased serum creatinine. In 6 out of 31 patients (19.3% of those referred for increased creatinine level) elevated serum creatinine was due to illegal substances or diet supplements use. Fifty-seven (57%) of patients were non-compliant. In univariate logistic regression models, all tested factors were non-significant. In most cases, patients were referred to nephrologist due to possible link between laboratory abnormalities and antiretroviral treatment. In one out of five cases, elevated creatinine level was linked with substance/dietary abuse. Poor compliance is an important problem in integrated nephrological care, however we were not able to identify any factors associated with non-compliance.

Almond supplementation reduces serum uric acid in coronary artery disease patients: a randomized controlled trial.

OBJECTIVE: Elevated serum uric acid (UA), a biomarker of renal insufficiency, is also an independent prognostic marker for morbidity in coronary artery disease (CAD) and poses serious health risks. This study reports the effect of almond consumption on UA in CAD patients. STUDY DESIGN: A randomized controlled clinical trial was conducted with three groups: no-intervention (NI), Pakistani almonds (PA) or American almonds (AA). Patients were recruited from the Cardiology Clinics, Aga Khan University Hospital. Two follow-ups were scheduled at week-6 and week-12. 150 patients were randomly divided in three groups (50 per group). NI was not given almonds, whereas the PA and AA were given Pakistani and American almond varieties (10 g/day), respectively; with instruction to soak overnight and eat before breakfast. RESULTS: Almonds supplementation significantly reduced (p < 0.05) serum UA among groups, and over time. At week-6, UA concentrations were -13 to -16 % less in PA and AA; at week-12 the concentrations were -14 to -18 % less, compared to NI. Systolic and diastolic blood pressure and body weights of the participants remained fairly constant among all the groups. CONCLUSION: Almonds (10 g/day), eaten before breakfast, reduces serum UA in CAD patients. Prevention of hyperuricemia can confer protection from kidney and vascular damage and if extrapolated for general population, dietary almonds can offer grander health benefit. Trial is registered at Australian New Zealand Clinical trial registry as ACTRN12614000036617.

Evaluation of Dose-Reduced Direct Oral Anticoagulant Therapy.

BACKGROUND: Compared with vitamin K antagonists, direct-acting oral anticoagulants (DOACs) have fixed dosing, limited drug interactions, and do not require therapeutic drug level monitoring. Dose adjustments are recommended for moderate renal dysfunction, low body weight, and select drug interactions. OBJECTIVES: The aim of our study is to determine if DOAC dose reductions were appropriate based on the manufacturer labeling recommendations for each agent. We also followed patients' treatment outcomes. METHODS: We retrospectively reviewed patients administered a DOAC at a reduced dose between January 2011 and August 2014. The primary outcome was adherence to current manufacturer dose recommendations. The secondary outcome measures were the incidence of thromboembolic events or any bleeding episodes, regardless of severity, while on therapy. RESULTS: Of 224 patients included in the analysis, 43.3% of patients fit criteria for a dose adjustment according to manufacturer recommendations. Only 3 of 28 (10.7%) patients treated with apixaban met 2 out of 3 clinical criteria required for a dose reduction per manufacturer recommendations. Only 54.7% of rivaroxaban-treated patients and 32.2% of dabigatran-treated patients had renal insufficiency requiring a dose reduction. Half of our patient population received aspirin therapy, with 6.3% of patients on triple antithrombotic therapy (dual antiplatelet agents plus an anticoagulant). A past medical history significant for bleeding was prevalent in patients treated with a reduced-dose DOAC (32.1%, 20.4%, and 25.4% of patients in the apixaban-, rivaroxaban-, and dabigatran-treated groups, respectively). Thromboembolic events occurred in 10.7%, 3.6%, and 5.1% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively. Frequency of bleeding complications, regardless of severity, was 17.9%, 18.2%, and 23.7% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively. CONCLUSION: We found that dose-adjusted DOAC therapy was often prescribed in a dose that was lower than package insert recommendations.